|
1
|
Bitzer M, Groß S, Albert J, Blödt S, Boda-Heggemann J, Borucki K, Brunner T, Caspari R, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Gebert J, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, Fougère CL, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Ott J, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ringe K, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schütte K, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Utzig M, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wenzel G, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:293-336. [PMID: 40064174 DOI: 10.1055/a-2446-2408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2025]
Affiliation(s)
- Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Katrin Borucki
- Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Klinische Chemie und Pathobiochemie
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Jamila Gebert
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Julia Ott
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Digestive Diseases and Nutrition, Gastroenterology, University of Kentucky
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | - Kristina Ringe
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Kerstin Schütte
- Klinik für Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken, Marienhospital Osnabrück
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Martin Utzig
- Abteilung Zertifizierung, Deutsche Krebsgesellschaft e.V., Berlin
| | - Arndt Vogel
- Institute of Medical Science, University of Toronto
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Gregor Wenzel
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| |
Collapse
|
|
2
|
Bitzer M, Groß S, Albert J, Blödt S, Boda-Heggemann J, Borucki K, Brunner T, Caspari R, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Gebert J, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, La Fougère C, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Ott J, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ringe K, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schütte K, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Utzig M, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wenzel G, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:e159-e260. [PMID: 40064172 DOI: 10.1055/a-2460-6298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2025]
Affiliation(s)
- Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Katrin Borucki
- Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Klinische Chemie und Pathobiochemie
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Jamila Gebert
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Julia Ott
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Digestive Diseases and Nutrition, Gastroenterology, University of Kentucky
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | - Kristina Ringe
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Kerstin Schütte
- Klinik für Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken, Marienhospital Osnabrück
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Martin Utzig
- Abteilung Zertifizierung, Deutsche Krebsgesellschaft e.V., Berlin
| | - Arndt Vogel
- Institute of Medical Science, University of Toronto
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Gregor Wenzel
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| |
Collapse
|
|
3
|
Chen H, Li H, Li H, Zhang Z. Umbrella review of adjuvant photodynamic therapy for cholangiocarcinoma palliative treatment. Photodiagnosis Photodyn Ther 2025; 51:104472. [PMID: 39761808 DOI: 10.1016/j.pdpdt.2025.104472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 12/31/2024] [Accepted: 01/03/2025] [Indexed: 01/24/2025]
Abstract
BACKGROUND Cholangiocarcinoma is a rare and often fatal malignancy. Numerous studies have demonstrated promising outcomes and survival rates associated with adjuvant photodynamic therapy (PDT) in the palliative treatment of cholangiocarcinoma. OBJECTIVE To systematically evaluate the existing meta-analyses on PDT for cholangiocarcinoma, assessing evidence quality and strength while performing updated meta-analyses to refine survival outcomes. METHODS PubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched up to September 18, 2024, to identify meta-analyses and clinical studies on PDT in patients with cholangiocarcinoma. The random-effects model was employed to re-synthesize existing meta-analyses, with a comprehensive evaluation of methodological quality. Updated meta-analyses of survival data were conducted, including subgroup analyses stratified by cholangiocarcinoma type and intervention modality. RESULTS A total of 5 meta-analyses and 21 clinical studies were included. The findings indicated that combining PDT with stenting or chemotherapy can significantly improve overall survival in patients with cholangiocarcinoma and reduce mortality rate, without increasing the risk of adverse events (AEs) such as cholangitis or abscess formation. For extrahepatic cholangiocarcinoma, adding PDT to stenting demonstrated a notable improvement in the 2-year survival rate. Meanwhile, for hilar cholangiocarcinoma, the addition of chemotherapy to PDT showed a more pronounced enhancement in the 1-year survival rate. CONCLUSION Current evidence indicates that PDT combined with stenting or chemotherapy in the palliative treatment of cholangiocarcinoma decreases overall mortality and enhances OS without increasing the incidence of AEs. Adding PDT to stenting or chemotherapy may be more beneficial for long-term efficacy.
Collapse
Affiliation(s)
- Hanhan Chen
- Department of Breast and Thyroid Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Honglin Li
- Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Huijie Li
- Department of Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China
| | - Zhen Zhang
- Department of Radiation Oncology, The Third Affiliated Hospital of Shandong First Medical University (Affiliated Hospital of Shandong Academy of Medical Sciences), Jinan, Shandong, China.
| |
Collapse
|
|
4
|
An W, Zhang K, Li G, Zheng S, Cao Y, Liu J. Hypericin mediated photodynamic therapy induces ferroptosis via inhibiting the AKT/mTORC1/GPX4 axis in cholangiocarcinoma. Transl Oncol 2025; 52:102234. [PMID: 39674093 PMCID: PMC11700288 DOI: 10.1016/j.tranon.2024.102234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 09/27/2024] [Accepted: 11/28/2024] [Indexed: 12/16/2024] Open
Abstract
Cholangiocarcinoma remains a challenging primary hepatobiliary malignancy with dismal prognosis. Photodynamic therapy (PDT),a less invasive treatment, has been found to inhibit the proliferation and induce ferroptosis, apoptosis and necrosis in other tumor cells in recent years. Regrettably, the role and exact molecule mechanism of PDT is still incompletely clear in cholangiocarcinoma cells. Ferroptosis is a novel regulated cell death(RCD), which is controlled by glutathione peroxidase4(GPX4) with the characteristics of iron dependent and excessive intracellular accumulation of lipid peroxides. This novel form of RCD has attracted great attention as a potential new target in clinical oncology during recent years. In this study, we observed that hypericin mediated PDT(HY-PDT) could significantly inhibit the proliferation of the cholangiocarcinoma cells and suppress migration and the epithelial mesenchymal transition (EMT) as well. Then, we conducted transcriptome sequencing and bioinformatics analysis and observed that HY-PDT was most likely involved in ferroptosis, apoptosis, the EMT process and AKT/mTORC1 signaling pathways in cholangiocarcinoma cells. Next, a series of in vitro and in vivo experiments were performed to confirm that HY-PDT could trigger cholangiocarcinoma cells ferroptosis through inhibiting the expression of GPX4 protein. In terms of molecular mechanism, we found that HY-PDT induced ferroptosis by decreasing GPX4 expression via suppression of the AKT/mTORC1 signaling pathway. In addition, we also found that HY-PDT inhibit cholangiocarcinoma cells migration and the EMT process by inhibiting the AKT/mTORC1 pathway. Our study illustrated a new mechanism of action for HY-PDT and might throw light on the individualized precision therapy for cholangiocarcinoma patients.
Collapse
Affiliation(s)
- Wei An
- Department of Hepatobiliary surgery, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong 250031, China; Department of Hepatobiliary surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China
| | - Kai Zhang
- Department of Hepatobiliary surgery, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong 250031, China
| | - Guangbing Li
- Department of Hepatobiliary surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China
| | - Shunzhen Zheng
- Department of Hepatobiliary surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China
| | - Yukun Cao
- Department of Hepatobiliary surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China
| | - Jun Liu
- Department of Hepatobiliary surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China.
| |
Collapse
|
|
5
|
Groß S, Bitzer M, Albert J, Blödt S, Boda-Heggemann J, Borucki K, Brunner T, Caspari R, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Gebert J, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, Fougère CL, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Ott J, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ringe K, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schütte K, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Utzig M, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wenzel G, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:e82-e158. [PMID: 39919781 DOI: 10.1055/a-2460-6347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Affiliation(s)
- Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Katrin Borucki
- Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Klinische Chemie und Pathobiochemie
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Jamila Gebert
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Julia Ott
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Digestive Diseases and Nutrition, Gastroenterology, University of Kentucky
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | - Kristina Ringe
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Kerstin Schütte
- Klinik für Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken, Marienhospital Osnabrück
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Martin Utzig
- Abteilung Zertifizierung, Deutsche Krebsgesellschaft e.V., Berlin
| | - Arndt Vogel
- Institute of Medical Science, University of Toronto
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Gregor Wenzel
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| |
Collapse
|
|
6
|
Groß S, Bitzer M, Albert J, Blödt S, Boda-Heggemann J, Borucki K, Brunner T, Caspari R, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Gebert J, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, La Fougère C, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Ott J, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ringe K, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schütte K, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Utzig M, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wenzel G, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:169-203. [PMID: 39919782 DOI: 10.1055/a-2446-2454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Affiliation(s)
- Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Katrin Borucki
- Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Klinische Chemie und Pathobiochemie
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Jamila Gebert
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Julia Ott
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Digestive Diseases and Nutrition, Gastroenterology, University of Kentucky
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | - Kristina Ringe
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg
| | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Kerstin Schütte
- Klinik für Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken, Marienhospital Osnabrück
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Martin Utzig
- Abteilung Zertifizierung, Deutsche Krebsgesellschaft e. V., Berlin
| | - Arndt Vogel
- Institute of Medical Science, University of Toronto
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Gregor Wenzel
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| |
Collapse
|
|
7
|
Sun Z, Xu H, Yang L, Wang X, Shu B, Yang M, Ren Z, Xiang C, Zhang Y, Yang S. mFOLFOX-HAIC+lenvatinib+PD-1 inhibitors versus GC/GS/GEMOX chemotherapy as a first line therapy for advanced biliary tract cancer: A single-center retrospective cohort study. Biosci Trends 2025; 18:599-609. [PMID: 39401897 DOI: 10.5582/bst.2024.01286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2025]
Abstract
Biliary tract tumors (BTC) account for about 3% of all digestive system tumors, with rising incidence and limited treatment options, particularly for advanced stages, underscoring the need for innovative therapies. This retrospective cohort study evaluated the safety and efficacy of a novel regimen combining hepatic artery infusion chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX-HAIC) alongside lenvatinib and programmed cell death protein-1 (PD-1) inhibitors (mFOLFOX-HAIC+lenvatinib+PD-1i) compared to standard regimens of gemcitabine plus cisplatin, gemcitabine plus S1, or gemcitabine plus oxaliplatin (GC/GS/GEMOX) in advanced BTC patients treated from March 2019 to November 2023. A total of 89 patients were analyzed, with 55 receiving hepatic arterial infusion chemotherapy and 34 receiving the GC/GS/GEMOX regimens. Among these, 23 patients were in the mFOLFOX-HAIC+lenvatinib+PD-1i group, while 24 were in the GC/GS/GEMOX group. The median progression-free survival (mPFS) for the mFOLFOX-HAIC+lenvatinib+PD-1i group was 15 months compared to 6 months for the GC/GS/GEMOX group. Similarly, the median overall survival (mOS) was 20 months for the mFOLFOXHAIC+lenvatinib+PD-1i group versus 13 months for the GC/GS/GEMOX group. The objective response rate (ORR) and disease control rate (DCR) for the mFOLFOX-HAIC+lenvatinib+PD-1i group were 48.5% and 87.0%, respectively, both significantly higher than those observed in the GC/GS/GEMOX group at three months of treatment. The incidence of adverse events (AEs) was similar between the mFOLFOX-HAIC+lenvatinib+PD-1i group and the GC/GS/GEMOX group, at 86.5% and 84.2%, respectively, with no statistically significant difference in complication rates. Overall, mFOLFOX-HAIC+lenvatinib+PD-1i appears to be a safe and well-tolerated treatment for advanced BTC, demonstrating superior mPFS and mOS compared to standard regimens.
Collapse
Affiliation(s)
- Zhipeng Sun
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Institute for Precision Medicine, Key Laboratory of Digital Intelligence Hepatology (Ministry of Education), Tsinghua University; Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
- Department of Hepatopancreatobiliary Surgery, Affiliated Hospital, School of Clinical Medicine, Qinghai University, Xining, Qinghai, China
| | - Hai Xu
- Department of Hepatopancreatobiliary Surgery, Affiliated Hospital, School of Clinical Medicine, Qinghai University, Xining, Qinghai, China
| | - Lei Yang
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Institute for Precision Medicine, Key Laboratory of Digital Intelligence Hepatology (Ministry of Education), Tsinghua University; Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Xiaojuan Wang
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Institute for Precision Medicine, Key Laboratory of Digital Intelligence Hepatology (Ministry of Education), Tsinghua University; Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Bin Shu
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Institute for Precision Medicine, Key Laboratory of Digital Intelligence Hepatology (Ministry of Education), Tsinghua University; Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Ming Yang
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Institute for Precision Medicine, Key Laboratory of Digital Intelligence Hepatology (Ministry of Education), Tsinghua University; Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Zhizhong Ren
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Institute for Precision Medicine, Key Laboratory of Digital Intelligence Hepatology (Ministry of Education), Tsinghua University; Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Canhong Xiang
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Institute for Precision Medicine, Key Laboratory of Digital Intelligence Hepatology (Ministry of Education), Tsinghua University; Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Yuewei Zhang
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Institute for Precision Medicine, Key Laboratory of Digital Intelligence Hepatology (Ministry of Education), Tsinghua University; Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Shizhong Yang
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Institute for Precision Medicine, Key Laboratory of Digital Intelligence Hepatology (Ministry of Education), Tsinghua University; Research Unit of Precision Hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| |
Collapse
|
|
8
|
Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | | |
Collapse
|
|
9
|
Xie X, Sun T, Pan H, Ji D, Xu Z, Gao G, Miao J, Wang L, Zhang Y, Liu J, Ling Y, Su X. Development of Novel β-Carboline/Furylmalononitrile Hybrids as Type I/II Photosensitizers with Chemo-Photodynamic Therapy and Minimal Toxicity. Mol Pharm 2024; 21:3553-3565. [PMID: 38816926 DOI: 10.1021/acs.molpharmaceut.4c00238] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/01/2024]
Abstract
Chemo-photodynamic therapy is a treatment method that combines chemotherapy and photodynamic therapy and has demonstrated significant potential in cancer treatment. However, the development of chemo-photodynamic therapeutic agents with fewer side effects still poses a challenge. Herein, we designed and synthesized a novel series of β-carboline/furylmalononitrile hybrids 10a-i and evaluated their chemo-photodynamic therapeutic effects. Most of the compounds were photodynamically active and exhibited cytotoxic effects in four cancer cells. In particular, 10f possessed type-I/II photodynamic characteristics, and its 1O2 quantum yield increased by 3-fold from pH 7.4 to 4.5. Most interestingly, 10f exhibited robust antiproliferative effects by tumor-selective cytotoxicities and hypoxic-overcoming phototoxicities. In addition, 10f generated intracellular ROS and induced hepatocellular apoptosis, mitochondrial damage, and autophagy. Finally, 10f demonstrated extremely low acute toxicity (LD50 = 1415 mg/kg) and a high tumor-inhibitory rate of 80.5% through chemo-photodynamic dual therapy. Our findings may provide a promising framework for the design of new photosensitizers for chemo-photodynamic therapy.
Collapse
Affiliation(s)
- Xudong Xie
- Department of Pharmacy, Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong 226001, China
- School of Pharmacy and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong Key Laboratory of Small Molecular Drug Innovation, Nantong University, Nantong 226001, China
| | - Tiantian Sun
- School of Pharmacy and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong Key Laboratory of Small Molecular Drug Innovation, Nantong University, Nantong 226001, China
| | - Heyu Pan
- Department of Pharmacy, Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong 226001, China
- School of Pharmacy and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong Key Laboratory of Small Molecular Drug Innovation, Nantong University, Nantong 226001, China
| | - Dongliang Ji
- Department of Pharmacy, Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong 226001, China
- School of Pharmacy and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong Key Laboratory of Small Molecular Drug Innovation, Nantong University, Nantong 226001, China
| | - Zhongyuan Xu
- School of Pharmacy and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong Key Laboratory of Small Molecular Drug Innovation, Nantong University, Nantong 226001, China
| | - Ge Gao
- Department of Pharmacy, Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong 226001, China
- School of Pharmacy and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong Key Laboratory of Small Molecular Drug Innovation, Nantong University, Nantong 226001, China
| | - Jiefei Miao
- Department of Pharmacy, Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong 226001, China
- Department of Oncology, Affiliated Hospital of Nantong University, Nantong 226001, China
| | - Lei Wang
- School of Pharmacy and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong Key Laboratory of Small Molecular Drug Innovation, Nantong University, Nantong 226001, China
| | - Yanan Zhang
- School of Pharmacy and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong Key Laboratory of Small Molecular Drug Innovation, Nantong University, Nantong 226001, China
| | - Ji Liu
- Department of Pharmacy, Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong 226001, China
- School of Pharmacy and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong Key Laboratory of Small Molecular Drug Innovation, Nantong University, Nantong 226001, China
| | - Yong Ling
- Department of Pharmacy, Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong 226001, China
- School of Pharmacy and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong Key Laboratory of Small Molecular Drug Innovation, Nantong University, Nantong 226001, China
| | - Xing Su
- Department of Pharmacy, Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong 226001, China
- School of Pharmacy and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong Key Laboratory of Small Molecular Drug Innovation, Nantong University, Nantong 226001, China
| |
Collapse
|
|
10
|
Li Y, Li Y, Song Y, Liu S. Advances in research and application of photodynamic therapy in cholangiocarcinoma (Review). Oncol Rep 2024; 51:53. [PMID: 38334150 DOI: 10.3892/or.2024.8712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Accepted: 01/18/2024] [Indexed: 02/10/2024] Open
Abstract
Cholangiocarcinoma (CCA) is a disease characterized by insidious clinical manifestations and challenging to diagnose. Patients are usually diagnosed at an advanced stage and miss the opportunity for radical surgery. Therefore, effective palliative therapy is the main treatment approach for unresectable CCA. Current common palliative treatments include biliary drainage, chemotherapy, radiotherapy, targeted therapy and immunotherapy. However, these treatments only offer limited improvement in quality of life and survival. Photodynamic therapy (PDT) is a novel local treatment method that is considered a safe tumor ablation method for numerous cancers. It has shown good efficacy in various studies of CCA and is expected to become an important treatment for CCA. In the present study, the mechanisms of PDT in the treatment of CCA were systematically explored and the progress in the research of photosensitizers was discussed. The current study focused on the various PDT protocols and their therapeutic effects in CCA, with the objective of providing a new horizon for future research and clinical applications of PDT in the treatment of CCA.
Collapse
Affiliation(s)
- Yufeng Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, P.R. China
| | - Yuhang Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, P.R. China
| | - Yinghui Song
- Central Laboratory of Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan 410005, P.R. China
| | - Sulai Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, P.R. China
| |
Collapse
|
|
11
|
Groß S, Bitzer M, Albert J, Blödt S, Boda-Heggemann J, Brunner T, Caspari R, De Toni E, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, La Fougère C, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ritterbusch U, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Tholen R, Trojan J, van Thiel I, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:e213-e282. [PMID: 38364849 DOI: 10.1055/a-2189-8567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/18/2024]
Affiliation(s)
- Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein, Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e. V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Klinik für Innere Medizin, Gesundheit Nord, Klinikverbund Bremen
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | | | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg
| | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Reina Tholen
- Deutscher Bundesverband für Physiotherapie (ZVK) e. V
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Arndt Vogel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| |
Collapse
|
|
12
|
Nabi Z, Żorniak M, Reddy DN. Multimodal treatment with endoscopic ablation and systemic therapy for cholangiocarcinoma. Best Pract Res Clin Gastroenterol 2024; 68:101893. [PMID: 38522890 DOI: 10.1016/j.bpg.2024.101893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 02/03/2024] [Accepted: 02/15/2024] [Indexed: 03/26/2024]
Abstract
Cholangiocarcinoma (CCA) are primary malignancies of biliary system and usually unresectable at the time of diagnosis. As a consequence, majority of these cases are candidates for palliative care. With the advances in chemotherapeutic agents and multidisciplinary care, the survival rate has improved in cases with inoperable malignant biliary obstruction. As a consequence, there is a need to provide effective and durable palliative care in these patients. The main role of endoscopic palliation in the vast majority of CCA includes biliary stenting for obstructive jaundice. Recent advances in the endoscopic palliation and multimodal approach appear promising in imparting durable relief of symptoms. Use of radiofrequency ablation, photodynamic therapy and intraluminal brachytherapy has been shown to improve the survival rates as well as the patency of biliary stents. Infact, intraductal ablation may act synergistically with chemotherapy by modulating tumour signalling pathways and immune microenvironment.
Collapse
Affiliation(s)
- Zaheer Nabi
- Asian Institute of Gastroenterology, Hyderabad, India.
| | - Michał Żorniak
- Endoscopy Unit, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Poland.
| | | |
Collapse
|
|
13
|
Li Q, Chen S, Wang X, Cai J, Huang H, Tang S, He D. Cisplatin-Based Combination Therapy for Enhanced Cancer Treatment. Curr Drug Targets 2024; 25:473-491. [PMID: 38591210 DOI: 10.2174/0113894501294182240401060343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 03/04/2024] [Accepted: 03/15/2024] [Indexed: 04/10/2024]
Abstract
Cisplatin, a primary chemotherapeutic drug, is of great value in the realm of tumor treatment. However, its clinical efficacy is strictly hindered by issues, such as drug resistance, relapse, poor prognosis, and toxicity to normal tissue. Cisplatin-based combination therapy has garnered increasing attention in both preclinical and clinical cancer research for its ability to overcome resistance, reduce toxicity, and enhance anticancer effects. This review examines three primary co-administration strategies of cisplatin-based drug combinations and their respective advantages and disadvantages. Additionally, seven types of combination therapies involving cisplatin are discussed, focusing on their main therapeutic effects, mechanisms in preclinical research, and clinical applications. This review also discusses future prospects and challenges, aiming to offer guidance for the development of optimal cisplatin-based combination therapy regimens for improved cancer treatment.
Collapse
Affiliation(s)
- Qi Li
- Institute of Pharmacy & Pharmacology, University of South China, Hengyang, Hunan, China
| | - Siwei Chen
- Institute of Pharmacy & Pharmacology, University of South China, Hengyang, Hunan, China
| | - Xiao Wang
- Institute of Pharmacy & Pharmacology, University of South China, Hengyang, Hunan, China
| | - Jia Cai
- Institute of Pharmacy & Pharmacology, University of South China, Hengyang, Hunan, China
| | - Hongwu Huang
- Institute of Pharmacy & Pharmacology, University of South China, Hengyang, Hunan, China
| | - Shengsong Tang
- Hunan Province Key Laboratory for Antibody-Based Drug and Intelligent Delivery System, Hunan University of Medicine, Huaihua, China
| | - Dongxiu He
- Institute of Pharmacy & Pharmacology, University of South China, Hengyang, Hunan, China
| |
Collapse
|
|
14
|
Peirce V, Paskow M, Qin L, Dadzie R, Rapoport M, Prince S, Johal S. A Systematised Literature Review of Real-World Treatment Patterns and Outcomes in Unresectable Advanced or Metastatic Biliary Tract Cancer. Target Oncol 2023; 18:837-852. [PMID: 37751011 PMCID: PMC10663194 DOI: 10.1007/s11523-023-01000-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/08/2023] [Indexed: 09/27/2023]
Abstract
BACKGROUND Biliary tract cancers are rare aggressive malignancies typically diagnosed when the disease is metastatic or unresectable, precluding curative treatment. OBJECTIVE We aimed to identify treatment guidelines, real-world treatment patterns, and outcomes for unresectable advanced or metastatic biliary tract cancers in adult patients. METHODS Databases (MEDLINE, Embase, Cochrane Database of Systematic Reviews) were systematically searched between 1 January, 2000 and 25 November, 2021, and supplemented by hand searches. Eligible records were (1) treatment guidelines and (2) observational studies reporting real-world treatment outcomes, for unresectable advanced or metastatic biliary tract cancers. Only studies performed in the UK, Germany, France, Australia, Canada and South Korea were extracted, to moderate the number of records for synthesis while maintaining representation of a wide range of biliary tract cancer incidences. RESULTS A total of 66 relevant unique full-text records were extracted, including 16 treatment guidelines and 50 observational studies. Among guidelines, chemotherapies were most strongly recommended at first line (1L); the combination of gemcitabine and cisplatin (GEMCIS) was recommended as the standard of care in 1L. Recommendations for systemic chemotherapy in the second line (2L) conflicted because of uncertainties around survival benefit. Guidelines on further lines of treatment included a range of locoregional modalities and stenting or best supportive care without providing clear recommendations because of data paucity. Fifty observational studies reporting real-world treatment outcomes were extracted, of which 25 (50%) and 9 (18%) reported outcomes in 1L and 2L, respectively; 22 (44%) reported outcomes for treatments described as 'palliative'. In 1L, outcomes for systemic chemotherapy were most frequently described (23/25 studies), and GEMCIS was the most common systemic chemotherapy used (10/23 studies) in line with guidelines. Median overall survival with 1L systemic chemotherapy was < 12 months in most studies (16/23; range 4.7-22.3 months). Most 2L studies (10/11) described outcomes for systemic chemotherapy, most commonly for fluoropyrimidine-based regimen (5/10 studies). Median overall survival with 2L systemic chemotherapy was < 12 months in 5/10 studies (range 4.9-21.5 months). Median progression-free survival was reported more rarely than median overall survival. Some studies with small sample sizes or specifically selected patient populations (e.g. higher performance status, or patients who had already responded to treatment) achieved higher median overall survival. CONCLUSIONS At the time of this review, treatment options for unresectable advanced or metastatic biliary tract cancers confer poor real-world survival. For over a decade, GEMCIS remained the 1L standard of care, highlighting the lack of therapeutic innovation in this indication and the urgent unmet need for novel treatments with improved outcomes in this aggressive condition. Additional observational studies are needed to further understand the effectiveness of currently available treatments, as well as newly available therapies including the addition of immunotherapy in the evolving treatment landscape.
Collapse
Affiliation(s)
- Vivian Peirce
- AstraZeneca, Academy House, 132-136 Hills Road, Cambridge, CB2 8PA, UK.
| | | | - Lei Qin
- AstraZeneca, Gaithersburg, MD, USA
| | | | | | | | - Sukhvinder Johal
- AstraZeneca, Academy House, 132-136 Hills Road, Cambridge, CB2 8PA, UK
| |
Collapse
|
|
15
|
Möhring C, Khan O, Zhou T, Sadeghlar F, Mahn R, Kaczmarek DJ, Dold L, Toma M, Marinova M, Glowka TR, Matthaei H, Manekeller S, Kalff JC, Strassburg CP, Weismüller TJ, Gonzalez-Carmona MA. Comparison between regular additional endobiliary radiofrequency ablation and photodynamic therapy in patients with advanced extrahepatic cholangiocarcinoma under systemic chemotherapy. Front Oncol 2023; 13:1227036. [PMID: 37711210 PMCID: PMC10497756 DOI: 10.3389/fonc.2023.1227036] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 07/31/2023] [Indexed: 09/16/2023] Open
Abstract
Background and aims Extrahepatic cholangiocarcinoma (eCCA) remains a malignancy with a dismal prognosis. The first-line standard of care includes systemic chemotherapy (SC) and biliary drainage through stenting. Endobiliary ablative techniques, such as photodynamic therapy (ePDT) and radio-frequency ablation (eRFA), have demonstrated feasibility and favorable survival data. This study aimed to compare the oncologic outcome in patients treated with SC and concomitant eRFA or ePDT. Method All patients with eCCA were evaluated for study inclusion. Sixty-three patients receiving a combination of SC and at least one endobiliary treatment were retrospectively compared. Results Patients were stratified into three groups: SC + ePDT (n = 22), SC + eRFA (n = 28), and SC + ePDT + eRFA (n = 13). The median overall survival (OS) of the whole cohort was 14.2 months with no statistically significant difference between the three therapy groups but a trend to better survival for the group receiving ePDT as well as eRFA, during SC (ePDT + SC, 12.7 months; eRFA + SC, 13.8 months; ePDT + eRFA + SC, 20.2 months; p = 0.112). The multivariate Cox regression and subgroup analysis highlighted the beneficial effect of eRFA on OS. Overall, combined therapy was well tolerated. Only cholangitis occurred more often in the SC + eRFA group. Conclusion Additional endobiliary ablative therapies in combination with SC were feasible. Both modalities, eRFA and ePDT, showed a similar benefit in terms of survival. Interestingly, patients receiving both regimes showed the best OS indicating a possible synergism between both ablative therapeutic techniques.
Collapse
Affiliation(s)
- Christian Möhring
- Department of Medicine I, University Hospital of Bonn, Bonn, Germany
| | - Oliver Khan
- Department of Medicine I, University Hospital of Bonn, Bonn, Germany
| | - Taotao Zhou
- Department of Medicine I, University Hospital of Bonn, Bonn, Germany
| | | | - Robert Mahn
- Department of Medicine I, University Hospital of Bonn, Bonn, Germany
| | | | - Leona Dold
- Department of Medicine I, University Hospital of Bonn, Bonn, Germany
| | - Marieta Toma
- Department of Pathology, University Hospital of Bonn, Bonn, Germany
| | - Milka Marinova
- Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany
| | - Tim R. Glowka
- Department of Surgery, University Hospital of Bonn, Bonn, Germany
| | - Hanno Matthaei
- Department of Surgery, University Hospital of Bonn, Bonn, Germany
| | | | - Jörg C. Kalff
- Department of Surgery, University Hospital of Bonn, Bonn, Germany
| | | | - Tobias J. Weismüller
- Department of Medicine I, University Hospital of Bonn, Bonn, Germany
- Department of Gastroenterology and Oncology, Vivantes Humboldt Hospital, Berlin, Germany
| | | |
Collapse
|
|
16
|
Zeng W, Mao R, Zhang Z, Chen X. Combination Therapies for Advanced Biliary Tract Cancer. J Clin Transl Hepatol 2023; 11:490-501. [PMID: 36643047 PMCID: PMC9817051 DOI: 10.14218/jcth.2022.00277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Revised: 08/09/2022] [Accepted: 08/18/2022] [Indexed: 01/18/2023] Open
Abstract
Biliary tract cancers (BTCs) are a group of malignant neoplasms that have recently increased in incidence and have a poor prognosis. Surgery is the only curative therapy. However, most patients are only indicated for palliative therapy because of advanced-stage disease at diagnosis and rapid progression. The current first-line treatment for advanced BTC is gemcitabine and cisplatin chemotherapy. Nonetheless, many patients develop resistance to this regimen. Over the years, few chemotherapy regimens have managed to improve the overall survival of patients. Accordingly, novel therapies such as targeted therapy have been introduced to treat this patient population. Extensive research on tumorigenesis and the genetic profiling of BTC have revealed the heterogenicity and potential target pathways, such as EGFR, VEGF, MEK/ERK, PI3K and mTOR. Moreover, mutational analysis has documented the presence of IDH1, FGFR2, HER2, PRKACA, PRKACB, BRAF, and KRAS gene aberrations. The emergence of immunotherapy in recent years has expanded the treatment landscape for this group of malignancies. Cancer vaccines, adoptive cell transfer, and immune checkpoint inhibitors have been extensively investigated in trials of BTC. Therefore, patient stratification and a combination of various therapies have become a reasonable and important clinical strategy to improve patient outcomes. This review elaborates the literature on combined treatment strategies for advanced BTC from the past few years and ongoing clinical trials to provide new inspiration for the treatment of advanced BTC.
Collapse
Affiliation(s)
- Weifeng Zeng
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, Wuhan, Hubei, China
- Hubei key laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ruiqi Mao
- Clinic Center of Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhanguo Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, Wuhan, Hubei, China
- Hubei key laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Correspondence to: Zhanguo Zhang and Xiaoping Chen, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, Huazhong University of Science and Technology, Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, 1095 Jiefang Avenue, Wuhan, Hubei 430030, China. ORCID: https://orcid.org/0000-0002-4527-4975 (ZZ). Tel: +86-27-83663400, Fax: +86-27-83662851, E-mail: (ZZ) and (XC)
| | - Xiaoping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, Wuhan, Hubei, China
- Hubei key laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Correspondence to: Zhanguo Zhang and Xiaoping Chen, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, Huazhong University of Science and Technology, Hubei Province for the Clinical Medicine Research Center of Hepatic Surgery, 1095 Jiefang Avenue, Wuhan, Hubei 430030, China. ORCID: https://orcid.org/0000-0002-4527-4975 (ZZ). Tel: +86-27-83663400, Fax: +86-27-83662851, E-mail: (ZZ) and (XC)
| |
Collapse
|
|
17
|
Inoue T, Yoneda M. Recent Updates on Local Ablative Therapy Combined with Chemotherapy for Extrahepatic Cholangiocarcinoma: Photodynamic Therapy and Radiofrequency Ablation. Curr Oncol 2023; 30:2159-2168. [PMID: 36826127 PMCID: PMC9954800 DOI: 10.3390/curroncol30020166] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/25/2023] [Accepted: 02/06/2023] [Indexed: 02/12/2023] Open
Abstract
Although chemotherapy constitutes of the first-line standard therapy for unresectable extrahepatic cholangiocarcinoma, the treatment outcomes are unsatisfactory. In recent years, local ablative therapy, which is delivered to the cholangiocarcinoma lesion via the percutaneous or endoscopic approach, has garnered attention for the treatment of unresectable, extrahepatic cholangiocarcinoma. Local ablative therapy, such as photodynamic therapy and radiofrequency ablation, can achieve local tumor control. A synergistic effect may also be expected when local ablative therapy is combined with chemotherapy. However, it is a long way from being entrenched as an established therapeutic technique, and several unresolved problems persist, including the paucity of evidence comparing photodynamic therapy and radiofrequency ablation. Clinical application of photodynamic therapy and radiofrequency ablation requires sound comprehension and assimilation of the available evidence to truly benefit each individual patient. In this study, we reviewed the current status, issues, and future prospects of photodynamic therapy and radiofrequency ablation for extrahepatic cholangiocarcinoma, with a special focus on their combination with chemotherapy.
Collapse
Affiliation(s)
- Tadahisa Inoue
- Department of Gastroenterology, Aichi Medical University, 1-1 Yazakokarimata, Nagakute 480-1195, Japan
| | | |
Collapse
|
|
18
|
Yu Y, Wang N, Wang Y, Shi Q, Yu R, Gu B, Maswikiti EP, Chen H. Photodynamic therapy combined with systemic chemotherapy for unresectable extrahepatic cholangiocarcinoma: A systematic review and meta-analysis. Photodiagnosis Photodyn Ther 2023; 41:103318. [PMID: 36738903 DOI: 10.1016/j.pdpdt.2023.103318] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 12/21/2022] [Accepted: 01/31/2023] [Indexed: 02/05/2023]
Abstract
BACKGROUND Extrahepatic cholangiocarcinoma (ECC) is a tumor with high invasiveness and poor outcome. The current treatments for unresected ECC are not ideal. Novel strategies are needed to improve the outcomes of patients with unresected ECC. Photodynamic therapy (PDT) plus chemotherapy is one of the promising interventions for ECC patients. We conducted this systematic review to determine the efficacy and safety of PDT plus chemotherapy in unresected ECC patients. METHODS Databases of PubMed, Cochrane Library, Embase, and Web of science were searched from inception to July 2022. Studies that compared PDT plus chemotherapy to PDT alone or chemotherapy alone in patients with unresected ECC were included. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were pooled for overall survival (OS) and adverse events, respectively. RESULTS Seven eligible studies were finally included. There are four studies on PDT plus chemotherapy vs. chemotherapy alone and three studies on PDT plus chemotherapy vs. PDT alone. The meta-analysis showed that PDT plus chemotherapy had a significantly better OS than chemotherapy or PDT alone (PDT+chemotherapy vs. chemotherapy alone, HR: 0.69, p = 0.02; PDT+chemotherapy vs. PDT alone, HR:0.36, p<0.01). The occurrence of cholangitis, abscess, and photosensitivity reaction in PDT plus chemotherapy were comparable to either chemotherapy alone or PDT alone (p>0.05). CONCLUSION The combination of PDT and chemotherapy can improve patient survival for unresected ECC without increased adverse events. It may be a potential standard therapy in the future management of ECC.
Collapse
Affiliation(s)
- Yang Yu
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou 730030, China; The Second Clinical Medical College, Lanzhou University, Lanzhou 730030, China
| | - Na Wang
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou 730030, China; The Second Clinical Medical College, Lanzhou University, Lanzhou 730030, China
| | - Yingying Wang
- The Second Clinical Medical College, Lanzhou University, Lanzhou 730030, China
| | - Qianling Shi
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China
| | - Rong Yu
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou 730030, China; The Second Clinical Medical College, Lanzhou University, Lanzhou 730030, China
| | - Baohong Gu
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou 730030, China; The Second Clinical Medical College, Lanzhou University, Lanzhou 730030, China
| | - Ewetse Paul Maswikiti
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou 730030, China; The Second Clinical Medical College, Lanzhou University, Lanzhou 730030, China
| | - Hao Chen
- The Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou 730030, China.
| |
Collapse
|
|
19
|
Canakis A, Kahaleh M. Endoscopic palliation of malignant biliary obstruction. World J Gastrointest Endosc 2022; 14:581-596. [PMID: 36303806 PMCID: PMC9593514 DOI: 10.4253/wjge.v14.i10.581] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Revised: 08/20/2022] [Accepted: 10/05/2022] [Indexed: 02/05/2023] Open
Abstract
Malignant biliary obstruction often presents with challenges requiring the endoscopist to assess the location of the lesion, the staging of the disease, the eventual resectability and patient preferences in term of biliary decompression. This review will focus on the different modalities available in order to offer the most appropriate palliation, such as conventional endoscopic retrograde cholangiopancreatography, endoscopic ultrasound guided biliary drainage as well as ablative therapies including photodynamic therapy or radiofrequency ablation.
Collapse
Affiliation(s)
- Andrew Canakis
- Department of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD 21201, United States
| | - Michel Kahaleh
- Department of Gastroenterology and Hepatology, Robert Wood Johnson Medical Center, New Brunswick, NJ 08901, United States
| |
Collapse
|
|
20
|
Dias LM, de Keijzer MJ, Ernst D, Sharifi F, de Klerk DJ, Kleijn TG, Desclos E, Kochan JA, de Haan LR, Franchi LP, van Wijk AC, Scutigliani EM, Fens MH, Barendrecht AD, Cavaco JEB, Huang X, Xu Y, Pan W, den Broeder MJ, Bogerd J, Schulz RW, Castricum KC, Thijssen VL, Cheng S, Ding B, Krawczyk PM, Heger M. Metallated phthalocyanines and their hydrophilic derivatives for multi-targeted oncological photodynamic therapy. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY. B, BIOLOGY 2022; 234:112500. [PMID: 35816857 DOI: 10.1016/j.jphotobiol.2022.112500] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 04/27/2022] [Accepted: 06/11/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND AND AIM A photosensitizer (PS) delivery and comprehensive tumor targeting platform was developed that is centered on the photosensitization of key pharmacological targets in solid tumors (cancer cells, tumor vascular endothelium, and cellular and non-cellular components of the tumor microenvironment) before photodynamic therapy (PDT). Interstitially targeted liposomes (ITLs) encapsulating zinc phthalocyanine (ZnPC) and aluminum phthalocyanine (AlPC) were formulated for passive targeting of the tumor microenvironment. In previous work it was established that the PEGylated ITLs were taken up by cultured cholangiocarcinoma cells. The aim of this study was to verify previous results in cancer cells and to determine whether the ITLs can also be used to photosensitize cells in the tumor microenvironment and vasculature. Following positive results, rudimentary in vitro and in vivo experiments were performed with ZnPC-ITLs and AlPC-ITLs as well as their water-soluble tetrasulfonated derivatives (ZnPCS4 and AlPCS4) to assemble a research dossier and bring this platform closer to clinical transition. METHODS Flow cytometry and confocal microscopy were employed to determine ITL uptake and PS distribution in cholangiocarcinoma (SK-ChA-1) cells, endothelial cells (HUVECs), fibroblasts (NIH-3T3), and macrophages (RAW 264.7). Uptake of ITLs by endothelial cells was verified under flow conditions in a flow chamber. Dark toxicity and PDT efficacy were determined by cell viability assays, while the mode of cell death and cell cycle arrest were assayed by flow cytometry. In vivo systemic toxicity was assessed in zebrafish and chicken embryos, whereas skin phototoxicity was determined in BALB/c nude mice. A PDT efficacy pilot was conducted in BALB/c nude mice bearing human triple-negative breast cancer (MDA-MB-231) xenografts. RESULTS The key findings were that (1) photodynamically active PSs (i.e., all except ZnPCS4) were able to effectively photosensitize cancer cells and non-cancerous cells; (2) following PDT, photodynamically active PSs were highly toxic-to-potent as per anti-cancer compound classification; (3) the photodynamically active PSs did not elicit notable systemic toxicity in zebrafish and chicken embryos; (4) ITL-delivered ZnPC and ZnPCS4 were associated with skin phototoxicity, while the aluminum-containing PSs did not exert detectable skin phototoxicity; and (5) ITL-delivered ZnPC and AlPC were equally effective in their tumor-killing capacity in human tumor breast cancer xenografts and superior to other non-phthalocyanine PSs when appraised on a per mole administered dose basis. CONCLUSIONS AlPC(S4) are the safest and most effective PSs to integrate into the comprehensive tumor targeting and PS delivery platform. Pending further in vivo validation, these third-generation PSs may be used for multi-compartmental tumor photosensitization.
Collapse
Affiliation(s)
- Lionel Mendes Dias
- Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China; CICS-UBI, Health Sciences Research Center, University of Beira Interior, Covilhã, Portugal; Department of Medical Biology, Cancer Center Amsterdam, Amsterdam UMC Location Academic Medical Center, Amsterdam, the Netherlands; Laboratory of Experimental Oncology, Department of Pathology, Erasmus MC, Rotterdam, the Netherlands
| | - Mark J de Keijzer
- Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands; Membrane Biochemistry and Biophysics, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, the Netherlands
| | - Daniël Ernst
- Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China; Laboratory of Experimental Oncology, Department of Pathology, Erasmus MC, Rotterdam, the Netherlands
| | - Farangis Sharifi
- Department of Medical Biology, Cancer Center Amsterdam, Amsterdam UMC Location Academic Medical Center, Amsterdam, the Netherlands; Laboratory of Experimental Oncology and Radiobiology (LEXOR), Cancer Center Amsterdam, Amsterdam UMC Location Academic Medical Center, Amsterdam, the Netherlands
| | - Daniel J de Klerk
- Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China; Laboratory of Experimental Oncology, Department of Pathology, Erasmus MC, Rotterdam, the Netherlands
| | - Tony G Kleijn
- Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China; Laboratory of Experimental Oncology, Department of Pathology, Erasmus MC, Rotterdam, the Netherlands; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Emilie Desclos
- Department of Medical Biology, Cancer Center Amsterdam, Amsterdam UMC Location Academic Medical Center, Amsterdam, the Netherlands; Laboratory of Experimental Oncology and Radiobiology (LEXOR), Cancer Center Amsterdam, Amsterdam UMC Location Academic Medical Center, Amsterdam, the Netherlands
| | - Jakub A Kochan
- Department of Medical Biology, Cancer Center Amsterdam, Amsterdam UMC Location Academic Medical Center, Amsterdam, the Netherlands; Laboratory of Experimental Oncology and Radiobiology (LEXOR), Cancer Center Amsterdam, Amsterdam UMC Location Academic Medical Center, Amsterdam, the Netherlands
| | - Lianne R de Haan
- Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China; Laboratory of Experimental Oncology, Department of Pathology, Erasmus MC, Rotterdam, the Netherlands
| | - Leonardo P Franchi
- Department of Biochemistry and Molecular Biology, Institute of Biological Sciences (ICB 2), Federal University of Goiás (UFG), Goiânia, Goiás, Brazil
| | - Albert C van Wijk
- Department of Surgery, Amsterdam UMC location VUmc, Amsterdam, the Netherlands
| | - Enzo M Scutigliani
- Department of Medical Biology, Cancer Center Amsterdam, Amsterdam UMC Location Academic Medical Center, Amsterdam, the Netherlands; Laboratory of Experimental Oncology and Radiobiology (LEXOR), Cancer Center Amsterdam, Amsterdam UMC Location Academic Medical Center, Amsterdam, the Netherlands
| | - Marcel H Fens
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands
| | | | - José E B Cavaco
- CICS-UBI, Health Sciences Research Center, University of Beira Interior, Covilhã, Portugal
| | - Xuan Huang
- Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China
| | - Ying Xu
- Department of Cell Biology, College of Medicine, Jiaxing University, Jiaxing, PR China
| | - Weiwei Pan
- Department of Cell Biology, College of Medicine, Jiaxing University, Jiaxing, PR China
| | - Marjo J den Broeder
- Reproductive Biology Group, Division Developmental Biology, Institute of Biodynamics and Biocomplexity, Department of Biology, Faculty of Science, Utrecht University, the Netherlands
| | - Jan Bogerd
- Reproductive Biology Group, Division Developmental Biology, Institute of Biodynamics and Biocomplexity, Department of Biology, Faculty of Science, Utrecht University, the Netherlands
| | - Rüdiger W Schulz
- Reproductive Biology Group, Division Developmental Biology, Institute of Biodynamics and Biocomplexity, Department of Biology, Faculty of Science, Utrecht University, the Netherlands
| | - Kitty C Castricum
- Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, the Netherlands
| | - Victor L Thijssen
- Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, the Netherlands
| | - Shuqun Cheng
- Department of Hepatic Surgery VI, The Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, PR China
| | - Baoyue Ding
- Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China.
| | - Przemek M Krawczyk
- Department of Medical Biology, Cancer Center Amsterdam, Amsterdam UMC Location Academic Medical Center, Amsterdam, the Netherlands; Laboratory of Experimental Oncology and Radiobiology (LEXOR), Cancer Center Amsterdam, Amsterdam UMC Location Academic Medical Center, Amsterdam, the Netherlands
| | - Michal Heger
- Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing, Zhejiang, PR China; Laboratory of Experimental Oncology, Department of Pathology, Erasmus MC, Rotterdam, the Netherlands; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands; Membrane Biochemistry and Biophysics, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, the Netherlands.
| |
Collapse
|
|
21
|
Zhou T, Mahn R, Möhring C, Sadeghlar F, Meyer C, Toma M, Kreppel B, Essler M, Glowka T, Matthaei H, Kalff JC, Strassburg CP, Gonzalez-Carmona MA. Case Report: Sustained complete remission on combination therapy with olaparib and pembrolizumab in BRCA2-mutated and PD-L1-positive metastatic cholangiocarcinoma after platinum derivate. Front Oncol 2022; 12:933943. [PMID: 35957899 PMCID: PMC9359099 DOI: 10.3389/fonc.2022.933943] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Accepted: 06/27/2022] [Indexed: 12/15/2022] Open
Abstract
Cholangiocarcinoma (CCA) still has a poor prognosis and remains a major therapeutic challenge. When curative resection is not possible, palliative systemic chemotherapy with gemcitabine and platinum derivate as first line followed by a 5-FU doublet combination as second line is the standard therapy. Recently, targeted therapy and immunotherapy have rapidly emerged as personalized therapeutic approaches requiring previous tumor sequencing and molecular profiling. BRCA mutations are well-characterized targets for poly (ADP-ribose) polymerase inhibitors (PARPi). However, BRCA gene mutations in CCA are rare and few data of PARPi in the treatment of CCA are available. Immunotherapy with programmed death receptor-1 (PD-1) has been shown to be effective in combination with chemotherapy or in PD-L1-positive CCA. However, data from immunotherapy combined with targeted therapy, including PARPi, are lacking. In this report, we present the case of a male patient with PD-L1-positive and BRCA2-mutated metastatic intrahepatic cholangiocarcinoma, who was treated with a combined therapy with PARP (PARPi), olaparib, and a PD-1 antibody, pembrolizumab, as second-line therapy after gemcitabine/platinum derivate failure. Combined therapy was able to induce a long-lasting complete remission for over 15 months. The combined therapy was feasible and well tolerated. Only mild anemia and immune-related thyroiditis were observed, which were easily manageable and did not result in discontinuation of olaparib and pembrolizumab.
Collapse
Affiliation(s)
- Taotao Zhou
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany
- *Correspondence: Taotao Zhou, ; Maria A. Gonzalez-Carmona,
| | - Robert Mahn
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany
| | - Christian Möhring
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany
| | - Farsaneh Sadeghlar
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany
| | - Carsten Meyer
- Department of Radiology, University Hospital of Bonn, Bonn, Germany
| | - Marieta Toma
- Department of Pathology, University Hospital of Bonn, Bonn, Germany
| | - Barbara Kreppel
- Department of Nuclear Medicine, University Hospital of Bonn, Bonn, Germany
| | - Markus Essler
- Department of Nuclear Medicine, University Hospital of Bonn, Bonn, Germany
| | - Tim Glowka
- Department of Visceral Surgery, University Hospital of Bonn, Bonn, Germany
| | - Hanno Matthaei
- Department of Visceral Surgery, University Hospital of Bonn, Bonn, Germany
| | - Jörg C. Kalff
- Department of Visceral Surgery, University Hospital of Bonn, Bonn, Germany
| | | | - Maria A. Gonzalez-Carmona
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany
- *Correspondence: Taotao Zhou, ; Maria A. Gonzalez-Carmona,
| |
Collapse
|
|
22
|
Li X, Lu H, Ji M, Sun K, Pu F, Ding Y, Hu A. Synthesis and biological properties of maleimide-based macrocyclic lactone enediynes. Org Biomol Chem 2022; 20:5481-5488. [PMID: 35775821 DOI: 10.1039/d2ob00571a] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Natural enediyne antibiotics are powerful DNA-cleavage agents due to the presence of the highly reactive hex-3-ene-1,5-diyne units. However, the complicated chemical structure and thermal instability make their synthesis, derivatization, and storage challenging. Heterocycle-fused enediynes, which exhibit strong antineoplastic activity, are promising analogues of natural enediynes for medicinal applications. To this end, a series of maleimide-based enediynes with macrocyclic lactone moieties were synthesized through the Sonagashira coupling reaction. Differential scanning calorimetry and electron paramagnetic resonance results showed that these macrocyclic enediynes exhibited a rather low onset temperature and the ability to generate radicals at physiological temperature. In addition, the structure-activity relationship of enediynes was analyzed by changing the ring size and the substituents on the propargyl group. Cellular experiments indicated that the diradicals produced by these enediynes efficiently cleaved DNA and disrupted the cell cycle distribution, and consequently induced tumor cell death via an apoptosis pathway at low half inhibitory concentrations. Computational studies suggested that the maleimide moiety promoted the propargyl-allenyl rearrangement of the cyclic enediyne, enabling the generation of diradical species through the Myers-Saito cyclization, and then abstracted hydrogen atoms from the H-donors.
Collapse
Affiliation(s)
- Xiaoxuan Li
- Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
| | - Haotian Lu
- Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
| | - Mingming Ji
- Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
| | - Ke Sun
- Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
| | - Fangxu Pu
- Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
| | - Yun Ding
- Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
| | - Aiguo Hu
- Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
| |
Collapse
|
|
23
|
Advantages of combined photodynamic therapy in the treatment of oncological diseases. Biophys Rev 2022; 14:941-963. [DOI: 10.1007/s12551-022-00962-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 05/24/2022] [Indexed: 12/22/2022] Open
|
|
24
|
Mohammad T, Kahaleh M. Comparing palliative treatment options for cholangiocarcinoma: photodynamic therapy vs. radiofrequency ablation. Clin Endosc 2022; 55:347-354. [PMID: 35578751 PMCID: PMC9178148 DOI: 10.5946/ce.2021.274] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Accepted: 01/06/2022] [Indexed: 11/24/2022] Open
Abstract
Referral to an endoscopist is often done once curative resection is no longer an option for cholangiocarcinoma management. In such cases, palliation has become the main objective of the treatment. Photodynamic therapy and radiofrequency ablation can be performed to achieve palliation, with both procedures associated with improved stent patency and survival. Despite the greatly increased cost and association with photosensitivity, photodynamic therapy allows transmission to the entire biliary tree. In contrast, radiofrequency ablation is cheaper and faster to apply, but requires intraductal contact. This paper reviews both modalities and compares their efficacy and safety for bile duct cancer palliation.
Collapse
Affiliation(s)
- Tayyaba Mohammad
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| | - Michel Kahaleh
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| |
Collapse
|
|
25
|
Multiple Light-Activated Photodynamic Therapy of Tetraphenylethylene Derivative with AIE Characteristics for Hepatocellular Carcinoma via Dual-Organelles Targeting. Pharmaceutics 2022; 14:pharmaceutics14020459. [PMID: 35214196 PMCID: PMC8877525 DOI: 10.3390/pharmaceutics14020459] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 01/07/2022] [Accepted: 01/17/2022] [Indexed: 12/16/2022] Open
Abstract
Photodynamic therapy (PDT) has emerged as a promising locoregional therapy of hepatocellular carcinoma (HCC). The utilization of luminogens with aggregation-induced emission (AIE) characteristics provides a new opportunity to design functional photosensitizers (PS). PSs targeting the critical organelles that are susceptible to reactive oxygen species damage is a promising strategy to enhance the effectiveness of PDT. In this paper, a new PS, 1-[2-hydroxyethyl]-4-[4-(1,2,2-triphenylvinyl)styryl]pyridinium bromide (TPE-Py-OH) of tetraphenylethylene derivative with AIE feature was designed and synthesized for PDT. The TPE-Py-OH can not only simultaneously target lipid droplets and mitochondria, but also stay in cells for a long period (more than 7 days). Taking advantage of the long retention ability of TPE-Py-OH in tumor, the PDT effect of TPE-Py-OH can be activated through multiple irradiations after one injection, which provides a specific multiple light-activated PDT effect. We believe that this AIE-active PS will be promising for the tracking and photodynamic ablation of HCC with sustained effectiveness.
Collapse
|
|
26
|
Bitzer M, Voesch S, Albert J, Bartenstein P, Bechstein W, Blödt S, Brunner T, Dombrowski F, Evert M, Follmann M, La Fougère C, Freudenberger P, Geier A, Gkika E, Götz M, Hammes E, Helmberger T, Hoffmann RT, Hofmann WP, Huppert P, Kautz A, Knötgen G, Körber J, Krug D, Lammert F, Lang H, Langer T, Lenz P, Mahnken A, Meining A, Micke O, Nadalin S, Nguyen HP, Ockenga J, Oldhafer K, Paprottka P, Paradies K, Pereira P, Persigehl T, Plauth M, Plentz R, Pohl J, Riemer J, Reimer P, Ringwald J, Ritterbusch U, Roeb E, Schellhaas B, Schirmacher P, Schmid I, Schuler A, von Schweinitz D, Seehofer D, Sinn M, Stein A, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Tholen R, Vogel A, Vogl T, Vorwerk H, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wittekind C, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e186-e227. [PMID: 35148560 DOI: 10.1055/a-1589-7854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Affiliation(s)
- M Bitzer
- Medizinische Klinik I, Universitätsklinikum Tübingen
| | - S Voesch
- Medizinische Klinik I, Universitätsklinikum Tübingen
| | - J Albert
- Abteilung für Gastroenterologie, Hepatologie und Endokrinologie, Robert-Bosch-Krankenhaus, Stuttgart
| | - P Bartenstein
- Klinik und Poliklinik für Nuklearmedizin, LMU Klinikum, München
| | - W Bechstein
- Klinik für Allgemein-, Viszeral-, Transplantations- und Thoraxchirurgie, Universitätsklinikum Frankfurt
| | - S Blödt
- AWMF-Geschäftsstelle, Berlin
| | - T Brunner
- Klinik für Strahlentherapie, Universitätsklinikum Magdeburg
| | - F Dombrowski
- Institut für Pathologie, Universitätsmedizin Greifswald
| | - M Evert
- Institut für Pathologie, Regensburg
| | - M Follmann
- Office des Leitlinienprogrammes Onkologie, c/o Deutsche Krebsgesellschaft e.V., Berlin
| | - C La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Tübingen
| | | | - A Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - E Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | | | - E Hammes
- Lebertransplantierte Deutschland e. V., Ansbach
| | - T Helmberger
- Institut für Radiologie, Neuroradiologie und minimal-invasive Therapie, München Klinik Bogenhausen, München
| | - R T Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Dresden
| | - W P Hofmann
- Gastroenterologie am Bayerischen Platz, medizinisches Versorgungszentrum, Berlin
| | - P Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühl
| | - A Kautz
- Deutsche Leberhilfe e.V., Köln
| | - G Knötgen
- Konferenz onkologischer Kranken- und Kinderkrankenpflege, Hamburg
| | - J Körber
- Klinik Nahetal, Fachklinik für onkologische Rehabilitation und Anschlussrehabilitation, Bad Kreuznach
| | - D Krug
- Klinik für Strahlentherapie, Universitätsklinikum Schleswig-Holstein, Kiel
| | | | - H Lang
- Klinik für Allgemein-, Viszeral und Transplantationschirurgie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz
| | - T Langer
- Office des Leitlinienprogrammes Onkologie, c/o Deutsche Krebsgesellschaft e.V., Berlin
| | - P Lenz
- Universitätsklinikum Münster, Zentrale Einrichtung Palliativmedizin, Münster
| | - A Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Gießen und Marburg GmbH, Marburg
| | - A Meining
- Medizinische Klinik und Poliklinik II des Universitätsklinikums Würzburg
| | - O Micke
- Klinik für Strahlentherapie und Radioonkologie, Franziskus Hospital Bielefeld
| | - S Nadalin
- Universitätsklinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen
| | | | - J Ockenga
- Medizinische Klinik II, Klinikum Bremen-Mitte, Bremen
| | - K Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Semmelweis Universität, Asklepios Campus Hamburg
| | - P Paprottka
- Abteilung für interventionelle Radiologie, Klinikum rechts der Isar der Technischen Universität München
| | - K Paradies
- Konferenz onkologischer Kranken- und Kinderkrankenpflege, Hamburg
| | - P Pereira
- Abteilung für interventionelle Radiologie, Klinikum rechts der Isar der Technischen Universität München
| | - T Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | | | - R Plentz
- Klinikum Bremen-Nord, Innere Medizin, Bremen
| | - J Pohl
- Interventionelles Endoskopiezentrum und Schwerpunkt Gastrointestinale Onkologie, Asklepios Klinik Altona, Hamburg
| | - J Riemer
- Lebertransplantierte Deutschland e. V., Bretzfeld
| | - P Reimer
- Institut für diagnostische und interventionelle Radiologie, Städtisches Klinikum Karlsruhe gGmbH, Karlsruhe
| | - J Ringwald
- Psychosomatische Medizin und Psychotherapie, Universitätsklinikum Tübingen
| | | | - E Roeb
- Medizinische Klinik II, Universitätsklinikum Gießen und Marburg GmbH, Gießen
| | - B Schellhaas
- Medizinische Klinik I, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen
| | - P Schirmacher
- Pathologisches Institut, Universitätsklinikum Heidelberg
| | - I Schmid
- Zentrum Pädiatrische Hämatologie und Onkologie, Dr. von Haunersches Kinderspital, Klinikum der Universität München
| | - A Schuler
- Medizinische Klinik, Alb Fils Kliniken GmbH, Göppingen
| | | | - D Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - M Sinn
- Medizinische Klinik II, Universitätsklinikum Hamburg-Eppendorf
| | - A Stein
- Hämatologisch-Onkologischen Praxis Eppendorf, Hamburg
| | - A Stengel
- Psychosomatische Medizin und Psychotherapie, Universitätsklinikum Tübingen
| | | | - C Stoll
- Klinik Herzoghöhe Bayreuth, Bayreuth
| | - A Tannapfel
- Institut für Pathologie der Ruhr-Universität Bochum am Berufsgenossenschaftlichen Universitätsklinikum Bergmannsheil, Bochum
| | - A Taubert
- Kliniksozialdienst, Universitätsklinikum Heidelberg, Bochum
| | - J Trojan
- Medizinische Klinik I, Universitätsklinikum Frankfurt, Frankfurt am Main
| | | | - R Tholen
- Deutscher Verband für Physiotherapie e. V., Köln
| | - A Vogel
- Klinik für Gastroenterologie, Hepatologie, Endokrinologie der Medizinischen Hochschule Hannover, Hannover
| | - T Vogl
- Universitätsklinikum Frankfurt, Institut für Diagnostische und Interventionelle Radiologie, Frankfurt
| | - H Vorwerk
- Klinik für Strahlentherapie, Universitätsklinikum Gießen und Marburg GmbH, Marburg
| | - F Wacker
- Institut für Diagnostische und Interventionelle Radiologie der Medizinischen Hochschule Hannover, Hannover
| | - O Waidmann
- Medizinische Klinik I, Universitätsklinikum Frankfurt, Frankfurt am Main
| | - H Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie Medizinische Hochschule Hannover, Hannover
| | - H Wege
- Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg
| | - D Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Lauf an der Pegnitz
| | - C Wittekind
- Institut für Pathologie, Universitätsklinikum Leipzig, Leipzig
| | - M A Wörns
- Medizinische Klinik und Poliklinik, Universitätsklinikum Mainz, Mainz
| | - P Galle
- Medizinische Klinik und Poliklinik, Universitätsklinikum Mainz, Mainz
| | - N Malek
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
| |
Collapse
|
|
27
|
Mohan BP, Chandan S, Khan SR, Kassab LL, Ponnada S, Artifon ELA, Otoch JP, McDonough S, Adler DG. Photodynamic Therapy (PDT), Radiofrequency Ablation (RFA) With Biliary Stents in Palliative Treatment of Unresectable Extrahepatic Cholangiocarcinoma: A Systematic Review and Meta-analysis. J Clin Gastroenterol 2022; 56:e153-e160. [PMID: 33780214 DOI: 10.1097/mcg.0000000000001524] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 01/29/2021] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIM Extrahepatic unresectable cholangiocarcinoma carries a dismal prognosis. In addition to biliary drainage by stent placement; photodynamic therapy (PDT) and radiofrequency ablation (RFA) have been tried to prolong survival. In this meta-analysis, we appraise the current known data on the use of PDT, RFA in the palliative treatment of extrahepatic unresectable cholangiocarcinoma. METHODS We searched multiple databases from inception through July 2020 to identify studies that reported on PDT and RFA. Pooled rates of survival, stent patency, 30-, 90-day mortality, and adverse events were calculated. Study heterogeneity was assessed using I2% and 95% prediction interval. RESULTS A total of 55 studies (2146 patients) were included. A total of 1149 patients underwent treatment with PDT (33 studies), 545 with RFA (22 studies), and 452 patients with stent-only strategy. The pooled survival rate with PDT, RFA, and stent-only groups was 11.9 [95% confidence interval (CI): 10.7-13.1] months, 8.1 (95% CI: 6.4-9.9) months, and 6.7 (95% CI: 4.9-8.4) months, respectively. The pooled time of stent patency with PDT, RFA, and stent-only groups was 6.1 (95% CI: 4.2-8) months, 5.5 (95% CI: 4.2-6.7) months, and 4.7 (95% CI: 2.6-6.7) months, respectively. The pooled rate of 30-day mortality with PDT was 3.3% (95% CI: 1.6%-6.7%), with RFA was 7% (95% CI: 4.1%-11.7%) and with stent-only was 4.9% (95% CI: 1.7%-13.1%). The pooled rate of 90-day mortality with PDT was 10.4% (95% CI: 5.4%-19.2%) and with RFA was 16.3% (95% CI: 8.7%-28.6%). CONCLUSION PDT seemed to demonstrate better overall survival and 30-day mortality rates than RFA and/or stent-only palliation.
Collapse
Affiliation(s)
- Babu P Mohan
- Division of Gastroenterology and Hepatology, University of Utah School of Medicine, Salt Lake City, UT
| | - Saurabh Chandan
- Department of Gastroenterology and Hepatology, CHI-Creighton University Medical Center, Omaha, NE
| | - Shahab R Khan
- Section of Gastroenterology, Rush University Medical Center, Chicago, IL
| | - Lena L Kassab
- Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - Suresh Ponnada
- Department of Internal Medicine, Carilion Roanoke Memorial Hospital, Roanoke, VA
| | - Everson L A Artifon
- Gastrointestinal Endoscopy Unit, Hospital Das Clinicas, University of Sao Paulo, Sao Paulo, Brazil
| | - Jose P Otoch
- Gastrointestinal Endoscopy Unit, Hospital Das Clinicas, University of Sao Paulo, Sao Paulo, Brazil
| | - Stephanie McDonough
- Division of Gastroenterology and Hepatology, University of Utah School of Medicine, Salt Lake City, UT
| | - Douglas G Adler
- Division of Gastroenterology and Hepatology, University of Utah School of Medicine, Salt Lake City, UT
| |
Collapse
|
|
28
|
Gonzalez-Carmona MA, Möhring C, Mahn R, Zhou T, Bartels A, Sadeghlar F, Bolch M, Vogt A, Kaczmarek DJ, Heling DJ, Dold L, Nattermann J, Branchi V, Matthaei H, Manekeller S, Kalff JC, Strassburg CP, Mohr RU, Weismüller TJ. Impact of regular additional endobiliary radiofrequency ablation on survival of patients with advanced extrahepatic cholangiocarcinoma under systemic chemotherapy. Sci Rep 2022; 12:1011. [PMID: 35046437 PMCID: PMC8770452 DOI: 10.1038/s41598-021-04297-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Accepted: 12/07/2021] [Indexed: 12/12/2022] Open
Abstract
Prognosis of patients with advanced extrahepatic cholangiocarcinoma (eCCA) is poor. The current standard first-line treatment is systemic chemotherapy (CT) with gemcitabine and a platinum derivate. Additionally, endobiliary radiofrequency ablation (eRFA) can be applied to treat biliary obstructions. This study aimed to evaluate the additional benefit of scheduled regular eRFA in a real-life patient cohort with advanced extrahepatic cholangiocarcinoma under standard systemic CT. All patients with irresectable eCCA treated at University Hospital Bonn between 2010 and 2020 were eligible for inclusion. Patients were stratified according to treatment: standard CT (n = 26) vs. combination of eRFA with standard CT (n = 40). Overall survival (OS), progression free survival (PFS), feasibility and toxicity were retrospectively analyzed using univariate and multivariate approaches. Combined eRFA and CT resulted in significantly longer median OS (17.3 vs. 8.6 months, p = 0.004) and PFS (12.9 vs. 5.7 months, p = 0.045) compared to the CT only group. While groups did not differ regarding age, sex, tumor stage and chemotherapy treatment regimen, mean MELD was even higher (10.1 vs. 6.7, p = 0.015) in the eRFA + CT group. The survival benefit of concomitant eRFA was more evident in the subgroup with locally advanced tumors. Severe hematological toxicities (CTCAE grades 3 - 5) did not differ significantly between the groups. However, therapy-related cholangitis occurred more often in the combined treatment group (p = 0.031). Combination of eRFA and systemic CT was feasible, well-tolerated and could significantly prolong survival compared to standard CT alone. Thus, eRFA should be considered during therapeutic decision making in advanced eCCA.
Collapse
Affiliation(s)
- Maria A Gonzalez-Carmona
- Department of Internal Medicine I, University Hospital of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.
| | - Christian Möhring
- Department of Internal Medicine I, University Hospital of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Robert Mahn
- Department of Internal Medicine I, University Hospital of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Taotao Zhou
- Department of Internal Medicine I, University Hospital of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Alexandra Bartels
- Department of Internal Medicine I, University Hospital of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Farsaneh Sadeghlar
- Department of Internal Medicine I, University Hospital of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Maximilian Bolch
- Department of Internal Medicine I, University Hospital of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Annabelle Vogt
- Department of Internal Medicine I, University Hospital of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Dominik J Kaczmarek
- Department of Internal Medicine I, University Hospital of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Dominik J Heling
- Department of Internal Medicine I, University Hospital of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Leona Dold
- Department of Internal Medicine I, University Hospital of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Jacob Nattermann
- Department of Internal Medicine I, University Hospital of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Vittorio Branchi
- Department of Surgery, University Hospital of Bonn, Bonn, Germany
| | - Hanno Matthaei
- Department of Surgery, University Hospital of Bonn, Bonn, Germany
| | | | - Jörg C Kalff
- Department of Surgery, University Hospital of Bonn, Bonn, Germany
| | - Christian P Strassburg
- Department of Internal Medicine I, University Hospital of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Raphael U Mohr
- Department of Internal Medicine I, University Hospital of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany
| | - Tobias J Weismüller
- Department of Internal Medicine I, University Hospital of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.
| |
Collapse
|
|
29
|
Privitera L, Paraboschi I, Cross K, Giuliani S. Above and Beyond Robotic Surgery and 3D Modelling in Paediatric Cancer Surgery. Front Pediatr 2021; 9:777840. [PMID: 34988038 PMCID: PMC8721224 DOI: 10.3389/fped.2021.777840] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 11/17/2021] [Indexed: 12/15/2022] Open
Abstract
Although the survival rates for children's cancers have more than doubled in the last few decades, the surgical practise has not significantly changed. Among the most recent innovations introduced in the clinic, robotic surgery and augmented reality are two of the most promising, even if they are not widespread. The increased flexibility of the motion, the magnification of the surgical field and the tremor reduction provided by robotic surgery have been beneficial to perform complex oncological procedures in children. Besides, augmented reality has been proven helpful in planning for tumour removal, facilitating early discrimination between cancer and healthy organs. Nowadays, research in the field of surgical oncology is moving fast, and new technologies and innovations wich will help to shape a new way to perform cancer surgery. Paediatric surgeons need to be ready to adopt these novel devices and intraoperative techniques to allow more radical tumour resections with fewer complications. This review aims to present the mechanism of action and indications of several novel technologies such as optical imaging surgery, high definition cameras, and intraoperative loco-regional treatments. We hope this will enhance early adoption and more research on how to employ technology for the benefit of children.
Collapse
Affiliation(s)
- Laura Privitera
- Wellcome/Engineering and Physical Sciences Research Council Centre for Interventional & Surgical Sciences, University College London, London, United Kingdom
- Developmental Biology and Cancer Department, University College London Great Ormond Street Institute of Child Health, London, United Kingdom
| | - Irene Paraboschi
- Wellcome/Engineering and Physical Sciences Research Council Centre for Interventional & Surgical Sciences, University College London, London, United Kingdom
- Developmental Biology and Cancer Department, University College London Great Ormond Street Institute of Child Health, London, United Kingdom
| | - Kate Cross
- Department of Specialist Neonatal and Paediatric Surgery, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
| | - Stefano Giuliani
- Wellcome/Engineering and Physical Sciences Research Council Centre for Interventional & Surgical Sciences, University College London, London, United Kingdom
- Developmental Biology and Cancer Department, University College London Great Ormond Street Institute of Child Health, London, United Kingdom
- Department of Specialist Neonatal and Paediatric Surgery, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
| |
Collapse
|
|
30
|
Yang Y, Li J, Yao L, Wu L. Effect of Photodynamic Therapy on Gemcitabine-Resistant Cholangiocarcinoma in vitro and in vivo Through KLF10 and EGFR. Front Cell Dev Biol 2021; 9:710721. [PMID: 34805140 PMCID: PMC8595284 DOI: 10.3389/fcell.2021.710721] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 09/16/2021] [Indexed: 12/15/2022] Open
Abstract
Cholangiocarcinoma is a relatively rare neoplasm with increasing incidence. Although chemotherapeutic agent such as gemcitabine has long been used as standard treatment for cholangiocarcinoma, the interindividual variability in target and drug sensitivity and specificity may lead to therapeutic resistance. In the present study, we found that photodynamic therapy (PDT) treatment inhibited gemcitabine-resistant cholangiocarcinoma cells via repressing cell viability, enhancing cell apoptosis, and eliciting G1 cell cycle arrest through modulating Cyclin D1 and caspase 3 cleavage. In vivo, PDT treatment significantly inhibited the growth of gemcitabine-resistant cholangiocarcinoma cell-derived tumors. Online data mining and experimental analyses indicate that KLF10 expression was induced, whereas EGFR expression was downregulated by PDT treatment; KLF10 targeted the EGFR promoter region to inhibit EGFR transcription. Under PDT treatment, EGFR overexpression and KLF10 silencing attenuated the anti-cancer effects of PDT on gemcitabine-resistant cholangiocarcinoma cells by promoting cell viability, inhibiting apoptosis, and increasing S phase cell proportion. Importantly, under PDT treatment, the effects of KLF10 silencing were significantly reversed by EGFR silencing. In conclusion, PDT treatment induces KLF10 expression and downregulates EGFR expression. KLF10 binds to EGFR promoter region to inhibit EGFR transcription. The KLF10/EGFR axis participates in the process of the inhibition of PDT on gemcitabine-resistant cholangiocarcinoma cells.
Collapse
Affiliation(s)
- Yang Yang
- Department of Clinical Pathology, Hunan Cancer Hospital, Changsha, China.,Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Jigang Li
- Department of Clinical Pathology, Hunan Cancer Hospital, Changsha, China
| | - Lei Yao
- Academician Expert Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Lile Wu
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| |
Collapse
|
|
31
|
John ES, Tarnasky PR, Kedia P. Ablative therapies of the biliary tree. Transl Gastroenterol Hepatol 2021; 6:63. [PMID: 34805585 DOI: 10.21037/tgh.2020.02.03] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 01/23/2020] [Indexed: 01/04/2023] Open
Abstract
Cholangiocarcinoma, a malignancy of the epithelial cells in the intrahepatic or extrahepatic biliary tree, is often diagnosed at later stages. Median survival duration ranges from 3 to 9 months with a less than ten percent 5-year survival rate. Thus, often treatment strategies are aimed more towards palliation instead of cure. With the majority of patients presenting with unresectable disease at the time of diagnosis, surgical intervention is not feasible, making less invasive endoscopic therapies more suitable. Initially, biliary stents were utilized for biliary decompression to mitigate cholestatic symptoms and prevent cholangitis; however, this strategy did not prove to provide significant survival benefit. Therefore, efforts to treat the tumor burden itself in addition to maintaining biliary patency became a focus of innovation and research in the endoscopic field. This study has led to the advent of therapies such as photodynamic therapy, radiofrequency ablation, and intraluminal brachytherapy. These options combined with biliary stenting have shown to not only offer the benefit of biliary decompression, but also to potentially improve stent patency and survival. Further, there is an anti-tumor effect of each of these modalities, portending an additional benefit in this subset of patients. Despite numerous retrospective and prospective studies assessing these ablative therapies, there is still a paucity of appropriately powered randomized controlled trials, and further research has yet to be done in the field. This review details the current literature entailing endobiliary ablative strategies.
Collapse
Affiliation(s)
- Elizabeth S John
- Department of Gastroenterology, Methodist Dallas Medical Center, Dallas, TX, USA
| | - Paul R Tarnasky
- Department of Gastroenterology, Methodist Dallas Medical Center, Dallas, TX, USA
| | - Prashant Kedia
- Department of Gastroenterology, Methodist Dallas Medical Center, Dallas, TX, USA
| |
Collapse
|
|
32
|
Weisheit S, Wegner CS, Ailte I, Radulovic M, Weyergang A, Kristian Selbo P, Brech A. Inhibiting autophagy increases the efficacy of low-dose photodynamic therapy. Biochem Pharmacol 2021; 194:114837. [PMID: 34780750 DOI: 10.1016/j.bcp.2021.114837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 11/08/2021] [Accepted: 11/09/2021] [Indexed: 11/24/2022]
Abstract
Rupture and permeabilization of endocytic vesicles can be triggered by various causes, such as pathogenic invasions, amyloid proteins, and silica crystals leading to cell death and degeneration. A cellular quality control process, called lysophagy was recently described to target damaged lysosomes for autophagic sequestration within isolation membranes in order to protect the cell from the consequences of lysosomal leakage. This protective process, however, might interfere with treatment conditions, such as photodynamic therapy (PDT) and the intracellular drug delivery method photochemical internalization (PCI). PCI-induced permeabilization of endosomes and lysosomes is purposely triggered to release drugs that are sequestered in these organelles into the cytosol in order to synergistically kill cancer cells. Here, we show that photochemical treatment with the PCI-photosensitizer TPCS2a/fimaporfin results in both induction of autophagy and inhibition of the autophagic flux. The autophagic response is accompanied by recruitment of ubiquitin (Ubq), p62, and microtubule-associated protein 1A/1B-light chain 3 (LC3) to damaged vesicles, marked by Galectin 3 (Gal3). Furthermore, ultrastructural analysis revealed a homogenously thick p62-positive layer surrounding these permeabilized vesicles. Although p62 seems to be important during the selective autophagic sequestration, we show that its presence is not essential for the effective removal of damaged vesicles or the recovery of the lysosomal content. An active autophagic response and the presence of p62, however, is important for cancer cells to survive low-dose TPCS2a-PDT. Thus, targeting both p62 and autophagy together and independently, in a light-controlled/PCI based delivery of cancer therapeutics could increase the effectiveness of the treatment regime.
Collapse
Affiliation(s)
- Sabine Weisheit
- Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0379 Oslo, Norway
| | - Catherine S Wegner
- Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0379 Oslo, Norway
| | - Ieva Ailte
- Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0379 Oslo, Norway
| | - Maja Radulovic
- Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0379 Oslo, Norway
| | - Anette Weyergang
- Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0379 Oslo, Norway
| | - Pål Kristian Selbo
- Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0379 Oslo, Norway
| | - Andreas Brech
- Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0379 Oslo, Norway.
| |
Collapse
|
|
33
|
Sobhani N, Samadani AA. Implications of photodynamic cancer therapy: an overview of PDT mechanisms basically and practically. J Egypt Natl Canc Inst 2021; 33:34. [PMID: 34778919 DOI: 10.1186/s43046-021-00093-1] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 09/24/2021] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Tumor eradication is one of the most important challengeable categories in oncological studies. In this account, besides the molecular genetics methods including cell therapy, gene therapy, immunotherapy, and general cancer therapy procedures like surgery, radiotherapy, and chemotherapy, photodynamic adjuvant therapy is of great importance. Photodynamic therapy (PDT) as a relatively noninvasive therapeutic method utilizes the irradiation of an appropriate wavelength which is absorbed by a photosensitizing agent in the presence of oxygen. In this procedure, a series of events lead to the direct death of malignant cells such as damage to the microvasculature and also the induction of a local inflammatory function. PDT has participated with other treatment modalities especially in the early stage of malignant tumors and has resulted in decreasing morbidity besides improving survival rate and quality of life. High spatial resolution of PDT has attracted considerable attention in the field of image-guided photodynamic therapy combined with chemotherapy of multidrug resistance cancers. Although PDT outcomes vary across the different tumor types, minimal natural tissue toxicity, minor systemic effects, significant reduction in long-term disease, lack of innate or acquired resistance mechanisms, and excellent cosmetic effects, as well as limb function, make it a valuable treatment option for combination therapies. SHORT CONCLUSION In this review article, we tried to discuss the potential of PDT in the treatment of some dermatologic and solid tumors, particularly all its important mechanisms.
Collapse
Affiliation(s)
- Nafiseh Sobhani
- Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Ali Akbar Samadani
- Healthy Ageing Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran. .,Clinical Research Development Unit of Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran.
| |
Collapse
|
|
34
|
Möhring C, Feder J, Mohr RU, Sadeghlar F, Bartels A, Mahn R, Zhou T, Marinova M, Feldmann G, Brossart P, von Websky M, Matthaei H, Manekeller S, Glowka T, Kalff JC, Weismüller TJ, Strassburg CP, Gonzalez-Carmona MA. First Line and Second Line Chemotherapy in Advanced Cholangiocarcinoma and Impact of Dose Reduction of Chemotherapy: A Retrospective Analysis. Front Oncol 2021; 11:717397. [PMID: 34858809 PMCID: PMC8631360 DOI: 10.3389/fonc.2021.717397] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 10/22/2021] [Indexed: 12/30/2022] Open
Abstract
OBJECTIVE Prognosis of patients with irresectable cholangiocarcinoma is still poor. The ABC-02 trial established the current first line (1L) standard systemic chemotherapy (CT) with gemcitabine/platinum derivate for advanced cholangiocarcinoma. However, the majority of patients needed therapy adaptions. Thus, the aim of this study was to evaluate 1L and second line (2L) therapy regimens and the impact of therapy adaptions in an unselected real-life cohort of patients with advanced cholangiocarcinoma. MATERIALS AND METHODS This is a single institution retrospective analysis of patients with irresectable cholangiocarcinoma who were treated with gemcitabine/platinum derivate from 2010 to 2018. Overall survival (OS), progression-free survival (PFS) and toxicity were analyzed for all patients, especially with regard to CT de-escalation. RESULTS Fifty-eight patients receiving gemcitabine/platinum derivate were included in the analysis. Median OS and PFS were 12.2 and 6.9 months. Interestingly, 41 patients (71%) needed therapy de-escalation. However, despite reduced CT exposition, there was no-significant difference in OS (10.8 months vs. 15.6 months, p = 0.127), and patients suffered from less adverse events during CT. 21 (36%) patients reached 2L CT, most often with FOLFIRI (57%). Survival beyond the end of 1L CT was 7.1 months with 2L CT vs. 2.9 months with BSC. CONCLUSION In our study, the combination of gemcitabine/platinum derivate showed similar OS and PFS as randomized prospective phase II/III trials. Therapy regimen adaptions were needed in the majority of patients. However, individualized modifications of the therapy regimen allowed better tolerance as well as continuation of therapy and did not significantly influence median OS. Furthermore, our study revealed a potential survival benefit with 2L CT for selected patients.
Collapse
Affiliation(s)
- Christian Möhring
- Department of Internal Medicine I, University Hospital, Bonn, Germany
| | - Jan Feder
- Department of Internal Medicine I, University Hospital, Bonn, Germany
| | - Raphael U. Mohr
- Department of Internal Medicine I, University Hospital, Bonn, Germany
| | | | - Alexandra Bartels
- Department of Internal Medicine I, University Hospital, Bonn, Germany
| | - Robert Mahn
- Department of Internal Medicine I, University Hospital, Bonn, Germany
| | - Taotao Zhou
- Department of Internal Medicine I, University Hospital, Bonn, Germany
| | - Milka Marinova
- Department of Radiology, University Hospital, Bonn, Germany
| | - Georg Feldmann
- Department of Internal Medicine III, University Hospital, Bonn, Germany
| | - Peter Brossart
- Department of Internal Medicine III, University Hospital, Bonn, Germany
| | - Martin von Websky
- Department of Internal Medicine III, University Hospital, Bonn, Germany
| | - Hanno Matthaei
- Department of Internal Medicine III, University Hospital, Bonn, Germany
| | | | - Tim Glowka
- Department of Internal Medicine III, University Hospital, Bonn, Germany
| | - Jörg C. Kalff
- Department of Internal Medicine III, University Hospital, Bonn, Germany
| | | | | | | |
Collapse
|
|
35
|
Could Photodynamic Therapy Be a Promising Therapeutic Modality in Hepatocellular Carcinoma Patients? A Critical Review of Experimental and Clinical Studies. Cancers (Basel) 2021; 13:cancers13205176. [PMID: 34680325 PMCID: PMC8534013 DOI: 10.3390/cancers13205176] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 09/22/2021] [Accepted: 10/02/2021] [Indexed: 12/16/2022] Open
Abstract
Simple Summary Hepatocellular Carcinoma (HCC) is one of the leading causes of cancer-associated mortality worldwide. With a limited number of therapeutic options available and a lack of effective anti-tumoral immune responses by the therapies, there is a dire need to search for new translational treatment options. Photodynamic Therapy (PDT), in recent years, has proven itself as an effective anti-cancer therapy. In this review, we discuss the mechanism of PDT, its evolution as an anti-cancer modality, with a special focus on HCC. We also highlight the immune response generated by PDT and how it could be essential in HCC treatment. Finally, we proposed an intraoperative procedure for the treatment of HCC by combining hepatectomy with PDT. Abstract Photodynamic Therapy (PDT) relies on local or systemic administration of a light-sensitive dye, called photosensitizer, to accumulate into the target site followed by excitation with light of appropriate wavelength and fluence. This photo-activated molecule reacts with the intracellular oxygen to induce selective cytotoxicity of targeted cells by the generation of reactive oxygen species. Hepatocellular carcinoma (HCC), one of the leading causes of cancer-associated mortality worldwide, has insufficient treatment options available. In this review, we discuss the mechanism and merits of PDT along with its recent developments as an anti-cancerous therapy. We also highlight the application of this novel therapy for diagnosis, visualization, and treatment of HCC. We examine the underlying challenges, some pre-clinical and clinical studies, and possibilities of future studies associated with PDT. Finally, we discuss the mechanism of an active immune response by PDT and thereafter explored the role of PDT in the generation of anti-tumor immune response in the context of HCC, with an emphasis on checkpoint inhibitor-based immunotherapy. The objective of this review is to propose PDT as a plausible adjuvant to existing therapies for HCC, highlighting a feasible combinatorial approach for HCC treatment.
Collapse
|
|
36
|
Nguyen MLT, Toan NL, Bozko M, Bui KC, Bozko P. Cholangiocarcinoma Therapeutics: An Update. Curr Cancer Drug Targets 2021; 21:457-475. [PMID: 33563168 DOI: 10.2174/1568009621666210204152028] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 11/12/2020] [Accepted: 11/20/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Cholangiocarcinoma (CCA) is the second most common hepatobiliary cancer and associated with a poor prognosis. Only one-third of CCA cases are diagnosed at operable stages. However, a high rate of relapse has been observed postoperatively. Besides screening for operable individuals, efficacious therapeutic for recurrent and advanced CCA is urgently needed. The treatment outcome of available therapeutics is important to clarify clinical indication and facilitate the development of treatment strategies. OBJECTIVE This review aims to compare the treatment outcome of different therapeutics based on both overall survival and progression-free survival. METHODS Over one hundred peer-reviewed articles were examined. We compared the treatment outcome between different treatment methods, including tumor resection with or without postoperative systematic therapy, chemotherapies including FOFLOX, and targeted therapies, such as IDH1, K-RAS, and FGFR inhibitors. Notably, the scientific basis and outcome of available treatment methods were compared with the standard first-line therapy. RESULTS CCAs at early stages should firstly undergo tumor resection surgery, followed by postoperative treatment with Capecitabine. Chemotherapy can be considered as a preoperative option for unresectable CCAs. Inoperable CCAs with genetic aberrances like FGFR alterations, IDH1, and KRAS mutations should be considered with targeted therapies. Fluoropyrimidine prodrug (S-1)/Gemcitabine/Cisplatin and nab-Paclitaxel/Gemcitabine/Cisplatin show favorable outcome which hints at the triplet regimen to be superior to Gemcitabine/Cisplatin on CCA. The triplet chemotherapeutic should be tested further compared to Gemcitabine/Cisplatin among CCAs without genetic alterations. Gemcitabine plus S-1 was recently suggested as the convenient and equivalent standard first-line for advanced/recurrent biliary tract cancer. CONCLUSION This review provides a comparative outcome between novel targeted therapies and currently available therapeutics.
Collapse
Affiliation(s)
- Mai Ly Thi Nguyen
- Department of Internal Medicine I, Universitätsklinikum Tübingen, Tübingen, Germany
| | - Nguyen Linh Toan
- Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam
| | - Maria Bozko
- Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Poland
| | - Khac Cuong Bui
- Department of Internal Medicine I, Universitätsklinikum Tübingen, Tübingen, Germany
| | - Przemyslaw Bozko
- Department of Internal Medicine I, Universitätsklinikum Tübingen, Tübingen, Germany
| |
Collapse
|
|
37
|
Lu H, Wang W, Li X, Zhang M, Cheng X, Sun K, Ding Y, Li X, Hu A. A carrier-free nanoparticle with dual NIR/acid responsiveness by co-assembly of enediyne and IR820 for combined PTT/chemotherapy. J Mater Chem B 2021; 9:4056-4064. [PMID: 33949615 DOI: 10.1039/d1tb00279a] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Combined photothermal therapy/chemotherapy by co-delivery of a photosensitizer (PS) and a chemotherapeutic drug has demonstrated great potential for cancer treatment. The intrinsic drawbacks of traditional drug delivery systems (DDSs), such as tedious synthetic procedures, side effects originated from the carrier materials, low loading efficiency, and uncontrolled drug release, however, have impaired their further advancement. On the other hand, enediyne antibiotics are highly cytotoxic toward cancer cells through the generation of lethal carbon radicals via thermal-induced cyclization, endowing them with great potential to achieve enhanced synergistic anticancer performance by incorporation with the photothermal effect of PS. To this end, a carrier-free and NIR/acid dual-responsive DDS was constructed for combined photothermal therapy/chemotherapy. The facile co-assembly of maleimide-based enediyne and PS IR820 was achieved in aqueous solution to give nanoparticles (EICN) with a hydrodynamic diameter of 90 nm and high stability. In vitro study confirmed the acid/NIR dual-responsive degradation and drug release, free radical generation and DNA-cleaving ability of EICN, which was accomplished by the corporation of enediyne and IR820 moieties. Further tests on HeLa cells verified the excellent synergistic anticancer performance of EICN including the improved cellular uptake, NIR-enhanced drug release, DNA damage and histone deacetylase inhibitor capacity. Overall, this carrier-free DDS with dual acid/NIR-responsivity would potentially provide new insights for the development of combined photothermal/chemotherapy.
Collapse
Affiliation(s)
- Haotian Lu
- Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
| | - Wenbo Wang
- Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
| | - Xiaoxuan Li
- Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
| | - Mengsi Zhang
- Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
| | - Xiaoyu Cheng
- Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
| | - Ke Sun
- Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
| | - Yun Ding
- Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
| | - Xinxin Li
- Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
| | - Aiguo Hu
- Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
| |
Collapse
|
|
38
|
Zheng YW, Miao XY, Xiong L, Chen B, Kong FH, Zhou JJ, Liu ZT, Wen Y, Zhang ZJ, Zou H. Sulfasalazine Sensitizes Polyhematoporphyrin-Mediated Photodynamic Therapy in Cholangiocarcinoma by Targeting xCT. Front Pharmacol 2021; 12:723488. [PMID: 34483935 PMCID: PMC8414975 DOI: 10.3389/fphar.2021.723488] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 07/27/2021] [Indexed: 01/17/2023] Open
Abstract
Cholangiocarcinoma (CCA), which is highly malignant, shows a relatively poor prognosis, due to the insensitivity of the tumour to chemotherapy and radiotherapy. Photodynamic therapy (PDT) has become a promising palliative therapeutic option for patients with unresectable cholangiocarcinoma (CCA), while the functional amount of ROS is limited by intracellular redox systemen. Sulfasalazine (SASP), a well-known anti-inflammatory agent, which also acts as an inhibitor of the amino acid transport system xc (xCT), decreases the intracellular glutathione (GSH) level, thus weakening the antioxidant defence of the cell by inhibition of the antiporter. However, the combination of SASP and PDT remains unexplored. We have reported that polyhematoporphyrin (PHP)-mediated PDT inhibits the cell viability of CCA cells and organoids. Furthermore, in PHP-enriched HCCC-9810 and TFK-1CCA cells, SASP enhances the sensitivity to PHP-mediated PDT through a GSH-dependent mechanism. We found that PHP-PDT can up-regulate xCT expression to promote cells against overloaded ROS, while SASP reduces GSH levels. After the combination of SASP and PHP-PDT, cell viability and GSH levels were significantly inhibited. xCT was also observed to be inhibited by SASP in human organoid samples. Our findings suggest that, in combination with PDT, SASP has potential as a promising approach against CCA.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | - Yu Wen
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Zi-Jian Zhang
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Heng Zou
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China
| |
Collapse
|
|
39
|
Yang PC, Chen YJ, Li XY, Hsiao CY, Cheng BB, Gao Y, Zhou BZ, Chen SY, Hu SQ, Zeng Q, Huang KW. Irreversible Electroporation Treatment With Intraoperative Biliary Stenting for Unresectable Perihilar Cholangiocarcinoma: A Pilot Study. Front Oncol 2021; 11:710536. [PMID: 34277454 PMCID: PMC8278819 DOI: 10.3389/fonc.2021.710536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Accepted: 06/16/2021] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Treating perihilar cholangiocarcinoma (PHCC) is particularly difficult due to the fact that it is usually in an advanced stage at the time of diagnosis. Irreversible electroporation treatment (IRE) involves the local administration of a high-voltage electric current to target lesions without causing damage to surrounding structures. This study investigated the safety and efficacy of using IRE in conjunction with intraoperative biliary stent placement in cases of unresectable PHCC. METHODS This study enrolled 17 patients with unresectable Bismuth type III/IV PHCC who underwent IRE in conjunction with intraoperative biliary stent placement (laparotomic) in two medical centers in Asia between June 2015 and July 2018. Analysis focused on the perioperative clinical course, the efficacy of biliary decompression, and outcomes (survival). RESULTS Mean total serum bilirubin levels (mg/dL) on postoperative day (POD) 7, POD30, and POD90 were significantly lower than before IRE (respectively 3.46 vs 4.54, p=0.007; 1.21 vs 4.54, p<0.001; 1.99 vs 4.54, p<0.001). Mean serum carbohydrate antigen 19-9 (CA19-9, U/ml) levels were significantly higher on POD3 than before the operation (518.8 vs 372.4, p=0.001) and significantly lower on POD30 and POD90 (respectively 113.7 vs 372.4, p<0.001; 63.9 vs 372.4, p<0.001). No cases of Clavien-Dindo grade III/IV adverse events or mortality occurred within 90 days post-op. The median progression-free survival was 21.5 months, and the median overall survival was 27.9 months. All individuals who survived for at least one year did so without the need to carry percutaneous biliary drainage (PTBD) tubes. CONCLUSIONS It appears that IRE treatment in conjunction with intraoperative biliary stent placement is a safe and effective approach to treating unresectable PHCC. The decompression of biliary obstruction without the need for PTBD tubes is also expected to improve the quality of life of patients.
Collapse
Affiliation(s)
- Po-Chih Yang
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Surgery, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City, Taiwan
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Yan-Jun Chen
- Department of Hepatopancreatobiliary Surgery, The Fifth Affiliated Hospital, Zhengzhou University, Zhengzhou, China
| | - Xiao-Yong Li
- Department of Hepatopancreatobiliary Surgery, The Fifth Affiliated Hospital, Zhengzhou University, Zhengzhou, China
| | - Chih-Yang Hsiao
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Traumatology, National Taiwan University Hospital, Taipei, Taiwan
- Department of Surgery & Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Bing-Bing Cheng
- Department of Hepatopancreatobiliary Surgery, The Fifth Affiliated Hospital, Zhengzhou University, Zhengzhou, China
| | - Yu Gao
- Department of Hepatopancreatobiliary Surgery, The Fifth Affiliated Hospital, Zhengzhou University, Zhengzhou, China
| | - Bai-Zhong Zhou
- Department of Hepatopancreatobiliary Surgery, The Fifth Affiliated Hospital, Zhengzhou University, Zhengzhou, China
| | - Sheng-Yang Chen
- Department of Hepatopancreatobiliary Surgery, The Fifth Affiliated Hospital, Zhengzhou University, Zhengzhou, China
| | - Shui-Quan Hu
- Department of Hepatopancreatobiliary Surgery, The Fifth Affiliated Hospital, Zhengzhou University, Zhengzhou, China
| | - Quan Zeng
- Endoscopic Center, the Fifth Affiliated Hospital, Zhengzhou University, Zhengzhou, China
| | - Kai-Wen Huang
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Surgery & Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| |
Collapse
|
|
40
|
Zhang PJ, Liu MD, Fan FY, Liu KX. A Study on Mesoporous Silica Loaded With Novel Photosensitizers HCE6 and Oxaliplatin for the Treatment of Cholangiocarcinoma. Front Oncol 2021; 11:665182. [PMID: 34268112 PMCID: PMC8276239 DOI: 10.3389/fonc.2021.665182] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 05/06/2021] [Indexed: 12/16/2022] Open
Abstract
Purpose Cholangiocarcinoma (CCA) is a malignant tumor with a high incidence. The therapeutic effect of conventional chemotherapy and radiotherapy is not obvious. Photodynamic therapy (PDT) is an ideal modality to fight cancer, and the nature of photosensitizer limits its application in clinical therapy. The aim of this study was to explore a novel mode of drug delivery for the intervention of bile duct cancer. Methods Oxaliplatin and photosensitizer HCE6 were loaded with mesoporous silica nanoparticles (MSNs) to synthesize Oxaliplatin/HCE6-MSNs (OH-MSNs); the structure of OH-MSNs was characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS), the drug release rate was detected by high performance liquid chromatography; the cellular activity, apoptosis level, and the expression levels of intracellular apoptosis and autophagy-related factors of OH-MSNs on cholangiocarcinoma cells were observed by CCK-8, flow cytometry, colony formation assay, and Western blot; the effects of OH-MSNs on cholangioma growth were observed by mouse tumor formation, immunohistochemistry, and tissue Tunel staining. Results The release of OH-MSNs to Oxaliplatin was enhanced under acidic conditions; compared with Oxaliplatin or O-MSNs, OH-MSNs showed more potent killing effects against cholangiocarcinoma cells (P<0.05), and exerted notably inhibitory effects on the activity of cholangiocarcinoma cells (P<0.05), promoted their apoptosis (P<0.05), and greatly facilitated the expression of pro-apoptotic factors and autophagic factors in cholangiocarcinoma cells (P<0.05), and markedly inhibited the expression of anti-apoptotic factors and autophagic inhibitory factors (P<0.05); moreover, OH-MSNs could significantly suppress the growth of mouse cholangiocarcinoma (P<0.05) and induce apoptosis of tumor cells compared with Oxaliplatin or O-MSNs (P<0.05). Conclusion MSNs loading greatly increases the killing effect of Oxaliplatin on cholangiocarcinoma cells and upgrades the autophagic level of cholangiocarcinoma cells, while OH-MSNs synthesized by further loading HCE6 have a more apparent killing effect on cholangiocarcinoma cells.
Collapse
Affiliation(s)
- Pei-Jian Zhang
- Department of General Surgery Endoscopy, Cangzhou Central Hospital, Cangzhou, China
| | - Meng-Dong Liu
- Department of Pain, Cangzhou People's Hospital, Cangzhou, China
| | - Fang-Yong Fan
- Department of General Surgery, Huanghua People's Hospital, Huanghua, China
| | - Ke-Xia Liu
- Department of General Surgery Endoscopy, Cangzhou Central Hospital, Cangzhou, China
| |
Collapse
|
|
41
|
Ma Z, Li H, Liu L. Combining PD-1 Inhibitor with VEGF/VEGFR2 Inhibitor in Chemotherapy: Report of a Patient with End-Stage Cholangiocarcinoma and Review of Literature. Recent Pat Anticancer Drug Discov 2021; 16:101-107. [PMID: 33390149 DOI: 10.2174/1574892815999201231215311] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 09/06/2020] [Accepted: 10/14/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND Cholangiocarcinoma is the second-largest liver cancer, and develops from the biliary epithelium, where it discretely progresses. Unfortunately, many patients miss the opportunity of performing surgery when diagnosed with cholangiocarcinoma, and due to its chemotherapeutic insensitivity, its control has always been considered difficult. OBJECTIVE Here, we present a case of stage 4 cholangiocarcinoma being controlled by the combination of chemotherapy with PD-1 and VEGF/VEGFR2 inhibitors. CASE PRESENTATION The patient is a 58-year-old male who was diagnosed with a progressed cholangiocarcinoma 2 years ago. From the beginning, metastases were discovered in multiple places, and the patient was unsuccessfully treated with 3 chemotherapy regimens. Therefore, a new therapeutic method was considered, and that involved the testing of a new combination of chemotherapy with PD-1 and VEGF/VEGFR2 inhibitors. RESULTS After 6 courses of treatment with this combination, the patient's lesions became smaller and stable. CONCLUSION Our case highlights the possibility of combining chemotherapy with PD-1 and VEGF/ VEGFR2 inhibitors for the treatment of cholangiocarcinoma patients. This combination may herald new hope for patients who run out of regimens.
Collapse
Affiliation(s)
- Zhenjiang Ma
- The First Affiliated Hospital of Sun Yat sen University No.183 Huangpu East Road, Huangpu District, Guangzhou City, Guangdong Province, China
| | - Heping Li
- The First Affiliated Hospital of Sun Yat sen University No.183 Huangpu East Road, Huangpu District, Guangzhou City, Guangdong Province, China
| | - Liangshuai Liu
- The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital) No. 36 Mingxin Road, Liwan District, Guangzhou City, Guangdong Province, China
| |
Collapse
|
|
42
|
Weismüller TJ. Role of Intraductal RFA: A Novel Tool in the Palliative Care of Perihilar Cholangiocarcinoma. Visc Med 2021; 37:39-47. [PMID: 33718482 PMCID: PMC7923928 DOI: 10.1159/000513970] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 12/21/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Patients with irresectable perihilar cholangiocarcinoma (PHC) have a limited prognosis with median survival times still less than 1 year. In addition to the current standard first-line systemic chemotherapy (gemcitabine and a platinum derivate), endoscopic treatment aims to ensure adequate drainage of the biliary system by placing biliary plastic or metal stents. Local ablative procedures like intraluminal biliary brachytherapy (ILBT) or photodynamic therapy (PDT) are used to improve local tumor control and to optimize the stent patency. SUMMARY Intraductal radiofrequency ablation (RFA) is another promising tool in the therapeutic armamentarium for the endoscopic management and tumor ablation of extrahepatic cholangiocarcinoma (eCCA). By applying thermal energy to the tissue through high-frequency alternating current, RFA induces coagulative necrosis and causes local destruction of the tumor. It is established as a first line percutaneous treatment of solid liver tumors, and since 2011 an endoscopic catheter is available that allows intraductal RFA in the biliary or pancreatic ducts. While the first pilot studies primarily evaluated this new method in patients with distal eCCA, there is now evidence accumulating also for PHC. Two retrospective and two prospective studies demonstrated a significantly improved overall survival and a longer stent patency with intraductal RFA, which overall had a favorable safety profile and was not associated with a significant increase in adverse events. However, prospective studies comparing the efficacy and safety of intraductal RFA, PDT, and/or ILBT are lacking. KEY MESSAGES Recent studies suggest that intraductal RFA is an effective and well-tolerated additional treatment option with regard to stent patency but also overall survival. Since RFA has fewer systemic side effects and requires less logistical effort when compared to ILBT and PDT, intraductal RFA should be considered as another safe and feasible adjuvant method for the palliative care of patients with advanced PHC. Since comparative studies are lacking, the choice of the local ablative method remains in each case an individual decision.
Collapse
|
|
43
|
Kucinska M, Plewinski A, Szczolko W, Kaczmarek M, Goslinski T, Murias M. Modeling the photodynamic effect in 2D versus 3D cell culture under normoxic and hypoxic conditions. Free Radic Biol Med 2021; 162:309-326. [PMID: 33141030 DOI: 10.1016/j.freeradbiomed.2020.10.304] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 10/01/2020] [Accepted: 10/20/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND Photodynamic therapy (PDT), mainly as a combined therapy, can still be considered a promising technology for targeted cancer treatment. Besides the several and essential benefits of PDT, there are some concerns and limitations, such as complex dosimetry, tumor hypoxia, and other mechanisms of resistance. In this study, we present how the cell culture model and cell culture conditions may affect the response to PDT treatment. It was studied by applying two different 3D cell culture, non-scaffold, and hydrogel-based models under normoxic and hypoxic conditions. In parallel, a detailed mechanism of the action of zinc phthalocyanine M2TG3 was presented. METHODS Hydrogel-based and tumor spheroids consisting of LNCaP cells, were used as 3D cell culture models in experiments performed under normoxic and hypoxic (1% of oxygen) conditions. Several analyses were performed to compare the activity of M2TG3 under different conditions, such as cytotoxicity, the level of proapoptotic and stress-related proteins, caspase activity, and antioxidant gene expression status. Additionally, we tested bioluminescence and fluorescence assays as a useful approach for a hydrogel-based 3D cell culture. RESULTS We found that M2TG3 might lead to apoptotic cancer cell death and is strongly dependent on the model and oxygen availability. Moreover, the expression of the genes modulated in the antioxidative system in 2D and 3D cell culture models were presented. The tested bioluminescence assay revealed several advantages, such as repetitive measurements on the same sample and simultaneous analysis of different parameters due to the non-lysing nature of this assay. CONCLUSIONS It was shown that M2TG3 can effectively cause cancer cell death via a different mechanism, depending on cell culture conditions such as the model and oxygen availability.
Collapse
Affiliation(s)
- Malgorzata Kucinska
- Department of Toxicology, Poznan University of Medical Sciences, Dojazd 30 Street, 60-631, Poznan, Poland.
| | - Adam Plewinski
- Centre for Advanced Technologies, Adam Mickiewicz University, Uniwersytet Poznanski 10 Street, 61-614, Poznan, Poland
| | - Wojciech Szczolko
- Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Grunwaldzka 6 Street, 60-780, Poznan, Poland
| | - Mariusz Kaczmarek
- Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, Garbary 15 Street, 61-866, Poznan, Poland; Department of Cancer Diagnostics and Immunology, Gene Therapy Unit, Greater Poland Cancer Centre, Garbary 15 Street, 61-866, Poznan, Poland
| | - Tomasz Goslinski
- Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Grunwaldzka 6 Street, 60-780, Poznan, Poland
| | - Marek Murias
- Department of Toxicology, Poznan University of Medical Sciences, Dojazd 30 Street, 60-631, Poznan, Poland; Centre for Advanced Technologies, Adam Mickiewicz University, Uniwersytet Poznanski 10 Street, 61-614, Poznan, Poland.
| |
Collapse
|
|
44
|
Wang M, Chen Z, Guo P, Wang Y, Chen G. Therapy for advanced cholangiocarcinoma: Current knowledge and future potential. J Cell Mol Med 2020; 25:618-628. [PMID: 33277810 PMCID: PMC7812297 DOI: 10.1111/jcmm.16151] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 10/21/2020] [Accepted: 11/22/2020] [Indexed: 01/07/2023] Open
Abstract
Cholangiocarcinoma (CCA) is a biliary epithelial tumour that can emerge at any point in the biliary tree. It is commonly classified based on its anatomical site of development into intrahepatic cholangiocarcinoma (ICC), perihilar cholangiocarcinoma (PCC) and distal cholangiocarcinoma (DCC), each of which is associated with varying patient demographics, molecular characteristics and treatment options. CCA patients have poor overall prognoses and 5‐year survival rates. Additionally, CCA is often diagnosed at an advanced stage, with surgical treatment restricted to early‐stage disease. Owing to an increase in the incidence of ICC, that of CCA is also on the rise, with a corresponding increase in the associated mortality, particularly in South America and Asia. Therefore, the development of an effective treatment is crucial to improve the survival of CCA patients. We aimed to systematically review the current understanding of advanced CCA treatment and discuss potential effective strategies.
Collapse
Affiliation(s)
- Mingxun Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China
| | - Ziyan Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China
| | - Pengyi Guo
- Department of Cardiothoracic Surgery, Ningbo Yinzhou NO.2 Hospital, Ningbo, China
| | - Yi Wang
- Department of Epidemiology and Biostatistics, Public Health and Management School, Wenzhou Medical University, Wenzhou, China
| | - Gang Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China
| |
Collapse
|
|
45
|
Gaddam S, Coté GA. The importance of the "endoscopic oncologist" in the treatment of nonoperable cholangiocarcinoma. Gastrointest Endosc 2020; 92:1213-1215. [PMID: 33236993 DOI: 10.1016/j.gie.2020.06.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 06/07/2020] [Indexed: 12/11/2022]
Affiliation(s)
- Srinivas Gaddam
- Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Gregory A Coté
- Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| |
Collapse
|
|
46
|
Dechêne A, Kasper S, Olivecrona H, Schirra J, Trojan J. Photochemical internalization and gemcitabine combined with first-line chemotherapy in perihilar cholangiocarcinoma: observations in three patients. Endosc Int Open 2020; 8:E1878-E1883. [PMID: 33269324 PMCID: PMC7695516 DOI: 10.1055/a-1276-6366] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 08/17/2020] [Indexed: 12/22/2022] Open
Abstract
Photochemical internalization (PCI) is a technology to induce a localized, intracellular enhancement of therapeutics that are processed through endosomal pathways, including gemcitabine in malignant cells. In addition to a direct phototoxic and tumoricidal effect, PCI specifically disrupts endosomal membranes and, thereby, the compartmentalization of certain cytotoxic compounds to enhance a drug's intended intracellular target reach within the tissue treated. Non-resectable extrahepatic cholangiocarcinoma (eCCA) is a common primary tumor and gemcitabine/cisplatin chemotherapy is widely considered standard of care for it. PCI is well suited as an endoscopic intervention, and clinical observations in three subjects participating in a phase I/IIa dose escalation safety trial are described. The trial included patients with perihilar, non-resectable CCA suitable for standard-of-care chemotherapy. Per protocol, a single endoscopic PCI procedure with gemcitabine was conducted at the initiation of standard gemcitabine/cisplatin therapy. Sixteen patients enrolled in the initial dose escalation phase of the trial, which later was extended to explore the safety of a second PCI procedure during chemotherapy. While limited to a case series, the various clinical observations described here serve to illustrate the effects of localized, perihilar tumor targeting in appropriate patients by any safe methodology, including PCI. As previously indicated by clinical data using other localized treatment modalities, adding a directed, tumor-targeting treatment to systemic therapy to ameliorate the progressively expanding extrahepatic tumor burden can have important effects on the overall outcome of systemic treatment in many patients who have incurable eCCA.
Collapse
Affiliation(s)
- Alexander Dechêne
- Dept. of Gastroenterology and Endocrinology, Klinikum Nürnberg, Paracelsus Medical University, Nürnberg, Germany
| | - Stefan Kasper
- Dept of Medical Oncology West German Cancer Center, University Hospital Essen, Germany
| | | | - Joerg Schirra
- Medical Department II, University Hospital, Ludwig Maximilians-University, Munich, Germany
| | - Joerg Trojan
- Goethe University Medical Center, Frankfurt, Germany
| |
Collapse
|
|
47
|
Ma B, Meng H, Tian Y, Wang Y, Song T, Zhang T, Wu Q, Cui Y, Li H, Zhang W, Li Q. High expression of HVEM is associated with improved prognosis in intrahepatic cholangiocarcinoma. Oncol Lett 2020; 21:69. [PMID: 33365080 PMCID: PMC7716701 DOI: 10.3892/ol.2020.12330] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 10/29/2020] [Indexed: 01/03/2023] Open
Abstract
Herpesvirus entry mediator (HVEM) displays dual signals in T-cell activation according to the ligands and intracytoplasmic effectors it interacts with. High HVEM expression may play an immunosuppressive role in several malignancies. The present study investigated the clinical impact of HVEM on intrahepatic cholangiocarcinoma (ICC), including its prognostic value, and association with clinicopathological features and immune status. The clinical data of 102 consecutive patients with ICC who underwent surgical treatment from January 2012 to December 2017 were collected. The expression of HVEM and different types of tumor-infiltrating lymphocytes (TILs) were investigated in ICC tissue samples by immunohistochemical staining. HVEM expression was detected in the tumor tissues of 92 (90.2%) patients with ICC. Patients with high HVEM expression were more likely to have increased peripheral blood lymphocyte (PBL) concentrations (P=0.031), decreased CEA (P=0.036), low TNM stage (P=0.043) and high frequencies of small-duct histological type (P=0.021) and BAP1 retained expression (P=0.010). Survival analysis showed that high HVEM expression was a favorable independent predictor of overall postoperative survival (P=0.034, hazard ratio=0.486, 95% confidence interval=0.249–0.945). In addition, no significant association of HVEM expression with CD4+ (P=0.512), CD8+ (P=0.750) or CD45RO+ (P=0.078) TILs was identified in the ICC tissues. These results indicate that HVEM may serve as a favorable prognostic marker for ICC. Furthermore, co-stimulatory signals from HVEM may play a dominant role in the progression of ICCs, which can be explained by an increase in the number of PBLs rather than a change in the number of TILs. However, the function of the HVEM network in ICC progression is complex and requires further study.
Collapse
Affiliation(s)
- Bingqi Ma
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China.,Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261031, P.R. China
| | - Huijuan Meng
- Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261031, P.R. China
| | - Ye Tian
- Department of Senior Ward, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China
| | - Yingying Wang
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China
| | - Tianqiang Song
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China
| | - Ti Zhang
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China
| | - Qiang Wu
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China
| | - Yunlong Cui
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China
| | - Huikai Li
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China
| | - Wei Zhang
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China
| | - Qiang Li
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China
| |
Collapse
|
|
48
|
Abstract
Endoscopic and percutaneous therapies have been shown to prolong life and reduce morbidity for patients with unresectable advanced stages of primary hepatobiliary malignancies. This article reviews pertinent studies published within the last 5 years that involve locoregional techniques to manage hepatocellular carcinoma, perihilar and distal cholangiocarcinoma. A major emphasis is placed on photodynamic therapy, radiofrequency ablation, irreversible electroporation, and microwave ablation. Technical advances, combinational therapies, and postintervention outcomes are discussed. Despite widespread application, high-quality evidence does not show superiority of any particular locoregional technique for treating advanced hepatobiliary cancers.
Collapse
|
|
49
|
Wu L, Merath K, Farooq A, Hyer JM, Tsilimigras DI, Paredes AZ, Mehta R, Sahara K, Shen F, Pawlik TM. Photodynamic therapy may provide a benefit over systemic chemotherapy among non-surgically managed patients with extrahepatic cholangiocarcinoma. J Surg Oncol 2020; 121:286-293. [PMID: 31742706 DOI: 10.1002/jso.25773] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 11/11/2019] [Indexed: 01/24/2023]
Abstract
BACKGROUND Systemic chemotherapy is the standard treatment for patients with unresectable extrahepatic cholangiocarcinoma (ECC), however, the survival benefit of chemotherapy is limited. Photodynamic therapy (PDT) has been associated with improved survival among patients with advanced ECC, yet utilization of PDT remains low. We sought to compare the outcomes of patients with unresectable ECC following treatment with PDT versus chemotherapy. METHODS A review of the National Cancer Database was conducted to identify patients with ECC who were nonsurgically managed between 2004 and 2013. Overall survival (OS) of patients receiving PDT vs systemic chemotherapy was compared using propensity score matching. RESULTS After propensity matching (PDT, n = 59; chemotherapy, n = 177), 5-year OS was 17.6% (95% confidence interval [CI], 9.0%-28.6%) among patients who underwent PDT vs 3.8% (95%CI, 0.4%-14.0%) among patients receiving chemotherapy (P < .001). On multivariable analysis PDT was associated with an OS benefit (hazard ratio, 0.72; 95%CI, 0.52-0.998; P = .048). Subset analysis of patients receiving PDT only (n = 45) and patients receiving chemotherapy demonstrated similar results. In subset analysis of patients undergoing PDT-only vs PDT-chemotherapy, OS was comparable. CONCLUSION PDT was associated with a survival benefit compared with chemotherapy alone among patients with unresectable ECC.
Collapse
Affiliation(s)
- Lu Wu
- Department of Hepatic Surgery, Eastern Hepato-biliary Surgery Hospital, Second Military Medical University, Shanghai, China.,Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, Ohio
| | - Katiuscha Merath
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, Ohio
| | - Ayesha Farooq
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, Ohio
| | - J Madison Hyer
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, Ohio
| | - Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, Ohio
| | - Anghela Z Paredes
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, Ohio
| | - Rittal Mehta
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, Ohio
| | - Kota Sahara
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, Ohio
| | - Feng Shen
- Department of Hepatic Surgery, Eastern Hepato-biliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, Ohio
| |
Collapse
|
|
50
|
Tanaka E, Uchida D, Shiraha H, Kato H, Ohyama A, Iwamuro M, Watanabe M, Kumon H, Okada H. Promising Gene Therapy Using an Adenovirus Vector Carrying REIC/Dkk-3 Gene for the Treatment of Biliary Cancer. Curr Gene Ther 2020; 20:64-70. [PMID: 32148193 DOI: 10.2174/1566523220666200309125709] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 02/18/2020] [Accepted: 02/26/2020] [Indexed: 01/06/2023]
Abstract
BACKGROUND We previously demonstrated that the reduced expression in immortalized cells (REIC)/dikkopf-3 (Dkk-3) gene was downregulated in various malignant tumors, and that an adenovirus vector carrying the REIC/Dkk-3 gene, termed Ad-REIC induced cancer-selective apoptosis in pancreatic cancer and hepatocellular carcinoma. OBJECTIVE In this study, we examined the therapeutic effects of Ad-REIC in biliary cancer using a second- generation Ad-REIC (Ad-SGE-REIC). METHODS Human biliary cancer cell lines (G-415, TFK-1) were used in this study. The cell viability and apoptotic effect of Ad-SGE-REIC were assessed in vitro using an MTT assay and Hoechst staining. The anti-tumor effect in vivo was assessed in a mouse xenograft model. We also assessed the therapeutic effects of Ad-SGE-REIC therapy with cisplatin. Cell signaling was assessed by Western blotting. RESULTS Ad-SGE-REIC reduced cell viability, and induced apoptosis in biliary cancer cell lines via the activation of the c-Jun N-terminal kinase pathway. Ad-SGE-REIC also inhibited tumor growth in a mouse xenograft model. This effect was further enhanced in combination with cisplatin. CONCLUSION Ad-SGE-REIC induced apoptosis and inhibited tumor growth in biliary cancer cells. REIC/Dkk-3 gene therapy using Ad-SGE-REIC is an attractive therapeutic tool for biliary cancer.
Collapse
Affiliation(s)
- Emi Tanaka
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Daisuke Uchida
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
- Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Hidenori Shiraha
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Hironari Kato
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Atsushi Ohyama
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Masaya Iwamuro
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Masami Watanabe
- Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Hiromi Kumon
- Innovation Center Okayama for Nanobio-Targeted Therapy, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| |
Collapse
|