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Wu Y, Jiang Y, Jiang L, Peng Y, Zhou T, Xia X, Hou F, Yuan Q, Ye L, Wei W, Zhang J, Chen Q, Feng X. Phospho-cofilin predicts efficiency of Fasudil for oral squamous cell carcinoma treatment through Yes-associated protein inhibition. Arch Oral Biol 2025; 172:106185. [PMID: 39893996 DOI: 10.1016/j.archoralbio.2025.106185] [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: 11/27/2024] [Revised: 01/26/2025] [Accepted: 01/29/2025] [Indexed: 02/04/2025]
Abstract
OBJECTIVES This study evaluates Fasudil, a Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor, for its potential to inhibit oral squamous cell carcinoma (OSCC) growth and explores phospho-cofilin as a potential biomarker for prediction treatment efficiency of Fasudil in OSCC. DESIGN A cohort of 109 OSCC patients provided tissue samples for phospho-cofilin expression analysis and survival analysis. The study examined the effect of Fasudil on OSCC cell lines HSC-3, UM1, and CAL33, assessing tumor growth inhibition through various in vitro and in vivo experiments. ROCK inhibition response and downstream mechanisms were explored by RNA sequencing, q-PCR, and immunofluorescence. RESULTS High phospho-cofilin expression in OSCC tissues correlated with poor patient outcomes and was a reliable biomarker for ROCK activity. Fasudil inhibited growth in OSCC cell lines, particularly those with high phospho-cofilin expression. ROCK inhibition led to downregulation of Yes-associated protein (YAP) activity, resulting in suppressed tumor proliferation and increased apoptosis both in vitro and in vivo. CONCLUSIONS Inhibition of ROCK/phospho-cofilin/YAP by Fasudil could suppress OSCC proliferation, while phospho-cofilin served as a potential biomarker of OSCC.
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Affiliation(s)
- Ying Wu
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, PR China
| | - Yuchen Jiang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, PR China
| | - Lanxin Jiang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, PR China
| | - Yang Peng
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, PR China
| | - Tong Zhou
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, PR China
| | - Xiaoqiang Xia
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, PR China
| | - Feifei Hou
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, PR China
| | - Qiuyun Yuan
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, PR China
| | - Lu Ye
- School of Basic Medicine, Chengdu University, Chengdu, Sichuan 610106, PR China
| | - Weideng Wei
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, PR China
| | - Jiuge Zhang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, PR China
| | - Qianming Chen
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, PR China; Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, Zhejiang 310000, PR China.
| | - Xiaodong Feng
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, Department of Oral Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, PR China.
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2
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Borsotti E, Nava FL, Benedicenti F, Cini L, Magarotto A, Ferrari D, Cantù P, Vitellaro M, Rausa E, Cavalcoli F. Hereditary Colorectal Cancer Syndromes: Small Bowel Cancer Risk and Endoscopic Surveillance Strategies. Diagnostics (Basel) 2025; 15:819. [PMID: 40218169 PMCID: PMC11988710 DOI: 10.3390/diagnostics15070819] [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: 02/10/2025] [Revised: 03/05/2025] [Accepted: 03/20/2025] [Indexed: 04/14/2025] Open
Abstract
Background: Hereditary colorectal cancer syndromes, including familial adenomatous polyposis (FAP), Lynch syndrome (LS), and Peutz-Jeghers syndrome (PJS), are associated with an increased risk of small bowel cancer (SBC). Due to the low incidence and non-specific presentation of SBC, effective surveillance strategies are essential for early detection and management. This review aims to evaluate and compare current endoscopic techniques for small bowel surveillance in these patients. Methods: A comprehensive review was conducted using peer-reviewed studies sourced from PubMed. Various endoscopic modalities, including capsule endoscopy (CE), device-assisted enteroscopy (DAE), and intraoperative enteroscopy (IOE), were assessed for their diagnostic yield, safety, and clinical utility. Surveillance recommendations of the different syndromes were also examined. Results: CE offers high sensitivity but lacks histological sampling capability. DAE, including double-balloon enteroscopy (DBE) and single-balloon enteroscopy (SBE), enables direct visualization, biopsy, and therapeutic interventions, albeit with greater procedural complexity. In FAP, duodenal surveillance follows the Spigelman classification to stratify cancer risk, while jejunal and ileal polyps remain less studied. LS patients have an increased SBC risk, warranting tailored endoscopic approaches. In PJS, surveillance aims to mitigate intussusception risks and allow early malignancy detection. Conclusions: Optimized surveillance strategies in hereditary colorectal cancer syndromes require a multimodal approach, integrating advanced endoscopic techniques with genetic risk stratification. Centralized care in tertiary centers improves outcomes by ensuring standardized surveillance protocols and enhancing early cancer detection. Artificial intelligence (AI) applied to CE and DAE is shaping promising prospects for the future surveillance of small bowel polyps by enhancing diagnostic accuracy and reducing the duration of the diagnostic process. Further research should investigate AI-assisted imaging and molecular biomarkers to optimize screening strategies.
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Affiliation(s)
- Edoardo Borsotti
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (E.B.); (L.C.); (A.M.); (P.C.); (F.C.)
| | - Francesca Laura Nava
- Colorectal Surgery Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy;
| | - Felice Benedicenti
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (E.B.); (L.C.); (A.M.); (P.C.); (F.C.)
| | - Laura Cini
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (E.B.); (L.C.); (A.M.); (P.C.); (F.C.)
| | - Andrea Magarotto
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (E.B.); (L.C.); (A.M.); (P.C.); (F.C.)
| | - Davide Ferrari
- Unit of Hereditary Digestive Tract Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (D.F.); (M.V.); (E.R.)
| | - Paolo Cantù
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (E.B.); (L.C.); (A.M.); (P.C.); (F.C.)
| | - Marco Vitellaro
- Unit of Hereditary Digestive Tract Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (D.F.); (M.V.); (E.R.)
| | - Emanuele Rausa
- Unit of Hereditary Digestive Tract Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (D.F.); (M.V.); (E.R.)
| | - Federica Cavalcoli
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy; (E.B.); (L.C.); (A.M.); (P.C.); (F.C.)
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3
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Scafetta G, Rampioni Vinciguerra GL, Giglio S, Faruq O, Cirombella R, Segatto I, Citron F, Mattevi MC, Di Renzi E, Cascione L, Gasparini P, Belletti B, Baldassarre G, Sacconi A, Blandino G, Vecchione A. miR-1297 is frequently downmodulated in flat epithelial atypia of the breast and promotes mammary neoplastic transformation via EphrinA2 regulation. J Exp Clin Cancer Res 2025; 44:96. [PMID: 40082972 PMCID: PMC11908103 DOI: 10.1186/s13046-025-03354-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 02/26/2025] [Indexed: 03/16/2025] Open
Abstract
Breast cancer ranks as the most prevalent form of cancer globally. Currently, advanced screening methods have significantly improved early detection rates. These achievements have led to more non-invasive cancer diagnoses and underscored the clinical relevance of precursor lesions like flat epithelial atypia (FEA), a histological condition characterized by mild atypical changes in the normal epithelium lining the mammary ducts. Despite the increasing detection of FEA in mammary biopsy, our understanding of the biological behavior of this entity remains limited and, as a consequence, the clinical management of patients is still being debated. Evidence from the literature indicates that dysregulation of microRNAs contributes to all stages of breast cancer progression, potentially serving as valuable markers of disease evolution. In this study, through a comparison of the microRNA profiles of normal mammary epithelium, FEA, and non-invasive breast cancer in three cohorts of patients, we identified downregulation of miR-1297 as a common feature in both FEA and non-invasive breast cancer compared to the normal counterpart. Mechanistically, overexpression of miR-1297 inhibits the growth of breast cancer cells by targeting the oncogenic receptor tyrosine kinase EphrinA2. In contrast, downregulation of miR-1297 increases proliferation and alters the morphology of normal mammary epithelial cells in a three-dimensional context. These findings pinpoint the downregulation of miR-1297 as an early event in mammary transformation and suggest its potential role as a driver of progression in FEA, harboring the capacity to evolve into malignancy.
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Affiliation(s)
- Giorgia Scafetta
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sant'Andrea Hospital, University of Rome "Sapienza", 00189, Rome, Italy
- Translational Oncology Research Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Gian Luca Rampioni Vinciguerra
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sant'Andrea Hospital, University of Rome "Sapienza", 00189, Rome, Italy.
| | - Simona Giglio
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sant'Andrea Hospital, University of Rome "Sapienza", 00189, Rome, Italy
| | - Omar Faruq
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sant'Andrea Hospital, University of Rome "Sapienza", 00189, Rome, Italy
| | - Roberto Cirombella
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sant'Andrea Hospital, University of Rome "Sapienza", 00189, Rome, Italy
| | - Ilenia Segatto
- Unit of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081, Aviano, Italy
| | - Francesca Citron
- Unit of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081, Aviano, Italy
| | - Maria Chiara Mattevi
- Unit of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081, Aviano, Italy
| | - Elisabetta Di Renzi
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sant'Andrea Hospital, University of Rome "Sapienza", 00189, Rome, Italy
| | - Luciano Cascione
- Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland
| | - Pierluigi Gasparini
- Department of Cancer Biology and Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA
| | - Barbara Belletti
- Unit of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081, Aviano, Italy
| | - Gustavo Baldassarre
- Unit of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081, Aviano, Italy
| | - Andrea Sacconi
- Clinical Trial Center, Biostatistics and Bioinformatics Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Giovanni Blandino
- Translational Oncology Research Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Andrea Vecchione
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sant'Andrea Hospital, University of Rome "Sapienza", 00189, Rome, Italy.
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4
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Alves TM, Prata WM, Borin MC, de Carvalho AR, Dias CZ, Cherchiglia ML, de Figueiredo LO, de Assis Acurcio F, Alvares-Teodoro J, Júnior AAG. Seven-year overall survival of trastuzumabe versus alternative systemic therapies in a Brazilian breast cancer cohort. Sci Rep 2025; 15:5296. [PMID: 39939346 PMCID: PMC11821829 DOI: 10.1038/s41598-025-88575-3] [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: 10/22/2024] [Accepted: 01/29/2025] [Indexed: 02/14/2025] Open
Abstract
This study analyzed breast cancer patients treated with trastuzumab in Brazil's unified health system (SUS) from 2008 to 2015. A non-concurrent cohort study using SUS data applied propensity score matching to reduce bias between trastuzumab and non-trastuzumab groups. Survival probabilities were estimated via Kaplan-Meier, with subgroup analysis using the log-rank test. Hazard ratios (HR) were calculated using Cox proportional hazards models. Among 20,852 patients, the overall survival rate was 92%, with 94% in the trastuzumab group and 90% in the non-trastuzumab group. Younger, black patients and those in the North region had poorer survival. Advanced disease stages and palliative treatments were linked to higher mortality, while adjuvant therapy and radiotherapy were protective. During follow-up, 8.1% of patients died, with better outcomes observed in the trastuzumab group (p < 0.0001). Late initiation of trastuzumab (after 16 months) improved survival, especially in early stages (I and II). Invasive tumors and stage IV disease were associated with worse prognoses. The study demonstrates trastuzumab's effectiveness in SUS, underscores survival disparities related to sociodemographic factors, and emphasizes the need for early detection, equitable access, and optimized treatment timelines to improve outcomes in public healthcare.
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Affiliation(s)
- Thaís Monteiro Alves
- Graduate Program in Medicines and Pharmaceutical Assistance, School of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil.
| | - Wallace Mateus Prata
- Graduate Program in Medicines and Pharmaceutical Assistance, School of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil
- Ezequiel Dias Foundation, Belo Horizonte, Brazil
| | - Marcus Carvalho Borin
- Graduate Program in Medicines and Pharmaceutical Assistance, School of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | | | - Carolina Zampirolli Dias
- Graduate Program in Public Health, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Mariangela Leal Cherchiglia
- Graduate Program in Public Health, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil
- Department of Preventive and Social Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | | | - Francisco de Assis Acurcio
- Graduate Program in Medicines and Pharmaceutical Assistance, School of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil
- Department of Social Pharmacy, School of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Juliana Alvares-Teodoro
- Graduate Program in Medicines and Pharmaceutical Assistance, School of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil
- Department of Social Pharmacy, School of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Augusto Afonso Guerra Júnior
- Graduate Program in Medicines and Pharmaceutical Assistance, School of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil.
- Department of Social Pharmacy, School of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil.
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5
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Caretto M, Gadducci A, Pistolesi S, Mattiussi Tome D, Fanelli GN, Naccarato AG, Simoncini T. Deciphering the stromal molecular landscape: the correlation between p16 and α-SMA in epithelial ovarian cancer. J Cancer Res Clin Oncol 2025; 151:79. [PMID: 39937250 PMCID: PMC11821793 DOI: 10.1007/s00432-025-06120-1] [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: 10/08/2024] [Accepted: 01/23/2025] [Indexed: 02/13/2025]
Abstract
INTRODUCTION The tumor microenvironment (TME) plays an essential role in promoting cancer initiation, progression and metastasis. Cancer-associated fibroblasts (CAFs) are a major constituent of the TME, but universal CAFs' markers have not yet been identified. We selected several new biomarkers [p16 and α-smooth muscle actin (α-SMA)] to investigate the molecular landscape in epithelial ovarian cancer (EOC), given to the unique TME of this malignancy. METHODS In total, 64 patients with a diagnosis of EOC who underwent primary debulking surgery (PDS) at the Department of Gynecology and Obstetrics of the University of Pisa were enrolled between January 2019 and June 2021. The stromal expression of α-SMA and p16 was investigated by using immunohistochemistry, and the correlations between p16 and α-SMA immunoreactivity and BRCA mutational status were analyzed. RESULTS Positive p16 stromal expression was found in 6 out of 38 (15,78%) patients with wild-type BRCA and in only 1 of the 22 (4,50%) patients with mutated BRCA. Conversely, positive α-SMA expression was detected in 34 of 38 patients with wild-type BRCA (89,47%) and in 21 of 22 patients (95,45%) with mutated BRCA. There was a significant difference (r = -0,32) between the negative stromal p16 expression and the positive stromal expression of α-SMA. CONCLUSION This study suggests a new correlation between stromal expression of p16 and α-SMA and BRCA mutational status in EOC. Further investigations are strongly warranted to improve the understanding of the landscape of this malignancy.
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Affiliation(s)
- Marta Caretto
- Department of Clinical and Experimental Medicine, Division of Obstetrics and Gynecology I, University of Pisa, Pisa, Italy.
| | - Angiolo Gadducci
- Department of Clinical and Experimental Medicine, Division of Obstetrics and Gynecology I, University of Pisa, Pisa, Italy
| | - Sabina Pistolesi
- First Division of Pathology, Department of Laboratory Medicine, Pisa University Hospital, Pisa, Italy
| | - Diletta Mattiussi Tome
- Department of Clinical and Experimental Medicine, Division of Obstetrics and Gynecology I, University of Pisa, Pisa, Italy
| | - Giuseppe Nicolò Fanelli
- First Division of Pathology, Department of Laboratory Medicine, Pisa University Hospital, Pisa, Italy
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Antonio Giuseppe Naccarato
- First Division of Pathology, Department of Laboratory Medicine, Pisa University Hospital, Pisa, Italy
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Tommaso Simoncini
- Department of Clinical and Experimental Medicine, Division of Obstetrics and Gynecology I, University of Pisa, Pisa, Italy
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Aguirre N, Chung SK, Foote MB, Shia J, Vakiani E, Gowda T, Paty PB, Weiser MR, Garcia-Aguilar J, Karagkounis G, Cercek A, Nash GM. Predictors of Recurrence in Nonmetastatic Appendiceal Epithelial Cancers: An Updated Single-Center Experience Over 25 Years. Ann Surg Oncol 2025; 32:695-702. [PMID: 39604747 PMCID: PMC11813631 DOI: 10.1245/s10434-024-16366-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Accepted: 10/01/2024] [Indexed: 11/29/2024]
Abstract
BACKGROUND Appendiceal epithelial tumors are rare and encompass a broad set of adenocarcinoma histologies, including mucinous (mAC), colonic-type (cAC), and goblet cell (GCA) adenocarcinomas. It has previously been reported that nodal disease predicted recurrence in patients with nonmetastatic appendiceal adenocarcinomas, supporting diagnostic laparoscopy with right hemicolectomy for staging and assessment for risk of recurrence. In this update, we sought to identify predictors of nodal disease on initial diagnostic pathology in nonmetastatic adenocarcinomas. METHODS Patients with nonmetastatic appendiceal adenocarcinoma at a single institution from 1994 to 2020 were included. Clinicopathologic characteristics that predict recurrence and lymph node metastasis were analyzed. Workup included staging laparoscopy with right hemicolectomy, seriel imaging and biochemical monitoring. RESULTS A total of 147 patients with mAC (18%), cAC (22%), and GCAs (59%) were included. After median follow-up of 53 months, 23 (16%) patients recurred, most commonly in the peritoneal cavity (17/23, 74%). Recurrence rates were higher among node-positive patients (59% vs. 5%, P < 0.001). Nodal disease was more common in mAC (27%) and cAC (37%) than in GCA (11%); however, adenocarcinoma grade was not associated with nodal involvement. CONCLUSIONS Nodal metastasis was more common in mAC and cAC compared with GCA and was the only significant predictor of recurrence in appendix cancer.
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Affiliation(s)
- Nicole Aguirre
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Sebastian K Chung
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michael B Foote
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jinru Shia
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Efsevia Vakiani
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Tina Gowda
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Philip B Paty
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Martin R Weiser
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Julio Garcia-Aguilar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Georgios Karagkounis
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Andrea Cercek
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Garrett M Nash
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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7
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Schneider E, Tiefenboeck TM, Böhler C, Noebauer-Huhmann IM, Lang S, Krepler P, Funovics PT, Windhager R. Primary malignant bone and soft-tissue tumours of the spine and appendicular sacrum. Bone Jt Open 2025; 6:109-118. [PMID: 39889749 PMCID: PMC11785419 DOI: 10.1302/2633-1462.62.bjo-2024-0169.r1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2025] Open
Abstract
Aims The aim of the present study was to analyze the oncological and neurological outcome of patients undergoing interdisciplinary treatment for primary malignant bone and soft-tissue tumours of the spine within the last seven decades, and changes over time. Methods We retrospectively analyzed our single-centre experience of prospectively collected data by querying our tumour registry (Medical University of Vienna). Therapeutic, pathological, and demographic variables were examined. Descriptive data are reported for the entire cohort. Kaplan-Meier analysis and multivariate Cox regression analysis were applied to evaluate survival rates and the influence of potential risk factors. Results A total of 119 consecutive patients (mean age 38 years (SD 37; 1 to 83), mean follow-up 66 months (SD 26; 0 to 505) were investigated. Histological entities included Ewing's sarcoma (EWS; 33), chondrosarcoma (CSA; 20), osteosarcoma (OSA; 22), and soft-tissue sarcoma (STS; 44). Surgery was performed in 88 patients (74%). Neurological parameters improved in 18 patients (20%) after surgery. Overall, 32 patients (36%) suffered from surgical complications requiring revision. The median survival was 42 months (IQR 10 to 204). The one-, five-, and ten-year survival rates were 73%, 47%, and 39%, respectively. Corresponding five-year survival rates for EWS, CSA, OSA, and STS were 63%, 61%, 40%, and 32%, respectively. The decade of diagnosis, histological entity, surgical intervention, resection margin, and the presence of metastases had significant influence on survival. (Neo-)adjuvant therapies alone had no significant influence on overall survival. Conclusion Our study clearly demonstrates the positive impact of improved surgical techniques, as well as refined imaging methods and evolved adjuvant therapy options, on survival rate in all tumour entities. However, despite a multimodal treatment plan, the long-term mortality of these tumours remains high.
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Affiliation(s)
- Eleonora Schneider
- Division of Orthopaedics, Department of Orthopaedics and Trauma Surgery, Medical University of Vienna Waehringer Guertel, Vienna, Austria
| | - Thomas M. Tiefenboeck
- Division of Trauma Surgery, Department of Orthopaedics and Traumatology, Medical University of Vienna, Vienna, Austria
| | - Christoph Böhler
- Division of Orthopaedics, Department of Orthopaedics and Trauma Surgery, Medical University of Vienna Waehringer Guertel, Vienna, Austria
| | | | - Susanna Lang
- Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria
| | - Petra Krepler
- Division of Orthopaedics, Department of Orthopaedics and Trauma Surgery, Medical University of Vienna Waehringer Guertel, Vienna, Austria
| | - Philipp T. Funovics
- Division of Orthopaedics, Department of Orthopaedics and Trauma Surgery, Medical University of Vienna Waehringer Guertel, Vienna, Austria
| | - Reinhard Windhager
- Division of Orthopaedics, Department of Orthopaedics and Trauma Surgery, Medical University of Vienna Waehringer Guertel, Vienna, Austria
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Jarmoshti J, Siddique A, Rane A, Mirhosseini S, Adair SJ, Bauer TW, Caselli F, Swami NS. Neural Network-Enabled Multiparametric Impedance Signal Templating for High throughput Single-Cell Deformability Cytometry Under Viscoelastic Extensional Flows. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2025; 21:e2407212. [PMID: 39439143 PMCID: PMC11798358 DOI: 10.1002/smll.202407212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Revised: 10/08/2024] [Indexed: 10/25/2024]
Abstract
Cellular biophysical metrics exhibit systematic alterations during processes, such as metastasis and immune cell activation, which can be used to identify and separate live cell subpopulations for targeting drug screening. Image-based biophysical cytometry under extensional flows can accurately quantify cell deformability based on cell shape alterations but needs extensive image reconstruction, which limits its inline utilization to activate cell sorting. Impedance cytometry can measure these cell shape alterations based on electric field screening, while its frequency response offers functional information on cell viability and interior structure, which are difficult to discern by imaging. Furthermore, 1-D temporal impedance signal trains exhibit characteristic shapes that can be rapidly templated in near real-time to extract single-cell biophysical metrics to activate sorting. We present a multilayer perceptron neural network signal templating approach that utilizes raw impedance signals from cells under extensional flow, alongside its training with image metrics from corresponding cells to derive net electrical anisotropy metrics that quantify cell deformability over wide anisotropy ranges and with minimal errors from cell size distributions. Deformability and electrical physiology metrics are applied in conjunction on the same cell for multiparametric classification of live pancreatic cancer cells versus cancer associated fibroblasts using the support vector machine model.
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Affiliation(s)
- Javad Jarmoshti
- Electrical & Computer EngineeringUniversity of VirginiaCharlottesvilleVA22904USA
| | | | - Aditya Rane
- Chemistry, University of VirginiaUniversity of VirginiaCharlottesvilleVA22904USA
| | | | - Sara J. Adair
- Surgery, School of MedicineUniversity of VirginiaCharlottesvilleVA22903USA
| | - Todd W. Bauer
- Surgery, School of MedicineUniversity of VirginiaCharlottesvilleVA22903USA
| | - Federica Caselli
- Civil Engineering and Computer ScienceUniversity of Rome Tor VergataRome00133Italy
| | - Nathan S. Swami
- Electrical & Computer EngineeringUniversity of VirginiaCharlottesvilleVA22904USA
- Chemistry, University of VirginiaUniversity of VirginiaCharlottesvilleVA22904USA
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9
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Ataollahi F, Amirheidari B, Amirheidari Z, Ataollahi M. Clinical and mechanistic insights into biomedical application of Se-enriched probiotics and biogenic selenium nanoparticles. Biotechnol Lett 2025; 47:18. [PMID: 39826010 DOI: 10.1007/s10529-024-03559-z] [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: 06/14/2024] [Revised: 11/13/2024] [Accepted: 12/16/2024] [Indexed: 01/20/2025]
Abstract
Selenium is an essential element with various industrial and medical applications, hence the current considerable attention towards the genesis and utilization of SeNPs. SeNPs and other nanoparticles could be achieved via physical and chemical methods, but these methods would not only require expensive equipment and specific reagents but are also not always environment friendly. Biogenesis of SeNPs could therefore be considered as a less troublesome alternative, which opens an excellent window to the selenium and nanoparticles' world. bSeNPs have proved to exert higher bioavailability, lower toxicity, and broader utility as compared to their non-bio counterparts. Many researchers have reported promising features of bSeNP such as anti-oxidant and anti-inflammatory, in vitro and in vivo. Considering this, bSeNPs have been tried as effective agents for health disorders, especially as constituents of probiotics. This article briefly reviews selenium, selenium nanoparticles, Se-enriched probiotics, and bSeNPs' usage in an array of health disorders. Obviously, there are very many articles on bSeNPs, but we wanted to summarize studies on prominent bSeNPs features published in the twenty-first century. This review is hoped to give an outlook to researchers for their future investigations, ultimately serving better care of health disorders.
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Affiliation(s)
- Farshid Ataollahi
- Extremophile and Productive Microorganisms Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Bagher Amirheidari
- Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
- Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Medical University Campus, Haft-Bagh Highway, Kerman, 76169-13555, Iran.
| | - Zohreh Amirheidari
- Extremophile and Productive Microorganisms Research Center, Kerman University of Medical Sciences, Kerman, Iran
- Pharmaceutical Sciences and Cosmetic Products Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Mahshid Ataollahi
- Extremophile and Productive Microorganisms Research Center, Kerman University of Medical Sciences, Kerman, Iran
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10
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Tuergan T, Abulaiti A, Tulahong A, Zhang R, Yuan Z, Lin Y, Shao Y, Aji T. Seeing beyond words: nanotechnology in hepatocellular carcinoma - a bibliometric study. Front Oncol 2025; 14:1487198. [PMID: 39882441 PMCID: PMC11774701 DOI: 10.3389/fonc.2024.1487198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 12/17/2024] [Indexed: 01/31/2025] Open
Abstract
Background Nanotechnology has increasingly been applied in the diagnosis and treatment of hepatocellular carcinoma (HCC) over the past two decades. This study aims to explore the utilization of nanotechnology in HCC through a bibliometric analysis, identifying key themes, trends, and contributions in this field. Methods The study utilized VOSviewer and CiteSpace software to perform a bibliometric analysis, evaluating scholarly contributions related to nanotechnology in HCC. The analysis focused on co-occurrence network relationships, publications, citations, and contributions from various entities and authors. Results The analysis revealed a total of 2,968 articles, with China and the USA being the most prominent contributors in terms of publications and citations. Notable contributions were made by the Chinese Academy of Sciences and authors Gao Jie and Li Yan. LLOVET JM emerged as the most co-cited author, indicating a leadership role in the field. The "International Journal of Nanomedicine" was identified as the leading publisher, while "Biomaterials" ranked highest in citations. The research mainly focused on drug delivery systems and apoptosis, highlighting significant advancements in utilizing nanotechnology for HCC treatment. Conclusion This bibliometric study underscores the critical role of nanotechnology in advancing the diagnosis and treatment of hepatocellular carcinoma, with a particular emphasis on drug delivery and apoptosis. The findings highlight the contributions of key countries, institutions, and authors, reflecting the global effort and collaboration in this rapidly evolving field.
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Affiliation(s)
- Talaiti Tuergan
- Hepatobiliary and Echinococcosis Surgery Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
- State Key Laboratory of Pathogenesis, Prevention and Management of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, China
| | - Aimitaji Abulaiti
- Hepatobiliary and Echinococcosis Surgery Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Alimu Tulahong
- Hepatobiliary and Echinococcosis Surgery Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
- State Key Laboratory of Pathogenesis, Prevention and Management of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, China
| | - Ruiqing Zhang
- Hepatobiliary and Echinococcosis Surgery Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
- State Key Laboratory of Pathogenesis, Prevention and Management of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, China
| | - Zhongdian Yuan
- Hepatobiliary and Echinococcosis Surgery Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
- State Key Laboratory of Pathogenesis, Prevention and Management of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, China
| | - Yanze Lin
- Hepatobiliary and Echinococcosis Surgery Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
- State Key Laboratory of Pathogenesis, Prevention and Management of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, China
| | - Yingmei Shao
- Hepatobiliary and Echinococcosis Surgery Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
- State Key Laboratory of Pathogenesis, Prevention and Management of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, China
- Xinjiang Clinical Research Center for Echinococcosis and Hepatobiliary Diseases, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Tuerganaili Aji
- Hepatobiliary and Echinococcosis Surgery Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
- State Key Laboratory of Pathogenesis, Prevention and Management of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, China
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11
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Zhou Y, Chen L, Wang T. Nanoparticles in gynecologic cancers: a bibliometric and visualization analysis. Front Oncol 2025; 14:1465987. [PMID: 39845315 PMCID: PMC11750695 DOI: 10.3389/fonc.2024.1465987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 12/16/2024] [Indexed: 01/24/2025] Open
Abstract
Background Gynecological cancers are characterized by uncontrolled cell proliferation within the female reproductive organs. These cancers pose a significant threat to women's health, impacting life expectancy, quality of life, and fertility. Nanoparticles, with their small size, large surface area, and high permeability, have become a key focus in targeted cancer therapy. The aim of this study is to review recent advancements in nanoparticles applied to gynecologic cancers, providing valuable insights for future research. Methods We retrieved all literature on nanoparticles in gynecologic cancers from the Web of Science Core Collection (WOSCC) database between January 1, 2004, and June 4, 2024. Data analysis and visualization were conducted using R software (version 4.4.0), VOSviewer (version 1.6.19.0), and CiteSpace (version 6.1). Results A total of 2,843 publications from January 1, 2004, to June 4, 2024 were searched. Over the past 20 years, there has been a significant increase in publications. The leading countries and institutions in terms of productivity are China and the Chinese Academy of Sciences. The most prolific author and the most co-cited author are Sood, A K and Siegel, Rl. The top journals are the International Journal of Nanomedicine (n=97), followed by ACS Applied Materials & Interfaces (n=72) and Journal of Materials Chemistry B (n=53). Keyword analysis shows current research focuses on two main areas: the application of nanoparticles for drug delivery and their broader applications in gynecologic cancers. Future research will likely focus on "silver nanoparticles," "gold nanoparticles," and "green synthesis." Conclusions Over the past two decades, nanoparticles have rapidly advanced in the field of gynecologic cancers. Research has primarily focused on the applications of nanoparticles in drug delivery and applications. Future trends point toward optimizing synthesis techniques and advancing preclinical studies to clinical applications, particularly for silver and gold nanoparticles. These findings provide valuable scientific insights for researchers.
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Affiliation(s)
| | - Lizhang Chen
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
| | - Tingting Wang
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
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12
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Lin CK, Wu SH, Chua YW, Fan HJ, Cheng YC. TransEBUS: The interpretation of endobronchial ultrasound image using hybrid transformer for differentiating malignant and benign mediastinal lesions. J Formos Med Assoc 2025; 124:28-37. [PMID: 38702216 DOI: 10.1016/j.jfma.2024.04.016] [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: 08/28/2023] [Revised: 03/14/2024] [Accepted: 04/24/2024] [Indexed: 05/06/2024] Open
Abstract
The purpose of this study is to establish a deep learning automatic assistance diagnosis system for benign and malignant classification of mediastinal lesions in endobronchial ultrasound (EBUS) images. EBUS images are in the form of video and contain multiple imaging modes. Different imaging modes and different frames can reflect the different characteristics of lesions. Compared with previous studies, the proposed model can efficiently extract and integrate the spatiotemporal relationships between different modes and does not require manual selection of representative frames. In recent years, Vision Transformer has received much attention in the field of computer vision. Combined with convolutional neural networks, hybrid transformers can also perform well on small datasets. This study designed a novel deep learning architecture based on hybrid transformer called TransEBUS. By adding learnable parameters in the temporal dimension, TransEBUS was able to extract spatiotemporal features from insufficient data. In addition, we designed a two-stream module to integrate information from three different imaging modes of EBUS. Furthermore, we applied contrastive learning when training TransEBUS, enabling it to learn discriminative representation of benign and malignant mediastinal lesions. The results show that TransEBUS achieved a diagnostic accuracy of 82% and an area under the curve of 0.8812 in the test dataset, outperforming other methods. It also shows that several models can improve performance by incorporating two-stream module. Our proposed system has shown its potential to help physicians distinguishing benign and malignant mediastinal lesions, thereby ensuring the accuracy of EBUS examination.
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Affiliation(s)
- Ching-Kai Lin
- Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Department of Mechanical Engineering, College of Engineering, National Yang Ming Chiao Tung University, Hsin-Chu, Taiwan
| | - Shao-Hua Wu
- Department of Department of Mechanical Engineering, College of Engineering, National Yang Ming Chiao Tung University, Hsin-Chu, Taiwan.
| | - Yi-Wei Chua
- Department of Department of Mechanical Engineering, College of Engineering, National Yang Ming Chiao Tung University, Hsin-Chu, Taiwan
| | - Hung-Jen Fan
- Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Biomedical Park Hospital, Hsin-Chu County, 302, Taiwan
| | - Yun-Chien Cheng
- Department of Department of Mechanical Engineering, College of Engineering, National Yang Ming Chiao Tung University, Hsin-Chu, Taiwan.
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13
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Wang Z, Tan Y, Zeng K, Tan H, Xiao P, Su G. Bone density measurement in patients with spinal metastatic tumors using chest quantitative CT deep learning model. J Bone Oncol 2024; 49:100641. [PMID: 40134559 PMCID: PMC11934287 DOI: 10.1016/j.jbo.2024.100641] [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: 06/25/2024] [Revised: 09/25/2024] [Accepted: 09/26/2024] [Indexed: 03/27/2025] Open
Abstract
Objective This study aims to develop a deep learning model using the 3DResUNet architecture to predict vertebral volumetric bone mineral density (vBMD) from Quantitative Computed Tomography (QCT) scans in patients with spinal metastatic tumors, enhancing osteoporosis screening capabilities. Methods 749 patients with spinal metastatic tumors underwent QCT vertebral vBMD measurements. The dataset was randomly split into training (599 cases) and test sets (150 cases). The 3DResUNet model was trained for vBMD classification and prediction using QCT images processed with automated bone segmentation and ROI extraction. Results The deep learning model demonstrated strong performance with Spearman correlation coefficients of 0.923 (training set) and 0.918 (test set) between predicted and QCT-measured vBMD values. Bland-Altman analysis showed a slight bias of -1.42 mg/cm3 (training set) and -1.14 mg/cm3 (test set) between the model predictions and QCT measurements. The model achieved an area under the curve (AUC) of 0.977 (training set) and 0.966 (test set) for diagnosing Osteoporosis based on vBMD. Conclusion The developed deep learning model using 3DResUNet effectively predicts vertebral vBMD from QCT scans in patients with spinal metastatic tumors. It provides accurate and automated vBMD measurements, potentially facilitating widespread osteoporosis screening in clinical practice, mainly where DXA availability is limited.
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Affiliation(s)
- Zhi Wang
- Department of Orthopedics, Changsha Traditional Chinese Medicine Hospital, Changsha 410002, China
| | - Yiyun Tan
- Department of Orthopedics, Changsha Traditional Chinese Medicine Hospital, Changsha 410002, China
| | - Kaibin Zeng
- Department of Orthopedics, Changsha Traditional Chinese Medicine Hospital, Changsha 410002, China
| | - Hao Tan
- Department of Orthopedics, Changsha Traditional Chinese Medicine Hospital, Changsha 410002, China
| | - Pingsen Xiao
- Department of Orthopedics, Changsha Traditional Chinese Medicine Hospital, Changsha 410002, China
| | - Guanghui Su
- Department of Orthopedics, Affiliated Hengyang Hospital, Hunan Normal University (Hengyang Central Hospital), Hengyang, Hunan 421001, China
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Madabhavi IV, Sarkar MS, Sagar RD. Metronomic Chemotherapy After Palliative Radiotherapy in Rare Soft Tissue Sarcomas: An Insight into Radiation Therapy and the Immune Response. Indian J Surg Oncol 2024; 15:677-683. [PMID: 39555377 PMCID: PMC11564421 DOI: 10.1007/s13193-024-01966-2] [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: 11/14/2023] [Accepted: 05/19/2024] [Indexed: 11/19/2024] Open
Abstract
Soft tissue sarcomas (STSs) account for less than 1% of the overall human burden of malignant tumors. The intent of treatment in metastatic STSs is palliative and prognosis is dismal. This study aims to evaluate the role of low-dose radiotherapy and low-dose oral metronomic therapy in heavily pretreated metastatic infrequent STSs. This study was conducted in a prospective observational manner in a tertiary care center. A total of 16 cases met the inclusion criteria for enrollment in the study group. The diagnosis of all subtypes of STS was confirmed by histopathology and immunohistochemistry or cytogenetic studies. All the enrolled patients with metastatic STSs who were treated with surgery and two lines of chemotherapy were initially treated with low-dose radiotherapy of 20 Gy in 5 fractions or 30 Gy in 10 fractions according to the ECOG performance status of the patient. Out of 16 patients, seven patients (43.75%) were treated with 20 Gy, 5#, and 9 patients (56.25%) were treated with 30 Gy, 10# radiotherapy (RT). Out of 16 patients, four were of malignant fibrohistiocytic sarcoma, three were angiosarcoma, three were malignant phylloides tumor of the breast, two were fibrosarcoma, and one patient from each of the following subtypes inflammatory myofiroblastic tumor, leiomyosarcoma, synovial sarcoma, and dermato fibrosarcoma protuberance. Out of 16 patients, seven (43.75%) had a partial response (PR), nine (56.25%) had stable disease (SD) at 3 months, and all the patients had SD at 6 months of evaluation. All the patients had enjoyed a better quality of life as compared to their life during injectable chemotherapy. Targeted low-dose radiation and metronomic chemotherapy leads to quantifiable antiangiogeneic effects and immune effects in the local tumor microenvironment, and influences circulating immune mediators and anti-angiogenesis that could potentially help eradicate disease both within and outside the radiation treatment field.
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Affiliation(s)
- Irappa V. Madabhavi
- Department of Medical and Pediatric Oncology, J N Medical College, and KLE Academy of Higher Education and Research (KAHER), Belagavi, Karnataka India
- Kerudi Cancer Hospital, Bagalkot, Karnataka India
- Nanjappa Hospital, Davanagere, Karnataka India
- Dr. N B Patil Hospital, Gadag, Karnataka India
| | - Malay S. Sarkar
- Department of Pulmonary Medicine, Indira Gandhi Medical College, Shimla, Himachal Pradesh India
| | - Raghavendra D. Sagar
- Department of Radiation Oncology, J N Medical College, Belagavi, Karnataka India
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He M, Ao X, Yang Y, Xu Y, Liu T, Ao L, Guo W, Xing W, Xu J, Qian C, Yu J, Xu X, Yi P. Construction of self-driving anti-αFR CAR-engineered NK cells based on IFN-γ and TNF-α synergistically induced high expression of CXCL10. Neoplasia 2024; 58:101065. [PMID: 39366148 PMCID: PMC11489333 DOI: 10.1016/j.neo.2024.101065] [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: 05/21/2024] [Accepted: 09/25/2024] [Indexed: 10/06/2024]
Abstract
INTRODUCTION Ovarian cancer is the most malignant gynecological tumor. Previous studies have demonstrated that chimeric antigen receptor (CAR)-engineered NK-92 cells targeting folate receptor α (αFR) (NK-92-αFR-CAR) can specifically kill αFR-positive ovarian cancer cells. However, the migration barrier restricts antitumor effects of CAR-engineered cells. OBJECTIVES To elucidate the mechanism by which NK-92-αFR-CAR cells induce the secretion of chemokine CXCL10 during killing ovarian cancer cells. It is speculated that NK-92-αFR-CAR-CXCR3A can target αFR and have chemotaxis of CXCL10, and they may have stronger killing effect of ovarian cancer. METHODS Study the mechanism of CXCL10 expression strongly induced by TNF-α and IFN-γ combined stimulation in ovarian cancer cells. Construct the fourth generation of NK-92-αFR-CAR-CXCR3A cells, which were co-expressed CXCR3A and αFR-CAR. Evaluate the killing and migration effects of NK-92-αFR-CAR-CXCR3A in vitro and in vivo. RESULTS RNA sequencing (RNA-seq) first revealed that the expression level of the chemokine CXCL10 was most significantly increased in ovarian cancer cells co-cultured with NK-92-αFR-CAR. Secondly, cytokine stimulation experiments confirmed that IFN-γ and TNF-α secreted by NK-92-αFR-CAR synergistically induced high CXCL10 expression in ovarian cancer cells. Further signaling pathway experiments showed that IFN-γ and TNF-α enhanced the activation level of the IFN-γ-IFNGR-JAK1/2-STAT1-CXCL10 signaling axis. Cytotoxicity experiments showed that NK-92-αFR-CAR-CXCR3A cells could not only efficiently kill αFR-positive ovarian cancer cells in vitro but also secrete IFN-γ and TNF-α. Higher migration than that of NK-92-αFR-CAR was detected in NK-92-αFR-CAR-CXCR3A using transwell assay. NK-92-αFR-CAR-CXCR3A effectively killed tumor cells in different mouse xenograft models of ovarian cancer and increased infiltration into tumor tissue. CONCLUSION This study confirmed that IFN-γ and TNF-α secreted by αFR-CAR-engineered NK cells can synergistically induce high expression of CXCL10 in ovarian cancer cells and constructed self-driving αFR-CAR-engineered NK cells that can break through migration barriers based on CXCL10, which may provide a new therapeutic weapon for ovarian cancer.
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MESH Headings
- Chemokine CXCL10/metabolism
- Chemokine CXCL10/genetics
- Killer Cells, Natural/immunology
- Killer Cells, Natural/metabolism
- Tumor Necrosis Factor-alpha/metabolism
- Humans
- Interferon-gamma/metabolism
- Female
- Mice
- Animals
- Cell Line, Tumor
- Ovarian Neoplasms/immunology
- Ovarian Neoplasms/metabolism
- Ovarian Neoplasms/pathology
- Ovarian Neoplasms/genetics
- Receptors, Chimeric Antigen/immunology
- Receptors, Chimeric Antigen/metabolism
- Receptors, Chimeric Antigen/genetics
- Xenograft Model Antitumor Assays
- Immunotherapy, Adoptive/methods
- Folate Receptor 1/metabolism
- Folate Receptor 1/genetics
- Receptors, CXCR3/metabolism
- Receptors, CXCR3/genetics
- Cytotoxicity, Immunologic
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Affiliation(s)
- Min He
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Gynecology and Obstetrics, The 958th Hospital, Southwest Hospital, Army Medical University, Chongqing, China
| | - Xiang Ao
- Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, China; Department of orthopedics, 953 Hospital of PLA Army, Shigatse Branch of Xinqiao Hospital, Army Medical University, Shigatse, China
| | - Yu Yang
- Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, China
| | - Yanmin Xu
- Chongqing Key Laboratory of Gene and Cell Therapy, Chongqing Precision Biotech Co., Ltd., Chongqing, China
| | - Tao Liu
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Luoquan Ao
- Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, China
| | - Wei Guo
- Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, China
| | - Wei Xing
- Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, China
| | - Jing Xu
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Cheng Qian
- Chongqing Key Laboratory of Gene and Cell Therapy, Chongqing Precision Biotech Co., Ltd., Chongqing, China
| | - Jianhua Yu
- Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, California 91010, USA; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, California 91010, USA.
| | - Xiang Xu
- Department of Stem Cell & Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, China.
| | - Ping Yi
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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Gafer N, Gebre N, Jabeen I, Ashrafizadeh H, Rassouli M, Mahmoud L. A model for integrating palliative care into Eastern Mediterranean health systems with a primary care approach. BMC Palliat Care 2024; 23:264. [PMID: 39543584 PMCID: PMC11566464 DOI: 10.1186/s12904-024-01590-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 10/29/2024] [Indexed: 11/17/2024] Open
Abstract
BACKGROUND AND AIMS Palliative care in the Eastern Mediterranean Region (EMR) faces challenges despite the high number of patients in need. To provide accessible, affordable, and timely services, it is crucial to adopt a suitable care model. World health organization (WHO) recommends integrating palliative care with primary health care (PHC). Given the unique conditions of EMR countries, there is a need to design a model tailored to these contexts. METHODS This study is a multi-method research project conducted through several sub-studies, including a literature review, policy analysis, expert opinion (Delphi Method), dimension-specific analysis, model development, and its validation and refinement (Delphi Method). Drawing from the WHO model, six dimensions: policy, drug availability, education, community integration, service delivery, and research were considered to developing the model and implementation requirements. Within each dimension, evidence-based solutions tailored to the region's context were explored. RESULTS A successful palliative care model requires, in the policy dimension, oversight by the Ministry of Health (MOH). Having a focal-person or working group within the MOH is crucial for policy-making, formulation, and approval of clinical guidelines, as well as addressing care challenges. It is essential to provide access to morphine and other essential medications, along with facilitating the administration and consumption of morphine at home. Conducting empowerment courses for care providers, can address various challenges. Community involvement through volunteers, charities, and non-governmental organizations (NGOs) is also important. To ensure service provision, monitoring and evaluating systems are crucial, along with striving for service continuity through an appropriate payment system. Lastly, research is necessary for needs assessment, evidence-based practice, and designing evaluation indicators. The proposed model relies on community health workers, especially nurses, as multitasking professionals available for community palliative care. In the presented model, special attention has been given to networking, collaboration, and the use of digital health technologies to support nurses. CONCLUSION The model proposed for integrating palliative care into PHC should serve as a framework that enhances access to available and affordable services for countries in the region. While this model was developed based on the overall conditions of the region, each country can tailor it to its unique strengths and opportunities.
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Affiliation(s)
- Nahla Gafer
- Head Palliative Care Unit, Khartoum Oncology Hospital, King's College London, Cairo, Egypt
| | - Nuhamin Gebre
- Kings College London, Cicely Saunders Institute, Ministry of Health, Addis Ababa, Ethiopia
| | - Ismat Jabeen
- Section of Palliative Medicine, Department of Oncology, The Aga Khan University, Karachi, Pakistan
| | | | - Maryam Rassouli
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Lamia Mahmoud
- Noncommunicable Disease Prevention, World Health Organization Regional Office for the Eastern Mediterranean, Cairo, Egypt
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Rezaeian AH, Wei W. Molecular signaling and clinical implications in the human aging-cancer cycle. Semin Cancer Biol 2024; 106-107:28-42. [PMID: 39197809 PMCID: PMC11625621 DOI: 10.1016/j.semcancer.2024.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 08/07/2024] [Accepted: 08/09/2024] [Indexed: 09/01/2024]
Abstract
It is well documented that aging is associated with cancer, and likewise, cancer survivors display accelerated aging. As the number of aging individuals and cancer survivors continues to grow, it raises additional concerns across society. Therefore, unraveling the molecular mechanisms of aging in tissues is essential to developing effective therapies to fight the aging and cancer diseases in cancer survivors and cancer patients. Indeed, cellular senescence is a critical response, or a natural barrier to suppress the transition of normal cells into cancer cells, however, hypoxia which is physiologically required to maintain the stem cell niche, is increased by aging and inhibits senescence in tissues. Interestingly, oxygen restriction or hypoxia increases longevity and slows the aging process in humans, but hypoxia can also drive angiogenesis to facilitate cancer progression. In addition, cancer treatment is considered as one of the major reasons that drive cellular senescence, subsequently followed by accelerated aging. Several clinical trials have recently evaluated inhibitors to eliminate senescent cells. However, some mechanisms of aging typically can also retard cancer cell growth and progression, which might require careful strategy for better clinical outcomes. Here we describe the molecular regulation of aging and cancer in crosstalk with DNA damage and hypoxia signaling pathways in cancer patients and cancer survivors. We also update several therapeutic strategies that might be critical in reversing the cancer treatment-associated aging process.
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Affiliation(s)
- Abdol-Hossein Rezaeian
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
| | - Wenyi Wei
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
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18
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Zhang W, Guo G, Li X, Lin J, Zheng Z, Huang P, Lin C, Lin Y, Chen X, Lin K, Zheng C, Lin H, Lu Y, Zhang H. A bibliometric analysis of bladder cancer and microRNA research: Trends and advances from 2008 to 2022. Medicine (Baltimore) 2024; 103:e40289. [PMID: 39470484 PMCID: PMC11521070 DOI: 10.1097/md.0000000000040289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Revised: 08/22/2024] [Accepted: 10/10/2024] [Indexed: 10/30/2024] Open
Abstract
Bladder cancer (BC) is a significant global health issue with high incidence and mortality rates. MicroRNAs (miRNAs) play a crucial role in regulating gene expression and have been found to be dysregulated in BC. Understanding the role of miRNAs in BC development could lead to targeted therapies and improved patient management. Our study presents a thorough examination of the correlation between BC and miRNA research from 2008 to 2022. With the help of 3 powerful methods, including VOSviewer, Biblioshiny, and CiteSpace software, we analyzed the retrieved documents from "Core Collection databases online" on the Web of Science. In total, 798 articles were extracted from the Web of Science, and the number of published papers showed an upward trend from 2008 to 2019. The total number of citations was 21,233, of which the highest paper was a review article written by Chan Jiajia et al in 2018 with 752 citations. Based on the result of the coauthor analysis, Seki Naohiko was the most productive writer and China had the highest volume of published articles. Co-citation analysis was used to reveal the knowledge structure of the research field. In addition to the keywords "Bladder cancer" and "miRNA," "Proliferation," "Biomarkers," and "Apoptosis" were the high-frequency used keywords. Recently, increasingly researchers have paid more attention to the field about BC and miRNA around the worldwide. Through in-depth communication and close collaboration, the veil of miRNA in BC has gradually been unveiled. Bibliometric analysis helps to identify hotspots in research and areas for future investigation.
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Affiliation(s)
- Wei Zhang
- Department of Urology, Jieyang People’s Hospital, Jieyang, Guangdong, P. R. China
| | - Gaowei Guo
- Department of Urology, Jieyang People’s Hospital, Jieyang, Guangdong, P. R. China
| | - Xinji Li
- Department of Urology, Jieyang People’s Hospital, Jieyang, Guangdong, P. R. China
| | - Jinming Lin
- Department of Urology, Jieyang People’s Hospital, Jieyang, Guangdong, P. R. China
| | - Zexian Zheng
- Department of Urology, Jieyang People’s Hospital, Jieyang, Guangdong, P. R. China
| | - Peidong Huang
- Department of Urology, Jieyang People’s Hospital, Jieyang, Guangdong, P. R. China
| | - Chuqi Lin
- Department of Urology, Jieyang People’s Hospital, Jieyang, Guangdong, P. R. China
| | - Yurong Lin
- Department of Urology, Jieyang People’s Hospital, Jieyang, Guangdong, P. R. China
| | - Xiaosheng Chen
- Department of Urology, Jieyang People’s Hospital, Jieyang, Guangdong, P. R. China
| | - Kuncheng Lin
- Department of Urology, Jieyang People’s Hospital, Jieyang, Guangdong, P. R. China
| | - Changzheng Zheng
- Department of Urology, Jieyang People’s Hospital, Jieyang, Guangdong, P. R. China
| | - Huirong Lin
- Department of Urology, Jieyang People’s Hospital, Jieyang, Guangdong, P. R. China
| | - Yong Lu
- Department of Urology, Jieyang People’s Hospital, Jieyang, Guangdong, P. R. China
| | - Hui Zhang
- Department of Urology, Jieyang People’s Hospital, Jieyang, Guangdong, P. R. China
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Sardar S, McNair CM, Ravindranath L, Chand SN, Yuan W, Bogdan D, Welti J, Sharp A, Ryan NK, Knudsen LA, Schiewer MJ, DeArment EG, Janas T, Su XA, Butler LM, de Bono JS, Frese K, Brooks N, Pegg N, Knudsen KE, Shafi AA. AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer. Oncogene 2024; 43:3197-3213. [PMID: 39266679 PMCID: PMC11493679 DOI: 10.1038/s41388-024-03148-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 08/20/2024] [Accepted: 08/28/2024] [Indexed: 09/14/2024]
Abstract
Castration resistant prostate cancer (CRPC) remains an incurable disease stage with ineffective treatments options. Here, the androgen receptor (AR) coactivators CBP/p300, which are histone acetyltransferases, were identified as critical mediators of DNA damage repair (DDR) to potentially enhance therapeutic targeting of CRPC. Key findings demonstrate that CBP/p300 expression increases with disease progression and selects for poor prognosis in metastatic disease. CBP/p300 bromodomain inhibition enhances response to standard of care therapeutics. Functional studies, CBP/p300 cistrome mapping, and transcriptome in CRPC revealed that CBP/p300 regulates DDR. Further mechanistic investigation showed that CBP/p300 attenuation via therapeutic targeting and genomic knockdown decreases homologous recombination (HR) factors in vitro, in vivo, and in human prostate cancer (PCa) tumors ex vivo. Similarly, CBP/p300 expression in human prostate tissue correlates with HR factors. Lastly, targeting CBP/p300 impacts HR-mediate repair and patient outcome. Collectively, these studies identify CBP/p300 as drivers of PCa tumorigenesis and lay the groundwork to optimize therapeutic strategies for advanced PCa via CBP/p300 inhibition, potentially in combination with AR-directed and DDR therapies.
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Affiliation(s)
- Sumaira Sardar
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
- The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA
| | | | - Lakshmi Ravindranath
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
- The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA
| | - Saswati N Chand
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
| | - Wei Yuan
- The Institute of Cancer Research, London, United Kingdom
| | - Denisa Bogdan
- The Institute of Cancer Research, London, United Kingdom
| | - Jon Welti
- The Institute of Cancer Research, London, United Kingdom
| | - Adam Sharp
- The Institute of Cancer Research, London, United Kingdom
- The Royal Marsden Hospital, London, United Kingdom
| | - Natalie K Ryan
- South Australian Immunogenomics Cancer Institute, The University of Adelaide, Adelaide, SA, Australia
- South Australian Health and Medical Research Institute, Adelaide, SA, Australia
| | - Liam A Knudsen
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
| | - Matthew J Schiewer
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
| | - Elise G DeArment
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
- The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA
| | - Thomas Janas
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
- The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA
| | - Xiaofeng A Su
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
- The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Lisa M Butler
- South Australian Immunogenomics Cancer Institute, The University of Adelaide, Adelaide, SA, Australia
- South Australian Health and Medical Research Institute, Adelaide, SA, Australia
| | - Johann S de Bono
- The Institute of Cancer Research, London, United Kingdom
- The Royal Marsden Hospital, London, United Kingdom
| | - Kris Frese
- CellCentric Ltd., Cambridge, United Kingdom
| | | | - Neil Pegg
- CellCentric Ltd., Cambridge, United Kingdom
| | | | - Ayesha A Shafi
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
- The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA.
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20
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Wu N, Luan Z, Zhou Z, Wang H, Du S, Chen Y, Wang X, Li J, Peng X. Relationships Between Chemotherapy-Related Cognitive Impairment, Self-Care Ability, and Quality of Life in Breast Cancer Survivors: A Cross-Sectional Study. Semin Oncol Nurs 2024; 40:151690. [PMID: 38971689 DOI: 10.1016/j.soncn.2024.151690] [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: 04/10/2024] [Revised: 06/10/2024] [Accepted: 06/10/2024] [Indexed: 07/08/2024]
Abstract
OBJECTIVES It is not clear how chemotherapy-related cognitive impairment and self-care ability affect the quality of life of women with breast cancer. The purpose of this study was to explore the relationships between chemotherapy-related cognitive impairment, self-care ability, and quality of life in breast cancer patients, and test whether self-care ability plays a mediating role in the association between cognitive impairment and quality of life. METHODS This study was a cross-sectional study, conducted in China in 2022. Self-reported scales were used to assess cognitive function, self-care ability, and quality of life. Data were analyzed using descriptive statistics, spearman correlation analysis and hierarchical multiple regression analyses, the SPSS Process program was used to explore the mediating effect of self-care ability. RESULTS A total of 218 participants were investigated, and approximately 79.3% of patients experienced mild chemotherapy-related cognitive impairment, the mean quality of life score was 59.96 ± 14.15, and the mean self-care ability score was 107.4 ± 24.09. Significant correlations among cognitive impairment, self-care ability, and quality of life were observed (P < .05). Additionally, self-care ability played a partial mediating role between cognitive impairment and quality of life (P < .05), accounting for 24.3% and 22.3%, respectively. CONCLUSIONS Chemotherapy-related cognitive impairment and self-care ability are factors affecting the quality of life of breast cancer survivors. Self-care ability mediates the relationship between cognitive impairment and quality of life. Enhancing patients' self-care ability can improve the quality of life of patients with cognitive impairment. IMPLICATIONS FOR NURSING PRACTICE In the future, oncology nurses should not only pay attention to the severity of cognitive impairment, but also assess the level of patients' self-care ability, provide relevant medical and healthcare guidance, train self-management behavior and strengthen self-care ability by integrating multidisciplinary forces to improve the quality of life of breast cancer patients effectively.
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Affiliation(s)
- Nan Wu
- School of Nursing, Jilin University, Changchun, Jilin Province, China
| | - Ze Luan
- The First Hospital of Jilin University, Changchun, Jilin province, China
| | - Zijun Zhou
- Breast Surgery, Jilin Provincial Tumor Hospital, Changchun, Jilin Province, China
| | - He Wang
- Breast Surgery, Jilin Provincial Tumor Hospital, Changchun, Jilin Province, China
| | - Shiyuan Du
- School of Nursing, Jilin University, Changchun, Jilin Province, China
| | - Yulu Chen
- School of Nursing, Jilin University, Changchun, Jilin Province, China
| | - Xinxin Wang
- School of Nursing, Jilin University, Changchun, Jilin Province, China
| | - Jiong Li
- School of Nursing, Jilin University, Changchun, Jilin Province, China
| | - Xin Peng
- School of Nursing, Jilin University, Changchun, Jilin Province, China.
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21
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Liu X, Jiang L, Peng X, Xu L, Huang L, Wan Q. Evaluating the effects of dyadic intervention for informal caregivers of palliative patients with lung cancer: A systematic review and meta-analysis. Int J Nurs Pract 2024; 30:e13217. [PMID: 37963770 DOI: 10.1111/ijn.13217] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 09/13/2023] [Accepted: 10/22/2023] [Indexed: 11/16/2023]
Abstract
AIM To investigate the effects of dyadic intervention on anxiety, depression, care burden and quality of life in informal caregivers of palliative patients with lung cancer. BACKGROUND Informal caregivers of palliative lung cancer patients bear a large number of negative emotions during the process of caring for the patients. Dyadic intervention has the potential for improving them but the overall effect is unclear. DESIGN A systematic review and meta-analysis. DATA SOURCES All randomized controlled trials were retrieved from the following databases until 4 May 2023: Web of Science, Embase Ovid, PubMed, Cochrane Central Register of Randomized Controlled Trials, Weipu, Wanfang and Chinese National Knowledge Infrastructure databases. REVIEW METHODS This review was performed by Stata 12.0 and Review Manager 5.3. RESULTS Thirteen randomized controlled trials were in accordance with the inclusion and exclusion criteria (n = 1807). The results revealed that dyadic intervention significantly improved family caregivers' anxiety, depression and caregiver burden of palliative patients with lung cancer. There was no significant difference in quality of life between the dyadic intervention group and family caregivers who did not receive the dyadic intervention. CONCLUSIONS Dyadic intervention positively impacts the experience of family caregivers of palliative patients with lung cancer.
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Affiliation(s)
- Xin Liu
- Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China
| | - Li Jiang
- Department of Respiratory and Critical Care Medicine, Huaxi Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China
| | - Xi Peng
- Department of Respiratory and Critical Care Medicine, Huaxi Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China
| | - Ling Xu
- Department of Respiratory and Critical Care Medicine, Huaxi Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China
| | - Lingling Huang
- Department of Respiratory and Critical Care Medicine, Huaxi Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China
| | - Qunfang Wan
- Department of Respiratory and Critical Care Medicine, Huaxi Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China
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22
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Miller CS, Lecavalier-Barsoum M, Ma K, Santos Dutra M, Kaitoukov Y, Bahoric B, Tomic N, Dinelle F, Enger S, Batist G, Yang S, Laporta D, Kavan P, Sahai A, Roberge D, Donath D. Feasibility and safety of endoscopic ultrasound-guided diffusing alpha emitter radiation therapy for advanced pancreatic cancer: Preliminary data. Endosc Int Open 2024; 12:E1085-E1091. [PMID: 39398444 PMCID: PMC11469937 DOI: 10.1055/a-2379-1591] [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: 05/29/2024] [Accepted: 08/02/2024] [Indexed: 10/15/2024] Open
Abstract
Background and study aims Pancreatic cancer is a devastating disease with limited locoregional treatment options. Diffusing alpha-emitter radiation therapy (Alpha DaRT), a novel cancer treatment using alpha-particle interstitial radiotherapy, may help address this challenge. The aim of this study was to evaluate the feasibility and safety of endoscopic ultrasound (EUS)-guided Alpha DaRT for advanced pancreatic cancer. Patients and methods Patients with inoperable locally advanced or metastatic pancreatic adenocarcinoma were treated with EUS-guided Alpha DaRT insertion. The Alpha DaRT sources were delivered into pancreatic tumors using a standard EUS needle with a novel proprietary applicator. Adverse events (AEs) were assessed based on the Common Terminology Criteria for Adverse Events version 5.0. Tumor response was evaluated by imaging 4 to 6 weeks post treatment. Results The first five patients were treated between March and September 2023. The procedure was technically successful in all cases, with Alpha DaRT sources inserted into the target tumor. Estimated gross tumor volume coverage ranged from 8% to 44%. Fourteen AEs were reported among three patients. Four were serious AEs, none of which was associated with the treatment, but rather, with disease progression or medical assistance in dying. Only two AEs (mild) were deemed possibly related to the study device. At the 35-day visit, two patients had progressive disease and three had stable disease, with one of the latter showing partial response 2 months post procedure. Conclusions Preliminary results from this first-in-human trial indicate that EUS-guided Alpha DaRT treatment for unresectable pancreatic cancer is feasible and safe, with no device-associated serious AEs. Further investigation of this promising novel modality is underway.
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Affiliation(s)
- Corey S Miller
- Gastroenterology, Jewish General Hospital, Montreal, Canada
- Medicine, McGill University Faculty of Medicine, Montreal, Canada
- McGill Centre for Translational Research in Cancer, Lady Davis Institute for Medical Research, Montreal, Canada
| | - Magali Lecavalier-Barsoum
- Medicine, McGill University Faculty of Medicine, Montreal, Canada
- McGill Centre for Translational Research in Cancer, Lady Davis Institute for Medical Research, Montreal, Canada
- Radiation Oncology, Jewish General Hospital, Montreal, Canada
| | - Kim Ma
- Medicine, McGill University Faculty of Medicine, Montreal, Canada
- Oncology, Jewish General Hospital, Montreal, Canada
| | - Miriam Santos Dutra
- McGill Centre for Translational Research in Cancer, Lady Davis Institute for Medical Research, Montreal, Canada
| | - Youri Kaitoukov
- Medicine, McGill University Faculty of Medicine, Montreal, Canada
- Radiology, Jewish General Hospital, Montreal, Canada
| | - Boris Bahoric
- McGill Centre for Translational Research in Cancer, Lady Davis Institute for Medical Research, Montreal, Canada
- Radiation Oncology, Jewish General Hospital, Montreal, Canada
| | - Nada Tomic
- Medical Physics Unit, McGill University, Montreal, Canada
| | - Francine Dinelle
- Quality and Transformation Unit, Jewish General Hospital, Montreal, Canada
| | - Shirin Enger
- McGill Centre for Translational Research in Cancer, Lady Davis Institute for Medical Research, Montreal, Canada
- Oncology, Jewish General Hospital, Montreal, Canada
- Medical Physics Unit, McGill University, Montreal, Canada
| | - Gerald Batist
- McGill Centre for Translational Research in Cancer, Lady Davis Institute for Medical Research, Montreal, Canada
- Oncology, Jewish General Hospital, Montreal, Canada
| | - Stephen Yang
- Medicine, McGill University Faculty of Medicine, Montreal, Canada
- Anesthesia, Jewish General Hospital, Montreal, Canada
| | - Donald Laporta
- Medicine, McGill University Faculty of Medicine, Montreal, Canada
- Adult Critical Care and Respirology, Jewish General Hospital, Montreal, Canada
| | - Petr Kavan
- McGill Centre for Translational Research in Cancer, Lady Davis Institute for Medical Research, Montreal, Canada
- Oncology, Jewish General Hospital, Montreal, Canada
| | - Anand Sahai
- Gastroenterology, Centre Hospitalier de l’Université de Montréal, Montreal, Canada
| | - David Roberge
- Radiation Oncology, Centre Hospitalier de l'Université de Montréal, Montreal, Canada
| | - David Donath
- Radiation Oncology, Centre Hospitalier de l'Université de Montréal, Montreal, Canada
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23
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Wulan SN, Anggraini JA, Hidayat W. In Vitro Anticancer Potential of Eugenol on Oral Cancer Cell Lines: A Systematic Review. Malays J Med Sci 2024; 31:10-31. [PMID: 39416730 PMCID: PMC11477475 DOI: 10.21315/mjms2024.31.5.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 06/20/2024] [Indexed: 10/19/2024] Open
Abstract
Oral cancer is one of the most common types of cancer and has become a global health concern. Oral squamous cell carcinoma (OSCC) is the most prevalent form of oral cancer worldwide. Eugenol, an aromatic phenolic compound, exhibits various pharmacological activities, including anticancer effects. Several studies have reported the anticancer activity of eugenol against OSCC via different pathways. However, no current review has discussed the extent of eugenol anticancer research on oral cancer cell lines using in vitro studies. This systematic review aimed to discuss the anticancer potential of eugenol against oral cancer cell lines in vitro. Articles were selected from PubMed, ScienceDirect, SpringerLink and EBSCOhost databases based on specified inclusion and exclusion criteria. Additional articles were identified through manual hand searching. The selection process followed PRISMA guidelines. A risk-of-bias assessment was performed to evaluate the reliability and relevance of the in vitro studies. Thirteen articles with high-quality results were assessed and analysed for further investigation. These studies investigated the ability of eugenol to induce cell death through apoptotic and non-apoptotic pathways, inhibit cell proliferation and affect oxidative stress, contributing to cell death in several oral cancer cell lines. Therefore, eugenol is a potential anticancer agent for OSCC, as it exhibited anticancer activity in oral cancer cell lines in vitro studies.
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Affiliation(s)
- Shafa Nafisa Wulan
- Undergraduate Dentistry Study Program, Faculty of Dentistry, Universitas Padjadjaran, Indonesia
| | - Jamas Ari Anggraini
- Department of Oral Biology, Faculty of Dentistry, Universitas Padjadjaran, Indonesia
| | - Wahyu Hidayat
- Department of Oral Medicine, Faculty of Dentistry, Universitas Padjadjaran, Indonesia
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24
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Thaklaewphan P, Wikan N, Potikanond S, Nimlamool W. Oxyresveratrol Enhances the Anti-Cancer Effect of Cisplatin against Epithelial Ovarian Cancer Cells through Suppressing the Activation of Protein Kinase B (AKT). Biomolecules 2024; 14:1140. [PMID: 39334906 PMCID: PMC11430010 DOI: 10.3390/biom14091140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 09/05/2024] [Accepted: 09/06/2024] [Indexed: 09/30/2024] Open
Abstract
Epithelial ovarian carcinoma poses a significant challenge due to its resistance to chemotherapy and propensity for metastasis, thereby reducing the effectiveness of conventional treatments. Hence, the identification of novel compounds capable of augmenting the anti-cancer efficacy of platinum-based chemotherapy is imperative. Oxyresveratrol (OXY), a derivative of resveratrol, has been demonstrated to possess antiproliferative and apoptosis-inducing effects across various cancer cell lines. Notably, OXY appears to exert its effects by inhibiting the PI3K/AKT/mTOR signaling pathway. However, the synergistic potential of OXY in combination with cisplatin against epithelial ovarian cancer has not yet been elucidated. The current study investigated the synergistic effects of OXY and cisplatin on the ovarian cancer cell lines SKOV3 and TOV21G. We found that OXY significantly enhanced cisplatin's ability to reduce cell viability, induce apoptosis, induce cell cycle arrest, and increase the proportion of cells in the sub-G1 phase. Furthermore, OXY treatment alone dose-dependently inhibited the production of anti-apoptotic proteins including Mcl-1, Bcl-xL, and XIAP under EGF activation. Mechanistically, OXY suppressed the PI3K/AKT/mTOR signaling pathway by reducing phosphorylated AKT, while having no discernible effect on the MAPK pathway. These findings highlight OXY's potential to enhance ovarian cancer cell sensitivity to chemotherapy, suggesting its development as a pharmaceutical adjunct for clinical use in combination therapies.
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Affiliation(s)
- Phatarawat Thaklaewphan
- Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (P.T.); (N.W.); (S.P.)
- Graduate School, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Nitwara Wikan
- Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (P.T.); (N.W.); (S.P.)
| | - Saranyapin Potikanond
- Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (P.T.); (N.W.); (S.P.)
| | - Wutigri Nimlamool
- Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (P.T.); (N.W.); (S.P.)
- Lanna Rice Research Center, Chiang Mai University, Chiang Mai 50200, Thailand
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25
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Hagiyama M, Yoneshige A, Otani T, Wada A, Takeuchi F, Shoya Y, Inoue T, Ito A. An antibody-drug conjugate for endometrioid carcinoma based on the expression of cell adhesion molecule 1. Mol Cell Oncol 2024; 11:2399379. [PMID: 39252827 PMCID: PMC11382700 DOI: 10.1080/23723556.2024.2399379] [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: 05/08/2024] [Revised: 08/27/2024] [Accepted: 08/28/2024] [Indexed: 09/11/2024]
Abstract
Cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, is expressed in endometrial glandular cells highly during the proliferative phase but lowly during the secretory phase. Previously, a CADM1-targeting antibody-drug conjugate (ADC) was generated, in which a humanized anti-CADM1 ectodomain antibody h3E1 was linked with monomethyl auristatin E (h3E1-MMAE ADC). The present study aimed at probing whether this ADC could be useful for the treatment of endometrial neoplasm. Firstly, immunohistochemistry for CADM1 was conducted on proliferative-phase endometrium (n = 13), endometrial hyperplasia (n = 35), and endometrioid carcinoma at various stages (n = 166). CADM1 immunostaining intensity was highest in atypical endometrial hyperplasia and endometrioid carcinoma confined within the endometrium and was decreased stepwise as the carcinoma stage progressed. Next, h3E1-MMAE ADC was examined for its cytotoxicity in vitro using human endometrial adenocarcinoma cell lines expressing CADM1; HEC-1B, HEC-50B, JHUM-3, and OMC-2. The ADC killed these cells in a dose-dependent manner with half maximal inhibitory concentration (IC50) of 12.02 nM for HEC-1B and 2.04 nM for HEC-50B. Collectively, h3E1-MMAE ADC may serve as a noninvasive alternative to simple hysterectomy in the treatment of endometrioid carcinoma confined within the endometrium.
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Affiliation(s)
- Man Hagiyama
- Department of Pathology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, Japan
| | - Azusa Yoneshige
- Department of Pathology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, Japan
| | - Tomoyuki Otani
- Department of Pathology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, Japan
| | - Akihiro Wada
- Department of Pathology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, Japan
| | - Fuka Takeuchi
- Division of Molecular Pathology, Graduate School of Medicine, Kindai University, Osaka-sayama, Osaka, Japan
| | - Yuji Shoya
- Division of Molecular Pathology, Graduate School of Medicine, Kindai University, Osaka-sayama, Osaka, Japan
- Pharma Foods International Co., Ltd., Ohara, Nishikyo-Ku, Kyoto, Japan
| | - Takao Inoue
- Department of Pathology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, Japan
| | - Akihiko Ito
- Department of Pathology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka, Japan
- Division of Molecular Pathology, Graduate School of Medicine, Kindai University, Osaka-sayama, Osaka, Japan
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Martins C, Padilha R, Okumura L, Melo A, Costa R. Microcosting Analysis of Advanced Ovarian Cancer: Real-World Evidence From the Perspective of a Reference Public Brazilian Hospital. Value Health Reg Issues 2024; 43:100999. [PMID: 38714096 DOI: 10.1016/j.vhri.2024.100999] [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: 12/04/2023] [Revised: 02/22/2024] [Accepted: 04/04/2024] [Indexed: 05/09/2024]
Abstract
OBJECTIVES Evaluate the cost of advanced ovarian cancer, using the microcosting technique, based on real-world evidence from the perspective of a reference Brazilian public hospital. METHODS Retrospective cohort study of patients newly diagnosed with advanced ovarian cancer in 2017 and followed-up for up to 5 years. A bottom-up microcosting method was applied, using the activity-based cost approach, which evaluates service costs based on activity consumption throughout patients' journey. RESULTS The results indicate a median overall survival of 35.3 months and a median age of 57 years (33-80 years old). The average cost per patient was USD 34 991.595 over a period of 35.3 months, with admissions because of the disease progression and end-of-life care being the most relevant. CONCLUSIONS The results show that the costs of activities currently involved in the treatment of advanced ovarian cancer represent an important economic impact for the public health system. These data can support future analyses on the impact of incorporating new technologies for the treatment of ovarian cancer and on the financing and sustainability of the Brazilian public healthcare system.
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Affiliation(s)
- Carolina Martins
- Hospital do Câncer II, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil
| | - Raquelaine Padilha
- Hospital do Câncer II, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil
| | | | - Andreia Melo
- Divisão de Pesquisa Clínica e Desenvolvimento Tecnológico, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil
| | - Rodrigo Costa
- Hospital do Câncer II, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil.
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Kobayahshi K, Nojiri K, Suwa H, Yoshida K, Masui H. Radical Resection of Small Bowel Adenocarcinoma With Multiple Liver Metastases Following Neoadjuvant Chemotherapy: A Case Report. Cureus 2024; 16:e69776. [PMID: 39429309 PMCID: PMC11490939 DOI: 10.7759/cureus.69776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/20/2024] [Indexed: 10/22/2024] Open
Abstract
Small bowel adenocarcinoma (SBA) is a relatively rare disease that is difficult to detect in the early stages; therefore, it often has a poor prognosis. We present a rare case of SBA and multiple liver metastases in a patient who underwent curative resection combined with neoadjuvant chemotherapy (NAC). A 70-year-old woman presented to the emergency department complaining of abdominal pain and bloating. She was diagnosed with bowel obstruction due to a primary jejunal tumor and was admitted to the hospital. After further imaging and histopathological examination, the patient was diagnosed with primary jejunal adenocarcinoma with multiple liver metastases, all of which were considered resectable. Since she had developed bowel obstruction due to the primary tumor, jejunal resection with draining lymph node removal was initially performed. The remaining multiple liver metastases were treated with four courses of capecitabine and oxaliplatin (CAPEOX) with bevacizumab as NAC, followed by hepatectomy. After NAC, the patient underwent radical liver resection. Based on a pathological examination, the five liver tumors were all diagnosed as liver metastases from jejunal adenocarcinoma. Six months after the liver resection, a single recurrence was observed in segment V of the liver. Therefore, four courses of CAPEOX with bevacizumab were administered again as NAC, and liver resection was performed again. At the time of writing this report, she has survived for more than four years after the first surgery, with no apparent recurrence. This is a rare case of a patient who underwent radical resection of SBA with multiple liver metastases following CAPEOX and bevacizumab as NAC.
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Affiliation(s)
- Kei Kobayahshi
- Department of Gastrointestinal Surgery, Yokosuka Kyosai Hospital, Yokosuka, JPN
| | - Kazunori Nojiri
- Department of Gastrointestinal Surgery, Yokosuka Kyosai Hospital, Yokosuka, JPN
| | - Hirokazu Suwa
- Department of Gastrointestinal Surgery, Yokosuka Kyosai Hospital, Yokosuka, JPN
| | - Kenichi Yoshida
- Department of Gastrointestinal Surgery, Yokosuka Kyosai Hospital, Yokosuka, JPN
| | - Hidenobu Masui
- Department of Gastrointestinal Surgery, Yokosuka Kyosai Hospital, Yokosuka, JPN
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Yang DH, Park SH, Yoon S. Differential Diagnosis of Pancreatic Cancer and its Mimicking Lesions. JOURNAL OF THE KOREAN SOCIETY OF RADIOLOGY 2024; 85:902-915. [PMID: 39416316 PMCID: PMC11473986 DOI: 10.3348/jksr.2023.0100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 12/02/2023] [Accepted: 02/12/2024] [Indexed: 10/19/2024]
Abstract
Pancreatic cancer is usually detected through contrast-enhanced CT and MRI. However, pancreatic cancer is occasionally overlooked because of its small size or is misdiagnosed as other conditions due to atypical imaging features that present diagnostic challenges. Considering the rapid growth and poor prognosis associated with pancreatic cancer, the ability to accurately detect and differentiate pancreatic lesions is crucial for appropriate surgical intervention. Reviewing diverse challenging cases of pancreatic cancer at an early stage and other mimicking lesions may help us accurately interpret the imaging features of pancreatic cancer on CT and MRI scans. Therefore, we aimed to illustrate various imaging features of pancreatic cancer and its mimicking lesions and provide valuable insights for differential diagnosis.
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Bresadola L, Weber D, Ritzel C, Löwer M, Bukur V, Akilli-Öztürk Ö, Schuster C, Gargano A, Becker J, Mehanna H, Schrörs B, Vascotto F, Sahin U, Kong A. Temporal evolution and inter-patient heterogeneity in primary and recurrent head and neck squamous cell carcinoma. BJC REPORTS 2024; 2:62. [PMID: 39516649 PMCID: PMC11524138 DOI: 10.1038/s44276-024-00091-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 07/15/2024] [Accepted: 08/09/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Head and neck squamous cell carcinomas (HNSCCs) are heterogeneous in terms of origin and aetiology. In addition, there is uncertainty about the genetic evolution from initial diagnosis to recurrence after primary treatments and further disease progression following systemic treatment. Changes in the genetic profile have implications on the selection of appropriate treatments for patients, especially in the era of targeted therapies and immunotherapies. METHODS We analysed a cohort of nine HNSCC patients with metachronous recurrence. All patients had paired primary and recurrent samples suitable for whole-exome sequencing, while transcriptomic data from seven patients could be analysed (multiple recurrent samples collected at different time points were available for three patients). RESULTS At the genomic level, the recurrences shared a fraction of the somatic single nucleotide variants (SNVs) with the index primary tumours, but they also acquired many additional mutations, while losing only a few others. A similar behaviour was also observed when examining the changes of mutational signatures between primary and recurrent samples. Overall, recurrences appeared thus more genetically diverse than the respective primary tumours. The transcriptomic analysis showed that recurrent samples had lower immune cell presence, which was also confirmed by the multiplex immunofluorescence (IF) histology assays performed on the PhenoCycler platform. Several genes related to immune response were significantly downregulated compared to the primary samples. CONCLUSIONS Our results underline the importance of analysing multiple samples per patient to obtain a more complete picture of the patient's tumour and advocate a re-biopsy in the event of recurrence and treatment failure, in order to select the most appropriate therapeutic strategy.
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Affiliation(s)
- Luisa Bresadola
- TRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - David Weber
- TRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Christoph Ritzel
- University Medical Center at the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Martin Löwer
- TRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Valesca Bukur
- TRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Özlem Akilli-Öztürk
- TRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Christian Schuster
- TRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Alessandra Gargano
- TRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Julia Becker
- TRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Hisham Mehanna
- Institute of Head and Neck Studies (InHANSE), Birmingham, UK
| | - Barbara Schrörs
- TRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Fulvia Vascotto
- TRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Ugur Sahin
- TRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
- University Medical Center at the Johannes Gutenberg University Mainz, Mainz, Germany.
- HI-TRON, Helmholtz Institute for Translational Oncology Mainz - A Helmholtz Institute of the DKFZ, Mainz, Germany.
| | - Anthony Kong
- TRON-Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
- Institute of Head and Neck Studies (InHANSE), Birmingham, UK.
- Comprehensive Cancer Centre, King's College London, London, UK.
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Fang Z, Bunston C, Xu Y, Ruge F, Sui L, Liu M, Al-Sarireh B, Griffiths P, Murphy K, Pugh MR, Hao C, Jiang WG, Ye L. Implication of Capillary Morphogenesis Gene 2 (CMG2) in the Disease Progression and Peritoneal Metastasis of Pancreatic Cancer. Cancers (Basel) 2024; 16:2893. [PMID: 39199664 PMCID: PMC11352480 DOI: 10.3390/cancers16162893] [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: 06/06/2024] [Revised: 08/13/2024] [Accepted: 08/17/2024] [Indexed: 09/01/2024] Open
Abstract
Capillary morphogenesis gene 2 (CMG2) mediates cell-matrix interactions to facilitate cell adhesion and migration. CMG2 has been implicated in the disease progression of breast cancer, prostate cancer and gastric cancer. The present study aims to determine the role of CMG2 in the disease progression and peritoneal metastasis of pancreatic cancer. Pancreatic tumour samples were collected from Peking University Cancer Hospital. CMG2 expression was determined using quantitative PCR. After the creation of knockdown and overexpression of CMG2 in pancreatic cancer cells, the effect of CMG2 on several cell functions and adhesion to the peritoneum was examined. Potential pathways regulated by CMG2 were found via proteomics analysis and drug tests. CMG2 was upregulated in pancreatic cancer tissues and associated with a poor prognosis. CMG2 was increased in metastatic lesions and those primary tumours with distant metastases. CMG2 promotes cell-cell, cell-matrix and cell-hyaluronic acid adhesion, which may be mediated by epidermal growth factor receptor (EGFR) and focal adhesion kinase (FAK) pathway activation.
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Affiliation(s)
- Ziqian Fang
- Cardiff China Medical Research Collaborative, Division of Cancer & Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK; (Z.F.); (Y.X.); (F.R.); (L.S.); (M.L.); (W.G.J.)
| | - Carly Bunston
- Cardiff China Medical Research Collaborative, Division of Cancer & Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK; (Z.F.); (Y.X.); (F.R.); (L.S.); (M.L.); (W.G.J.)
| | - Yali Xu
- Cardiff China Medical Research Collaborative, Division of Cancer & Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK; (Z.F.); (Y.X.); (F.R.); (L.S.); (M.L.); (W.G.J.)
| | - Fiona Ruge
- Cardiff China Medical Research Collaborative, Division of Cancer & Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK; (Z.F.); (Y.X.); (F.R.); (L.S.); (M.L.); (W.G.J.)
| | - Laijian Sui
- Cardiff China Medical Research Collaborative, Division of Cancer & Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK; (Z.F.); (Y.X.); (F.R.); (L.S.); (M.L.); (W.G.J.)
| | - Ming Liu
- Cardiff China Medical Research Collaborative, Division of Cancer & Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK; (Z.F.); (Y.X.); (F.R.); (L.S.); (M.L.); (W.G.J.)
| | - Bilal Al-Sarireh
- Department of Surgery, Morriston Hospital, ABM University Health Board, Swansea SA6 6NL, UK;
| | - Paul Griffiths
- Department of Pathology, Morriston Hospital, ABM University Health Board, Swansea SA6 6NL, UK; (P.G.); (M.R.P.)
| | - Kate Murphy
- Department of Pathology, Morriston Hospital, ABM University Health Board, Swansea SA6 6NL, UK; (P.G.); (M.R.P.)
| | - Matthew R. Pugh
- Department of Pathology, Morriston Hospital, ABM University Health Board, Swansea SA6 6NL, UK; (P.G.); (M.R.P.)
| | - Chunyi Hao
- Key Laboratory of Carcinogenesis and Translational Research, Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China;
| | - Wen G. Jiang
- Cardiff China Medical Research Collaborative, Division of Cancer & Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK; (Z.F.); (Y.X.); (F.R.); (L.S.); (M.L.); (W.G.J.)
| | - Lin Ye
- Cardiff China Medical Research Collaborative, Division of Cancer & Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK; (Z.F.); (Y.X.); (F.R.); (L.S.); (M.L.); (W.G.J.)
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Tabrizi L, M. Jones A, Romero-Canelon I, Erxleben A. Multiaction Pt(IV) Complexes: Cytotoxicity in Ovarian Cancer Cell Lines and Mechanistic Studies. Inorg Chem 2024; 63:14958-14968. [PMID: 39083592 PMCID: PMC11323244 DOI: 10.1021/acs.inorgchem.4c01586] [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] [Received: 04/18/2024] [Revised: 07/16/2024] [Accepted: 07/16/2024] [Indexed: 08/02/2024]
Abstract
Ovarian cancer has the worst case-to-fatality ratio of all gynecologic malignancies. The main reasons for the high mortality rate are relapse and the development of chemoresistance. In this paper, the cytotoxic activity of two new multiaction platinum(IV) derivatives of cisplatin and oxaliplatin in a panel of ovarian cancer cells is reported. Cis,cis,trans-[Pt(NH3)2Cl2(IPA)(DCA)] (1) and trans-[Pt(DACH)(OX)(IPA)(DCA)] (2) (IPA = indole-3-propionic acid, DCA = dichloroacetate, DACH = 1R,2R-1,2-diaminocyclohexane, OX = oxalate) were synthesized and characterized by elemental analysis, ESI-MS, FT-IR, and 1H, 13C, and195Pt NMR spectroscopy. The biological activity was evaluated in A2780, PEA1, PEA2, SKOV3, SW626, and OVCAR3 cells. Both complexes are potent cytotoxins. Remarkably, complex 2 is 14 times more active in OVCAR3 cells than cisplatin and is able to overcome cisplatin resistance in PEA2 and A2780cis cells, which are models of post-treatment patient-developed and laboratory-induced resistance. This complex also shows activity in 3D cancer models of the A2780 cells. Mechanistic studies revealed that the complexes induce apoptosis via DNA damage and ROS generation.
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Affiliation(s)
- Leila Tabrizi
- School
of Biological and Chemical Sciences, University
of Galway, Galway H91 TK33, Ireland
- School
of Chemical Sciences, Dublin City University, Dublin D09W6Y4, Ireland
| | - Alan M. Jones
- School
of Pharmacy, University of Birmingham, Birmingham B15 2TT, U.K.
| | - Isolda Romero-Canelon
- School
of Pharmacy, University of Birmingham, Birmingham B15 2TT, U.K.
- Department
of Chemistry, University of Warwick, Coventry CV4 7AL, U.K.
| | - Andrea Erxleben
- School
of Biological and Chemical Sciences, University
of Galway, Galway H91 TK33, Ireland
- Synthesis
and Solid State Pharmaceutical Centre (SSPC), Limerick V94 T9PX, Ireland
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Du F, Zhou H, Niu Y, Han Z, Sui X. Transformaer-based model for lung adenocarcinoma subtypes. Med Phys 2024; 51:5337-5350. [PMID: 38427790 DOI: 10.1002/mp.17006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 01/27/2024] [Accepted: 01/27/2024] [Indexed: 03/03/2024] Open
Abstract
BACKGROUND Lung cancer has the highest morbidity and mortality rate among all types of cancer. Histological subtypes serve as crucial markers for the development of lung cancer and possess significant clinical values for cancer diagnosis, prognosis, and prediction of treatment responses. However, existing studies only dichotomize normal and cancerous tissues, failing to capture the unique characteristics of tissue sections and cancer types. PURPOSE Therefore, we have pioneered the classification of lung adenocarcinoma (LAD) cancer tissues into five subtypes (acinar, lepidic, micropapillary, papillary, and solid) based on section data in whole-slide image sections. In addition, a novel model called HybridNet was designed to improve the classification performance. METHODS HybridNet primarily consists of two interactive streams: a Transformer and a convolutional neural network (CNN). The Transformer stream captures rich global representations using a self-attention mechanism, while the CNN stream extracts local semantic features to optimize image details. Specifically, during the dual-stream parallelism, the feature maps of the Transformer stream as weights are weighted and summed with those of the CNN stream backbone; at the end of the parallelism, the respective final features are concatenated to obtain more discriminative semantic information. RESULTS Experimental results on a private dataset of LAD showed that HybridNet achieved 95.12% classification accuracy, and the accuracy of five histological subtypes (acinar, lepidic, micropapillary, papillary, and solid) reached 94.5%, 97.1%, 94%, 91%, and 99% respectively; the experimental results on the public BreakHis dataset show that HybridNet achieves the best results in three evaluation metrics: accuracy, recall and F1-score, with 92.40%, 90.63%, and 91.43%, respectively. CONCLUSIONS The process of classifying LAD into five subtypes assists pathologists in selecting appropriate treatments and enables them to predict tumor mutation burden (TMB) and analyze the spatial distribution of immune checkpoint proteins based on this and other clinical data. In addition, the proposed HybridNet fuses CNN and Transformer information several times and is able to improve the accuracy of subtype classification, and also shows satisfactory performance on public datasets with some generalization ability.
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Affiliation(s)
- Fawen Du
- School of Information Science and Engineering, Shandong Normal University, Jinan, Shandong, China
| | - Huiyu Zhou
- School of Computing and Mathematic Sciences, University of Leicester, Leicester, UK
| | - Yi Niu
- School of Information Science and Engineering, Shandong Normal University, Jinan, Shandong, China
| | - Zeyu Han
- School of Mathematics and Statistics, Shandong University, Weihai, China
| | - Xiaodan Sui
- School of Information Science and Engineering, Shandong Normal University, Jinan, Shandong, China
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Rincon-Torroella J, Dal Molin M, Mog B, Han G, Watson E, Wyhs N, Ishiyama S, Ahmedna T, Minn I, Azad NS, Bettegowda C, Papadopoulos N, Kinzler KW, Zhou S, Vogelstein B, Gabrielson K, Sur S. ME3BP-7 is a targeted cytotoxic agent that rapidly kills pancreatic cancer cells expressing high levels of monocarboxylate transporter MCT1. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2023.07.23.550207. [PMID: 37546808 PMCID: PMC10401962 DOI: 10.1101/2023.07.23.550207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/08/2023]
Abstract
Nearly 30% of Pancreatic ductal adenocarcinoma (PDAC)s exhibit a marked overexpression of Monocarboxylate Transporter 1 (MCT1) offering a unique opportunity for therapy. However, biochemical inhibitors of MCT1 have proven unsuccessful in clinical trials. In this study we present an alternative approach using 3-Bromopyruvate (3BP) to target MCT1 overexpressing PDACs. 3BP is a cytotoxic agent that is known to be transported into cells via MCT1, but its clinical usefulness has been hampered by difficulties in delivering the drug systemically. We describe here a novel microencapsulated formulation of 3BP (ME3BP-7), that is effective against a variety of PDAC cells in vitro and remains stable in serum. Furthermore, systemically administered ME3BP-7 significantly reduces pancreatic cancer growth and metastatic spread in multiple orthotopic models of pancreatic cancer with manageable toxicity. ME3BP-7 is, therefore, a prototype of a promising new drug, in which the targeting moiety and the cytotoxic moiety are both contained within the same single small molecule. One Sentence Summary ME3BP-7 is a novel formulation of 3BP that resists serum degradation and rapidly kills pancreatic cancer cells expressing high levels of MCT1 with tolerable toxicity in mice.
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Imamura T, Komatsu S, Nishibeppu K, Kiuchi J, Ohashi T, Konishi H, Shiozaki A, Yamamoto Y, Moriumura R, Ikoma H, Ochiai T, Otsuji E. Urinary microRNA-210-3p as a novel and non-invasive biomarker for the detection of pancreatic cancer, including intraductal papillary mucinous carcinoma. BMC Cancer 2024; 24:907. [PMID: 39069624 DOI: 10.1186/s12885-024-12676-x] [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: 08/18/2023] [Accepted: 07/23/2024] [Indexed: 07/30/2024] Open
Abstract
BACKGROUND This study aims to explore novel microRNAs in urine for screening and predicting clinical characteristics in pancreatic cancer (PC) patients using a microRNA array-based approach. METHODS We used the Toray® 3D-Gene microRNA array-based approach to compare urinary levels between PC patients and healthy volunteers. RESULTS (1) Four oncogenic microRNAs (miR-744-5p, miR-572, miR-210-3p, and miR-575) that were highly upregulated in the urine of PC patients compared to healthy individuals were identified by comprehensive microRNA array analysis. (2) Test-scale analysis by quantitative RT-PCR for each group of 20 cases showed that miR-210-3p was significantly upregulated in the urine of PC patients compared to healthy individuals (P = 0.009). (3) Validation analysis (58 PC patients and 35 healthy individuals) confirmed that miR-210-3p was significantly upregulated in the urine of PC patients compared to healthy individuals (P < 0.001, area under the receiver operating characteristic curve = 0.79, sensitivity: 0.828, specificity: 0.743). We differentiated PC patients into invasive ductal carcinoma (IDCa) and intraductal papillary mucinous carcinoma (IPMC) groups. In addition to urinary miR-210-3p levels being upregulated in IDCa over healthy individuals (P = 0.009), urinary miR-210-3p levels were also elevated in IPMC over healthy individuals (P = 0.0018). Urinary miR-210-3p can differentiate IPMC from healthy individuals by a cutoff of 8.02 with an AUC value of 0.762, sensitivity of 94%, and specificity of 63%. (4) To test whether urinary miR210-3p levels reflected plasma miR-210-3p levels, we examined the correlation between urinary and plasma levels. Spearman's correlation analysis showed a moderate positive correlation (ρ = 0.64, P = 0.005) between miR-210-3p expression in plasma and urine. CONCLUSIONS Urinary miR-210-3p is a promising, non-invasive diagnostic biomarker of PC, including IPMC. TRIAL REGISTRATION Not applicable.
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MESH Headings
- Humans
- MicroRNAs/urine
- MicroRNAs/blood
- MicroRNAs/genetics
- Female
- Male
- Biomarkers, Tumor/urine
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/blood
- Pancreatic Neoplasms/urine
- Pancreatic Neoplasms/genetics
- Pancreatic Neoplasms/diagnosis
- Pancreatic Neoplasms/blood
- Middle Aged
- Aged
- Adenocarcinoma, Mucinous/urine
- Adenocarcinoma, Mucinous/genetics
- Adenocarcinoma, Mucinous/diagnosis
- ROC Curve
- Case-Control Studies
- Gene Expression Regulation, Neoplastic
- Adult
- Carcinoma, Pancreatic Ductal/urine
- Carcinoma, Pancreatic Ductal/genetics
- Carcinoma, Pancreatic Ductal/diagnosis
- Carcinoma, Pancreatic Ductal/blood
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Affiliation(s)
- Taisuke Imamura
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Shuhei Komatsu
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
| | - Keiji Nishibeppu
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Jun Kiuchi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Takuma Ohashi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Hirotaka Konishi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Atsushi Shiozaki
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Yusuke Yamamoto
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Ryo Moriumura
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Hisashi Ikoma
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Toshiya Ochiai
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Eigo Otsuji
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii- cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
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Sharan KC, Srinivasan R, Uppal R, Rohilla M, Dey P, Kakkar N, Mavuduru RS. Utility of UroVysion Fluorescence in situ Hybridization in Improving the Diagnostic Performance of Urine Cytology. Acta Cytol 2024; 68:423-435. [PMID: 39047715 DOI: 10.1159/000540070] [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: 02/16/2024] [Accepted: 06/18/2024] [Indexed: 07/27/2024]
Abstract
INTRODUCTION The atypical urothelial cell (AUC) category in The Paris System (TPS) in urine cytology (UrCy) is a challenging area. This study aimed to evaluate the UroVysion fluorescence in situ hybridization (U-FISH) assay in predicting the outcome of AUC. Additionally, we explored the association of abnormal U-FISH results in high-grade urothelial carcinoma (HGUC) concerning muscularis propria invasion (MPI). METHODS This is a retrospective study, and U-FISH was done on archived Papanicolaou-stained smears. Four cohorts were included: non-neoplastic AUC (AUC-NN), neoplastic AUC (AUC-N), muscle-invasive HGUC (HGUC-MI), and muscle-free HGUC (HGUC-MF) outcome on histopathology (HPE) and with clinical follow-up of 12-29 months. U-FISH was evaluated for diagnostic purposes, and MPI and tumor stage prediction by urine FISH score (UFS; high vs. low) based on copy number gain of chromosomes (Chr). RESULTS U-FISH was performed on 70 cases (20 AUC-NN, 20 AUC-N, 15 HGUC-MI, and 15 HGUC-MF) and was successful in 58/70 (82.85%) cases. All UC cases showed polysomy of ≥2Chr, and all the AUC-NN cases reported non-neoplastic on HPE were negative for U-FISH. U-FISH picked up all carcinoma cases in the AUC-N cohort. Chr 3 polysomy was statistically significant in differentiating HGUC-MI from HGUC-MF and low-grade urothelial carcinoma cases. Chr 3 signals with a cut-off of 6 signals could identify MPI with a sensitivity of 80.95% and specificity of 41.94%. The UFS of the HGUC-MI group was significantly higher than HGUC-MF. CONCLUSIONS U-FISH successfully identified all cases of AUC with neoplastic outcomes. In the HGUC group, there was a difference in cases with and without MPI, which requires further confirmation in a larger prospective cohort.
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Affiliation(s)
- K C Sharan
- Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Radhika Srinivasan
- Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Radha Uppal
- Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Manish Rohilla
- Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Pranab Dey
- Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Nandita Kakkar
- Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ravimohan S Mavuduru
- Department of Urology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Ou Y, Zheng Y, Wang D, Ren S, Liu Y. Analysis of preoperative nutrition, immunity and inflammation correlation index on the prognosis of upper tract urothelial carcinoma surgical patients: a retrospective single center study. BMC Surg 2024; 24:208. [PMID: 39010005 PMCID: PMC11251250 DOI: 10.1186/s12893-024-02496-y] [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: 02/21/2024] [Accepted: 07/01/2024] [Indexed: 07/17/2024] Open
Abstract
BACKGROUND SII, PNI, SIRI, AAPR, and LIPI are prognostic scores based on inflammation, nutrition, and immunity. The purpose of this study was to examine the prognostic value of the SII, PNI, SIRI, AAPR, and LIPI in patients with UTUC who underwent radical nephroureterectomy with bladder cuff excision. MATERIALS AND METHODS Data of UTUC patients in Sichuan Provincial People's Hospital from January 2017 to December 2021 were collected. The optimal critical values of SII, PNI, SIRI, and AAPR were determined by ROC curve, and LIPI was stratified according to the dNLR and LDH. The Kaplan-Meier method was used to draw the survival curve, and Cox proportional hazard model was used to analyze the factors affecting the prognosis of UTUC patients. RESULTS A total of 81 patients with UTUC were included in this study. The optimal truncation value of PNI, SII, SIRI and AAPR were determined to be 48.15, 596.4, 1.45 and 0.50, respectively. Univariate Cox proportional hazard regression showed that low PNI, high SII, high SIRI, low AAPR and poor LIPI group were effective predictors of postoperative prognosis of UTUC patients. Multivariate Cox proportional hazard regression showed that high SII was an independent risk factor for postoperative prognosis of UTUC patients. According to ROC curve, the prediction efficiency of fitting indexes of PNI, SII, SIRI, AAPR and LIPI is better than that of using them alone. CONCLUSIONS The SII, PNI, SIRI, AAPR, and LIPI was a potential prognostic predictor in UTUC patients who underwent radical nephroureterectomy with bladder cuff excision.
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Affiliation(s)
- Yong Ou
- Department of Urology, Xichang People's Hospital, Xichang, Sichuan, China
| | - Yang Zheng
- Department of Robotic Minimally Invasive Surgery Center, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital and Affiliated Hospital of the University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Dong Wang
- Department of Robotic Minimally Invasive Surgery Center, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital and Affiliated Hospital of the University of Electronic Science and Technology of China, Chengdu, 610072, China
| | - Shangqing Ren
- Department of Robotic Minimally Invasive Surgery Center, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital and Affiliated Hospital of the University of Electronic Science and Technology of China, Chengdu, 610072, China.
| | - Yisha Liu
- Department of Pathology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.
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Lin H, Zhang X, Feng Y, Gong Z, Li J, Wang W, Fan J. Advancing lung adenocarcinoma prognosis and immunotherapy prediction with a multi-omics consensus machine learning approach. J Cell Mol Med 2024; 28:e18520. [PMID: 38958523 PMCID: PMC11221067 DOI: 10.1111/jcmm.18520] [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: 04/16/2024] [Revised: 05/16/2024] [Accepted: 06/04/2024] [Indexed: 07/04/2024] Open
Abstract
Lung adenocarcinoma (LUAD) is a tumour characterized by high tumour heterogeneity. Although there are numerous prognostic and immunotherapeutic options available for LUAD, there is a dearth of precise, individualized treatment plans. We integrated mRNA, lncRNA, microRNA, methylation and mutation data from the TCGA database for LUAD. Utilizing ten clustering algorithms, we identified stable multi-omics consensus clusters (MOCs). These data were then amalgamated with ten machine learning approaches to develop a robust model capable of reliably identifying patient prognosis and predicting immunotherapy outcomes. Through ten clustering algorithms, two prognostically relevant MOCs were identified, with MOC2 showing more favourable outcomes. We subsequently constructed a MOCs-associated machine learning model (MOCM) based on eight MOCs-specific hub genes. Patients characterized by a lower MOCM score exhibited better overall survival and responses to immunotherapy. These findings were consistent across multiple datasets, and compared to many previously published LUAD biomarkers, our MOCM score demonstrated superior predictive performance. Notably, the low MOCM group was more inclined towards 'hot' tumours, characterized by higher levels of immune cell infiltration. Intriguingly, a significant positive correlation between GJB3 and the MOCM score (R = 0.77, p < 0.01) was discovered. Further experiments confirmed that GJB3 significantly enhances LUAD proliferation, invasion and migration, indicating its potential as a key target for LUAD treatment. Our developed MOCM score accurately predicts the prognosis of LUAD patients and identifies potential beneficiaries of immunotherapy, offering broad clinical applicability.
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Affiliation(s)
- Haoran Lin
- Department of Thoracic SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
| | - Xiao Zhang
- Department of Thoracic SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
| | - Yanlong Feng
- Department of Thoracic SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
| | - Zetian Gong
- Department of Thoracic SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
| | - Jun Li
- Department of Thoracic SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
| | - Wei Wang
- Department of Thoracic SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
| | - Jun Fan
- Department of Thoracic SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
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Tayal S, Gurjar M, Shukla V, Venkatachalam MM, Kumar R, Jain Y. Time-efficient HPLC Validation Methodology for the Qualitative Analysis of 68Ga PSMA-11 in Routine Clinical Usage under Isocratic Method. Indian J Nucl Med 2024; 39:265-271. [PMID: 39790815 PMCID: PMC11708805 DOI: 10.4103/ijnm.ijnm_42_24] [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: 04/06/2024] [Revised: 06/08/2024] [Accepted: 06/14/2024] [Indexed: 01/12/2025] Open
Abstract
Background Prostate-specific membrane antigen (PSMA) has shown to be a promising agent for prostate cancer imaging under PET-CT. With the automation in radiolabeling with 68Ga, using iTG 68Ge/68Ga generator, it has helped introduce various new diagnostic agents and achieve good manufacturing practices (GMP) simultaneously. However, before any radiopharmaceutical is put into clinical usage, it should always be checked for its radiochemical purity and other quality parameters before injecting in the patient. Chromatography techniques such as Gas Chromatography (GC), High-Performance Liquid Chromatography (HPLC), and Thin-Layer Chromatography (TLC) are the most frequently utilized separation technique for purity analysis. A rapid quality control HPLC based methodology was required for radiopharmaceuticals. Aim & Objective In our current setting, we conducted quality control analysis and standardized and validated HPLC method for the routine quality check of 68Ga-PSMA-11. Materials and Methods The QC of 68Ga PSMA-11 was performed under ITLC and HPLC. Results Linearity, accuracy, precision and specificity were assessed and quantified in accordance with International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use (Q2 (R1) ICH) guidelines, which can be implemented in resource-limited settings to check the quality. Conclusion The current HPLC based methodology is rapid, with a retention time of 2.24 min, rendering it a favorable analytical standard operating procedure for QC analysis of 68Ga-PSMA-11.
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Affiliation(s)
- Sachin Tayal
- Department of Nuclear Medicine and Molecular Imaging, Homi Bhabha Cancer Hospital and Mahamana Pandit Madan Mohan Malaviya Cancer Centre, Tata Memorial Centre, Homi Bhabha National Institute, Varanasi, Uttar Pradesh, India
| | - Murari Gurjar
- Department of Nuclear Medicine and Molecular Imaging, Homi Bhabha Cancer Hospital and Mahamana Pandit Madan Mohan Malaviya Cancer Centre, Tata Memorial Centre, Homi Bhabha National Institute, Varanasi, Uttar Pradesh, India
| | - Varun Shukla
- Department of Nuclear Medicine and Molecular Imaging, Homi Bhabha Cancer Hospital and Mahamana Pandit Madan Mohan Malaviya Cancer Centre, Tata Memorial Centre, Homi Bhabha National Institute, Varanasi, Uttar Pradesh, India
| | - Manikandan Marappagounder Venkatachalam
- Department of Nuclear Medicine and Molecular Imaging, Homi Bhabha Cancer Hospital and Mahamana Pandit Madan Mohan Malaviya Cancer Centre, Tata Memorial Centre, Homi Bhabha National Institute, Varanasi, Uttar Pradesh, India
| | - Rohit Kumar
- Department of Nuclear Medicine and Molecular Imaging, Homi Bhabha Cancer Hospital and Mahamana Pandit Madan Mohan Malaviya Cancer Centre, Tata Memorial Centre, Homi Bhabha National Institute, Varanasi, Uttar Pradesh, India
| | - Yash Jain
- Department of Nuclear Medicine and Molecular Imaging, Homi Bhabha Cancer Hospital and Mahamana Pandit Madan Mohan Malaviya Cancer Centre, Tata Memorial Centre, Homi Bhabha National Institute, Varanasi, Uttar Pradesh, India
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Jeong EJ, Choi JJ, Lee SY, Kim YS. The Effects of ML385 on Head and Neck Squamous Cell Carcinoma: Implications for NRF2 Inhibition as a Therapeutic Strategy. Int J Mol Sci 2024; 25:7011. [PMID: 39000120 PMCID: PMC11241175 DOI: 10.3390/ijms25137011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 06/19/2024] [Accepted: 06/22/2024] [Indexed: 07/16/2024] Open
Abstract
Head and neck squamous cell carcinoma (HNSCC) affects squamous cells in the head and neck region and is currently ranked as the sixth most common cancer worldwide. NF-E2-related factor 2 (NRF2) plays a crucial role in cellular protection and defence mechanisms and NRF2 over-expression has been linked to various cancers; however, its role in the response of HNSCC cells remains elusive. We investigated the effects of ML385, a selective NRF2 inhibitor, on HNSCC to understand the underlying molecular mechanisms, and to assess the potential of ML385 as a therapeutic agent. We treated HNSCC cell lines with ML385 and observed a significant reduction in the expression of NRF2 and its downstream target, heme oxygenase-1 (HO-1), using Western blotting. We evaluated its effects on various cellular processes, including cell proliferation, cloning, migration, and wound healing, in HNSCC cell lines. ML385 treatment substantially reduced NRF2 expression, promoting a decrease in the investigated cellular activities. Additionally, we examined changes in the expression of cell-cycle-related proteins and found that ML385 induced cell cycle arrest at the G1/S phase in HNSCC cell lines. Our findings suggest that ML385 can regulate cell cycle progression, inhibit HNSCC growth, and have potential as a therapeutic agent for HNSCC.
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Affiliation(s)
- Eun-Jeong Jeong
- Department of Otorhinolaryngology, Myunggok Medical Research Institute, Konyang University Hospital, Konyang University College of Medicine, Daejeon 35365, Republic of Korea (J.J.C.); (S.Y.L.)
| | - Jong Joong Choi
- Department of Otorhinolaryngology, Myunggok Medical Research Institute, Konyang University Hospital, Konyang University College of Medicine, Daejeon 35365, Republic of Korea (J.J.C.); (S.Y.L.)
| | - Sun Young Lee
- Department of Otorhinolaryngology, Myunggok Medical Research Institute, Konyang University Hospital, Konyang University College of Medicine, Daejeon 35365, Republic of Korea (J.J.C.); (S.Y.L.)
| | - Yeon Soo Kim
- Department of Otorhinolaryngology, Korea University Anam Hospital, Korea University College of Medicine, Seoul 02841, Republic of Korea
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Cash CJ, Pearson JM, Milikowski C, Feun L, Ritch C, Möller MG. Management of intramuscular melanoma metastases to the psoas. BMJ Case Rep 2024; 17:e257500. [PMID: 38839419 DOI: 10.1136/bcr-2023-257500] [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: 06/07/2024] Open
Abstract
We detail a case of a woman in her 40s with isolated melanoma skeletal muscle metastasis (MSMM) to the right psoas muscle. This patient underwent R0 surgical resection through a novel pelvic approach. She received subsequent adjuvant immunotherapy with Braftovi/Mektov along with adjuvant radiation. She is currently disease free at 9 months post surgery. Here, we describe our novel surgical approach including description of the tumour pathology. We explain our multidisciplinary management of MSMM consisting of a multidisciplinary surgical approach by surgical oncology, gynecological oncology and urology as well as multidisciplinary medical management by oncology, radiation oncology and pathology. Finally, we discuss best current options for therapeutic management.
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Affiliation(s)
- Charles Joseph Cash
- Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Joseph Matthew Pearson
- Gynecologic Oncology, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Clara Milikowski
- Department of Pathology and Laboratory Medicine, University of Miami School of Medicine, Miami, Florida, USA
| | - Lynn Feun
- Department of Hematology and Oncology, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Chad Ritch
- Department of Urologic Oncology, University of Miami Miller School of Medicine, Miami, Flordia, USA
| | - Mecker G Möller
- University of Miami Miller School of Medicine, Miami, Florida, USA
- Surgical Oncology, The University of Chicago Pritzker School of Medicine, Chicago, Illinois, USA
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41
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Hosseinzadeh A, Jamshidi Naeini A, Sheibani M, Gholamine B, Reiter RJ, Mehrzadi S. Melatonin and oral diseases: possible therapeutic roles based on cellular mechanisms. Pharmacol Rep 2024; 76:487-503. [PMID: 38607587 DOI: 10.1007/s43440-024-00593-6] [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: 12/27/2023] [Revised: 03/29/2024] [Accepted: 04/02/2024] [Indexed: 04/13/2024]
Abstract
Oral diseases, including periodontal disorders, oral cancer, periodontitis, and mucositis are the major challenges for both patients and healthcare providers. These conditions often involve inflammation, oxidative stress, and impaired cellular processes, leading to symptoms ranging from discomfort to severe debilitation. Conventional treatments for such oral diseases exhibit constraints, prompting the investigation of innovative therapeutic approaches. Considering the anti-inflammatory, anti-oxidant, and anti-cancer effects of melatonin, this study was carried out to investigate the potential protective effects of melatonin in mitigating the severity of oral diseases. Studies indicate that melatonin influences the differentiation of periodontal stem cells, inhibits oral cancer progression, reduces inflammation associated with periodontitis, and alleviates the severity of oral mucositis. Melatonin has demonstrated potential efficacy in both preclinical and clinical investigations; however, findings are frequently heterogeneous and contingent upon contextual factors. This review provides a comprehensiveoverview of current state of knowledge in this domain, elucidating the multifaceted role that melatonin may assume in combatingoral diseases. Further research should be directed toward determining the most effective dosing, timing, and administration methods for melatonin-based therapies for oral diseases.
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Affiliation(s)
- Azam Hosseinzadeh
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Jamshidi Naeini
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Sheibani
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Babak Gholamine
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Russel J Reiter
- Department of Cell Systems and Anatomy, UT Health San Antonio, San Antonio, TX, USA
| | - Saeed Mehrzadi
- Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
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Shah NN, Dave BP, Shah KC, Shah DD, Maheshwari KG, Chorawala MR. Disable 2, A Versatile Tissue Matrix Multifunctional Scaffold Protein with Multifaceted Signaling: Unveiling Role in Breast Cancer for Therapeutic Revolution. Cell Biochem Biophys 2024; 82:501-520. [PMID: 38594547 DOI: 10.1007/s12013-024-01261-5] [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] [Accepted: 03/22/2024] [Indexed: 04/11/2024]
Abstract
The Disabled-2 (DAB2) protein, found in 80-90% of various tumors, including breast cancer, has been identified as a potential tumor suppressor protein. On the contrary, some hypothesis suggests that DAB2 is associated with the modulation of the Ras/MAPK pathway by endocytosing the Grb/Sos1 signaling complex, which produces oncogenes and chemoresistance to anticancer drugs, leading to increased tumor growth and metastasis. DAB2 has multiple functions in several disorders and is typically under-regulated in several cancers, making it a potential target for treatment of cancer therapy. The primary function of DAB2 is the modulation of transforming growth factor- β (TGF-β) mediated endocytosis, which is involved in several mechanisms of cancer development, including tumor suppression through promoting apoptosis and suppressing cell proliferation. In this review, we will discuss in detail the mechanisms through which DAB2 leads to breast cancer and various advancements in employing DAB2 in the treatment of breast cancer. Additionally, we outlined its role in other diseases. We propose that upregulating DAB2 could be a novel approach to the therapeutics of breast cancer.
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Affiliation(s)
- Nidhi N Shah
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Navrangpura, Ahmedabad, 380009, Gujarat, India
| | - Bhavarth P Dave
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Navrangpura, Ahmedabad, 380009, Gujarat, India
| | - Kashvi C Shah
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Navrangpura, Ahmedabad, 380009, Gujarat, India
| | - Disha D Shah
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Navrangpura, Ahmedabad, 380009, Gujarat, India
| | - Kunal G Maheshwari
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Navrangpura, Ahmedabad, 380009, Gujarat, India
| | - Mehul R Chorawala
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Navrangpura, Ahmedabad, 380009, Gujarat, India.
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Bannan A, Mourad A, Nguyen BN, Antaki R. Pelvic Diagnostic Challenges of Appendiceal Neoplasm Mimicking a Hematosalpinx: A Case Report. Cureus 2024; 16:e61945. [PMID: 38978911 PMCID: PMC11230616 DOI: 10.7759/cureus.61945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/08/2024] [Indexed: 07/10/2024] Open
Abstract
Appendiceal mucinous neoplasms are rare and can be easily misdiagnosed as adnexal masses. Fertility is a concern in cases requiring cytoreductive surgery involving the ovaries and if hyperthermic intraperitoneal chemotherapy is considered. We present the case of a 35-year-old patient with primary infertility who was suspected to have a hematosalpinx on ultrasonography and magnetic resonance imaging (MRI) but was found to have an appendiceal mucinous neoplasm on laparoscopy. Fertility preservation was offered to this patient. Appendiceal mucinous neoplasms should be considered in the differential diagnosis of patients in their reproductive years presenting with adnexal masses. Fertility preservation should be discussed with these patients, especially when gonadotoxic treatments are planned.
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Affiliation(s)
- Amro Bannan
- Obstetrics and Gynaecology, University of Jeddah, Jeddah, SAU
- Obstetrics and Gynaecology, University of Montreal Health Centre (CHUM), Montreal, CAN
| | - Ali Mourad
- Obstetrics and Gynaecology, University of Montreal Health Centre (CHUM), Montreal, CAN
| | - Bich N Nguyen
- Pathology and Laboratory Medicine, University of Montreal Health Centre (CHUM), Montreal, CAN
| | - Roland Antaki
- Obstetrics and Gynaecology, University of Montreal Health Centre (CHUM), Montreal, CAN
- Obstetrics and Gynaecology, Ovo Fertility Center, Montreal, CAN
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Umapathy VR, Natarajan PM, Swamikannu B. Molecular and Therapeutic Roles of Non-Coding RNAs in Oral Cancer-A Review. Molecules 2024; 29:2402. [PMID: 38792263 PMCID: PMC11123887 DOI: 10.3390/molecules29102402] [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: 03/15/2024] [Revised: 05/09/2024] [Accepted: 05/12/2024] [Indexed: 05/26/2024] Open
Abstract
Oral cancer (OC) is among the most common malignancies in the world. Despite advances in therapy, the worst-case scenario for OC remains metastasis, with a 50% survival rate. Therefore, it is critical to comprehend the pathophysiology of the condition and to create diagnostic and treatment plans for OC. The development of high-throughput genome sequencing has revealed that over 90% of the human genome encodes non-coding transcripts, or transcripts that do not code for any proteins. This paper describes the function of these different kinds of non-coding RNAs (ncRNAs) in OC as well as their intriguing therapeutic potential. The onset and development of OC, as well as treatment resistance, are linked to dysregulated ncRNA expression. These ncRNAs' potentially significant roles in diagnosis and prognosis have been suggested by their differing expression in blood or saliva. We have outlined every promising feature of ncRNAs in the treatment of OC in this study.
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Affiliation(s)
- Vidhya Rekha Umapathy
- Department of Public Health Dentistry, Dr. M.G.R. Educational and Research Institute, Thai Moogambigai Dental College and Hospital, Chennai 600107, Tamil Nadu, India
| | - Prabhu Manickam Natarajan
- Department of Clinical Sciences, Centre of Medical and Bio-Allied Health Sciences and Research Ajman University, Ajman P.O. Box 346, United Arab Emirates
| | - Bhuminathan Swamikannu
- Department of Prosthodontics, Sree Balaji Dental College and Hospital, Pallikaranai, BIHER, Chennai 600100, Tamil Nadu, India;
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Sardar S, McNair CM, Ravindranath L, Chand SN, Yuan W, Bogdan D, Welti J, Sharp A, Ryan NK, Schiewer MJ, DeArment EG, Janas T, Su XA, Butler LM, de Bono JS, Frese K, Brooks N, Pegg N, Knudsen KE, Shafi AA. AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.05.07.592966. [PMID: 38766099 PMCID: PMC11100730 DOI: 10.1101/2024.05.07.592966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2024]
Abstract
Castration resistant prostate cancer (CRPC) remains an incurable disease stage with ineffective treatments options. Here, the androgen receptor (AR) coactivators CBP/p300, which are histone acetyltransferases, were identified as critical mediators of DNA damage repair (DDR) to potentially enhance therapeutic targeting of CRPC. Key findings demonstrate that CBP/p300 expression increases with disease progression and selects for poor prognosis in metastatic disease. CBP/p300 bromodomain inhibition enhances response to standard of care therapeutics. Functional studies, CBP/p300 cistrome mapping, and transcriptome in CRPC revealed that CBP/p300 regulates DDR. Further mechanistic investigation showed that CBP/p300 attenuation via therapeutic targeting and genomic knockdown decreases homologous recombination (HR) factors in vitro, in vivo, and in human prostate cancer (PCa) tumors ex vivo. Similarly, CBP/p300 expression in human prostate tissue correlates with HR factors. Lastly, targeting CBP/p300 impacts HR-mediate repair and patient outcome. Collectively, these studies identify CBP/p300 as drivers of PCa tumorigenesis and lay the groundwork to optimize therapeutic strategies for advanced PCa via CBP/p300 inhibition, potentially in combination with AR-directed and DDR therapies.
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Affiliation(s)
- Sumaira Sardar
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, 20817, USA
- The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, 20817 USA
| | - Christopher M. McNair
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, 19107, USA
| | - Lakshmi Ravindranath
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, 20817, USA
- The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, 20817 USA
| | - Saswati N. Chand
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, 19107, USA
| | - Wei Yuan
- The Institute of Cancer Research, London, United Kingdom
| | - Denisa Bogdan
- The Institute of Cancer Research, London, United Kingdom
| | - Jon Welti
- The Institute of Cancer Research, London, United Kingdom
| | - Adam Sharp
- The Institute of Cancer Research, London, United Kingdom
- The Royal Marsden Hospital, London, United Kingdom
| | - Natalie K. Ryan
- South Australian Immunogenomics Cancer Institute, The University of Adelaide, Australia
- South Australian Health and Medical Research Institute, Adelaide, Australia
| | - Matthew J. Schiewer
- Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, 19107, USA
| | - Elise G. DeArment
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, 20817, USA
- The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, 20817 USA
| | - Thomas Janas
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, 20817, USA
- The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, 20817 USA
| | - Xiaofeng A. Su
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, 20817, USA
- The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, 20817 USA
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Lisa M. Butler
- South Australian Immunogenomics Cancer Institute, The University of Adelaide, Australia
- South Australian Health and Medical Research Institute, Adelaide, Australia
| | - Johann S. de Bono
- The Institute of Cancer Research, London, United Kingdom
- The Royal Marsden Hospital, London, United Kingdom
| | - Kris Frese
- CellCentric Ltd., Cambridge, United Kingdom
| | | | - Neil Pegg
- CellCentric Ltd., Cambridge, United Kingdom
| | - Karen E. Knudsen
- The American Cancer Society, Philadelphia, Pennsylvania, 19103, USA
| | - Ayesha A. Shafi
- Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, 20817, USA
- The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, 20817 USA
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Karati D, Mukherjee S, Roy S. Deciphering the molecular mechanistic paths describing the chemotherapeutic potential and epigenetic regulation of curcumin in lung cancer: a mini review. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:2715-2725. [PMID: 37982888 DOI: 10.1007/s00210-023-02838-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 11/03/2023] [Indexed: 11/21/2023]
Abstract
In an uncontrolled inflammatory environment, the complex process of lung carcinogenesis occurs. Lung cancer remains the leading cause of cancer-related mortality worldwide. The average 5-year survival rate is still low despite significant advancements in our knowledge of lung carcinogenesis and the development of innovative therapies in recent decades. Research on adjuvant treatment, lung carcinogenesis pathways, and possible prognostic indicators has to be refocused using an innovative approach. The majority of lung cancers are discovered at an advanced stage when there is little chance of recovery. It has grown in popularity in recent years to supplement already available chemotherapeutic therapies with adjuvant herbal medications, which may lessen toxicity and adverse effects without sacrificing therapeutic efficiency. One such prospective contender is curcumin. In-depth research has been done on curcumin as a multi-target anti-tumor and anti-inflammatory molecule. A pharmacologically active polyphenol produced from turmeric is called curcumin. Over the past few decades, curcumin's therapeutic potential has been thoroughly studied, and data indicate that curcumin may play a part in a variety of biological processes, most notably its potent anticancer activity. Being a pleiotropic chemical, curcumin regulates a variety of molecules that are key players in many cell signaling pathways. It has been shown to stifle transformation, restrain proliferation, and trigger apoptosis. Curcumin can reduce the development of non-small cell LC by downregulating Circular RNA hsa_circ_0007580, which in turn controls the expression of integrin subunit beta 1 by adsorbing miR-384. Nevertheless, despite all these advantages, curcumin's effectiveness is still restricted because of its weak bioavailability, poor absorption within the systemic circulation, and quick removal from the body. In an effort to overcome these constraints, scientists from all around the world are working to develop a synthetic and improved curcuminoid by appropriately altering the parent skeleton structurally. These curcuminoids will simultaneously improve the physicochemical properties and efficacy. This review presents evidence from the most recent clinical trials coupled with the molecular mechanisms of curcumin in LC.
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Affiliation(s)
- Dipanjan Karati
- Department of Pharmaceutical Technology, School of Pharmacy, Techno India University, Kolkata, 700091, West Bengal, India
| | - Swarupananda Mukherjee
- Department of Pharmaceutical Technology, NSHM Knowledge Campus, Kolkata, 124 B.L. Saha Road, Kolkata, West Bengal, 700053, India
| | - Souvik Roy
- Department of Pharmaceutical Technology, NSHM Knowledge Campus, Kolkata, 124 B.L. Saha Road, Kolkata, West Bengal, 700053, India.
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Díaz-Abad J, Aranaz-Murillo A, Mayayo-Sinues E, Canchumanya-Huatuco N, Schaye V. Lessons in clinical reasoning - pitfalls, myths, and pearls: shoulder pain as the first and only manifestation of lung cancer. Diagnosis (Berl) 2024; 11:212-217. [PMID: 38387019 DOI: 10.1515/dx-2023-0063] [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: 06/02/2023] [Accepted: 01/16/2024] [Indexed: 02/24/2024]
Abstract
OBJECTIVES Lung cancer is the leading cause of cancer-related death and poses significant challenges in diagnosis and management. Although muscle metastases are exceedingly rare and typically not the initial clinical manifestation of neoplastic processes, their recognition is crucial for optimal patient care. CASE PRESENTATION We present a case report in which we identify the unique scenario of a 60-year-old man with shoulder pain and a deltoid muscle mass, initially suggestive of an undifferentiated pleomorphic sarcoma. However, further investigations, including radiological findings and muscle biopsy, revealed an unexpected primary lung adenocarcinoma. We performed a systematic literature search to identify the incidence of SMM and reflect on how to improve and build on better diagnosis for entities as atypical as this. This atypical presentation highlights the importance of recognizing and addressing cognitive biases in clinical decision-making, as acknowledging the possibility of uncommon presentations is vital. By embracing a comprehensive approach that combines imaging studies with histopathological confirmation, healthcare providers can ensure accurate prognoses and appropriate management strategies, ultimately improving patient outcomes. CONCLUSIONS This case serves as a reminder of the need to remain vigilant, open-minded, and aware of cognitive biases when confronted with uncommon clinical presentations, emphasizing the significance of early recognition and prompt evaluation in achieving optimal patient care.
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Affiliation(s)
- Julia Díaz-Abad
- Department of Internal Medicine, Clínico San Cecilio University Hospital, Granada, Spain
| | | | | | | | - Verity Schaye
- Department of Medicine, NYU Grossman School of Medicine, New York City, NY, USA
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Chakraborty S, Ghosh S. CCND1 Amplification in Pancreatic Ductal and Ampullary Adenocarcinoma and Its Impact on Patients' Survival: a Single-Center Observational Study. Indian J Surg Oncol 2024; 15:226-231. [PMID: 38817999 PMCID: PMC11133249 DOI: 10.1007/s13193-022-01685-6] [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: 10/19/2021] [Accepted: 11/07/2022] [Indexed: 11/15/2022] Open
Abstract
Studies conducted worldwide in the last few decades have demonstrated that various high- and low-frequency inherited and somatic mutations play important roles in the pathogenesis of periampullary carcinoma. Owing to relatively inaccessible location and lack of specific early diagnostic signs, majority of periampullary tumors are difficult to manage. Limited chemotherapeutic options that are available are highly toxic and not very efficacious. CyclinD1, if found to be amplified in these malignancies, might become an important gene to be targeted for monoclonal antibody therapy. An analytical retrospective-prospective study was done on 35 patients of operable periampullary carcinoma, in Medical College, Kolkata from January 2019 to July 2020. After isolating DNA from tumor and corresponding normal tissue by Qiagen DNEasy kit, CyclinD1 amplification was assessed by RT-PCR using Taqman DNA copy number in the laboratory of Indian Statistical Institute. Survival analysis was done by Kaplan-Meier estimator and all statistical calculations performed through SPSS software. Six (17%) out of 35 patients were found to have > twofold amplifications of CyclinD1 gene. However, no positive correlation was found between CyclinD1 amplification and overall survival of the patients (p value 0.21). Positive correlation was not found in our study between CCND1 amplification and periampullary malignancy. However, a single large study conducted in Japan by Yamazaki showed reduced survival and higher metastasis in CyclinD1 positive periampullary carcinoma. So there is reasonable scope in future for large-scale population-based studies to establish similar association in our subcontinent as well.
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Affiliation(s)
- Shuchismita Chakraborty
- Department of General Surgery, Medical College Kolkata, 88, College Street, Kolkata, 700073 West Bengal India
- Kolkata, India
| | - Shibajyoti Ghosh
- Department of General Surgery, Medical College Kolkata, 88, College Street, Kolkata, 700073 West Bengal India
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Aga SS, Yasmeen N, Al-Mansour M, Khan MA, Nissar S, Khawaji B, Awadh A, Alasmari MM, Abushouk A. Knowledge, awareness and attitude towards breast cancer: Risk factors, signs and screening among Health and Allied students: A prospective study. J Family Med Prim Care 2024; 13:1804-1824. [PMID: 38948630 PMCID: PMC11213396 DOI: 10.4103/jfmpc.jfmpc_1720_23] [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: 10/23/2023] [Revised: 12/04/2023] [Accepted: 12/14/2023] [Indexed: 07/02/2024] Open
Abstract
Introduction Breast cancer (BC) is the second most common cancer in Saudi women. Therefore, understanding BC and its related risk factors, symptoms, and screening is critical for early detection and intervention. The current study was meant to explore the knowledge, awareness, and attitude (KAA) gap in BC: risk factors, symptoms, and screening. Material and Methods This cross-sectional investigation was carried out with Health Professions Students (HPS) using a predesigned and validated study questionnaire to examine HPS knowledge and attitudes concerning BC and associated risk factors, symptoms, and screening. Results A total of 277 female students responded to the survey. The frequency of correct answers for the BC knowledge questions varied from the lowest of 27.8% to the highest of 88.8%, with only 5 out of 15 questions (33.3%) answered correctly by more than 60% of the participants, displaying poor knowledge and awareness of BC. A majority (>60%) of the participants identified only 7 of the 18 risk factors of BC correctly, whereas 11 of the 13 early warning signs of BC were identified correctly by the majority (>60%) of the participants. Among the participants, only 26.4% were aware of the breast cancer screening center, but 94.6% of them agreed that early detection of breast cancer is important and 82.7% agreed to participate in the screening program if offered. Conclusion Participants' knowledge and awareness of BC were found to be relatively low; however, their attitudes towards BC screening were positive. As a result, it is critical to develop effective education programs, curricular activities, and awareness campaigns to address the lack of awareness of BC and to have an appropriate response to screening to reduce disease burden.
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Affiliation(s)
- Syed S. Aga
- Department of Basic Medical Sciences, College of Medicine, King Saud Bin Abdul Aziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Centre (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), King Abdulaziz Medical City, Jeddah, Saudi Arabia
- Molecular Diseases and Diagnostics Division, Infinity Biochemistry Pvt. Ltd, Sajjad Abad, Chattabal, Srinagar, Kashmir, India
| | - Nusrath Yasmeen
- Department of Pharmacy, College of Nursing, King Saud Bin Abdul Aziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Centre (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), King Abdulaziz Medical City, Jeddah, Saudi Arabia
| | - Mubarak Al-Mansour
- Department of Medical Education, College of Medicine, King Saud Bin Abdul Aziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Centre (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), King Abdulaziz Medical City, Jeddah, Saudi Arabia
- Adult Medical Oncology, Princess Noorah Oncology Center, King Abdullah International Medical Research Centre (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), King Abdulaziz Medical City, Jeddah, Saudi Arabia
| | - Muhammad A. Khan
- Department of Medical Education, College of Medicine, King Saud Bin Abdul Aziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Centre (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), King Abdulaziz Medical City, Jeddah, Saudi Arabia
| | - Saniya Nissar
- Molecular Diseases and Diagnostics Division, Infinity Biochemistry Pvt. Ltd, Sajjad Abad, Chattabal, Srinagar, Kashmir, India
| | - Bader Khawaji
- Department of Basic Medical Sciences, College of Medicine, King Saud Bin Abdul Aziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Centre (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), King Abdulaziz Medical City, Jeddah, Saudi Arabia
| | - Abdullah Awadh
- Department of Basic Medical Sciences, College of Medicine, King Saud Bin Abdul Aziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Centre (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), King Abdulaziz Medical City, Jeddah, Saudi Arabia
- Department of Medical Education, College of Medicine, King Saud Bin Abdul Aziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Centre (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), King Abdulaziz Medical City, Jeddah, Saudi Arabia
| | - Moudi M. Alasmari
- Department of Basic Medical Sciences, College of Medicine, King Saud Bin Abdul Aziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Centre (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), King Abdulaziz Medical City, Jeddah, Saudi Arabia
| | - Amir Abushouk
- Department of Basic Medical Sciences, College of Medicine, King Saud Bin Abdul Aziz University for Health Sciences (KSAU-HS), King Abdullah International Medical Research Centre (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), King Abdulaziz Medical City, Jeddah, Saudi Arabia
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Fang TZ, Wu XQ, Zhao TQ, Wang SS, Fu GMZ, Wu QL, Zhou CW. Influence of blood glucose fluctuations on chemotherapy efficacy and safety in type 2 diabetes mellitus patients complicated with lung carcinoma. World J Diabetes 2024; 15:645-653. [PMID: 38680689 PMCID: PMC11045413 DOI: 10.4239/wjd.v15.i4.645] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 12/15/2023] [Accepted: 02/21/2024] [Indexed: 04/11/2024] Open
Abstract
BACKGROUND Patients with type 2 diabetes mellitus (T2DM) have large fluctuations in blood glucose (BG), abnormal metabolic function and low immunity to varying degrees, which increases the risk of malignant tumor diseases and affects the efficacy of tumor chemotherapy. Controlling hyperglycemia may have important therapeutic implications for cancer patients. AIM To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma (LC). METHODS The clinical data of 60 T2DM + LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively analyzed. All patients underwent chemotherapy and were grouped as a control group (CG; normal BG fluctuation with a mean fluctuation < 3.9 mmol/L) and an observation group (OG; high BG fluctuation with a mean fluctuation ≥ 3.9 mmol/L) based on their BG fluctuations, with 30 cases each. BG-related indices, tumor markers, serum inflammatory cytokines and adverse reactions were comparatively analyzed. Pearson correlation analysis was performed to analyze the correlation between BG fluctuations and tumor markers. RESULTS The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG, together with markedly higher mean amplitude of glycemic excursions (MAGE), mean of daily differences, largest amplitude of glycemic excursions and standard deviation of blood glucose (P < 0.05). In addition, the OG exhibited evidently higher levels of carbohydrate antigen 19-9, carbohydrate antigen 125, carcinoembryonic antigen, neuron-specific enolase, cytokeratin 19, tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein than the CG (P < 0.05). Pearson analysis revealed a positive association of MAGE with serum tumor markers. The incidence of adverse reactions was significantly higher in the OG than in the CG (P < 0.05). CONCLUSION The greater the BG fluctuation in LC patients after chemotherapy, the more unfavorable the therapeutic effect of chemotherapy; the higher the level of tumor markers and inflammatory cytokines, the more adverse reactions the patient experiences.
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Affiliation(s)
- Tian-Zheng Fang
- Department of Thoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Xian-Qiao Wu
- Department of Thoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Ting-Qi Zhao
- Department of Endocrine, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Shan-Shan Wang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Guo-Mei-Zhi Fu
- Department of Thoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Qing-Long Wu
- Department of Thoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Cheng-Wei Zhou
- Department of Thoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
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