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Tagliero LE, Jones TL, Sherman CE, Aziz KT. Upper Extremity Mass as First Presentation of Metastatic Urothelial Carcinoma. Orthopedics 2025; 48:e52-e55. [PMID: 39699163 DOI: 10.3928/01477447-20241213-01] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2024]
Abstract
A 77-year-old woman presented with metastatic urothelial carcinoma as an elbow mass. To our knowledge, this is only the third reported case of urothelial carcinoma metastasizing to the upper extremity. The presence of metastatic disease at the time of diagnosis of urothelial carcinoma is rare, with metastases to the upper extremities even less common. This case is interesting given that the mass occurred after a direct trauma, causing a delay in diagnosis. It highlights the importance of a multidisciplinary oncology approach, and the need for more research to understand the biology of metastases. [Orthopedics. 2025;48(1):e52-e55.].
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Ganina A, Askarov M, Kozina L, Karimova M, Shayakhmetov Y, Mukhamedzhanova P, Brimova A, Berikbol D, Chuvakova E, Zaripova L, Baigenzhin A. Prospects for Treatment of Lung Cancer Using Activated Lymphocytes Combined with Other Anti-Cancer Modalities. Adv Respir Med 2024; 92:504-525. [PMID: 39727496 PMCID: PMC11673795 DOI: 10.3390/arm92060045] [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: 10/18/2024] [Revised: 11/20/2024] [Accepted: 12/03/2024] [Indexed: 12/28/2024]
Abstract
This review explores the significance and prospects of using diverse T-cell variants in the context of combined therapy for lung cancer treatment. Recently, there has been an increase in research focused on understanding the critical role of tumor-specific T lymphocytes and the potential benefits of autologous T-cell-based treatments for individuals with lung cancer. One promising approach involves intravenous administration of ex vivo-activated autologous lymphocytes to improve the immune status of patients with cancer. Investigations are also exploring the factors that influence the success of T-cell therapy and the methods used to stimulate them. Achieving a comprehensive understanding of the characteristics of activated lymphocytes and deciphering the mechanisms underlying their activation of innate anti-tumor immunity will pave the way for numerous clinical trials and the development of innovative strategies for cancer therapy like combined immunotherapy and radiation therapy.
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Affiliation(s)
- Anastasia Ganina
- JSC National Scientific Medical Center, Astana 010009, Kazakhstan; (M.A.); (L.K.); (M.K.); (E.C.); (L.Z.); (A.B.)
| | - Manarbek Askarov
- JSC National Scientific Medical Center, Astana 010009, Kazakhstan; (M.A.); (L.K.); (M.K.); (E.C.); (L.Z.); (A.B.)
| | - Larissa Kozina
- JSC National Scientific Medical Center, Astana 010009, Kazakhstan; (M.A.); (L.K.); (M.K.); (E.C.); (L.Z.); (A.B.)
| | - Madina Karimova
- JSC National Scientific Medical Center, Astana 010009, Kazakhstan; (M.A.); (L.K.); (M.K.); (E.C.); (L.Z.); (A.B.)
| | - Yerzhan Shayakhmetov
- International Oncological Tomotherapy Center “YMIT”, Astana 010009, Kazakhstan; (Y.S.); (P.M.); (A.B.); (D.B.)
| | - Perizat Mukhamedzhanova
- International Oncological Tomotherapy Center “YMIT”, Astana 010009, Kazakhstan; (Y.S.); (P.M.); (A.B.); (D.B.)
| | - Aigul Brimova
- International Oncological Tomotherapy Center “YMIT”, Astana 010009, Kazakhstan; (Y.S.); (P.M.); (A.B.); (D.B.)
| | - Daulet Berikbol
- International Oncological Tomotherapy Center “YMIT”, Astana 010009, Kazakhstan; (Y.S.); (P.M.); (A.B.); (D.B.)
| | - Elmira Chuvakova
- JSC National Scientific Medical Center, Astana 010009, Kazakhstan; (M.A.); (L.K.); (M.K.); (E.C.); (L.Z.); (A.B.)
| | - Lina Zaripova
- JSC National Scientific Medical Center, Astana 010009, Kazakhstan; (M.A.); (L.K.); (M.K.); (E.C.); (L.Z.); (A.B.)
| | - Abay Baigenzhin
- JSC National Scientific Medical Center, Astana 010009, Kazakhstan; (M.A.); (L.K.); (M.K.); (E.C.); (L.Z.); (A.B.)
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Song J, Ye X, Peng Q, Ying X, Xiao H. Circulating Tumor cells and multiple indicators combined to identify the risk of poorer prognosis in patients with resected non-small cell lung cancer. BMC Cancer 2024; 24:1491. [PMID: 39627742 PMCID: PMC11616275 DOI: 10.1186/s12885-024-13245-y] [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: 09/24/2024] [Accepted: 11/25/2024] [Indexed: 12/06/2024] Open
Abstract
BACKGROUND Surgical resection is an important treatment option for patients with non-small cell lung cancer (NSCLC). However, recurrence and survival rates remain a cause of concern. To further improve prognosis, more studies have focused on liquid biopsy, which has significant value as a prognostic factor for defining the risk stratification of postoperative NSCLC patients. This study aimed to identify circulating tumor cells (CTCs) as biomarkers that indicate a poor prognosis, combined with multiple indicators to determine prognostic risks in advance and develop individualized treatment strategies. METHODS Between November 2015 and August 2018, 65 radical resected patients with NSCLC were analyzed. Preoperative CTCs were collected, and follow-up lasted until August 2023. Overall survival (OS) and disease-free survival (DFS) were the primary outcomes. RESULTS With an 11 CTC unit threshold, the high preoperative CTC level group had worse OS and DFS than the low-level group, suggesting that preoperative CTC levels have prognostic value. Time-dependent receiver operating characteristic (ROC) curves also showed satisfactory predictive efficiency of CTCs. Univariate analysis revealed that preoperative CTC levels were significantly associated with increasing risks for OS and DFS. Moreover, we combined CTCs and multiple indicators to provide a reference for a group at high risk of adverse outcomes. CONCLUSIONS CTCs serve as feasible biomarkers for predicting postoperative prognosis in NSCLC patients. The combination of hematological, radiological, and pathological features could be valuable tools to guide postoperative management and treatment decisions in these patients. A multimodal prognostic approach is important for the clinical evaluation of lung cancer.
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Affiliation(s)
- Jinghan Song
- Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiong Ye
- School of Clinical Medicine, Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Qianqian Peng
- Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xinnan Ying
- Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hui Xiao
- Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Sugai K, Mori T, Bilal T, Furukawa A, Sekine Y, Kobayashi N, Kikuchi S, Goto Y, Ichimura H, Masuda T, Arai F, Sato Y, Matsusaka S. Detection of circulating tumor cells in patients with lung cancer using a rare cell sorter: a pilot study. BMC Cancer 2024; 24:1291. [PMID: 39425044 PMCID: PMC11488178 DOI: 10.1186/s12885-024-12945-9] [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: 03/05/2024] [Accepted: 09/12/2024] [Indexed: 10/21/2024] Open
Abstract
BACKGROUND We developed a Rare Cell Sorter (RCS) for collecting single cell including circulating tumor cells (CTCs). This single-institution pilot study evaluated the ability of this device to detect tumor-like cells in patients with lung cancer and confirmed their genuineness based on the epidermal growth factor receptor (EGFR) mutation concordance with tissue samples. METHODS This study included patients treated for lung cancer from September 2021 to August 2022 in University of Tsukuba Hospital. Peripheral blood samples were obtained before surgery or during periodic medical checks for patients treated with drugs. We used the RCS to capture cells based on size. The cells were stained, and the Hoechst-positive, CD45-negative, and epithelial celladhesion molecule (EpCAM)- positive cells were defined as CTCs, were collected. The presumptive CTCs were counted and tested using digital droplet polymerase chain reaction for EGFR mutations and compared with the tissue EGFR status to check concordance. RESULTS Eighteen patients were included in this study and CTCs were detected in 6 patients (33%). The CTCs from three patients showed EGFR mutation, and the EGFR mutation status of CTCs concorded with that of tissue samples in 83% of the cases (5/6). Only one CTC showed a different status from the tissue, and the concordance rate of EGFR status between CTCs and the tissue was 96% (24/25). CONCLUSION The ability of the RCS to detect CTCs in patients with lung cancer was demonstrated based on the concordance of EGFR status in this pilot study. This novel hybrid method of CTC recovery using the RCS has the potential to recover a wide range of CTCs regardless of EpCAM. Further validation through a large-scale study is needed.
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Affiliation(s)
- Kazuto Sugai
- Department of Thoracic Surgery, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305- 8577, Japan
| | - Tomoko Mori
- Department of Clinical Research and Regional Innovation, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan
| | - Turan Bilal
- Department of Mechanical Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8654, Japan
| | - Atsuko Furukawa
- Department of Clinical Research and Regional Innovation, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan
| | - Yasuharu Sekine
- Department of Thoracic Surgery, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305- 8577, Japan
| | - Naohiro Kobayashi
- Department of Thoracic Surgery, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305- 8577, Japan
| | - Shinji Kikuchi
- Department of Thoracic Surgery, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305- 8577, Japan
- Department of Thoracic Surgery, Ibaraki Prefectural Hospital, Koibuchi, Kasama, 6528, 309- 1703, Japan
| | - Yukinobu Goto
- Department of Thoracic Surgery, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305- 8577, Japan
| | - Hideo Ichimura
- Department of Thoracic Surgery, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305- 8577, Japan
| | - Taisuke Masuda
- Department of Mechanical Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8654, Japan
| | - Fumihito Arai
- Department of Mechanical Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8654, Japan
| | - Yukio Sato
- Department of Thoracic Surgery, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305- 8577, Japan
| | - Satoshi Matsusaka
- Department of Clinical Research and Regional Innovation, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
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Pouyiourou M, Bochtler T, Coith C, Wikman H, Kraft B, Hielscher T, Stenzinger A, Riethdorf S, Pantel K, Krämer A. Frequency and Prognostic Value of Circulating Tumor Cells in Cancer of Unknown Primary. Clin Chem 2024; 70:297-306. [PMID: 38175594 DOI: 10.1093/clinchem/hvad180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Accepted: 10/02/2023] [Indexed: 01/05/2024]
Abstract
BACKGROUND Cancer of unknown primary (CUP) is defined as a primary metastatic malignancy, in which the primary tumor remains elusive in spite of a comprehensive diagnostic workup. The frequency and prognostic value of circulating tumor cells (CTCs), which are considered to be the source of metastasis, has not yet been systematically evaluated in CUP. METHODS A total of 110 patients with a confirmed diagnosis of CUP according to the European Society for Medical Oncology (ESMO) guidelines, who presented to our clinic between July 2021 and May 2023, provided blood samples for CTC quantification using CellSearch methodology. CTC counts were correlated with demographic, clinical, and molecular data generated by comprehensive genomic profiling of tumor tissue. RESULTS CTCs were detected in 26% of all patients at initial presentation to our department. The highest CTC frequency was observed among patients with unfavorable CUP (35.5%), while patients with single-site/oligometastatic CUP harbored the lowest CTC frequency (11.4%). No statistically significant association between CTC positivity and the number of affected organs (P = 0.478) or disease burden (P = 0.120) was found. High CTC levels (≥5 CTCs/7.5 mL; 12/95 analyzed patients) predicted for adverse overall survival compared to negative or low CTC counts (6-months overall survival rate 90% vs 32%, log-rank P < 0.001; HR 5.43; 95% CI 2.23-13.2). CTC dynamics were also prognostic for overall survival by landmark analysis (log-rank P < 0.001, HR 10.2, 95% CI 1.95-52.9). CONCLUSIONS CTC frequency is a strong, independent predictor of survival in patients with CUP. CTC quantification provides a useful prognostic tool in the management of these patients.
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Affiliation(s)
- Maria Pouyiourou
- Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
- Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
| | - Tilmann Bochtler
- Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
- Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
- National Center for Tumor Diseases (NCT), University of Heidelberg, Heidelberg, Germany
| | - Cornelia Coith
- Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Harriet Wikman
- Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Bianca Kraft
- Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
| | - Thomas Hielscher
- Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Albrecht Stenzinger
- Institute of Pathology, University of Heidelberg, Heidelberg, Germany
- Center for Personalized Medicine (ZPM), University of Heidelberg, Heidelberg, Germany
| | - Sabine Riethdorf
- Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Klaus Pantel
- Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Alwin Krämer
- Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
- Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
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Cai R, Liao X, Li G, Xiang J, Ye Q, Chen M, Feng S. The use of non-steroid anti-inflammatory drugs during radical resection correlated with the outcome in non-small cell lung cancer. World J Surg Oncol 2023; 21:358. [PMID: 37986068 PMCID: PMC10662740 DOI: 10.1186/s12957-023-03247-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Accepted: 11/13/2023] [Indexed: 11/22/2023] Open
Abstract
AIMS The use of non-steroid anti-inflammatory drugs (NSAIDs) is conventional in management of postoperative pain in cancer patients, and further investigations have reported that some of these drugs correlated with the outcome in cancers. However, the prognostic value of the use of NSAIDs during surgery in non-small cell lung cancer (NSCLC) patients has been less addressed. METHODS NSCLC patients staged I-III are retrospectively enrolled, and the data of the use of NSAIDs during surgery are collected. Patients are divided into two subgroups according to the use intensity (UI) (low or high) of the NSAIDs, which was calculated by the accumulate dosage of all the NSAIDs divided by the length of hospitalization. The differences of the clinical features among these groups were checked. And the disease-free survival (DFS) and overall survival (OS) differences in these groups were compared by Kaplan-Meier analysis; risk factors for survival were validated by using a Cox proportional hazards model. RESULTS The UI was significant in predicting the DFS (AUC = 0.65, 95% CI: 0.57-0.73, P = 0.001) and OS (AUC = 0.70, 95% CI: 0.59-0.81, P = 0.001). Clinical features including type of resection (P = 0.001), N stages (P < 0.001), and TNM stages (P = 0.004) were significantly different in UI low (< 74.55 mg/day) or high (≥ 74.55 mg/day) subgroups. Patients in UI-high subgroups displayed significant superior DFS (log rank = 11.46, P = 0.001) and OS (log rank = 7.63, P = 0.006) than the UI-low ones. At last, the UI was found to be an independent risk factor for DFS (HR: 0.52, 95% CI: 0.28-0.95, P = 0.034). CONCLUSIONS The use of NSAIDs during radical resection in NSCLC patients correlated with the outcome and patients with a relative high UI has better outcome.
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Affiliation(s)
- Renzhong Cai
- Department of Thoracic Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou City, Hainan Province, 570311, People's Republic of China
| | - Xuqiang Liao
- Department of Thoracic Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou City, Hainan Province, 570311, People's Republic of China
| | - Gao Li
- Department of Thoracic Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou City, Hainan Province, 570311, People's Republic of China
| | - Jia Xiang
- Department of Oncology, Hainan Hospital of PLA General Hospital, Sanya City, Hainan Province, 572000, People's Republic of China
| | - Qianwen Ye
- Department of Oncology, Hainan Hospital of PLA General Hospital, Sanya City, Hainan Province, 572000, People's Republic of China
| | - Minbiao Chen
- Department of Thoracic Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou City, Hainan Province, 570311, People's Republic of China.
| | - Shouhan Feng
- Department of Oncology, Huzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Huzhou City, Zhejiang Province, 313000, People's Republic of China.
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Bates M, Mohamed BM, Ward MP, Kelly TE, O'Connor R, Malone V, Brooks R, Brooks D, Selemidis S, Martin C, O'Toole S, O'Leary JJ. Circulating tumour cells: The Good, the Bad and the Ugly. Biochim Biophys Acta Rev Cancer 2023; 1878:188863. [PMID: 36796527 DOI: 10.1016/j.bbcan.2023.188863] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 01/06/2023] [Accepted: 01/21/2023] [Indexed: 02/17/2023]
Abstract
This review is an overview of the current knowledge regarding circulating tumour cells (CTCs), which are potentially the most lethal type of cancer cell, and may be a key component of the metastatic cascade. The clinical utility of CTCs (the "Good"), includes their diagnostic, prognostic, and therapeutic potential. Conversely, their complex biology (the "Bad"), including the existence of CD45+/EpCAM+ CTCs, adds insult to injury regarding their isolation and identification, which in turn hampers their clinical translation. CTCs are capable of forming microemboli composed of both non-discrete phenotypic populations such as mesenchymal CTCs and homotypic and heterotypic clusters which are poised to interact with other cells in the circulation, including immune cells and platelets, which may increase their malignant potential. These microemboli (the "Ugly") represent a prognostically important CTC subset, however, phenotypic EMT/MET gradients bring additional complexities to an already challenging situation.
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Affiliation(s)
- Mark Bates
- Department of Histopathology, Trinity College Dublin, Dublin 2, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women & Infants University Hospital, Dublin 8, Ireland; Trinity St James's Cancer Institute, Dublin 8, Ireland.
| | - Bashir M Mohamed
- Department of Histopathology, Trinity College Dublin, Dublin 2, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women & Infants University Hospital, Dublin 8, Ireland; Trinity St James's Cancer Institute, Dublin 8, Ireland
| | - Mark P Ward
- Department of Histopathology, Trinity College Dublin, Dublin 2, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women & Infants University Hospital, Dublin 8, Ireland; Trinity St James's Cancer Institute, Dublin 8, Ireland
| | - Tanya E Kelly
- Department of Histopathology, Trinity College Dublin, Dublin 2, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women & Infants University Hospital, Dublin 8, Ireland; Trinity St James's Cancer Institute, Dublin 8, Ireland
| | - Roisin O'Connor
- Department of Histopathology, Trinity College Dublin, Dublin 2, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women & Infants University Hospital, Dublin 8, Ireland; Trinity St James's Cancer Institute, Dublin 8, Ireland; Department of Pathology, Coombe Women & Infants University Hospital, Dublin 8, Ireland
| | - Victoria Malone
- Department of Histopathology, Trinity College Dublin, Dublin 2, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women & Infants University Hospital, Dublin 8, Ireland; Trinity St James's Cancer Institute, Dublin 8, Ireland; Department of Pathology, Coombe Women & Infants University Hospital, Dublin 8, Ireland
| | - Robert Brooks
- Cancer Research Institute, University of South Australia, Adelaide, SA 5001, Australia
| | - Doug Brooks
- Department of Histopathology, Trinity College Dublin, Dublin 2, Ireland; Trinity St James's Cancer Institute, Dublin 8, Ireland; Cancer Research Institute, University of South Australia, Adelaide, SA 5001, Australia
| | - Stavros Selemidis
- School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology, Bundoora, VIC 3083, Australia
| | - Cara Martin
- Department of Histopathology, Trinity College Dublin, Dublin 2, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women & Infants University Hospital, Dublin 8, Ireland; Trinity St James's Cancer Institute, Dublin 8, Ireland; Department of Pathology, Coombe Women & Infants University Hospital, Dublin 8, Ireland
| | - Sharon O'Toole
- Department of Histopathology, Trinity College Dublin, Dublin 2, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women & Infants University Hospital, Dublin 8, Ireland; Trinity St James's Cancer Institute, Dublin 8, Ireland; Department of Obstetrics and Gynaecology, Trinity College Dublin, Dublin 2, Ireland
| | - John J O'Leary
- Department of Histopathology, Trinity College Dublin, Dublin 2, Ireland; Emer Casey Molecular Pathology Research Laboratory, Coombe Women & Infants University Hospital, Dublin 8, Ireland; Trinity St James's Cancer Institute, Dublin 8, Ireland; Department of Pathology, Coombe Women & Infants University Hospital, Dublin 8, Ireland
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Marcu LG, Moghaddasi L, Bezak E. Cannot Target What Cannot Be Seen: Molecular Imaging of Cancer Stem Cells. Int J Mol Sci 2023; 24:ijms24021524. [PMID: 36675033 PMCID: PMC9864237 DOI: 10.3390/ijms24021524] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 12/29/2022] [Accepted: 01/10/2023] [Indexed: 01/15/2023] Open
Abstract
Cancer stem cells are known to play a key role in tumour development, proliferation, and metastases. Their unique properties confer resistance to therapy, often leading to treatment failure. It is believed that research into the identification, targeting, and eradication of these cells can revolutionise oncological treatment. Based on the principle that what cannot be seen, cannot be targeted, a primary step in cancer management is the identification of these cells. The current review aims to encompass the state-of-the-art functional imaging techniques that enable the identification of cancer stem cells via various pathways and mechanisms. The paper presents in vivo molecular techniques that are currently available or await clinical implementation. Challenges and future prospects are highlighted to open new research avenues in cancer stem cell imaging.
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Affiliation(s)
- Loredana G. Marcu
- Faculty of Informatics and Science, University of Oradea, 1 Universitatii Str., 410087 Oradea, Romania
- Cancer Research Institute, University of South Australia, Adelaide, SA 5001, Australia
- Correspondence:
| | - Leyla Moghaddasi
- Northern Sydney Cancer Centre, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia
- School of Physical Sciences, University of Adelaide, Adelaide, SA 5005, Australia
| | - Eva Bezak
- Cancer Research Institute, University of South Australia, Adelaide, SA 5001, Australia
- School of Physical Sciences, University of Adelaide, Adelaide, SA 5005, Australia
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Wang Z, Zhang XC, Feng WN, Zhang L, Liu XQ, Guo WB, Deng YM, Zou QF, Yang JJ, Zhou Q, Wang BC, Chen HJ, Tu HY, Yan HH, Wu YL. Circulating tumor cells dynamics during chemotherapy predict survival and response in advanced non-small-cell lung cancer patients. Ther Adv Med Oncol 2023; 15:17588359231167818. [PMID: 37113733 PMCID: PMC10126699 DOI: 10.1177/17588359231167818] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 03/17/2023] [Indexed: 04/29/2023] Open
Abstract
Background Circulating tumor cells (CTCs) are prognostic biomarker in non-small-cell lung cancer (NSCLC). CTCs could also be used as predictor of efficacy of systemic treatments in advanced NSCLC. Objectives We described the dynamic changes of CTCs during first-line platinum-based chemotherapy in advanced NSCLC and clarified the correlation between CTC counts and efficacy of chemotherapy. Design Chemotherapy is administered and blood specimens are collected at four time points from baseline to disease progression for CTC detection. Methods This multicenter prospective study enrolled patients with previously untreated stage III or IV NSCLC fit for standard platinum-based chemotherapy. Bloods were sampled as per standard operating procedures at baseline, cycle 1 and cycle 4 of chemotherapy, and at disease progression for CTC analysis using the CellSearch system. Results Among 150 patients enrolled, median overall survival (OS) was 13.8, 8.4, and 7.9 months in patients with CTC-, KIT-CTC, and KIT+CTC at baseline (p = 0.002). Patients with persistent negative CTC (46.0%) had longer progression-free survival [5.7 months, 95% confidence interval (CI): 5.0-6.5 versus 3.0 months, 0.6-5.4; hazard ratio (HR): 0.34, 95% CI: 0.18-0.67) and OS (13.1 months, 10.9-15.3 versus 5.6 months, 4.1-7.1; HR: 0.17, 0.08-0.36) compared with patients with persistent positive CTC (10.7%), which was not impacted by chemotherapy. Chemotherapy decreased CTC from 36.0% (54/150) to 13.7% (13/95). Conclusions CTC persistent presence during treatment represents poor prognosis and resistance to chemotherapy in advanced NSCLC. Chemotherapy could effectively eliminate CTCs. Molecular characterization and the functionalization of CTC will be warranted for further intensive investigation. Trial registration NCT01740804.
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Affiliation(s)
| | | | | | - Li Zhang
- Cancer Center, Sun Yat-sen University, Guangzhou, China
| | | | - Wei-Bang Guo
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Yan-Ming Deng
- The First People’s Hospital of Foshan, Foshan, China
| | - Qing-Feng Zou
- Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China
| | - Jin-Ji Yang
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Qing Zhou
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Bin-Chao Wang
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Hua-Jun Chen
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Hai-Yan Tu
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | | | - Yi-Long Wu
- Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 106 Zhongshan Er Rd, Guangzhou 510080, China
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10
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Carvalho Â, Guimarães-Teixeira C, Constâncio V, Fernandes M, Macedo-Silva C, Henrique R, Monteiro FJ, Jerónimo C. One sample fits all: a microfluidic-assisted methodology for label-free isolation of CTCs with downstream methylation analysis of cfDNA in lung cancer. Biomater Sci 2022; 10:3296-3308. [PMID: 35583893 DOI: 10.1039/d2bm00044j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Lung cancer (LC) is a major cause of mortality. Late diagnosis, associated with limitations in tissue biopsies for adequate tumor characterization contribute to limited survival of lung cancer patients. Liquid biopsies have been introduced to improve tumor characetrization through the analysis of biomarkers, including circulating tumour cells (CTCs) and cell-free DNA (cfDNA). Considering their availability in blood, several enrichment strategies have been developed to augment circulating biomarkers for improving diagnostic, prognostic and treament efficacy assessment; often, however, only one biomarker is tested. In this work we developed and implemented a microfluidic chip for label-free enrichment of CTCs with a methodology for subsequent cfDNA analysis from the same cryopreserved sample. CTCs were successfully isolated in 38 of 42 LC patients with the microfluidic chip. CTCs frequency was significantly higher in LC patients with advanced disease. A cut-off of 1 CTC per mL was established for diagnosis (sensitivity = 76.19%, specificity = 100%) and in patients with late stage lung cancer, the presence of ≥5 CTCs per mL was significantly associated with shorter overall survival. MIR129-2me and ADCY4me panel of cfDNA methylation performed well for LC detection, whereas MIR129-2me combined with HOXA11me allowed for patient risk stratification. Analysis of combinations of biomarkers enabled the definition of panels for LC diagnosis and prognosis. Overall, this study demonstrates that multimodal analysis of tumour biomarkers via microfluidic devices may significantly improve LC characterization in cryopreserved samples, constituting a reliable source for continuous disease monitoring.
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Affiliation(s)
- Ângela Carvalho
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal. .,INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.,Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
| | - Catarina Guimarães-Teixeira
- Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.,Cancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
| | - Vera Constâncio
- Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.,Cancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
| | - Mariana Fernandes
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal. .,INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
| | - Catarina Macedo-Silva
- Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.,Cancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
| | - Rui Henrique
- Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.,Cancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.,Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.,Department of Pathology and Molecular Immunology, School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal
| | - Fernando Jorge Monteiro
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal. .,INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.,Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.,Faculdade de Engenharia, Departamento de Engenharia Metalúrgica e Materiais, Universidade do Porto, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal
| | - Carmen Jerónimo
- Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.,Cancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.,Department of Pathology and Molecular Immunology, School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal
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11
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Barrera-Saldaña HA, Fernández-Garza LE, Barrera-Barrera SA. Liquid biopsy in chronic liver disease. Ann Hepatol 2021; 20:100197. [PMID: 32444248 DOI: 10.1016/j.aohep.2020.03.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 03/25/2020] [Indexed: 02/04/2023]
Abstract
Chronic liver diseases account for a considerable toll of incapacities, suffering, deaths, and resources of the nation's health systems. They can be prevented, treated or even cured when the diagnosis is made on time. Traditional liver biopsy remains the gold standard to diagnose liver diseases, but it has several limitations. Liquid biopsy is emerging as a superior alternative to surgical biopsy given that it surpasses the limitations: it is more convenient, readily and repeatedly accessible, safe, cheap, and provides a more detailed molecular and cellular representation of the individual patient's disease. Progress in understanding the molecular and cellular bases of diseased tissues and organs that normally release cells and cellular components into the bloodstream is catapulting liquid biopsy as a source of biomarkers for diagnosis, prognosis, and prediction of therapeutic response, thus supporting the realization of the promises of precision medicine. The review aims to summarize the evidence of the usefulness of liquid biopsy in liver diseases, including the presence of different biomarkers as circulating epithelial cells, cell-free nucleic acids, specific species of DNA and RNA, and the content of extracellular vesicles.
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Affiliation(s)
- Hugo A Barrera-Saldaña
- Innbiogem SC at National Laboratory for Services of Research, Development, and Innovation for the Pharma and Biotech Industries (LANSEDI) of CONACyT Vitaxentrum group, Monterrey, N.L., Mexico; Center for Biotechnological Genomics of National Polytechnical Institute, Reynosa, Tamps., Mexico.
| | - Luis E Fernández-Garza
- Innbiogem SC at National Laboratory for Services of Research, Development, and Innovation for the Pharma and Biotech Industries (LANSEDI) of CONACyT Vitaxentrum group, Monterrey, N.L., Mexico
| | - Silvia A Barrera-Barrera
- Innbiogem SC at National Laboratory for Services of Research, Development, and Innovation for the Pharma and Biotech Industries (LANSEDI) of CONACyT Vitaxentrum group, Monterrey, N.L., Mexico; National Institute of Pediatrics, Mexico City, Mexico
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12
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Wang C, Xu Y, Zhao X, Li S, Qian Q, Wang W, Mi X. A double-tetrahedral DNA framework based electrochemical biosensor for ultrasensitive detection and release of circulating tumor cells. Analyst 2021; 146:6474-6481. [PMID: 34585683 DOI: 10.1039/d1an01470f] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Detecting circulating tumor cells (CTCs) in patients' blood is essential for early diagnosis, precise treatment and prognosis of cancer. Yet due to CTCs being extremely rare in the peripheral blood of patients, it is still a challenge to detect CTCs with high sensitivity and high selectivity. Here, we developed a double-tetrahedral DNA framework (DTDF) based electrochemical biosensor system (E-CTC sensor system) for ultrasensitive detection and release of CTCs. In this work, an upright tetrahedral DNA framework (UTDF) was used as a rigid scaffold to modify a screen-printed gold electrode (SPGE), and an inverted tetrahedral DNA framework (ITDF) provided three vertex chains to multivalently bind with aptamers. Meanwhile, a streptavidin tagged horseradish peroxidase homopolymer (SA-polyHRP) was linked to biotin-modified aptamers to significantly amplify the signal. Moreover, the captured CTCs could be effectively released via benzonase nuclease with little cell damage. Our E-CTC sensor system achieved a linear range from 1 to 105 MCF-7 cells with an ultralow detection limit of 1 cell. The release efficiency reached 88.1%-97.6% and the viability of the released cells reached up to 98%. We also detected the MCF-7 cells in mimic whole blood samples, suggesting that the E-CTC sensor system shows promise for use in clinical research.
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Affiliation(s)
- Chenguang Wang
- Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.,University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yi Xu
- Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China
| | - Xiaoshuang Zhao
- Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China.
| | - Shuainai Li
- Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.,University of Chinese Academy of Sciences, Beijing 100049, China
| | - Qiuling Qian
- Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.,University of Chinese Academy of Sciences, Beijing 100049, China
| | - Wei Wang
- Shanghai Pudong New District Zhoupu Hospital (Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital), Shanghai 201318, China.
| | - Xianqiang Mi
- Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.,University of Chinese Academy of Sciences, Beijing 100049, China.,Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China. .,CAS Center for Excellence in Superconducting Electronics (CENSE), Shanghai 200050, China.,Key Laboratory of Systems Health Science of Zhejiang Province, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 310024 Hangzhou, China
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13
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Carvalho Â, Ferreira G, Seixas D, Guimarães-Teixeira C, Henrique R, Monteiro FJ, Jerónimo C. Emerging Lab-on-a-Chip Approaches for Liquid Biopsy in Lung Cancer: Status in CTCs and ctDNA Research and Clinical Validation. Cancers (Basel) 2021; 13:cancers13092101. [PMID: 33925308 PMCID: PMC8123575 DOI: 10.3390/cancers13092101] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 04/16/2021] [Accepted: 04/25/2021] [Indexed: 01/31/2023] Open
Abstract
Simple Summary Lung cancer (LCa) remains the leading cause of cancer-related mortality worldwide, with late diagnosis and limited therapeutic approaches still constraining patient’s outcome. In recent years, liquid biopsies have significantly improved the disease characterization and brought new insights into LCa diagnosis and management. The integration of microfluidic devices in liquid biopsies have shown promising results regarding circulating biomarkers isolation and analysis and these tools are expected to establish automatized and standardized results for liquid biopsies in the near future. Herein, we review the status of lab-on-a-chip approaches for liquid biopsies in LCa and highlight their current applications for circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) research and clinical validation studies. Abstract Despite the intensive efforts dedicated to cancer diagnosis and treatment, lung cancer (LCa) remains the leading cause of cancer-related mortality, worldwide. The poor survival rate among lung cancer patients commonly results from diagnosis at late-stage, limitations in characterizing tumor heterogeneity and the lack of non-invasive tools for detection of residual disease and early recurrence. Henceforth, research on liquid biopsies has been increasingly devoted to overcoming these major limitations and improving management of LCa patients. Liquid biopsy is an emerging field that has evolved significantly in recent years due its minimally invasive nature and potential to assess various disease biomarkers. Several strategies for characterization of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have been developed. With the aim of standardizing diagnostic and follow-up practices, microfluidic devices have been introduced to improve biomarkers isolation efficiency and specificity. Nonetheless, implementation of lab-on-a-chip platforms in clinical practice may face some challenges, considering its recent application to liquid biopsies. In this review, recent advances and strategies for the use of liquid biopsies in LCa management are discussed, focusing on high-throughput microfluidic devices applied for CTCs and ctDNA isolation and detection, current clinical validation studies and potential clinical utility.
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Affiliation(s)
- Ângela Carvalho
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; (G.F.); (D.S.); (F.J.M.)
- INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
- Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal; (C.G.-T.); (R.H.); (C.J.)
- Correspondence: ; Tel.: +351-226-074-900
| | - Gabriela Ferreira
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; (G.F.); (D.S.); (F.J.M.)
- INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
- Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal; (C.G.-T.); (R.H.); (C.J.)
| | - Duarte Seixas
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; (G.F.); (D.S.); (F.J.M.)
- INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
- Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal; (C.G.-T.); (R.H.); (C.J.)
- Cancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
| | - Catarina Guimarães-Teixeira
- Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal; (C.G.-T.); (R.H.); (C.J.)
- Cancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
| | - Rui Henrique
- Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal; (C.G.-T.); (R.H.); (C.J.)
- Cancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
- Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
- Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal
| | - Fernando J. Monteiro
- i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; (G.F.); (D.S.); (F.J.M.)
- INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
- Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal; (C.G.-T.); (R.H.); (C.J.)
- Faculdade de Engenharia, Departamento de Engenharia Metalúrgica e Materiais, Universidade do Porto, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal
| | - Carmen Jerónimo
- Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal; (C.G.-T.); (R.H.); (C.J.)
- Cancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
- Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal
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14
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Molodysky E, Grant R. Person-to-Person Cancer Transmission via Allogenic Blood Transfusion. Asian Pac J Cancer Prev 2021; 22:641-649. [PMID: 33773525 PMCID: PMC8286663 DOI: 10.31557/apjcp.2021.22.3.641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Accepted: 11/03/2021] [Indexed: 11/25/2022] Open
Abstract
Despite the recognized capability of Circulating Tumor Cells (CTCs) to seed tumors, allogenic blood transfusions are not presently screened for the presence of CTCs. Previous research has examined blood transfusions and the associated risk of cancer recurrence, but not cancer of unknown primary (CUP) occurrence. The Hypothesis explored in this paper proposes that there is potential for cancers to be transmitted from donor-to-patient via CTCs in either blood transfusions or organ transplants or both. This proposed haematogenic tumor transmission will be discussed in relation to two scenarios involving the introduction of donor-derived CTC's from allogeneic blood transfusions into either known cancer surgery patients or into non-cancer patients. The source of CTCs arises either from the donor with a 'clinically dormant cancer' or a 'pre-clinical cancer' existing as yet undiagnosed, in the donor. Given the significant number of allogenic blood transfusions that occur worldwide on a yearly basis, allogenic blood transfusions have the potential to expose a substantial number of non-cancer recipients to the transmission of CTCs and associated tumor risk. This risk is greatly amplified in the low-income nations where the blood collection and processing protocols, including exclusion and screening criteria are less stringent than those in high-income countries.
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Affiliation(s)
- Eugen Molodysky
- Sydney Medical School, University of Sydney, Sydney, Australia.
| | - Ross Grant
- Sydney Medical School, University of Sydney, Sydney, Australia.
- School of Medical Sciences, University of NSW, Sydney, Australia.
- Australasian Research Institute, Sydney Adventist Hospital, Wahroonga, Sydney Australia.
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15
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De Rosa V, Fonti R, Del Vecchio S, Iommelli F. Non-invasive detection of epithelial mesenchymal transition phenotype and metastatic dissemination of lung cancer by liquid biopsy. EXPLORATION OF TARGETED ANTI-TUMOR THERAPY 2021; 2:36-47. [PMID: 36046089 PMCID: PMC9400761 DOI: 10.37349/etat.2021.00032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 01/12/2021] [Indexed: 11/19/2022] Open
Abstract
The occurrence of phenotype switch from an epithelial to a mesenchymal cell state during the activation of the epithelial mesenchymal transition (EMT) program in cancer cells has been closely associated with the generation of invasive tumor cells that contribute to metastatic dissemination and treatment failure. Liquid biopsy represents an emergent non-invasive tool that may improve our understanding of the molecular events leading to cancer progression and initiating the metastatic cascade through the dynamic analysis of tumor-derived components isolated from body fluids. The present review will primarily focus on the applications of liquid biopsy in lung cancer patients for identifying EMT signature, elucidating molecular mechanisms underlying the acquisition of an invasive phenotype and detecting new targets for therapy.
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Affiliation(s)
- Viviana De Rosa
- Institute of Biostructures and Bioimaging, National Research Council, 80145 Naples, Italy
| | - Rosa Fonti
- Institute of Biostructures and Bioimaging, National Research Council, 80145 Naples, Italy
| | - Silvana Del Vecchio
- Department of Advanced Biomedical Sciences, University “Federico II”, 80131 Naples, Italy
| | - Francesca Iommelli
- Institute of Biostructures and Bioimaging, National Research Council, 80145 Naples, Italy
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16
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Dai S, Ren P, Ren J, Yang L, Li W. The Relationship between Lymphocyte Subsets and the Prognosis and Genomic Features of Lung Cancer: A Retrospective Study. Int J Med Sci 2021; 18:2228-2234. [PMID: 33859531 PMCID: PMC8040422 DOI: 10.7150/ijms.56928] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 03/15/2021] [Indexed: 02/05/2023] Open
Abstract
Background: It has been shown that the prognosis of malignant tumors was closely related to the composition and function of immune system, which was associated with genomic features. However, the prognostic value of peripheral T lymphocyte subsets and its relationship with genomic features in lung cancer has not been analyzed extensively. Therefore, this study was intended to evaluate the relationship between lymphocyte subsets and the prognosis and genomic features of lung cancer. Methods: 598 lung cancer patients with complete data were included in this study between 2011 and 2018. Kaplan-Meier method and Pearson analyses were conducted to study the prognostic value of CD3+, CD4+, CD8+ T lymphocytes and the rate of CD4/CD8. Results: Patients with EGFR mutation has lower mean percentage of CD8+ lymphocytes than patients with EGFR wild-type (24.71 versus 26.62, respectively, P=0.041). Patients with high CD3 had better OS than those with low (27 versus 14 months, P=0.002). Patients with higher CD4 and CD4/CD8 rate had longer OS than with lower (27 versus 12 months, P=0.002; 25 versus 9 months, P=0.008, respectively). Patients with high CD8 had poor PFS than low group (6 versus 11 months, P=0.009). There was a negative correlation between CD3+ and CD4+ cells and OS in smoking stage Ⅱ female lung cancer patients (PCC = 0.626, P<0.05; PCC = 0.534, P<0.05, respectively). In stage Ⅰ male lung cancer patients, CD8+T cell is negatively correlated with OS and PFS (PCC = 0.295, P<0.05; PCC = 0.280, P<0.05, respectively) Conclusions: Lung cancer patients with EGFR mutation had lower percentage of CD8+ lymphocytes. Lymphocyte subsets might be potential prognostic biomarkers of lung cancer, but they are affected by gender and tumor stage.
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Affiliation(s)
- Shuiping Dai
- Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Pengwei Ren
- Clinical Research Center for Respiratory Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Jing Ren
- Nursing Department, West China Hospital, Sichuan University, Chengdu, China
| | - Lan Yang
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Weimin Li
- Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China
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17
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Wu S, Pan Y, Mao Y, Chen Y, He Y. Current progress and mechanisms of bone metastasis in lung cancer: a narrative review. Transl Lung Cancer Res 2021; 10:439-451. [PMID: 33569325 PMCID: PMC7867745 DOI: 10.21037/tlcr-20-835] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Lung cancer is a kind of malignant tumor with rapid progression and poor prognosis. Distant metastasis has been the main cause of mortality among lung cancer patients. Bone is one of the most common sites. Among all lung cancer patients with bone metastasis, most of them are osteolytic metastasis. Some serious clinical consequences like bone pain, pathological fractures, spinal instability, spinal cord compression and hypercalcemia occur as well. Since the severity of bone metastasis in lung cancer, it is undoubtedly necessary to know how lung cancer spread to bone, how can we diagnose it and how can we treat it. Here, we reviewed the process, possible mechanisms, diagnosis methods and current treatment of bone metastasis in lung cancer. We divided the process of bone metastasis in lung cancer into three steps: tumor invasion, tumor cell migration and invasion in bone tissue. It may be influenced by genetic factors, microenvironment and other adhesion-related factors. Imaging examination, laboratory examination, and pathological examination are used to diagnose lung cancer metastasis to bone. Surgery, radiotherapy, targeted therapy, bisphosphonate, radiation therapy and chemotherapy are the common clinical treatment methods currently. We also found some problems remained to be solved. For example, drugs for skeletal related events mainly target on osteoclasts at present, which increase the ratio of patients in osteoporosis and fractures in the long term. In all, this review provides the direction for future research on bone metastasis in lung cancer.
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Affiliation(s)
- Shengyu Wu
- Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.,Medical School, Tongji University, Shanghai, China
| | - Yue Pan
- Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.,Medical School, Tongji University, Shanghai, China
| | - Yanyu Mao
- Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.,Medical School, Tongji University, Shanghai, China
| | - Yu Chen
- Spine Center, Orthopedic department, Shanghai Changzheng Hospital, Shanghai, China
| | - Yayi He
- Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China
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18
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Dong Z, Xue X, Liang H, Guan J, Chang L. DNA Nanomachines for Identifying Cancer Biomarkers in Body Fluids and Cells. Anal Chem 2020; 93:1855-1865. [PMID: 33325676 DOI: 10.1021/acs.analchem.0c03518] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Identifying molecular biomarkers promises to significantly improve the accuracy in cancer diagnosis at its early stage. DNA nanomachines, which are designable and switchable nanostructures made of DNA, show broad potential to detect tumor biomarkers with noninvasive, inexpensive, highly sensitive, and highly specific advantages. This Feature summarizes the recent DNA nanomachine-based platforms for the early detection of cancer biomarkers, both from body fluids and in cells.
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Affiliation(s)
- Zaizai Dong
- Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
| | - Xinying Xue
- Department of Respiratory and Critical Care, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.,Department of Respiratory and Critical Care, Chinese PLA General Hospital, Beijing 100853, China
| | - Hailun Liang
- School of Public Administration and Policy, Renmin University of China, Beijing 100872, China
| | - Jingjiao Guan
- Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, Florida 32310, United States
| | - Lingqian Chang
- Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.,School of Biomedical Engineering, Research and Engineering Center of Biomedical Materials, Anhui Medical University, Hefei 230032, China
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19
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Electrochemical Detection and Point-of-Care Testing for Circulating Tumor Cells: Current Techniques and Future Potentials. SENSORS 2020; 20:s20216073. [PMID: 33114569 PMCID: PMC7663783 DOI: 10.3390/s20216073] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 10/18/2020] [Accepted: 10/23/2020] [Indexed: 12/13/2022]
Abstract
Circulating tumor cells (CTCs) are tumor cells that escaped from the primary tumor or the metastasis into the blood and they play a major role in the initiation of metastasis and tumor recurrence. Thus, it is widely accepted that CTC is the main target of liquid biopsy. In the past few decades, the separation of CTC based on the electrochemical method has attracted widespread attention due to its convenience, rapidness, low cost, high sensitivity, and no need for complex instruments and equipment. At present, CTC detection is not widely used in the clinic due to various reasons. Point-of-care CTC detection provides us with a possibility, which is sensitive, fast, cheap, and easy to operate. More importantly, the testing instrument is small and portable, and the testing does not require specialized laboratories and specialized clinical examiners. In this review, we summarized the latest developments in the electrochemical-based CTC detection and point-of-care CTC detection, and discussed the challenges and possible trends.
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20
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Evaluation of sensitivity and specificity of CanPatrol™ technology for detection of circulating tumor cells in patients with non-small cell lung cancer. BMC Pulm Med 2020; 20:274. [PMID: 33081780 PMCID: PMC7576719 DOI: 10.1186/s12890-020-01314-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Accepted: 10/13/2020] [Indexed: 02/06/2023] Open
Abstract
Background The early diagnosis of non-small cell lung cancer is of great significance to the prognosis of patients. However, traditional histopathology and imaging screening have certain limitations. Therefore, new diagnostical methods are urgently needed for the current clinical diagnosis. In this study we evaluated the sensitivity and specificity of CanPatrol™ technology for the detection of circulating tumor cells in patients with non-small cell lung cancer (NSCLC). Methods CTCs in the peripheral blood of 98 patients with NSCLC and 38 patients with benign pulmonary diseases were collected by the latest typing of CanPatrol™ detection technology. A 3-year follow-up was performed to observe their recurrence and metastasis. Kruskal-Wallis test was used to compare multiple groups of data, Mann-Whitney U test was used to compare data between the two groups, and ROC curve analysis was used to obtain the critical value. The COX risk regression and Kaplan-Meier survival analysis were performed in the 63 NSCLC patients who were effectively followed up. Results The epithelial, epithelial-mesenchymal, and total CTCs were significantly higher in NSCLC patients than that in patients with benign lung disease (P < 0.001). The mesenchymal CTCs of NSCLC patients was slightly higher than that of benign lung diseases (P = 0.013). The AUC of the ROC curve of the total CTCs was 0.837 (95% CI: 0.76-0.914), and the cut-off value corresponding to the most approximate index was 0.5 CTCs/5 ml, at which point the sensitivity was 81.6% and the specificity was 86.8%. COX regression analysis revealed that the clinical stage was correlated with patient survival (P = 0.006), while gender, age, and smoking were not (P > 0.05). After excluding the confounders of staging, surgery, and chemotherapy, Kaplan-Meier survival analysis showed that patients in stage IIIA with CTCs ≥0.5 had significantly lower DFS than those with CTCs < 0.5 (P = 0.022). Conclusions CTC positive can well predict the recurrence of NSCLC patients. CanPatrol™ technology has good sensitivity and specificity in detecting CTCs in peripheral blood of NSCLC patients and has a certain value for clinical prognosis evaluation. Supplementary information Supplementary information accompanies this paper at 10.1186/s12890-020-01314-4.
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21
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Wang S, Zhou Y, Qin X, Nair S, Huang X, Liu Y. Label-free detection of rare circulating tumor cells by image analysis and machine learning. Sci Rep 2020; 10:12226. [PMID: 32699281 PMCID: PMC7376046 DOI: 10.1038/s41598-020-69056-1] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 06/22/2020] [Indexed: 12/14/2022] Open
Abstract
Detection and characterization of rare circulating tumor cells (CTCs) in patients' blood is important for the diagnosis and monitoring of cancer. The traditional way of counting CTCs via fluorescent images requires a series of tedious experimental procedures and often impacts the viability of cells. Here we present a method for label-free detection of CTCs from patient blood samples, by taking advantage of data analysis of bright field microscopy images. The approach uses the convolutional neural network, a powerful image classification and machine learning algorithm to perform label-free classification of cells detected in microscopic images of patient blood samples containing white blood cells and CTCs. It requires minimal data pre-processing and has an easy experimental setup. Through our experiments, we show that our method can achieve high accuracy on the identification of rare CTCs without the need for advanced devices or expert users, thus providing a faster and simpler way for counting and identifying CTCs. With more data becoming available in the future, the machine learning model can be further improved and can serve as an accurate and easy-to-use tool for CTC analysis.
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Affiliation(s)
- Shen Wang
- Department of Mechanical Engineering and Mechanics, Lehigh University, Bethlehem, PA, 18015, USA
| | - Yuyuan Zhou
- Department of Bioengineering, Lehigh University, Bethlehem, PA, 18015, USA
| | - Xiaochen Qin
- Department of Bioengineering, Lehigh University, Bethlehem, PA, 18015, USA
| | - Suresh Nair
- Lehigh Valley Health Network, Lehigh Valley Cancer Institute, Allentown, PA, 18103, USA
| | - Xiaolei Huang
- College of Information Sciences and Technology and Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, 16802, USA.
| | - Yaling Liu
- Department of Mechanical Engineering and Mechanics, Lehigh University, Bethlehem, PA, 18015, USA. .,Department of Bioengineering, Lehigh University, Bethlehem, PA, 18015, USA.
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22
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Ivanova E, Ward A, Wiegmans AP, Richard DJ. Circulating Tumor Cells in Metastatic Breast Cancer: From Genome Instability to Metastasis. Front Mol Biosci 2020; 7:134. [PMID: 32766277 PMCID: PMC7378584 DOI: 10.3389/fmolb.2020.00134] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Accepted: 06/05/2020] [Indexed: 12/12/2022] Open
Abstract
The emergence of clinical resistance in repeatedly treated cancers extends from the primary tumor's capability to exploit genome instability to adapt, escape, and progress. Triple negative breast cancer serves as a good example of such a response demonstrating poor clinical outcome due to a high rate of cellular heterogeneity resulting in metastatic relapse. The capability to effectively track the emergence of therapeutic resistance in real-time and adapt the clinical response is the holy grail for precision medicine and has yet to be realized. In this review we present liquid biopsy using CTCs and ctDNA as a potential replacement and/or addition to the current diagnostic tests to deliver personalized therapies to patients with advanced breast cancer. We outline current uses of liquid biopsy in the metastatic breast cancer setting and discuss their limitations. In addition, we provide a detailed overview of common genome instability events in patients with metastatic breast cancer and how these can be tracked using liquid biopsy.
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Affiliation(s)
- Ekaterina Ivanova
- Cancer and Ageing Research Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Woolongabba, QLD, Australia.,Centre for Tumour and Immune Biology (ZTI), Philipps University Marburg, Marburg, Germany
| | - Ambber Ward
- Tumor Microenvironment Laboratory, QIMR Berghofer, Herston, QLD, Australia
| | - Adrian P Wiegmans
- Cancer and Ageing Research Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Woolongabba, QLD, Australia
| | - Derek John Richard
- Cancer and Ageing Research Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Woolongabba, QLD, Australia
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23
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Chen H, Li Y, Zhang Z, Wang S. Immunomagnetic separation of circulating tumor cells with microfluidic chips and their clinical applications. BIOMICROFLUIDICS 2020; 14:041502. [PMID: 32849973 PMCID: PMC7440929 DOI: 10.1063/5.0005373] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 08/04/2020] [Indexed: 06/11/2023]
Abstract
Circulating tumor cells (CTCs) are tumor cells detached from the original lesion and getting into the blood and lymphatic circulation systems. They potentially establish new tumors in remote areas, namely, metastasis. Isolation of CTCs and following biological molecular analysis facilitate investigating cancer and coming out treatment. Since CTCs carry important information on the primary tumor, they are vital in exploring the mechanism of cancer, metastasis, and diagnosis. However, CTCs are very difficult to separate due to their extreme heterogeneity and rarity in blood. Recently, advanced technologies, such as nanosurfaces, quantum dots, and Raman spectroscopy, have been integrated with microfluidic chips. These achievements enable the next generation isolation technologies and subsequent biological analysis of CTCs. In this review, we summarize CTCs' separation with microfluidic chips based on the principle of immunomagnetic isolation of CTCs. Fundamental insights, clinical applications, and potential future directions are discussed.
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Affiliation(s)
- Hongmei Chen
- School of Mathematics and Physics of Science and Engineering, Anhui University of Technology, Maanshan 243002, China
| | - Yong Li
- School of Mathematics and Physics of Science and Engineering, Anhui University of Technology, Maanshan 243002, China
| | - Zhifeng Zhang
- Department of Engineering Science and Mechanics, The Pennsylvania State University, State College, Pennsylvania 16802, USA
| | - Shuangshou Wang
- School of Chemistry and Chemical Engineering, Anhui University of Technology, Maanshan 243002, China
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24
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Shin H, Oh S, Hong S, Kang M, Kang D, Ji YG, Choi BH, Kang KW, Jeong H, Park Y, Hong S, Kim HK, Choi Y. Early-Stage Lung Cancer Diagnosis by Deep Learning-Based Spectroscopic Analysis of Circulating Exosomes. ACS NANO 2020; 14:5435-5444. [PMID: 32286793 DOI: 10.1021/acsnano.9b09119] [Citation(s) in RCA: 246] [Impact Index Per Article: 49.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
Lung cancer has a high mortality rate, but an early diagnosis can contribute to a favorable prognosis. A liquid biopsy that captures and detects tumor-related biomarkers in body fluids has great potential for early-stage diagnosis. Exosomes, nanosized extracellular vesicles found in blood, have been proposed as promising biomarkers for liquid biopsy. Here, we demonstrate an accurate diagnosis of early-stage lung cancer, using deep learning-based surface-enhanced Raman spectroscopy (SERS) of the exosomes. Our approach was to explore the features of cell exosomes through deep learning and figure out the similarity in human plasma exosomes, without learning insufficient human data. The deep learning model was trained with SERS signals of exosomes derived from normal and lung cancer cell lines and could classify them with an accuracy of 95%. In 43 patients, including stage I and II cancer patients, the deep learning model predicted that plasma exosomes of 90.7% patients had higher similarity to lung cancer cell exosomes than the average of the healthy controls. Such similarity was proportional to the progression of cancer. Notably, the model predicted lung cancer with an area under the curve (AUC) of 0.912 for the whole cohort and stage I patients with an AUC of 0.910. These results suggest the great potential of the combination of exosome analysis and deep learning as a method for early-stage liquid biopsy of lung cancer.
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Affiliation(s)
- Hyunku Shin
- Department of Bio-convergence Engineering, Korea University, Seoul 02841, Republic of Korea
| | - Seunghyun Oh
- School of Biomedical Engineering, Korea University, Seoul 02841, Republic of Korea
| | - Soonwoo Hong
- Department of Bio-convergence Engineering, Korea University, Seoul 02841, Republic of Korea
| | - Minsung Kang
- Department of Bioengineering, Korea University, Seoul 02841, Republic of Korea
| | - Daehyeon Kang
- School of Biomedical Engineering, Korea University, Seoul 02841, Republic of Korea
| | - Yong-Gu Ji
- Exopert Corporation, Seoul 02841, Republic of Korea
| | - Byeong Hyeon Choi
- Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Republic of Korea
- Department of Thoracic and Cardiovascular Surgery, College of Medicine, Korea University Guro Hospital, Seoul 08308, Republic of Korea
| | - Ka-Won Kang
- Division of Hematology-Oncology, Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea
| | - Hyesun Jeong
- School of Biosystems and Biomedical Sciences, Korea University, Seoul 02841, Republic of Korea
| | - Yong Park
- Division of Hematology-Oncology, Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea
| | - Sunghoi Hong
- School of Biosystems and Biomedical Sciences, Korea University, Seoul 02841, Republic of Korea
| | - Hyun Koo Kim
- Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Republic of Korea
- Department of Thoracic and Cardiovascular Surgery, College of Medicine, Korea University Guro Hospital, Seoul 08308, Republic of Korea
| | - Yeonho Choi
- Department of Bio-convergence Engineering, Korea University, Seoul 02841, Republic of Korea
- School of Biomedical Engineering, Korea University, Seoul 02841, Republic of Korea
- Department of Bioengineering, Korea University, Seoul 02841, Republic of Korea
- Exopert Corporation, Seoul 02841, Republic of Korea
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25
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Papale M, Buccarelli M, Mollinari C, Russo MA, Pallini R, Ricci-Vitiani L, Tafani M. Hypoxia, Inflammation and Necrosis as Determinants of Glioblastoma Cancer Stem Cells Progression. Int J Mol Sci 2020; 21:ijms21082660. [PMID: 32290386 PMCID: PMC7215563 DOI: 10.3390/ijms21082660] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 04/08/2020] [Accepted: 04/09/2020] [Indexed: 12/14/2022] Open
Abstract
Tumor hypoxic microenvironment causes hypoxia inducible factor 1 alpha (HIF-1α) activation and necrosis with alarmins release. Importantly, HIF-1α also controls the expression of alarmin receptors in tumor cells that can bind to and be activated by alarmins. Human tumor tissues possess 1–2% of cancer stem cells (CSCs) residing in hypoxic niches and responsible for the metastatic potential of tumors. Our hypothesis is that hypoxic CSCs express alarmin receptors that can bind alarmins released during necrosis, an event favoring CSCs migration. To investigate this aspect, glioblastoma stem-like cell (GSC) lines were kept under hypoxia to determine the expression of hypoxic markers as well as receptor for advanced glycation end products (RAGE). The presence of necrotic extracts increased migration, invasion and cellular adhesion. Importantly, HIF-1α inhibition by digoxin or acriflavine prevented the response of GSCs to hypoxia alone or plus necrotic extracts. In vivo, GSCs injected in one brain hemisphere of NOD/SCID mice were induced to migrate to the other one in which a necrotic extract was previously injected. In conclusion, our results show that hypoxia is important not only for GSCs maintenance but also for guiding their response to external necrosis. Inhibition of hypoxic pathway may therefore represent a target for preventing brain invasion by glioblastoma stem cells (GSCs).
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Affiliation(s)
- Marco Papale
- Department of Experimental Medicine, Sapienza University, 00161 Rome, Italy;
| | - Mariachiara Buccarelli
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome Italy; (M.B.); (L.R.-V.)
| | - Cristiana Mollinari
- Institute of Translational Pharmacology, National Research Council, 00133 Rome, Italy;
- Department of Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy
| | - Matteo A. Russo
- IRCCS San Raffaele Pisana, 00163 Rome, Italy;
- MEBIC Consortium, San Raffaele Open University, 00166 Rome, Italy
| | - Roberto Pallini
- Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy;
- Institute of Neurosurgery, Catholic University School of Medicine, 00168 Rome, Italy
| | - Lucia Ricci-Vitiani
- Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome Italy; (M.B.); (L.R.-V.)
| | - Marco Tafani
- Department of Experimental Medicine, Sapienza University, 00161 Rome, Italy;
- Correspondence: ; Tel.: +39-06-49918234
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26
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Tang Q, Yin D, Wang Y, Du W, Qin Y, Ding A, Li H. Cancer Stem Cells and Combination Therapies to Eradicate Them. Curr Pharm Des 2020; 26:1994-2008. [PMID: 32250222 DOI: 10.2174/1381612826666200406083756] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Accepted: 02/13/2020] [Indexed: 12/23/2022]
Abstract
Cancer stem cells (CSCs) show self-renewal ability and multipotential differentiation, like normal stem or progenitor cells, and which proliferate uncontrollably and can escape the effects of drugs and phagocytosis by immune cells. Traditional monotherapies, such as surgical resection, radiotherapy and chemotherapy, cannot eradicate CSCs, however, combination therapy may be more effective at eliminating CSCs. The present review summarizes the characteristics of CSCs and several promising combination therapies to eradicate them.
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Affiliation(s)
- Qi Tang
- College of Pharmacy and Biological Engineering, Chengdu University, Chengdu, China.,Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu, China
| | - Dan Yin
- Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu, China
| | - Yao Wang
- College of Pharmacy and Biological Engineering, Chengdu University, Chengdu, China
| | - Wenxuan Du
- College of Pharmacy and Biological Engineering, Chengdu University, Chengdu, China
| | - Yuhan Qin
- College of Pharmacy and Biological Engineering, Chengdu University, Chengdu, China
| | - Anni Ding
- College of Pharmacy and Biological Engineering, Chengdu University, Chengdu, China
| | - Hanmei Li
- College of Pharmacy and Biological Engineering, Chengdu University, Chengdu, China
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27
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Cheng Y, Shen J, Yuan L, Yang Y, Shen X, Qian H, Yu L, Li R, Lv X, Yan T, Li Y, Wang L, Liu B. A novel device to capture circulating tumor cells: Quantification and molecular analysis in lung cancer patients. J Biomater Appl 2020; 35:49-58. [PMID: 32223499 DOI: 10.1177/0885328220914408] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Here, we describe a novel microfilter device to capture circulating tumor cells in an efficient and low-cost manner. Then, we validated the safety and clinical utility of the novel microfilter device. We next performed mutation analysis from circulating tumor cells collected from lung cancer patients using this new device. Our results indicate that this microfilter system can be used to investigate the genome landscape of circulating tumor cells collected from lung cancer patients. Further, our results highlight a proof-of-concept demonstration indicating that circulating tumor cell can be used for mutation profiling during tumor evolution, therapy prediction, and monitoring, with immediate clinical applicability.
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Affiliation(s)
- Yuxin Cheng
- The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
| | - Jie Shen
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Ling Yuan
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Yan Yang
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Xiaoyan Shen
- The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
| | - Hanqing Qian
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Lixia Yu
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Rutian Li
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Xin Lv
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Tingting Yan
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Yan Li
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Lifeng Wang
- The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.,The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
| | - Baorui Liu
- The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.,The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China
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28
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Wu CY, Lee CL, Wu CF, Fu JY, Yang CT, Wen CT, Liu YH, Liu HP, Hsieh JCH. Circulating Tumor Cells as a Tool of Minimal Residual Disease Can Predict Lung Cancer Recurrence: A longitudinal, Prospective Trial. Diagnostics (Basel) 2020; 10:diagnostics10030144. [PMID: 32155787 PMCID: PMC7151004 DOI: 10.3390/diagnostics10030144] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 02/27/2020] [Accepted: 03/05/2020] [Indexed: 12/01/2022] Open
Abstract
Background: The role of circulating tumor cells (CTCs) for predicting the recurrence of cancer in lung cancer patients after surgery remains unclear. Methods: A negatively selected protocol of CTC identification was applied. For all the enrolled patients, CTC testing was performed before and after surgery on the operation day (day 0), postoperative day 1, and day 3. The daily decline and trend of CTCs were analyzed to correlate with cancer relapse. The mixed model repeated measures (MMRM) adjusted by cancer characteristics was applied for statistical significance. Results: Fifty patients with lung mass undergoing surgery were enrolled. Among 41 primary lung cancers, 26 (63.4%) were pathological stage Tis and I. A total of 200 CTC tests were performed. MMRM analysis indicated that surgery could contribute to a CTC decline after surgery in all patients with statistical significance (p = 0.0005). The daily decrease of CTCs was statistically different between patients with and without recurrence (p = 0.0068). An early rebound of CTC counts on postoperative days 1 and 3 was associated with recurrence months later. Conclusion: CTC testing can potentially serve as a tool for minimal residual disease detection in early-staged lung cancer after curative surgery.
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Affiliation(s)
- Ching-Yang Wu
- Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou 333423, Taiwan; (C.-Y.W.); (C.-F.W.); (C.-T.W.); (Y.-H.L.); (H.-P.L.)
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan; (J.-Y.F.); (C.-T.Y.)
| | - Chia-Lin Lee
- Department of Medicine, School of Medicine, National Yang-Ming University, Taipei 112304, Taiwan;
- Department of Medical Research, Taichung Veterans General Hospital, Taichung 407752, Taiwan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 407752, Taiwan
| | - Ching-Feng Wu
- Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou 333423, Taiwan; (C.-Y.W.); (C.-F.W.); (C.-T.W.); (Y.-H.L.); (H.-P.L.)
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan; (J.-Y.F.); (C.-T.Y.)
| | - Jui-Ying Fu
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan; (J.-Y.F.); (C.-T.Y.)
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou 333423, Taiwan
| | - Cheng-Ta Yang
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan; (J.-Y.F.); (C.-T.Y.)
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou 333423, Taiwan
| | - Chi-Tsung Wen
- Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou 333423, Taiwan; (C.-Y.W.); (C.-F.W.); (C.-T.W.); (Y.-H.L.); (H.-P.L.)
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan; (J.-Y.F.); (C.-T.Y.)
| | - Yun-Hen Liu
- Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou 333423, Taiwan; (C.-Y.W.); (C.-F.W.); (C.-T.W.); (Y.-H.L.); (H.-P.L.)
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan; (J.-Y.F.); (C.-T.Y.)
| | - Hui-Ping Liu
- Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou 333423, Taiwan; (C.-Y.W.); (C.-F.W.); (C.-T.W.); (Y.-H.L.); (H.-P.L.)
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan; (J.-Y.F.); (C.-T.Y.)
| | - Jason Chia-Hsun Hsieh
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan; (J.-Y.F.); (C.-T.Y.)
- Circulating Tumor Cell Lab., Division of Hematology and Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou 333423, Taiwan
- Correspondence: ; Tel.: +886-3-3281200 (ext. 2118)
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29
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Yao Y, Li Y, Liu Q, Zhou K, Zhao W, Liu S, Yang J, Jiang Y, Sui G. Rapid detection of hepatocellular carcinoma metastasis using reverse transcription loop-mediated isothermal amplification. Talanta 2020; 208:120402. [PMID: 31816739 DOI: 10.1016/j.talanta.2019.120402] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 09/25/2019] [Accepted: 09/27/2019] [Indexed: 12/12/2022]
Abstract
The main therapies of hepatocellular carcinoma (HCC) are hepatectomy and liver transplantation, but the recurrence rate of HCC after radical resection remains high. We established a novel method based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) for the rapid identification of four cancer stem cell-specific biomarkers to estimate the potential risk of HCC metastasis. After optimizing the final concentrations of Mg2+ and betaine, the sensitivity limits for detection of CK19 and EpCAM could reach 10 to 20 copies, while the sensitivity limits for the detection of CD133 and CD90 could reach 10 copies. We detected clinical specimens from 10 HCC patients and performed analysis before and after receiving hepatectomy using RT-LAMP and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The results of both were consistent, but RT-LAMP was proved to be a more rapid, more sensitive, and more economic approach. This novel method is expected to estimate the recurrence and metastasis of HCC for clinical application by combining various low-cost circulating tumor cell sorting and detection tools.
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Affiliation(s)
- Yuhan Yao
- Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP(3)), Department of Environmental Science & Engineering, Fudan University, 2205 Songhu Road, Shanghai, 200433, PR China
| | - Yuancheng Li
- Institute of Biomedical Science, Fudan University, No. 138 Yixueyuan Road, Shanghai, 200032, PR China
| | - Qi Liu
- Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP(3)), Department of Environmental Science & Engineering, Fudan University, 2205 Songhu Road, Shanghai, 200433, PR China
| | - Kaiqian Zhou
- The Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China
| | - Wang Zhao
- Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP(3)), Department of Environmental Science & Engineering, Fudan University, 2205 Songhu Road, Shanghai, 200433, PR China
| | - Sixiu Liu
- Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP(3)), Department of Environmental Science & Engineering, Fudan University, 2205 Songhu Road, Shanghai, 200433, PR China
| | - Jielin Yang
- Technical Center for Animal, Plant and Food Inspection and Quarantine of Shanghai Customs, Shanghai, 200131, PR China
| | - Yuan Jiang
- Technical Center for Animal, Plant and Food Inspection and Quarantine of Shanghai Customs, Shanghai, 200131, PR China
| | - Guodong Sui
- Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP(3)), Department of Environmental Science & Engineering, Fudan University, 2205 Songhu Road, Shanghai, 200433, PR China; Jiangsu Collaborative Innovation Center of Atmospheric Environment and Equipment Technology (CICAEET), Nanjing University of Information Science & Technology, Nanjing, 210044, PR China.
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A comparative study on EpCAM antibody immobilization on gold surfaces and microfluidic channels for the detection of circulating tumor cells. Colloids Surf B Biointerfaces 2020; 188:110808. [PMID: 31991289 DOI: 10.1016/j.colsurfb.2020.110808] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Revised: 01/15/2020] [Accepted: 01/16/2020] [Indexed: 01/09/2023]
Abstract
Detection of circulating tumor cells (CTCs) from the bloodstream holds great importance to diagnose cancer at early stages. However, CTCs being extremely rare in blood makes them difficult to reach. In this paper, we introduced different surface modification techniques for the enrichment and detection of MCF-7 in microfluidic biosensor applications using gold surface and EpCAM antibody. Mainly, two different mechanisms were employed to immobilize the antibodies; covalent bonding and bioaffinity interaction. Self-assembled monolayers (SAMs) formed on the gold surfaces were treated further for the immobilization of the antibody. The bioaffinity-based studies were performed with streptavidin and biotinylated EpCAM over the SAM coated surfaces. The cell attachment events were monitored using fluorescent microscope. Comparisons were made considering the length and functional end of alkanethiols and the positioning of the antibody. Then, these methods were integrated into a microfluidic channel system. Surface characterizations were performed with X-ray Photoelectron Spectroscopy, Atomic Force Microscopy, and contact angle measurements. The selectivity studies were carried out with EpCAM negative K562 leukaemia cell lines and the experiments were repeated for different types of surfaces, such as glass and polymer. Studies showed that long (n>10) and aromatic ring containing alkanethiols lead to better cell capture events compared to shorter ones. Results obtained from the comparisons are of importance for the gold surface-based microfluidic biosensor designs aimed for CTC detection.
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Elkhider A, Wang B, Ouyang X, Al-Azab M, Walana W, Sun X, Li H, Tang Y, Wei J, Li X. Aquaporin 5 promotes tumor migration and angiogenesis in non-small cell lung cancer cell line H1299. Oncol Lett 2020; 19:1665-1672. [PMID: 32194658 PMCID: PMC7039099 DOI: 10.3892/ol.2020.11251] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Accepted: 07/03/2019] [Indexed: 01/08/2023] Open
Abstract
Non-small cell lung cancer (NSCLC) constitutes the majority of all lung-cancer cases. Aquaporin 5 (AQP5) may be involved in NSCLC by promoting lung-cancer initiation and progression. The present study aimed to determine the role of AQP5 in migration and angiogenesis using NSCLC cells and HUVECs. AQPs 1, 3, 4, 5, 8 and 9 were screened in the NSCLC cell line H1299, and the present results showed that AQP5 mRNA was upregulated compared with the other AQP genes. At the protein level, AQP5 was significantly increased in H1299 cells compared with 16HBE cells. AQP5 knockdown in H1299 cells significantly decreased cell migration compared with untransfected cells, as demonstrated by both Transwell and wound closure assays. The present study further investigated H1299 ability to promote HUVEC vascularisation. The supernatants of both transfected and untransfected H1299 cells were used as conditioned medium for HUVECs, and tube formation was measured. The supernatant of AQP5-downregulated cells exhibited significantly low tube formation potential compared with untransfected cells. Similarly, vascular endothelial growth factor was significantly increased in control cells (si-NC) compared with cells transfected with small interfering RNA targeting AQP5. The present study found that AQP5 downregulation significantly decreased the phosphorylation level of epidermal growth factor receptor and the activity of the ERK1/2 pathway. In summary, the present study suggested that AQP5 influenced migration and angiogenesis in NSCLCs in vitro and may potentially exhibit similar in vivo effects.
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Affiliation(s)
- Abdalkhalig Elkhider
- Department of Immunology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
| | - Bing Wang
- Department of Immunology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
| | - Xunli Ouyang
- Department of Immunology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
| | - Mahmoud Al-Azab
- Department of Immunology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
| | - Williams Walana
- Department of Immunology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
| | - Xiaotong Sun
- Department of Immunology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
| | - Han Li
- Department of Immunology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
| | - Yawei Tang
- Department of Immunology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
| | - Jing Wei
- Department of Immunology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
| | - Xia Li
- Department of Immunology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
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Circulating Tumour Cells in Lung Cancer. Recent Results Cancer Res 2019. [PMID: 31605226 DOI: 10.1007/978-3-030-26439-0_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] [Indexed: 08/25/2023]
Abstract
Circulating tumour cells (CTCs) constitute a potential tumour surrogate that could serve as "liquid biopsy" with the advantage to be a minimally invasive approach compared to traditional tissue biopsies. As CTCs are thought to be the source of metastatic lesions, their analysis represents a potential means of tracking cancer cells from the primary tumour en route to distant sites, thus providing valuable insights into the metastatic process. However, several problems, such as their rarity in the peripheral blood, the technical limitations of single-cell downstream analysis and their phenotypic variability, make CTC detection and molecular characterisation very challenging. Nevertheless, in the last decade, there has been an exponential increase of interest in the development of powerful cellular and molecular methodologies applied to CTCs. In this chapter, we focus on the recent advances of functional studies and molecular profiling of CTCs. We will also highlight the clinical relevance of CTC detection and enumeration, and discuss their potential as tumour biomarkers with special focus on lung cancer.
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Kamyabi N, Bernard V, Maitra A. Liquid biopsies in pancreatic cancer. Expert Rev Anticancer Ther 2019; 19:869-878. [PMID: 31533487 PMCID: PMC6824837 DOI: 10.1080/14737140.2019.1670063] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Accepted: 09/16/2019] [Indexed: 02/07/2023]
Abstract
Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a disease of high lethality. Invasive tissue biopsies of primary or metastatic lesions remain the gold standard for diagnosis, but repeated sampling is infeasible. Noninvasive liquid biopsies offer new opportunities for early diagnosis for high-risk cohorts, and for the longitudinal analysis of tumor evolution and progression in patients on therapy. Liquid biopsies can capture tumor-associated components, such as circulating tumor DNA (ctDNA), extracellular vesicles (EVs), and circulating tumor cells (CTCs), each of which provides genomic and molecular information about the underlying PDAC that can potentially inform clinical decisions. Areas covered: Here, we reviewed current knowledge and recent technological advances regarding liquid biopsy in PDAC and mention the pitfalls and benefits in each methodology. We also discuss clinical correlative studies for diagnosis and prognosis in PDAC. Expert opinion:In pancreatic cancer where tissue samples are limited and repeated tissue biopsies are mostly invasive and infeasible, liquid biopsies opened a new window for tumor diagnosis, molecular stratification, and treatment monitoring. While none of the isolation and analysis methods have gained widespread clinical acceptance, it is imperative that the advantages and limitations of each platform for isolation and analysis of tumor associated components are taken into consideration.
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Affiliation(s)
- Nabiollah Kamyabi
- Department of Translational Molecular Pathology and Sheikh Ahmed Center for Pancreatic Cancer Research, UT MD Anderson Cancer Center, Houston, Texas, 77030
| | - Vincent Bernard
- Department of Translational Molecular Pathology and Sheikh Ahmed Center for Pancreatic Cancer Research, UT MD Anderson Cancer Center, Houston, Texas, 77030
| | - Anirban Maitra
- Department of Translational Molecular Pathology and Sheikh Ahmed Center for Pancreatic Cancer Research, UT MD Anderson Cancer Center, Houston, Texas, 77030
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Kamyabi N, Huang J, Lee JJ, Bernard V, Semaan A, Stephens B, Hurd MW, Vanapalli SA, Maitra A, Guerrero PA. A microfluidic device for label-free isolation of tumor cell clusters from unprocessed blood samples. BIOMICROFLUIDICS 2019; 13:044111. [PMID: 31462955 PMCID: PMC6701978 DOI: 10.1063/1.5111888] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Accepted: 08/01/2019] [Indexed: 05/05/2023]
Abstract
Primary cancers disseminate both single circulating tumor cells (CTCs) and CTC "clusters," the latter of which have been shown to demonstrate greater metastatic propensity and adverse impact on prognosis. Many devices developed to isolate single CTCs also capture CTC clusters, but there is translational potential for a platform specifically designed to isolate CTC clusters. Herein, we introduce our microfluidic device for isolating CTC clusters ("Microfluidic Isolation of CTC Clusters" or MICC), which is equipped with ∼10 000 trap chambers that isolate tumor cell clusters based on their large sizes and dynamic force balance against a pillar obstacle in the trap chamber. Whole blood is injected, followed by a wash step to remove blood cells and a final backflush to release intact clusters for downstream analysis. Using clusters from tumor cell-line and confocal microscopy, we verified the ability of the MICC platform to specifically capture tumor cell clusters in the trap chambers. Our flow rate optimization experiments identified 25 μl/min for blood injection, 100 μl/min as wash flow rate, and 300 μl/min as the release flow rate - indicating that 1 ml of whole blood can be processed in less than an hour. Under these optimal flow conditions, we assessed the MICC platform's capture and release performance using blood samples spiked with different concentrations of clusters, revealing a capture efficiency of 66%-87% and release efficiency of 76%-90%. The results from our study suggest that the MICC platform has the potential to isolate CTC clusters from cancer patient blood, enabling it for clinical applications in cancer management.
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Affiliation(s)
| | | | | | | | | | | | | | - Siva A. Vanapalli
- Department of Chemical Engineering, Texas Tech University, Lubbock, Texas 79409, USA
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Wu Z, Yang Z, Dai Y, Zhu Q, Chen LA. Update on liquid biopsy in clinical management of non-small cell lung cancer. Onco Targets Ther 2019; 12:5097-5109. [PMID: 31303765 PMCID: PMC6611714 DOI: 10.2147/ott.s203070] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Accepted: 05/14/2019] [Indexed: 12/18/2022] Open
Abstract
Lung cancer, a leading cause of cancer-related mortality, has a low rate of early diagnosis and a poor prognosis for advanced stages. Recent advances in further mastery of the biology of tumors promote the diagnosis and therapy, especially for non-small cell lung cancer (NSCLC). However, tumor tissue-based information is often not available in most cases due to the invasive and high risk nature of the tumor biopsy procedures. Liquid biopsy, based on the multiple liquid samples including circulating tumor cells (CTC), circulating tumor DNA (ctDNA), and tumor-derived exosome obtained from blood or urine as well as other body fluids, can also provide valuable tumor-related information, playing an important role in management of NSCLC in clinical practice. It is widely believed that concordance of detection for tumor by liquid samples in comparison with tissue biopsy for both early and advanced stage NSCLC patients is optimistic. We herein review the current and future clinical application of liquid biopsy, including early diagnosis and management of precise personalized treatment in lung cancer. The future directions of development for liquid biopsy are also discussed in this review.
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Affiliation(s)
- Zhen Wu
- Respiratory Department, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Zhen Yang
- Respiratory Department, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Yu Dai
- Respiratory Department, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Qiang Zhu
- Respiratory Department, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Liang-An Chen
- Respiratory Department, Chinese PLA General Hospital, Beijing, People’s Republic of China
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Mohammed SI, Torres‐Luquis O, Walls E, Lloyd F. Lymph-circulating tumor cells show distinct properties to blood-circulating tumor cells and are efficient metastatic precursors. Mol Oncol 2019; 13:1400-1418. [PMID: 31026363 PMCID: PMC6547792 DOI: 10.1002/1878-0261.12494] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Revised: 03/11/2019] [Accepted: 04/25/2019] [Indexed: 01/09/2023] Open
Abstract
The leading cause of breast cancer-associated death is metastasis. In 80% of solid tumors, metastasis via the lymphatic system precedes metastasis via the vascular system. However, the molecular properties of tumor cells as they exit the primary tumor into the afferent lymphatics en route to the sentinel lymph nodes (SLNs) are not yet known. Here, we developed an innovative technique that enables the collection of lymph and lymph-circulating tumor cells (LCTCs) en route to the SLN in an immunocompetent animal model of breast cancer metastasis. We found that the gene and protein expression profiles of LCTCs and blood-circulating tumor cells (BCTCs) as they exit the primary tumor are similar, but distinct from those of primary tumors and lymph node metastases (LNMs). LCTCs, but not BCTCs, exist in clusters, display a hybrid epithelial/mesenchymal phenotype and cancer stem cell-like properties, and are efficient metastatic precursors. These results demonstrate that tumor cells that metastasize through the lymphatic system are different from those spread by blood circulation. Understanding the relative contribution of these cells to overall peripheral blood-circulating tumor cells is important for cancer therapy. Whether these two types of cell occur in cancer patients remains to be determined.
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Affiliation(s)
- Sulma I. Mohammed
- Department of Comparative Pathobiology and Purdue University Center for Cancer ResearchPurdue UniversityWest LafayetteINUSA
| | - Odalys Torres‐Luquis
- Department of Comparative Pathobiology and Purdue University Center for Cancer ResearchPurdue UniversityWest LafayetteINUSA
| | - Elwood Walls
- Department of Basic Medical SciencesPurdue UniversityWest LafayetteINUSA
| | - Frank Lloyd
- Department of Biomedical EngineeringPurdue UniversityWest LafayetteINUSA
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Ruzycka M, Cimpan MR, Rios-Mondragon I, Grudzinski IP. Microfluidics for studying metastatic patterns of lung cancer. J Nanobiotechnology 2019; 17:71. [PMID: 31133019 PMCID: PMC6537392 DOI: 10.1186/s12951-019-0492-0] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Accepted: 05/04/2019] [Indexed: 01/09/2023] Open
Abstract
The incidence of lung cancer continues to rise worldwide. Because the aggressive metastasis of lung cancer cells is the major drawback of successful therapies, the crucial challenge of modern nanomedicine is to develop diagnostic tools to map the molecular mechanisms of metastasis in lung cancer patients. In recent years, microfluidic platforms have been given much attention as tools for novel point-of-care diagnostic, an important aspect being the reconstruction of the body organs and tissues mimicking the in vivo conditions in one simple microdevice. Herein, we present the first comprehensive overview of the microfluidic systems used as innovative tools in the studies of lung cancer metastasis including single cancer cell analysis, endothelial transmigration, distant niches migration and finally neoangiogenesis. The application of the microfluidic systems to study the intercellular crosstalk between lung cancer cells and surrounding tumor microenvironment and the connection with multiple molecular signals coming from the external cellular matrix are discussed. We also focus on recent breakthrough technologies regarding lab-on-chip devices that serve as tools for detecting circulating lung cancer cells. The superiority of microfluidic systems over traditional in vitro cell-based assays with regard to modern nanosafety studies and new cancer drug design and discovery is also addressed. Finally, the current progress and future challenges regarding printable and paper-based microfluidic devices for personalized nanomedicine are summarized.
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Affiliation(s)
- Monika Ruzycka
- Department of Applied Toxicology, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, 02-097, Warsaw, Poland
| | - Mihaela R Cimpan
- Biomaterials - Department for Clinical Dentistry, University of Bergen, Årstadveien 19, 5009, Bergen, Norway
| | - Ivan Rios-Mondragon
- Biomaterials - Department for Clinical Dentistry, University of Bergen, Årstadveien 19, 5009, Bergen, Norway
| | - Ireneusz P Grudzinski
- Department of Applied Toxicology, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, 02-097, Warsaw, Poland.
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Gao W, Zhang X, Yuan H, Wang Y, Zhou H, Jin H, Jia C, Jin Q, Cong H, Zhao J. EGFR point mutation detection of single circulating tumor cells for lung cancer using a micro-well array. Biosens Bioelectron 2019; 139:111326. [PMID: 31129389 DOI: 10.1016/j.bios.2019.111326] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Revised: 04/26/2019] [Accepted: 05/13/2019] [Indexed: 01/06/2023]
Abstract
In view of their critical function in metastasis, characterization of single circulating tumor cells (CTCs) can provide important clinical information to monitor tumor progression and guide personal therapy. Single-cell genetic analysis methods based on microfluidics have some inherent shortcomings such as complicated operation, low throughput, and expensive equipment requirements. To overcome these barriers, we developed a simple and open micro-well array containing 26,208 units for either nuclear acids or single-cell genetic analysis. Through modification of the polydimethylsiloxane surface and optimization of chip packaging, we addressed protein adsorption and solution evaporation for PCR amplification on a chip. In the detection of epidermal growth factor receptor (EGFR) exon gene 21, this micro-well array demonstrated good linear correlation at a DNA concentration from 1 × 101 to 1 × 105 copies/μL (R2 = 0.9877). We then successfully integrated cell capture, lysis, PCR amplification, and signal read-out on the micro-well array, enabling the rapid and simple genetic analysis of single cells. This device was used to detect duplex EGFR mutation genes of lung cancer cell lines (H1975 and A549 cells) and normal leukocytes, demonstrating the ability to perform high-throughput, massively parallel duplex gene analysis at the single-cell level. Different types of point mutations (EGFR-L858R mutation or EGFR-T790M mutation) were detected in single H1975 cells, further validating the significance of single-cell level gene detection. In addition, this method showed a good performance in the heterogeneity detection of individual CTCs from lung cancer patients, required for micro-invasive cancer monitoring and treatment selection.
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Affiliation(s)
- Wanlei Gao
- The Faculty of Electrical Engineering and Computer Science, Ningbo University, Ningbo, Zhejiang, 315211, China; State Key Laboratories of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China
| | - Xiaofen Zhang
- Center of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226000, China
| | - Haojun Yuan
- State Key Laboratories of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China
| | - Yanmin Wang
- State Key Laboratories of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China
| | - Hongbo Zhou
- State Key Laboratories of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China
| | - Han Jin
- The Faculty of Electrical Engineering and Computer Science, Ningbo University, Ningbo, Zhejiang, 315211, China
| | - Chunping Jia
- State Key Laboratories of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China.
| | - Qinghui Jin
- The Faculty of Electrical Engineering and Computer Science, Ningbo University, Ningbo, Zhejiang, 315211, China.
| | - Hui Cong
- Center of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226000, China.
| | - Jianlong Zhao
- The Faculty of Electrical Engineering and Computer Science, Ningbo University, Ningbo, Zhejiang, 315211, China
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Teishima J, Inoue S, Hayashi T, Matsubara A. Current status of prognostic factors in patients with metastatic renal cell carcinoma. Int J Urol 2019; 26:608-617. [PMID: 30959579 DOI: 10.1111/iju.13956] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Accepted: 03/03/2019] [Indexed: 12/12/2022]
Abstract
In recent years, the induction of novel agents, including molecular-targeted agents and immune checkpoint inhibitors, have dramatically changed therapeutic options and their outcomes for metastatic renal cell carcinoma. Several prognostic models based on the data of patients with metastatic renal cell carcinoma treated with targeted agents or cytokine therapy have been useful in real clinical practice. Serum or peripheral blood markers related to inflammatory response have been reported to be associated with their prognosis or therapeutic efficacy. In addition to them, investigation for novel predictive factors that represent the efficacy of agents, the risk of adverse events and the prognosis are required for the advance of therapeutic strategies. The present review discusses the conventional prognostic models and clinical factors, and recent advances of the identification of some of the most promising molecules as novel biomarkers for metastatic renal cell carcinoma.
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Affiliation(s)
- Jun Teishima
- Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shogo Inoue
- Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tetsutaro Hayashi
- Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Akio Matsubara
- Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Rothé F, Maetens M, Rouas G, Paesmans M, Van den Eynde M, Van Laethem JL, Vergauwe P, Deboever G, Bareche Y, Vandeputte C, Ignatiadis M, Hendlisz A. CTCs as a prognostic and predictive biomarker for stage II/III Colon Cancer: a companion study to the PePiTA trial. BMC Cancer 2019; 19:304. [PMID: 30943928 PMCID: PMC6446374 DOI: 10.1186/s12885-019-5528-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Accepted: 03/27/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Adjuvant therapy improves the prognosis of stage II & III colon cancer patients. Unfortunately, most patients do not benefit from this treatment. PePITA (NCT00994864) is a prospective, multicenter, non-randomized study whose primary objective is to predict the outcome of adjuvant therapy in colon cancer. METHODS The primary objective was to determine the prognostic and predictive value of circulating tumor cell (CTC) detection before therapy and after one course of preoperative FOLFOX. RESULTS Out of the 58 first patients accrued in PePiTA trial, 36 patients participated in the CTC companion study, of whom 32 had at least one evaluable sample. Only 5 patients (14, 95% CI = 5-30%) had ≥1 CTC/22.5 ml blood in at least one of the two timepoints with 2 patients having ≥1 CTC/22.5 ml at baseline (6, 95% CI: 1-19%). The detection rate of patients with CTCs at baseline being lower than expected, the inclusion of patients in the PePiTA CTC substudy was stopped. The limited sample size did not allow us to investigate the prognostic and predictive value of CTCs in locally advanced colon cancer. CONCLUSIONS Our data illustrate the need for further standardized studies in order to find the most reliable prognostic/predictive biomarker in early-stage colon cancer. TRIAL REGISTRATION This trial was prospectively registered at Jules Bordet institute ( NCT00994864 ) on the October 14, 2009.
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Affiliation(s)
- Françoise Rothé
- J.-C. Heuson Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
| | - Marion Maetens
- J.-C. Heuson Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Ghizlane Rouas
- J.-C. Heuson Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Marianne Paesmans
- Data centre, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Marc Van den Eynde
- Department of Medical Oncology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | | | - Philippe Vergauwe
- Department of Gastroenterology, General Hospital Groeninge, Kortrijk, Belgium
| | - Guido Deboever
- Department of Gastroenterology, Digestive Oncology, AZ Damiaan Ziekenhuis, Oostende, Belgium
| | - Yacine Bareche
- J.-C. Heuson Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Caroline Vandeputte
- Gastrointestinal Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Michail Ignatiadis
- Medical Oncology Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Alain Hendlisz
- Medical Oncology Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
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Loyez M, Larrieu JC, Chevineau S, Remmelink M, Leduc D, Bondue B, Lambert P, Devière J, Wattiez R, Caucheteur C. In situ cancer diagnosis through online plasmonics. Biosens Bioelectron 2019; 131:104-112. [DOI: 10.1016/j.bios.2019.01.062] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Revised: 01/23/2019] [Accepted: 01/27/2019] [Indexed: 12/20/2022]
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Zhang Q, Nong J, Wang J, Yan Z, Yi L, Gao X, Liu Z, Zhang H, Zhang S. Isolation of circulating tumor cells and detection of EGFR mutations in patients with non-small-cell lung cancer. Oncol Lett 2019; 17:3799-3807. [PMID: 30881500 PMCID: PMC6403494 DOI: 10.3892/ol.2019.10016] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Accepted: 11/02/2018] [Indexed: 01/07/2023] Open
Abstract
The aim of the present study was to develop a procedure for the isolation of circulating tumor cells (CTCs), and to evaluate its application in the detection of epidermal growth factor receptor (EGFR) mutations, and potential heterogeneity in patients with non-small-cell lung cancer (NSCLC). Peripheral blood samples were collected from 91 patients with lung cancer, 10 patients with benign disease and 10 healthy volunteers. CTCs were enriched by positive immunomagnetic separation, detected by immunocytochemistry, and processed for single-cell capture. Pure CTC DNA was amplified, and the EGFR gene was analyzed using the amplification refractory mutation system (ARMS) and digital polymerase chain reaction (dPCR). The CTC capture rate in patients with lung cancer was 61.5% (56/91), whereas no CTCs were detected in patients with benign lung disease or in healthy volunteers. The CTC-positive detection rates were 69.3% (52/75) and 25.0% (4/16) in patients with TNM stage III and IV disease, respectively. Markedly more CTCs were captured from patients with small-cell lung cancer compared with patients with other types of cancer. In patients who were positive for EGFR mutations, the detection rate of these mutations was low (16.67%, 2/12), at the single CTC level. The sensitivity increased as the number of CTCs per sample increased. A total of four patients displayed consistent detection of EGFR mutations at the 10-cell level, and one patient exhibited a clear, inconsistent and rare mutation (G719×) between CTCs. A simplified technique for isolating CTCs from blood was established, though multiple CTCs were required to sensitively detect mutations in these cells. The detection of EGFR mutations in CTCs and tissue specimens was generally homogeneous, and therefore, the CTC-level mutation analysis may potentially contribute to the discovery of heterogeneous mutations.
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Affiliation(s)
- Qi Zhang
- Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, P.R. China
| | - Jingying Nong
- Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, P.R. China
| | - Jinghui Wang
- Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, P.R. China
| | - Zhuohong Yan
- Department of Central Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, P.R. China
| | - Ling Yi
- Department of Central Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, P.R. China
| | - Xin Gao
- Department of Central Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, P.R. China
| | - Zhidong Liu
- Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, P.R. China
| | - Hongtao Zhang
- Department of Central Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, P.R. China
| | - Shucai Zhang
- Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, P.R. China
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43
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Wang X, Tao YX, Zhang M, Wu WB, Yang DP, Wang M. Solitary thin-walled cystic lung cancer with extensive extrapulmonary metastasis: A case report and review of the literature. Medicine (Baltimore) 2018; 97:e12950. [PMID: 30412112 PMCID: PMC6221603 DOI: 10.1097/md.0000000000012950] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
RATIONALE Asymptomatic, isolated, and thin-walled cystic lung cancer with extensive extrapulmonary metastasis is rare, and the risk of pulmonary cyst developing into lung cancer is poorly understood. The efficacy of apatinib for end-stage pulmonary adenosquamous carcinoma has not been clarified yet. PATIENT CONCERNS We herein report a rare case of primary lung cancer that appeared as an isolated thin-walled cystic lesion on computed tomography (CT) image, who was initially misdiagnosed as having pulmonary cyst empirically. DIAGNOSES Fluorine-18-fluorodeoxyglucose-positron emission tomography and CT-guided liver biopsy of the patient revealed extra-pulmonary metastasis of lung cancer. INTERVENTIONS Eight cycles of cisplatin-based chemotherapy were administered, followed by oral apatinib for 6 months. Thereafter, best supportive care was given for this patient. OUTCOMES The pulmonary cystic lesion indicated stable disease through the therapy, but the hepatic tumors were progressed gradually after anticancer treatment. The patient died 16 months after the correct diagnosis. LESSONS Solitary thin-walled cystic lung cancer should be kept in mind during the differential diagnosis of pulmonary cavitary lesions. Chest CT alone is insufficient for surveillance of these cystic diseases. Timely biopsy and resection are essential to avoid delayed management. Besides, apatinib may play a role in the treatment of end-stage pulmonary adenosquamous carcinoma.
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Affiliation(s)
| | | | | | | | | | - Min Wang
- Department of Respiratory Medicine, Xuzhou Central Hospital of Southeast University, Xuzhou, China
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44
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Chitty JL, Filipe EC, Lucas MC, Herrmann D, Cox TR, Timpson P. Recent advances in understanding the complexities of metastasis. F1000Res 2018; 7. [PMID: 30135716 DOI: 10.12688/f1000research.15064.1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/24/2018] [Indexed: 12/14/2022] Open
Abstract
Tumour metastasis is a dynamic and systemic process. It is no longer seen as a tumour cell-autonomous program but as a multifaceted and complex series of events, which is influenced by the intrinsic cellular mutational burden of cancer cells and the numerous bidirectional interactions between malignant and non-malignant cells and fine-tuned by the various extrinsic cues of the extracellular matrix. In cancer biology, metastasis as a process is one of the most technically challenging aspects of cancer biology to study. As a result, new platforms and technologies are continually being developed to better understand this process. In this review, we discuss some of the recent advances in metastasis and how the information gleaned is re-shaping our understanding of metastatic dissemination.
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Affiliation(s)
- Jessica L Chitty
- Garvan Institute of Medical Research & the Kinghorn Cancer Centre, Cancer Division, Sydney, NSW, 2010, Australia
| | - Elysse C Filipe
- Garvan Institute of Medical Research & the Kinghorn Cancer Centre, Cancer Division, Sydney, NSW, 2010, Australia
| | - Morghan C Lucas
- Garvan Institute of Medical Research & the Kinghorn Cancer Centre, Cancer Division, Sydney, NSW, 2010, Australia
| | - David Herrmann
- Garvan Institute of Medical Research & the Kinghorn Cancer Centre, Cancer Division, Sydney, NSW, 2010, Australia.,St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW , 2010, Australia
| | - Thomas R Cox
- Garvan Institute of Medical Research & the Kinghorn Cancer Centre, Cancer Division, Sydney, NSW, 2010, Australia.,St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW , 2010, Australia
| | - Paul Timpson
- Garvan Institute of Medical Research & the Kinghorn Cancer Centre, Cancer Division, Sydney, NSW, 2010, Australia.,St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW , 2010, Australia
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45
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Chitty JL, Filipe EC, Lucas MC, Herrmann D, Cox TR, Timpson P. Recent advances in understanding the complexities of metastasis. F1000Res 2018; 7. [PMID: 30135716 PMCID: PMC6073095 DOI: 10.12688/f1000research.15064.2] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/05/2018] [Indexed: 12/14/2022] Open
Abstract
Tumour metastasis is a dynamic and systemic process. It is no longer seen as a tumour cell-autonomous program but as a multifaceted and complex series of events, which is influenced by the intrinsic cellular mutational burden of cancer cells and the numerous bidirectional interactions between malignant and non-malignant cells and fine-tuned by the various extrinsic cues of the extracellular matrix. In cancer biology, metastasis as a process is one of the most technically challenging aspects of cancer biology to study. As a result, new platforms and technologies are continually being developed to better understand this process. In this review, we discuss some of the recent advances in metastasis and how the information gleaned is re-shaping our understanding of metastatic dissemination.
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Affiliation(s)
- Jessica L Chitty
- Garvan Institute of Medical Research & the Kinghorn Cancer Centre, Cancer Division, Sydney, NSW, 2010, Australia
| | - Elysse C Filipe
- Garvan Institute of Medical Research & the Kinghorn Cancer Centre, Cancer Division, Sydney, NSW, 2010, Australia
| | - Morghan C Lucas
- Garvan Institute of Medical Research & the Kinghorn Cancer Centre, Cancer Division, Sydney, NSW, 2010, Australia
| | - David Herrmann
- Garvan Institute of Medical Research & the Kinghorn Cancer Centre, Cancer Division, Sydney, NSW, 2010, Australia.,St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW , 2010, Australia
| | - Thomas R Cox
- Garvan Institute of Medical Research & the Kinghorn Cancer Centre, Cancer Division, Sydney, NSW, 2010, Australia.,St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW , 2010, Australia
| | - Paul Timpson
- Garvan Institute of Medical Research & the Kinghorn Cancer Centre, Cancer Division, Sydney, NSW, 2010, Australia.,St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW , 2010, Australia
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46
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Li WM, Zhou LL, Zheng M, Fang J. Selection of Metastatic Breast Cancer Cell-Specific Aptamers for the Capture of CTCs with a Metastatic Phenotype by Cell-SELEX. MOLECULAR THERAPY. NUCLEIC ACIDS 2018; 12:707-717. [PMID: 30098503 PMCID: PMC6083002 DOI: 10.1016/j.omtn.2018.07.008] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/22/2017] [Revised: 07/11/2018] [Accepted: 07/11/2018] [Indexed: 12/22/2022]
Abstract
Circulating tumor cells (CTCs) have the potential to predict metastasis, and the capture of CTCs based on their surface markers is mostly applied for CTC detection. Considering that the CTCs with a metastatic phenotype preferably form a metastatic focus and that aptamers have the ability to bind targets with high specificity and affinity, we selected aptamers directed toward metastatic cells by subtractive Cell-SELEX technology using highly metastatic MDA-MB-231 cells as the target cell and low-metastatic MCF-7 cells as the negative cell for the capture of metastatic CTCs. Affinity and selectivity assays showed that aptamer M3 had the highest affinity, with a KD of 45.6 ± 1.2 nM, and had good specificity against several other types of metastatic cancer cells. Based on these findings, we developed an M3-based capture system for CTC enrichment, which has the capability to specifically capture the metastatic cells MDA-MB-231 mixed with non-metastatic MCF-7 cells and CTCs derived from the peripheral blood from metastatic breast cancer patients. A further comparative analysis with the anti-EpCAM probe showed that M3 probe captured epithelial feature-deletion metastatic cells. We developed an aptamer-based CTC capture system through the selection of aptamers by taking whole metastatic cells, not known molecules, as targets, which provided a new insight into CTC capture and Cell-SELEX application.
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Affiliation(s)
- Wan-Ming Li
- Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China
| | - Lin-Lin Zhou
- Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China; Institute of Immunotherapy, Fujian Medical University, Fuzhou 350122, China
| | - Min Zheng
- Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, China
| | - Jin Fang
- Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China.
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47
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Emerging functional markers for cancer stem cell-based therapies: Understanding signaling networks for targeting metastasis. Semin Cancer Biol 2018; 53:90-109. [PMID: 29966677 DOI: 10.1016/j.semcancer.2018.06.006] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Revised: 06/20/2018] [Accepted: 06/28/2018] [Indexed: 12/18/2022]
Abstract
Metastasis is one of the most challenging issues in cancer patient management, and effective therapies to specifically target disease progression are missing, emphasizing the urgent need for developing novel anti-metastatic therapeutics. Cancer stem cells (CSCs) gained fast attention as a minor population of highly malignant cells within liquid and solid tumors that are responsible for tumor onset, self-renewal, resistance to radio- and chemotherapies, and evasion of immune surveillance accelerating recurrence and metastasis. Recent progress in the identification of their phenotypic and molecular characteristics and interactions with the tumor microenvironment provides great potential for the development of CSC-based targeted therapies and radical improvement in metastasis prevention and cancer patient prognosis. Here, we report on newly uncovered signaling mechanisms controlling CSC's aggressiveness and treatment resistance, and CSC-specific agents and molecular therapeutics, some of which are currently under investigation in clinical trials, gearing towards decisive functional CSC intrinsic or surface markers. One special research focus rests upon subverted regulatory pathways such as insulin-like growth factor 1 receptor signaling and its interactors in metastasis-initiating cell populations directly related to the gain of stem cell- and EMT-associated properties, as well as key components of the E2F transcription factor network regulating metastatic progression, microenvironmental changes, and chemoresistance. In addition, the study provides insight into systems biology tools to establish complex molecular relationships behind the emergence of aggressive phenotypes from high-throughput data that rely on network-based analysis and their use to investigate immune escape mechanisms or predict clinical outcome-relevant CSC receptor signaling signatures. We further propose that customized vector technologies could drastically enhance systemic drug delivery to target sites, and summarize recent progress and remaining challenges. This review integrates available knowledge on CSC biology, computational modeling approaches, molecular targeting strategies, and delivery techniques to envision future clinical therapies designed to conquer metastasis-initiating cells.
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48
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Shi Y, Pang X, Wang J, Liu G. NanoTRAIL-Oncology: A Strategic Approach in Cancer Research and Therapy. Adv Healthc Mater 2018. [PMID: 29527836 DOI: 10.1002/adhm.201800053] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
TRAIL is a member of the tumor necrosis factor superfamily that can largely trigger apoptosis in a wide variety of cancer cells, but not in normal cells. However, insufficient exposure to cancer tissues or cells and drug resistance has severely impeded the clinical application of TRAIL. Recently, nanobiotechnology has brought about a revolution in advanced drug delivery for enhanced anticancer therapy using TRAIL. With the help of materials science, immunology, genetic engineering, and protein engineering, substantial progress is made by expressing fusion proteins with TRAIL, engineering TRAIL on biological membranes, and loading TRAIL into functional nanocarriers or conjugating it onto their surfaces. Thus, the nanoparticle-based TRAIL (nanoTRAIL) opens up intriguing opportunities for efficient and safe bioapplications. In this review, the mechanisms of action and biological function of TRAIL, as well as the current status of TRAIL treatment, are comprehensively discussed. The application of functional nanotechnology combined with TRAIL in cancer therapy is also discussed.
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Affiliation(s)
- Yesi Shi
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine; School of Public Health; Xiamen University; Xiamen 361102 China
| | - Xin Pang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine; School of Public Health; Xiamen University; Xiamen 361102 China
| | - Junqing Wang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine; School of Public Health; Xiamen University; Xiamen 361102 China
- Collaborative Innovation Center of Guangxi Biological Medicine and the; Medical and Scientific Research Center; Guangxi Medical University; Nanning 530021 China
| | - Gang Liu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine; School of Public Health; Xiamen University; Xiamen 361102 China
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49
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Kimura H, Matsui Y, Ishikawa A, Nakajima T, Iizasa T. Randomized controlled phase III trial of adjuvant chemoimmunotherapy with activated cytotoxic T cells and dendritic cells from regional lymph nodes of patients with lung cancer. Cancer Immunol Immunother 2018; 67:1231-1238. [PMID: 29855695 PMCID: PMC6097784 DOI: 10.1007/s00262-018-2180-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 05/28/2018] [Indexed: 12/25/2022]
Abstract
Randomized controlled trial of adjuvant chemoimmunotherapy for lung cancer indicated a significant advantage in patients receiving immunotherapy. Herein we report the final results and immunological analysis with a median follow-up of 59.6 months. Patients with post-surgical lung cancer were randomly designated to receive either chemoimmunotherapy (group A, immunotherapy arm) or chemotherapy (group B, control arm). The immunotherapy comprised the adoptive transfer of autologous activated killer T cells and dendritic cells (AKT-DC). The 2- and 5-year overall survival (OS) rates were 96.0 and 69.4% in group A and 64.7 and 45.1% in group B, respectively. Multivariate analysis results revealed that the hazard ratio was 0.439. The 2- and 5-year recurrence-free survival rates were 70.0 and 57.9% in group A and 43.1 and 31.4% in group B, respectively. Subgroup analysis for the OS between treatment groups indicated that younger patients (≤ 55 years: HR 0.098), males (HR 0.474), patients with adenocarcinoma (HR 0.479), patients with stage III cancer (HR 0.399), and those who did not receive preoperative chemotherapy (HR 0.483) had lower HRs than those in the other groups. Immunological analysis of cell surface markers in regional lymph nodes of subjects receiving immunotherapy indicated that the CD8+/CD4+ T-cell ratio was elevated in survivors. Patients with non-small-cell lung cancer benefited from adoptive cellular immunotherapy as an adjuvant to surgery. Patients with stage III cancer, those with adenocarcinoma, and those not receiving preoperative chemotherapy were good candidates. Lastly, cytotoxic T cells were important for a favorable chemoimmunotherapy outcome.
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Affiliation(s)
- Hideki Kimura
- Department of Thoracic Surgery, Saiseikai-Narashino Hospital, Izumi-cho 1-1-1, Narashino, Chiba, 275-8580, Japan.
| | - Yukiko Matsui
- Department of Thoracic Surgery, Chiba Cancer Center, Chiba, Japan
| | - Aki Ishikawa
- Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Takahiro Nakajima
- Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Toshihiko Iizasa
- Department of Thoracic Surgery, Chiba Cancer Center, Chiba, Japan
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50
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Bayarri-Lara CI, de Miguel Pérez D, Cueto Ladrón de Guevara A, Rodriguez Fernández A, Puche JL, Sánchez-Palencia Ramos A, Ruiz Zafra J, Giraldo Ospina CF, Delgado-Rodríguez M, Expósito Ruiz M, Moyano Rodriguez MJ, Lorente JA, Serrano MJ. Association of circulating tumour cells with early relapse and 18F-fluorodeoxyglucose positron emission tomography uptake in resected non-small-cell lung cancers. Eur J Cardiothorac Surg 2018; 52:55-62. [PMID: 28369376 DOI: 10.1093/ejcts/ezx049] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Accepted: 01/03/2017] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVES More than 20% of lung cancer patients develop a recurrence, even after curative resection. We hypothesized that relapse may arise from the dissemination of circulating tumour cells (CTCs). This study evaluates the significance of CTC detection as regards the recurrence of non-small-cell lung cancer (NSCLC) in surgically resected patients. Secondly, we investigated the association between CTCs and the uptake of 18 F-fluorodeoxyglucose (FDG) by the primary tumour on a positron emission tomographic (PET) scan. METHODS In this single-centre prospective study, blood samples for analysis of CTCs were obtained from 102 patients with Stage I-IIIA NSCLC both before (CTC1) and 1 month after (CTC2) radical resection. CTCs were isolated using immunomagnetic techniques. The presence of CTCs was correlated with the maximum standardized uptake value (SUVmax) measured on preoperative FDG PET/computed tomographic scans. Recurrence free survival (RFS) analysis was performed. RESULTS CTCs were detected in 39.2% of patients before and in 27.5% 1 month after the operation. The presence of CTCs after the operation was significantly correlated with SUVmax on PET scans, pathological stage and surgical approach. Only SUVmax was an independent predictor for the presence of CTC2 on multivariate analysis. Postoperative CTCs were significantly correlated with a shorter RFS ( P = 0.005). In multivariate analysis, the presence of CTC2 was associated with RFS, independent of disease staging. CONCLUSIONS Detection of CTCs 1 month after radical resection might be a useful marker to predict early recurrence in Stage I-III NSCLC. The SUVmax value of the primary tumour on preoperative PET scans was associated with the presence of CTC 1 month after the operation.
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Affiliation(s)
- Clara I Bayarri-Lara
- Department of Thoracic Surgery, Virgen de las Nieves University Hospital, Granada, Spain
| | - Diego de Miguel Pérez
- Liquid Biopsy and Metastasis Research Group, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government-PTS Granada, Granada, Spain.,Laboratory of Genetic Identification, Legal Medicine and Toxicology Department, Faculty of Medicine, University of Granada, Granada, Spain
| | | | | | - Jose L Puche
- Liquid Biopsy and Metastasis Research Group, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government-PTS Granada, Granada, Spain.,Division of Integral Oncology, University Hospital of Granada, Granada, Spain
| | | | - Javier Ruiz Zafra
- Department of Thoracic Surgery, Virgen de las Nieves University Hospital, Granada, Spain
| | | | | | - Manuela Expósito Ruiz
- Division for Methodological Assessment, Alejandro Otero Biomedical Research Fundation (FIBAO), Granada, Spain
| | | | - Jose A Lorente
- Liquid Biopsy and Metastasis Research Group, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government-PTS Granada, Granada, Spain.,Laboratory of Genetic Identification, Legal Medicine and Toxicology Department, Faculty of Medicine, University of Granada, Granada, Spain
| | - Maria José Serrano
- Liquid Biopsy and Metastasis Research Group, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government-PTS Granada, Granada, Spain.,Division of Preventive Medicine and Public Health, University of Jaén, Jaén, Spain
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