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Mui M, Clark M, Vu TMSH, Clemons N, Hollande F, Roth S, Ramsay R, Michael M, Heriot AG, Kong JCH. Use of patient-derived explants as a preclinical model for precision medicine in colorectal cancer: A scoping review. Langenbecks Arch Surg 2023; 408:392. [PMID: 37816905 PMCID: PMC10564805 DOI: 10.1007/s00423-023-03133-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Accepted: 10/02/2023] [Indexed: 10/12/2023]
Abstract
PURPOSE Whilst the treatment paradigm for colorectal cancer has evolved significantly over time, there is still a lack of reliable biomarkers of treatment response. Treatment decisions are based on high-risk features such as advanced TNM stage and histology. The role of the tumour microenvironment, which can influence tumour progression and treatment response, has generated considerable interest. Patient-derived explant cultures allow preservation of native tissue architecture and tumour microenvironment. The aim of the scoping review is to evaluate the utility of patient-derived explant cultures as a preclinical model in colorectal cancer. METHODS A search was conducted using Ovid MEDLINE, EMBASE, Web of Science, and Cochrane databases from start of database records to September 1, 2022. We included all peer-reviewed human studies in English language which used patient-derived explants as a preclinical model in primary colorectal cancer. Eligible studies were grouped into the following categories: assessing model feasibility; exploring tumour microenvironment; assessing ex vivo drug responses; discovering and validating biomarkers. RESULTS A total of 60 studies were eligible. Fourteen studies demonstrated feasibility of using patient-derived explants as a preclinical model. Ten studies explored the tumour microenvironment. Thirty-eight studies assessed ex vivo drug responses of chemotherapy agents and targeted therapies. Twenty-four studies identified potential biomarkers of treatment response. CONCLUSIONS Given the preservation of tumour microenvironment and tumour heterogeneity, patient-derived explants has the potential to identify reliable biomarkers, treatment resistance mechanisms, and novel therapeutic agents. Further validation studies are required to characterise, refine and standardise this preclinical model before it can become a part of precision medicine in colorectal cancer.
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Affiliation(s)
- Milton Mui
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
| | - Molly Clark
- Department of Colorectal Surgery, Alfred Hospital, Melbourne, Victoria, Australia
| | - Tamara M S H Vu
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia
| | - Nicholas Clemons
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia
| | - Frédéric Hollande
- Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia
- Victorian Comprehensive Cancer Centre, The University of Melbourne Centre for Cancer Research, Melbourne, Victoria, Australia
| | - Sara Roth
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia
| | - Robert Ramsay
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia
| | - Michael Michael
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia
- Division of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Alexander G Heriot
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
- Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia
| | - Joseph C H Kong
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
- Department of Colorectal Surgery, Alfred Hospital, Melbourne, Victoria, Australia
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Cheng YL, Zhang GY, Li C, Lin J. Screening for novel protein targets of indomethacin in HCT116 human colon cancer cells using proteomics. Oncol Lett 2013; 6:1222-1228. [PMID: 24179499 PMCID: PMC3813814 DOI: 10.3892/ol.2013.1560] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2013] [Accepted: 08/21/2013] [Indexed: 02/04/2023] Open
Abstract
Non-steroidal anti-inflammatory drugs, such as indomethacin (IN), inhibit colorectal cancer (CRC) growth through cyclooxygenase (COX)-independent mechanisms, however, the precise biological mechanisms are not completely understood. The aim of the present study was to investigate new molecular factors potentially associated with IN in HCT116 human CRC cells, which do not express COX, using a proteomic approach. The total proteins from the IN-treated and untreated groups were separated by immobilized pH gradient-based two-dimensional gel electrophoresis. The differentially-expressed proteins were identified by peptide mass fingerprint (PMF) based on matrix-assisted laser desorption/ionization time of flight mass spectrometry. The PMF maps were searched in the SWISS-PROT/TrEMBL database using the PeptIdent software. Between the IN-treated and untreated groups, a total of 45 differential protein spots were detected and 15 differentially-expressed proteins were identified by PMF. IN downregulated Wnt1-inducible signaling pathway protein 1, Bcl-2-related protein A1 and mitogen-activated protein kinase, inhibited HCT116 cell growth and induced apoptosis. In conclusion, IN may exert its effects on CRC to induce HCT116 cell apoptosis and suppress growth through COX-independent pathways.
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Affiliation(s)
- Yan-Li Cheng
- Department of Gastroenterology, The First Hospital of Tsinghua University, Beijing 100016, P.R. China
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Abstract
There is an ever pressing need to develop new drugs for the treatment of cancer. Gallium nitrate, a group IIIa metal salt, inhibits the proliferation of tumor cells in vitro and in vivo and has shown activity against non-Hodgkin's lymphoma and bladder cancer in clinical trials. Gallium can function as an iron mimetic and perturb iron-dependent proliferation and other iron-related processes in tumor cells. Gallium nitrate lacks crossresistance with conventional chemotherapeutic drugs and is not myelosuppressive; it can be used when other drugs have failed or when the blood count is low. Given the therapeutic potential of gallium, newer generations of gallium compounds are now in various phases of preclinical and clinical development. These compounds hold the promise of greater anti-tumor activity against a broader spectrum of cancers. The development of gallium compounds for cancer treatment and their mechanisms of action will be discussed.
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Cheng YL, Zhang GY, Xiao ZQ, Tang FQ. Two-dimensional polyacrylamide gel electrophoresis analysis of indomethacin-treated human colon cancer cells. World J Gastroenterol 2005; 11:2420-5. [PMID: 15832411 PMCID: PMC4305628 DOI: 10.3748/wjg.v11.i16.2420] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To establish the two-dimensional gel electrophoresis (2-DE) profiles of indomethacin (IN)-treated human colon cancer cell line HCT116, and to provide a new way to study its anti-tumor molecular mechanism through analyzing a variety of protein maps.
METHODS: Two-DE profiles of HCT116 were established in IN-treated and untreated groups. Total proteins were separated by immobilized pH gradient-based 2-DE. The gels were stained by silver, scanned by ImageScanner, and analyzed with Image Master software.
RESULTS: Clear background, well-resolved and reproducible 2-DE patterns of HCT116 cells were acquired in IN-treated and untreated group. The average deviation of spot position was 0.896±0.177 mm in IEF direction and 1.106±0.289 mm in SDS-PAGE direction respectively. In IN-treated group, 1169±36 spots were detected and 1061±32 spots were matched, the average matching rate was 90.6% in three gels. In untreated group, 1256±50 spots were detected and 1168±46 spots were matched, the average matching rate was 93.0% in three gels. Forty-five differential protein spots were displayed between IN-treated and untreated groups. Of which, 34 protein spots decreased and 9 showed higher expression in IN-treated group, and only two protein spots showed an expression in untreated cells.
CONCLUSION: Two-DE profiles of IN-treated and untreated HCT116 cells were established. Apparent 45 different protein spots were detected in IN-treated and untreated HCT116 cells. The analysis on differential protein spots may serve as a new way to study the molecule mechanism of IN-treated colon cancer.
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Affiliation(s)
- Yan-Li Cheng
- Department of Gastroenterology, Xiangya Hospital, Central South University, Xiangya Road, Changsha 410008, Hunan Province, China
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