Prognostic significance of BIRC7/Livin, Bcl-2, p53, Annexin V, PD-L1, DARC, MSH2 and PMS2 in colorectal cancer treated with FOLFOX chemotherapy with or without aspirin
| العنوان: | Prognostic significance of BIRC7/Livin, Bcl-2, p53, Annexin V, PD-L1, DARC, MSH2 and PMS2 in colorectal cancer treated with FOLFOX chemotherapy with or without aspirin |
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| المؤلفون: | Muhammad Manko, John Idoko, Kasimu Umar Adoke, Adamu Abdullahi, Abdullahi Mohammed, Surajo Mohammed Aminu, Sani Abubakar, Sani Ibrahim, Yawale Iliyasu, Halimatu Sadiya Musa, Khalid Zahir Shah, Ahmed Adamu, Aishatu Maude Suleiman, Mohammed Faruk, Abdulmumini Hassan Rafindadi, Cheh Agustin Awasum, Rakiya Saidu, Abdullahi Jibril Randawa, Atara Ntekim |
| المصدر: | PLoS ONE, Vol 16, Iss 1, p e0245581 (2021) PLoS ONE BASE-Bielefeld Academic Search Engine |
| بيانات النشر: | Public Library of Science (PLoS), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Organoplatinum Compounds, Colorectal cancer, medicine.medical_treatment, Protein Expression, Cancer Treatment, Leucovorin, Apoptosis, Aminotransferases, Biochemistry, DNA Mismatch Repair, B7-H1 Antigen, Metastasis, Inhibitor of Apoptosis Proteins, FOLFOX, Antineoplastic Combined Chemotherapy Protocols, Medicine and Health Sciences, Drug Interactions, Annexin A5, Mismatch Repair Endonuclease PMS2, Multidisciplinary, Cell Death, Prognosis, Enzymes, Neoplasm Proteins, Chemistry, MutS Homolog 2 Protein, Oncology, Proto-Oncogene Proteins c-bcl-2, Cell Processes, Barium, Physical Sciences, Medicine, Fluorouracil, Anatomy, Colorectal Neoplasms, medicine.drug, Research Article, Chemical Elements, Histology, Combination therapy, Colon, Science, Receptors, Cell Surface, Research and Analysis Methods, Folinic acid, Transferases, Cell Line, Tumor, medicine, Gene Expression and Vector Techniques, Biomarkers, Tumor, Animals, Humans, Molecular Biology Techniques, Molecular Biology, Adaptor Proteins, Signal Transducing, Colorectal Cancer, Chemotherapy, Molecular Biology Assays and Analysis Techniques, Aspirin, business.industry, Cancers and Neoplasms, Biology and Life Sciences, Proteins, Cell Biology, medicine.disease, Xenograft Model Antitumor Assays, digestive system diseases, Oxaliplatin, Rats, Gastrointestinal Tract, MSH2, Cancer research, Enzymology, Tumor Suppressor Protein p53, business, Duffy Blood-Group System, Digestive System |
| الوصف: | Evasion of apoptosis is associated with treatment resistance and metastasis in colorectal cancer (CRC). Various cellular processes are associated with evasion of apoptosis. These include overexpression of pro-apoptotic proteins (including p53 and PD-L1), anti-apoptotic proteins (BIRC7/Livin and Bcl-2), chemokine receptors (including DARC), and dysregulation of DNA mismatch repair proteins (including MSH2 and PMS2). The aim of this study was to determine the effect of folinic acid, 5-FU and oxaliplatin (FOLFOX) as a single agent and aspirin plus FOLFOX in various combinations on the aforementioned proteins in human CRC, SW480 cell line and rat models of N-Methyl-N-Nitrosourea (NMU)-induced CRC. In addition, effects of the NMU-induced CRC and chemotherapeutic regimens on haematological and biochemical parameters in the rat models were studied. Immunohistochemistry, immunofluorescence and immunoblot techniques were used to study the expression pattern of the related proteins in the human CRC cells pre- and post-treatment. Double contrast barium enema, post-mortem examination and histological analyses were used to confirm tumour growth and the effect of the treatmentin vivoin rat models. Notably, we found in human mucinous CRC, a significant increase in expression of the BIRC7/Livin post-FOLFOX treatment compared with pre-treatment (p= 0.0001). This increase provides new insights into the prognostic role of BIRC7/Livin in evasion of apoptosis and facilitation of treatment resistance, local recurrence and metastasis particularly among mucinous CRCs post-FOLFOX chemotherapy. These poor prognostic features in the CRC may be further compounded by the significant suppression of DARC, PD-L1, PMS2 and overexpression of MSH2 and anti-apoptotic Bcl-2 and p53 proteins observed in our study (p < 0.05). Importantly, we found a significant reduction in expression of BIRC7/Livin and reactivation of DARC and PD-L1 with a surge in Annexin V expression in rat models of CRC cells post-treatment with a sequential dose of aspirin plus FOLFOX compared with other treatmentsin vivo(p |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3fa356990a40b313f7e6a430efea1aa4 https://doaj.org/article/3f66918bc47043f7beddbf4d0dd01de6 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3fa356990a40b313f7e6a430efea1aa4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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