1. Adiponectin and colorectal cancer
Kensuke Otani, et al. Surg Today. 2017 Feb;47(2):151-158. doi: 10.1007/s00595-016-1334-4. Epub 2016 Apr 9.
Colorectal cancer is an obesity-related malignancy. Adiponectin is an adipokine produced exclusively by adipose tissue, and its concentration in the serum is reduced in obesity. A low serum level of adiponectin is associated with an increased risk of various types of malignancies including colorectal cancer. These facts suggest that the epidemiological link between obesity and cancer may have a significant association with adiponectin. Although numerous studies of colorectal cancer have been reported, the results are conflicting about the anti-cancer effect of adiponectin, and how adiponectin affects carcinogenesis or cancer development remains controversial. Because adiponectin has multiple systemic effects and exists as a high serum concentration protein, the main role of adiponectin should be regulation of homeostasis, and it would not likely act as an anti-cancerous hormone. However, as epidemiological evidence shows, a low adiponectin level may be a basic risk factor for colorectal cancer. We speculate that when the colonic epithelium is stimulated or damaged by another carcinogen under the condition of a low adiponectin level, carcinogenesis is promoted and cancer development is facilitated. In this report, we summarize recent findings of the correlation between adiponectin and colorectal cancer and investigate the effect of adiponectin on colorectal cancer.
2. CD8 T Cell Score as a Prognostic Biomarker for Triple Negative Breast Cancer
Masanori Oshi, Mariko Asaoka, Yoshihisa Tokumaru, Li Yan, Ryusei Matsuyama, Takashi Ishikawa, Itaru Endo, Kazuaki Takabe Int J Mol Sci. 2020 Sep 22;21(18):6968. doi: 10.3390/ijms21186968.
CD8 T cell is an essential component of tumor-infiltrating lymphocytes (TIL) and tumor immune microenvironment (TIME). Using the xCell CD8 T cell score of whole tumor gene expression data, we estimated these cells in total of 3837 breast cancer patients from TCGA, METABRIC and various GEO cohorts. The CD8 score correlated strongly with expression of CD8 genes. The score was highest for triple-negative breast cancer (TNBC), and a high score was associated with high tumor immune cytolytic activity and better survival in TNBC but not other breast cancer subtypes. In TNBC, tumors with a high CD8 score had enriched expression of interferon (IFN)-α and IFN-γ response and allograft rejection gene sets, and greater infiltration of anti-cancerous immune cells. The score strongly correlated with CD4 memory T cells in TNBC, and tumors with both a high CD8 score and high CD4 memory T cell abundance had significantly better survival. Finally, a high CD8 score was significantly associated with high expression of multiple immune checkpoint molecules. In conclusion, a high CD8 T cell score is associated with better survival in TNBC, particularly when tumor CD4 memory T cells were elevated. Our findings also suggest a possible use of the score as a predictive biomarker for response to immune checkpoint therapy.
3. In silico and In vitro Investigation of a Likely Pathway for Anti-Cancerous Effect of Thrombocidin-1 as a Novel Anticancer Peptide
Abbas Tanhaian, Elyas Mohammadi, Roghayyeh Vakili-Ghartavol, Mohammad Reza Saberi, Mehdi Mirzayi, Mahmoud Reza Jaafari Protein Pept Lett. 2020;27(8):751-762. doi: 10.2174/0929866527666200219115129.
Background: Antimicrobial and antifungal activities of Thrombocidin-1 (TC-1) is shown previously, however,.the anti-cancerous feature of this peptide is still uncovered. Objective: The objective is to evaluate anti-cancerous feature of recombinant TC-1. Methods: In this study, based on the significant similarity of rTC-1 and IL-8 in case of coding sequence, tertiary structure, and also docking and molecular dynamic simulation (MD) results with CXCR1, a receptor which has positive correlation with different cancers, a likely pathway for anticancerous effect of rTC-1 was proposed. In addition, the coding sequence of TC-1+6xhistidine (rTC-1) was inserted into the pET22b(+) vector and cloned and expressed by E. coli BL21 and finally purified through nickel affinity column. Afterward, the retrieved rTC-1 was used in MTT assay against mouse colon adenocarcinoma, hepatocellular carcinoma, chondrosarcoma, mouse melanoma, and breast adenocarcinoma cell lines to investigate its probable anticancer application. Results: Docking and MD simulation results showed that rTC-1 and IL-8 share almost the same residues in the interaction with CXCR1 receptor. Besides, the stability of the rTC-1_CXCR11-38 complex was shown during 100ns MD simulation. In addition, the successful expression and purification of rTC-1 depict an 8kD peptide. The IC50 results of MTT assay revealed that rTC-1 has cytotoxic effect on C26-A and SW1353 cancerous cell lines. Conclusion: Therefore, apart from probable anti-cancerous effect of rTC-1 on C26-A and SW1353 cell lines, this peptide may be able to mimic the anti-cancerous pathway of IL-8.
