Search

Background: Colorectal cancer (CRC) is the deadliest malignancy in the world. The first-line chemotherapy used for CRC is 5-fluorouracil (5-FU). 5-FU completely eradicates rapidly proliferating and terminally differentiated tumor cells but fails to target cancer stem cells (CSCs). As a result, the tumor may shrink temporarily, but remnant CSC multiplies and forms a tumor again more aggressively. The recurrence and resistance lead to metastasis. Methodology: CRC was induced in 12 Sprague–Dawley (RPCP/IAEC/2019-20/R2) rats by 1,2 dimethyl hydrazine. Later, animals were treated with 5-FU for 7 weeks at a 10 mg/kg dose by the subcutaneous route. At the end of treatment, half population was sacrificed (6), whereas the remaining half (6) was left without treatment of 5-FU for 5 weeks and then sacrificed. Parameters such as body weight, complete blood count (CBC), immune cell subset (CD4, CD8, and NK cells), colon length to weight index, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) level, occult blood in stool, tumor multiplicity, and liver metastasis were estimated. In addition, the dissected colon was fixed in formalin and sent to the histology lab for hematoxylin-eosin staining and immunohistochemistry at both intervals. Results: All blood and tissue-based markers have shown significant differences (p < 0.05) between the animals sacrificed at the end of the 27th week and the end of the 32nd week for 5-FU treatment. Conclusion: It can be concluded that 5-FU up-regulates inflammatory cytokines and cell surface markers of CSC that promote CRC stemness via the Wnt/β-catenin pathway. Also, involvement of Nf-κB, fibronectin, MMP-9, and RANKL leads to tumorigenesis, disease aggressiveness, metastasis, and resistance. [ABSTRACT FROM AUTHOR]

Purpose: Nonhomologous end-joining (NHEJ) is critical for the repair of either pathologic double-strand breaks (DSBs) and/or for the repair of physiologic DSBs created during radiotherapy to kill the tumor cell. Therefore, patients with higher expression of NHEJ repair proteins might develop resistance to ionizing radiation, allowing the disease to recur. As cancer of the oral cavity is a serious health problem globally, the present study aimed to examine the expression of Ku70/80, X-ray repair cross-complementing protein 4 (XRCC4) and DNA ligase IV-core molecules of the NHEJ pathway in patients with oral cancer. Materials and Methods: Protein expression of Ku70/80, XRCC4, and DNA ligase IV were studied by Immunohistochemistry and mRNA expression of Ku70 and Ku80 were studied using reverse transcription polymerase chain reaction. Data were analyzed statistically using SPSS. Results: A univariate survival analysis revealed an association of Ku70 mRNA with shorter overall survival (OS). While protein expression of XRCC4 showed an association with reduced relapse-free survival and shorter OS. Multivariate survival analysis demonstrated that XRCC4 and DNA ligase IV are independent prognosticators for predicting adverse disease outcomes. Conclusion: Strong expression of repair proteins – XRCC4 and DNA ligase IV is associated with unfavorable disease outcome in patients with oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Introduction: Wnt signaling pathway is often dysregulated in the pathogenesis of various malignancies, including breast cancer. This might be related to methylation of the genes encoding antagonists of this signaling pathway. Aim: The aim of the study was to analyze the methylation status of the promoter regions of Wnt antagonists-secreted frizzled-related protein 1 (sFRP1) and Dickkopf 3 (DKK3) and to determine their correlation with clinicopathological parameters and survival outcome in patients with primary invasive ductal breast cancer. Materials and Methods: The methylation status of sFRP1 and DKK3 was analyzed in 160 breast tumor samples using methylation-specific polymerase chain reaction. Statistical analysis was performed using SPSS software. P ≤ 0.05 was considered as statistically significant. Results: The promoter region of sFRP1 and DKK3 genes was found to be methylated in 76% and 64% of total invasive ductal breast cancer patients, respectively. The promoter methylation in sFRP1 and DKK3 genes was significantly associated with larger tumor size, positive lymph nodes, advanced stage, and perinodal extension of breast tumors. Further, sFRP1 methylation was associated with human epidermal growth factor receptor 2-positive tumors while DKK3 methylation was associated with Grade 3 tumors. Survival analysis demonstrated that sFRP1 methylation was correlated with reduced overall survival in breast cancer patients. Conclusion: Promoter methylation of Wnt pathway antagonists is frequent in breast cancer ultimately leading to probable upregulation of the pathway in these tumors. Hence, sFRP1 and DKK3 methylation may be used as a valuable biomarker in clinical breast cancer management. [ABSTRACT FROM AUTHOR]