The Potential of Wnt Signaling Pathway in Cancer: A Focus on Breast Cancer

Cancer development and progression as well as tumor recurrence are largely due to the presence of cancer stem cells (CSCs) that are maintained through various pathways. Wnt/β-catenin signaling is the fundamental pathway, which when deregulated leads to tumor development by sustaining CSC population. Along with the upregulation of its various components, Wnt pathway is highly active in cancer cells resulting in increased expression of the target genes. In breast cancer condition, convincing results are available wherein the Wnt pathway activation in breast cancer cells increases the cell motility while its blockade suppresses their aggressive behavior in vitro. Further, numerous reports on breast cancer patients have documented the importance of activation of Wnt pathway and its components to an extent that the regulation can be exploited therapeutically with promising results. In addition, recent research has laid emphasis on the significance of Wnt pathway in the triple-negative breast cancer, a molecular subtype of breast cancer, which lacks targeted therapy till date. Hence, understanding of Wnt signaling and its targeting to treat such patients can be an assuring approach

Clinical utility of interleukin-18 in breast cancer patients: A pilot study

Aim: The aim of this study is to analyze the protein expression of interleukin 18 (IL-18) in patients with untreated breast cancer and further to evaluate its clinical efficacy in predicting treatment outcome. Methods: In the present study, a total of 50 untreated patients with invasive ductal carcinoma of breast were included in the study. Expression of IL-18 was studied by immunohistochemistry method. Statistical analysis was carried out using Statistical Package for Social Sciences statistical software and P ≤ 0.05 was considered statistically significant. Results: Seventy-two percent of the breast cancer patients showed the presence of cytoplasmic and/or nuclear IL-18 immunoreactivity. IL-18 expression was significantly and positively correlated with the stromal response (χ2 = 3.97, r = 0.282, P = 0.044). Further, the IL-18 immunoreactivity was significantly higher in patients with HER2 amplification as compared to luminal B (χ2 = 2.82, r = −0.523, P = 0.047) breast cancer patients. Moreover, a trend of increased IL-18 expression was observed in estrogen/progesterone receptor (ER/PR) negative patients as compared to ER/PR positive patients (χ2 = 3.41, r = −0.282, P = 0.066). Conclusion: IL-18 could be used as a potential predictive marker and guide clinicians for recommendations to newer treatment. It might serve as a potential therapeutic target to establish novel treatment approaches along with the current treatment protocol used

Influence of thymidylate synthase expression on survival in patients with colorectal cancer

Background: Thymidylate synthase (TS) plays a critical role in nucleotide metabolism and is an important target for 5-fluorouracil (5-FU), the standard chemotherapeutic drug for treatment of colorectal cancer (CRC). Aims and Methods: The present study aimed to evaluate TS variable number tandem repeat sequences (VNTR) polymorphism by polymerase chain reaction and TS protein expression by immunohistochemistry and its association with clinicopathological parameters in untreated CRC patients (n = 100). Further, the prognostic and predictive role of TS has been evaluated. Results: For TS VNTR polymorphism, the observed frequencies of 2R/2R, 2R/3R, and 3R/3R genotypes were 22%, 51%, and 27%, respectively. When immunohistochemical localization was studied, cytoplasmic staining for TS was observed in 70% of patients. A significant inverse correlation was noted between TS protein expression and tumor, node, metastasis staging (P = 0.027), Dukes' staging (P = 0.039), and lymph node status (P = 0.012) of CRC patients. However, there was no significant correlation between TS VNTR polymorphism and TS protein expression. On survival analysis, a significantly shorter overall survival (OS) was seen in CRC patients with negative protein expression (P = 0.031). Moreover, the subgroup of CRC patients treated only with surgery also showed a trend of poor OS in patients with negative TS protein expression (P = 0.058). However, neither TS polymorphism nor its protein expression was able to predict relapse-free survival. Conclusion: Negative TS protein expression may be related to unfavorable clinical outcome in CRC patients. However, further studies in a larger set of patients are necessary to better assess TS as a prognostic and predictive marker for 5-FU response in CRC patients

ERCC1 expression in patients with colorectal cancer: a pilot study

Aim: Excision repair cross complementation group 1 (ERCC1) has a key role in enhanced DNA damage repair caused by oxaliplatin-based therapy and may lead to resistance of these platinum drugs in colorectal cancer (CRC) patients. Hence, the present preliminary study aimed to explore the role of ERCC1 C/T polymorphism at codon 118 as well as its immunoreactivity in patients with primary CRC. Methods: ERCC1 polymorphism was studied using PCR-RFLP and ERCC1 protein expression was examined by immunohistochemistry in 50 CRC patients. Results: ERCC1 codon 118 C/T polymorphism analysis reported the predominance of C/T (52%) genotype as compared to C/C (38%) and T/T (10%) genotypes. Furthermore, 72% of patients showed positive ERCC1 protein expression. Significant correlation was not observed between clinicopathological parameters and ERCC1 polymorphism, while ERCC1 protein expression significantly correlated only with tumor site (colon vs. rectum) (P = 0.046). Further, the present study failed to demonstrate the role of ERCC1 C118T polymorphism or protein expression as useful prognostic markers in CRC patients. Conclusion: ERCC1-positive protein expression may be a useful marker for rectal cancer patients. However, further evaluation in a larger set of CRC patients is required to better understand the role of ERCC1

Significance of TNF-α and the Adhesion Molecules: L-Selectin and VCAM-1 in Papillary Thyroid Carcinoma

Circulating levels of TNF-α and the adhesion molecules L-Selectin and VCAM-1 as well as their expression in the primary tumors of patients with benign thyroid diseases and papillary thyroid carcinoma (PTC) have been determined in this study. The serum levels of TNF-α, L-Selectin, and VCAM-1 were significantly higher in patients with both benign thyroid diseases and PTC as compared to the healthy individuals. However, the levels of only TNF-α and L-Selectin, and not VCAM-1, were significantly higher in patients with PTC in comparison to those observed in patients with benign thyroid diseases. Further the expression of TNF-α and L-Selectin was also significantly higher in the primary tumors of PTC patients, relative to the benign thyroid diseases. The expression of L-Selectin and VCAM-1 significantly correlated with aggressive tumor behavior. In PTC patients, the circulating TNF-α levels significantly positively correlated with the levels of L-Selectin, while TNF-α immunoreactivity was significantly associated with VCAM-1 expression. Serum TNF-α was found to be a significant prognosticator for OS in PTC patients. Overall the results signify that the interaction between TNF-α and the adhesion molecules may have a role in thyroid carcinogenesis and understanding this complexity may offer potential therapeutic targets for better management of thyroid cancer