Meta-analysis of NFKB1-94 ATTG Ins/Del Polymorphism and Risk of Breast Cancer.

BACKGROUND: Breast cancer (BC) accounts for one of the most prevalent malignancies in the world. Inflammatory molecules modulate tumor microenvironment in BC that promotes tumor growth and metastasis. NF-κB (a transcription factor) that regulates multiple immune functions and acts as a crucial mediator of inflammatory responses. OBJECTIVE: The present study is aimed to quantitatively summarize the relation of NFKB1-94 ATTG (I, insertion/D, deletion) variant and risk of BC. METHODS: Further, the meta-analysis includes three independent case-control investigations that focus on NFKB1-94, ATTG I/D polymorphism, and BC patients. Web of Science, PubMed and Embase databases were used to retrieve relevant data. OR and 95% confidence interval of pooled studies were analyzed by using the MetaGenyo web tool. RESULTS: This study revealed a high heterogeneity. In all three genetic comparison models, the NFKB1-94 ATTG I/D variant is not related to the risk of BC. Further, no publication bias on the connection between NFKB1-94 ATTG I/D variant and risk of BC was observed. CONCLUSION: To summarize, our meta-analysis demonstrates that the NFKB1-94 ATTG I/D polymorphism is not a major risk factor for BC.

Small molecule tyrosine kinase inhibitors and pancreatic cancer-Trials and troubles.

Pancreatic cancer (PC) is an aggressive carcinoma and the fourth cause of cancer deaths in Western countries. Although surgery is the most effective therapeutic option for PC, the management of unresectable, locally advanced disease is highly challenging. Our improved understanding of pancreatic tumor biology and associated pathways has led to the development of various treatment modalities that can control the metastatic spread of PC. This review intends to present trials of small molecule tyrosine kinase inhibitors (TKIs) in PC management and the troubles encountered due to inevitable acquired resistance to TKIs.

Adiponectin: Its role in obesity-associated colon and prostate cancers.

Adipose tissue synthesizes many proteins and hormones collectively called adipokines, which are linked to a number of diseases, including cancer. Low levels of adiponectin are reported to be a risk factor for obesity-related cancers including colorectal and prostate cancers. Accordingly, obesity/lifestyle-related diseases, including certain cancers, may be treated by developing drugs that act specifically on adiponectin levels in circulation. Adiponectin may also serve as a clinical biomarker in obesity-related diseases. Adiponectin-based therapies are known to inhibit cancer advancement and thus may provide a therapeutic approach to delay cancer progression. Better understanding of the function of adiponectin is of great significance in the fight against cancer. This timely review is concentrated on the role of adiponectin and the impact of obesity on the development of cancers, especially colorectal and prostate cancers.

Role of hypoxia-inducible factors (HIF) in the maintenance of stemness and malignancy of colorectal cancer.

Hypoxia is a condition of insufficient tissue oxygenation, which is observed during normal development as well as tumorigenesis and its response at the cellular level is primarily mediated through hypoxia inducible factors (HIFs). HIFs have a significant role in the maintenance of stemness in both stem cells as well as in cancer stem cells (CSC) by acting as transcription factors. The CSCs are proposed to be the driving force of colon tumorigenesis and malignancy. These HIFs play a significant role in a wide range of diseases including colon cancer. HIF's signaling functions with stemness, and maintaining Wnt/ß-catenin signaling pathways. Due to HIFs functional significance in stemness maintenance in malignancy, targeting HIFs might provide a new approach for development of new therapy for colon cancer. In this review, we will be briefing on the colon and its stem cells, various molecular signaling pathways involved in stemness preservation, and the role hypoxia and its HIFs in the maintenance of stemness in colon stem cells and colon cancer stem cells.

Manganese-superoxide dismutase (Mn-SOD) overexpression is a common event in colorectal cancers with mitochondrial microsatellite instability.

Mitochondrial displacement loop (D-loop) is a hot spot for mitochondrial DNA (mtDNA) alterations that effects cellular reactive oxygen species (ROS) generation. Manganese-superoxide dismutase (Mn-SOD) is a major antioxidant enzyme that protects cells from ROS-mediated damage. In the present study, we investigated the relationship between sequence alterations of mitochondrial D-loop and Mn-SOD expression in colorectal cancer (CRC). Genotyping of entire mitochondrial D-loop (1124 bp) was carried out on mtDNA of analogous tumor and normal tissues from 35 CRC patients of south Indian origin by PCR-sequencing analysis. Tumor-specific large-scale mtDNA deletions and Mn-SOD expression was analyzed by PCR and Western blot analysis, respectively. We identified 87 polymorphisms in the D-loop region of tumor and/or control tissues. Polymorphisms were predominantly located in hypervariable region I (67.9 %) than in II (32.1 %) of D-loop. Significantly increased mtDNA microsatellite instability (mtMSI) [310'C' insertion (P = 0.00001) and T16189C (P = 0.0007)] and elevated Mn-SOD expression was observed in tumor tissues compared with controls. Interestingly, mtMSI was significantly high in tumors with Mn-SOD overexpression. Tumor-specific large-scale mtDNA deletions were not observed in CRC tissues. In conclusion, mtMSI and Mn-SOD overexpression are a common event in CRC. The analysis of mtMSI and/or Mn-SOD expression might help to identify patients at high risk for disease outcome, thereby helping to refine therapeutic decisions in CRC.

Hypoxia inducible factor-1α: Its role in colorectal carcinogenesis and metastasis.

Tumor growth creates a hypoxic microenvironment, which promotes angiogenesis and aggressive tumor growth and invasion. HIF1α is a central molecule involved in mediating these effects of hypoxia. In colorectal cancer (CRC), hypoxia stabilizes the transcription factor HIF1α, leading to the expression of genes that are involved in tumor vascularization, metastasis/migration, cell survival and chemo-resistance. Therefore, HIF1α is a rational target for the development of new therapeutics for CRC. This article reviews the central role of HIF1α in CRC angiogenesis, metastasis, and progression as well as the strategies to target HIF1α stabilization.