The toll-like receptor (TLR) signaling pathway plays a key role in inducing immune responses and were shown to be expressed in immune cells and tumor cells, and is involved in the progression of several malignancies including breast cancer. These findings provide a proof of the concept of targeting this pathway as a potential therapeutic option in the treatment of breast cancer. Moreover, there is a growing body of data showing the activation of TLRs in the tumor microenvironment and its dual function as anti-tumoral (dendritic T and natural killer cells activation) or pro-tumoral activity (cell proliferation, and drug resistance). Several agents have been developed for targeting of this pathway and one of these inhibitors, called Bacillus Calmette-Guerin (an agonist of TLR2 and TLR4), is recently being approved by FDA for immunotherapy of bladder cancer. This review summarizes the current knowledge of the mechanisms of action of TLR pathways in the development/progression of cancer for a better management of this disease.
Background: The incidence of colorectal cancer (CRC) has increased during recent years in Iran and other developing countries. Clinical studies suggest that essential folate dietary intake and moderate deficiency of methylenetetrahydrofolate reductase (MTHFR) may protect and reduce the risk of CRC.The aim of the present study was to investigate the clinical significance of C677T polymorphism within MTHFR gene and its correlation with the serum folate and Vit B12 in the Iranian population suffering from CRC.Methods: Blood samples were taken from 1017 Iranian individuals (517 cases and 500 controls) who were referred for colonoscopy. TaqMan probe assay was performed for C677T MTHFR polymorphism. Sera were fractionated from the blood samples of 43 patients and controls and folate and Vit B12 concentrations were measured by a monobind kit. The correlation of MTHFR polymorphisms and folate/vitamin-B12 with CRC risk were analyzed.Results: In the current study, we found the frequency of three different genotypes of MTHFR polymorphism in the Iranian population i.e., CC, CT and TT, to be 51.31, 26.73, 21.96 and 61, 32.2, 6.8 in case and control groups, respectively. The homozygote genotype of MTHFR rs1801133 polymorphism is associated with increased risk of CRC by 3.68, 1.42 and 3.74-fold in codominant, dominant and recessive models respectively (p value< 0.01). Our study revealed that there was no significant difference between the amount of folate and Vit B12 in case and control groups (p value> 0.05).Conclusions: This study revealed that there was no significant difference between the amount of folate and Vit B12 in the case and control groups. Furthermore, our results demonstrated a higher risk association for 677TT and 677TT+C677T genotypes of MTHFR compared with 677CC carriers among CRC patients.
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