Immunotherapy is considered a promising approach for cancer treatment. An important strategy for cancer immunotherapy is the use of cancer vaccines, which have been widely used for cancer treatment. Despite the great potential of cancer vaccines for cancer treatment, their therapeutic effects in clinical settings have been limited. The main reason behind the lack of significant therapeutic outcomes for cancer vaccines is believed to be the immunosuppressive tumor microenvironment (TME). The TME counteracts the therapeutic effects of immunotherapy and provides a favorable environment for tumor growth and progression. Therefore, overcoming the immunosuppressive TME can potentially augment the therapeutic effects of cancer immunotherapy in general and therapeutic cancer vaccines in particular. Among the strategies developed for overcoming immunosuppression in TME, the use of toll-like receptor (TLR) agonists has been suggested as a promising approach to reverse immunosuppression. In this paper, we will review the application of the four most widely studied TLR agonists including agonists of TLR3, 4, 7, and 9 in cancer immunotherapy.

Our data showed that CXCL12 and CXCR4 are expressed simultaneously in colorectal carcinoma tissues, suggesting that expression of these chemokines and corresponding receptors may play a pivotal role in colorectal tumorigenesis, although it cannot be as a predictive factor for disease progression.

Background: Breast cancer is among the five most common cancers and ranks first among cancers diagnosed in Iranian women. Screening and treatment of this disease with molecular methods, especially regarding high incidences at early age and advanced stage, is essential. Several genes with altered expression have been identified by cDNA microarray studies in breast cancer, with the Bcl-2 gene indicated as a likely candidate. In this study, we studied Bcl-2 gene expression levels in parallel tumor and non-tumor breast tissues. Materials and Methods: Forty samples including 21 tumor, 16 non tumor (marginal) and 3 benign breast tissues which were all pathologically diagnosed, were subjected to RNA extraction and polyA RT-PCR with the expression level of Bcl-2 quantified using real-time PCR. Results: There is higher expression levels of the Bcl-2 gene in tumor samples compared with marginal samples, but not attaining significance(p>0.05). Bcl-2 expression in 14 (66.7%) of the cases of tumor samples and 9 (56.3%) cases of the marginal samples were positive. Comparison of the expression of the Bcl-2 gene in histological grade showed that a high expression of Bcl-2 was associated with a high histological grade (p<0.41). Conclusions: Our data suggests that dysregulated Bcl-2 gene expression is potentially involved in the pathogenesis of breast cancer. Using gene expression analysis may significantly improve our ability for screening cancer patients and will prove a powerful tool in the diagnosis and prognostic evaluation of the disease whilst aiding the cooperative group trials in the Bcl-2 based therapy project.

Background: Familial Mediterranean fever (FMF) is common in Azari-Turkish people, one of the biggest ethnic groups in Iran. In this study, we sought to investigate the mutation spectrum of the MEFV gene and any genotype-phenotype correlations. Methods and materials: 400 unrelated Azari-Turkish FMF patients were analyzed in this study. Mutations in exons 2, 3, 5, and 10 of the MEFV gene were investigated using direct Sanger sequencing, and their correlations with the clinical features of the patients were analyzed.Results: At least one mutation was detected in 248 (62%) patients. The most common mutations were M694V (26.25%) and E148Q (24.75%), respectively. Abdominal pain (65.2%) and fever 204 (51%) were the most frequent clinical problems in all subjects.The analysis recognized a novel missense mutation in the coding region of the MEFV gene, named P313H, which is the first report of a new mutation in exon 2 of the MEFV gene in an Azari-Turkish family.Conclusion: Genotype-phenotype correlations obtained from this study would be helpful in the diagnosis and management of FMF patients in clinical situations. This novel missense mutation may provide useful evidence for further studies of FMF pathogenesis.

Recently, combination therapies have become a promising option with hopeful therapeutic outcomes due to their strong antitumor effects. Among them, despite the great success of cancer chemoimmunotherapy, it has not been able to improve the outcome of patients. Immunosuppressive tumor microenvironment (TME) has been recognized as the main barrier to immunotherapy. So, it has been assumed that targeting HIF-1α as a reshaping of TME combined with chemoimmunotherapy can capably enhance the antitumor response of therapy. Herein, we have studied the therapeutic effects of HIF-1α inhibition combined with chemoimmunotherapy. We established CT26 mouse models to assess the synergistic effect of genetic silencing of HIF-1α combined with oxaliplatin (OXA) and imiquimod (IMQ) on tumor growth and TME. We showed that in comparison with dual combination therapy, mice treated with triple combination therapy exhibited a significant delay in tumor growth, which was correlated with high levels of cellular immune-related cytokines. Besides, mice without HIF-1α siRNA treatment exhibited high tumor growth and high levels of immunosuppressive factors, indicating an immunosuppressive phenotype. Briefly, we found that HIF-1α inhibition could synergize with OXA and IMQ to inhibit tumor growth in vivo. Our data suggest that targeting HIF-1α represents a promising strategy to enhance the antitumor response of chemoimmunotherapy.

Background: Her-2 and ESR1 genes, that interact in the cell signaling pathway, are the most important molecular markers of breast cancer, which have been amplified or overexpressed in 30% and 70%, respectively. This study was performed to evaluate the gene expression levels of Her-2 and ESR1 genes in tumor cells and its adjacent normal tissue of breast cancer patients and compared them whit clinical-pathological features. Methods: In total, 80 tissue specimens from 40 patients, with an average age of 48.47 years, were examined by Real-time PCR technique, and ultimately evaluated the expression level of Her-2 and ESR1genes. The data were analyzed by REST 2009 V2.0.13 statistical software. Results: HER2 and ESR1 overexpression was identified in 19 (48%) and 12 (30%) of 40 patients respectively, which was higher and lower than that recorded in international statistics, respectively. ESR1 overexpression was associated with Stage 3A and lymph node involvement 2 (N2) (P = 0.04 and P = 0.047, respectively). No significant correlation was observed between the expression of HER2 and ESR1 and other clinical-pathological features, however, the relative differences were identified in the expression levels of genes between main group and groups that were classified according to the clinical-pathological features and age. Conclusions: Overexpression of Her-2 and ESR1 genes in the patients of our study are higher and lower than international statistics, respectively, indicating the differences in genetic, environmental and ethnic factors that involved in the developing of breast cancer.

Background. Chronic hepatitis B is associated with different long-term outcomes in various regions. One of the critical predictors of clinical outcomes is the genotype of Hepatitis B virus (HBV). The current study investigated the frequency of worldwide and Iranian national HBV genotypes. Methods. Electronic search was performed through Medline (via Ovid), Embase, Web of Science, and Persian databases. Furthermore, the references of eligible articles were manually checked. The quantitative synthesis was conducted using the 2nd version of comprehensive Meta-analysis software (CMA.2). Results. In total, 5817 records were retrieved, and after removing duplicate studies, 3701 were screened at the title/abstract level. A total of 350 eligible studies were identified in the end.D genotype had the highest frequency (43.50%; 95% CI: 39.60 to 47.50), and the H genotype had the lowest frequency (1.2%; 95% CI: 0.6 to 2.7) globally. In 29 studies conducted in Iran (97.0%), genotype D was identified. Genotype E was the most prevalent in the African Region, followed by A in the American Region, B and C in the South-East Asian Region, D in the European Region, and C in the Western Pacific Region. Conclusion. The most prevalent genotype of HCV worldwide and in Iran is D. Furthermore, HBV genotype frequencies vary according to WHO regions. A prediction of progression could be made based on these results. Practical Implications. 1.According to the results of the meta-analyses, the D genotype had the highest frequency (43.50%; 95% CI: 39.60 to 47.50) and the genotype H had the lowest frequency (1.2%; 95% CI: 0.6 to 2.7) globally. 2.In 29 studies conducted in Iran (97.0%), genotype D was identified. 3. Genotype E was the most prevalent in the African Region, followed by A in the American Region, B and C in the South-East Asian Region, D in the European Region, and C in the Western Pacific Region.

Background: Recently, combination therapy has become a promising approach to overcoming chemotherapy problems. In the present study, we describe a combinational treatment regime using cisplatin (Cis) and imiquimod (IMQ) to increase the antitumor response of the therapy in A549 lung cancer cells. Methods: A549 cells were either treated with increasing concentrations of Cis or IMQ or with Cis-IMQ combinations for 24h. Cell growth inhibition, cell cycle analysis, and inductive apoptosis were evaluated using MTT assay and annexin V assay using flow cytometry, respectively. Kruskal-Wallis was used to analyze differences in cell groups’ means. Results: A549 cell viability was affected by single therapy of Cis and IMQ in a dose and time-dependent manner (P<0.001). The combination index (CI) analysis revealed that the combined effect of Cis-IMQ exerted a wide range of synergy in lung cancer cells as well as 0.58 to 0.84 for IC10 to IC90. More interestingly, the combination of Cis and IMQ reduced the dose of Cis by 1.86-fold. In terms of cell apoptosis induction, Cis (IC20)-IMQ (IC90) displayed a synergistic effect on A549 cells, compared to the single drug (P<0.0001). Co-treatment of A549 cells with Cis and IMQ significantly caused SubG1 arrest compared to Single therapy and control group. Conclusion: These results indicated that an IMQ-based combination using Cis has synergistic effects on cell proliferation and apoptosis induction in A549 cells and deserves further preclinical and clinical studies.