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.

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purpose Recently, combination therapies have become a promising approach 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 known as the main barrier to therapy. It has been assumed that targeting HIF-1α as a reshaping of TME combined with chemoimmunotherapy can capably enhance the antitumor response of therapy. Methods 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. Results We showed that cotreatment of HIF-1α siRNA with OXA + IMQ 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. Conclusions Our data suggest that targeting HIF-1α represents a promising option to augment the antitumor response of chemoimmunotherapy.

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: 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.