Advancements in Melanoma Therapies: From Surgery to Immunotherapy.

OPINION STATEMENT: Melanoma is defined as the most aggressive and deadly form of skin cancer. The treatment of melanoma depends on the disease stage, tumor location, and extent of its spread from its point of origin. Melanoma treatment has made significant advances, notably in the context of targeted and immunotherapies. Surgical resection is the main therapeutic option for earlystage melanoma, and it provides favourable outcomes. With disease metastasis, systemic treatments such as immunotherapy and targeted therapy become increasingly important. The identification of mutations that lead to melanoma has influenced treatment strategies. Targeted therapies focusing on these mutations offer improved response rates and fewer toxicities than conventional chemotherapy. Furthermore, developing immunotherapies, including checkpoint inhibitors and tumor-infiltrating lymphocyte (TIL) therapies, has demonstrated encouraging outcomes in effectively combating cancer cells. These therapeutic agents demonstrate superior effectiveness and a more tolerable side-effect profile, improving the quality of life for patients receiving treatment. The future of melanoma treatment may involve a multimodal approach consisting of a combination of surgery, targeted therapy, and immunotherapy adapted to each patient's profile. This approach may improve survival rates and health outcomes.

Association of Interleukin-10 Polymorphisms with Susceptibility to Colorectal Cancer and Gastric Cancer: an Updated Meta-analysis Based on 106 Studies.

BACKGROUND: The purpose of this study was to explore the association of IL-10 polymorphisms with susceptibility to colorectal cancer (CRC) and gastric cancer (GC). METHODS: PubMed, Scopus, Embase, SciELO, medRxiv, China Biology Medicine Disc, DeepDyve, CNKI, and Web of Science were used to identify all relevant articles published up to 20th June 2021, without any restrictions on ethnicity. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were used to determine the strength of the associations. RESULTS: A total of 106 case-control studies were included. For CRC, 15 studies with 2772 cases and 3719 controls on -1082A/G, 11 studies with 3259 cases and 4992 controls on -592C/A, and 3 studies with 477 cases and 544 controls on -819 T/C were selected. For GC, 31 studies with 6229 cases and 8666 controls on -1082A/G, 27 studies with 5457 cases and 8381 controls on -592C/A, and 19 studies with 3556 cases and 6218 controls on -819 T/C were included. Pooled data showed a significant association between IL-10-819 T/C polymorphism and CRC susceptibility in overall population, but not for IL-10-1082A/G and -592C/A polymorphisms. However, IL-10-592C/A polymorphism was associated with CRC risk in Asians. A significant association of IL-10-1082A/G polymorphism with the GC risk was found. In the ethnicity subgroup analysis, a significant association was found between IL-10-1082A/G polymorphism and GC risk among Asians. The IL-10-819 T/C was not associated with GC risk in overall population and by ethnicity. CONCLUSIONS: Our pooled data show a significant association of IL-10-819 T/C and IL-10-1082A/G polymorphisms with CRC and GC in overall population, respectively. However, other factors may influence these associations, and large-scale studies with adequate methodological quality are necessary to confirm the impact on CRC and GC risk.

A Meta-Analysis for Association of XRCC3 rs861539, MTHFR rs1801133, IL-6 rs1800795, IL-12B rs3212227, TNF-α rs1800629, and TLR9 rs352140 Polymorphisms with Susceptibility to Cervical Carcinoma.

BACKGROUND: In spite of substantial declines in both incidence and mortality rates in the past 50 years, cervical cancer remains one of the leading causes of cancer associated mortality among women globally. We performed this meta-analysis to explore the role of XRCC3 rs861539, MTHFR rs1801133, IL-6 rs1800795, IL-12B rs3212227, TNF-α rs1800629 and TLR9 rs352140 polymorphism with susceptibility to cervical carcinoma. METHODS: The search databases include PubMed, SciELO, MedRxiv, Web of Science, Scopus, Cochrane Library, China National Knowledge Infrastructure, and China Biology Medicine disc up to 30 June 2021. The language is limited to English and Chinese. The comparison between the polymorphisms and cervical cancer was assessed using pooled odds ratio (OR) and 95% confidence interval (CI). The data are statistically analyzed by Comprehensive Meta-Analysis (CMA) 2.0 software. RESULTS: A total of 59 studies including seven studies with 1,112 cases and 1,233 controls on XRCC3 rs861539, 14 studies with 2,694 cases and 3349 controls MTHFR rs1801133, four studies with 1,121 cases and 1,109 controls on IL-12B rs3212227, seven studies with 1,452 cases and 2,186 controls on IL-6 rs1800795, 20 studies with 4,781 cases and 4909 controls on TNF-α rs1800629, and seven studies with 1743 cases and 2292 controls on TLR9 rs352140 were included. There was a significant association between XRCC3 RS861539, TNF-α rs1800629, and IL-6 rs1800795 polymorphisms and an increased risk of cervical carcinoma in overall population. However, the MTHFR rs1801133, IL-12B rs3212227 and TLR9 rs352140 polymorphisms were not associated. CONCLUSION: The pooled analysis showed that XRCC3 RS861539, TNF-α rs1800629, and IL-6 rs1800795 were associated with cervical carcinoma susceptibility, but not MTHFR rs1801133, IL-12B rs3212227 and TLR9 rs352140 polymorphisms.

Evidence from a meta-analysis for association of MC4R rs17782313 and FTO rs9939609 polymorphisms with susceptibility to obesity in children.

BACKGROUND AND AIM: The aim of this study was to evaluate the association of MC4R rs17782313 and FTO rs9939609 polymorphisms with childhood obesity. METHODS: A universal search was performed up to May 2021. RESULTS: A total of 31 studies including 13 studies with 9565 cases and 11956 controls on MC4R rs17782313 and 18 studies with 4789 cases and 15918 controls on FTO rs9939609 were selected. CONCLUSIONS: Pooled data showed that FTO rs9930506 and MC4R rs17782313 polymorphisms were significantly associated with obesity in children. Stratified analyses revealed that these genetic variants were associated with childhood obesity in Caucasian and Asian children.

Association of SERPINE1 rs1799889 polymorphism with arterial ischemic stroke in children: a systematic review and meta-analysis.

Inherited thrombophilias are well-established predisposing factors for venous thromboembolism, but their role in arterial ischemic stroke (AIS) in children, remains unclear. The association between SERPINE1 rs1799889 polymorphism and AIS in children was evaluated by several studies, whereas the results were conflicting. Thus, we performed this meta-analysis to combine and analyze the available studies in order to provide a more accurate result on the association. PubMed, Scopus, EMBASE, SciELO, MedRxiv, China Biology Medicine Disk, DeepDyve, CNKI, and Web of Science were used to identify all relevant articles published up to 30 November 2020, without any restrictions on ethnicity. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were used to determine the strength of the associations. A total of eight case-control studies with 600 cases and 2,156 controls were selected. No significant association between SERPINE1 rs1799889 polymorphism and AIS in children susceptibility was noted. In the stratified analyses by ethnicity, source of controls, genotyping methods, and age groups, there was still no significant association between SERPINE1 rs1799889 polymorphism and AIS risk in children. This study suggested that SERPINE1 rs1799889 polymorphism might be not related to etiology of AIS in children. Moreover, well-designed, large-scale and multicenter clinical studies are required to improve and validate these results.Supplemental data for this article is available online at https://doi.org/10.1080/15257770.2021.1966798 .

Association of IL-6 -174G>C and -572G>C Polymorphisms with Susceptibility to Cervical Cancer and Ovarian Cancer.

BACKGROUND: During the past decades, the expansion of molecular development has had a key role in understanding the basis of gynecological cancer. Interleukin-6 (IL-6) is known to be involved in the pathogenesis of different cancers. Here, we evaluated the association of IL-6 -174G>C and -572 G>C polymorphisms with susceptibility to cervical and ovarian cancers in an Iranian population. METHODS: A total of 131 cases with ovarian cancer, 124 cases with cervical cancer and 140 healthy subjects were enrolled to the study. DNA was extracted from peripheral blood cells of subjects to genotype the IL-6 -174G>C and -572 G>C polymorphisms by amplification refractory mutation system (RFLP) polymerase chain reaction (PCR). RESULTS: There was a significant association of IL-6 -174G>C CC genotype (OR= 3.231, 95% CI: 1.130-9.239, p=0.029) and C allele (OR = 1.915; 95%CI: 1.266-2.896, p=0.002) with an increased risk of ovarian cancer. Moreover, the IL-6 -174G>C CC genotype (OR= 3.162, 95% CI: 1.094-9.141, p=0.034) and C allele (OR = 1.724; 95%CI: 1.129-2.633, p=0.012) was associated with increased risk of cervical cancer. CONCLUSIONS: This study showed that the IL-6 -174G>C polymorphism was associated with ovarian cancer and cervical cancer risk. However, IL-6 -572 G>C polymorphism was not associated.