Melanoma is the most aggressive form of skin cancer, with a high mortality rate and with 96,480 new cases expected in 2019 in the USS. BRAF V600E , the most common driver mutation, is found in around 50% of melanomas, contributing to tumor growth, angiogenesis, and metastatic progression. Dacarbazine (DTIC), an alkylate agent, was the first chemotherapeutic agent approved by the US Food and Drug Administration (FDA) used as a standard treatment. Since then, immunotherapies have been approved for metastatic melanoma (MM) including ipilimumab and pembrolizumab checkpoint inhibitors that help decrease the risk of progression. Moreover, Mycobacterium bovis Bacillus Calmette-Guerin (BCG) serves as an adjuvant therapy that induces the recruitment of natural killer NK, CD4 + , and CD8 + T cells and contributes to antitumor immunity. BCG can be administered in combination with chemotherapeutic and immunotherapeutic agents and can be genetically manipulated to produce recombinant BCG (rBCG) strains that express heterologous proteins or overexpress immunogenic proteins, increasing the immune response and improving patient survival. In this review, we highlight several studies utilizing rBCG immunotherapy for MM in combination with other therapeutic agents.

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In the present study, we aimed to evaluate the cytotoxic effect of chiral β-Aryl-chalcogenium azide compounds in vitro against the human bladder cancer cell line 5637. The cell growth inhibition was evaluated by MTT assay. The apoptosis induction and cellular viability were measured by DAPI staining and live/ dead assay, respectively. Also, gene expression of pro-apoptotic, anti-apoptotic and oxidative stress pathways were investigated by qRT-PCR. Finally, in silico molecular docking between the compounds and proteins involved in apoptotic and cell growth pathways was performed as well. Our results showed that 5c [(S)-(2-azido-1-phenyl-3-telurophenyl)propane)] and 5j [(S)-(2-azido-1-phenyl-3-teluro-p-methoxyphenyl)-propane)] compounds presented concentration-de-pendent cytotoxicity. Apoptosis analysis showed chromatin condensation in 13 % and 20.3 % of cells treated with compounds 5 c and 5 j, respectively, compared to untreated cells (2.34 %). Moreover, 5 c increased the relative expression of p53, Caspase-3, Caspase-9, SOD and CAT genes. Meanwhile, 5 j increased the expression of p53, p21, Caspase-3, Caspase-9, Bax, SOD, CAT, GPx, GR and iNOS genes. Finally, molecular docking showed that 5 c has a binding affinity to Survivin, Bcl-XL, RSK2, SGK1, while 5 j showed binding affinity to the SGK1 protein only. These findings suggest that β-Aryl-chalcogenium azide compounds could have a potential antitumoral effect in bladder cancer cells in vitro.