Targeting ferroptosis as a cell death pathway in Melanoma: From molecular mechanisms to skin cancer treatment.

Melanoma, the most aggressive form of human skin cancer, has been under investigation to reach the most efficient treatment. Surgical resection for early-diagnosed primary melanoma, targeted therapies, and immune checkpoint inhibitors for advanced/metastatic melanoma is the best clinical approach. Ferroptosis, a newly identified iron-dependent cell death pathway, which is morphologically and biochemically different from apoptosis and necrosis, has been reported to be involved in several cancers. Ferroptosis inducers could provide therapeutic options in case of resistance to conventional therapies for advanced/metastatic melanoma. Recently developed ferroptosis inducers, MEK and BRAF inhibitors, miRNAs such as miR-137 and miR-9, and novel strategies for targeting major histocompatibility complex (MHC) class II in melanoma can provide new opportunities for melanoma treatment. Combining ferroptosis inducers with targeted therapies or immune checkpoint inhibitors increases patient response rates. Here we review the mechanisms of ferroptosis and its environmental triggers. We also discuss the pathogenesis and current treatments of melanoma. Moreover, we aim to elucidate the relationship between ferroptosis and melanoma and ferroptosis implications to develop new therapeutic strategies against melanoma.

The pro-tumorigenic responses in metastatic niches: an immunological perspective

Metastasis is the leading cause of mortality related to cancer. In the course of metastasis, cancer cells detach from the primary tumor, enter the circulation, extravasate at secondary sites, and colonize there. All of these steps are rate limiting and decrease the efficiency of metastasis. Prior to their arrival, tumor cells can modify the secondary sites. These favorable microenvironments increase the probability of successful dissemination and are referred to as pre-metastatic niches. Cancer cells use different mechanisms to induce and maintain these niches, among which immune cells play prominent roles. The immune system, including innate and adaptive, enhances recruitment, extravasation, and colonization of tumor cells at distant sites. In addition to immune cells, stromal cells can also contribute to forming pre-metastatic niches. This review summarizes the pro-metastatic responses conducted by immune cells and the assistance of stromal cells and endothelial cells in the induction of pre-metastatic niches (AU)

The pro-tumorigenic responses in metastatic niches: an immunological perspective.

Metastasis is the leading cause of mortality related to cancer. In the course of metastasis, cancer cells detach from the primary tumor, enter the circulation, extravasate at secondary sites, and colonize there. All of these steps are rate limiting and decrease the efficiency of metastasis. Prior to their arrival, tumor cells can modify the secondary sites. These favorable microenvironments increase the probability of successful dissemination and are referred to as pre-metastatic niches. Cancer cells use different mechanisms to induce and maintain these niches, among which immune cells play prominent roles. The immune system, including innate and adaptive, enhances recruitment, extravasation, and colonization of tumor cells at distant sites. In addition to immune cells, stromal cells can also contribute to forming pre-metastatic niches. This review summarizes the pro-metastatic responses conducted by immune cells and the assistance of stromal cells and endothelial cells in the induction of pre-metastatic niches.

Serum vitamin D levels and COVID-19 during pregnancy: A systematic review and meta-analysis.

BACKGROUND: Serum vitamin D levels are reported to be associated with the risk of incidence and severity of COVID-19 in the general population. During pregnancy, immune system alterations in line with changes in vitamin D metabolism may affect the course of COVID-19. Thus, we aimed to systematically review the association between vitamin D, pregnancy, and COVID-19. METHODS: A systematic literature search was conducted in PubMed, Scopus, Web of Science, Embase, and Google Scholar until the end of May 2022. Mean differences (MD) with 95% CI were used as desired effect sizes to assess the association of serum vitamin D levels with the risk of incidence and severity of COVID-19 in pregnant women. RESULTS: Among 259 records, 7 and 6 studies were included in the systematic review and meta-analysis, respectively. All included studies had acceptable quality. Our results demonstrated an insignificant difference between infected women and non-infected controls (MD = -2.55 ng/ml, 95% CI: -6.85 - 1.74). But serum vitamin D levels in severe/moderate cases compared to mild ones (MD = -2.71 ng/ml, 95% CI: -4.18 to -1.24) are significantly lower. CONCLUSION: Based on the current evidence, serum vitamin D level does not associate with the risk of SARS-CoV-2 infection among pregnant women, but we find a significant association with the severity of the disease. These findings may be helpful in similar conditions and future studies to better understand the complex immune alterations during pregnancy.