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Prostate cancer is the second most commonly diagnosed cancer in men. The mammalian insulin-like growth factor (IGF) family is made up of three ligands (IGF-I, IGF-II, and insulin), three receptors (IGF-I receptor (IGF-1R), insulin receptor (IR), and IGF-II receptor (IGF-2R)), and six IGF-binding proteins (IGFBPs). IGF-I and IGF-II were identified as potent mitogens and were previously associated with an increased risk of cancer development including prostate cancer. Several reports showed controversy about the expression of the IGF family and their connection to prostate cancer risk due to the high degree of heterogeneity among prostate tumors, sampling bias, and evaluation techniques. Despite that, it is clear that several IGF family members play a role in prostate cancer development, metastasis, and androgen-independent progression. In this review, we aim to expand our understanding of prostate tumorigenesis and regulation through the IGF system. Further understanding of the role of IGF signaling in PCa shows promise and needs to be considered in the context of a comprehensive treatment strategy. [ABSTRACT FROM AUTHOR]

Background: Embryonic pluripotency markers are recognized for their role in ER− BC aggressiveness, but their significance in ER+ BC remains unclear. This study aims to investigate the prevalence of expression of pluripotency markers in ER+ BC and their effect on survival and prognostic indicators. Methods: We analyzed data of ER+ BC patients from three large cancer datasets to assess the expression of three pluripotency markers (NANOG, SOX‐2, and OCT4), and the stem cell marker ALDH1A1. Additionally, we investigated associations between gene expression, through mRNA‐Seq analysis, and overall survival (OS). The prevalence of mutational variants within these genes was explored. Using immunohistochemistry (IHC), we examined the expression and associations with clinicopathologic prognostic indicators of the four markers in 81 ER+ BC patients. Results: Through computational analysis, NANOG and ALDH1A1 genes were significantly upregulated in ER+ BC compared to ER‐ BC patients (p < 0.001), while POU5F1 (OCT4) was downregulated (p < 0.001). NANOG showed an adverse impact on OS whereas ALDH1A1 was associated with a highly significant improved survival in ER+ BC (p = 4.7e‐6), except for the PR− and HER2+ subgroups. Copy number alterations (CNAs) ranged from 0.4% to 1.6% in these genes, with the highest rate detected in SOX2. In the IHC study, approximately one‐third of tumors showed moderate to strong expression of each of the four markers, with 2–4 markers strongly co‐expressed in 56.8% of cases. OCT‐4 and ALDH1A1 showed a significant association with a high KI‐67 index (p = 0.009 and 0.008, respectively), while SOX2 showed a significant association with perinodal fat invasion (p = 0.017). Conclusion: Pluripotency markers and ALDH1A1 are substantially expressed in ER+ BC tumors with different, yet significant, associations with prognostic and survival outcomes. This study suggests these markers as targets for prospective clinical validation studies of their prognostic value and their possible therapeutic roles. [ABSTRACT FROM AUTHOR]

Simple Summary: This review brings attention to a crucial yet under-investigated subject which is vitamin–drug interactions. Fat-soluble vitamins such as vitamins A, D, E, and K have been proven to possess many beneficial effects in the treatment and prevention of COVID-19. Moreover, it has been reported that deficiencies of fat-soluble vitamins have been directly linked to COVID-19 infection-related morbidity and mortality, especially in high-risk populations such as cancer and autoimmune patients. However, many vitamin–drug interactions exist between most of the newly COVID-19 FDA-approved medications and fat-soluble vitamins. Hence, this mandates personalizing the COVID-19 treatment protocols, especially for patients who have any deficiency in any of these vital vitamins. Weighing the risk-to-benefit ratio of supplementing any of these fat-soluble vitamins with COVID-19 medications is considered crucial to maximize the therapeutic benefit and decrease the side effects of these drugs. COVID-19 is a recent pandemic that mandated the scientific society to provide effective evidence-based therapeutic approaches for the prevention and treatment for such a global threat, especially to those patients who hold a higher risk of infection and complications, such as patients with autoimmune diseases and cancer. Recent research has examined the role of various fat-soluble vitamins (vitamins A, D, E, and K) in reducing the severity of COVID-19 infection. Studies showed that deficiency in fat-soluble vitamins abrogates the immune system, thus rendering individuals more susceptible to COVID-19 infection. Moreover, another line of evidence showed that supplementation of fat-soluble vitamins during the course of infection enhances the viral clearance episode by promoting an adequate immune response. However, more thorough research is needed to define the adequate use of vitamin supplements in cancer and autoimmune patients infected with COVID-19. Moreover, it is crucial to highlight the vitamin–drug interactions of the COVID-19 therapeutic modalities and fat-soluble vitamins. With an emphasis on cancer and autoimmune patients, the current review aims to clarify the role of fat-soluble vitamins in SARS-CoV-2 infection and to estimate the risk-to-benefit ratio of a fat-soluble supplement administered to patients taking FDA-approved COVID-19 medications such as antivirals, anti-inflammatory, receptor blockers, and monoclonal antibodies. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system is common amongst young adults, leading to major personal and socioeconomic burdens. However, it is still considered complex and challenging to understand and treat, in spite of the efforts made to explain its etiopathology. Despite the discovery of many genetic and environmental factors that might be related to its etiology, no clear answer was found about the causes of the illness and neither about the detailed mechanism of these environmental triggers that make individuals susceptible to MS. In this review, we will attempt to explore the major contributors to MS autoimmunity including genetic, epigenetic and ecological factors with a particular focus on toxins, chemicals or drugs that may trigger, modify or prevent MS disease. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC), the most prevalent among the urogenital cancers, accounts for around 3% of new cancer cases worldwide. Significantly, the incidence of RCC has doubled in developed world countries, ranking it as the sixth most common cancer in males, who represent two-thirds of RCC cases. Males with RCC exhibit a higher mortality rate and tend to develop a more aggressive form of the disease than females. Sex-related risk factors, including lifestyle and biological variations, explain this difference. The androgen receptor (AR) oncogenic signaling pathway has been extensively studied among the biological factors that affect RCC. Recent advancements in high-throughput RNA sequencing techniques have underscored the significant roles played by noncoding-RNAs (ncRNAs), previously dismissed as "junk". The oncogenic potential of AR is manifested through its dysregulation of the ncRNAs' availability and function, promoting RCC tumorigenesis. This review offers a summary of the most recent findings on the role and molecular mechanisms of the AR in dysregulating the ncRNAs that play a role in the progression of RCC and the possibility of utilizing ncRNAs to target AR as a potential therapeutic strategy.