Let's talk about sex: A biological variable in immune response against melanoma.

As science culture gravitates toward a more holistic inclusion of both males and females in research design, the outlining of sex differences and their respective intersections with disease physiology and pathophysiology should see reciprocal expansion. Melanoma skin cancer, for example, has observed a female advantage in incidence, mortality, and overall survival since the early 1970s. The exact biological mechanism of this trend, however, is unclear and further complicated by a layering of clinical variables such as skin phototype, age, and body mass index. In this perspective, we highlight epidemiological evidence of sex differences in melanoma and summarize the landscape of their potential origin. Among several biological hallmarks, we make a note of sex-specific immune profiles-along with divergent hormonal regulation, social practices, DNA damage and oxidative stress responses, body composition, genetic variants, and X-chromosome expression-as probable drivers of disparity in melanoma initiation and progression. This review further focuses the conversation of sex as an influencing factor in melanoma development and its potential implication for disease management and treatment strategies.

It's About Time: Advances in Understanding the Circadian Regulation of DNA Damage and Repair in Carcinogenesis and Cancer Treatment Outcomes.

The circadian rhythm is established by a coordinated network of peripheral clocks interlocked and regulated by a central pacemaker. This network is maintained by the rhythmic expression of core clock genes, which in turn generate oscillatory expression patterns of different sets of target proteins in a tissue-specific manner. Precise regulation of biological processes driven by the body's circadian network in response to periodic changes in the environment determines healthy life. The delicate balance in the cycling of enzymes, metabolites, cofactors, and immune regulators is essential to achieve cellular homeostasis. Disruption of this circadian homeostasis has been linked with the development and progression of various diseases including cancer. Over the years, circadian regulation of drug metabolism and processing has been employed in the treatment of diabetes, hypertension, peptic ulcers, and allergic rhinitis. Although time dictated drug administration was demonstrated many decades ago, its application in cancer treatment is limited due to insufficient mechanistic data supporting experimental results and inconsistency between clinical trials. However, timed administration of anti-cancer drugs is rapidly gaining attention as studies with animal and human models unveil molecular intricacies involved in the circadian control of biological pathways. In this regard, striking a balance between maximizing tumor responsiveness and minimizing side effects is crucial to achieve positive patient outcomes. This review focuses on regulation of the circadian clock in carcinogenesis outcomes through DNA damage and repair mechanisms and its application in therapy with specific emphasis on skin and breast cancers.

Chemoprotective Effects of Dietary Grape Powder on UVB Radiation-Mediated Skin Carcinogenesis in SKH-1 Hairless Mice.

Skin cancer is the most frequently diagnosed cancer in the United States, and solar UVR is an established causative factor for approximately 90% of these cases. Despite efforts aimed at UV protection, including use of sunscreen and clothing, annual cases of skin cancer continue to rise. Here, we report that dietary grape powder mitigates UVB-mediated skin carcinogenesis in an SKH-1 hairless mouse model. Using a UVB initiation-promotion protocol, whereby mice were exposed to 180 mJ/cm2 UVB two times per week for 28 weeks, we determined the effects of a grape powder-fortified diet (3% or 5%) on skin carcinogenesis. Grape powder consumption at both doses resulted in marked inhibition in tumor incidence, as well as a delay in onset of tumorigenesis. Molecular analyses of skin and tumor tissue showed that grape powder-mediated protective response against UVB-induced skin cancer was accompanied by enhanced DNA damage repair, reduced proliferation, increased apoptosis, and modulations in several oxidative stress markers specifically related to inhibition of oxidative stress and increased reactive oxygen species metabolism. NRF2, an activator of cellular antioxidant response, was decreased by grape powder feeding, suggesting a supportive role in tumor cell survival. Overall, our study suggested that dietary grape, containing several antioxidants in natural amalgamation, may protect against UVB-mediated skin carcinogenesis.