Non-melanoma skin cancer is one of the major ailments in the United States. Effective drugs that can cure skin cancers are limited. Moreover, the available drugs have toxic side effects. Therefore, skin cancer drugs with less toxic side effects are urgently needed. To achieve this goal, we focused our work on identifying potent lead compounds from marine natural products. Five lead compounds identified from a class of pyrroloiminoquinone natural products were evaluated for their ability to selectively kill squamous cell carcinoma (SCC13) skin cancer cells using an MTT assay. The toxicity of these compounds was also evaluated against the normal human keratinocyte HaCaT cell line. The most potent compound identified from these studies, C278 was further evaluated for its ability to inhibit cancer cell migration and invasion using a wound-healing assay and a trans-well migration assay, respectively. To investigate the molecular mechanism of cell death, the expression of apoptotic and autophagy proteins was studied in C278 treated cells compared to untreated cells using western blot. Our results showed that all five compounds effectively killed the SCC13 cells, with compound C278 being the most effective. Compound C278 was more effective in killing the SCC13 cells compared to HaCaT cells with a two-fold selectivity. The migration and the invasion of the SCC13 cells were also inhibited upon treatment with compound C278. The expression of pro-apoptotic and autophagy proteins with concomitant downregulation in the expression of survival proteins were observed in C278 treated cells. In summary, the marine natural product analog compound C278 showed promising anticancer activity against human skin cancer cells and holds potential to be developed as an effective anticancer agent to combat skin cancer.
Interferons (IFNs) have demonstrated therapeutic potential in various skin cancers, specifically squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma. The precise mechanism through which type I IFNs exert their antitumor effects in skin cancers is still being studied. However, intralesional type I IFN can be used as an alternative to surgery for select patient populations, and high-dose systemic IFN therapy has been shown to be promising in patients with operable high-risk or metastatic melanoma. Despite the therapeutic potential of IFNs in skin cancer treatment, the toxicity profile often prevents the completion of treatment and further expansion of its clinical application. Type I and III IFNs use the same Janus Kinases (JAKs) for signal transduction, which are pathways initiated at a cell surface receptor that mediates the activation of target genes in the nucleus, based on this shared signaling pathway. Due to selective tumor targeting and the ability to generate both innate and adaptive immune responses, we concluded that type III IFNs have minimal side effects compared with established treatments due to selective tumor targeting. While IFN-λ, a type III IFN, shows therapeutic potential as stand-alone or in combination with another IFN, further studies need to be conducted to explore the therapeutic potential of IFN-λ in skin cancer and the underlying physiological roles and mechanisms of action. In this review, we evaluate whether treatment of skin cancer with type III IFN will have minimal side effects compared with established treatments.
Introduction:The benefits of peer tutoring programs in improving peer tutees' overall academic performance are well-documented in the context of various academic settings, including allopathic medical schools. However, there exists very few published studies that have evaluated the impact of such peer tutoring programs in an osteopathic medical school setting. The goal of this retrospective study is to evaluate the impact of peer tutoring program, namely the Academic Assistance Program (AAP) in academic performance of peer tutees at the Alabama College of Osteopathic Medicine (ACOM).Methods: Twenty-eight peer tutees in their first-year and fifteen peer tutors in their second-year at ACOM participated in the AAP. To evaluate the academic performance of peer tutees, we compared their final exam test scores (individual courses and cumulative) with their corresponding test scores before enrolling in AAP, which consisted of scores from their first exam in the beginning of calendar year (Exam 1), undergraduate study, and MCAT. Results:The peer tutees' final test scores (for both category: individual courses and cumulative) were significantly higher than their Exam 1 scores as assessed by two-tailed, unpaired t-test (both cases, p < 0.005). We also found that the peer tutees' final cumulative scores (without lab scores) do not correlate with neither their MCAT scores (r = -0.13) nor with their undergraduate science GPA (r = 0.15). While their Exam 1 scores showed a weak correlation with their undergraduate science GPA (r = 0.38), no such correlation was found when compared to their MCAT scores (r = -0.02). Discussion and Conclusion:Our data suggest that peer tutoring programs such as the AAP can contribute to improving students' overall academic performance. Additional comparative study should be conducted to assess long-term impact of such programs on not only peer tutees but also peer tutors.
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