Abstract Since Merkel cell polyomavirus (MCPyV) was linked as the predominant etiology of Merkel cell carcinoma (MCC) in 2008, three additional human polyomaviruses (HPyV) have been definitively linked to cutaneous diseases—trichodysplasia spinulosa virus (TSPyV) and human polyomavirus 6 and 7 (HPyV6, HPyV7). TSPyV contributes to the development of trichodysplasia spinulosa (TS), and HPyV6/7 is associated closely with the eruption of pruritic and dyskeratotic dermatoses (PDD). Clinically, MCC is treated with surgical excision and radiation with adjuvant chemotherapy, although newer treatment options include immune checkpoint inhibition. These novel immunotherapies hold promise for the treatment of metastatic MCC, but resistance and side effects prevent a significant proportion of patients from realizing their benefits. Based on previous case reports, the standard of care for the less deadly but disfiguring cutaneous disease TS include immunosuppressant (IS) reduction, the use of antivirals such as cidofovir (CDV) or valganciclovir (VGCV), or a combination of these treatments. Similar treatments were attempted for PDD, but oral acitretin was found to be most effective. As MCC, TS, and PDD are rare diseases, further research is required for effective treatments. In this review, we summarize clinical trials, preclinical studies, and case reports that present outcomes and side effects of current and emerging treatments for HPyV‐associated cutaneous diseases, offering a comprehensive resource for clinical application and prospective clinical trials.
Merkel cell carcinoma (MCC) is a highly lethal cutaneous carcinoma, which in ~80% of cases in the USA is aetiologically linked to Merkel cell polyomavirus (MCPyV). Immune checkpoint inhibitors (ICIs) can successfully treat ~50% of patients with metastatic MCC, but some MCCs are refractory to ICIs, possibly due to altered DNA damage response (DDR). Selinexor, an anticancer therapy that is currently approved in combination with chemotherapy for multiple myeloma, downregulates the small T and large T tumour antigens in MCC through selective inhibition of nuclear exportin 1 (XPO1). We examined the effect of varying doses of selinexor on DDR protein expression in MCPyV-positive and MCPyV-negative MCC cells. Selinexor was found to inhibit DDR protein expression in both MCPyV-positive and MCPyV-negative cells. Addition of selinexor alone or combined with ICI may be a promising treatment for MCC, but further in vivo research and clinical trials are required to validate these findings.
Silicon photonics is a rapidly progressing field, where silicon structures are developed for optical information generation, transmission and processing. Although substantial progress has been achieved in the fields of transmission and processing, significant challenges remain to be addressed in generating light on silicon. In this paper we show that by integrating a silicon resonator with organic semiconductors, light generation on silicon chips can be achieved in the visible spectral range. Unlike similar attempts in the telecommunication spectral region, the signal from our device can be directly measured by silicon photodetectors.
Abstract Background : Merkel cell carcinoma (MCC) is a deadly skin cancer that primarily affects the elderly and immunocompromised, with mortality rates ranging from 50% to 80%. Merkel cell polyomavirus (MCPyV) is associated with 80% of cases of MCC. The primary treatment for MCC is immune checkpoint inhibitors; however, many patients are unresponsive to or do not meet criteria for treatment. The Warburg effect has linked cancer cell survival to increased glycolytic metabolism to maintain increased cellular energy demands. While initial hypotheses suggested that increased glycolysis itself was directly upregulated and important in cancer cell proliferation, more recent ideas suggest a “moonlighting” role for glycolysis genes. In general, these “moonlighting” proteins’ non-metabolic functions are equally as important if not more important than their catalytic functions. Previous research on MCPyV-positive MCC demonstrated that selinexor targeted and decreased the expression of viral T antigens, inhibited the DNA damage response, and downregulated lipogenesis proteins. More recently, these metabolic genes have been found to regulate many oncogenes and tumor suppressors. Selinexor, an approved treatment for multiple myeloma, acts as a selective inhibitor of nuclear export by blocking exportin 1 and blocking translation of key proto-oncogenes. Objectives : Here, we report the effects of selinexor on expression of glycolytic and metabolic genes, specifically discussing the catalytic effects on metabolic function and their indirect non-catalytic effects. Methods : Immunoblotting quantified through densitometric analysis determined the protein expression in MS-1 cell lines. T-tests were used to determine statistical significance. Results : Analysis revealed highly statistically significant (p<0.001) or statistically significant (p<0.01) downregulations of protein expression of GLUD1, GLUT3, Hexokinase 1, PFKFB2, amphiregulin, LDHA, PDHK1, and MCT1. Conclusion : In the MCC cell line MS-1, selinexor significantly downregulated expression of many genes in cellular energy metabolism and cellular proliferation in a statistically significant relevant manner. These results suggest that selinexor may be a novel viable option for the treatment of MCC, but further studies in vivo and clinical trials are required to validate these findings.
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