Treatment of Unresectable Cutaneous Squamous Cell Carcinoma with Cemiplimab in a Patient on Dialysis.

Program death-1 inhibitors, a class of immune-checkpoint inhibitors, are now the standard of care in a variety of cancer settings, including cutaneous malignancies, such as melanomas, Merkel cell, and cutaneous squamous cell carcinomas (cSCCs). The clinical trials that led to the approval of the programmed death-1 inhibitor cemiplimab-rwlc (Libtayo®) for use in advanced cSCC excluded patients with autoimmune disease and those that required systemic immunosuppressive treatments, or had undergone solid-organ transplantation. Also, to be eligible, patients had to have adequate organ function. Here, we present the first report of a patient that has been successfully treated with cemiplimab for locally advanced cSCC while simultaneously on dialysis for treatment of renal failure following renal transplant.

The association of bladder cancer and Cannabis: A systematic review.

OBJECTIVE: To assess the association between Cannabis use and bladder cancer. METHODS: A systematic literature review was performed using studies published in electronic databases including PubMed, MEDLINE, and Google Scholar. Due to the scarcity of literature on this topic, the search was not limited to a specific design, year of publication, or human studies. The studies were screened by two reviewers in the following steps; first, the studies were discovered according to the predetermined search strategy; second, the unrelated studies and duplicates were eliminated by screening the abstracts, titles, and keywords; third, the full text of relevant and eligible papers were critically appraised and assessed for the risk of bias using the respective tool. The two review authors independently assessed the risk of bias and outcome levels using the Newcastle-Ottawa Scale for the outcomes in observational studies. Any disagreements were settled by a third party. RESULTS: The search strategy yielded 39 research articles. After removing 21 duplicates, 18 publications were eligible for title and abstract review. Thirteen studies were found to be irrelevant and subsequently excluded. Only three full-text articles were evaluated and included in the qualitative synthesis. CONCLUSIONS: The role of Cannabis in bladder cancer has been seldom studied. The small number of studies show contradictory findings; potential carcinogenic versus protective effect. The growing interest in Cannabis use after legalization necessitates further investigations with a robust design to assess the long-term effect of Cannabis on bladder cancer.

Microenvironment proteinases, proteinase-activated receptor regulation, cancer and inflammation.

We propose that in the microenvironment of inflammatory tissues, including tumours, extracellular proteinases can modulate cell signalling in part by regulating proteinase-activated receptors (PARs). We have been exploring this mechanism in a variety of inflammation and tumour-related settings that include tumour-derived cultured cells from prostate and bladder cancer, as well as immune inflammatory cells that are involved in the pathology of inflammatory diseases including multiple sclerosis. Our work showed that proteinase signalling via the PARs affects prostate and bladder cancer-derived tumour cell behaviour and can regulate calcium signalling in human T-cell and macrophage-related inflammatory cells as well as in murine splenocytes. Further, we found that the tumour-derived prostate cancer cells and immune-related cells (Jurkat, THP1, mouse splenocytes) can produce PAR-regulating proteinases (including kallikreins: kallikrein-related peptidases), that can control tissue function by both a paracrine and autocrine mechanism. We suggest that this PAR-driven signalling process involving secreted microenvironment proteinases can play a key role in cancer and inflammatory diseases including multiple sclerosis.

Study of the tumor microenvironment during breast cancer progression.

BACKGROUND: Different cells and mediators in the tumor microenvironment play important roles in the progression of breast cancer. The aim of this study was to determine the composition of the microenvironment during tumor progression in order to discover new related biomarkers and potentials for targeted therapy. METHODS: In this study, breast cancer biopsies from four different stages, and control breast biopsies were collected. Then, the mRNA expression of several markers related to different CD4+ T cell subsets including regulatory T cells (Treg), T helper (Th) type 1, 2 and 17 were determined. In addition, we investigated the expression of two inflammatory cytokines (TNF-α and IL-6) and inflammatory mediators including FASL, IDO, SOCS1, VEGF, and CCR7. RESULTS: The results showed that the expression of Th1 and Th17 genes was decreased in tumor tissues compared to control tissues. In addition, we found that the gene expression related to these two cell subsets decreased during cancer progression. Moreover, the expression level of TNF-α increased with tumor progression. CONCLUSION: We conclude that the expression of genes related to immune response and inflammation is different between tumor tissues and control tissues. In addition, this difference was perpetuated through the different stages of cancer.