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Objectives: To evaluate the effects of the anti-inflammatory hydroxystilbene, resveratrol, on Propionibacterium acnes growth.Methods: Three different strains of P. acnes were tested against resveratrol at concentrations between 0 and 200 mg/L. Piceatannol was included as a second hydroxystilbene to compare with resveratrol, and erythromycin and benzoyl peroxide were used as positive controls.Results: After 24 h of treatment with resveratrol, the average 50% inhibitory concentration (IC 50 ) was 73 mg/L and the average 100% inhibitory concentration (IC 100 ) was 187 mg/L for the three strains of P. acnes tested. The IC 50 and IC 100 of piceatannol were 123 and 234 mg/L, respectively. The highest concentration of resveratrol tested (200 mg/L) was bactericidal, whereas lower concentrations were bacteriostatic. Conclusions:Resveratrol, an anti-inflammatory hydroxystilbene, is capable of inhibiting P. acnes growth.

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Program death receptor-1 (PD-1) and program death receptor-1 ligand (PD-L1) inhibitors are increasingly being used in the clinic to treat a growing number of malignancies, including many genitourinary (GU) malignancies. These immune-based therapies have demonstrated a distinct toxicity profile compared to traditional chemotherapy and the targeted therapies directed at the vascular endothelial growth factor pathway or the mammalian target of rapamycin pathway. Autoimmune toxicity targeting the skin, gastrointestinal tract, or the endocrine organs are some of the more common adverse events (AEs) noted with these therapies. Here in, we report the results of a systematic review of the incidence of toxicities in GU cancers reported in the phase II or phase III clinical trials using single-agent PD-1 or PD-L1 inhibitors. Overall, the rate of serious (grades 3–4) AEs was noted in approximately 15% of patients. The AEs noted were similar between all the agents tested, highlighting the overall class effect of these therapies. The incidence in GU cancers is similar to those seen in other malignancies. Given the widespread and high volume real-world use of these agents, it is important for oncologists to be familiar with these side effects to minimize the risks for patients while undergoing therapy.

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Rationale A well-developed coronary collateral circulation improves the morbidity and mortality of patients following an acute coronary occlusion. Although regenerative medicine has great potential in stimulating vascular growth in the heart, to date there have been mixed results, and the ideal cell type for this therapy has not been resolved. Objective To generate induced vascular progenitor cell(s) (iVPC(s)) from endothelial cells, which can differentiate into vascular smooth muscle cells (VSMC(s)) or endothelial cells (EC(s)), and test their capability to stimulate coronary collateral growth. Methods and Results We reprogrammed rat ECs with the transcription factors Oct4, Klf4, Sox2 and c-Myc. A population of reprogrammed cells was derived which expressed pluripotent markers Oct4, SSEA-1, Rex1 and AP and hemangioblast markers CD133, Flk1, and c-kit. These cells were designated iVPCs because they remained committed to vascular lineage and could differentiate into vascular ECs and VSMCs in vitro. The iVPCs demonstrated better in vitro angiogenic potential (tube network on 2D culture, tube formation in growth factor reduced Matrigel) than native ECs. The risk of teratoma formation in iVPCs is also reduced compared to fully reprogrammed induced pluripotent stem cell(s) (iPSC(s)). When iVPCs were implanted into myocardium, they engrafted into blood vessels and increased coronary collateral flow (microspheres) and improved cardiac function (echocardiography) better than iPSCs, mesenchymal stem cells, native ECs and sham treatments. Conclusions We conclude that iVPCs, generated by partially reprogramming ECs, are an ideal cell type for cell-based therapy designed to stimulate coronary collateral growth.

IntroductionTumor tissue and circulating tumor DNA (ctDNA) next-generation sequencing (NGS) testing are frequently performed to detect genomic alterations (GAs) to help guide treatment in metastatic renal cell carcinoma (mRCC), especially after progression on standard systemic therapy. Our objective was to assess if GAs detected by ctDNA NGS are different from those detected by tumor tissue NGS, specifically in patients with mRCC, and if these platforms are interchangeable or complimentary.ResultsWhen controlling for genes tested by both platforms, the median mutation rate for ctDNA was similar to tissue (median 3.0 vs. 1.0, p = 0.14). However, the concordance rate between the two platforms was only 8.6%. When comparing GAs by molecular pathway, GAs in tumor tissue were more common for the DNA repair and epigenetic pathways.Materials and MethodsResults of NGS testing from tumor tissue and ctDNA from 19 sequential mRCC patients were compared. GAs in each were statistically evaluated using the Wilcoxon signed-rank test. The Fischer's exact test was used to compare the incidence of mutations in selected molecular pathways.ConclusionsWhen controlling for genes tested by both platforms, similar number of GAs were detected by both tissue and ctDNA based NGS. However, there was discordance in the type of GAs detected suggesting that ctDNA NGS may be more reflective of dynamic tumor genomic heterogeneity. Hence, these two platforms may be considered complementary to each other, rather than interchangeable, for assessment of tumor GAs to guide selection of targeted clinical trial therapies.

In vivo studies suggest that vascular endothelial cells (ECs) can acquire and cross-present exogenous Ag on MHC-I but the cellular mechanisms underlying this observation remain unknown. We tested whether primary female mouse aortic ECs could cross-present exogenous male Ag to the T cell hybridoma, MHH, specific for HYUty plus Db. MHC-I-deficient male spleen cells provided a source of male Ag that could not directly stimulate the MHH cells. Addition of male but not female MHC-I-deficient spleen cells to wild-type syngeneic female EC induced MHH stimulation, demonstrating EC cross-presentation. Lactacystin treatment of the donor male MHC-I-deficient spleen cells, to inhibit proteasome function, markedly enhanced EC cross-presentation showing that the process is most efficient for intact proteins rather than degraded peptide fragments. Additional experiments revealed that this EC Ag-processing pathway is both proteasome and TAP1 dependent. These studies demonstrate that cultured murine aortic ECs can process and present MHC-I-restricted Ag derived from a separate, live cell, and they offer insight into the molecular requirements involved in this EC Ag presentation process. Through this pathway, ECs expressing cross-presented peptides can participate in the effector phase of T cell-mediated inflammatory responses such as autoimmunity, anti-tumor immunity, and transplant rejection.