Hickeywillis8343

Inferior ST-segment myocardial infarction (STEMI) is often due to acute occlusion of the right coronary artery (RCA) or left circumflex artery (LCx). Anatomically, distal occlusion of a dominant left anterior descending artery (LAD) wrapping around the apex supplying posterior descending artery (PDA) can also lead to inferior wall MI. The occurrence of inferior MI with LAD occlusion is underappreciated. We are presenting a case of proximal LAD occlusion leading to inferior wall MI in the presence of non-occlusive right coronary artery (RCA). Physicians should keep in mind the possibility of inferior myocardial infarction with LAD occlusion and interventional cardiologists should perform a complete angiogram to identify the faulty lesion in inferior STEMI before deciding on a RCA or LCx as the culprit artery. Isolated IWMI (inferior wall myocardial infarction) from proximal occlusion of the wrapped around LAD as noted in our patient is a rare occurrence.Prostate cancers are considered "cold" tumors characterized by minimal T cell infiltrates, absence of a type I interferon (IFN) signature, and the presence of immunosuppressive cells. This non-inflamed phenotype is likely responsible for the lack of sensitivity of prostate cancer patients to immune checkpoint blockade (ICB) therapy. Oncolytic virus therapy can potentially overcome this resistance to immunotherapy in prostate cancers by transforming cold tumors into "hot," immune cell-infiltrated tumors. We investigated whether the combination of intratumoral oncolytic reovirus, followed by targeted blockade of Programmed cell death protein 1 (PD-1) checkpoint inhibition and/or the immunomodulatory CD73/Adenosine system can enhance anti-tumor immunity. Treatment of subcutaneous TRAMP-C2 prostate tumors with combined intratumoral reovirus and anti-PD-1 or anti-CD73 antibody significantly enhanced survival of mice compared with reovirus or either antibody therapy alone. Only combination therapy led to rejection of pre-established tumors and protection from tumor re-challenge. This therapeutic effect was dependent on CD4+ T cells and natural killer (NK) cells. NanoString immune profiling of tumors confirmed that reovirus increased tumor immune cell infiltration and revealed an upregulation of the immune-regulatory receptor, B- and T-lymphocyte attenuator (BTLA). This expression of BTLA on innate antigen-presenting cells (APCs) and its ligand, Herpesvirus entry mediator (HVEM), on T cells from reovirus-infected tumors was in keeping with a role for the HVEM-BTLA pathway in promoting the potent anti-tumor memory response observed.Characterization of the intratumoral immune status is important for developing immunotherapies and evaluating their antitumor effectiveness. CD8+ T cells are one of the most important cell types that directly and indirectly contribute to antitumor efficacy by releasing cytolytic molecules and inflammatory cytokines in the tumor microenvironment. Previously, we engineered a tumor-selective oncolytic vaccinia virus that encodes interleukin-7 (IL-7) and IL-12 and demonstrated its usefulness as an agent for in situ vaccination against tumors, with data showing that antitumor efficacy was reliant upon CD8+ T cells recruited by viral treatment. Here, we investigated the phenotypic changes in intratumoral CD8+ T cells caused by this oncolytic virus and found increased expression of inducible co-stimulator (ICOS) in PD-1-CD8+ T cells. Unlike previously reported ICOS+CD8+ T cells, a subset of ICOS+PD-1-CD8+ T cells showed effector function characterized by granzyme B expression. ICOS expression was induced by the backbone virus, which did not encode any immune transgenes and was independent of upregulation of the type I interferon pathway. Not only did we identify a novel effector cell subset characterized by ICOS expression, but our findings also shed light on a potential unknown aspect of the mechanism of oncolytic vaccinia virotherapy.Immunotherapy is a potential way to save the lives of patients with bladder cancer, but it only benefits approximately 20% of them. A total of 4,028 bladder cancer patients were collected for this study. Unsupervised non-negative matrix factorization and the nearest template prediction algorithms were employed for the classification. We identified the immune and non-immune classes from The Cancer Genome Atlas Bladder Urothelial Carcinoma (TCGA-BLCA) training cohort. The 150 most differentially expressed genes between these two classes were extracted, and the classification reappeared in 20 validation cohorts. For the activated and exhausted subgroups, a stromal activation signature was assessed by the NTP algorithm. Patients in the immune class showed highly enriched signatures of immunocytes, while the exhausted subgroup also exhibited activated transforming growth factor (TGF)-β1, and cancer-associated extracellular matrix signatures. Patients in the immune-activated subgroup showed a lower genetic alteration and better overall survival. Anti-PD-1/PD-L1 immunotherapy was more beneficial for the immune-activated subgroup, while immune checkpoint blockade therapy plus a TGF-β inhibitor or an EP300 inhibitor might achieve greater efficacy for patients in the immune-exhausted subgroup. Novel immune molecular classifier was identified for the innovative immunotherapy of patients with bladder cancer.Prognosis for advanced oral carcinoma remains poor. Oncolytic virotherapy uses replication-competent viruses to infect and kill only the tumor cells. However, it has been difficult to investigate the oncolytic activity of viruses against oral carcinomas in mouse models. This study established a mouse model of oral cancer and investigated the in vitro and in vivo anti-tumor effects of HF10, a highly attenuated, replication-competent herpes simplex virus (HSV)-1. Mouse tongue cancer was induced by injecting 4-nitroquinoline 1-oxide into the mouse tongue. The murine oral cancer cell line isolated from this tumor, named NMOC1, formed invasive carcinoma within a week when injected into mouse tongue. HF10 successfully infected, replicated, and spread in the cancer cells in vitro. HF10 was able to kill cancer cells isolated from human or mouse tongue tumor. HF10 injection into tongue carcinomas prolonged mouse survival without any side effects or weight loss. selleck Intertumoral injection of GFP-expressing HF10 confirmed that viral spread was confined within the tumors. Immunohistochemical staining showed that HF10 induced infiltration of CD8-positive T cells around HSV-infected cells in the tumor mass, implying increased anti-tumor immunity. We successfully established an oral cancer cell line and showed that HF10 is a promising therapeutic agent for oral cancer.Gene vectors regulated by tumor-specific promoters to express transgenes specifically in cancer cells are an emerging approach for cancer diagnosis and treatment. Minicircles are shortened plasmids stripped of prokaryotic sequences that have potency and safety characteristics beneficial for clinical translation. Previously, we developed minicircles driven by the tumor-specific survivin promoter, which exhibits elevated transcriptional activity in aggressive cancers, to express a secreted reporter for blood-based cancer detection. Here we present the first activatable, cancer theranostic minicircle system featuring a pair of diagnostic and therapeutic minicircles expressing Gaussia luciferase for urine-based cancer detection or cytosine deaminaseuracil phosphoribosyltransferase for gene-directed enzyme prodrug therapy. Diagnostic minicircles revealed urinary reporter output related to cellular survivin levels. Notably, mice with aggressive prostate tumors exhibited significantly higher urine reporter activity than mice with non-aggressive tumors and healthy mice after intratumoral minicircle administration. Therapeutic minicircles displayed specific cytotoxicity in survivin-rich cancer cells and significantly attenuated growth of aggressive orthotopic prostate tumors in mice. Use of these minicircles together creates a theranostic system that can first identify individuals carrying aggressive prostate cancer via a urinary test, followed by stringent control of tumor progression in stratified individuals who carry high-risk prostate lesions.Glioma is a highly heritable disease with a strong genetic component. The N6-methyladenosine (m6A) modification core genes play important roles in the context of cancer. However, the effects of polymorphisms in the m6A modification core genes on the risk of pediatric glioma remain undefined. Here, we intended to demonstrate the relationship between 24 functional single-nucleotide polymorphisms (SNPs) in eight m6A modification core genes and glioma risk. Case-control design and multinomial logistic regression were used to develop models to estimate the risk of glioma while accounting for the subtypes of glioma. A total of 171 glioma cases and 228 controls from South China were genotyped using a TaqMan assay. The WTAP rs7766006, YTHDF2 rs3738067, and FTO rs9939609 variants conferred a statistically significant increased risk of glioma, respectively. YTHDC1 rs2293595, YTHDC1 rs3813832, and FTO rs8047395 were associated with a significant inverse association with risk of glioma, respectively. The significant associations were more predominant in stratification analyses of certain subgroups. Functional annotations revealed that WTAP rs7766006 and YTHDF2 rs3738067 could be potential functional variants by increasing expression of WTAP and YTHDF2 mRNA, respectively. Overall, these findings implicate variants in the m6A modification core genes as playing a role in pediatric glioma etiology.Previously, we showed that mouse immunity-related guanosine triphosphatase (GTPase) family M protein 1 (Irgm1) promotes malignant melanoma progression by inducing cellular autophagy flux and metastasis. Human IRGM, a truncated protein functionally distinct from its mouse counterpart, has several splice isoforms. In this study, we analyzed the association of IRGM and human melanoma clinical prognosis and investigated the function of IRGM in human melanoma cells. Data from the training cohort (n = 144) showed that overexpression of IRGM is proportional to melanoma genesis and clinical stages in human tissue chips. A validation cohort (n = 78) further confirmed that IRGM is an independent risk factor promoting melanoma progression and is associated with poor survival of patients. Among IRGM isoforms, we found that IRGMb is responsible for such correlation. In addition, IRGM promoted melanoma cell survival through autophagy, both in vitro and in vivo. We further showed that the blockade of translocation of high-mobility group box 1 (HMGB1) from the nucleus to cytoplasm inhibits IRGM1-mediated cellular autophagy and reduces cell survival. IRGM functions as a positive regulator of melanoma progression through autophagy and may serve as a promising prognostic marker and therapeutic target.Myocardial infarction (MI) is a life-threatening disease resulting from irreversible death of cardiomyocytes (CMs) and weakening of the heart blood-pumping function. Stem cell-based therapies have been studied for MI treatment over the last two decades with promising outcome. In this review, we critically summarize the past work in this field to elucidate the advantages and disadvantages of treating MI using pluripotent stem cells (PSCs) including both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), adult stem cells, and cardiac progenitor cells. The main advantage of the latter is their cytokine production capability to modulate immune responses and control the progression of healing. However, human adult stem cells have very limited (if not 'no') capacity to differentiate into functional CMs in vitro or in vivo. In contrast, PSCs can be differentiated into functional CMs although the protocols for the cardiac differentiation of PSCs are mainly for adherent cells under 2D culture. Derivation of PSC-CMs in 3D, allowing for large-scale production of CMs via modulation of the Wnt/β-catenin signal pathway with defined chemicals and medium, may be desired for clinical translation.