The role of TAOK3 in cancer progression and development as a prognostic marker: A pan-cancer analysis study.

The protein kinase TAOK3, belongs to the MAP kinase family, is one of three closely related members, namely TAOK1, TAOK2, and TAOK3. We performed a pan-cancer investigation of TAOK3 across different cancer types, including uterine carcinosarcoma, adenocarcinoma of the stomach and pancreas, and endometrial carcinoma of the uterus, to better understand TAOK3's role in cancer. In at least 16 types of cancer, our findings indicate that TAOK3 expression levels differ considerably between normal and tumor tissues. In addition, our study is the first to identify the oncogenic role of TAOK3 locus S331 and S471 in renal clear cell carcinoma, Glioblastoma Multiforme, hepatocellular carcinoma, Lung adenocarcinoma, and Pancreatic adenocarcinoma, indicating their involvement in cancer progression. In addition, our data analysis indicates that copy number variation is the most prevalent form of mutation in the TAOK3 gene, and that there is a negative correlation between TAOK3 mRNA and DNA promoter methylation. Moreover, our analysis suggests that TAOK3 may serve as a prognostic marker for several kinds of cancer, including Colon adenocarcinoma, renal clear cell carcinoma, Lower Grade Glioma, Lung adenocarcinoma, Mesothelioma, and hepatocellular carcinoma. In addition, our research on signature cancer genes has uncovered a positive association between TAOK3 and SMAD2, SMAD4, and RNF168 in most of the malignancies we have examined. TAOK3 is also correlated with the frequency of mutations and microsatellite instability in four types of cancer. Numerous immune-related genes are closely associated with TAOK3 levels in numerous malignancies. TAOK3 expression is positively correlated with immune infiltrates, which include activated CD4 T cells, CD8 T cells, and type 2T helper cells. Our pan-cancer analysis of TAOK3 provides vital insight into its potential role across a variety of cancer types.

Clinical characteristics and risk factors of patients with severe COVID-19 in Riyadh, Saudi Arabia: A retrospective study.

BACKGROUND: COVID-19 is newly emerging infectious disease that spread globally at unpredictable and unique pattern to the extent that the World Health Organization announced COVID-19 as a pandemic in the first couple months of 2020. This study aims to describe clinical and demographic features of COVID-19 patients and the influence of various risk factors on the severity of disease. METHODS: This research is a retrospective study based on Saudi Arabia's ministry of health's Covid-19 data. The analysis relies on data of all COVID-19 patients recorded in Riyadh between 1st, March 2020 and 30th, July 2020. Statistical analyses were performed to investigate the effect of demographic characteristic, clinical presentation, and comorbidities on infection severity. RESULTS: A total number of 1026 COVID-19 patients were identified based on the demographic data as follows: 709 cases (69% of cases) were males and 559 cases (54% of cases) were Saudi. Most of patients were diagnosed with mild signs and symptoms 697 (68% of cases), while 164 patient (16% of cases) demonstrated moderate signs and symptoms, and 103 cases (10%) were severe and 62 (6%) had critical febrile illness. Fever, cough, sore throat, and shortness of breath were the most common symptoms among patients with COVID-19. Among studied comorbidities in COVID-19 patients, diabetes mellitus and hypertension were the most prevalent. The results from the bivariate logistic regression analysis revealed that older age, diabetes mellitus, asthma, smoking, and fever are associated with severe or critically ill cases. CONCLUSION: The findings of this study show that old age, fever, and comorbidities involving diabetes mellitus, asthma, and smoking were significantly associated with infection severity.

Pharmacological inhibition of HDAC1/3-interacting proteins induced morphological changes, and hindered the cell proliferation and migration of hepatocellular carcinoma cells.

Liver diseases are particularly severe health problems, but the options available for preventing and treating them remain limited. Accumulating evidence has shown that there is altered expression of individual histone deacetylase (HDAC) family members in hepatocellular carcinoma cells. In a previous study, we have identified a set of proteins which interact with histone deacetylase 1 and 3 (HDAC1/3) in hepatocellular carcinoma cell lines HepG2 by proteomic approach. This study was designed to investigate the therapeutic potential and expression of HDAC1/3-interacting genes in a human hepatocellular carcinoma cell line (HepG2). Pharmacological and transcriptional inhibition of HDAC1/3 resulted in the suppression of cancer cell proliferation, change of cell morphology, and downregulation of HDAC1/3 genes in HepG2 cells. The pharmacological inhibition also resulted in inhibition of liver cancer cell migration by wound scratch assay. Taken together, the results from this study show that the upregulation of HDAC1/3 in hepatocellular carcinoma resulted in the overexpression of CNOT1, PFDN2/6, and HMG20B, and that these genes could serve as novel molecular targets in liver cancer.

Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review.

Medulloblastoma is a common fatal pediatric brain tumor. More treatment options are required to prolong survival and decrease disability. mTOR proteins play an essential role in the disease pathogenesis, and are an essential target for therapy. Three generations of mTOR inhibitors have been developed and are clinically used for immunosuppression and chemotherapy for multiple cancers. Only a few mTOR inhibitors have been investigated for the treatment of medulloblastoma and other pediatric tumors. The first-generation mTOR, sirolimus, temsirolimus, and everolimus, went through phase I clinical trials. The second-generation mTOR, AZD8055 and sapanisertib, suppressed medulloblastoma cell growth; however, limited studies have investigated possible resistance pathways. No clinical trials have been found to treat medulloblastoma using third-generation mTOR inhibitors. This systematic review highlights the mechanisms of resistance of mTOR inhibitors in medulloblastoma and includes IDO1, T cells, Mnk2, and eIF4E, as they prolong malignant cell survival. The findings promote the importance of combination therapy in medulloblastoma due to its highly resistant nature.

Glioma-derived IL-33 orchestrates an inflammatory brain tumor microenvironment that accelerates glioma progression.

Despite a deeper molecular understanding, human glioblastoma remains one of the most treatment refractory and fatal cancers. It is known that the presence of macrophages and microglia impact glioblastoma tumorigenesis and prevent durable response. Herein we identify the dual function cytokine IL-33 as an orchestrator of the glioblastoma microenvironment that contributes to tumorigenesis. We find that IL-33 expression in a large subset of human glioma specimens and murine models correlates with increased tumor-associated macrophages/monocytes/microglia. In addition, nuclear and secreted functions of IL-33 regulate chemokines that collectively recruit and activate circulating and resident innate immune cells creating a pro-tumorigenic environment. Conversely, loss of nuclear IL-33 cripples recruitment, dramatically suppresses glioma growth, and increases survival. Our data supports the paradigm that recruitment and activation of immune cells, when instructed appropriately, offer a therapeutic strategy that switches the focus from the cancer cell alone to one that includes the normal host environment.

Development of a peptide-based delivery platform for targeting malignant brain tumors.

Despite extensive molecular characterization, human glioblastoma remains a fatal disease with survival rates measured in months. Little improvement is seen with standard surgery, radiotherapy and chemotherapy. Clinical progress is hampered by the inability to detect and target glioblastoma disease reservoirs based on a diffuse invasive pattern and the presence of molecular and phenotypic heterogeneity. The goal of this study was to target the invasive and stem-like glioblastoma cells that evade first-line treatments using agents capable of delivering imaging enhancers or biotherapeutic cargo. To accomplish this, a combinatorial phage display library was biopanned against glioblastoma cell model systems that accurately recapitulate the intra- and inter-tumor heterogeneity and infiltrative nature of the disease. Candidate peptides were screened for specificity and ability to target glioblastoma cells in vivo. Cargo-conjugated peptides delivered contrast-enhancing agents to highly infiltrative tumor populations in intracranial xenograft models without the obvious need for blood brain barrier disruption. Simultaneous use of five independent targeting peptides provided greater coverage of this complex tumor and selected peptides have the capacity to deliver a therapeutic cargo (oncolytic virus VSVΔM51) to the tumor cells in vivo. Herein, we have identified a series of peptides with utility as an innovative platform to assist in targeting glioblastoma for the purpose of diagnostic or prognostic imaging, image-guided surgery, and/or improved delivery of therapeutic agents to glioblastoma cells implicated in disease relapse.