Genomic and transcriptomic landscape of human gastrointestinal stromal tumors.

Gastrointestinal stromal tumor (GISTs) are clinically heterogenous exhibiting varying degrees of disease aggressiveness in individual patients. We comprehensively describe the genomic and transcriptomic landscape of a cohort of 117 GISTs including 31 low-risk, 18 intermediate-risk, 29 high-risk, 34 metastatic and 5 neoadjuvant GISTs from 105 patients. GISTs have notably low tumor mutation burden but widespread copy number variations.

Tumor cell-intrinsic SETD2 inactivation sensitizes cancer cells to immune checkpoint blockade through the NR2F1-STAT1 pathway.

Background: Cancer immunotherapies can induce durable tumor regression, but most patients do not respond. mutation has been linked to the efficacy of immune checkpoint inhibitors (ICIs) immunotherapy. The functional importance of the SETD2 inactivation and how to modulate immunotherapy response remains unclear.

Characteristic Evaluation of Recombinant MiSp/Poly(lactic--glycolic) Acid (PLGA) Nanofiber Scaffolds as Potential Scaffolds for Bone Tissue Engineering.

Biomaterial-based nanofibrous scaffolds are the most effective alternative to bone transplantation therapy. Here, two recombinant minor ampullate spidroins (spider silk proteins), R1SR2 and NR1SR2C, were blended with Poly(lactic-co-glycolic) Acid (PLGA), respectively, to generate nanofiber scaffolds by electrospinning. The N-terminal (N), C-terminal (C), repeating (R1 and R2) and spacer (S) modules were all derived from the minor ampullate spidroins (MiSp).

E3 ligase MKRN3 is a tumor suppressor regulating PABPC1 ubiquitination in non-small cell lung cancer.

Central precocious puberty (CPP), largely caused by germline mutations in the MKRN3 gene, has been epidemiologically linked to cancers. MKRN3 is frequently mutated in non-small cell lung cancers (NSCLCs) with five cohorts. Genomic MKRN3 aberrations are significantly enriched in NSCLC samples harboring oncogenic KRAS mutations.

Integrated Screens Identify CDK1 as a Therapeutic Target in Advanced Gastrointestinal Stromal Tumors.

Oncogenic KIT or PDGFRA receptor tyrosine kinase mutations are compelling therapeutic targets in gastrointestinal stromal tumor (GIST), and treatment with the KIT/PDGFRA inhibitor imatinib is the standard of care for patients with advanced GIST. Polyclonal emergence of secondary mutations is the main mechanism of imatinib progression, making it challenging to overcome KIT/PDGFRA-inhibitor resistance. It is unclear whether there are other therapeutic targets in advanced GIST.

Comparative Lipid-Lowering/Increasing Efficacy of 7 Statins in Patients with Dyslipidemia, Cardiovascular Diseases, or Diabetes Mellitus: Systematic Review and Network Meta-Analyses of 50 Randomized Controlled Trials.

Objective: The drug efficacy may differ among different statins, and evidence from head-to-head comparisons is sparse and inconsistent. The study is aimed at comparing the lipid-lowering/increasing effects of 7 different statins in patients with dyslipidemia, cardiovascular diseases, or diabetes mellitus by conducting systematic review and network meta-analyses (NMA) of the lipid changes after certain statins' use.

Methods: In this study, we searched four electronic databases for randomized controlled trials (RCTs) published through February 25, 2020, comparing the lipid-lowering efficacy of no less than two of the included statins (or statin vs.

Oncogenic and drug-sensitive RET mutations in human epithelial ovarian cancer.

Background: Epithelial ovarian cancer (EOC) is a highly lethal malignancy. Improvement in genetic characterization of EOC patients is required to propose new potential targets, since surgical resection coupled to chemotherapy, presents several limits such as cancer recurrence and drug resistance. Targeted therapies have more efficacy and less toxicity than standard treatments.

Spectrum of activity of dasatinib against mutant KIT kinases associated with drug-sensitive and drug-resistant gastrointestinal stromal tumors.

Background: The majority of GISTs express mutationally activated KIT. Imatinib and sunitinib are approved KIT-inhibiting therapies. Their efficacy is usually hampered by the acquired multiple secondary drug-resistance KIT mutations.

Effect of pharmacist-led interventions on medication adherence and inhalation technique in adult patients with asthma or COPD: A systematic review and meta-analysis.

Objective: In patients with asthma and chronic obstructive pulmonary disease (COPD), disease control is still suboptimal-incorrect inhalation technique and medication non-adherence are two important reasons for this outcome. Pharmacists' interventions have been shown to have a positive effect on the clinical outcomes of asthma and COPD. Quantitative assessment of the efficacy of pharmacist-led interventions, mainly on inhalation techniques and medication adherence, is needed.

Bistachybotrysin K, one new phenylspirodrimane dimer from with potent cytotoxic activity.

Bistachybotrysin K (), one new phenylspirodrimane dimer with a central 6/7 oxygen heterocycle core, was isolated from the fungus CGMCC 3.5365. Its structure was elucidated by extensive spectroscopic data and single-crystal X-ray diffraction.

Mutational inactivation of mTORC1 repressor gene in human gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most common human sarcoma and are initiated by activating mutations in the or receptor tyrosine kinases. Chromosome 22q deletions are well-recognized frequent abnormalities in GISTs, occurring in ∼50% of GISTs. These deletions are thought to contribute to the pathogenesis of this disease via currently unidentified tumor suppressor mechanisms.

A Cox-Based Risk Prediction Model for Early Detection of Cardiovascular Disease: Identification of Key Risk Factors for the Development of a 10-Year CVD Risk Prediction.

Background And Objective: Current cardiovascular disease (CVD) risk models are typically based on traditional laboratory-based predictors. The objective of this research was to identify key risk factors that affect the CVD risk prediction and to develop a 10-year CVD risk prediction model using the identified risk factors.

Methods: A Cox proportional hazard regression method was applied to generate the proposed risk model.

Bistachybotrysins F-J, five new phenylspirodrimane dimers with a central cyclopentanone linkage from Stachybotrys chartarum.

Bistachybotrysins F-J (1-5), five new phenylspirodrimane dimers with a central cyclopentanone core were isolated from Stachybotrys chartarum CGMCC 3.5365. The structures of 1-5 were elucidated through extensive spectroscopic data analysis, including 1D/2D NMR, HR-MS, and ECD spectra.

Oncogenic ERBB2 aberrations and KRAS mutations cooperate to promote pancreatic ductal adenocarcinoma progression.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with few therapeutic options, representing one of the great challenges in oncology. Activating KRAS mutation, occurring in >90% PDACs, is present in pancreatic intraepithelial neoplasia lesions, the precursor ductal lesions of PDAC, indicating additional genetic alterations contribute to the pathogenesis of PDAC. PDAC sequencing projects identify recurrent genomic ERBB2 alterations, mutations and amplifications, in 8.

Three new phenylspirodrimane derivatives with inhibitory effect towards potassium channel Kv1.3 from the fungus .

Three new phenylspirodrimanes derivatives named stachybotrysins H and I ( and ) and stachybotrin E (), together with one known compound stachybotrylactam (), were isolated from CGMCC 3.5365. Their structures were determined by extensive NMR data and mass spectroscopic analysis.

Genetic progression in gastrointestinal stromal tumors: mechanisms and molecular interventions.

Gastrointestinal stromal tumors (GISTs) are the most common sarcomas in humans. Constitutively activating mutations in the KIT or PDGFRA receptor tyrosine kinases are the initiating oncogenic events. Most metastatic GISTs respond dramatically to therapies with KIT/PDGFRA inhibitors.