Cetuximab combined with chemotherapy for simultaneous esophageal squamous cell carcinoma and colon adenocarcinoma: A case report.

Background: Multiple primary carcinomas (MPCs) are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual. Synchronous MPCs are rarer than solitary cancers or metachronous MPCs. Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases.

Structure-Based Design of Active-Site-Directed, Highly Potent, Selective, and Orally Bioavailable Low-Molecular-Weight Protein Tyrosine Phosphatase Inhibitors.

Protein tyrosine phosphatases constitute an important class of drug targets whose potential has been limited by the paucity of drug-like small-molecule inhibitors. We recently described a class of active-site-directed, moderately selective, and potent inhibitors of the low-molecular-weight protein tyrosine phosphatase (LMW-PTP). Here, we report our extensive structure-based design and optimization effort that afforded inhibitors with vastly improved potency and specificity.

Sleep patterns and potential risk factors for disturbed sleep quality in patients after surgery for infective endocarditis.

Background: The current study aimed to investigate the sleep quality of patients after valve replacement surgery due to infective endocarditis and identify risk factors for disturbed sleep post hospitalisation.

Methods: Eighty patients were assessed postoperatively using subjective scale measures, the Pittsburgh sleep quality index (PSQI) and the Epworth sleepiness scale, and an objective measure, actigraphy. Scale measures were assessed approximately 2 weeks and 6 months after surgery.

MicroRNA-181a-5p Promotes Osteosarcoma Progression via PTEN/AKT Pathway.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents with poor prognosis. MicroRNA-181a-5p (miR-181a-5p) is involved in the progression of various tumors; however, its role and underlying mechanism in osteosarcoma remains unclear. In this study, we found that miR-181a-5p was upregulated in human osteosarcoma cells and tissues.

Analysis of sleep characteristics and clinical outcomes of 139 adult patients with infective endocarditis after surgery.

Background: Little is known about the postoperative sleep quality of infective endocarditis patients during hospitalization and after discharge.

Aim: To investigate the sleep characteristics of infective endocarditis patients and to identify potential risk factors for disturbed sleep quality after surgery.

Methods: The Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale were used to assess patient sleep quality.

The Assessment of Sleep Quality in Patients Following Valve Repair and Valve Replacement for Infective Endocarditis: A Retrospective Study at a Single Center.

BACKGROUND The aim of this study was to measure sleep quality among patients who underwent infective endocarditis (IE) surgery and identify the risk factors involved in sleep disorders. MATERIAL AND METHODS In this study, we used actigraphy, the Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleep Scale (ESS) to determine the clinical characteristics of sleep disorders in 116 patients with IE who were in rehabilitation after surgery. RESULTS Our results showed that 46 (39.

Phase Separation of Disease-Associated SHP2 Mutants Underlies MAPK Hyperactivation.

The non-receptor protein tyrosine phosphatase (PTP) SHP2, encoded by PTPN11, plays an essential role in RAS-mitogen-activated protein kinase (MAPK) signaling during normal development. It has been perplexing as to why both enzymatically activating and inactivating mutations in PTPN11 result in human developmental disorders with overlapping clinical manifestations. Here, we uncover a common liquid-liquid phase separation (LLPS) behavior shared by these disease-associated SHP2 mutants.

Mechanistic insights explain the transforming potential of the T507K substitution in the protein-tyrosine phosphatase SHP2.

The protein-tyrosine phosphatase SHP2 is an allosteric enzyme critical for cellular events downstream of growth factor receptors. Mutations in the gene have been linked to many different types of human diseases, including developmental disorders, leukemia, and solid tumors. Unlike most SHP2-activating mutations, the T507K substitution in SHP2 is unique in that it exhibits oncogenic Ras-like transforming activity.

Identification of as a novel key gene in chromophobe renal cell carcinoma through bioinformatics analysis.

Chromophobe renal cell carcinoma (chRCC), the third most common histological subtype of RCC, comprises 5-7% of all RCC cases. The aim of the present study was to identify potential biomarkers for chRCC and to examine the underlying mechanisms. A total of 4 profile datasets were downloaded from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs).

Identification of EGFR as a Novel Key Gene in Clear Cell Renal Cell Carcinoma (ccRCC) through Bioinformatics Analysis and Meta-Analysis.

Clear cell renal cell carcinoma (ccRCC) was the most aggressive histological type of renal cell carcinoma (RCC) and accounted for 70-80% of cases of all RCC. The aim of this study was to identify the potential biomarker in ccRCC and explore their underlying mechanisms. Four profile datasets were downloaded from the GEO database to identify DEGs.

The Association of Vitamin D Receptor Gene Polymorphism with Lung Cancer Risk: An Update Meta-analysis.

The association between vitamin D receptor (VDR) genetic polymorphism and lung cancer risk has been evaluated by the previous meta-analyses. Due to the emergence of novel studies and inappropriate inclusion of overlapping populations, an updated meta-analysis on recent evidences is necessarily needed. We comprehensively searched databases of PubMed, Web of Science and Chinese National Knowledge Infrastructure and finally obtained 7 eligible studies according to the inclusion criteria.

Saikosaponin D inhibits proliferation of human osteosarcoma cells via the p53 signaling pathway.

Saikosaponin D (SSd), the major monomeric terpenoid extracted from , a traditional Chinese medicinal herb, exerts various pharmacological properties, including antitumor, anti-inflammatory and antiviral. The present study aimed to investigate the role of SSd in human osteosarcoma (OS) cell growth. In the investigation MTS and EdU assays were applied and flow cytometric analyses of cell cycle and apoptosis were performed.

Therapeutic Targeting of Oncogenic Tyrosine Phosphatases.

Protein tyrosine phosphatases (PTP) are exciting and novel targets for cancer drug discovery that work in concert with protein tyrosine kinases (PTK) in controlling cellular homeostasis. Given the activating role that some PTKs play in initiating growth factor-mediated cellular processes, PTPs are usually perceived as the negative regulators of these events and therefore tumor suppressive in nature. However, mounting evidence indicate that PTPs do not always antagonize the activity of PTKs in regulating tyrosine phosphorylation, but can also play dominant roles in the initiation and progression of signaling cascades that regulate cell functions.

HMGB1 promotes HLF-1 proliferation and ECM production through activating HIF1-α-regulated aerobic glycolysis.

Aerobic glycolysis is a crucial event in fibroblast differentiation, and extracellular matrix (ECM) production in the progression of pulmonary fibrosis (PF). Abnormal high mobility group protein B1 (HMGB1) activation is involved in the pathogenesis of PF. However, whether aerobic glycolysis contributes to HMGB1-induced fibroblast proliferation and ECM production in PF has not yet been determined.

Regulatory Mechanisms and Novel Therapeutic Targeting Strategies for Protein Tyrosine Phosphatases.

An appropriate level of protein phosphorylation on tyrosine is essential for cells to react to extracellular stimuli and maintain cellular homeostasis. Faulty operation of signal pathways mediated by protein tyrosine phosphorylation causes numerous human diseases, which presents enormous opportunities for therapeutic intervention. While the importance of protein tyrosine kinases in orchestrating the tyrosine phosphorylation networks and in target-based drug discovery has long been recognized, the significance of protein tyrosine phosphatases (PTPs) in cellular signaling and disease biology has historically been underappreciated, due to a large extent to an erroneous assumption that they are largely constitutive and housekeeping enzymes.

Inhibition of Low Molecular Weight Protein Tyrosine Phosphatase by an Induced-Fit Mechanism.

The low molecular weight protein tyrosine phosphatase (LMW-PTP) is a regulator of a number of signaling pathways and has been implicated as a potential target for oncology and diabetes/obesity. There is significant therapeutic interest in developing potent and selective inhibitors to control LMW-PTP activity. We report the discovery of a novel class of LMW-PTP inhibitors derived from sulfophenyl acetic amide (SPAA), some of which exhibit greater than 50-fold preference for LMW-PTP over a large panel of PTPs.

SHP2 phosphatase as a novel therapeutic target for melanoma treatment.

Melanoma ranks among the most aggressive and deadly human cancers. Although a number of targeted therapies are available, they are effective only in a subset of patients and the emergence of drug resistance often reduces durable responses. Thus there is an urgent need to identify new therapeutic targets and develop more potent pharmacological agents for melanoma treatment.

Discovery and Evaluation of PRL Trimer Disruptors for Novel Anticancer Agents.

Overexpression of PRL phosphatases (PRL1, PRL2, and PRL3) has been found in a variety of late-stage tumors and their distant metastatic sites. Therefore, the oncogenic PRL phosphatases represent intriguing targets for cancer therapy. There is considerable interest in identifying small molecule inhibitors targeting PRLs as novel anticancer agents.

Novel Anticancer Agents Based on Targeting the Trimer Interface of the PRL Phosphatase.

Phosphatase of regenerating liver (PRL) oncoproteins are phosphatases overexpressed in numerous types of human cancer. Elevated levels of PRL associate with metastasis and poor clinical outcomes. In principle, PRL phosphatases offer appealing therapeutic targets, but they remain underexplored due to the lack of specific chemical probes.

Cefsulodin Inspired Potent and Selective Inhibitors of mPTPB, a Virulent Phosphatase from Mycobacterium tuberculosis.

mPTPB is a virulent phosphatase from Mycobacterium tuberculosis and a promising therapeutic target for tuberculosis. To facilitate mPTPB-based drug discovery, we identified α-sulfophenylacetic amide (SPAA) from cefsulodin, a third generation β-lactam cephalosporin antibiotic, as a novel pTyr pharmacophore for mPTPB. Structure-guided and fragment-based optimization of SPAA led to the most potent and selective mPTPB inhibitor 9, with a K i of 7.

Exploring the Existing Drug Space for Novel pTyr Mimetic and SHP2 Inhibitors.

Protein tyrosine phosphatases (PTPs) are potential therapeutic targets for many diseases. Unfortunately, despite considerable drug discovery efforts devoted to PTPs, obtaining selective and cell permeable PTP inhibitors remains highly challenging. We describe a strategy to explore the existing drug space for previously unknown PTP inhibitory activities.

A potent and selective inhibitor for the UBLCP1 proteasome phosphatase.

The ubiquitin-like domain-containing C-terminal domain phosphatase 1 (UBLCP1) has been implicated as a negative regulator of the proteasome, a key mediator in the ubiquitin-dependent protein degradation. Small molecule inhibitors that block UBLCP1 activity would be valuable as research tools and potential therapeutics for human diseases caused by the cellular accumulation of misfold/damaged proteins. We report a salicylic acid fragment-based library approach aimed at targeting both the phosphatase active site and its adjacent binding pocket for enhanced affinity and selectivity.

[Effect of triptolide on the expression of RANTES in the renal tissue of diabetic nephropathy rats].

Objective: To investigate the effect of triptolide (TPL) on the renal tissue of diabetic rats and its possible mechanisms.

Methods: SD rats were randomly divided into the normal control group (as the normal group), the diabetic model group (the model group), the low dose TPL treatment group (the low dose TPL group, TPL 0.2 mg/kg by gastrogavage), the high dose TPL treatment group (the high dose TPL group, TPL 0.