Интернет-журнал "Паблиш Украина": в виду чего его советуют?

Tight junction and gap junction are major cell junctions that play important roles in cellular communication and structural integrity. Alterations of these junctions are known to be involved in cancer pathogenesis. Claudins and connexins are major tight and gap junction proteins, but genetic alterations of these genes have not been reported in gastric (GC) and colorectal cancers (CRC) with microsatellite instability (MSI). Claudin genes CLDN5 and CKDN6, and connexin genes GJB6 and GJB7 have mononucleotide repeats in the coding sequences that might be mutation targets in the cancers with MSI. We analyzed 79 GCs and 145 CRCs, and found CLDN5 frameshift mutations in 3 (3%) CRCs and 1 (2.9%) GC, CLDN6 frameshift mutations in 6 (6%) CRCs, GJB6 frameshift mutations in 5 (5%) CRCs and GJB7 frameshift mutation in one CRC (1%) with high MSI (MSI-H). We also analyzed intratumoral heterogeneity (ITH) of the frameshift mutations in 16 CRCs and found that CLDN6 and GJB6 frameshift mutations showed regional ITH in 2 (12.5%) and 2 (12.5%) cases, respectively. Our results show that CLDN5, CLDN6, GJB6 and GJB7 genes harbor not only frameshift mutations but also mutational ITH, which together may be features of GC and CRC with MSI-H. Based on the roles of cellular junctions in cancers, frameshift mutations of tight junction and gap junction genes might contribute to tumorigenesis by altering their functions in GC and CRC.The radioresistance of oesophageal squamous cell carcinoma (OSCC) is a critical factor leading to a poor prognosis among patients. The expression of PBX1 is abnormally high in a broad range of human tissues, and this gene plays a key role in tumour proliferation. This research intended to explore the radiosensitization of OSCC by silencing PBX1. The OSCC cell lines KYSE450 and KYSE150 were subjected to PBX1 silencing and/or irradiation (IR). Cell proliferation, colony formation, and apoptosis were tested to evaluate the radiosensitization ability of PBX1 silencing. The levels of STAT3 and p-STAT3 in the OSCC cells were tested by Western blotting. Furthermore, KYSE150 cells with or without PBX1 silencing were xenografted into nude mice with or without radiation exposure. Concomitant PBX1 silencing and IR can obviously suppress growth and enhance radiosensitivity in OSCC cells and xenografts. Moreover, the downregulation of PBX1 inhibits the expression of STAT3 and p-STAT3. The downregulation of PBX1 may increase radiosensitivity in OSCC cells and xenografts via the PBX1/STAT3 pathway. Our findings demonstrate that PBX1 may be a potential target for promoting the effect of radiation therapy in OSCC patients.The pharmacokinetics of monoclonal antibodies is highly variable among patients. Several factors of variability, referred to as covariates in pharmacokinetic modeling, are known to influence this variability, such as body size, sex, antigen mass, serum albumin levels, or the presence of anti-drug antibodies. We propose a quantitative overview of the occurrence of assessment and detection of the main covariates associated with monoclonal antibody pharmacokinetics by comprehensively examining all population pharmacokinetic studies of monoclonal antibodies in humans. If some covariates are often assessed and detected (such as body size, antigen mass, or serum albumin levels), others are less frequently assessed but still may be relevant (e.g., anti-drug antibodies or endogenous immunoglobulin G levels). There is still a large heterogeneity in the relevance, availability, measurement, coding, detection, and interpretation of covariates. These issues deserve thorough investigation, which will help to design the optimal dosing strategy for every monoclonal antibody during its entire lifespan.A 70-year-old man diagnosed with lung adenocarcinoma was referred to our department for an evaluation of acute onset of nephrotic syndrome with acute kidney injury (AKI) after the 7th course of pembrolizumab treatment. Renal biopsy could not be performed, because he needed anticoagulation therapy for venous thrombosis. Pembrolizumab was discontinued, and prednisolone was started. Hemodialysis was also started, because oliguria was not resolved, and dyspnea due to pulmonary congestion appeared even with the high dose of diuretics. Hemodialysis was successfully withdrawn within 5-week duration because of renal function recovery and increase of urine volume. Complete remission was achieved 4 months after initiating prednisolone. He has never experienced hemodialysis again and remains remission of nephrotic syndrome even the dose of prednisolone was tapered for 8 months. MTP-131 Renal pathology in the current case was uncertain. However, minimal change disease seemed to be a plausible cause of nephrotic syndrome with AKI because of a good response to steroid therapy and acute onset of nephrotic syndrome. In addition, renal pathology in all of the reported cases of pembrolizumab-associated nephrotic syndrome with AKI was minimal change disease. Our case shows for the first time that renal function could be reversible with prednisolone in pembrolizumab-associated nephrotic syndrome with severe AKI even after progression of renal failure which needs dialysis.Complementary and alternative medicine (CAM) usage amongst cancer patients is high globally and in Australia. CAM use in cancer care has the ability to increase chemotherapy toxicity or cause sub-therapy due to altered metabolism as well as increase a patient's bleeding risk. Furthering these risks, people with cancer are largely obtaining their CAM use information from non-evidence-based sources. This study aimed to determine whether the implementation of a CAM education influenced decision-making with regard to CAM usage amongst cancer patients. Twenty people with cancer were recruited for participation in this study. The aims of this study were achieved by surveying patients via questionnaire, both prior to and following receiving an evidence-based CAM education, in either or both written or audiovisual format. This exploratory study found, consistent with the literature, that the majority of participants were obtaining their CAM use information from non-evidenced-based sources. Additionally, it found that the participants wanted more CAM use information and that they demonstrated some altered decision-making after receiving evidenced-based information.