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Connor Jernigan posted an update 6 months ago
A RAF-1/MEK/ERK pathway was founded to be associated with AG-221 and ATRA-induced differentiation in IDH2-mutant AML cells. IDH-associated changes in histone methylation markers decreased after AG-221 and ATRA combination treatment.
Our preliminary evidence indicates that the addition of ATRA to treatments with IDH2 inhibitor may lead to further improvements or increases in response rates in IDH2-mutant AML patients who do not appear to benefit from treatments with IDH2 inhibitor alone.
Our preliminary evidence indicates that the addition of ATRA to treatments with IDH2 inhibitor may lead to further improvements or increases in response rates in IDH2-mutant AML patients who do not appear to benefit from treatments with IDH2 inhibitor alone.
Gastric cancer (GC) is a malignant tumor with a high mortality rate. Drug resistance is a major obstacle to GC therapy. This study aimed to investigate the role and mechanism of exosomal circPRRX1 in doxorubicin resistance in GC.
HGC-27 and AGS cells were exposed to different doses of doxorubicin to construct doxorubicin-resistant cell lines. Levels of circPRRX1, miR-3064-5p, and nonreceptor tyrosine phosphatase 14 (PTPN14) were detected by quantitative real-time PCR or Western blot assay. Then, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, transwell, and Western blot assays were used to explore the function of circPRRX1 in GC cells. Interactions among circPRRX1, miR-3064-5p, and PTPN14 were confirmed by dual-luciferase reporter assay. The in vivo function of circPRRX1 was analyzed in a xenograft tumor model.
CircPRRX1 was highly expressed in doxorubicin-resistant GC cell lines. Knockdown of circPRRX1 reversed doxorubicin resistance in doxorubicin-resistant GC cells. Additionally, extracellular circPRRX1 was carried by exosomes to spread doxorubicin resistance. CircPRRX1 silencing reduced doxorubicin resistance by targeting miR-3064-5p or regulating PTPN14. In GC patients, high levels of circPRRX1 in serum exosomes were associated with poor responses to doxorubicin treatment. Moreover, depletion of circPRRX1 reduced doxorubicin resistance in vivo.
CircPRRX1 strengthened doxorubicin resistance by modulating miR-3064-5p/PTPN14 signaling and might be a therapeutic target for GC patients.
CircPRRX1 strengthened doxorubicin resistance by modulating miR-3064-5p/PTPN14 signaling and might be a therapeutic target for GC patients.
Non-vitamin K antagonist oral anticoagulants (NOACs) are widely used in patients with atrial fibrillation (AF) because of their effectiveness in preventing stroke and their better safety, compared with warfarin. However, there are concerns for an increased risk of bleeding associated with concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) or selective serotonin reuptake inhibitors (SSRIs) with NOACs. In this study, we aimed to evaluate the risk of bleeding events in individuals taking concomitant NSAIDs or SSRIs with NOACs after being diagnosed with AF.
A nested case-control analysis to assess the safety of NSAIDs and SSRIs among NOAC users with AF was performed using data from Korean National Health Insurance Service from January 2012 to December 2017. Among patients who were newly prescribed NOACs, 1233 cases hospitalized for bleeding events were selected, and 24660 controls were determined.
The risk of bleeding events was higher in patients receiving concomitant NSAIDs or SSRIs (aOR 1.92; 95% CI 1.52-2.42) with NOACs, compared to no use of either drug, respectively. The risk of upper gastrointestinal bleeding was higher in patients receiving concomitant NSAIDs or SSRIs without proton pump inhibitors (PPIs) (NSAIDs aOR 2.47; 95% CI 1.26-4.83, SSRI aOR 10.8; 95% CI 2.41-2.48) compared to no use.
When NSAIDs or SSRIs are required for NOAC users with AF, physicians need to monitor bleeding events and consider the use of PPIs, especially for combined use of both drugs or when initiating NOACs treatment.
When NSAIDs or SSRIs are required for NOAC users with AF, physicians need to monitor bleeding events and consider the use of PPIs, especially for combined use of both drugs or when initiating NOACs treatment.The zebrafish (Danio rerio), a small agastric teleost fish, has become a popular species to model diseases of the gastrointestinal tract. CM 4620 Remarkably, its rostral digestive tract has been largely understudied. To allow for accurate reporting and to improve the translational potential of this research model, the present study first proposes terminology for the different regions of the rostral digestive tract in zebrafish. Based on markers (in particular mucin histochemistry) which are easy to apply in routine histopathology laboratories, five regions are identified, in line with descriptions for carp, a close relative of zebrafish. The mucin histochemical staining is specific and distinct in each region identified, and can be used as a tool to assess health of the rostral digestive tract. In addition, we identify a transitional zone between the oesophagus and intestinal bulb which may represent a remnant of a rudimentary stomach.There are two seemingly unrelated approaches to weighting in observational studies. One of them maximizes the fit of a model for treatment assignment to then derive weights-we call this the modeling approach. The other directly optimizes certain features of the weights-we call this the balancing approach. The implementations of these two approaches are related the balancing approach implicitly models the propensity score, while instances of the modeling approach impose balance conditions on the covariates used to estimate the propensity score. In this article, we review and compare these two approaches to weighting. Previous review papers have focused on the modeling approach, emphasizing the importance of checking covariate balance. However, as we discuss, the dispersion of the weights is another important aspect of the weights to consider, in addition to the representativeness of the weighted sample and the sample boundedness of the weighted estimator. In particular, the dispersion of the weights is important because it translates into a measure of effective sample size, which can be used to select between alternative weighting schemes.