- |||||||||| doxorubicin hydrochloride / Generic mfg.
Journal, IO Biomarker: MiR-181c protects cardiomyocyte injury by preventing cell apoptosis through PI3K/Akt signaling pathway. (Pubmed Central) - Sep 26, 2020 In this study, we are focused to identify the role of miRNA-181c in the regulating of myocardial tissue apoptosis in the doxorubicin (DOX) or hypoxia/reoxygenation (H/R) induced H9C2 cardiomyocyte injury...Under the stimulation of H/R or DOX, miR-181c could downregulate protein expression of Fas, IL-6 and TNF-α, and upregulated Bcl2 and the phosphorylation of Akt. Our study revealed that miR-181c protected heart failure by impeding cardiomyocyte apoptosis through PI3K/Akt pathway, implying the therapeutic role of miR-181c during the exacerbation of the cardiovascular disease.
- |||||||||| Nexavar (sorafenib) / Bayer, Amgen
Journal: GHR knockdown enhances the sensitivity of HCC cells to sorafenib. (Pubmed Central) - Sep 25, 2020 and the inactivation of PI3K/AKT/ERK1/2 signaling pathway may be the underlying mechanisms. This highlights the absence of GHR as a promising way to enhance sorafenib efficacy in HCC.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Zinc induces iron egress from intestinal Caco-2 cells via induction of Hephaestin: A role for PI3K in intestinal iron absorption. (Pubmed Central) - Sep 25, 2020 LY294002, an inhibitor of PI3K, inhibited the zinc-induced iron transport, DMT1, HEPH mRNA and protein expression...These results suggest that intestinal cell zinc status is a critical determinant of iron absorption and effects are mediated via activation of PI3K. Further, PI3K pathway appears to selectively modulate the expression of iron transporters and iron absorption, therefore this might serve as a therapeutic target in iron overload disorders.
- |||||||||| low molecular weight dextran sulfate (ILB) / TikoMed, quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Glutamine relieves oxidative stress through PI3K/Akt signaling pathway in DSS-induced ulcerative colitis mice. (Pubmed Central) - Sep 25, 2020 The mice in the experimental group drank 4% dextran sulfate sodium salt (DSS) for 7 consecutive days...Administration of Gln to the DSS-induced colitis mice led to a clearly reduction in oxidative stress-induced injury. The Gln is confirmed as inhibiting the PI3K/Akt signaling pathway activity.
- |||||||||| Journal: An Active Micropump-mixer for Rapid Anti-platelet Drug Screening in Whole Blood. (Pubmed Central) - Sep 23, 2020
In a proof-of-concept pre-clinical application we utilize this system to investigate the way in which rapid dosing of human whole blood with isoform se-lective inhibitors of phosphatidylinositol 3-kinase dose dependently modulate platelet thrombus dynamics. This modular sys-tem exhibits utility as an automated multiplexable assay system with applications to high-content chemical library screening of new antiplatelet therapies.
- |||||||||| Journal: Activation leads to a significant shift in the intracellular redox homeostasis of neutrophil-like cells. (Pubmed Central) - Sep 23, 2020
Furthermore, inhibition of PI3K, which abrogates cytosolic oxidation, did not fully prevent NETosis induced by phagocytosis of bacteria. Thus, we conclude that NET-formation is regulated in a multifactorial way, in part by changes of the cytosolic thiol redox homeostasis in neutrophils, depending on the circumstance under which the generation of NETs was initiated.
- |||||||||| Leustatin (cladribine) / J&J, Opdivo (nivolumab) / Ono Pharma, BMS, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
[VIRTUAL] New drugs for low grade lymphoproliferative diseases (ATİLLA YALÇIN HALL) - Sep 23, 2020 - Abstract #EHOC2020EHOC_28; Tazemetostat a novel EZH2 inhibitor recently received accelerated approval by FDA for patients with RR-FL and EZH2 gene mutations, following the results of a phase-II study...Immune check point inhibitors (Nivolumab, Pemprolizumab, Atezolizumab) are promising as third line treatment and beyond. Other agents under investigation include the inhibitor of nuclear export selinexor, the SYK inhibitor entospletinib, the dual SYK/JAK inhibitor certulatinib and the CDK inhibitors flavopiridol and dinaciclib.
- |||||||||| Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
[VIRTUAL] How can we estimate early relapsed follicular lymphoma and how can we treat? (ATİLLA YALÇIN HALL) - Sep 23, 2020 - Abstract #EHOC2020EHOC_20; For fit patients age <65 years without an appropriate clinical trial option consolidative autologous stem cell transplant should be considered to induce prolonged remissions and improve prognosis. Nevertheless, there is an unmet need for better identification and treatment of POD 24 patients.
- |||||||||| Preclinical, Journal: Cardiac Contractility Modulation Attenuates Chronic Heart Failure in a Rabbit Model via the PI3K/AKT Pathway. (Pubmed Central) - Sep 23, 2020
The levels of Akt, FOXO3, Beclin, mTOR, GSK-3β, and TORC2 were significantly downregulated, but Pi3k concentration was greatly upregulated after CCM utilization. Based on these findings, it was concluded that CCM could elicit positive effects on HF therapy, which was potentially due to the variation in the Pi3k/Akt signaling pathway.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, elacestrant (RAD1901) / Menarini
Review, Journal: The Future of ER+/HER2- Metastatic Breast Cancer Therapy: Beyond PI3K Inhibitors. (Pubmed Central) - Sep 23, 2020 In addition, promising therapeutic options include targeting other surface receptors or their downstream pathways, as well as targeting the apoptotic machinery and boosting the immune response which is initially insufficient in these cancers. A selection of new drugs in advanced development for ER+/HER2- breast cancer will be discussed in this review.
- |||||||||| Piqray (alpelisib) / Novartis, GDC-0077 / Roche
Review, Journal: PI3K inhibitors: review and new strategies. (Pubmed Central) - Sep 23, 2020 A second (GDC0077), classified as PI3Kα isoform-specific, is undergoing clinical trials...Here we briefly review PI3Kα mutations, focus on PI3K drug repertoire and propose new, to-date unexplored PI3Kα therapeutic strategies. These include (1) an allosteric and orthosteric inhibitor combination and (2) taking advantage of allosteric rescue mutations to guide drug discovery.
- |||||||||| Journal: Effects of forced swimming stress on expression and phosphorylation of PI3K/Akt signal pathway in pancreas of type 2 diabetic rats. (Pubmed Central) - Sep 23, 2020
Blood glucose and insulin levels in the diabetic model stress group were significantly lower than those in the diabetic model group, and the protein levels of PI3K, p-AKT, and mTOR in the pancreas of the diabetic model stress group were significantly higher than those of the diabetic model group. One-week swimming stress can decrease the blood glucose level and improve insulin indexes in type 2 diabetic rats and increase the expression and phosphorylation of pancreatic PI3K/Akt signal pathway proteins.
- |||||||||| Journal: Soluble Klotho Improves Hepatic Glucose and Lipid Homeostasis in Type 2 Diabetes. (Pubmed Central) - Sep 23, 2020
Mechanistic studies in vitro and in vivo demonstrated that sKL could inhibit the PI3K/AKT/mTORC1 signaling to upregulate peroxisome proliferator-activated receptor α (PPARα) expression by directly interacting with type 1 insulin-like growth factor receptor (IGF1R) in HFD-fed T2D mice. Thus, sKL could improve hepatic glucolipid homeostasis to ameliorate diabetic phenotypes and lipid accumulation and may function as a potential therapeutic target for the treatment of T2D and reduce the risk of NAFLD.
- |||||||||| fluvastatin / Generic mfg., Zelboraf (vemurafenib) / Roche
Journal: Fluvastatin exerts an antitumor effect in vemurafenib-resistant melanoma cells. (Pubmed Central) - Sep 21, 2020 Intriguingly, application of a statin-related drug, fluvastatin, also resulted in a synergistic increase of sensitivity to vemurafenib in the VR cells (combination index: 0.73-0.86) probably by alleviating constitutive AKT activation, whereas the same treatment did not notably alter the vemurafenib sensitivity of the parental cells. Our results suggest the possible usefulness of statin-related drugs for overcoming vemurafenib resistance acquired through constitutive activation of the PI3K-AKT axis.
- |||||||||| fingolimod / Generic mfg., Novus Therap
Journal: FTY720 Inhibits MPP-Induced Microglial Activation by Affecting NLRP3 Inflammasome Activation. (Pubmed Central) - Sep 21, 2020 These findings provide novel insights into the mechanisms underlying the therapeutic effects of FTY720, suggesting its potential as a novel therapeutic strategy against PD. Graphical Abstract FTY720 may reduce ROS production by inhibiting the PI3K/AKT/GSK-3β signaling pathway, while at the same time reducing p65 phosphorylation, thus decreasing NLRP3 inflammasome activation through these two pathways, ultimately reducing microglia activation-induced neuronal damage.
- |||||||||| Journal: miRNA-30-3p improves myocardial ischemia via the PTEN/PI3K/AKT signaling pathway. (Pubmed Central) - Sep 21, 2020
The pathological observations, cell apoptosis, LDH, SOD, MDA, and relative protein expressions were evaluated with hematoxylin and eosin, enzyme-linked immunosorbent assay, terminal deoxynucleotide transferase dUTP nick-end labeling or immunohistochemical methods. The results show that miRNA-30-3p had the effect of improving cell apoptosis induced by myocardial ischemia in vitro and in vivo studies by the regulation of the PTEN/PI3K/AKT pathway.
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