- |||||||||| quercetin (LY294002) / Eli Lilly, Tamoxis (tamoxifen) / Bioprofarma, U0126 / Promega
Journal: Fibrauretine reduces ischemia/reperfusion injury via RISK/eNOS activation. (Pubmed Central) - Dec 8, 2019
It is suggested that eNOS plays an important role in the protective effect of fibrauretine on the heart. Therefore, the results of this study show that the protective effect of fibrauretine on myocardial I/R injury is closely associated with eNOS expression, GR/ER-induced Akt phosphorylation and ERK1/2 activation.
- |||||||||| Review, Journal: Does Ras Activate Raf and PI3K Allosterically? (Pubmed Central) - Dec 8, 2019
Thus, RTKs allosterically activate PI3Kα; however, merging their action with Ras accomplishes full activation. Here we review their activation mechanisms in this light and draw attention to implications for their pharmacology.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: NCAPG Promotes The Proliferation Of Hepatocellular Carcinoma Through PI3K/AKT Signaling. (Pubmed Central) - Dec 8, 2019
LY294002, a PI3K inhibitor, could eliminate the NCAPG role of promoting HCC cell proliferation and reducing HCC cell apoptosis, while 740Y-P, a PI3K activator, contributed to the opposite effect. NCAPG functions as an oncogene in HCC and plays a role in promoting cell proliferation and antiapoptosis through activating the PI3K/AKT/FOXO4 pathway.
- |||||||||| International Retrospective Study of Allogeneic Hematopoietic Cell Transplantation (HCT) for Activated Phosphoinositide 3-Kinase Delta (PI3K) Syndrome (World Center Marriott - Palms: Sabal) - Dec 8, 2019 - Abstract #TCTASTCTCIBMTR2020TCT_585;
While we found no association with GF or DCI for discrete elements such as serotherapy use, donor source, or conditioning intensity, small numbers preclude conclusions regarding the optimal HCT approach, and more HCTs with longer follow up are needed to refine these preliminary findings. Post-HCT mTOR inhibitor exposure was associated with need for subsequent unplanned DCI, perhaps by providing a survival advantage to host lymphocytes, and may thus be detrimental in these patients during the early post-HCT timeframe.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: The Cytoplasmic Expression Of CLDN12 Predicts An Unfavorable Prognosis And Promotes Proliferation And Migration Of Osteosarcoma. (Pubmed Central) - Dec 8, 2019
The results also demonstrated that the overexpression of CLDN12 increased the activation of Thr308 site in Akt in fetal osteoblast cells, and the PI3K inhibitor LY294002 partially decreased CLDN12-promoted proliferation and metastasis. In conclusion, the results of the present study indicated that CLDN12 promoted cell proliferation and migration through the PI3K/Akt signaling pathway in osteosarcoma cells, suggesting that CLDN12 may be a potential agent in the treatment of patients with osteosarcoma.
- |||||||||| quercetin (LY294002) / Eli Lilly, U0126 / Promega
Journal: Tanshinone IIA reverses EGF- and TGF-β1-mediated epithelial-mesenchymal transition in HepG2 cells via the PI3K/Akt/ERK signaling pathway. (Pubmed Central) - Dec 8, 2019
Furthermore, western blot analysis confirmed that blocking the function of PI3K/Akt and ERK with LY294002 and U0126 resulted in upregulation of E-cadherin expression, and downregulation of vimentin and Snail expression in EGF- and TGF-β1-treated HepG2 cells. In conclusion, to the best of our knowledge, the results of the present study are the first to indicate that Tan IIA may suppress EGF- and TGF-β1-induced EMT in HepG2 cells by deactivating the PI3K/Akt/ERK pathway.
- |||||||||| pregabalin / Generic mfg., sirolimus / Generic mfg.
Preclinical, Journal: Electroacupuncture attenuates chronic fibromyalgia pain through the phosphorylated phosphoinositide 3-kinase signaling pathway in the mouse brain. (Pubmed Central) - Dec 8, 2019
Although medications including pregabalin, duloxetine, and milnacipran are used to treat FM, the results are unsatisfying...Phosphorylated phosphatidylinositol 3-kinase (pPI3K), protein kinase B, mechanistic target of rapamycin, and nuclear factor kappa-light-chain-enhancer of activated B cells were unaltered in the mouse dorsal root ganglion (DRG) and spinal cord (SC) after inducing FM and administering EA treatment...These data suggest that EA has a significant effect on a signaling pathway in brain areas of FM mice. These findings suggest the value of EA for clinical practice.
- |||||||||| azacitidine / Generic Mfg.
Journal: Loss of epigenetic regulator TET2 and oncogenic KIT regulate myeloid cell transformation via PI3K pathway. (Pubmed Central) - Dec 6, 2019
Utilizing a mouse model in which the loss of TET2 precedes the expression of oncogenic Kit, similar to the human disease, results in the development of a non-mast cell lineage neoplasm (AHNMD), which is responsive to PI3K inhibition. Thus, therapeutic approaches involving hypomethylating agents, ascorbic acid, and isoform-specific PI3K inhibitors are likely to be useful for treating patients with TET2 and KIT mutations.
- |||||||||| Journal: Crosstalk between PKCα and PI3K/AKT Signaling Is Tumor Suppressive in the Endometrium. (Pubmed Central) - Dec 6, 2019
PKCα tumor suppression involves PP2A-family-dependent inactivation of AKT, which can occur even in the context of genetic hyperactivation of PI3K/AKT signaling by coincident mutations in PTEN, PIK3CA, and/or PIK3R1. Together, our data point to PKCα as a crucial tumor suppressor in the endometrium, with deregulation of a PKCα→PP2A/PP2A-like phosphatase signaling axis contributing to robust AKT activation and enhanced endometrial tumorigenesis.
- |||||||||| pictilisib (GDC-0941) / Roche
Journal: Macrophages confer resistance to PI3K inhibitor GDC-0941 in breast cancer through the activation of NF-κB signaling. (Pubmed Central) - Dec 6, 2019
Consistently, the combination treatment also effectively reduced tumor burden, macrophage infiltration and pulmonary metastasis in in vivo 4T1 breast tumor model. Together, our results suggested macrophages in microenvironment may contribute to the resistance of breast cancer cells to PI3K inhibition and reveal a new combination paradigm to improve the efficacy of PI3K-targeted therapy.
- |||||||||| Journal: TLR Crosstalk Activates LRP1 to Recruit Rab8a and PI3Kγ for Suppression of Inflammatory Responses. (Pubmed Central) - Dec 6, 2019
CRISPR-mediated knockout of LRP1 in macrophages alters Akt/mTOR signaling and produces a pro-inflammatory bias in cytokine outputs, mimicking the Rab8a knockout and PI3Kγ-null phenotype. Thus, TLR-LRP1 crosstalk activates the Rab8a/PI3Kγ complex for reprogramming macrophages, revealing this as a key mechanism through which LRP1 helps to suppress inflammation.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal, MSi-H Biomarker, PD(L)-1 Biomarker, IO Biomarker: Functional loss of ARID1A is tightly associated with high PD-L1 expression in gastric cancer. (Pubmed Central) - Dec 6, 2019
Loss of ARID1A increased PD-L1 via activating AKT signaling, while LY294002 (PI3K inhibitor) decreased PD-L1 levels...Our results strongly indicate that loss of ARID1A is tightly associated with high PD-L1 expression in GC. These results would increase our understanding of the oncogenic mechanism of PD-L1 regulation in GC, and also help to find the optimal candidates for immunotherapy.
- |||||||||| PIK-75 / Pathway Therapeutics, U0126 / Promega, PD98059 / Wayne State University
Journal: Role of PI3K/Akt and MEK/ERK Signalling in cAMP/Epac-Mediated Endothelial Barrier Stabilisation. (Pubmed Central) - Dec 5, 2019
Inhibition of MEK/ERK but not PI3K/Akt signalling enhances barrier stabilising and barrier protective effects of cAMP/Epac activation. 8-pCPT-2'-O-Me-cAMP (PubChem CID: 9913268); Akt inhibitor VIII (PubChem CID: 10196499); AS-252424 (PubChem CID: 11630874); IC-87114 (PubChem CID: 9908783); PD 98059 (PubChem CID: 4713); PIK-75 (PubChem CID: 10275789); TGX-221 (PubChem CID: 9907093); Thrombin (PubChem CID: 90470996); U0126 (PubChem CID: 3006531); Wortmannin (PubChem CID: 312145).
- |||||||||| AZD4547 / AstraZeneca, buparlisib (BKM120) / Novartis, Adlai Nortye, dactolisib (RTB101) / Novartis, PureTech
Preclinical, Journal: In vitro antitumor effects of FGFR and PI3K inhibitors on human papillomavirus positive and negative tonsillar and base of tongue cancer cell lines. (Pubmed Central) - Dec 5, 2019
HPV UM-SCC-47 and UPCI-SCC-154 cells, and HPV UT-SSC-60A cells had no common FGFR3 or PIK3CA mutations, but were sensitive to FGFR inhibitor AZD4547, and PI3K inhibitors BEZ235 and BKM120. Furthermore, the latter two cell lines were particularly sensitive to combinations of AZD4547 and BEZ235.
- |||||||||| Piqray (alpelisib) / Novartis, Faslodex (fulvestrant) / AstraZeneca
Plasma sequencing demonstrates that breast cancer patients have a higher prevalence of clonal and multiple PIK3CA mutations than other solid tumor patients (Hall 1) - Dec 2, 2019 - Abstract #SABCS2019SABCS_2072;
PIK3CA-mutated breast cancer patients were more likely to have clonal PIK3CA mutations and multiple PIK3CA and PI3K pathway mutations compared to patients with other tumor types, which may suggest greater PI3K pathway dependency and sensitivity to treatment with PI3Kα inhibitors. Ongoing whole exome and RNA sequencing of 21 pairs of pre- and post-treatment tissue biopsies of breast cancer patients treated with PI3Kα inhibitors will provide additional genomic and transcriptomic context to these plasma-based results.
- |||||||||| Journal: Pharmacological inactivation of the PI3K p110δ prevents breast tumour progression by targeting cancer cells and macrophages. (Pubmed Central) - Dec 2, 2019
Adoptive transfer of δ macrophages into mice with defected macrophages suppressed tumour growth, eliminated the recruitment of macrophages to tumour sites and prevented metastasis compared with mice that received WT macrophages further establishing that inactivation of p110δ in macrophage prevents tumour progression. Our work provides the first in vivo evidence for a critical role of p110δ in cancer cells and macrophages during solid tumour growth and may pave the way for the use of p110δ inhibitors in breast cancer treatment.
- |||||||||| Journal: Fas-L promotes the stem cell potency of adipose-derived mesenchymal cells. (Pubmed Central) - Dec 2, 2019
Thus, Fas-L signaling in ASCs leads to their expansion and phenotypic shift toward a more potent stem cell state. We speculate that these reactions ensure the survival of ASC progenitor cells encountering Fas-L-enriched environments during tissue damage and inflammation and may also enhance ASC survival following their administration in vivo.
- |||||||||| KU-55933 / AstraZeneca
Journal: Evaluation of ATM Kinase Inhibitor KU-55933 as Potential Anti-Toxoplasma gondii Agent. (Pubmed Central) - Dec 2, 2019
The combination of KU-55933 and other DNA damaging agents such as methyl methane sulfonate (MMS) and CPT produce a synergic effect, suggesting that TgATM kinase inhibition sensitizes the parasite to damaged DNA. By contrast, hydroxyurea (HU) did not further inhibit tachyzoite replication when combined with KU-55933.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Formaldehyde induces the apoptosis of BMCs of BALB/c mice via the PTEN/PI3K/Akt signal transduction pathway. (Pubmed Central) - Nov 29, 2019
Following the application of LY294002 to inhibit the PTEN/PI3K/Akt signal transduction pathway, the numbers of cells arrested in the G0/G1 phase were significantly increased in the PI3K inhibitor group compared with the control (P0.05). The results of the present study suggested that the PTEN/PI3K/Akt signal transduction pathway served an important role in the process of FA‑induced apoptosis, which may be associated with regulating the cell cycle; thus, cell proliferation may be affected.
- |||||||||| Journal, PARP Biomarker: Cellular Effects of Butyrate on Vascular Smooth Muscle Cells are Mediated through Disparate Actions on Dual Targets, Histone Deacetylase (HDAC) Activity and PI3K/Akt Signaling Network. (Pubmed Central) - Nov 29, 2019
Along with previously reported Ser9 phosphorylation-mediated GSK3 inactivation leading to stability, increased expression and accumulation of cyclin D1, and epigenetic histone modifications, inactivation of Akt by butyrate results in: transcriptional activation of FOXO1 and FOXO3 promoting G1 arrest through p21Cip1/Waf1 and p15INK4B upregulation; inactivation of mTOR inhibiting activation of its targets p70S6K and 4E-BP1 impeding protein synthesis; inhibition of caspase 3 cleavage and downregulation of PARP preventing apoptosis. Our findings imply butyrate abrogates Akt activation, causing differential effects on Akt targets promoting convergence of cross-talk between their complimentary actions leading to VSMC growth by arresting proliferation and inhibiting apoptosis through its effect on dual targets, HDAC activity and PI3K/Akt pathway network.
- |||||||||| MK-2206 / Merck (MSD)
Preclinical, Journal: Cardioprotective role of IGF-1 in the hypertrophied myocardium of the spontaneously hypertensive rats: A key effect on NHE-1 activity. (Pubmed Central) - Nov 29, 2019
Our findings imply butyrate abrogates Akt activation, causing differential effects on Akt targets promoting convergence of cross-talk between their complimentary actions leading to VSMC growth by arresting proliferation and inhibiting apoptosis through its effect on dual targets, HDAC activity and PI3K/Akt pathway network. IGF-1 exerts a cardioprotective role on the hypertrophied hearts of the SHR, in which the inhibition of NHE-1 hyperactivity, as well as the positive inotropic and antioxidant effects, emerges as key players.
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