- |||||||||| Preclinical, Journal: Methylene blue offers neuroprotection after intracerebral hemorrhage in rats through the PI3K/Akt/GSK3β signaling pathway. (Pubmed Central) - Mar 18, 2020
In addition, wortmannin, a selective inhibitor of phosphoinositide 3-kinase (PI3K), could reverse the antiapoptotic and anti-inflammatory effects of MB, which suggested that the PI3K-Akt pathway played an important role. In conclusion, these data suggested that MB could inhibit apoptosis and ameliorate neuroinflammation after ICH, and its neuroprotective effects might be exerted via the activation of the PI3K/Akt/GSK3β pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: The role of PI3K-mediated AMPA receptor changes in post-conditioning of propofol in brain protection. (Pubmed Central) - Mar 18, 2020
The short-term neuroprotective effect was contributed by enhanced GluR2 subunits trafficking to membrane and postsynaptic membranes of neurons, as well as down-regulated the expression of pGluR2 in damaged hippocampus. Finally, the above-mentioned protective mechanism might be contributed by increased combination of PI3K to AMPAR GluR2 subunit, thus maintained the expression and activation of AMPAR GluR2 in the ipsilateral hippocampus.
- |||||||||| Journal: A PDGFRβ-PI3K signaling axis mediates periosteal cell activation during fracture healing. (Pubmed Central) - Mar 17, 2020
Our studies showed that depletion of PDGFRβ signaling within these progenitors in the early phase of fracture healing significantly abrogates PI3K-mediated periosteal activation and proliferation three days after fracture. Combined, these results suggest that PDGFRβ signaling through PI3K is necessary for robust periosteal activation in the earliest phases of fracture healing.
- |||||||||| paclitaxel / Generic mfg.
Journal: Triterpenoids from Liquidambar Fructus induced cell apoptosis via a PI3K-AKT related signal pathway in SMMC7721 cancer cells. (Pubmed Central) - Mar 17, 2020
Among the isolates, ursolic acid, 3,6-dion-20(29)-lupen-28-oic acid, and 3-oxo-12α-hydroxyoleanan-28,13β-olide induced a significant apoptosis in SMMC7721 cells in the flow cytometer experiment with apoptosis rates of 94.5%, 57.3% and 89.9% at 8.0 μM, respectively, exhibiting near equivalent apoptosis-inducing abilities to that positive drug taxol (apoptotic rate of 71.2% at 1.4 μM)...Further studies indicated that the pro-apoptotic effects of these three compounds were associated with PI3K-AKT pathway inhibition. Taken together, these studies provide evidence that triterpenoids from L. Fructus are promising candidates for the hepatocellular carcinoma therapy.
- |||||||||| quercetin (LY294002) / Eli Lilly
Co-Cultured BM-MSCs Enhance Phagocytosis and Down-Regulate Autophagy of Macrophages Via PI3K/Akt Signaling Pathway (PENNSYLVANIA CONVENTION CENTER, Hall D-E (200 Level), Area D) - Mar 15, 2020 - Abstract #ATS2020ATS_8597;
We found that the modulations of BM-MSCs on macrophages were through enhancingphagocytosis, reducing apoptosis, down-regulating autophagy, decreasing expressions of inflammatory mediators and promoting M1 polarization,viaPI3K/Akt signalingpathway.Vise versa, pre-conditioned with LY294002, the inhibitor of PI3K, macrophages reversely expressed those biomarks in this co-culture systems, strongly suggesting the crucial role of PI3K/Akt signaling pathway underlying the modulations of BM-MSCs on macrophages. This work also further highlights the importance of BM-MSCs and its beneficial modulations on macrophages under OGD/R circumstance.
- |||||||||| Non-Genomic Effects of Glucocorticoids Differentially Modulate Glucocorticoid Receptor Site-Specific Phosphorylation (PENNSYLVANIA CONVENTION CENTER, Hall D-E (200 Level), Area C) - Mar 15, 2020 - Abstract #ATS2020ATS_6138;
The role of protein synthesis as well as GR was also examined using cycloheximide and RU486, respectively...While SB203580 and LY294002 had little effect on CB-induced pGR-ser226, PD98059 and SP600125 dramatically reduced pGR-ser226...Conclusion Together, our findings show that the non-genomic effects of GC i) differentially affect GR phosphorylation by upregulating pGR-ser226, but not pGR-ser211, in a manner that is GR-independent but ERK/JNK dependent and ii) rapidly activate MAPK pathways. Further studies are still needed to determine the role of GR-independent early events such as nonspecific interactions with the cell membrane in regulating later GC genomic activities.
- |||||||||| Loss of WWOX Triggers PI3K/AKT Signaling in Pulmonary Arterial Smooth Muscle Cells (PENNSYLVANIA CONVENTION CENTER, Hall D-E (200 Level), Area B) - Mar 15, 2020 - Abstract #ATS2020ATS_5817;
On the other hand, PASMC proliferation can be controlled with increased WWOX expression and apoptosis induction. Better understanding of the mechanisms underlying WWOX loss during hypoxia-induced pulmonary vascular remodeling may potentially lead to the identification of new therapeutic strategies in PAH.
- |||||||||| PI3K/AKT Pathway Mediates Enhanced Activation of Eosinophils in Eosinophilic Asthma Phenotype (PENNSYLVANIA CONVENTION CENTER, Room 113 A (100 Level)) - Mar 15, 2020 - Abstract #ATS2020ATS_4552;
Significant upregulation in PI3K p110 gamma, PI3K p110 delta, phospho-PI3K p85 alpha, phospho-AKT(T308), phospho-AKT(S473) expression was observed in EA patients, both in baseline and under PGD2 stimulation.CONCLUSIONSThe results indicated that peripheral eosinophils in EA patients were more activated in baseline and after PGD2 stimulation compared with that in NEA patients and healthy controls. The upregulation of PI3K/AKT pathway might be related to the increased activation of eosinophils in EA patients, leading to the “susceptibility” to eosinophilic phenotype in certain group of patients.
- |||||||||| Decadron (dexamethasone) / Merck (MSD)
Corticosteroids Phosphorylate Glucocorticoid Receptor at the Newly Described Residue Serine 134 in Airway Smooth Muscle Cells (PENNSYLVANIA CONVENTION CENTER, Room 126 A-B (100 Level)) - Mar 15, 2020 - Abstract #ATS2020ATS_3500;
Conclusion Collectively, we demonstrated for the first time in primary cells that GC phosphorylates GR at ser134 residue by involving non-genomic mechanisms that are mGR/JNK-dependent. Further studies are still needed to determine the role of pGRser134 in i) mediating non-genomic effects of GC and in regulating later GC genomic activities and ii) GR signaling and GC actions in cells derived from healthy and asthmatic patients.
- |||||||||| Cytovene (ganciclovir) / Roche
Review, Journal: HCMV modulation of cellular PI3K/AKT/mTOR signaling: New opportunities for therapeutic intervention? (Pubmed Central) - Mar 15, 2020
Current approved therapies, including ganciclovir, are only moderately efficacious, with many transplant patients suffering from a variety of side effects...In this review, we will examine the role that the PI3K/Akt/mTOR signaling axis plays during the different stages of HCMV's lifecycle, and describe the advantages of targeting this cellular pathway as an antiviral strategy. In particular, we focus on the potential of exploiting the unique modifications HCMV imparts on the PI3K/Akt/mTOR pathway during quiescent infection of monocytes, which serve an essential role in the viral dissemination strategy of the virus.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal, IO Biomarker: Chlamydia muridarum infection induces CD4+ T cells apoptosis via PI3K/AKT signal pathway. (Pubmed Central) - Mar 13, 2020
The present study demonstrated that phosphatidylinositol 3-kinase (PI3K) p110δ mRNA and phosphorylation of protein kinase B (p-AKT) level were significantly increased in lung cells and spleen cells at day 3 and day 7 post-infection, p-AKT level was inhibited when adding PI3K inhibitor LY294002...The related apoptosis proteins Bcl-2 and Mcl-1 uneven expression levels were induced in CD4+ T cells by Cm infection. These findings provided in vivo and in vitro evidence that Cm infection induces CD4+ T cells apoptosis possibly via PI3K/AKT signal pathway.
- |||||||||| dactolisib (RTB101) / Adicet Bio
Journal: Single-Dose Neoadjuvant AKT Pathway Inhibitor Reduces Growth of Hepatocellular Carcinoma after Laser Thermal Ablation in Small-Animal Model. (Pubmed Central) - Mar 13, 2020
Prior studies suggest that phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)-dependent protein kinase B (AKT) signaling mediates HCC cell survival caused by moderate heat stress in vitro, but these findings need in vivo validation.PurposeTo test the hypothesis that neoadjuvant inhibition of PI3K/mTOR/AKT signaling reduces HCC tumor growth in vivo after laser ablation and to evaluate the effects of moderate heat stress on molecular signaling and cellular function in HCC cells in vitro.Materials and MethodsHCC tumor-bearing mice were randomized to neoadjuvant PI3K/mTOR inhibitor (BEZ235) or control groups followed by an intentional partial laser ablation or sham ablation; there were at least nine mice per group...PI3K/mTOR inhibition prevented moderate heat stress-induced global effects on HCC molecular signaling and cellular function, including decreased cell survival, growth, and proliferation (Z-score, -0.3 to -3.2; P < .001) and increased apoptosis and cell death (Z-score, 0.4-1.1; P < .001).ConclusionModerate heat stress induces PI3K/mTOR/AKT-dependent global effects on hepatocellular carcinoma (HCC) cell survival, function, and death. Neoadjuvant PI3K/mTOR/AKT inhibition reduces postablation HCC tumor growth
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Shenfu Injection Promotes Vasodilation by Enhancing eNOS Activity Through the PI3K/Akt Signaling Pathway In Vitro. (Pubmed Central) - Mar 13, 2020
Furthermore, it promoted the expression of total eNOS and the phosphorylation of eNOS at serine (Ser) 1177 but inhibited the phosphorylation at threonine (Thr) 495, which was significantly reversed by PI3K-specific inhibitor LY294002. In conclusion, our study showed the vasodilation effect of SFI in thoracic aorta is mediated entirely by enhancing eNOS activity through the PI3K/Akt signaling pathway, providing novel knowledge on the effect of SFI on shock and HF for future clinical applications.
- |||||||||| Journal: Cellular Senescence as a Mechanism and Target in Chronic Lung Diseases. (Pubmed Central) - Mar 10, 2020
These miRNAs may be released from cells in extracellular vesicles that are taken up by other cells, thereby spreading senescence locally within the lung but outside the lung through the circulation; this may account for comorbidities of COPD and other lung diseases. Understanding the mechanisms of cellular senescence may result in new treatments for chronic lung disease, either by inhibiting PI3K-mTOR signaling, by inhibiting specific miRNAs or by deletion of senescent cells with senolytic therapies, already shown to be effective in experimental lung fibrosis.
- |||||||||| quercetin (LY294002) / Eli Lilly, gefitinib / Generic mfg., PD98059 / Wayne State University
Journal: EGF receptor stimulation shifts breast cancer cell glucose metabolism toward glycolytic flux through PI3 kinase signaling. (Pubmed Central) - Mar 10, 2020
Blocking EGFR activation with BIBX1382 or gefitinib completely abolished both FDG uptake and proliferation effects...Increased cell proliferation by EGFR stimulation was completely abolished by MAPK inhibition with PD98059 or by PI3K inhibition with LY294002...These findings suggest that the association between breast tumor EGFR expression and high FDG uptake might be contributed by stimulation of the PI3K pathway downstream of EGFR activation. This was in contrast to EGFR-mediated cell proliferation that required MAPK as well as PI3K signaling.
- |||||||||| Class in Session: Today’s Concepts on Targeted and CAR T-Cell Therapies Across B-Cell Malignancies (14-15) - Mar 9, 2020 - Abstract #HOPA2020HOPA_131;
Registration website: https://www.clinicaloptions.com/BCellTampa2020 Learning Objectives: Consider efficacy and safety profile of the novel classes of therapies (including BTK and PI3K inhibitors, antibodies, BCL-2 inhibitors, CAR T-cell, investigational agents, and immunotherapeutic strategies currently under evaluation) with patient characteristics and molecular features to individualize therapeutic strategies for patients with mature B-cell lymphomas Consider mechanisms of action and efficacy and safety profile differences among different agents in the same class of therapy to select treatments most likely to improve outcomes Assess challenging questions regarding the use of novel therapies in mature B-cell lymphomas and discuss the ways that pharmacists can optimize therapy, anticipate adverse effects, and optimize clinical outcomes alongside other members of the oncology healthcare team Manage unique adverse events associated with novel agent classes in the management of mature B-cell lymphomas to optimize care and quality of life Identify patients suitable for enrollment on ongoing clinical studies investigating novel therapies in mature B-cell lymphomas. Sponsored By: Abbvie, Inc., Janssen Biotech, Inc
- |||||||||| PI3K cooperates with MAPK to regulate mTOR signaling during lacrimal gland development (Exhibit Hall: Posterboard# A0448) - Mar 9, 2020 - Abstract #ARVO2020ARVO_3191;
As a result, inactivation of the mTOR complex 1 reproduced the loss of lacrimal gland phenotype in the PI3K and MAPK deletion mutants.Conclusions During the lacrimal gland development, 1) PI3K cross-activates the MAPK signaling, 2) mTOR signaling is controlled by both PI3K and MAPK pathways.Signalling pathways such as PI3K, MAPK, and mTOR control organ growth. Our study demonstrated the cooperation in the signalling network during tear gland development, which may contribute to the regenerative medicine for the dry eye disease.
- |||||||||| Distinct PI3K Pathways Regulate Elimination of Organelles and Nuclei during Lens Development (Room 307) - Mar 9, 2020 - Abstract #ARVO2020ARVO_2860;
We find that the premature elimination of nuclei following exposure to the pan-PI3K inhibitor replicates this same process.Conclusions Autophagy-dependent elimination of lens organelles to form the OFZ is induced by suppression of the PI3K/Akt signaling axis, while nuclear condensation, an essential intermediate in nuclear removal, is induced when Rac, also a downstream effector of PI3K, is inhibited. Although inhibition of either PI3K effector pathway is not alone sufficient for nuclear elimination, blocking all PI3K signaling results in premature loss of both nuclei and organelles, suggesting that nuclear loss involves suppression of multiple PI3K-dependent signaling pathways.
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