- |||||||||| Herceptin (trastuzumab) / Roche
Inhibition of the PI3K pathway in HER2-positive gastric cancer (Poster Area (Hall 4)) - Sep 11, 2019 - Abstract #ESMO2019ESMO_2452; Combinations of copanlisib and Tr offer greater benefit than either drug alone, and may restore sensitivity to Tr in cells with intrinsic resistance to Tr. The addition of copanlisib to HER2 targeted therapy warrants further investigation in HER2-positive GC.
- |||||||||| Review, Journal, PD(L)-1 Biomarker, IO Biomarker: PTEN Alterations as a Potential Mechanism for Tumor Cell Escape from PD-1/PD-L1 Inhibition. (Pubmed Central) - Sep 11, 2019
This review describes the role of PTEN loss as a mechanism responsible for resistance to anti PD-1/PD-L1 treatment. Moreover, combinatorial strategies between PD-1/PD-L1 inhibitors and PI3K/AKT targeting drugs are proposed as a new strategy to overcome resistance to immune checkpoint inhibition.
- |||||||||| ibrutinib / Generic mfg.
Journal: Auranofin Enhances Ibrutinib's Anticancer Activity in EGFR-Mutant Lung Adenocarcinoma. (Pubmed Central) - Sep 11, 2019 In mice, the combination of ibrutinib and auranofin significantly suppressed the growth of H1975 xenografted tumors without inducing obvious toxic effects. Our results demonstrate the feasibility of improving ibrutinib's anti-EGFR activity for NSCLC using combination therapy with auranofin.
- |||||||||| Review, Journal: The PI3K/AKT pathway in obesity and type 2 diabetes. (Pubmed Central) - Sep 11, 2019
We also summarize evidences for recently identified therapeutic targets of the PI3K/AKT pathway as treatments for obesity and type 2 diabetes mellitus. PI3K/AKT pathway damaged in various tissues of the body leads to obesity and type 2 diabetes as the result of insulin resistance, and in turn, insulin resistance exacerbates the PI3K/AKT pathway, forming a vicious circle.
- |||||||||| TriptoSar (triptolide) / Pierre Fabre
Journal: Triptolide Attenuates Renal Tubular Epithelial-mesenchymal Transition Via the MiR-188-5p-mediated PI3K/AKT Pathway in Diabetic Kidney Disease. (Pubmed Central) - Sep 11, 2019 Additionally, downregulation of miR-188-5p, which imitates the effects of triptolide, attenuated the activation of the PI3K/AKT pathway and HG-induced EMT, whereas miR-188-5p overexpression reversed the effects of triptolide on the PI3K/AKT pathway and EMT. In conclusion, we demonstrated that triptolide ameliorates renal EMT via the PI3K/AKT signaling pathway through the interaction between miR-188-5p and PTEN, indicating that miR-188-5p may be a therapeutic target of triptolide in DKD.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: The Effects of Autophagy and PI3K/AKT/m-TOR Signaling Pathway on the Cell-Cycle Arrest of Rats Primary Sertoli Cells Induced by Zearalenone. (Pubmed Central) - Sep 11, 2019 ...In order to explore the potential mechanism of ZEA male reproductive toxicity, we studied the effects of ZEA on cell proliferation, cell-cycle distribution, cell-cycle-related proteins and autophagy-related pathway the PI3K/Akt/mTOR signaling in primary cultured rats SCs, and the effects of autophagy and PI3K/AKT/m TOR signaling pathway on the SCs cell-cycle arrest induced by ZEA treated with the autophagy promoter RAPA, autophagy inhibitor CQ, and the PI3K inhibitor LY294002, respectively...Taken together, this study provides evidence that autophagy and PI3K/Akt/m TOR signaling pathway are involved in regulating rats primary SCs cell-cycle arrest due to ZEA in vitro. To some extent, ZEA-induced autophagy plays a protective role in this process.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Nitric oxide prevents HO-induced apoptosis in SK-N-MC human neuroblastoma cells. (Pubmed Central) - Sep 11, 2019 SNAP induced phosphorylation of Akt and Bad and then increased the interactions between 14-3-3β and p-Bad. These data suggest that the NO suppresses HO-induced SK-N-MC cell apoptosis by suppressing apoptosis signal mediating the interaction between 14-3-3β and Bad phosphorylation via PKG/PI3K/Akt.
- |||||||||| quercetin (LY294002) / Eli Lilly, PD98059 / Wayne State University
Journal: Hepatoprotective effects of limb ischemic post-conditioning in hepatic ischemic rat model and liver cancer patients via PI3K/ERK pathways. (Pubmed Central) - Sep 11, 2019 Moreover, through 16 cases of hepatocellular carcinoma resections, we found that short-term LIPOC treatment significantly suppressed the elevated alanine aminotransferase, aspartic transaminase, and total bilirubin in the early post-operation of liver resection, and reduced reperfusion injury to the ischemic liver. In summary, our study demonstrates that LIPOC could be an effective method for HIRI in the clinical implementation of liver resection and uncovers the potential mechanism of LIPOC in the protective effects of HIRI.
- |||||||||| chloroquine phosphate / Generic Mfg., quercetin (LY294002) / Eli Lilly
Journal: VDR agonists down regulate PI3K/Akt/mTOR axis and trigger autophagy in Kaposi's sarcoma cells. (Pubmed Central) - Sep 10, 2019 Since increment in autophagosomes not always indicates increment in autophagy activity, we used Chloroquine (CQ, 1 μM), an inhibitor of autophagy flow, to confirm autophagy after both VDR agonists treatment. In conclusion, VDR agonists, 1α,25(OH)D or TX 527, inhibited PI3K/Akt/mTOR axis and induced autophagy in endothelial cells expressing vGPCR by a VDR-dependent mechanism.
- |||||||||| quercetin (LY294002) / Eli Lilly, Sprycel (dasatinib) / BMS, Otsuka, Inhibikase
Journal: TWEAK promotes hepatic stellate cell migration through activating EGFR/Src and PI3K/AKT pathways. (Pubmed Central) - Sep 10, 2019 Inhibition of PI3K/AKT reduced the expression of MMP9 induced by TWEAK. The present study, for the first time, demonstrated that TWEAK promoted HSCs migration through the activation of EGFR/Src and PI3K/AKT pathways, which showed a novel potential mechanism of HSCs migration regulated by TWEAK.
- |||||||||| sirolimus / Generic mfg.
MODULATION OF CA125 EXPRESSION BY HTERT IN OVARIAN CANCER : POSSIBLE IMPLICATION OF PI3K/AKT/MTOR SIGNALING PATHWAY (E-Poster Area (Americas)) - Sep 10, 2019 - Abstract #IGCS2019IGCS_437; Objectives: To investigate the possible inter-relationship between Ca125 secretion and telomerase activity, and the possible implication of the PI3K/Akt/mTOR pathway in this modulation ovarian cancer cell lines OVCAR-3, SK-OV-3 and IGROV-1 were treated with three different telomerase inhibitors, BIBR-1532, Costunolide and MST-312, one activator, LPS, and various inhibitors of the PI3K/Akt/mTOR pathway, PI828, wortmanin, GSK692690 and rapamycin... Both inhibition of telomerase and PI3K/Akt/mTOR signaling pathway decreased the Ca125 secretion, while inhibition of Ca125 decreased hTERT expression and activity suggesting a mutual modulation and a substantial role of Ca125 in cancer initiation and progression
- |||||||||| Biomarker, Journal: Placental Basement Membrane Proteins are Required for Effective Cytotrophoblast Invasion in a 3D Bioprinted Placenta Model. (Pubmed Central) - Sep 8, 2019
Our results described, for the first time, the substantial effects of the ECM microenvironment on regulating cytotrophoblast invasion, an area that is less investigated but appear to be critical in the pathogenesis of preeclampsia. Moreover, the approach presented in this work that fabricates organ models with organ-specific ECM can be an attractive option to screen and develop novel therapeutics and biomarkers not only in preeclampsia but also other diseases such as cancer metastasis.
- |||||||||| Journal: Dopamine regulates cytokine secretion during innate and adaptive immune responses. (Pubmed Central) - Sep 8, 2019
Administration of DA and LPS to mice immunized with chicken ovalbumin (OVA) increased secretion of IL-5 by mouse lung lymphocytes, suggesting that DA promotes OVA-specific Th2-mediated immune responses by these cells. Taken together, these findings indicate that DA regulates cytokine secretion during innate and adaptive immune responses.
- |||||||||| Zydelig (idelalisib) / Gilead
Journal: PI3Kδ inhibition modulates regulatory and effector T-cell differentiation and function in chronic lymphocytic leukemia. (Pubmed Central) - Sep 8, 2019 Nonetheless, this PI3Kδ-mediated decrease in Tregs did not translate into better CD8 T-cell function, as PI3Kδ inhibition concomitantly abrogated T-cell receptor signaling in CD8 T-cells leading to decreased activation, effector cell differentiation and proliferation. Collectively, these data highlight the strong immunomodulatory effects of PI3Kδ inhibitors in CLL and are of relevance for a rational design of idelalisib-based combination therapies in CLL.
- |||||||||| Journal: Identification of CDC25 as a Common Therapeutic Target for Triple-Negative Breast Cancer. (Pubmed Central) - Sep 7, 2019
In accordance with increased PI3K signaling following long-term CDC25 inhibition, CDC25 and PI3K inhibitors effectively synergized to suppress TNBC growth both in vitro and in xenotransplantation models. These results provide a rationale for the development of CDC25-based therapies for diverse RB1/PTEN/TP53-deficient and -proficient TNBCs.
- |||||||||| pictilisib (GDC-0941) / Roche
Journal: KDM6B counteracts EZH2-mediated suppression of IGFBP5 to confer resistance to PI3K/AKT inhibitor treatment in breast cancer. (Pubmed Central) - Sep 7, 2019 ...Moreover, the IGFBP5 expression is upregulated upon acquired resistance to the PI3K inhibitor GDC-0941, which is associated with an epigenetic switch from H3K27me3 to H3K27Ac at the IGFBP5 gene promoter...Intriguingly, GDC-0941-resistant breast cancer cells remained sensitive to KDM6B or IGFBP5 inhibition, indicating the dependency on KDM6B-IGFBP5 axis to confer the survival advantage in GDC-0941-resistant cells. Our study reveals an epigenetic mechanism associated with resistance to targeted therapy and demonstrates that therapeutic targeting of KDM6B-mediated IGFBP5 expression may provide a useful approach to mitigate both intrinsic and acquired resistance to the PI3K inhibitor in breast cancer.
- |||||||||| buparlisib (BKM120) / Novartis, Adlai Nortye
Journal: Role of EphB3 receptor in mediating head and neck tumor growth, cell migration, and response to PI3K inhibitor. (Pubmed Central) - Sep 7, 2019 ...However, responsiveness of EphB3 knockdown tumors to the PI3K inhibitor, BKM120, was significantly decreased in terms of both tumor growth delay and survival...These data collectively indicate that progression of HNSCC selects for low/inhibited EphB3 activity to enhance their survival and migratory abilities and decrease response to PI3K signaling. Therefore, strategies focused on activating EphB3 might be helpful to inhibit tumor growth and enhance sensitivity to PI3K inhibitors in HNSCC.
- |||||||||| sirolimus / generics
Journal: BCAP links IL-1R to the PI3K-mTOR pathway and regulates pathogenic Th17 cell differentiation. (Pubmed Central) - Sep 7, 2019 More importantly, we found that BCAP is critical for IL-1R-induced phosphoinositide 3-kinase-Akt-mechanistic target of rapamycin (mTOR) activation, and minimal inhibition of mTOR completely abrogated IL-1β-induced differentiation of pathogenic Th17 cells, mimicking BCAP deficiency. This study establishes BCAP as a critical link between IL-1R and the metabolic status of activated T cells that ultimately regulates the differentiation of inflammatory Th17 cells.
- |||||||||| Journal, PD(L)-1 Biomarker, IO Biomarker: EBV-associated gastric cancer evades T-cell immunity by PD-1/PD-L1 interactions. (Pubmed Central) - Sep 6, 2019
Consequently, this miRNA has the potential to be a therapeutic target for conditions of bone loss. EBVaGC cells expressing high levels of PD-L1 suppress T-cell proliferation, and the IFN-γ signaling pathway is involved in the expression of PD-L1.
- |||||||||| Journal: PIK3IP1/TrIP restricts activation of T cells through inhibition of PI3K/Akt. (Pubmed Central) - Sep 6, 2019
Using an inducible knockout mouse model, we show that TrIP-deficient T cells exhibit more robust activation and can mediate clearance of Listeria monocytogenes infection faster than WT mice. Thus, TrIP is a negative regulator of T cell activation and may represent a novel target for immune modulation.
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