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  • ||||||||||  Imbruvica (ibrutinib) / AbbVie, J&J
    Combined inhibition of BTK and PI3K induces synergistic effects in canine B-cell lymphoma in vitro model (A6) -  Sep 30, 2019 - Abstract #DGHO2019DGHO_711;    
    The observed pronounced synergistic in vitro effect of Ibrutinib and AS605240 indicates that the combination represents a promising approach for further in vivo evaluation. As canine lymphoma represents a highly comparative model for the human counterpart, an experimental trail in dogs could bear significant value for both species.
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie, Aliqopa (copanlisib) / Bayer
    Synergy of PI3Kα / δ and BCL-2 inhibitors in genetically defined DLBCL subtypes (M4 / M5) -  Sep 30, 2019 - Abstract #DGHO2019DGHO_220;    
    As canine lymphoma represents a highly comparative model for the human counterpart, an experimental trail in dogs could bear significant value for both species. Taken together, these results provide pre-clinical evidence for the rational combination of PI3Kα/δ and BCL2 blockade and set the stage for clinical evaluation of copanlisib/venetoclax therapy in patients with genetically defined relapsed/refractory DLBCL.
  • ||||||||||  Tamoxis (tamoxifen) / Bioprofarma
    Journal:  SMAD4 Prevents Flow Induced Arterial-Venous Malformations by Inhibiting Casein Kinase 2. (Pubmed Central) -  Sep 30, 2019   
    No abstract available The authors generated tamoxifen-inducible, postnatal, endothelial-specific Smad4 mutant mice ( Smad4)...Conclusions-Our study reveals SMAD4 as an essential effector of BMP9-10/ALK1 signaling that affects AVM pathogenesis via regulation of CK2 expression and PI3K/AKT1 activation.
  • ||||||||||  Zelboraf (vemurafenib) / Roche
    Journal:  "Stroma-induced phenotypic plasticity offers phenotype-specific targeting to improve melanoma treatment". (Pubmed Central) -  Sep 28, 2019   
    We have disclosed an association between fibroblast-stimulated phenotype switching and resistance to the clinically used BRAF inhibitor (BRAFi) vemurafenib in malignant melanoma, revealing a challenge in targeting the fibroblast-induced phenotype...This suggests that the single drug drives the response to the combination treatment, depending on fibroblast presence or absence, consequently, phenotype. We propose that the BRAFi and GSK3i (or PI3Ki) combination exemplifies phenotype-specific combinatorial treatment that should be beneficial in phenotypically heterogeneous tumors rich in stromal interactions.
  • ||||||||||  perifosine (D21266) / AEterna Zentaris
    Journal:  GLI1 promotes cancer stemness through intracellular signaling pathway PI3K/Akt/NFκB in colorectal adenocarcinoma. (Pubmed Central) -  Sep 28, 2019   
    Importantly, Akt inhibitor Perifosine significantly inhibited the expression of pAkt and GLI1 in colorectal adenocarcinoma cells...We suggested that GLI1 may be a novel stem cell marker, and cancer stemness was activated via PI3K/Akt/NFκB pathway. In addition, co-targeting GLI1 and PI3K/Akt/NFκB signaling simultaneously might provide an alternative therapeutic strategy for colorectal adenocarcinoma patients.
  • ||||||||||  MK-2206 / Merck (MSD), quercetin (LY294002) / Eli Lilly
    Journal:  Hexabromocyclododecanes promoted autophagy through the PI3K/Akt/mTOR pathway in L02 cells. (Pubmed Central) -  Sep 27, 2019   
    These results indicated that PI3K/Akt/mTOR pathway was participated in regulating autophagy process promoted by HBCDs. In above, HBCDs could induce mitochondrial-dependent apoptosis and autophagy in L02 cells, which was modulated by PI3K/Akt/mTOR pathway.
  • ||||||||||  Journal:  Effect and mechanism of adipocyte co-culture on aquaporin-9 expression in HepG2 cells (Pubmed Central) -  Sep 27, 2019   
    WB results showed the expression levels of p-Akt protein (0.168 ± 0.006) and p-Akt/total Akt (0.265±0.009) in HepG2-AQP9 co-culture + IGF-1 group was significantly increased (t= 16.311, 8.769,P< 0.001) than HepG2-AQP9 co-culture group, while the expression levels of AQP9 mRNA (0.327 ± 0.034) and protein (0.375 ± 0.025) was significantly decreased (t= 33.573, 9.146,P< 0.001 and 0.001). Adipocytes co-culture can induce steatosis in HepG2 cells, and may participate in inhibiting PI3K-Akt signaling pathway to upregulate the expression of AQP9 in steatotic HepG2 cells.
  • ||||||||||  Journal:  Mechanical and Mechanosensing Properties of Tumor Affected Bone Cells Were Inhibited via PI3K/Akt Pathway. (Pubmed Central) -  Sep 27, 2019   
    It implied that a change in cell mechanical properties is not sufficient as an indicator of change in mechanosensing ability. Moreover, inhibition of phosphoinositide 3-kinase/Akt downstream signaling pathway of TGF-β1 alleviated the inhibition effects on mechanosensing in T-conditioned cells, further suggesting that growth factors such as TGF-β could be good therapeutic targets for osteoblast treatment.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Journal:  Blocking PI3K/AKT signaling inhibits bone sclerosis in subchondral bone and attenuates post-traumatic osteoarthritis. (Pubmed Central) -  Sep 26, 2019   
    We revealed a significant increase in PI3K/AKT signaling activation which was associated with aberrant bone formation in tibial subchondral bone following destabilizing the medial meniscus (DMM), which was effectively prevented by treatment with PI3K/AKT signaling inhibitor LY294002...Furthermore, PI3K/AKT signaling was found to enhance preosteoblast proliferation, differentiation, and expression of MMP-13 by activating NF-?B pathway. In conclusion, inhibition of PI3K/AKT/NF-?B axis was able to prevent aberrant bone formation and attenuate cartilage degeneration in OA mice.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Journal:  Dehydroepiandrosterone rehabilitate BRL-3A cells oxidative stress damage induced by hydrogen peroxide. (Pubmed Central) -  Sep 26, 2019   
    However, the rise in PI3K and p-Akt protein levels, and the decrease in Bax and capase-3 protein levels induced by DHEA treatment were reversed when the cells pretreated with LY294002 (PI3K inhibitor)...In addition, DHEA decreased the apoptosis by inhibiting caspase-3 and Bax protein levels and this action mainly achieved via the activation of PI3K/Akt signaling pathways in HO-induced BRL-3A cells. These results provided substantial information for DHEA as a nutritional supplement to treat oxidative stress and it related diseases in animals and humans.
  • ||||||||||  Primary Immunodeficiency-Associated Lymphoproliferative Disorders in Adults (Indolent B-Cell Lymphoma) -  Sep 26, 2019 - Abstract #SOHO2019SOHO_546;    
    May have similar clinical characteristics and are generally related to lymphoproliferation in patients with a history of growth disorders, respiratory tract infections, cytopenias and pulmonary problems. Treatment may consist of glucocorticoids, chemotherapy, immunotherapy or a specific treatment such as inhibitors of PI3K delta according to the disorder.
  • ||||||||||  Zydelig (idelalisib) / Gilead, Xpovio (selinexor) / Ono Pharma, Karyopharm, Antengene
    Selinexor in Combination with Chemotherapy or Idelalisib Elicits a Synergistic Cytotoxic Effect in Primary CLL Cells (Chronic Lymphocytic Leukemia) -  Sep 26, 2019 - Abstract #SOHO2019SOHO_480;    
    Selinexor was also capable to overcome the SC-mediated protection against drug-induced cell death. From the molecular standpoint, preliminary data showed that selinexor significantly potentiated the inhibitory effect exerted by single-agent idelalisib on NF-kB and Akt activity.Conclusions The combination of selinexor with chemotherapy or idelalisib has synergistic cytotoxic effects, also counteracting intrinsic or SC-mediated drug resistance.
  • ||||||||||  Copiktra (duvelisib) / Verastem
    Effect of Dose Modifications on Response to Duvelisib in Patients with Relapsed/Refractory (R/R) CLL/SLL in the DUO Trial (Chronic Lymphocytic Leukemia) -  Sep 26, 2019 - Abstract #SOHO2019SOHO_471;    
    Proportions of patients experiencing AESIs were stable or decreased over time after 3-6 months: 0-3 months, 64%; >3-6 months, 63%; >6-9 months, 47%; >9-12 months, 52%, and seldom led to discontinuation of duvelisib (≤10%).Conclusions DIs/DRs can contribute to the effective management of TEAEs with duvelisib. These findings suggest that DIs of >1 week do not negatively impact response to duvelisib or PFS.
  • ||||||||||  azacitidine / Generic Mfg.
    Novel Strategies in High-Risk AML () -  Sep 26, 2019 - Abstract #SOHO2019SOHO_274;    
    P1/2, P1b/
    In an initial study, Vyxeos (liposomal cytarabine and daunorubicin) improved overall survival compared with standard chemotherapy, especially among patients who underwent stem cell transplantation.34 In MDS and secondary AML, spliceosome mutations are nearly invariably heterozygous and mutually exclusive of one another, suggesting reliance on the residual wild type allele and non-affected pathways and providing an opportunity for synthetic lethality strategies.35,36 On-going efforts are developing targeted spliceosome inhibitors that may provide further activity in secondary AML and in MDS.37MRD following induction chemotherapy has been associated with adverse outcomes across diverse studies and cytotoxic regimens.6-9 To date, no therapy has been shown to convert MRD positive patients to MRD negative, although stem cell transplantation in first remission may abrogate the survival disadvantage of MRD positivity.9 There remain many important questions about MRD that have just begun to be addressed...Specifically, it reacts with TP53 Cys 124 and Cys277, and this facilitates refolding and reactivation of TP53 R174H and R273H mutants.41 Results from a small study of APR-246 in combination with azacitidine have been presented in abstract form.42 This combination led to complete responses in 4/5 patients with AML or MDS, and responses were associated with normalization of TP53 immunohistochemistry staining.COTI-2 is a thiosemicarbazone-related compound that reactivates mutant TP53 protein, inhibits PI3K/AKT signaling, synergizes with other chemotherapeutics, and inhibits a broad range of cancer cell lines with preferential inhibition of TP53 mutated lines.43,44 Abstract presentation suggests that COTI-2 is tolerable although nausea and vomiting are common, and it demonstrated evidence of stable disease in recurrent gynecological cancers.45A range of additional targeting agents have been developed, but have yet to reach clinical trials...Further work is required to understand how to measure and treat MRD. Future therapies are being developed that target the spliceosome and mutant TP53, and these may be important future strategies in secondary AML and TP53 mutated AML.Acknowledgments JSW is supported by U01 SPORE 2P50CA17963, R01 CA235622, R01 HL128447, and by the Evans Foundation.
  • ||||||||||  Journal:  Airway Microbiota Is Associated with Up-Regulation of the PI3K Pathway in Lung Cancer. (Pubmed Central) -  Sep 26, 2019   
    Future therapies are being developed that target the spliceosome and mutant TP53, and these may be important future strategies in secondary AML and TP53 mutated AML.Acknowledgments JSW is supported by U01 SPORE 2P50CA17963, R01 CA235622, R01 HL128447, and by the Evans Foundation. The data presented here shows that several transcriptomic signatures previously identified as relevant to lung cancer pathogenesis are associated with enrichment of the lower airway microbiota with oral commensals.
  • ||||||||||  Journal, IO Biomarker:  Maltol Improves APAP-Induced Hepatotoxicity by Inhibiting Oxidative Stress and Inflammation Response via NF-κB and PI3K/Akt Signal Pathways. (Pubmed Central) -  Sep 25, 2019   
    Immunoblotting results showed that maltol pretreatment downregulated the protein expression levels of the B-cell-lymphoma-2 (Bcl-2) family and caspase and altered the phosphorylation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) in a dose-dependent manner. In conclusion, our findings clearly demonstrate that maltol exerts a significant liver protection effect, which may partly be ascribed to its anti-inflammatory and anti-apoptotic action via regulation of the PI3K/Akt signaling pathway.