PI3K inhib 
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  • ||||||||||  Journal:  ADAM10 promotes the proliferation of ligamentum flavum cells by activating the PI3K/AKT pathway. (Pubmed Central) -  Jul 14, 2021   
    On the whole, the in vitro experimental results suggested that ADAM10 promoted the proliferation of ligamentum flavum cells by activating the PI3K/AKT pathway, which may represent a pathogenic mechanism of LFH. The findings of the present study may provide a basis and direction for further studies on the cellular mechanisms of LFH and present a potential novel therapeutic target and clinical approach.
  • ||||||||||  mesenchymal stem cell / Peking Union Medical College, Zhejiang University, Chinese Academy of Medical Sciences
    Journal:  Low-dose IL-34 has no effect on osteoclastogenesis but promotes osteogenesis of hBMSCs partly via activation of the PI3K/AKT and ERK signaling pathways. (Pubmed Central) -  Jul 14, 2021   
    Using real-world data, this is the first analysis comparing alpelisib combined with fulvestrant with standard treatments for HR+, HER2-, PIK3CA-mutant ABC in the post-CDK4/6i setting. Collectively, our study demonstrate that low-dose IL-34 regulates osteogenesis of hBMSCs partly via the PIK/AKT and ERK signaling pathway and enhances fracture healing, with neither promoting nor preventing osteoclastogenesis in vitro and osteoporosis in vivo.
  • ||||||||||  Kadcyla (ado-trastuzumab emtansine) / Roche, apitolisib (GDC-0980) / Roche
    Clinical, Journal, PARP Biomarker, PD(L)-1 Biomarker, IO biomarker:  A tipping-point for apoptosis following dual inhibition of HER2 signaling network by T-DM1 plus GDC-0980 maximizes anti-tumor efficacy. (Pubmed Central) -  Jul 13, 2021   
    In the following MARIANNE trial also, a combination of T-DM1 plus pertuzumab delivered a non-inferior but yet not superior PFS compared to trastuzumab plus a taxane...Interestingly, both trastuzumab and T-DM1 induce PD-L1 expression in HER2 amplified BC cells. Our data provide evidence that an oncogenic mutation of PIK3CA and HER2-amplification may represent biomarkers to identify patients who may benefit most from the use of GDC-0980 and an opportunity to include immunotherapy in the combination of anti-HER2 therapy.
  • ||||||||||  Piqray (alpelisib) / Novartis, alisertib (MLN8237) / Takeda
    Journal:  Alpelisib and radiotherapy treatment enhances Alisertib-mediated cervical cancer tumor killing. (Pubmed Central) -  Jul 13, 2021   
    Using MLN8237 (Alisertib), an oral, selective inhibitor of AURKs, we investigated whether Alisertib treatment can improve tumor response when combined with either radiotherapy (RT) treatment or with a PI3K inhibitor, BYL719 (Alpelisib). Indeed, both RT and Alpelisib significantly improved Alisertib-mediated tumor killing, and the promising achieved results warrant further development of these combinations, and potentially translating them to the clinics.
  • ||||||||||  Journal:  TIPE2 Suppresses Malignancy of Pancreatic Cancer Through Inhibiting TGFβ1 Mediated Signaling Pathway. (Pubmed Central) -  Jul 13, 2021   
    Moreover, the tumor-infiltrating lymphocytes from tumor-bearing mice were analyzed by flow cytometry, and showed that TIPE2 could promote T cell activation to exert an anti-tumor effect possibly through activation of DCs in a TGFβ1 dependent manner. In general, we described the multiple regulatory mechanisms of TIPE2 in pancreatic tumorigenesis and tumor microenvironment, which suggested TIPE2 may act as a potential therapeutic target in pancreatic cancer.
  • ||||||||||  Journal:  The Potential of PI3K/AKT/mTOR Signaling as a Druggable Target for Endometrial and Ovarian Carcinomas. (Pubmed Central) -  Jul 11, 2021   
    Although the rational of inhibiting the PAM-pathway has been demonstrated in several promising preclinical studies, no Phase III clinical trial is available to demonstrate a significant benefit of PAM-inhibitors. A way to manage targeted agents is to tailor their use to particular subpopulations most likely to obtain a considerable benefit, namely pursuing an individualized, precision-medicine approach.
  • ||||||||||  Journal, PARP Biomarker:  Aaptamine attenuates the proliferation and progression of non-small cell lung carcinoma. (Pubmed Central) -  Jul 10, 2021   
    Additionally, we also found that PI3K/AKT inhibitor LY294002 abolished the downregulation of PUMA mRNA by FSH in vitro, In conclusion, FSH inhibit the expression of PUMA induced by ROS through PI3K/AKT pathway in vivo and vitro. Aaptamine retarded the proliferation and invasion of NSCLC cells by selectively targeting the pathway PI3K/AKT/GSK3β suggesting it as a potential chemotherapeutic agent for repressing tumorigenesis and progression of NSCLC in humans.
  • ||||||||||  Review, Journal:  Skin-Associated B Cells in the Pathogenesis of Cutaneous Autoimmune Diseases-Implications for Therapeutic Approaches. (Pubmed Central) -  Jul 10, 2021   
    In this review, we describe current considerations of different B cell subsets and their assumed role in skin autoimmunity. Moreover, we discuss traditional and B cell-associated approaches for the treatment of autoimmune skin diseases, including drugs targeting B cells (e.g., CD19- and CD20-antibodies), plasma cells (e.g., proteasome inhibitors, CXCR4 antagonists), activated pathways (such as BTK- and PI3K-inhibitors) and associated activator molecules (BLyS, APRIL).
  • ||||||||||  Clinical, Review, Journal, Adverse events:  PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects. (Pubmed Central) -  Jul 10, 2021   
    There is a discussion of the drug-related toxicities, challenges associated with these PI3K inhibitors and the adverse events leading to treatment failure. In addition, novel PI3K drugs that have potential to be translated in the clinic are highlighted.
  • ||||||||||  Journal, IO biomarker:  Elevated HNF1A expression promotes radiation-resistance via driving PI3K/AKT signaling pathway in esophageal squamous cell carcinoma cells. (Pubmed Central) -  Jul 9, 2021   
    It was worth noting that HNF1A might be involved in radiation-induced DNA damage repair by regulating γH2AX though PI3K/AKT signal pathway. Our study preliminarily suggested that HNF1A was associated with the progression and radiosensitivity of ESCC cells, and it might reduce the radiosensitivity of ESCC cells by promoting cell proliferation, releasing G0/G1 phase arrest, reducing apoptosis, and regulating the expression of γH2AX protein though driving PI3K/AKT signal pathway.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Clinical, Journal:  Hypoxia promotes Chlamydia trachomatis L2/434/Bu growth in immortal human epithelial cells via activation of the PI3K-AKT pathway and maintenance of a balanced NAD/NADH ratio. (Pubmed Central) -  Jul 9, 2021   
    This activation was significantly diminished by LY-294002, a PI3K-AKT inhibitor, which decreased the number of CtL2 progeny...Furthermore, in normoxia, CtL2 infection changed the NAD/NADH ratio of cells with increased gapdh expression; in contrast, under hypoxia, the NAD/NADH ratio was the same in infected and uninfected cells with high and stable expression of gapdh, suggesting that CtL2-infected cells adapted better to hypoxia. Together, these data indicate that hypoxia promotes CtL2 growth in immortal human epithelial cells by activating the PI3K-AKT pathway and maintaining the NAD/NADH ratio with stably activated glycolysis.
  • ||||||||||  Biomarker, Review, Journal, Tumor microenvironment:  Emerging roles of class I PI3K inhibitors in modulating tumor microenvironment and immunity. (Pubmed Central) -  Jul 9, 2021   
    We discuss the modulation by PI3K inhibitors of the tumor-supportive microenvironment, including eliminating the regulatory immune cells, restoring cytotoxic cells or regulating angiogenesis. The potential combinations of PI3K inhibitors with other therapies to enhance the anti-tumor immunity are also described.