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  • ||||||||||  gefitinib / Generic mfg.
    Journal:  Epithelial-mesenchymal transition is associated with osteopontin-induced EGFR?TKI resistance in EGFR mutant non-small cell lung cancer. (Pubmed Central) -  Jul 10, 2023   
    Western blot (WB), quantitative real?time polymerase chain reaction (qRT-PCR), and immunofluorescence staining were used to analyze OPN and epithelial-mesenchymal transition (EMT)-related protein expression in the PC9 and PC9 gefitinib resistance (PC9GR) cells...This study showed that OPN increased EGFR-TKI resistance in NSCLC through the OPN-PI3K/AKT-EMT pathway. Our findings may provide a possible therapeutic target for overcoming EGFR-TKI resistance in this pathway.
  • ||||||||||  Piqray (alpelisib) / Novartis, Zarnestra (tipifarnib) / Kura Oncology
    Journal, Tumor mutational burden, PD(L)-1 Biomarker, IO biomarker:  Targeted treatment in a case series of AR+, HRAS/PIK3CA co-mutated salivary duct carcinoma. (Pubmed Central) -  Jul 10, 2023   
    Combination therapies, PI3K-inhibitors and immune therapy warrant further investigation, ideally in clinical trials. Future research should consider this rare subgroup of SDC.
  • ||||||||||  Journal:  Recent advances in treatment of nodal and gastrointestinal follicular lymphoma. (Pubmed Central) -  Jul 7, 2023   
    This editorial provides an overview of the recent therapeutic advances in nodal FL, including antibody-targeted therapy, bispecific antibody therapy, epigenetic modulation, and chimeric antigen receptor T-cell therapy, and reviews the latest therapeutic manuscripts published in the past year. Based on an understanding of the therapeutic advances in nodal FL, we also discuss future possibilities for gastroenterologists to treat gastrointestinal FL, especially in advanced cases.
  • ||||||||||  Piqray (alpelisib) / Novartis
    Journal:  Beyond Skin Rash: Alpelisib-Induced Anaphylactic Reactions. (Pubmed Central) -  Jul 7, 2023   
    Even if a reaction develops after days on treatment, a type-I allergic reaction cannot be excluded. A rechallenge can be dangerous and should always be well contemplated or even avoided.
  • ||||||||||  Journal:  Cadmium accelerates autophagy of osteocytes by inhibiting the PI3K/AKT/mTOR signaling pathway. (Pubmed Central) -  Jul 6, 2023   
    Further experiments revealed that addition of rapamycin, an autophagy inducer, enhanced autophagy and alleviated the Cd-induced damage to MLO-Y4 cells. The findings of our study reveal for the first time that Cd causes damage to both bone and osteocytes, as well as induces autophagy in osteocytes and inhibits PI3K/AKT/mTOR signaling, which could be a protective mechanism against Cd-induced bone injury.
  • ||||||||||  Journal, Metabolomic study:  Potential components and mechanism of Liangxue Tuezi Mixture in treating Henoch-Sch (Pubmed Central) -  Jul 3, 2023   
    The progression of HSP was related to metabolic abnormalities of glycerophospholipid and sphingolipid. The results indicate that the components in Liangxue Tuizi Mixture mainly treats HSP by regulating inflammation and immunity, providing a scientific basis for rational drug use in clinical practice.
  • ||||||||||  Journal:  Chaetocochin J exhibits anti-hepatocellular carcinoma effect independent of hypoxia. (Pubmed Central) -  Jul 2, 2023   
    as well as disrupt the binding of HIF-1?/p300 and subsequently inhibits the expression of its target genes under hypoxic condition. These results demonstrated that CJ possessed a hypoxia-independent anti-HCC effects in vitro and in vivo, which was mainly attributable to its inhibition on the upstream pathways of HIF-1?.
  • ||||||||||  Genome-wide CRISPR screening to identify regulators of hepatic insulin signalling (Hamburg Hall) -  Jul 2, 2023 - Abstract #EASD2023EASD_1538;    
    In summary, we have established a novel assay to identify genes regulating insulin-induced FoxO1 nuclear export. This provides a resource for unbiased identification of targets for the treatment of diseases associated with altered insulin signalling, such as type 2 diabetes.
  • ||||||||||  Glycine and ?-alanine promote pancreatic islet cell proliferation via activation of PI3K/mTORC1/p70S6K pathway (Short Oral Event E) -  Jul 2, 2023 - Abstract #EASD2023EASD_1076;    
    This effect is mediated via the activation of the GlyRs and the downstream PI3K/mTORC1/p70S6K signaling pathway. Moreover, this enhanced proliferation of pancreatic ?-cells could result in reduced glucose level and elevated insulin secretion in conditions associated with acute insulin resistance, providing novel therapeutic targets for the metabolic disorder.
  • ||||||||||  Journal:  Network pharmacology and molecular docking reveal the mechanism of Qinghua Xiaoyong Formula in Crohn's disease. (Pubmed Central) -  Jun 30, 2023   
    Finally, animal experiments were performed to further validate the findings, and the results revealed that QHXYF or quercetin inhibited 2,4,6-trinitrobenzenesulfonic acid-induced inflammation and oxidative stress processes by inhibiting the PI3K/AKT pathway, thereby improving CD symptoms. These findings suggest that QHXYF and quercetin may be potential novel treatments for CD.
  • ||||||||||  Journal:  Tyrosol: Repercussion of the Lack of a Hydroxyl-Group in the Response of MCF-7 Cells to Hypoxia. (Pubmed Central) -  Jun 28, 2023   
    Some of these results are positive to control tumor progression in a hypoxic environment; however, they are observed at doses unachievable with diet intake or nutraceutical presentations. Considering that EVOO phenols can have synergistic effects, a mixture of low doses of TYR and other phenols could be useful to achieve these beneficial effects.
  • ||||||||||  taselisib (GDC-0032) / Roche, pictilisib (GDC-0941) / Roche
    Journal, Gene Signature, IO biomarker:  Assessing of programmed cell death gene signature for predicting ovarian cancer prognosis and treatment response. (Pubmed Central) -  Jun 25, 2023   
    In addition, we found that patients in the low-risk group responded better to immunotherapy. Risk Score of 9-gene composition of PCD signature possesses promising clinical potential in OV prognosis, immunotherapy, immune microenvironment activity, and chemotherapeutic drug selection, and our study provides the basis for an in-depth investigation of the PCD mechanism in OV.
  • ||||||||||  Journal:  Polydom/SVEP1 binds to Tie1 and promotes migration of lymphatic endothelial cells. (Pubmed Central) -  Jun 24, 2023   
    LECs also exhibited nuclear exclusion of Foxo1, a signaling event downstream of Akt activation, which was impaired in Polydom-deficient mice. These findings indicate that Polydom is a physiological ligand for Tie1 and participates in lymphatic vessel development through activation of the PI3K/Akt pathway.
  • ||||||||||  Journal:  Extracellular vesicle-associated IGF2BP3 tunes Ewing sarcoma cell migration and affects PI3K/Akt pathway in neighboring cells. (Pubmed Central) -  Jun 24, 2023   
    Our data demonstrate that (i) IGF2BP3 is detected in cell supernatants, and it is released inside extracellular vesicles (EVs); (ii) EVs from IGF2BP3-positive or IGF2BP3-negative EWS cells reciprocally affect cell migration but not the proliferation of EWS recipient cells; (iii) EVs derived from IGF2BP3-silenced cells have a distinct miRNA cargo profile and inhibit the PI3K/Akt pathway in recipient cells; (iv) the 11 common differentially expressed miRNAs associated with IGF2BP3-positive and IGF2BP3-negative EVs correctly group IGF2BP3-positive and IGF2BP3-negative clinical tissue specimens. Overall, our data suggest that IGF2BP3 can participate in the modulation of phenotypic heterogeneity.
  • ||||||||||  Leukeran (chlorambucil) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Holdings, Roche
    Treatment Options for Marginal Zone Lymphoma (LEVEL 3, GENERAL ASSEMBLY) -  Jun 21, 2023 - Abstract #SOHO2023SOHO_203;    
    Bendamustine and chlorambucil are commonly used chemotherapy agents.13 A large, randomized study has shown that the combination of chlorambucil and rituximab is more effective than either chlorambucil or rituximab monotherapy.14 The choice of chemotherapy agents should consider patient age, fitness, and organ functions, as older/frail adults receiving bendamustinerituximab have shown higher rates of fatal toxicities. More intensive doxorubicin-containing combination regimens such as R-CHOP are active but more toxic and should be limited to patients with histological transformation or bulky masses...Second- and subsequent lines of treatment may include rituximab single agent, particularly after durable first remission, and chemotherapy or lenalidomide plus rituximab.15
  • ||||||||||  Novel Targeted Agents in T-Cell Lymphoma (LEVEL 3, GENERAL ASSEMBLY) -  Jun 21, 2023 - Abstract #SOHO2023SOHO_195;    
    The exception is represented by brentuximab vedotin, which has an indication in relapsed or refractory ALCL, however with much more disappointing results in other PTCL subtypes...Four agents currently under evaluation in clinical trials are reviewed in this paper: the phosphatidylinositol-3 kinase (PI3K) inhibitors duvelisib and linperlisib; the Janus kinase (JAK) 1 inhibitor golidocitinib (DZD4205); the enhancer of zeste homologs 1 and 2 (EZH1/ EZH2) inhibitor valemetostat...Conclusion Translational research, from the bench to the bed, provides better knowledge of the mechanisms of the disease and suggests novel targets to hit. Newer agents currently under evaluation in clinical trials, including the novel PI3K inhibitors, JAK1 inhibitors and EZH1/EZH2 inhibitors, may provide a step forward to the treatment of relapsed and refractory PTCL.
  • ||||||||||  Journal:  Discovery, SAR and mechanistic studies of quinazolinone-based acetamide derivatives in experimental visceral leishmaniasis. (Pubmed Central) -  Jun 19, 2023   
    In silico docking studies conducted with lead compound, F27 demonstrated plausible inhibition of Leishmania prolyl-tRNA synthetase, which was validated via detection of decreased proline levels in parasites and induction of amino acid starvation, leading to G cell cycle arrest and autophagy-mediated programmed cell death of L. donovani promastigotes. Structure-activity analysis and study of pharmacokinetic and physicochemical parameters suggest oral availability and underscore F27 as a promising lead for anti-leishmanial drug development.
  • ||||||||||  Journal, BRCA Biomarker:  Potential Phytochemicals for Prevention of Familial Breast Cancer with BRCA Mutations. (Pubmed Central) -  Jun 19, 2023   
    This manuscript reviews different approaches used to identify potential phytochemicals to mitigate the risk of familial breast cancer with BRCA mutations. The findings of this review can be extended for the prevention and cure of any BRCA-mutated cancer after proper experimental and clinical validation of the data.
  • ||||||||||  gemcitabine / Generic mfg.
    Squalene epoxidase promotes pancreatic ductal adenocarcinoma tumorigenesis and drives gemcitabine resistance by activating the PI3K-Akt pathway () -  Jun 16, 2023 - Abstract #IDDF2023IDDF_235;    
    Xenograft tumors with SQLE overexpression were administrated with SQLE inhibitor terbinafine or in combination with gemcitabine in mouse models...In keeping with this, targeting the PI3K-Akt pathway with PI3K inhibitor LY294002 sensitized PDAC cells to gemcitabine...Conclusions Our work suggests the oncogenic function of SQLE in PDAC that enhances RRM1 and reduces ENT1 and activates the PI3K-Akt signaling, which contributes to gemcitabine resistance. Targeting SQLE by pharmacological blockade combined with gemcitabine could be a promising therapy for PDAC patients.