- |||||||||| Journal, IO Biomarker: miR-144-3p Contributes to the Development of Thyroid Tumors Through the PTEN/PI3K/AKT Pathway. (Pubmed Central) - Nov 1, 2020
Rescue experiments revealed that the cell proliferation, invasion and apoptosis were not different from NC after co-transfection of miR-144-3p-mimics+sh-PTEN and miR-144-3p-inhibitor+si-PTEN into B-CPAP and HTh-7. Inhibition of miR-144-3p expression can up-regulate PTEN and affect cell proliferation, invasion and apoptosis, which may be a potential therapeutic target for TC.
- |||||||||| arecoline / Cogent
Journal: LDOC1 Suppresses Microbe-Induced Production of IL-1β in Human Normal and Cancerous Oral Cells through the PI3K/Akt/GSK-3β Axis. (Pubmed Central) - Nov 1, 2020 CA SC5314 increased OSCC incidence in 4-NQO (a synthetic tobacco carcinogen) and arecoline-cotreated mice...PI3K and Akt inhibitors and expression of the constitutively active mutant GSK-3β significantly reduced the CA SC5314-stimulated IL-1β production in LDOC1-deficient cells. These results indicate that the PI3K/Akt/pGSK-3β signaling pathway contributes to LDOC1-mediated inhibition of oral microbe-induced IL-1β production, suggesting that LDOC1 may determine the pathogenic role of oral microbes in POH-associated OSCC.
- |||||||||| dactolisib (RTB101) / resTORbio
Journal, Combination therapy: Synergistic antitumor effect of dual PI3K and mTOR inhibitor NVP-BEZ235 in combination with cisplatin on drug-resistant non-small cell lung cancer cell. (Pubmed Central) - Nov 1, 2020 The expression levels of drug efflux proteins, such as multidrug resistance-associated protein 1 and ATP-binding cassette sub-family G member 2, were significantly decreased when A549/DDP cells were treated with a combination of cisplatin and NVP-BEZ235 compared with the control group. Collectively, the present study indicated that the combined treatment of cisplatin and NVP-BEZ235 displayed synergistic antitumor effects on drug-resistant A549/DDP cells, by which the antiproliferative effects may occur via inhibition of the PI3K/Akt/mTOR signaling pathway and downregulation of drug efflux.
- |||||||||| Journal: PI3K activation within ventromedial prefrontal cortex regulates the expression of drug-seeking in two rodent species. (Pubmed Central) - Oct 31, 2020
Taken together, this cross-species, interdisciplinary, study provides convincing evidence that cocaine history produces an enduring increase in PI3K/Akt-dependent signaling within the more ventral aspect of the PFC that is relevant to behavioral reactivity to drug-associated cues/contexts. As such, PI3K inhibitors may well serve as an effective strategy for reducing drug cue reactivity and craving in cocaine addiction.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Aliqopa (copanlisib) / Bayer
Clinical, Journal: Combination of copanlisib with cetuximab improves tumor response in cetuximab-resistant patient-derived xenografts of head and neck cancer. (Pubmed Central) - Oct 30, 2020 While no correlation was observed between PI3K mutation status and response to either cetuximab or copanlisib, increased PI3K signaling activity evaluated through gene expression profiling showed a positive correlation with response to copanlisib. Together, these data support further investigation of PI3K inhibition in HNSCC and suggests gene expression patterns associated with PI3K signaling as a potential biomarker for predicting treatment responses.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Mechanical stress promotes biological functions of C2C12 myoblasts by activating PI3K/AKT/mTOR signaling pathway. (Pubmed Central) - Oct 28, 2020 The PI3K specific inhibitor LY294002 significantly decreased 4EBP1 expression and reduced p‑AKT and p‑mTOR expression compared with the mechanical stress group...In conclusion, mechanical stress promoted biological functions of C2C12 cells by activating the PI3K/AKT signaling pathway. These results may contribute to a better understanding of the effects of mechanical stress on cells.
- |||||||||| MK-2206 / Merck (MSD)
Journal: Role of the PI3K/AKT pathway and PTEN in otitis media. (Pubmed Central) - Oct 28, 2020 The Akt inhibitor MK2206 treatment inhibited the growth of middle ear mucosal explants in a dose-dependent manner...Unexpectedly, while PTEN is generally thought to act in opposition to AKT, the PTEN inhibitor BPV reduced mucosal explant growth in vitro. The results indicate that both AKT and PTEN are mediators of mucosal growth during OM, and could be potential therapeutic targets.
- |||||||||| Journal: Adiponectin attenuates the premature senescence of vascular smooth muscle cells induced by high glucose through mTOR signaling pathway. (Pubmed Central) - Oct 28, 2020
High glucose reduced telomerase activity of VSMCs via inhibition of the AMPK/TSC2/mTOR/S6K1 pathway and activation of the PI3K/Akt/mTOR/S6K1 pathway, while adiponectin treatment significantly increased telomerase activity of VSMCs through activation of AMPK/TSC2/mTOR/S6K1 signaling and inhibition of PI3K/Akt/mTOR/S6K1 signaling. Adiponectin attenuated the high-glucose-induced premature senescence of VSMCs via increasing telomerase activity of VSMCs, which was achieved by activation of AMPK/TSC2/mTOR/S6K1 signaling and inhibition of PI3K/Akt/mTOR/S6K1 signaling.
- |||||||||| Piqray (alpelisib) / Novartis
Journal: Pharmacological mTOR targeting enhances the antineoplastic effects of selective PI3Kα inhibition in medulloblastoma. (Pubmed Central) - Oct 27, 2020 Importantly, pharmacologic mTOR inhibition greatly enhanced the inhibitory effects of alpelisib on medulloblastoma tumour growth in vivo. In summary, these findings highlight a key role for PI3K/mTOR signalling in GLI1 regulation in HH-driven cancers and suggest that combined PI3Kα/mTOR inhibition may be particularly interesting for the development of effective treatment strategies in high-risk medulloblastomas.
- |||||||||| Journal: Immunological characterization of HM5023507, an orally active PI3Kδ/γ inhibitor. (Pubmed Central) - Oct 27, 2020
In addition, HM5023507 inhibited semiestablished collagen-induced arthritic inflammation in the rats (ED of 0.25mg/kg, p.o. BID or 0.5 mg/kg, QD, AUC: 1422 ng/mL*h), improved histopathology- and micro-computed tomography (µCT)-based indices of joint damage, bone destruction, and attenuated the levels of anti-collagen antibody, with an overall anti-inflammatory profile matching that of a TNFα neutralizing antibody. The PI3K δγ inhibitory profile of HM5023507 and its selectivity make it a useful tool to further delineate immunobiology of dual PI3K δγ targeting.
- |||||||||| Ogivri (trastuzumab biosimilar) / Biocon, Mylan
Journal, PD(L)-1 Biomarker, IO Biomarker: Immunomodulatory Protective Effects of Rb9 Cyclic-Peptide in a Metastatic Melanoma Setting and the Involvement of Dendritic Cells. (Pubmed Central) - Oct 27, 2020 The cyclic VHCDR3-derived peptide (Rb9) from RebMab200 antibody, directed to a NaPi2B phosphate-transport protein, displayed anti-metastatic melanoma activity at 50-300 μg intraperitoneally injected in syngeneic mice...Recently, the interaction MIF-CD74 has been associated to PD-L1 expression and IFN-γ, suggesting a target for melanoma treatment. The effects described for Rb9 and the protection against metastatic melanoma may suggest the possibility of a peptide reagent that could be relevant when associated to modern immunotherapeutic procedures.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, buparlisib (AN2025) / Novartis, Adlai Nortye
Biomarker, Enrollment change, Trial completion date, Combination therapy, Metastases: PI3K Inhibitor BKM120 and Cetuximab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer (clinicaltrials.gov) - Oct 27, 2020 P1/2, N=12, Active, not recruiting, The effects described for Rb9 and the protection against metastatic melanoma may suggest the possibility of a peptide reagent that could be relevant when associated to modern immunotherapeutic procedures. N=30 --> 12 | Trial completion date: Jun 2018 --> Jun 2021
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