- |||||||||| Journal, PD(L)-1 Biomarker, IO biomarker: Prediction of the Mechanism of Sodium Butyrate against Radiation-Induced Lung Injury in Non-Small Cell Lung Cancer Based on Network Pharmacology and Molecular Dynamic Simulations and Molecular Dynamic Simulations. (Pubmed Central) - Jul 17, 2022
NaB may protect patients from RILI in NSCLC through multiple target genes including AKT1, TP53, NOTCH1, SIRT1 and PTEN, with multiple signaling pathways involving, including PI3K-Akt pathway, p53 pathway, and FOXO pathways. Our findings effectively provide a feasible theoretical basis to further elucidate the mechanism of NaB in the treatment of RILI.
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Alpelisib-induced Diabetic Ketoacidosis (ENDOExpo, Pod 6) - Jul 16, 2022 - Abstract #ENDO2022ENDO_2887; Further research to identify patients at risk of developing such complication and to standardize management of alpelisib-induced DKA is warranted to maximize the clinical benefit of patients treated with alpelisib plus fulvestrant. Learning Objective 1: To recognize alpelisib-induced diabetic ketoacidosis (DKA) as a potential life-threatening complication of alpelisib, including in non-diabetic patients and to emphasis on the importance of blood glucose monitoring after initiation of therapy Learning Objective 2: To understand the pathophysiology of alpelisib-induced DKA and the importance of insulin treatment to achieve adequate glycemic control Science Topic(s) for Tumor Biology: Cancer Targets and Therapies
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Breast Cancer With Liver Metastasis Responds Poorly to Fulvestrant-Based Combination Therapy and Chemotherapy () - Jul 16, 2022 - Abstract #ENDO2022ENDO_1239; Fulvestrant combined with newer medications (CDK4/6 inhibitors, mTOR kinase inhibitors, and PI3K inhibitors) have held great promise in treating metastatic breast cancer, but we observe that similar survival benefits do not extend to patients with liver metastasis. Breast cancer with liver metastasis ultimately proves to be aggressive and difficult to treat, and current therapies are insufficient.
- |||||||||| Journal: A p53-phosphoinositide signalosome regulates nuclear AKT activation. (Pubmed Central) - Jul 16, 2022
The p53-PtdIns(3,4,5)P complex is dephosphorylated to p53-phosphatidylinositol 4,5-bisphosphate by PTEN to inhibit AKT activation. The nuclear p53-phosphoinositide signalosome is distinct from the canonical membrane-localized pathway and insensitive to PI3K inhibitors currently in the clinic, which underscores its therapeutic relevance.
- |||||||||| Journal: Cellular Mechanisms Underlying B Cell Abnormalities in Patients With Gain-of-Function Mutations in the PIK3CD Gene. (Pubmed Central) - Jul 16, 2022
Targeted therapy of PI3K inhibition partially restored B cell phenotypes. The present study suggests additional mechanistic insight into B cell pathology of APDS: (1) decreased peripheral B cell numbers may be due to the increased death of naïve B cells; (2) larger B cell sizes and expanded DNB population suggest enhanced activation and differentiation of naïve B cells into DNB cells; (3) the impaired CSR yet normal PB differentiation can predominantly generate IgM-secreting cells, resulting in elevated IgM levels.
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Journal: Isovalerylspiramycin I suppresses non-small cell lung carcinoma growth through ROS-mediated inhibition of PI3K/AKT signaling pathway. (Pubmed Central) - Jul 13, 2022 Some studies have shown that carrimycin, a Chinese Food and Drug Administration (CFDA)-approved macrolide antibiotic, possesses potent anti-tumor effects against oral squamous cell carcinoma...Moreover, we identified ROS accumulation and PI3K/AKT pathway inhibition in tumor xenograft models in vivo as well. Taken together, our study firstly reveals that ISP-I is a novel ROS inducer and may act as a promising candidate with multi-target and low biological toxicity for anti-NSCLC treatment.
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Journal: LGI3 promotes human keratinocyte migration in high-glucose environments by increasing the expression of β-catenin. (Pubmed Central) - Jul 2, 2022 Further results showed that LY294002, a specific inhibitor of phosphatidylinositol 3-kinase, reduced LGI3-induced cell migration...Taken together, these data indicate that LGI3 induces keratinocyte migration in high-glucose environments as a result of β-catenin accumulation via Akt phosphorylation. Therefore, LGI3 can be considered a new treatment option for diabetic wound healing.
- |||||||||| Journal: Androgens regulate tau phosphorylation through PI3K-Akt-GSK3β signaling. (Pubmed Central) - Jul 2, 2022
Together, these results suggest an AR-dependent pathway involving PI3K-Akt-GSK3β signaling through which androgens can reduce tau phosphorylation. These findings identify an additional protective mechanism of androgens that can improve neural health and inhibit development of AD.
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Preclinical, Journal: Oxytocin-induced endothelial nitric oxide dependent vasorelaxation and ERK1/2-mediated vasoconstriction in the rat aorta. (Pubmed Central) - Jun 30, 2022 The present study demonstrates that oxytocin can activate different signaling pathways to cause vasorelaxation or vasoconstriction. Oxytocin stimulation of PI3K/eNOS-derived nitric oxide may participate in maintenance of cardiovascular homeostasis, and different vascular reactivities to low or high dose of oxytocin suggest that oxytocin may have different regulatory effects on vascular tone under physiological or pathophysiological conditions.
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Journal: Eucalyptol targets PI3K/Akt/mTOR Pathway to inhibit Skin Cancer Metastasis. (Pubmed Central) - Jun 29, 2022 In Vivo,theanti-metastatic potential of EU was confirmed in C57BL/6 mouse. In conclusion,the EU inhibits migration and invasion of skin cancer by modulating PI3K/Akt/mTOR pathway both in In Vitro and In Vivoand might provide a new therapeutic approach in skin cancer.
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A CTC-Derived eXplant (CDX) model of a Merkel cell carcinoma to inform treatment opportunities (Poster Area) - Jun 28, 2022 - Abstract #EACR2022EACR_583; Results and Discussions A CDX was generated from a pre-treatment blood sample from a patient with a metastatic NEC of unknown origin who responded to platinum/etoposide (P/E)...Conclusion We report the generation of a MCC CDX from donor who is still alive 30 months from diagnosis. The CDX facilitated expansion of the donor’s tumour allowing comprehensive molecular characterisation, a vehicle for drug testing with potential to define new therapeutic opportunities including a PI3K inhibitor.
- |||||||||| PTCH1 C-terminal domain mutations enhance colon cancer tumorigenesis (Poster Area) - Jun 28, 2022 - Abstract #EACR2022EACR_406;
Complementary studies showed that both clones displayed an enhanced autophagic flux, reduced apoptosis and metabolic reprogramming. Conclusion Our study highlights the role of PTCH1 CTD mutations in cancer progression through dysregulation of non-canonical Hh signalling.
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New insights the analysis of circuloma: targeting PIK3CA actionable mutations in metastatic breast cancer (Poster Area) - Jun 28, 2022 - Abstract #EACR2022EACR_299; In advanced breast cancer (BC), hormone receptor (HR) positive, HER2 negative BC cases harboring PIK3CA actionable mutations (40%) can be treated with combination of PI3K inhibitor Alpelisib and Fulvestran...DNA EVs mutational profiles were consistent with the CTCs ones, suggesting that mutated EVs are released by CTCs. Conclusion This study generated proofs of concept data on molecular content of the different circulating markers and put in evidence a new CTCs sub-population to be considered for a more comprehensive mutational characterization of the disease.
- |||||||||| Journal: Exploring Degradation of Mutant and Wild-Type Epidermal Growth Factor Receptors Induced by Proteolysis-Targeting Chimeras. (Pubmed Central) - Jun 25, 2022
Interestingly, we found that the mutant but not the WT EGFR can effectively form EGFR-PROTAC-E3 ligase ternary complexes. Furthermore, we found that PI3K inhibition sensitized WT EGFR to PROTAC-induced degradation and combination treatment with a PI3K inhibitor enhanced antiproliferation activities of EGFR degraders in cancer cells harboring WT EGFR, providing a potential therapeutic strategy for patients with WT EGFR overexpression.
- |||||||||| Review, Journal, MSi-H Biomarker, PD(L)-1 Biomarker, IO biomarker: Precision Medicine in Cholangiocarcinoma: Past, Present, and Future. (Pubmed Central) - Jun 25, 2022
Additional targeted therapies, including other FGFR2 inhibitors, PI3K/AKT/mTOR inhibitors, and BRAF-directed targeted therapy, have been discussed for the management of CCA, and immune checkpoint inhibitors, particularly pembrolizumab, can be administered to patients with high microsatellite instability tumors. There is a further need for improvement in precision medicine therapies in the treatment of CCA and discuss the approved and potential targeted therapies for CCA.
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