- |||||||||| ALS-205 / Alsonex
Journal: Mild Hypothermia Alleviates Complement C5a-Induced Neuronal Autophagy During Brain Ischemia-Reperfusion Injury After Cardiac Arrest. (Pubmed Central) - Aug 26, 2022 Furthermore, C5a treatment induced autophagy and apoptosis and reduced the PI3K/Akt/mTOR pathway-related proteins in cultured neurons, which could be reversed by C5aR1 antagonist PMX205...Furthermore, C5a treatment induced autophagy and apoptosis and reduced the PI3K/Akt/mTOR pathway-related proteins in cultured neurons, which could be reversed by C5aR1 antagonist PMX205...HT may alleviate complement activation and then reduce C5a-induced autophagy to protect against brain I/R injury. HT, mild hypothermia; I/R, ischemia reperfusion.
- |||||||||| Journal: ARID1A-deficient bladder cancer is dependent on PI3K signaling and sensitive to EZH2 and PI3K inhibitors. (Pubmed Central) - Aug 25, 2022
Furthermore, ARID1A-deficient bladder cancer was sensitive to combination therapies with EZH2 and PI3K inhibitors in a synergistic manner. Thus, our studies suggest that bladder cancers with ARID1A mutations can be treated with inhibitors of EZH2 and/or PI3K and revealed mechanistic insights into the role of noncanonical PI3K constituents in bladder cancer biology.
- |||||||||| Zejula (niraparib) / GSK, J&J, Aliqopa (copanlisib) / Bayer
Trial completion date, Trial primary completion date: Niraparib and Copanlisib in Treating Patients With Recurrent Endometrial, Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - Aug 25, 2022 P1, N=44, Recruiting, Thus, our studies suggest that bladder cancers with ARID1A mutations can be treated with inhibitors of EZH2 and/or PI3K and revealed mechanistic insights into the role of noncanonical PI3K constituents in bladder cancer biology. Trial completion date: Apr 2022 --> Dec 2022 | Trial primary completion date: Apr 2021 --> Dec 2022
- |||||||||| cisplatin / Generic mfg.
Journal: Melatonin Sensitizes OVCAR-3 Cells to Cisplatin through Suppression of PI3K/Akt Pathway. (Pubmed Central) - Aug 24, 2022 Melatonin administration significantly increased intracellular ROS generation, the cleavage of caspase 3 and decreased phosphorylation of Akt. Combination therapy of cisplatin and melatonin increases apoptosis in the OVCAR-3 cells by inhibiting of PI3K/Akt signaling pathway and exacerbating oxidative stress.
- |||||||||| How to measure and improve drug adherence in clinical trials (Stars at Night Ballroom 1&2) - Aug 24, 2022 - Abstract #SABCS2022SABCS_98;
It remains unclear how this increased oral medication burden on BC survivors affects compliance with both ET and other chronic medications. Issues related to adherence measurement will be discussed.
- |||||||||| ranitidine hydrochloride / Generic mfg.
Preclinical, Journal: Manpixiao Decoction Halted the Malignant Transformation of Precancerous Lesions of Gastric Cancer: From Network Prediction to In-Vivo Verification. (Pubmed Central) - Aug 24, 2022 Then, we established a rat model of PLGC using a combination of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), sodium salicylate, irregular fasting, and ranitidine, and observed the effects after MPX treatment...It is showed that MPX can inhibit the phosphorylation of PI3K-AKT, and downregulates the EGFR, β-catenin, and N-cadherin protein levels. These results indicate that MPX halted the PLGC progression through inhibiting EGFR-PI3K-AKT related epithelial-mesenchymal transition process.
- |||||||||| dactolisib (RTB101) / Adicet Bio
Journal: Jagged-1 is induced by mTOR inhibitors in renal cancer cells through an Akt/ALK5/Smad4-dependent mechanism. (Pubmed Central) - Aug 24, 2022 Here we provide the first report that expression of the Notch ligand Jagged-1 (JAG1), which is associated with aggressiveness of RCCs, is induced by several inhibitors of mTOR (rapamycin (Rap), BEZ235, KU-0063794) in human clear cell RCC (ccRCC) cells...Moreover, inhibition of Notch signaling with γ-secretase inhibitors enhanced or permitted mTOR inhibitors to suppress the motility of ccRCC cells. We suggest targeting JAG1 may enhance therapeutic responses to mTOR inhibitors in ccRCCs.
- |||||||||| belnacasan (VX-765) / Vertex
Journal, IO biomarker: Secoisolariciresinol diglucoside induces pyroptosis by activating caspase-1 to cleave GSDMD in colorectal cancer cells. (Pubmed Central) - Aug 24, 2022 Consistent with this, SDG-induced GSDMD-N-terminal fragment cleavage and pyroptosis were reduced by siRNA-mediated silencing of caspase-1 or treatment with the specific caspase-1 inhibitor VX-765 treatment, suggesting that active caspase-1 further induces pyroptosis...In vivo results showed that SDG significantly inhibited tumor growth and induced pyroptosis in the HCT116-CRC nude mouse model. In conclusion, our findings suggest that the anticancer activity of SDG in CRC is associated with the induction of GSDMD-dependent pyroptosis by SDG through the generation of ROS/P13K/AKT/BAK-mitochondrail apoptosis pathway, providing insights into SDG in its potential new application in cancer treatment.
- |||||||||| Clinical, Review, Journal: Plant-Based and Ketogenic Diets As Diverging Paths to Address Cancer: A Review. (Pubmed Central) - Aug 24, 2022
Rigorous trial designs that adapt classical oncologic end points may identify populations that are likely to benefit from starkly contrasting diets. Current data support prioritization of plant-based diets, and future data could further personalize dietary recommendations in cancer populations.
- |||||||||| gemcitabine / Generic mfg.
Journal: Systematic exploration of the underlying mechanism of gemcitabine resistance in pancreatic adenocarcinoma. (Pubmed Central) - Aug 24, 2022 Single-cell analysis revealed that cancer cells in the same PDAC sample showed both the characteristics of sensitivity and resistance to gemcitabine, and the activation of the TGFβ signaling pathway could promote progression of PDAC. In brief, 28-GPS could robustly determine whether PDAC is resistant or sensitive to gemcitabine, and may be an auxiliary tool for clinical treatment.
- |||||||||| Journal: Matrine induces autophagy in human neuroblastoma cells via blocking the AKT-mTOR pathway. (Pubmed Central) - Aug 24, 2022
Matrine treatment significantly declined the phosphorylation of AKT and mTOR and enhanced the LC3 II/GAPDH ratio in NB xenografts. Altogether, our work uncovered the molecular mechanism underlying matrine-induced autophagy in NB and provided implications for matrine as a potential therapeutic agent against NB.
- |||||||||| Xtandi (enzalutamide capsule) / Pfizer, Astellas, taselisib (GDC-0032) / Roche
Trial termination, Combination therapy, Metastases: Taselisib and Enzalutamide in Treating Patients With Androgen Receptor Positive Triple-Negative Metastatic Breast Cancer (clinicaltrials.gov) - Aug 22, 2022 P1/2, N=30, Terminated, In conclusion, an unexpected cytoplasmic role for mSWI/SNF complexes in translation suggests potential new therapeutic opportunities for patients afflicted by cancers demonstrating alterations in their subunits. Active, not recruiting --> Terminated; Interim analysis - toxicity
- |||||||||| LY294002 / Eli Lilly
Journal: Role of PI3K in the bone resorption of apical periodontitis. (Pubmed Central) - Aug 22, 2022 Collectively, this work offers building blocks for developing iridium (III) complexes as clinical application potential. Under the inflammatory environment induced by LPS, PI3K participates in the occurrence and development of chronic apical periodontitis by regulating the proliferation and differentiation of osteoclasts and osteoblasts.
- |||||||||| Journal: Cutting Edge: Promoting T Cell Factor 1 T Cell Self-Renewal to Improve Programmed Cell Death Protein 1 Blockade. (Pubmed Central) - Aug 18, 2022
Combining anti-PD-1 and inhibitor of PI3K δ conferred superior protection compared with either monotherapy and was associated with higher frequency of TCF1 T cells in tumor and blood compared with anti-PD-1 alone. These findings reveal predictive importance of self-renewing T cells in anti-tumor immunity and suggest that resistance-directed strategies to enhance T cell self-renewal could potentiate the efficacy of PD-1 blockade.
- |||||||||| LY294002 / Eli Lilly
Preclinical, Journal: PDZK1 upregulates nitric oxide production through the PI3K/ERK2 pathway to inhibit porcine circovirus type 2 replication. (Pubmed Central) - Aug 17, 2022 A PI3K inhibitor (LY294002) and a NO synthase inhibitor (L-NAME hydrochloride) decreased the activity of PDZK1 in restricting PCV2 replication...PDZK1 affected IL-4 expression through the PI3K/ERK2 pathway, but PDZK1 modulation of PCV2 replication occurred independently of IL-4. Our results contribute to understanding the biological functions of PDZK1 and provide a theoretical basis for the pathogenic mechanisms of PCV2.
- |||||||||| LY294002 / Eli Lilly
Journal: Crosstalk between PI3K/Akt and Wnt/β-catenin pathways promote colorectal cancer progression regardless of mutational status. (Pubmed Central) - Aug 17, 2022 In addition, these effects were hindered after pretreatment with LY294002, a specific PI3K inhibitor, suggesting some dependence between these two signaling cascades. Our findings show that, regardless of mutational status, there is an interplay between the activity of PI3K/Akt and Wnt/β-catenin pathways that contributes to events related to CRC progression and that the reversal of such events using a PI3K inhibitor highlights the value of targeting these pathways for potential directed therapies in CRC patients.
- |||||||||| Herceptin (trastuzumab) / Roche
Journal: PI3K inhibitors in trastuzumab-resistant HER2-positive breast cancer cells with PI3K pathway alterations. (Pubmed Central) - Aug 16, 2022 In vivo effects of alpelisib plus trastuzumab were tested and confirmed in a mouse model, showing the combination strategy offered the best opportunity to achieve tumor volume reduction. With known safety profiles, this cytotoxic chemotherapy-free regimen warrants further attention as a biomarker-driven strategy for treating HER2-positive breast cancer.
- |||||||||| Journal: Mycoplasma bovis inhibits autophagy in bovine mammary epithelial cells via a PTEN/PI3K-Akt-mTOR-dependent pathway. (Pubmed Central) - Aug 14, 2022
In the present study, the number of intracellular M. bovis was inversely related to the change in the level of autophagy markers (e.g., LC3-II, SQSTM1/P62) within host cells induced by the low knockdown of Akt or PTEN. We concluded that M. bovis-infected bMECs alleviated cellular autophagy through a PI3K-Akt-mTOR pathway, and that PTEN acted as a protective gene regulating autophagy, a key step in controlling infection.
- |||||||||| Journal: Current status of phosphoinotiside-3 kinase inhibitors in blood cancers. (Pubmed Central) - Aug 13, 2022
With close monitoring and management of adverse events, PI3K inhibitors continue to have a role in therapy of R/R CLL and NHL. Strategies to mitigate adverse events and increase efficacy of PI3K inhibitors include time-limited combination approaches, intermittent dosing schedules.
- |||||||||| Journal: Hawthorn extract inhibited the PI3k/Akt pathway to prolong the lifespan of Drosophila melanogaster. (Pubmed Central) - Aug 12, 2022
Hawthorn is a kind of nutrient-rich substance that is rich in flavonoids and thus has many potential biological and pharmacological functions. Our results showed that HE has good antioxidant properties and can maintain intestinal homeostasis, which provides a good theoretical basis for the development and research using HE as an effective natural antioxidant for the elderly.
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