- |||||||||| monalizumab (IPH2201) / AstraZeneca, Innate, ezurpimtrostat (GNS561) / Genoscience Pharma, Genfit, avdoralimab (IPH5401) / Innate
Trial completion, Enrollment change, Metastases: IMMUNONCOVID: Prospective Study in Patients With Advanced or Metastatic Cancer and SARS-CoV-2 Infection (clinicaltrials.gov) - Sep 30, 2022 P2, N=19, Completed, Active, not recruiting --> Completed | N=219 --> 19
- |||||||||| Journal: Transient Systemic Autophagy Inhibition is Selectively and Irreversibly Deleterious to Lung Cancer. (Pubmed Central) - Sep 30, 2022
Importantly, intermittent transient systemic Atg5 knockdown, which resembles what would occur during autophagy inhibition for cancer therapy, significantly prolonged lifespan of KP lung tumor-bearing mice, resulting in recovery of normal tissues but not tumors. Thus, systemic autophagy supports the growth of established lung tumors by promoting immune evasion and sustaining cancer cell metabolism for energy production and biosynthesis, and the inability of tumors to recover from loss of autophagy provides further proof of concept that inhibition of autophagy is a valid approach to cancer therapy.
- |||||||||| Preclinical, Journal: Heidihuangwan alleviates renal fibrosis in rats with 5/6 nephrectomy by inhibiting autophagy. (Pubmed Central) - Sep 29, 2022
In conclusion, our study showed that HDHW inhibited autophagy by upregulating IGF-1 expression, promoting the binding of IGF-1 to IGF-1R, and activating the PI3K/Akt/mTOR signaling pathway, thereby reducing renal fibrosis and protecting renal function. This study provides support for the application and further study of HDHW.
- |||||||||| cisplatin / Generic mfg.
Journal: Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury via SIRT6-Mediated Autophagy Activation. (Pubmed Central) - Sep 29, 2022 The protective effect of PD manifested by the stimulating of autophagy flux, with the reducing of inflammatory response and oxidative stress, which included downregulation of tumor necrosis factor-α and interleukin-1β, decreased activity of myeloperoxidase and content of malondialdehyde, and increased activity of superoxide dismutase and level of glutathione, both in vivo and in vitro, was reversed by either inhibition of autophagy flux by chloroquine or downregulation of SIRT6 by OSS-128167. Taken together, the present findings provide the first evidence demonstrating that PD exhibited nephroprotective effects on CP-AKI by restoring SIRT6-mediated autophagy flux mechanisms.
- |||||||||| Biomarker, Journal: ASCL2 Maintains Stemness Phenotype through ATG9B and Sensitizes Gliomas to Autophagy Inhibitor. (Pubmed Central) - Sep 29, 2022
Furthermore, the highly effective blood-brain barrier (BBB)-permeable autophagy inhibitor ROC-325, which can significantly inhibit the progression of ASCL2-ATG9B axis gliomas as a single agent is investigated. These data demonstrate that a new ASCL2-ATG9B signaling axis is crucial for maintaining the stemness phenotype and tumor progression, revealing a potential autophagy inhibition strategy for adult diffuse gliomas.
- |||||||||| GYY4137 / National University of Singapore
Journal: HA-ADT suppresses esophageal squamous cell carcinoma progression via apoptosis promotion and autophagy inhibition. (Pubmed Central) - Sep 29, 2022 Our data suggested that HA-ADT exerted more potent effects than sodium hydrosulfide (NaHS, a fast HS-releasing donor) and morpholin-4-ium (4-methoxyphenyl)-morpholin-4-ylsulfanylidenesulfido-λ5-phosphane (GYY4137, a slow HS-releasing donor) on inhibiting the viability, proliferation, migration, and invasion of human ESCC cells...In conclusion, HA-ADT can suppress ESCC progression via apoptosis promotion and autophagy inhibition. HA-ADT might be efficacious for the treatment of cancer.
- |||||||||| Preclinical, Journal: MERS-CoV ORF4b is a virulence factor involved in the inflammatory pathology induced in the lungs of mice. (Pubmed Central) - Sep 29, 2022
Further analysis in MRC-5 cell line showed that, in the context of infection, MERS-CoV-MA 4b inhibited autophagy, as confirmed by the increase of p62 and the decrease of ULK1 protein levels, either by direct or indirect mechanisms. Together, these results correlated autophagy activation in the absence of 4b with downregulation of a pathogenic inflammatory response, thus contributing to attenuation of MERS-CoV-MA-Δ4b.
- |||||||||| Journal: Argpyrimidine bonded to RAGE regulates autophagy and cell cycle to cause periodontal destruction. (Pubmed Central) - Sep 29, 2022
APMD-induced autophagy, G0/G1 arrest, pro-inflammatory signals activating and periodontal destruction were reversed by RAGE knockdown while aggravated by PI3K inhibitor. This study provides the first evidence that APMD bind to RAGE to regulate autophagy and cell cycle of PDLCs through the PI3K/AKT/mTOR pathway, thereby promoting periodontal destruction.
- |||||||||| Journal: Norcantharidin induces ferroptosis via the suppression of NRF2/HO-1 signaling in ovarian cancer cells. (Pubmed Central) - Sep 29, 2022
More importantly, it was revealed that nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase 1 (HO-1), glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (xCT) expression levels were significantly decreased following NCTD treatment. Collectively, NCTD may represent a potent anticancer agent in OC cells, and NCTD-induced ferroptotic cell death may be achieved by inhibiting the NRF2/HO-1/GPX4/xCT axis.
- |||||||||| Serine and one-carbon metabolism adapting glioma cells to low glutamine microenvironment (West/Central Hall) - Sep 28, 2022 - Abstract #SNO2022SNO_1186;
In clinical samples, MTHFD2 expression was highest in the nutrient-poor areas around "pseudopalisading necrosis." Genetic and pharmacological suppression of MTHFD2 caused tumor cell death and growth inhibition of glioma cells upon glutamine deprivation as well as autophagy inhibition did. These results may have important implications for serine-dependent one-carbon metabolism for glioma cells to survive glutamine starvation and suggest a new therapeutic strategy for patients with malignant glioma.
- |||||||||| sirolimus / Generic mfg.
Journal: Staufen impairs autophagy in neurodegeneration. (Pubmed Central) - Sep 25, 2022 STAU1 interaction with mTOR drives its hyperactivation and inhibits autophagic flux in multiple models of neurodegeneration. Staufen, therefore, constitutes a novel target to modulate mTOR activity, autophagy, and for the treatment of neurodegenerative diseases.
- |||||||||| temozolomide / Generic mfg.
Journal, PARP Biomarker, Epigenetic controller: A Selective Histone Deacetylase Inhibitor Induces Autophagy and Cell Death via SCNN1A Downregulation in Glioblastoma Cells. (Pubmed Central) - Sep 25, 2022 We found that the HDAC4/HDAC5 inhibitor LMK235 at 0.5 µM significantly reduced the cell viability and colony formation of patient-derived, temozolomide-resistant GBM P#5 TMZ-R, U-87 MG, and T98G cells...Cell viability of SCNN1A-silenced cells were reduced, but cells were rescued while treated with an autophagy inhibitor bafilomycin A1. Conclusively, SCNN1A plays a role in LMK235-induced autophagy and cell death in GBM cells.
- |||||||||| Journal: HO-1/autophagic flux axis alleviated sepsis-induced acute lung injury via inhibiting NLRP3 inflammasome. (Pubmed Central) - Sep 24, 2022
Autophagic flux activator could suppress NLRP3 inflammasome activation and attenuate ALI, while autophagic flux inhibitor had the opposite effect. In conclusion, our study revealed increased HO-1 expression inhibited the level of NLRP3 inflammasome via regulating the activation of autophagic flux, thus attenuating inflammatory response and alleviating sepsis-induced ALI.
- |||||||||| Review, Journal: Effects of polymer carriers on the occurrence and development of autophagy in drug delivery. (Pubmed Central) - Sep 23, 2022
Interaction of autophagic flux or the signal pathway with macromolecules may cause autophagy inhibition or autophagy cell death. This review covers autophagy regulation pathways and macromolecular materials (including functional micelles, biodegradable and pH-sensitive polymers, biomacromolecules, dendrimers, coordination polymers, and hybrid nanoparticles) mediated autophagy modulation.
- |||||||||| cisplatin / Generic mfg., doxorubicin hydrochloride / Generic mfg.
Journal: Cathepsin L promotes chemresistance to neuroblastoma by modulating serglycin. (Pubmed Central) - Sep 23, 2022 Taken together, our findings indicate that the CTSL promotes chemoresistance to cisplatin and doxorubicin by up-regulating the expression of multi-drug resistance proteins and inhibiting the autophagy level and cell apoptosis in NB cells. Thus, CTSL may be a therapeutic target for overcoming chemoresistant to cisplatin and doxorubicin in NB patients.
- |||||||||| cyclophosphamide / Generic mfg.
Biomarker, Journal, Tumor microenvironment, IO biomarker: He-Wei Granule enhances anti-tumor activity of cyclophosphamide by changing tumor microenvironment. (Pubmed Central) - Sep 21, 2022 In addition, CD34 and EGFR immunohistochemistry assay suggest that high dose HWKL could significantly decrease micro-vessel density (MVD) and inhibit angiogenesis in H22 carcinoma. It can be concluded that high-dose HWKL enhanced CTX efficacy by promoting apoptosis, inhibiting autophagy and angiogenesis in tumor tissue while significantly alleviated CTX-induced toxicity, and could be applied along with CTX in clinical treatment as a supplement agent.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal: Britannin mediates apoptosis and glycolysis of T-cell lymphoblastic lymphoma cells by AMPK-dependent autophagy. (Pubmed Central) - Sep 21, 2022 Moreover, britannin promoted apoptosis and reduced glycolysis of T-LBL cells, which was reversed by the typical autophagic inhibitor chloroquine...Moreover, the induction of autophagy in T-LBL cells by britannin was restrained by Compound C, the inhibitor of AMPK. Taken together, britannin mediated apoptosis and glycolysis of T-LBL cells in an autophagy-dependent manner, which was achieved by regulating AMPK/mTOR/S6K1 signaling, demonstrating its therapeutic potential against T-LBL.
- |||||||||| Journal: Novel Bcl-2 Inhibitors Selectively Disrupt the Autophagy-Specific Bcl-2-Beclin 1 Protein-Protein Interaction. (Pubmed Central) - Sep 20, 2022
Our NMR analysis showed that compound 35 directly binds Bcl-2 and specifically inhibits the interaction between the Bcl-2 and Beclin 1 BH3 domains without disruption of the Bcl-2-Bax BH3 interaction. More broadly, this proof-of-concept study demonstrates that targeting protein-protein interactions of the intrinsic autophagy regulatory network can serve as a valuable strategy for the development of autophagy-based therapeutics.
- |||||||||| Torin1 / InvivoGen
Journal: Impaired Autophagy Response in Hepatocellular Carcinomas Enriches Glypican-3 in Exosomes, Not in the Microvesicles. (Pubmed Central) - Sep 20, 2022 The impact of autophagy modulation on GPC3 enrichment in exosomes and microvesicles was assessed by treating cells with Torin 1 and Bafilomycin A1...The frequency of GPC3-positive exosomes was higher in patients with HCC (12.4%) compared to exosomes isolated from non-cirrhotic and healthy controls (3.7% and 1.3% respectively, p<0.001). Our results show that GPC3 is enriched in the endolysosomal compartment and released in exosome fractions when autophagy is impaired.
- |||||||||| ABSK091 / Abbisko
Journal: AZD4547 and the Alleviation of Hepatoma Cell Sorafenib Resistance via the Promotion of Autophagy. (Pubmed Central) - Sep 20, 2022 Furthermore, 3-methyladenine inhibited autophagy and reversed the killing effect of the combination of AZD4547 and Sorafenib on Huh7R cells. Conclusion The inhibition of fibroblast growth factor receptor activity by AZD4547 can significantly enhance autophagy and immune response, as well as promote the death of Sorafenib-resistant hepatoma cells.
- |||||||||| chloroquine phosphate / Generic mfg.
Journal, IO biomarker: Rhein induces changes in the lysosomal compartment of HeLa cells. (Pubmed Central) - Sep 20, 2022 Inhibition of autophagy was done using chloroquine...Rhein also induced DNA damage and led to cycle arrest in the S phase. Our results indicate that rhein, by inducing changes in the lysosomal compartment, indirectly affects apoptosis of HeLa cells and in combination with autophagy inhibitors may be an effective form of anticancer therapy.
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