- |||||||||| Journal: Geniposide protection against Aβ toxicity correlates with mTOR inhibition and enhancement of autophagy. (Pubmed Central) - Nov 10, 2021
Results showed that Akt and mTOR's geniposide inhibited phosphorylation induced by Aβ, enhanced expression of the LC3II/LC3I ratio, and Atg7 and Beclin1 expression and inhibited expression of p62 induced by Aβ. Our results lead us to hypothesize that inhibition of the Akt/mTOR signaling pathway and autophagy enhancement are fundamental molecular mechanisms for geniposide to protect against Aβ toxicity.
- |||||||||| Journal: The Key Role of Autophagy in Silver Nanoparticle-Induced BV2 Cells Inflammation and Polarization. (Pubmed Central) - Nov 10, 2021
Inhibition of autophagy also increased the expression of inflammation-associated mRNA and proteins in BV2 cells. These results indicated that AgNPs could induce pro-inflammatory phenotypic polarization of microglia and the autophagy could play a key regulatory role in the pro-inflammatory phenotypic polarization of microglia induced by AgNPs.
- |||||||||| Journal: Diosmin Inhibits Glioblastoma Growth through Inhibition of Autophagic Flux. (Pubmed Central) - Nov 10, 2021
Importantly, diosmin did not exert serious cytotoxic effects toward control SVG-p12 astrocytes, though it did reduce astrocyte viability at high concentrations. These findings provide potentially helpful support to the development of new therapies for the treatment of GBM.
- |||||||||| sirolimus / Generic mfg.
Preclinical, Journal: Mycoplasma bovis subverts autophagy to promote intracellular replication in bovine mammary epithelial cells cultured in vitro. (Pubmed Central) - Nov 10, 2021 In contrast, activation of autophagy (with rapamycin or HBSS) overcame the M. bovis-induced blockade in phagosome maturation by increasing delivery of M. bovis to the lysosome, with a concurrent decrease in intracellular M. bovis replication...Therefore, we conclude that M. bovis subverted autophagy to promote its intracellular replication in bMEC. These findings are the impetus for future studies to further characterize interactions between M. bovis and mammalian host cells.
- |||||||||| Preclinical, Journal: Effect of lactate administration on mouse skeletal muscle under calorie restriction. (Pubmed Central) - Nov 10, 2021
Next, we found that lactate administration under calorie restriction enhanced mitochondrial enzyme activity (citrate synthase and succinate dehydrogenase) and the expression of oxidative phosphorylation (OXPHOS) protein expression. Our results suggest that lactate administration under caloric restriction not only suppresses muscle atrophy but also improves mitochondrial function.
- |||||||||| Review, Journal: Klotho as Potential Autophagy Regulator and Therapeutic Target. (Pubmed Central) - Nov 7, 2021
The present review examines the role of Klotho in regulating autophagy in Alzheimer's disease, kidney injury, cancer, COPD, vascular disease, muscular dystrophy and diabetes. Targeting Klotho may provide a new perspective for preventing and treating aging-related diseases.
- |||||||||| cisplatin / Generic mfg.
Journal, IO biomarker: miR-4486 reverses cisplatin-resistance of colon cancer cells via targeting ATG7 to inhibiting autophagy. (Pubmed Central) - Nov 7, 2021 Additionally, ATG7 was identified to be a target gene of miR-4486, where ATG7 overexpression could partially reverse the effects of miR-4486 on cell viability and apoptosis by promoting the formation of autophagosomes. In conclusion, the present results demonstrated that miR-4486 could reverse DDP resistance in HCT116/DDP and SW480/DDP cells by targeting ATG7 to inhibit autophagy.
- |||||||||| CEP-11981 / Teva
Journal, Checkpoint inhibition, IO biomarker: Autophagy Inhibition by Targeting PIKfyve Potentiates Response to Immune Checkpoint Blockade in Prostate Cancer. (Pubmed Central) - Nov 7, 2021 PIKfyve-knockdown recapitulated ESK981's anti-tumor activity and enhanced the therapeutic benefit of immune checkpoint blockade. Our study reveals that targeting PIKfyve via ESK981 turns tumors from cold into hot through inhibition of autophagy, which may prime the tumor immune microenvironment in advanced prostate cancer patients and be an effective treatment strategy alone or in combination with immunotherapies.
- |||||||||| Journal: Combined Inhibition of p38MAPK and PIKfyve Synergistically Disrupts Autophagy to Selectively Target Cancer Cells. (Pubmed Central) - Nov 6, 2021
Combined inhibition of PIKfyve and p38MAPK activities synergistically blocked autophagy-mediated protein degradation, prevented cathepsin maturation, and markedly reduced the viability of multiple cancer cell types without affecting the viability of normal cells. Furthermore, combined PIKfyve and p38MAPK inhibitors synergistically reduced tumor growth in mice bearing xenografts of human colorectal adenocarcinoma, suggesting a novel way to target cancer cells by prolonged inhibition of autophagy using lower drug concentrations.
- |||||||||| Journal, PARP Biomarker, IO biomarker: Eupafolin induces autophagy and apoptosis in B-cell non-Hodgkin lymphomas. (Pubmed Central) - Nov 6, 2021
Furthermore, combined PIKfyve and p38MAPK inhibitors synergistically reduced tumor growth in mice bearing xenografts of human colorectal adenocarcinoma, suggesting a novel way to target cancer cells by prolonged inhibition of autophagy using lower drug concentrations. Together, these results provide crucial evidences explaining the antitumour activity of eupafolin in human NHL cell line, OCI-LY-3.
- |||||||||| cisplatin / Generic mfg., temozolomide / Generic mfg.
Clinical, Journal: Temozolomide abrogates the aggressiveness of urothelial carcinoma cells by enhancing senescence and depleting the side population. (Pubmed Central) - Nov 6, 2021 TMZ is an alkylating agent with a target different from that of other anticancer drugs used to treat UC, such as cisplatin...Inhibiting the autophagic response using chloroquine synergistically augmented the cytotoxic effect of TMZ on UC cells...Considering that side population fraction is known to confer therapeutic resistance, it is noteworthy that the TMZ treatment markedly decreased side population fraction. Altogether, TMZ may have the potential to be applied as a part of an alternative treatment strategy to reduce the malignancy of UC cells.
- |||||||||| Journal: Induction of osteoclast formation by LOX mutant (LOXG473A) through regulation of autophagy. (Pubmed Central) - Nov 5, 2021
However, autophagy agonist RAPA reversed the effect of 3-MA on RAW264.7 with LOX mutation, indicating that promoting autophagy could enhance the ability of LOX to induce osteoclast formation. LOX mutant (LOX) might promote osteoclast formation for RAW264.7 by enhancing autophagy via the AMPK/mTOR pathway, which is a new direction for bone disease research.
- |||||||||| dexamethasone / Generic mfg., nintedanib / Generic mfg.
Targeting JAK2 Gene Rearrangements with a Novel Kinase Inhibitor in a Preclinical Model of Pediatric Acute Lymphoblastic Leukemia (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_2739; In combination with dexamethasone, we assessed a further decrease of viability between 10 to 95%...Importantly, combination of BIBF1120 and CHZ868 showed a synergistic effect (-45%, at IC50)...Indeed, active caspase 3 increased when ruxolitinib was given in combination with chloroquine, an autophagy inhibitor (+20% vs ruxolitinib alone, p<0.01)...CHZ868 is a promising candidate for treatment of BCP-ALL carrying JAK2 fusions, showing high efficacy and specificity, both ex vivo and in vivo . Further studies will include combination with standard chemotherapy drugs with the aim to maintain its efficacy by reducing the intensity and toxicity of chemotherapy.
- |||||||||| chloroquine phosphate / Generic mfg., bleomycin / Generic mfg.
Journal: Hirsutella sinensis mycelium regulates autophagy of alveolar macrophages via TLR4/NF-κB signaling pathway. (Pubmed Central) - Nov 5, 2021 The protective effect of HSM on macrophages of bleomycin (BLM)-induced pulmonary fibrotic mice remain unclear...In vitro, autophagosomes-lysosome fusion inhibitor chloroquine (CQ) was pre-incubated with RAW264.7 cells, and HSM reduced CQ-induced autophagosomes accumulation...In addition, the protein expressions of TLR4 and phospho-NF-κB p65 were markedly inhibited in cells treated with HSM. These results indicated that HSM could inhibit the autophagy of alveolar macrophages through TLR4/NF-κB signaling pathway to achieve anti-fibrotic effect.
- |||||||||| Journal, PARP Biomarker, IO biomarker: Arctigenin-mediated cell death of SK-BR-3 cells is caused by HER2 inhibition and autophagy-linked apoptosis. (Pubmed Central) - Nov 4, 2021
Inhibition of ER-to-mitochondria Ca transfer may represent a general therapeutic strategy against cancer cells regardless of their OXPHOS status. Taken together, this study indicates that autophagy-linked apoptosis is responsible for the anti-cancer activity of ATG in SK-BR-3 cells, and suggests that ATG is considered a potential therapeutic for the treatment of HER2-overexpressing breast cancer.
- |||||||||| cisplatin / Generic mfg., paclitaxel / Generic mfg.
Journal: BET inhibitors combined with chemotherapy synergistically inhibit the growth of NSCLC cells. (Pubmed Central) - Nov 4, 2021 Mechanistically, this combination of suppression of BET expression and chemotherapeutic treatment blocked NSCLC cell growth by inhibiting autophagy and promoting apoptosis, which were revealed by both western blot and ELISA results. The present findings revealed a new rationale for using a combination of BET inhibitors with chemotherapy in NSCLC treatment.
- |||||||||| Piqray (alpelisib) / Novartis
Preclinical, Journal: Effects of PI3K inhibition in AI-resistant breast cancer cell lines: autophagy, apoptosis, and cell cycle progression. (Pubmed Central) - Nov 4, 2021 These findings demonstrate that autophagy is indispensable for tissue homeostasis and regeneration in planarians and that 3-MA treatment is detrimental to planarian regeneration via its effect on the autophagy pathway. These results corroborate the lack of cross-resistance between AIs verified in the clinic, excluding autophagy as a mechanism of resistance to Ana or Let and supporting the ongoing clinical trials combining BYL-719 with AIs.
- |||||||||| Desferal (deferoxamine) / Kermanshah University of Medical Sciences, Novartis
Journal: Iron-Dependent Autophagic Cell Death Induced by Radiation in MDA-MB-231 Breast Cancer Cells. (Pubmed Central) - Nov 1, 2021 Iron chelator deferoxamine (DFO), the autophagy inhibitor 3MA, silencing of the autophagy-related genes ATG5, and Beclin 1 could decrease radiation induced cell death in MDA-MB-231 cells, while inhibitors of apoptosis such as Z-VAD-FMK, ferroptosis inhibitor ferrostatin-1 (Fer-1), and necroptosis inhibitor Necrostatin-1 showed no change...To summarize, for the first time, we found that radiation-induced autophagic cell death was iron-dependent in breast cancer MDA-MB-231 cells. These results provide new insights into the cell death process of cancers and might conduce to the development and application of novel therapeutic strategies for patients with apoptosis-resistant breast cancer.
- |||||||||| [VIRTUAL] EDU 26 - Radiation, Autophagy, and Senescence in Tumor Response: Mechanisms and Clinical Implications (McCormick Place West, Room W179 a/b) - Oct 30, 2021 - Abstract #ASTRO2021ASTRO_2380;
The speakers will demonstrate the important roles of cellular signaling, DNA repair, and the immune response in regulating the role of autophagy in radiation resistant tumors such as pancreatic, head and neck, and NSC lung cancers. To participate in Q&A or polls go to www.astro.org/AMSocialQA Understand the process of autophagy in supporting tumor cell growth Understand how autophagy may contribute to radiation resistance Understand the role of autophagy in tumor DNA repair and immune response
- |||||||||| Journal: Salmonella spvC Gene Inhibits Autophagy of Host Cells and Suppresses NLRP3 as Well as NLRC4. (Pubmed Central) - Oct 30, 2021
Together, our observations reveal a novel mechanism of spvC in Salmonella pathogenesis and host inflammatory response via inhibiting autophagy and NLRP3 as well as NLRC4. These pathways and their subversion by diverse pathogen virulence determinants are expected to throw light on the design of anti-infective agents.
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