- |||||||||| Biomarker, Review, Journal: Tumors Responsive to Autophagy-Inhibition: Identification and Biomarkers. (Pubmed Central) - Sep 4, 2020
In this context, we review the current literature on tumor (sub)types with elevated dependence on autophagy for their survival and highlight an exploitable vulnerability. We provide an inventory of microenvironmental factors, genetic alterations and therapies that may be exploited with autophagy-targeted approaches to improve efficacy of conventional anti-tumor therapies.
- |||||||||| Review, Journal: Epigenetic Control of Autophagy in Cancer Cells: A Key Process for Cancer-Related Phenotypes. (Pubmed Central) - Sep 2, 2020
Altogether, these recent data strongly support the idea that the determination of autophagy status could be crucial for future anticancer therapies. Indeed, the use of a combination of epidrugs and autophagy inhibitors could be beneficial for some cancer patients, whereas, in other cases, an increase of autophagy, which is frequently observed following the use of epidrugs, could lead to increased autophagy cell death.
- |||||||||| sirolimus / Generic mfg.
Journal: Sphingolipid-mediated inflammatory signaling leading to autophagy inhibition converts erythropoiesis to myelopoiesis in human hematopoietic stem/progenitor cells. (Pubmed Central) - Sep 2, 2020 The neutral SMase inhibitor GW4869 as well as the genetic inhibition of nSMase with small interfering RNA (siRNA) against sphingomyelin phosphodiesterase 3 (SMPD3) prevented the inhibition by TNFα, but not the acid SMase inhibitor desipramine...Moreover, rapamycin prevented the inhibitory effect of TNFα and ceramides on erythropoiesis while inhibiting induction of myelopoiesis...We demonstrate here that the TNFα/neutral SMase/ceramide pathway inhibits erythropoiesis to induce myelopoiesis via modulation of a hematopoietic TF/miR network and inhibition of late steps of autophagy. Altogether, our results reveal an essential role of autophagy in erythroid vs. myeloid differentiation.
- |||||||||| sirolimus / Generic mfg.
Journal: Acteoside inhibits autophagic apoptosis of retinal ganglion cells to rescue glaucoma-induced optic atrophy. (Pubmed Central) - Sep 2, 2020 Our results indicate that ICA prevents OVX-induced bone loss possibly by strengthening the osteogenic differentiation of BMSCs via increasing autophagic activity. In summary, we conclude that Acteoside inhibits autophagy-induced apoptosis in RGCs through the OPTN and PI3K/AKT/mTOR pathway, and glaucoma patients may benefit from Acteoside treatment alone or in combination with other autophagy inhibitors.
- |||||||||| Journal: Low-dose nicotine promotes autophagy of cardiomyocytes by upregulating HO-1 expression. (Pubmed Central) - Sep 1, 2020
Furthermore, low-dose nicotine improved the inhibited autophagy and increased apoptosis induced by palmitic acid (PA) in NMCMs and these effects were reversed by knocking down HO-1. In conclusion, our data suggested that low-dose nicotine promoted autophagy and inhibited apoptosis of cardiomyocytes by upregulating HO-1.
- |||||||||| sirolimus / Generic mfg.
Journal: Prolonged tau clearance and stress vulnerability rescue by pharmacological activation of autophagy in tauopathy neurons. (Pubmed Central) - Sep 1, 2020 These compounds are more potent than rapamycin, and robustly downregulate phosphorylated and insoluble tau, consequently reducing tau-mediated neuronal stress vulnerability...Notably, single-dose treatment followed by washout leads to a prolonged reduction of tau levels and toxicity for 12 days, which is mirrored by a sustained effect on mTORC1 inhibition and autophagy. This new insight into the pharmacodynamics of mTOR inhibitors in regulation of neuronal autophagy may contribute to development of therapies for tauopathies.
- |||||||||| Journal: Mechanical Stress-Dependent Autophagy Components Release via Extracellular Nanovesicles in Tumor Cells. (Pubmed Central) - Aug 30, 2020
More importantly, either increasing intracellular autophagosome accumulation or inhibiting autophagic degradation promoted AP-MVB accumulation but not induce autophagy-associated protein release via EVs expect under ASS, demonstrating the existence of a mechanical stress-dependent compensation pathway. Together, these findings revealed that EVs provide an additional protection mechanism for tumor cells and counteract autophagy to maintain cellular homeostasis under acute shear stress.
- |||||||||| sirolimus / Generic mfg.
Journal: Leucine regulates autophagy via acetylation of the mTORC1 component raptor. (Pubmed Central) - Aug 30, 2020 The mechanistic target of rapamycin complex 1 (mTORC1) is a well-conserved negative regulator of autophagy...Interestingly, in Leu deprivation conditions, the dominant effects on autophagy are mediated by decreased raptor acetylation causing mTORC1 inhibition, rather than by altered acetylation of other autophagy regulators. Thus, in most cell types we examined, Leu regulates autophagy via the impact of its metabolite AcCoA on mTORC1, suggesting that AcCoA and EP300 play pivotal roles in cell anabolism and catabolism.
- |||||||||| Jardiance (empagliflozin) / Eli Lilly, Boehringer Ingelheim
SGLT2 inhibitors contribute to renal protection in obesity-induced renal injury () - Aug 30, 2020 - Abstract #JSN2020JSN_814; In the past, we have shown the therapeutic effect of Empagliflozin on renal damage in obesity...[Method] 5-week-old C57BL/6J mice were bred for 10 weeks in a normal diet (ND) group and a high-fat diet (HFD) group, and Canagliflozin 10 mg/kg (Cana) or 0.5% HPMC (Control) of a solvent was used for 7 weeks... The therapeutic effect of SGLT2 inhibitor on autophagy failure of PTC in obesity was suggested.
- |||||||||| Autophagy controls albumin reabsorption in renal tubules () - Aug 30, 2020 - Abstract #JSN2020JSN_111;
Addition of BSA increased KIM-1 release from autophagy-inhibited cells. [Conclusion] It was suggested that inhibition of autophagy could inhibit albumin transcytosis in renal tubules due to impaired FcRn transport, resulting in tubular cell damage.
- |||||||||| everolimus / Generic mfg.
[VIRTUAL] Autophagy attenuates renal allograft interstitial fibrosis by regulating the EndMT induced by TNF-α (E-Poster Hall) - Aug 29, 2020 - Abstract #TTS2020TTS_968; Rat renal transplant model was established and intervened with different dose Everolimus, a specific inducer of autophagy, we found same results with human and the progression of EndMT and allograft interstitial fibrosis in low dose Everolimus group was significant reduced...In conclusion, autophagy plays a critical role in the development of EndoMT induced by TNF-α. Autophagy could be suggested as a novel target for the prevention and treatment of renal allograft interstitial fibrosis.
- |||||||||| Journal: Leishmania donovani parasite requires Atg8 protein for infectivity and survival under stress. (Pubmed Central) - Aug 29, 2020
This buildup was prevented when mitochondria generated reactive oxygen species that were quenched, suggesting them as possible signaling molecules for sensing mitochondrial instability. In summary, our study provides new evidences for a crucial role of Atg8 protein in sustaining Leishmania parasite survival during life cycle and stress exposure, differentiation to amastigotes, and their infective abilities.
- |||||||||| Journal, IO Biomarker: MLK3 silence induces cervical cancer cell apoptosis via the Notch-1/autophagy network. (Pubmed Central) - Aug 27, 2020
By co-treating Hela cells with MLK3 specific siRNA and pcDNA3.1-Notch-1 overexpression plasmid or autophagy inhibitor 3-MA, we found that MLK3 played its role in cervical cancer cells via the Notch-1/autophagy network. Our results demonstrate the importance of MLK3 in cervical cancer progression via modulating the Notch-1/autophagy network, and suggest that MLK3 is a promising therapeutic target for cervical cancer.
- |||||||||| omipalisib (GSK2126458) / GSK, chloroquine phosphate / Generic mfg., buparlisib (BKM120) / Novartis, Adlai Nortye
Journal: Dual Inhibition of Autophagy and PI3K/AKT/MTOR Pathway as a Therapeutic Strategy in Head and Neck Squamous Cell Carcinoma. (Pubmed Central) - Aug 24, 2020 We used acridine orange staining, immunoblotting, and tandem sensor Red Fluorescent Protein- Green Fluorescent Protein-, microtubule-associated protein 1 light chain 3 beta (RFP-GFP-LC3B) expression analysis to show that PI3K inhibitors increase autophagosomes in HNSCC cells, but that chloroquine treatment effectively inhibits the autophagy that is induced by PI3K inhibitors...Our results indicate that a strategy focusing on autophagy inhibition enhances the efficacy of therapeutics already in clinical trials. Our results suggest a broader application for this combination therapy that can be promptly translated to in vivo studies.
- |||||||||| Journal: The RAGE/STAT5/autophagy axis regulates senescence in mesangial cells. (Pubmed Central) - Aug 23, 2020
In conclusion, we found AGEs induced inhibition of autophagy and cellular senescence in mesangial cells via the RAGE/STAT5 pathway. Moreover, we found that RAGE/STAT5 acts as a key link between autophagy and senescence in the process of mesangial aging in vivo and in vitro.
- |||||||||| Alunbrig (brigatinib) / Takeda
Journal: Repurposing Brigatinib for the Treatment of Colorectal Cancer Based on Inhibition of ER-phagy. (Pubmed Central) - Aug 23, 2020 As such, combination of brigatinib with autophagy inhibitors significantly enhances the anti-CRC effect of brigatinib both in vitro and in vivo, supporting the repurposing of brigatinib in CRC, independently of ALK. The unearthed new molecular action of brigatinib suggests that therapeutic modulation of ER stress and autophagy might represent a valid strategy to treat CRC and perhaps other ALK-negative cancers.
- |||||||||| Journal: Stromal cells downregulate miR-23a-5p to activate protective autophagy in acute myeloid leukemia. (Pubmed Central) - Aug 23, 2020
Our work also demonstrates that this mechanism of bone marrow stromal cell mediated regulation of miR-23a-5p levels and subsequent molecular events are relevant predominantly in myeloid leukemia. Our results illustrate the critical and dynamic role of the bone marrow microenvironment in modulating miRNA expression in leukemic cells which could contribute significantly to drug resistance and subsequent relapse, possibly through persistence of minimal residual disease in this environment.
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