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- | Journal: Receptor-Interacting Protein Kinase 3 (RIPK3) inhibits autophagic flux during necroptosis in intestinal epithelial cells. (Pubmed Central) - May 6, 2021
These data indicate that necroptosis attenuates autophagic flux before the lysosome fusion step. Our findings may provide insights into human diseases involving necroptosis.
- | Journal: IL-17 Induced Autophagy Regulates Mitochondrial Dysfunction and Fibrosis in Severe Asthmatic Bronchial Fibroblasts. (Pubmed Central) - May 6, 2021
Taken together, our findings suggest that IL-17 induced autophagy promotes mitochondrial dysfunction and fibrosis in bronchial fibroblasts from both non-asthmatic and severe asthmatic subjects. Our study provides insights into the therapeutic potential of targeting autophagy in ameliorating fibrosis, particularly in severe asthmatic individuals.
- | chloroquine phosphate / Generic mfg.
Biomarker, Journal, Tumor microenvironment: Synergy of Tumor Microenvironment Remodeling and Autophagy Inhibition to Sensitize Radiation for Bladder Cancer Treatment. (Pubmed Central) - May 6, 2021
By taking advantage of the strong affinity between negatively charged MnO and positively charged chloroquine (CQ), the nanoparticles were fabricated by integrating MnO and CQ in human serum albumin (HSA)-based nanoplatform (HSA-MnO-CQ NPs)...Finally, a significant anti-tumor effect achieved by the enhanced autophagy inhibition and radiation sensitization. HSA-MnO-CQ NPs synergistically regulated the abnormal TME and inhibited autophagic flux, and effectively sensitized radiation therapy to treat bladder cancers.
- | sirolimus / Generic mfg.
Preclinical, Journal: Oxymatrine exerts a protective effect in myocardial ischemia/reperfusion‑induced acute lung injury by inhibiting autophagy in diabetic rats. (Pubmed Central) - May 6, 2021
These results indicated that diabetic lungs are more vulnerable to myocardial I/R, which was associated with aberrant autophagy. Furthermore, oxymatrine was observed to reverse and alleviate ALI in diabetic rats with myocardial I/R in a concentration‑dependent manner, the mechanism of which may be associated with the inhibition of autophagy.
- | hydroxychloroquine / Generic mfg.
Journal, Cancer stem cells: PIK3C3 Inhibition Promotes Sensitivity to Colon Cancer Therapy by Inhibiting Cancer Stem Cells. (Pubmed Central) - May 6, 2021
Moreover, specific and potent autophagy inhibitors are warranted as clinical trials with hydroxychloroquine have not been successful...Combination treatments were done using 5-fluorouracil (5-FU) and 36-077...Mechanistic studies revealed that combination therapy inhibited GSK-3β/Wnt/β-catenin signaling to inhibit CSC population. Autophagy promotes resistance to CRC-therapy by specifically promoting GSK-3β/Wnt/β-catenin signaling to promote CSC survival, and 36-077, a PIK3C3/VPS34 inhibitor, helps promote efficacy of CRC therapy.
- | Journal: The SARS-CoV-2 protein ORF3a inhibits fusion of autophagosomes with lysosomes. (Pubmed Central) - May 6, 2021
These results indicated the potential mechanism by which SARS-CoV-2 escapes degradation; that is, the virus interferes with autophagosome-lysosome fusion. Furthermore, our findings will facilitate strategies targeting autophagy for conferring potential protection against the spread of SARS-CoV-2.
- | Journal: Decursin inhibits cell growth and autophagic flux in gastric cancer via suppression of cathepsin C. (Pubmed Central) - May 6, 2021
We established spheroid and patient-derived organoid models and found that decursin decreased the growth of spheroids and patient-derived gastric organoids, as well as modulated the expression of CTSC and autophagy-related proteins. Hence, our findings uncovered a previously unknown mechanism by which decursin regulates cell growth and autophagy and suggests that decursin may act as a potential therapeutic agent that simultaneously inhibits cell growth and autophagy.
- | chloroquine phosphate / Generic mfg.
Journal, PARP Biomarker: A therapeutic approach with combination of interferon-gamma and autophagy inhibitor for oral squamous cell carcinoma. (Pubmed Central) - May 6, 2021
The synergistic effect of interferon-gamma and autophagy inhibitor (chloroquine) was evaluated in vitro and in vivo...Our findings suggest that Interferon-gamma-induced autophagy plays a cellular protective role, and blocking autophagy flux can promote Interferon-gamma mediated oral squamous cell carcinoma cell apoptosis. The combination of Interferon-gamma and autophagy inhibitors represents a novel strategy for oral squamous cell carcinoma therapy.
- | Journal: Penehyclidine hydrochloride alleviates lipopolysaccharide‑induced acute respiratory distress syndrome in cells via regulating autophagy‑related pathway. (Pubmed Central) - May 5, 2021
In addition, 3‑MA reversed the effects of PHC on proliferation, inflammation, apoptosis and autophagy in LPS‑induced BEAS‑2B cells. Therefore, the present study suggested that PHC demonstrated a protective effect in LPS‑induced ARDS by regulating an autophagy‑related pathway.
- | paclitaxel / Generic mfg.
Journal, PARP Biomarker: WWOX promotes apoptosis and inhibits autophagy in paclitaxel‑treated ovarian carcinoma cells. (Pubmed Central) - May 5, 2021
Finally, the interaction between WWOX, mTOR and autophagy was investigated via WWOX transfection experimentation, and indicated that WWOX activated mTOR whilst inhibiting autophagy. These data indicated that WWOX may serve a critical role in PTX‑induced apoptosis and could suppress autophagy by downregulating essential autophagic effectors in EOC cells via mTOR signaling.
- | Journal: Knockdown of FAM225B inhibits the progression of the hypertrophic scar following glaucoma surgery by inhibiting autophagy. (Pubmed Central) - May 5, 2021
Therefore, knockdown of FAM225B could inhibit scar fibroblast proliferation after glaucoma surgery by inhibiting autophagy. These findings may provide a novel perspective of developing treatment strategy for the patients with HSs after glaucoma surgery.
- | chloroquine phosphate / Generic mfg.
Journal: Mfn2 is involved in intervertebral disc degeneration through autophagy modulation. (Pubmed Central) - May 4, 2021
These findings may provide a novel perspective of developing treatment strategy for the patients with HSs after glaucoma surgery. Mfn2 repression is deeply involved in the pathogenesis of IVDD with its impairment on autophagy, leading to the aggravation of mitochondrial dysfunction and apoptotic cell death, which ought to be a promising therapeutic target for IVDD.
- | chloroquine phosphate / Generic mfg.
Preclinical, Journal: Complementary autophagy inhibition and glucose metabolism with rattle-structured polydopamine@mesoporous silica nanoparticles for augmented low-temperature photothermal therapy and in vivo photoacoustic imaging. (Pubmed Central) - May 4, 2021
PDA@hm was then loaded with autophagy inhibitor chloroquine (CQ) and conjugated with glucose consumer glucose oxidase (GOx) (PDA@hm@CQ@GOx), forming a corona-like structure nanoparticle...Furthermore, the PDA nanocore in the PDA@hm@CQ@GOx could be also used for PA imaging. Such a "drugs" loaded rattle-structured nanoparticle could be used for augmented low-temperature PTT through complementarily regulating glucose metabolism and inhibiting autophagy and in vivo photoacoustic imaging.
- | cisplatin / Generic mfg.
Journal: MicroRNA‑22 regulates autophagy and apoptosis in cisplatin resistance of osteosarcoma. (Pubmed Central) - May 4, 2021
Furthermore, the in vitro and in vivo expression levels of metadherin (MTDH) in the OS/OS‑CDDP‑resistant models were downregulated following transfection with the miR‑22 mimic. Therefore, the results of the present study suggested that miR‑22 promoted CDDP sensitivity by inhibiting autophagy and inducing apoptosis in OS cells, while MTDH may serve a positive role in inducing CDDP resistance of OS cells.
- | Journal: Suppression Of Metacaspase- And Autophagy-Dependent Cell Death Improves Stress-Induced Microspore Embryogenesis In Brassica Napus. (Pubmed Central) - May 4, 2021
Accordingly, inhibition of autophagy and MCA activity, either individually or in combination, suppressed cell death and increased the number of proembryos, indicating that both components play a pro-cell death role and account for decreased efficiency of early embryonic development. Therefore, MCAs and/or autophagy can be used as new biotechnological targets to improve in vitro embryogenesis in Brassica species and doubled-haploid plant production in crop breeding and propagation programmes.
- | Journal: Synthesis and evaluation of new compounds bearing 3-(4-aminopiperidin-1-yl)methyl magnolol scaffold as anticancer agents for the treatment of non-small cell lung cancer via targeting autophagy. (Pubmed Central) - May 4, 2021
Moreover, blocking autophagy by the autophagic inhibitor enhanced the anticancer activity of 30in vitro and in vivo, suggesting autophagy played a cytoprotective role on 30-induced cancer cell death. Taken together, our study implied that compound 30 combined with autophagic inhibitor could be another choice for NSCLC treatment in further investigation.
- | chloroquine phosphate / Generic mfg.
Journal: Citrate activates autophagic death of prostate cancer cells via downregulation CaMKII/AKT/mTOR pathway. (Pubmed Central) - May 4, 2021
That citrate activates autophagic cell death of prostate cancer via downregulation CaMKII/AKT/mTOR pathway and without remarkable toxicity in mice. This study suggests that citrate might be a promising therapeutic agent for the treatment of prostate cancer.
- | Journal, IO biomarker: IL37 overexpression inhibits autophagy and apoptosis induced by hepatic ischemia reperfusion injury via modulating AMPK/mTOR/ULLK1 signalling pathways. (Pubmed Central) - May 4, 2021
This study suggests that citrate might be a promising therapeutic agent for the treatment of prostate cancer. Endogenous and exogenous IL37 were found to ameliorate hepatic ischemia reperfusion injury by inhibiting excessive autophagy and apoptosis, these effects may be connected with the modulation of AMPK/mTOR/ULK1 signalling complex.
- | paclitaxel / Generic mfg.
Journal: Guaiazulene Triggers ROS-Induced Apoptosis and Protective Autophagy in Non-small Cell Lung Cancer. (Pubmed Central) - May 4, 2021
Notably, GYZ acts synergistically with paclitaxel in the suppression of NSCLC in vitro. Together, our results for the first time reported that GYZ suppressed the proliferation of NSCLC and suggested a potential strategy for inhibiting NSCLC growth by combinational use of GYZ and autophagy inhibitors.
- | Preclinical, Journal: CRISPR/dCas9-Mediated Parkin Inhibition Impairs Mitophagy and Aggravates Apoptosis of Rat Nucleus Pulposus Cells Under Oxidative Stress. (Pubmed Central) - May 4, 2021
Furthermore, repression of Parkin significantly attenuated mitophagy and exacerbated apoptosis. These results suggested that Parkin may play a protective role in alleviating the apoptosis of NP cells via mitophagy, and that targeting Parkin may provide a promising therapeutic strategy for the prevention of IDD.
- | sirolimus / Generic mfg.
Preclinical, Journal: Epidermal growth factor regulation by autophagy-mediated lncRNA H19 in murine intestinal tract after severe burn. (Pubmed Central) - May 1, 2021
Rapamycin and 3-methyladenine (3-MA) were used to activate and inhibit autophagy, and the changes in LC3 and Beclin1 levels were assessed by Western blotting...Taken together, intestinal autophagy is activated after a serious burn, which can increase the transcription level of lncRNA H19. lncRNA H19 may regulate the repair of EGF via let-7g following intestinal mucosa injury after a burn.
- | sirolimus / Generic mfg.
Journal: Inhibition of autophagy by geniposide protects against myocardial ischemia/reperfusion injury. (Pubmed Central) - May 1, 2021
The effects of GP were blocked by rapamycin (RAPA) administration. In summary, our results showed that GP protected against myocardial I/R injury and involved inhibition of autophagy, which might be through activating AKT/mTOR signaling pathways.
- | doxycycline / Generic mfg., Pierre Fabre
Journal: Effect of autophagy on irradiation‑induced damage in osteoblast‑like MC3T3‑E1 cells. (Pubmed Central) - May 1, 2021
Furthermore, the ratio of phosphorylated P38/P38 was observed to be higher following DOX treatment within 1 week of irradiation, which was reversed 2 weeks post‑irradiation. In conclusion, DOX‑inhibited autophagy aggravated X‑ray irradiation‑induced apoptosis at an early stage, but maintained cell proliferation and mineralization at a late stage in irradiated MC3T3‑E1 cells.
- || Clinical, Journal: High Expression of IL-36γ in Influenza Patients Regulates Interferon Signaling Pathway and Causes Programmed Cell Death During Influenza Virus Infection. (Pubmed Central) - May 1, 2021
Overall, these findings demonstrated IL-36γ is a critical host immune factor in response to IAV infection. It has potential activity in the regulation of the interferon signaling pathway and was involved in different types of programmed cell death in human airway epithelial cells as well.
- | chloroquine phosphate / Generic mfg.
Journal, PARP Biomarker: Quinacrine-Induced Autophagy in Ovarian Cancer Triggers Cathepsin-L Mediated Lysosomal/Mitochondrial Membrane Permeabilization and Cell Death. (Pubmed Central) - May 1, 2021
Importantly, we showed that upregulation of CTSL in QC-treated HeyA8MDR xenografts corresponds with attenuation of p62, upregulation of LC3BII, cytochrome-c, tBid, cleaved PARP, and caspase3. Taken together, the data suggest that QC-induced autophagy and CTSL upregulation promote a positive feedback loop leading to excessive autophagic flux, LMP, and MOMP to promote QC-induced cell death in ovarian cancer cells.
- | thioridazine / Generic mfg., promethazine / Generic mfg.
Journal: Inhibition of Autophagy Enhances the Antitumor Effect of Thioridazine in Acute Lymphoblastic Leukemia Cells. (Pubmed Central) - May 1, 2021
AMPK/PI3K/AKT/mTOR and MAPK/ERK pathways are involved in TR-induced cell death. The inhibition of the autophagic process enhanced the cytotoxicity of TR in Jurkat cells, highlighting autophagy as a targetable process for drug development purposes in ALL.
- | sirolimus / Generic mfg.
Journal: Down-Regulation of the Proteoglycan Decorin Fills in the Tumor-Promoting Phenotype of Ionizing Radiation-Induced Senescent Human Breast Stromal Fibroblasts. (Pubmed Central) - May 1, 2021
Interestingly, the secretome from a series of both untreated and irradiated human breast cancer cell lines with different molecular profiles inhibited decorin expression in young and senescent stromal fibroblasts, which was annulled by SU5402, a bFGF and VEGF inhibitor. The novel phenotypic trait of senescent human breast stromal fibroblasts revealed here is added to their already described cancer-promoting role via the formation of a tumor-permissive environment.
- | 5-fluorouracil / Generic mfg.
Journal: Cancer-Associated Fibroblast-Derived IL-6 Determines Unfavorable Prognosis in Cholangiocarcinoma by Affecting Autophagy-Associated Chemoresponse. (Pubmed Central) - May 1, 2021
The novel phenotypic trait of senescent human breast stromal fibroblasts revealed here is added to their already described cancer-promoting role via the formation of a tumor-permissive environment. Our data support a therapeutic strategy that includes autophagy-enhancing drugs along with adjuvants limiting the stromal inflammation (i.e., the secretion of IL-6) to improve the survival of CCA patients.
- chloroquine phosphate / Generic mfg.
[VIRTUAL] Tumor-Responsive, Multifunctional CAR-NK Cells Cooperate with Impaired Autophagy to Infiltrate and Target Glioblastoma () - Apr 30, 2021 - Abstract #ASGCT2021ASGCT_150;
To address insufficient homing of NK cells into the tumor bed, we combined these cells with chloroquine (CQ) as an adjuvant to inhibit autophagy in GBM and evaluated these cells against patient-derived intracranial GBM models in vivo (Fig.1D)... We built a novel, sophisticated combinatorial platform for GBM: a multifunctional immunotherapy based on genetically-engineered, human NK cells bearing multiple anti-tumor functions, including local tumor responsiveness, that addresses, for the first time, key drivers of GBM resistance to therapy: antigen escape, immunometabolic reprogramming of immune responses, and poor immune cell homing.
- | Journal: LRP6 regulates Rab7-mediated autophagy through the Wnt/β-catenin pathway to modulate trophoblast cell migration and invasion. (Pubmed Central) - Apr 30, 2021
LRP6 promotes Rab7-mediated autophagy by activating the Wnt/β-catenin pathway, which leads to increasing migration and invasion of trophoblast cells. Our study paves a new avenue for clinical treatment, and LRP6 may serve as an essential target in pre-eclampsia.
- | Journal: miR-145 inhibits the proliferation and migration of vascular smooth muscle cells by regulating autophagy. (Pubmed Central) - Apr 30, 2021
In addition, we found that the sirtuins are not direct targets of miR-145 in the proliferation and migration of VSMCs. These results suggest that miR-145 inhibits the proliferation and migration of VSMCs by suppressing the activation of autophagy.
- | Erleada (apalutamide) / J&J
Journal, Combination therapy: Apalutamide in combination with autophagy inhibitors improves treatment effects in prostate cancer cells. (Pubmed Central) - Apr 30, 2021
These data demonstrate that treatment with ARN-509 leads to increased autophagy levels in LNCaP cells. Furthermore, in combination with autophagy inhibitors, ARN-509 provided a significantly elevated antitumor effect, thus providing a new therapeutic approach potentially translatable to patients.
- | Preclinical, Journal: Colonic Dopaminergic Neurons Changed Reversely With Those in the Midbrain via Gut Microbiota-Mediated Autophagy in a Chronic Parkinson's Disease Mice Model. (Pubmed Central) - Apr 30, 2021
In conclusion, colonic dopaminergic neurons changed in the opposition direction with those in the midbrain via GM dysbiosis-mediated autophagy inhibition followed by suppressed apoptosis in response to chronic MPTP injection. Such a chronic PD mice model might not be an ideal model to study role of gut-brain axis in PD progression.
- || chloroquine phosphate / Generic mfg.
Review, Journal: Repurposing Chloroquine Against Multiple Diseases With Special Attention to SARS-CoV-2 and Associated Toxicity. (Pubmed Central) - Apr 30, 2021
Though much of the hope has been created by chloroquine and its derivatives against multiple diseases, repurposing it against SARS-CoV-2 requires large scale, collaborative, randomized and unbiased clinical trials to avoid false promises. This review summarizes the use and the mechanism of chloroquine against multiple diseases, its side-effects, mechanisms and the different clinical trials ongoing against "COVID-19".
- carboplatin / Generic mfg., paclitaxel / Generic mfg.
[VIRTUAL] Cellworks Omics Biology Model (CBM) to identify amplifications of chromosome 11p and 1p predict paclitaxel and carboplatin resistance. () - Apr 29, 2021 - Abstract #ASCO2021ASCO_5387;
This review summarizes the use and the mechanism of chloroquine against multiple diseases, its side-effects, mechanisms and the different clinical trials ongoing against "COVID-19". This study highlights how CBM simulation platform can help to identify novel patient segments for therapy response prediction and use drug re-purposing to overcome chemotherapy resistance.
- Abraxane (albumin-bound paclitaxel) / BMS, Otsuka
[VIRTUAL] Intratumoral T cell clonality and survival in a randomized phase II study of preoperative autophagy inhibition in combination with gemcitabine and nab-paclitaxel treatment in patients with resectable pancreatic cancer. () - Apr 29, 2021 - Abstract #ASCO2021ASCO_4177;
P1/2, P2
Intratumoral αβ T cell receptor clonality was associated with CA 19-9 response and improved overall survival . Combination treatment regimens increasing PDAC specific CD8 responses are warranted.
- | Journal: Tributyltin(IV) ferulate, a novel synthetic ferulic acid derivative, induces autophagic cell death in colon cancer cells: From chemical synthesis to biochemical effects. (Pubmed Central) - Apr 29, 2021
The autophagy inhibitor bafylomicin A1 markedly prevented the effect of TBT-F on colon cancer cells, thus indicating that autophagy is triggered as a cell death process. Taken together, our results strongly suggest that the novel ferulic derivative TBT-F is a promising therapeutic agent for colon cancer since it is capable of triggering autophagic (type-II) cell death that may be important in case of resistance to classic apoptosis.
- | Journal: KRT8 phosphorylation regulates the epithelial-mesenchymal transition in retinal pigment epithelial cells through autophagy modulation. (Pubmed Central) - Apr 29, 2021
Knockdown the expression or mutagenesis of the critical phosphorylated site of KRT8 would induce autophagy impairment, through affecting the fusion of autophagosomes and lysosomes. Therefore, this study may provide a new insight into the pathogenesis of PVR and suggests the potential therapeutic value of p-KRT8 in the prevention and treatment of PVR.
- | Journal, IO biomarker: BNIP3 decreases the LPS-induced inflammation and apoptosis of chondrocytes by promoting the development of autophagy. (Pubmed Central) - Apr 29, 2021
Therefore, this study may provide a new insight into the pathogenesis of PVR and suggests the potential therapeutic value of p-KRT8 in the prevention and treatment of PVR. BNIP3 decreased the LPS-induced inflammation and apoptosis of chondrocytes by activating the autophagy.
- | gefitinib / Generic mfg.
Journal: The mechanism of mA methyltransferase METTL3-mediated autophagy in reversing gefitinib resistance in NSCLC cells by β-elemene. (Pubmed Central) - Apr 29, 2021
Furthermore, METTL3 positively regulated autophagy by increasing the critical genes of autophagy pathway such as ATG5 and ATG7. In conclusion, our study unveiled the mechanism of METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by β-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.
- | raloxifene hydrochloride / Generic mfg.
Journal: Raloxifene prevents stress granule dissolution, impairs translational control and promotes cell death during hypoxia in glioblastoma cells. (Pubmed Central) - Apr 29, 2021
Genetic disruption of the SG-nucleating proteins G3BP1 and G3BP2 revealed that G3BP1 is required to sustain the raloxifene-mediated delay in SG dissolution. Together, these findings indicate that modulating the stress response can be used to exploit the hypoxic niche of GBM tumors, causing cell death by disrupting pro-survival stress responses and control of protein synthesis.
- | Journal: PDK4 promotes vascular calcification by interfering with autophagic activity and metabolic reprogramming. (Pubmed Central) - Apr 29, 2021
In addition, glycolysis serves as a metabolic adaptation to improve VSMCs oxidative stress resistance, whereas inhibition of glycolysis by 2-deoxy-D-glucose induces the apoptosis of VSMCs and increases the calcium deposition in VSMCs. Our results suggest that PDK4 plays a key role in vascular calcification through autophagy inhibition and metabolic reprogramming.
- Ibrance (palbociclib) / Pfizer
[VIRTUAL] Phase I safety and efficacy study of autophagy inhibition with hydroxychloroquine to augment the antiproliferative and biological effects of preoperative palbociclib plus letrozole for estrogen receptor-positive, HER2-negative metastatic breast cancer (MBC). () - Apr 28, 2021 - Abstract #ASCO2021ASCO_1362;
P1/2
The RP2D of HCQ is 800 mg/day with continuous dosing palbociclib at 75 mg/day and letrozole at 2.5 mg/day . The phase 2 trial will proceed in the neoadjuvant setting, with Ki67 proliferative index response as the primary endpoint.
- hydroxychloroquine / Generic mfg.
[VIRTUAL] A phase II study investigating biological effects of maintenance usage of hydroxychloroquine on Par-4 levels in patients with resected tumors. () - Apr 28, 2021 - Abstract #ASCO2021ASCO_892;
P1
We also demonstrate trend of PFS benefit especially for subjects having 2-fold increase of Par-4 induction . Identification of tumors more Par-4 sensitive and predictive biomarkers of Par-4 induction are necessary to continue our investigation.
- | pioglitazone / Generic mfg.
Journal: Pioglitazone attenuates advanced glycation end products-induced apoptosis and calcification by modulating autophagy in tendon-derived stem cells. (Pubmed Central) - Apr 28, 2021
We further confirmed the effect of Pio on autophagy, which ameliorated apoptosis and abnormal calcification caused by AGEs both in vitro and in vivo. Thus, we suggest that Pio ameliorates the dysfunctions of TDSCs against AGEs by promoting autophagy, and we also reveal that Pio is a potential pharmacological choice for tendinopathy.
- | Journal: Glucose restriction delays senescence and promotes proliferation of HUVECs via the AMPK/SIRT1-FOXA3-Beclin1 pathway. (Pubmed Central) - Apr 28, 2021
siRNA knock down of AMPKα1, SIRT1, FOXA3 or Beclin1 expression impaired the glucose restriction-induced inhibition of senescence, enhanced autophagy, increased migration, and induced proliferation of HUVECs. This study confirmed that glucose restriction can enhance autophagy, inhibit senescence, and enhance proliferation of HUVECs through the AMPK/SIRT1-FOXA3-Beclin1 pathway.
- | Journal: Shrm4 contributes to autophagy inhibition and neuroprotection following ischemic stroke by mediating GABA receptor activation. (Pubmed Central) - Apr 28, 2021
GABA activation using baclofen further reduced OGD-induced neuron damage in culture and stroke outcomes of MCAO, relative to Shrm4 alone. Taken together, Shrm4-mediated GABA activation confers neuroprotection by reducing neuronal autophagy in acute ischemic stroke.
- | Nexavar (sorafenib) / Bayer, Amgen
Journal: Hypoxia induces sorafenib resistance mediated by autophagy via activating FOXO3a in hepatocellular carcinoma. (Pubmed Central) - Apr 28, 2021
Finally, knockout of intratumoral FOXO3a significantly enhanced curative efficacy of sorafenib via inhibition of autophagy in xenograft tumors in nude mice. Collectively, our study suggests that FOXO3a plays a key role in regulating hypoxia-induced autophagy in sorafenib-treated HCC, and FOXO3-targeted therapy may serve as a promising approach to improve clinical prognosis of patients suffering from HCC.
- | Journal: Isoquercitrin induces apoptosis and autophagy in hepatocellular carcinoma cells via AMPK/mTOR/p70S6K signaling pathway. (Pubmed Central) - Apr 28, 2021
By contrast, application of a broad-spectrum caspase inhibitor failed to inhibit autophagy in ISO-treated cells. These data indicate that ISO simultaneously induced apoptosis and autophagy, and abnormal induction of autophagic flux contributed to ISO-triggered caspase-3-dependent apoptosis.
- | Mekinist (trametinib) / Novartis, BeiGene, Tafinlar (dabrafenib) / Novartis, BeiGene
Trial completion date, Trial primary completion date, Metastases: COMBI-R2: Dabrafenib/Trametinib/Hydroxychloroquine for Advanced Pretreated BRAF V600 Mutant Melanoma (clinicaltrials.gov) - Apr 28, 2021
P2, N=63, Recruiting, Sponsor: Universitair Ziekenhuis Brussel
These data indicate that ISO simultaneously induced apoptosis and autophagy, and abnormal induction of autophagic flux contributed to ISO-triggered caspase-3-dependent apoptosis. Trial completion date: Dec 2020 --> Jul 2022 | Trial primary completion date: Feb 2020 --> Dec 2021