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https://www.readbyqxmd.com/read/28055301/autophagy-orchestrates-adaptive-responses-to-targeted-therapy-in-endometrial-cancer
#1
Núria Eritja, Bo-Juen Chen, Ruth Rodríguez-Barrueco, Maria Santacana, Sònia Gatius, August Vidal, Maria Dolores Martí, Jordi Ponce, Laura Bergadà, Andree Yeramian, Mario Encinas, Joan Ribera, Jaume Reventós, Jeff Boyd, Alberto Villanueva, Xavier Matias-Guiu, Xavier Dolcet, David Llobet-Navàs
Targeted therapies in endometrial cancer (EC) using kinase inhibitors rarely result in complete tumor remission and are frequently challenged by the appearance of refractory cell clones, eventually resulting in disease relapse. Dissecting adaptive mechanisms is of vital importance to circumvent clinical drug resistance and improve the efficacy of targeted agents in EC. Sorafenib is an FDA-approved multitarget tyrosine and serine/threonine kinase inhibitor currently used to treat hepatocellular carcinoma, advanced renal carcinoma and radioactive iodine-resistant thyroid carcinoma...
January 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28007903/autophagy-activators-suppress-cystogenesis-in-an-autosomal-dominant-polycystic-kidney-disease-model
#2
Ping Zhu, Cynthia J Sieben, Xiaolei Xu, Peter C Harris, Xueying Lin
Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in either PKD1 or PKD2 It is one of the most common heritable human diseases with eventual development of renal failure; however, effective treatment is lacking. While inhibition of mechanistic target of rapamycin (mTOR) effectively slows cyst expansions in animal models, results from clinical studies are controversial, prompting further mechanistic studies of mTOR-based therapy. Here, we aim to establish autophagy, a downstream pathway of mTOR, as a new therapeutic target for PKD...
December 22, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27994511/autophagy-activation-protects-shock-wave-induced-renal-tubular-epithelial-cell-apoptosis-may-through-modulation-of-akt-gsk-3%C3%AE-pathway
#3
Qingzhi Long, Xiang Li, Hui He, Dalin He
PURPOSE: Extracorporeal shock wave lithotripsy (ESWL) is well documented to exert destructive effect to renal cells and its mechanism is not clear. Autophagy is one of cell basic response for stressful conditions and it is important to determine cell's fate. The aim of this study is to elucidate the role of autophagy in the process of shock wave-induced renal cells injury. METHODS: NRK-52E cell, a rat renal tubular epithelial cell, was exposed to shock wave at the voltage of 14KV...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27990015/the-renal-fanconi-syndrome-in-cystinosis-pathogenic-insights-and-therapeutic-perspectives
#4
REVIEW
Stephanie Cherqui, Pierre J Courtoy
Cystinosis is an autosomal recessive metabolic disease that belongs to the family of lysosomal storage disorders. It is caused by a defect in the lysosomal cystine transporter, cystinosin, which results in an accumulation of cystine in all organs. Despite the ubiquitous expression of cystinosin, a renal Fanconi syndrome is often the first manifestation of cystinosis, usually presenting within the first year of life and characterized by the early and severe dysfunction of proximal tubule cells, highlighting the unique vulnerability of this cell type...
February 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/27932476/high-fat-diet-induced-lysosomal-dysfunction-and-impaired-autophagic-flux-contribute-to-lipotoxicity-in-the-kidney
#5
Takeshi Yamamoto, Yoshitsugu Takabatake, Atsushi Takahashi, Tomonori Kimura, Tomoko Namba, Jun Matsuda, Satoshi Minami, Jun-Ya Kaimori, Isao Matsui, Taiji Matsusaka, Fumio Niimura, Motoko Yanagita, Yoshitaka Isaka
Excessive fat intake contributes to the progression of metabolic diseases via cellular injury and inflammation, a process termed lipotoxicity. Here, we investigated the role of lysosomal dysfunction and impaired autophagic flux in the pathogenesis of lipotoxicity in the kidney. In mice, a high-fat diet (HFD) resulted in an accumulation of phospholipids in enlarged lysosomes within kidney proximal tubular cells (PTCs). In isolated PTCs treated with palmitic acid, autophagic degradation activity progressively stagnated in association with impaired lysosomal acidification and excessive lipid accumulation...
December 8, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27928635/valproic-acid-attenuates-renal-fibrosis-through-the-induction-of-autophagy
#6
Koichiro Kawaoka, Shigehiro Doi, Ayumu Nakashima, Kyoko Yamada, Toshinori Ueno, Toshiki Doi, Takao Masaki
BACKGROUND: Renal fibrosis is a common pathological feature of the progression of chronic kidney disease. Although valproic acid (VPA) has been recently shown to induce autophagy, the effect of VPA-induced autophagy on renal fibrosis remains unknown. We, therefore, investigated whether VPA-induced autophagy suppresses renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO). METHODS: Male C57BL/6 mice were divided into five groups (n = 8 per group): (1) sham group; (2) vehicle group; (3) VPA-treated group; (4) 3-methyladenine (3-MA; autophagy inhibitor)-treated group; and (5) VPA plus 3-MA-treated group...
December 7, 2016: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/27919004/irbesartan-ameliorates-hyperlipidemia-and-liver-steatosis-in-type-2-diabetic-db-db-mice-via-stimulating-ppar-%C3%AE-ampk-akt-mtor-signaling-and-autophagy
#7
Juan Zhong, Wangqiu Gong, Lu Lu, Jing Chen, Zibin Lu, HongYu Li, Wenting Liu, Yangyang Liu, Mingqing Wang, Rong Hu, Haibo Long, Lianbo Wei
Irbesartan (Irb), a unique subset of angiotensin II receptor blockers (ARBs) with PPAR-γ activation function, has been reported to play a role in renal dysfunction, glucose metabolism, and abnormal lipid profile in diabetic animal models and humans. However, the underlying mechanisms that improve hyperlipidemia and liver steatosis are unclear. This study investigated the effects of Irb on lipid metabolism and hepatic steatosis using the spontaneous type 2 diabetic db/db mouse model. The results demonstrated body and liver weight, food consumption, lipid content in serum and liver tissue, and liver dysfunction as well as hepatic steatosis were increased in db/db mice compared with db/m mice, whereas the increases were reversed by Irb treatment...
January 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/27916082/-effects-of-ammonium-pyrrolidine-dithiocarbamate-pdtc-on-osteopontin-expression-and-autophagy-in-tubular-cells-in-streptozotocin-induced-diabetic-nephropathy-rat
#8
S Gao, J Y Jia, T K Yan, Y M Yu, W Y Shang, L Wei, Z F Zheng, P Fang, B C Chang, S Lin
Objective: To investigate the effects of ammonium pyrrolidine dithiocarbamate (PDTC) on tubulointerstitial inflammatory molecules and autophagy in diabetic nephropathy (DN) rats. Methods: Twenty-four male Sprague-Dawley rats were assigned to DN group (n=6) and DN+ PDTC group (n=6, PDTC, ip, 100 mg·kg(-1)·d(-1)), all received streptozotocin (STZ) 60 mg/kg intraperitoneally, and the other 12 rats were randomly divided into control group (n=6) and PDTC group (n=6). At the end of 12 weeks, after serum creatine (Scr) and 24-hour urinary protein were determined, rats were sacrificed to determined the renal pathological damages and the changes of nuclear factor (NF)-κB p65, p62, osteopontin (OPN), microtubule associated protein 1 light chain 3 (LC3)-Ⅱ/LC3-Ⅰ, nuclear p-NF-κB p65 by immunohistological stainning and Western blot, and ultrastructural changes of autophagic process was observed by electron microscopy (EM)...
November 29, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27900012/ubenimex-enhances-the-radiosensitivity-of-renal-cell-carcinoma-cells-by-inducing-autophagic-cell-death
#9
Shuai Liu, Xiaoqing Wang, Jiaju Lu, Liping Han, Yongfei Zhang, Zheng Liu, Sentai Ding, Zhao Liu, Dongbin Bi, Zhihong Niu
Renal cell carcinoma (RCC) is resistant to standard radiotherapy. Ubenimex, an aminopeptidase N inhibitor, is widely used as an adjunct therapy after surgery to enhance the function of immunocompetent cells and confer antitumor effects. Our previous study demonstrated that ubenimex induces autophagic cell death in RCC cells. Recently, the molecular mechanism of autophagy induction has been associated with radiosensitivity in RCC cells. In the present study, the ability of ubenimex to enhance RCC cell sensitivity to radiation via the induction of autophagic cell death was determined, and the mechanism of action of this effect was investigated...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27884046/effect-of-lycopene-and-rosmarinic-acid-on-gentamicin-induced-renal-cortical-oxidative-stress-apoptosis-and-autophagy-in-adult-male-albino-rat
#10
Naglaa A Bayomy, Reda H Elbakary, Marwa A A Ibrahim, Eman Z Abdelaziz
Gentamicin nephrotoxicity accounts for 10%-15% of all cases of acute renal failure. Several natural antioxidants were found to be effective against drug-induced toxicity. The possible protective effects of lycopene (Lyc) and rosmarinic acid (RA) alone or combined on gentamicin (Gen) induced renal cortical oxidative stress, apoptosis, and autophagy were evaluated. Sixty-three rats were randomly divided into seven groups named: control, group II received RA 50 mg/kg/day, group III received Lyc 4 mg/kg/day, group IV received Gen 100 mg/kg/day, group V (RA + Gen), group VI (Lyc + Gen), and group VII (RA + Lyc + Gen)...
November 24, 2016: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/27881580/disruption-of-autophagic-degradation-with-roc-325-antagonizes-renal-cell-carcinoma-pathogenesis
#11
Jennifer S Carew, Claudia M Espitia, Weiguo Zhao, Yingchun Han, Valeria Visconte, James G Phillips, Steffan T Nawrocki
PURPOSE: Although autophagy plays important roles in malignant pathogenesis and drug resistance, there are few clinical agents that disrupt this pathway and the potential therapeutic benefit of autophagy inhibition remains undetermined. We used medicinal chemistry approaches to generate a series of novel agents that inhibit autophagic degradation. EXPERIMENTAL DESIGN: ROC-325 was selected as a lead compound for further evaluation. Comprehensive in vitro and in vivo studies were conducted to evaluate the selectivity, tolerability, and efficacy of ROC-325 in preclinical models of renal cell carcinoma (RCC) with HCQ serving as a comparator...
November 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27880045/koelreuteria-formosana-extract-induces-growth-inhibition-and-cell-death-in-human-colon-carcinoma-cells-via-g2-m-arrest-and-lc3-ii-activation-dependent-autophagy
#12
Chi-Ting Horng, Yueh-Jung Wu, Pei-Ni Chen, Shu-Chen Chu, Chun-Miao Tsai, Yih-Shou Hsieh
Autophagy is a self-destructive process that degrades cytoplasmic constituents. In our previous study, Koelreuteria formosana ethanolic extract (KFEE), which is obtained from natural plants endemic to Taiwan, has inhibited cell metastasis in renal carcinoma cells. However, the anticancer effects of KFEE on colon cancer remain unclear. In this study, KFEE exerted a strong cytotoxic effect on DLD-1 and COLO 205 human colorectal cancer cell lines. KFEE effectively inhibited cancer cell proliferation, induced G2/M-phase arrest associated with downregulaton of cyclin E, cyclin B and cdc25C and upregulation of p21, and induced cell death by activating autophagy but did not cause apoptotic cell death...
January 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/27878656/mille-modis-morimur-we-die-in-a-thousand-ways
#13
Gaspar Banfalvi
Dying cells subjected to apoptotic programs are engulfed by neighboring cells or by professional phagocytes, without inflammation or immunological reactions in the tissue where apoptosis takes place. Apoptotic cells release danger-associated project signals to their neighbours, through different molecular patterns, stimulate antigen production and immune responses. Microenvironmental effects with several functional consequences indicate that cell death is a complex process and may take place in several ways...
November 23, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27827795/peroxisomal-protein-pex13-functions-in-selective-autophagy
#14
Ming Y Lee, Rhea Sumpter, Zhongju Zou, Shyam Sirasanagandla, Yongjie Wei, Prashant Mishra, Hendrik Rosewich, Denis I Crane, Beth Levine
PEX13 is an integral membrane protein on the peroxisome that regulates peroxisomal matrix protein import during peroxisome biogenesis. Mutations in PEX13 and other peroxin proteins are associated with Zellweger syndrome spectrum (ZSS) disorders, a subtype of peroxisome biogenesis disorder characterized by prominent neurological, hepatic, and renal abnormalities leading to neonatal death. The lack of functional peroxisomes in ZSS patients is widely accepted as the underlying cause of disease; however, our understanding of disease pathogenesis is still incomplete...
January 2017: EMBO Reports
https://www.readbyqxmd.com/read/27816967/ubenimex-attenuates-acquired-sorafenib-resistance-in-renal-cell-carcinoma-by-inhibiting-akt-signaling-in-a-lipophagy-associated-mechanism
#15
Shuai Liu, Mingwei Gao, Xiaoqing Wang, Sentai Ding, Jiaju Lv, Dexuan Gao, Zhiyang Wang, Zhihong Niu
Sorafenib is used as first line treatment of renal cell carcinoma (RCC) due to the poor sensitivity to radiotherapy and chemotherapy of this malignancy; however, acquired resistance limits the application of sorafenib and its analogues. In this study, we explored a new strategy to overcome acquired resistance to sorafenib. The RCC cell lines 786-O and ACHN were cultured in presence of increasing concentrations of sorafenib to generate sorafenib-resistant cell lines, 786-O-R and ACHN-R. Interestingly, treatment with ubenimex (0...
November 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27816946/advanced-glycation-end-products-mediated-cellular-and-molecular-events-in-the-pathology-of-diabetic-nephropathy
#16
Anil Kumar Pasupulati, P Swathi Chitra, G Bhanuprakash Reddy
Diabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetic patients and a leading cause of end-stage renal disease (ESRD). Degenerative changes such as glomerular hypertrophy, hyperfiltration, widening of basement membranes, tubulointerstitial fibrosis, glomerulosclerosis and podocytopathy manifest in various degrees of proteinuria in DN. One of the key mechanisms implicated in the pathogenesis of DN is non-enzymatic glycation (NEG). NEG is the irreversible attachment of reducing sugars onto free amino groups of proteins by a series of events, which include the formation of Schiff's base and an Amadori product to yield advanced glycation end products (AGEs)...
December 1, 2016: Biomolecular Concepts
https://www.readbyqxmd.com/read/27804885/the-functions-of-heparanase-in-human-diseases
#17
Hao Jin, Shaobo Zhou
The study of the heparanase has long been paid wide attention. Heparanase ,an endo-β-D-glucuronidase, is capable of specifically degrading heparan sulfate(HS), one of the excellular matrix(ECM) components. It exerts its enzymatic activity catalyzing the cleavage of the β (1,4)-glycosidic bond between glucuronic acid and glucosamine residue. HS cleavage results in remodelling of the extracellular matrix as well as in regulating the release of many HS-linked molecules such as growth factors, cytokines and enzymes involved in inflammation, wound healing and tumour invasion...
November 1, 2016: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/27799485/protein-kinase-c%C3%AE-suppresses-autophagy-to-induce-kidney-cell-apoptosis-in-cisplatin-nephrotoxicity
#18
Dongshan Zhang, Jian Pan, Xudong Xiang, Yu Liu, Guie Dong, Man J Livingston, Jian-Kang Chen, Xiao-Ming Yin, Zheng Dong
Nephrotoxicity is a major adverse effect in cisplatin chemotherapy, and renoprotective approaches are unavailable. Recent work unveiled a critical role of protein kinase Cδ (PKCδ) in cisplatin nephrotoxicity and further demonstrated that inhibition of PKCδ not only protects kidneys but enhances the chemotherapeutic effect of cisplatin in tumors; however, the underlying mechanisms remain elusive. Here, we show that cisplatin induced rapid activation of autophagy in cultured kidney tubular cells and in the kidneys of injected mice...
October 31, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27771075/autophagy-and-apoptosis-induced-by-chinese-giant-salamander-andrias-davidianus-iridovirus-cgsiv
#19
Jian Du, Liqing Wang, Yuanxian Wang, Jian Shen, Chuanyin Pan, Yan Meng, Changming Yang, Hong Ji, Wuzi Dong
The outbreak of Chinese Giant Salamander (Andrias davidianus, CGS) Iridovirus (CGSIV) caused massive death of CGSs. However, some CGSs with low level of CGSIV usually could survive. In our study, major capsid protein (MCP) DNA replicates of CGSIV in shedding skin were employed to assess the relative content of CGSIV in the living CGSs by qPCR. Furthermore, the examinations of autophagy and apoptosis in CGSs in vivo and in the primary renal cells in vitro were performed, respectively. The results showed that the relative contents of CGSIV in the shedding skin could reflect those in liver, spleen, and kidney of the CGSs...
November 15, 2016: Veterinary Microbiology
https://www.readbyqxmd.com/read/27762461/restoration-of-autophagy-by-puerarin-in-lead-exposed-primary-rat-proximal-tubular-cells-via-regulating-ampk-mtor-signaling
#20
Xiangbin Song, Zifa Li, Fei Liu, Zhenyong Wang, Lin Wang
Previous study has demonstrated that puerarin (PU) exerts nephroprotective effect against Pb-induced cytotoxicity in primary rat proximal tubular (rPT) cells. Autophagy can protect cells from various cytotoxic stimuli, but its role in the process of PU against Pb-induced nephrotoxicity is still unknown. This study aims to investigate whether PU can alleviate Pb-induced renal damage by recovering autophagy. Data showed that Pb inhibited the autophagic flux, as evidenced by the accumulation of LC3-II and p62 as well as the confocal microscopy analysis of GFP-LC3 puncta and punctate spots of monodansylcadaverine staining, whereas coadministration of PU could restore Pb-induced autophagy inhibition...
October 20, 2016: Journal of Biochemical and Molecular Toxicology
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