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https://www.readbyqxmd.com/read/29221116/the-addition-of-abemaciclib-to-sunitinib-induces-regression-of-renal-cell-carcinoma-xenograft-tumors
#1
Jeffrey Small, Erik Washburn, Karmaine Millington, Junjia Zhu, Sheldon L Holder
Multiple therapies currently exist for renal cell carcinoma, however, most do not result in cure and the development of acquired resistance is the rule rather than the exception. CDK4/6 and PIM1 kinases are potential new therapeutic targets in RCC. Abemaciclib is a potent CDK4/6 and PIM1 kinase inhibitor, thus we evaluated the effects of abemaciclib on renal cell carcinoma. In vitro, abemaciclib causes decreased cellular viability, increased apoptosis, and alterations in autophagy in renal cell carcinoma cell lines...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29218509/protective-effect-of-cadmium-induced-autophagy-in-rat-renal-mesangial-cells
#2
Hitomi Fujishiro, Ying Liu, Bilal Ahmadi, Douglas M Templeton
Cadmium damages renal cells, and in particular may cause mesangial cell death by necrosis or apoptosis, depending on exposure conditions in cultured cells. However, there is an uncertainty as to whether Cd2+-induced autophagy can protect mesangial cells against these other mechanisms of cell death. We have used autophagy-incompetent mouse embryonic fibroblast (MEF) cells lacking the Atg16 gene, as well as cultured rat mesangial cells (RMC) in which Atg16 has been silenced, to examine this issue. Measuring the processing of LC3-I to LC3-II and expression of sequestosome-1 (p62), we define conditions under which RMC can be induced to undergo autophagy in response to 0-20 µM CdCl2...
December 7, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29187371/effects-of-erythropoietin-receptor-activity-on-angiogenesis-tubular-injury-and-fibrosis-in-acute-kidney-injury-a-u-shaped-relationship
#3
Mingjun Shi, Brianna Flores, Peng Li, Nancy Gillings, Kathryn L McMillan, Jianfeng Ye, Lily June-Shen Huang, Sachdev S Sidhu, Yong-Ping Zhong, Maria T Grompe, Philip R Streeter, Orson W Moe, Ming Chang Hu
Erythropoietin receptor (EpoR) is widely expressed but its renoprotective action is unexplored. To examine the role of EpoR in vivo in the kidney, we induced acute kidney injury (AKI) by ischemia-reperfusion in mice with different EpoR bioactivities in the kidney. EpoR bioactivity was reduced by knock-in of wild type human EpoR, which is hypo-functional relative to murine EpoR, and a renal tubule-specific EpoR knockout. These mice had lower EPO/EpoR activity and lower autophagy flux in renal tubules. Upon AKI induction, they exhibited worse renal function and structural damage, and more apoptosis at the acute stage (< 7 days), and slower recovery with more tubulointerstitial fibrosis at the subacute stage (14 days)...
November 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29172924/pink1-prkn-park2-pathway-of-mitophagy-is-activated-to-protect-against-renal-ischemia-reperfusion-injury
#4
Chengyuan Tang, Hailong Han, Mingjuan Yan, Shiyao Zhu, Jing Liu, Zhiwen Liu, Liyu He, Jieqiong Tan, Yu Liu, Hong Liu, Lin Sun, Shaobin Duan, Youming Peng, Fuyou Liu, Xiao-Ming Yin, Zhuohua Zhang, Zheng Dong
Damaged or dysfunctional mitochondria are toxic to the cell by producing reactive oxygen species and releasing cell death factors. Therefore, timely removal of these organelles is critical to cellular homeostasis and viability. Mitophagy is the mechanism of selective degradation of mitochondria via autophagy. The significance of mitophagy in kidney diseases, including ischemic acute kidney injury (AKI), has yet to be established, and the involved pathway of mitophagy remains poorly understood. Here, we show that mitophagy is induced in renal proximal tubular cells in both in vitro and in vivo models of ischemic AKI...
November 26, 2017: Autophagy
https://www.readbyqxmd.com/read/29164562/resveratrol-transcriptionally-regulates-mirna-18a-5p-expression-ameliorating-diabetic-nephropathy-via-increasing-autophagy
#5
X-H Xu, D-F Ding, H-J Yong, C-L Dong, N You, X-L Ye, M-L Pan, J-H Ma, Q You, Y-B Lu
OBJECTIVE: To investigate the effects of resveratrol on autophagy in the chronically diabetic nephropathy and to study the effects of the different expression of microRNAs after resveratrol (RSV) treated in db/db mice (diabetic mice). MATERIALS AND METHODS: Db/m (non- diabetic) and db/db mice were randomly divided into intra gastric RSV treatment group or control group. Renal tissues were prepared for HE/PAS staining. In vitro, mouse podocytes cell lines were grown in different mediums with different dose of resveratrol treatment...
November 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29161706/endotoxin-effects-on-cardiac-and-renal-functions-and-cardiorenal-syndromes
#6
Grazia Maria Virzì, Anna Clementi, Alessandra Brocca, Claudio Ronco
Gram-negative sepsis is a major cause of morbidity and mortality in critical ill patients. Recent findings in molecular biology and in signaling pathways have enhanced our understanding of its pathogenesis and opened up opportunities of innovative therapeutic approaches. Endotoxin plays a pivotal role in the pathogenesis of multi-organ dysfunction in the setting of gram-negative sepsis. Indeed, heart and kidney impairments seem to be induced by the release of circulating pro-inflammatory and pro-apoptotic mediators triggered by endotoxin interaction with immune cells...
November 22, 2017: Blood Purification
https://www.readbyqxmd.com/read/29160038/endoplasmic-reticulum-in-health-and-disease-the-12th-international-calreticulin-workshop-delphi-greece
#7
REVIEW
Aristidis S Charonis, Marek Michalak, Jody Groenendyk, Luis B Agellon
Starting from 1994, every 2 years, an international workshop is organized focused on calreticulin and other endoplasmic reticulum chaperones. In 2017, the workshop took place at Delphi Greece. Participants from North and South America, Europe, Asia and Australia presented their recent data and discussed them extensively with their colleagues. Presentations dealt with structural aspects of calreticulin and calnexin, the role of Ca(2+) in cellular signalling and in autophagy, the endoplasmic reticulum stress and the unfolded protein response, the role of calreticulin in immune responses...
November 21, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29149834/cystatin-c-in-cerebrovascular-disorders
#8
Yaru Zhang, Li Sun
Cystatin C (CysC), a cysteine protease inhibitor, has been widely proven to be a highly sensitive biomarker to predict the kidney function. The similarity of the renal and cerebral small vessels has awakened a surge of studies suggesting that CysC plays a key role in various cerebrovascular disorders. This review focuses on four major mechanisms of CysC in a variety of cerebrovascular diseases. (1)The property of the CysC Leu-68-Gln (L68Q) variant to aggregate and the property of the wild type CysC protein to co-aggregate with Amyloid-β (Aβ); (2)The disruption of equilibrium between CysC and related cysteine proteases; (3)The function of CysC as an inflammatory inducing factor; (4)The ability of CysC to induce autophagy...
November 15, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/29145153/the-pro-apoptosis-effect-of-sinomenine-in-renal-carcinoma-via-inducing-autophagy-through-inactivating-pi3k-akt-mtor-pathway
#9
Fei Deng, Yue-Xian Ma, Liang Liang, Ping Zhang, Jing Feng
Renal cell carcinoma (RCC) is a heterogeneous histological disease and the most common kidney cancer. The mortality rate of RCC remains high despite the improved treatment. Sinomenine is an isoquinoline extracted from Chinese medicinal plant Sinomenium acutum, famous for its ability to suppress several cancer cell types. Our research aimed to explore the anti-cancer potential of sinomenine in RCC. Results showed that sinomenine reduced the viability by reducing sphere-forming ability and enhancing pro-apoptosis effect in ACHN cells in a dose dependent manner...
November 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29142990/the-chemical-chaperone-pba-reduces-er-stress-and-autophagy-and-increases-collagen-iv-%C3%AE-5-expression-in-cultured-fibroblasts-from-men-with-x-linked-alport-syndrome-and-missense-mutations
#10
Dongmao Wang, Mardhiah Mohammad, Yanyan Wang, Rachel Tan, Lydia S Murray, Sharon Ricardo, Hayat Dagher, Tom van Agtmael, Judy Savige
Introduction: X-linked Alport syndrome (OMIM 301050) is caused by COL4A5 missense variants in 40% of families. This study examined the effects of chemical chaperone treatment (sodium 4-phenylbutyrate) on fibroblast cell lines derived from men with missense mutations. Methods: Dermal fibroblast cultures were established from 2 affected men and 3 normals. Proliferation rates were examined, the collagen IV α5 chain localized with immunostaining, and levels of the intra- and extracellular chains quantitated with an in-house enzyme-linked immunosorbent assay...
July 2017: KI Reports
https://www.readbyqxmd.com/read/29141242/chloroquine-autophagic-inhibition-rebalances-th17-treg-mediated-immunity-and-ameliorates-systemic-lupus-erythematosus
#11
Ning An, Yanwen Chen, Chao Wang, Chen Yang, Zhi-Hong Wu, Jing Xue, Lin Ye, Shujun Wang, Hua-Feng Liu, Qingjun Pan
BACKGROUND: Imbalanced cellular immunity is critical to the pathogenesis of systemic lupus erythematosus (SLE). Recently, autophagy has emerged as a key homeostatic mechanism in T lymphocytes. This study was conducted to explore the impact of autophagy on the Th17/ regulatory T (Treg) immune imbalance in SLE. METHODS: Peripheral Th17 and Treg cells from newly diagnosed patients with SLE and healthy controls were detected by flow cytometry. Additionally, the effects of chloroquine (CQ) autophagic inhibition on the Th17/Treg immune response were investigated in vitro...
November 14, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29125601/tm9sf4-is-a-novel-factor-promoting-autophagic-flux-under-amino-acid-starvation
#12
Lei Sun, Zhaoyue Meng, Yifei Zhu, Jun Lu, Zhichao Li, Qiannan Zhao, Yu Huang, Liwen Jiang, Xiaoqiang Yao
Autophagy is a highly complicated process with participation of large numbers of autophagy-related proteins. Under nutrient starvation, autophagy promotes cell survival by breaking down nonessential cellular components for recycling use. However, due to its high complexity, molecular mechanism of autophagy is still not fully understood. In the present study, we report a novel autophagy-related protein TM9SF4, which plays a functional role in the induction phase of autophagic process. TM9SF4 proteins were abundantly expressed in the kidney, especially in renal proximal tubular epithelial cells...
November 10, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29115429/resveratrol-mediated-apoptosis-in-renal-cell-carcinoma-via-the-p53-amp%C3%A2-activated-protein-kinase-mammalian-target-of-rapamycin-autophagy-signaling-pathway
#13
Qingjun Liu, Qiang Fang, Shiqi Ji, Zhixing Han, Wenlong Cheng, Haijian Zhang
Resveratrol, known as phytoalexin, is a natural compound. Clinical studies have revealed that resveratrol has a variety of effects including anti‑inflammatory, antivirus and tumor suppressor activities. It has been reported that it may serve an important role in renal cell carcinoma (RCC) however, the molecular mechanism underlying resveratrol‑induced apoptosis in RCC is still unclear. The aim of the present study was to determine whether resveratrol could suppress RCC progression. Analysis of apoptosis demonstrated that resveratrol may act as a RCC suppressor in a dose‑ and time‑dependent manner...
October 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29093603/pi3k-akt-mtor-pathway-in-ovarian-cancer-treatment-are-we-on-the-right-track
#14
Maria Luisa Gasparri, Erlisa Bardhi, Ilary Ruscito, Andrea Papadia, Ammad Ahmad Farooqi, Claudia Marchetti, Giorgio Bogani, Irene Ceccacci, Michael D Mueller, Pierluigi Benedetti Panici
The high recurrence rate and the low overall survival in ovarian cancer suggest that a more specific therapeutic approach in addition to conventional treatment is required. Translational and clinical research is investigating new molecular targets in order to find an alternative way to affect tumor growth and to minimize the overlap of toxicity of antiblastic agents. Given its implication in many cellular activities including regulation of cell growth, motility, survival, proliferation, protein synthesis, autophagy, transcription, as well as angiogenesis, PI3K/AKT/mTOR is one of the most investigated intracellular signaling pathways...
October 2017: Geburtshilfe und Frauenheilkunde
https://www.readbyqxmd.com/read/29070572/glucagon-like-peptide-1-analog-prevents-obesity-related-glomerulopathy-by-inhibiting-excessive-autophagy-in-podocytes
#15
HongLei Guo, Bin Wang, HongMei Li, LiLu Ling, Jianying Niu, Yong Gu
AIM: To investigate the role of glucagon-like peptide-1 analog (GLP-1) in high fat diet-induced obesity-related glomerulopathy (ORG). METHODS: Male C57BL/6 mice fed a high fat diet for 12 weeks were treated with GLP-1 (200 μg/kg) or 0.9% saline for 4 weeks. Fasting blood glucose and insulin and the expression of podocin, nephrin, phosphoinositide 3-kinase (PI3K), glucose transporter type (Glut4), and microtubule-associated protein 1A/1B-light chain 3 (LC3) were assayed...
October 25, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29066973/from-resistance-to-sensitivity-insights-and-implications-of-biphasic-modulation-of-autophagy-by-sunitinib
#16
REVIEW
Amal Kamal Abdel-Aziz, Ashraf B Abdel-Naim, Samia Shouman, Saverio Minucci, Mohamed Elgendy
Sunitinib, a multityrosine kinase inhibitor, is currently the standard first-line therapy in metastatic renal cell carcinoma (mRCC) and is also used in treating patients with pancreatic neuroendocrine and imatinib-resistant gastrointestinal stromal tumors (GIST). Nevertheless, most patients eventually relapse secondary to intrinsic or acquired sunitinib resistance. Autophagy has been reported to contribute to both chemo-sensitivity and -resistance. However, over the last few years, controversial regulatory effects of sunitinib on autophagy have been reported...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29063120/-advances-in-mechanism-of-autophagy-in-renal-tubular-injury
#17
Fan Yin, Li-Min Lu
Autophagy is a lysosome-dependent degradation process that eliminates damaged macromolecular proteins and aging organelles to maintain intracellular homeostasis. Autophagy is observed in almost all eukaryotic cells and plays important roles in many cellular physiological processes, including the cell proliferation and growth, cellular functional alteration and phenotypical transition. Renal tubule is an important target for renal injury under different pathological conditions. Following the discoveries of the molecular basis of autophagy, accumulated lines of evidence have indicated that autophagy dysfunction in tubule is involved in the pathogenesis of many renal diseases...
October 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28992279/targeting-new-cellular-disease-pathways-in-autosomal-dominant-polycystic-kidney-disease
#18
Ming-Yang Chang, Albert C M Ong
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of end-stage renal failure. Understanding the molecular and cellular pathogenesis of ADPKD could help to identify new targets for treatment. The classic cellular cystic phenotype includes changes in proliferation, apoptosis, fluid secretion, extracellular matrix and cilia function. Hoever, recent research, suggests that the cellular cystic phenotype could be broader and that changes, such as altered metabolism, autophagy, inflammation, oxidative stress and epigenetic modification, could play important roles in the processes of cyst initiation, cyst growth or disease progression...
August 29, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28987240/protein-tyrosine-phosphatase-1b-deficiency-in-podocytes-mitigates-hyperglycemia-induced-renal-injury
#19
Yoshihiro Ito, Ming-Fo Hsu, Ahmed Bettaieb, Shinichiro Koike, Aline Mello, Miguel Calvo-Rubio, Jose M Villalba, Fawaz G Haj
OBJECTIVE: Diabetic nephropathy is one of the most devastating complications of diabetes, and growing evidence implicates podocyte dysfunction in disease pathogenesis. The objective of this study was to investigate the contribution of protein tyrosine phosphatase 1B (PTP1B) in podocytes to hyperglycemia-induced renal injury. METHODS: To determine the in vivo function of PTP1B in podocytes we generated mice with podocyte-specific PTP1B disruption (hereafter termed pod-PTP1B KO)...
November 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28981387/aldh1a1-and-hltf-modulate-the-activity-of-lysosomal-autophagy-inhibitors-in-cancer-cells
#20
Shengfu Piao, Rani Ojha, Vito W Rebecca, Arabinda Samanta, Xiao-Hong Ma, Quentin Mcafee, Michael C Nicastri, Meghan Buckley, Eric Brown, Jeffrey D Winkler, Phyllis A Gimotty, Ravi K Amaravadi
Lysosomal autophagy inhibitors (LAI) such as hydroxychloroquine (HCQ) have significant activity in a subset of cancer cell lines. LAIs are being evaluated in cancer clinical trials, but genetic determinants of sensitivity to LAIs are unknown, making it difficult to predict which tumors would be most susceptible. Here we characterize differentially expressed genes in HCQ-sensitive (-S) and -resistant (-R) cancer cells. Notably, expression of canonical macroautophagy/autophagy genes was not associated with sensitivity to HCQ...
October 5, 2017: Autophagy
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