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autophagy AND pancreatitis

Yu-Huei Liu, Yui-Ping Weng, Hsin-Ying Tsai, Chao-Jung Chen, Der-Yen Lee, Ching-Liang Hsieh, Yang-Chang Wu, Jung-Yaw Lin
BACKGROUND: Pancreatic cancer (PC) remains the leading cause of cancer mortality, with limited therapeutic targets, and alterations in endoplasmic reticulum (ER)-related proteostasis may be a potential target for therapy. The root bark of Paeonia suffruticosa has been shown to inhibit cancer growth and metastasis, although its impact on PC is unknown. PURPOSE: To ascertain the anti-cancer effects of P. suffruticosa on oncogenic functions of PC and determine the detailed molecular mechanisms...
July 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Ruizhi He, Xiuhui Shi, Min Zhou, Yan Zhao, Shutao Pan, Chunle Zhao, Xingjun Guo, Min Wang, Xu Li, Renyi Qin
The lysosome is emerging as a central regulator of the autophagic process, which plays a critical role in tumor growth and chemoresistance. Alantolactone, which is a natural compound produced by Inula helenium, has been shown to induce apoptosis in numerous cancer types. However, the mechanism by which alantolactone regulates apoptosis is still poorly understood. In this work, we observed that alantolactone caused the accumulation of autophagosomes due to impaired autophagic degradation and substantially inhibited the activity and expression of CTSB/CTSD proteins that when depleted caused lysosomal dysfunction...
August 4, 2018: Toxicology and Applied Pharmacology
Yoshimitsu Kiriyama, Hiromi Nochi
Amylin, (or islet amyloid polypeptide; IAPP), a 37-amino acid peptide hormone, is released in response to nutrients, including glucose, lipids or amino acids. Amylin is co-stored and co-secreted with insulin by pancreatic islet β-cells. Amylin inhibits food intake, delays gastric emptying, and decreases blood glucose levels, leading to the reduction of body weight. Therefore, amylin as well as insulin play important roles in controlling the level of blood glucose. However, human amylin aggregates and human amylin oligomers cause membrane disruption, endoplasmic reticulum (ER) stress and mitochondrial damage...
August 6, 2018: Cells
Xian Zeng, Dianwen Ju
Hedgehog (Hh) pathway controls complex developmental processes in vertebrates. Abnormal activation of Hh pathway is responsible for tumorigenesis and maintenance of multiple cancers, and thus addressing this represents promising therapeutic opportunities. In recent years, two Hh inhibitors have been approved for basal cell carcinoma (BCC) treatment and show extraordinary clinical outcomes. Meanwhile, a series of novel agents are being developed for the treatment of several cancers, including lung cancer, leukemia, and pancreatic cancer...
August 3, 2018: International Journal of Molecular Sciences
Chih-Hsiung Hsieh, Chueh-Hsuan Lu, Yu-Yi Kuo, Wei-Ting Chen, Chih-Yu Chao
Cancer is one of the most troublesome diseases and a leading cause of death worldwide. Recently, novel treatments have been continuously developed to improve the disadvantages of conventional therapies, such as prodigious expenses, unwanted side effects, and tumor recurrence. Here, we provide the first non-invasive treatment that has combined epigallocatechin gallate (EGCG), the most abundant catechin in green tea, with a low strength pulsed electric field (PEF) and a low energy ultrasound (US). It has been observed that the cell viability of human pancreatic cancer PANC-1 was decreased approximately to 20% of the control after this combination treatment for 72 h...
2018: PloS One
Cai-Xia Li, Li-Hua Cui, Yu-Zhen Zhuo, Jian-Gong Hu, Nai-Qiang Cui, Shu-Kun Zhang
AIMS: Autophagy is an intracellular metabolic process that degrades and recycles own constituents to maintain homeostasis and supply substrates. Disruption of collagen degradation is one of the pathogenesis of pancreatic fibrosis. In this study, we investigated the effects of inhibiting autophagy on the collagen degradation of PSCs. MAIN METHODS: Rats were injected dibutyltin dichloride (DBTC) to induce chronic pancreatitis (CP) model. The expression of LC3B was measured by western blotting...
July 26, 2018: Life Sciences
Linghuan Li, Jiameng Qi, Hanbing Li
Autophagy is a conserved, regulated cellular process for the degradation of abnormal proteins and disrupted organelles. Literature has described that dysregulation of autophagy is closely related to the pathogenesis of diabetes mellitus in processes such as impaired pancreatic β cells function, peripheral insulin resistance and diabetic complications. Emerging evidence indicates that natural products may possess anti-diabetic activity via regulation of autophagy. In this review, we summarize natural products targeting the pathogenesis of diabetes mellitus through the regulation of autophagy and underline possible mechanisms, providing potential drug candidates or therapies for the treatment of diabetes mellitus...
July 25, 2018: Current Drug Targets
Ran Xue, Qinghua Meng, Di Lu, Xinjuan Liu, Yanbin Wang, Jianyu Hao
Aim: Pancreatic cancer is one of the most quickly fatal cancers around the world. Burgeoning researches have begun to prove that mitochondria play a crucial role in cancer treatment. Mitofusin2 (Mfn2) plays an indispensable role in mitochondrial fusion and adjusting function. However, the role and underlying mechanisms of Mfn2 on cell autophagy of pancreatic cancer is still unclear. Our aim was to explore the effect of Mfn2 on multiple biological functions involving cell autophagy in pancreatic cancer...
2018: Oxidative Medicine and Cellular Longevity
Stephen Bigelsen
Despite new and exciting research and renewed optimism about future therapy, current statistics of survival from pancreatic cancer remains dismal. Patients seeking alternative or complementary treatments should be warned to avoid the hype and instead look to real science. A variety of relatively safe and inexpensive treatment options that have shown success in preclinical models and/or retrospective studies are currently available. Patients require their physicians to provide therapeutic guidance and assistance in obtaining and administrating these various therapies...
2018: Cancer Management and Research
Alessandro Agnarelli, Marco Natali, Mercedes Garcia-Gil, Rossana Pesi, Maria Grazia Tozzi, Chiara Ippolito, Nunzia Bernardini, Robert Vignali, Renata Batistoni, Anna Maria Bianucci, Silvia Marracci
The natural alkaloid berberine has several pharmacological properties and recently received attention as a potential anticancer agent. In this work, we investigated the molecular mechanisms underlying the anti-tumor effect of berberine on glioblastoma U343 and pancreatic carcinoma MIA PaCa-2 cells. Human dermal fibroblasts (HDF) were used as non-cancer cells. We show that berberine differentially affects cell viability, displaying a higher cytotoxicity on the two cancer cell lines than on HDF. Berberine also affects cell cycle progression, senescence, caspase-3 activity, autophagy and migration in a cell-specific manner...
July 13, 2018: Scientific Reports
Rui Ju, Kailun Fei, Siang Li, Chen Chen, Lei Zhu, Juan Li, Dechang Zhang, Lei Guo, Caiying Ye
The anti-cancer and anti-inflammatory effects of carboxyamidotriazole (CAI) have been demonstrated in several studies, but the underlying mechanisms remain to be elucidated. This study showed that CAI caused metabolic reprogramming of pancreatic cancer cells. The inhibition of mitochondrial oxidative metabolism by CAI led to increased glutamine-dependent reductive carboxylation and enhanced glycolytic metabolism. The presence of environmental substances that affect cellular metabolism, such as glutamine and pyruvate, attenuated the anti-cancer efficacy of CAI...
July 12, 2018: Journal of Pharmacology and Experimental Therapeutics
Kiyoshi Iwahashi, Hayato Hikita, Yuki Makino, Minoru Shigekawa, Kenji Ikezawa, Teppei Yoshioka, Takahiro Kodama, Ryotaro Sakamori, Tomohide Tatsumi, Tetsuo Takehara
Basal autophagy degrades many kinds of proteins and organelles to maintain quality and plays important roles in cellular homeostasis. However, the impact of basal autophagy on zymogen granules in pancreatic acinar cells is unknown. In the present study, we examined the influence of autophagy impairment in acinar cells on zymogen granules and homeostasis of the pancreas, using mice with pancreas-specific autophagy impairment (Pdx1-Cre+/- Atg7fl/fl mice). The number of zymogen granules in acinar cells from these mice did not differ from that in acinar cells from their wild-type littermates at 3 weeks of age...
July 10, 2018: Biochemical and Biophysical Research Communications
Fengting Huang, Wenying Chen, Juanfei Peng, Yuanhua Li, Yanyan Zhuang, Zhe Zhu, Chunkui Shao, Wanling Yang, Herui Yao, Shineng Zhang
BACKGROUND: Defective autophagy is thought to contribute to the pathogenesis of many diseases, including cancer. Human plasmacytoma variant translocation 1 (PVT1) is an oncogenic long non-coding RNA that has been identified as a prognostic biomarker in pancreatic ductal adenocarcinoma, but how PVT1 operates in the regulation of autophagy in pancreatic ductal adenocarcinoma (PDA) is unclear. METHODS: PVT1 expression level was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and hybridization in situ (ISH)...
July 12, 2018: Molecular Cancer
Esther Amalia Guzmán, Tara Peterson Pitts, Maria Cristina Diaz, Amy Elizabeth Wright
Pancreatic cancer, the fourth leading cause of cancer death in the United States, has a negative prognosis because metastasis occurs before symptoms manifest. Although combination therapies are showing improvements in treatment, the survival rate for pancreatic cancer five years post diagnosis is only 8%, stressing the need for new treatments. The receptor for advanced glycation end products (RAGE) has recently emerged as a chemotherapeutic target in KRAS driven pancreatic cancers both for treatment and in chemoprevention...
July 12, 2018: Investigational New Drugs
Prakash C Thakur, Jennifer L Miller-Ocuin, Khanh Nguyen, Rina Matsuda, Aatur D Singhi, Herbert J Zeh, Nathan Bahary
BACKGROUND: Endoplasmic reticulum (ER) stress and its consequent unfolded protein response (UPR) are believed to be associated with progression, survival and chemoresistance of a variety of tumor cells through multiple cellular processes, including autophagy. Therefore, the ER stress-autophagy pathway presents a potential molecular target for therapeutic intervention. The objective of this study was to evaluate the therapeutic efficacy of ER stress and autophagy modulators in the context of pancreatic ductal adenocarcinoma (PDAC)...
July 9, 2018: Journal of Translational Medicine
Bingbing Wang, Cui Hu, Yongyu Mei, Junjun Bao, Shaozhen Ding, Xiaochang Liu, Qiao Mei, Jianming Xu
BACKGROUND: Acute pancreatitis (AP) is a common acute gastrointestinal disorders. Increasing evidence indicated that autophagy is involved in the development of AP. Resolvin D1 is an endogenous pro-resolving lipid mediator, which can protect mice from cerulein-induced acute pancreatitis and facilitate autophagy in macrophage, but its mechanism remians unclear. AIMS: To investigate the effect of resolvin D1 on autophagy in mouse models of cerulein-induced AP. METHODS: C57BL/6 mice were randomly divided into control group, AP group and resolvin D1 group...
July 5, 2018: Digestive Diseases and Sciences
Yang Yu, Xiao Feng, Shundong Cang
Background and aim: Some cancer-specific miRNAs are dysregulated in pancreatic adenocarcinoma (PAAD) and involved in cell autophagy, differentiation, proliferation, migration, invasion, and malignant transformation. The aim of our study was to determine a panel of new diagnostic and prognostic biomarkers for PAAD. Methods: We conducted a comprehensive analysis of global miRNA-expression profiles and corresponding prognosis information of 168 PAAD patients from the Cancer Genome Atlas data set...
2018: Cancer Management and Research
Matthew D Smith, Simon Wilkinson
The importance of selective macroautophagy/autophagy in cellular health is increasingly evident. The selective degradation of portions of the endoplasmic reticulum (ER), or reticulophagy, is an emerging example but requires further mechanistic detail and broad evidence of physiological relevance. In a recent study, we identified CCPG1, an ER-resident transmembrane protein that can bind to Atg8-family proteins and, independently and discretely, to RB1CC1/FIP200. Both of these interactions are required to facilitate CCPG1's function as a reticulophagy cargo receptor...
2018: Autophagy
Christine Bellanné-Chantelot, Barbara Schmaltz-Panneau, Caroline Marty, Odile Fenneteau, Isabelle Callebaut, Séverine Clauin, Aurélie Docet, Gandhi-Laurent Damaj, Thierry Leblanc, Isabelle Pellier, Cécile Stoven, Sylvie Souquere, Iléana Antony-Debré, Blandine Beaupain, Nathalie Aladjidi, Vincent Barlogis, Frédéric Bauduer, Philippe Bensaid, Odile Boespflug-Tanguy, Claire Berger, Yves Bertrand, Liana Carausu, Claire Fieschi, Claire Galambrun, Aline Schmidt, Hubert Journel, Françoise Mazingue, Brigitte Nelken, Thuan Chong Quah, Eric Oksenhendler, Marie Ouachée, Marlène Pasquet, Véronique Saada, Felipe Suarez, Gérard Pierron, William Vainchenker, Isabelle Plo, Jean Donadieu
Congenital neutropenias (CN) are rare heterogeneous genetic disorders with about 25% of patients without known genetic defects. Using whole-exome sequencing, we identified a heterozygous mutation in the SRP54 gene, encoding the signal recognition particle (SRP) 54 GTPase protein, in 3 sporadic cases and one autosomal dominant family. We subsequently sequenced the SRP54 gene in 66 probands from the French CN registry. In total, we identified 23 mutated cases (16 sporadic, 7 familial) with seven distinct germline SRP54 mutations including a recurrent in-frame deletion (Thr117del) in 14 cases...
June 18, 2018: Blood
Xiaozheng Yu, Chunyun Li, Hechao Song, Xueyan Wang, Yinan Guo, Lijian Cui, Xiaoya Liu, Cheng Chi, Ruixia Liu, Chenghong Yin
OBJECTIVES: The aim of this study was to investigate the effects of emodin on attenuating autophagy response in acute pancreatitis (AP) models. METHODS: Acute pancreatitis was induced in Wistar rats by injecting 3% sodium taurocholate into the biliopancreatic duct. Emodin (40 mg/kg per day) was then given intragastrically, administrated 2 hours after AP induction. Rats were killed 24 hours after AP induction. The pancreatic injury was assessed using biochemical and histological approaches...
August 2018: Pancreas
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