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https://www.readbyqxmd.com/read/28938696/the-molecular-mechanisms-of-chemoresistance-in-cancers
#1
REVIEW
Hua-Chuan Zheng
Overcoming intrinsic and acquired drug resistance is a major challenge in treating cancer patients because chemoresistance causes recurrence, cancer dissemination and death. This review summarizes numerous molecular aspects of multi-resistance, including transporter pumps, oncogenes (EGFR, PI3K/Akt, Erk and NF-κB), tumor suppressor gene (p53), mitochondrial alteration, DNA repair, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, and exosome. The chemoresistance-related proteins are localized to extracellular ligand, membrane receptor, cytosolic signal messenger, and nuclear transcription factors for various events, including proliferation, apoptosis, EMT, autophagy and exosome...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938622/profiling-cancer-related-gene-mutations-in-oral-squamous-cell-carcinoma-from-japanese-patients-by-targeted-amplicon-sequencing
#2
Takafumi Nakagaki, Miyuki Tamura, Kenta Kobashi, Ryota Koyama, Hisayo Fukushima, Tomoko Ohashi, Masashi Idogawa, Kazuhiro Ogi, Hiroyoshi Hiratsuka, Takashi Tokino, Yasushi Sasaki
Somatic mutation analysis is a standard practice in the study of human cancers to identify mutations that cause therapeutic sensitization and resistance. We performed comprehensive genomic analyses that used PCR target enrichment and next-generation sequencing on Ion Proton semiconductor sequencers. Forty-seven oral squamous cell carcinoma (OSCC) samples and their corresponding noncancerous tissues were used for multiplex PCR amplification to obtain targeted coverage of the entire coding regions of 409 cancer-related genes (covered regions: 95...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938613/high-phlpp1-expression-levels-predicts-longer-time-of-acquired-resistance-to-egfr-tyrosine-kinase-inhibitors-in-patients-with-lung-adenocarcinoma
#3
Youyou Xie, Dongqing Lv, Wei Wang, Minhua Ye, Xiaofeng Chen, Haihua Yang
BACKGROUND: In spite of an initial good response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in lung adenocarcinoma patients, resistance to treatment eventually occurs. Epidermal growth factor receptor (EGFR) activation stimulates Ras/Raf/Erk/MAPK and influences PI3K/Akt pathways, respectively. PHLPP negatively regulates PI3K/Akt and the RAF/RAS/ERK signaling pathways. Our study aimed to investigate the association between PH domain leucine-rich-repeats protein phosphatase (PHLPP) expression levels and the acquired resistance to EGFR TKIs in lung adenocarcinoma...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938574/the-dual-pi3k-mtor-inhibitor-gsk2126458-is-effective-for-treating-solid-renal-tumours-in-tsc2-mice-through-suppression-of-cell-proliferation-and-induction-of-apoptosis
#4
Kalin Narov, Jian Yang, Paulina Samsel, Ashley Jones, Julian R Sampson, Ming Hong Shen
Tuberous sclerosis (TSC) is an inherited tumour syndrome caused by mutations in TSC1 or TSC2 that lead to aberrant activation of mTOR. Tumour responses in TSC patients to rapamycin, an allosteric inhibitor of mTOR, or its analogs are partial and reversible probably due to feedback activation of Akt. In this study, we examined the efficacy of GSK2126458, an ATP-competitive dual inhibitor of PI3K/mTOR, in comparison to rapamycin for treatment of renal tumours in genetically engineered Tsc2(+/-) mice. We found that both GSK2126458 and rapamycin caused significant reduction in number and size of solid renal tumours...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938463/role-of-cyp51-in-the-regulation-of-t3-and-fsh-induced-steroidogenesis-in-female-mice
#5
Juan Liu, Ye Tian, Yu Ding, Dai Heng, Kaili Xu, Wenbo Liu, Cheng Zhang
Cytochrome P450 lanosterol 14α-demethylase (CYP51) is a key enzyme in sterols and steroids biosynthesis that involved in folliculogenesis and oocyte maturation, which is regulated by follicle stimulating hormone (FSH), as a key reproductive hormone during follicular development. Thyroid hormone (TH) is also important for normal reproductive function. Although T3 enhances FSH-induced preantral follicle growth, whether and how TH combines with FSH to regulate CYP51 expression during preantral to early antral transition stage is unclear...
August 18, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938395/aldose-reductase-mediates-nlrp3-inflammasome-initiated-innate-immune-response-in-hyperglycemia-induced-thp1-monocytes-and-male-mice
#6
Pabitra B Pal, Himangshu Sonowal, Kirtikar Shukla, Satish K Srivastava, Kota V Ramana
Despite recent studies that show oxidative stress-generated reactive oxygen species (ROS) regulate NLRP3-inflammasome-mediated innate immune response in various diabetic complications, the mechanism(s) of how ROS activate innate immune response is not well understood. We have shown earlier that aldose reductase (AR), besides reducing glucose, reduces lipid aldehydes and their glutathione conjugates and participates in various oxidative stress-induced inflammatory pathways. To understand the role of AR in ROS-induced innate immune response, we have investigated the mechanism(s) by which AR activates hyperglycemia-induced NLRP3-inflammsome- initiated innate immune response in Thp1 monocytes and in streptozotocin (STZ)-induced diabetic mice...
July 28, 2017: Endocrinology
https://www.readbyqxmd.com/read/28936923/egfr-pathway-subgroups-in-chilean-colorectal-cancer-patients-detected-by-mutational-and-expression-profiles-associated-to-different-clinicopathological-features
#7
Karin Alvarez, Paulina Orellana, Cynthia Villarroel, Luis Contreras, Hiroshi Kawachi, Maki Kobayashi, Ana Maria Wielandt, Marjorie De la Fuente, Juan Carlos Triviño, Udo Kronberg, Pilar Carvallo, Francisco López-Köstner
Colorectal cancer is a multistep process affecting several signaling pathways including EGFR (epidermal growth factor receptor), a therapeutic target for metastatic disease. Our aim was to characterize the mutational and expression profiles of the EGFR pathway in colorectal tumors and to integrate these results according to five previously defined groups. We screened seven genes for mutations ( KRAS-BRAF-PIK3CA-PIK3R1-AKT1-MAP2K1-PTEN) and six proteins (EGFR-p110α-p85α-PTEN-phosphoAKT-phosphoMEK1) by immunohistochemistry, PTEN deletion, and MSI...
September 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28936851/-research-of-reversal-effect-of-pesv-to-multi-drug-resistance-of-leukemia-stem-cell
#8
Xiang-Dong Yang, Xing-Li Wang, Wen-Hua Yang, Lei Zhao, Tian-Gai Yan
Using the BALB/c mouse multidrug resistance model of leukemia, the effect of peptide extract from scorpion venom (PESV) to the upstream signal factors of P-gp of MDR leukemia stem cells on the mouse tumor block was observed, and the mechanism of PESV to reverse the MDR of LSC was studied. At the same time, the expression of P-gp, MDR1 mRNA and PI3-K, NF-κB were respectively detected through flow cytometry, RT-PCR, Western blot and Elisa, and the mouse liver, spleen were examined via histopathological methods...
December 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28936683/trail-enhances-quinacrine-mediated-apoptosis-in-breast-cancer-cells-through-induction-of-autophagy-via-modulation-of-p21-and-dr5-interactions
#9
Sarita Das, Anmada Nayak, Sumit Siddharth, Deepika Nayak, Satya Narayan, Chanakya Nath Kundu
PURPOSE: Previously, we reported that quinacrine (QC) may cause apoptosis in breast and colon cancer cells by activating the death receptor 5 (DR5), resulting in autophagic cell death through p21 modulation. Here, we systematically evaluated the combined role of p21 and DR5 and their crosstalk in QC-mediated autophagy and apoptosis in breast cancer cells using in vitro and in vivo models. METHODS: Multiple breast cancer-derived cell lines (MCF-7, ZR-75-1, T47D, MDA-MB-231 and MCF-10A-Tr) and a mouse xenograft model were used...
September 21, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28936174/the-effect-of-velvet-antler-proteins-on-cardiac-microvascular-endothelial-cells-challenged-with-ischemia-hypoxia
#10
Xiang Xiao, Shuqiang Xu, Lin Li, Min Mao, Jinping Wang, Yanjun Li, Ziwei Wang, Fei Ye, Li Huang
Velvet antler (VA) is a precious traditional Chinese medicine that is capable of repeated regeneration. Based on the Chinese medicine theory of coordination the heart and kidneys, VA has been employed to treat heart diseases, including ischemic heart disease, heart failure, and arrhythmia. We examined the effects of VA proteins on primary cardiac microvascular endothelial cells (CMECs) that were subjected to ischemia-hypoxia (IH) to investigate their effects on and mechanism of action in the treatment of ischemic heart disease...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28935820/lack-of-serum-and-glucocorticoid-inducible-kinase-3-leads-to-podocyte-dysfunction
#11
Li-Qin Peng, Hong Zhao, Song Liu, Ya-Pei Yuan, Cheng-Yan Yuan, Mercy-Julian Mwamunyi, David Pearce, Li-Jun Yao
Serum- and glucocorticoid-inducible kinase 3 (SGK3) is a downstream mediator of PI3K, which is essential for maintaining the functional integrity of podocytes. However, little is known about the role of SGK3 in podocyte function. Herein, we demonstrated that SGK3 contributes to the maintenance of podocyte integrity. Conditionally immortalized mouse podocyte cells (MPCs) were treated with puromycin aminonucleoside (PAN). PAN treatment inhibited the activity of SGK3 and the expression of podocin. Short hairpin RNA (shRNA)-mediated knockdown of SGK3 also reduced podocin expression in the absence of PAN...
September 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28935395/the-role-of-tec-kinase-signaling-pathways-in-the-development-of-mallory-denk-bodies-in-balloon-cells-in-alcoholic-hepatitis
#12
N Afifiyan, B Tillman, B A French, O Sweeny, M Masouminia, S Samadzadeh, S W French
Several research strategies have been used to study the pathogenesis of alcoholic hepatitis (AH). These strategies have shown that various signaling pathways are the target of alcohol in liver cells. However, few have provided specific mechanisms associated with Mallory-Denk Bodies (MDBs) formed in Balloon cells in AH. The formation of MDBs in these hepatocytes is an indication that the mechanisms of protein quality control have failed. The MDB is the result of aggregation and accumulation of proteins in the cytoplasm of balloon degenerated liver cells...
September 18, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28934922/inhibition-of-phosphatidylinositide-3-kinase-impairs-the-benzyl-isothiocyanate-induced-accumulation-of-autophagic-molecules-and-nrf2-in-human-colon-cancer-cells
#13
Xiaoyang Liu, Naomi Abe-Kanoh, Yujia Liu, Beiwei Zhu, Shintaro Munemasa, Toshiyuki Nakamura, Yoshiyuki Murata, Yoshimasa Nakamura
The regulating role of phosphatidylinositide 3-kinase (PI3K) in benzyl isothiocyanate (BITC)-induced Nrf2 activation, contributing to the inducible expression of cytoprotective genes, was investigated. BITC significantly enhanced the accumulation of Nrf2 as well as autophagic molecules in human colorectal cancer HCT-116 cells. Experiments using a PI3K-specific inhibitor suggested that PI3K plays the key role in the non-canonical Nrf2 activation by BITC.
September 22, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28934754/cntn-1-enhances-chemoresistance-in-human-lung-adenocarcinoma-through-induction-of-epithelial-mesenchymal-transition-by-targeting-the-pi3k-akt-pathway
#14
Ruijie Zhang, Shenghua Sun, Fuyun Ji, Chun Liu, Hua Lin, Lihua Xie, Honghui Yang, Wenxiang Tang, Yan Zhou, Jianping Xu, Pei Li
BACKGROUND/AIMS: Chemoresistance has been a major obstacle to the effective treatment of lung cancer. Previously, we found that contactin-1 (CNTN-1) is related to cisplatin resistance in lung adenocarcinoma. Here, we aimed to investigate the underlying mechanism behind the role of CNTN-1 in cisplatin resistance in lung adenocarcinoma. METHODS: EMT-associated phenotypes, including alterations in cellular morphology and marker (E-cadherin, N-cadherin and Vimentin) expression, were compared between A549 cells and A549/DDP cells (a cisplatin-resistant cell line of lung adenocarcinoma with abnormal CNTN-1 expression) by using real-time time PCR and Western blotting...
September 1, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28934384/short-syndrome-due-to-a-novel-de-novo-mutation-in-prkce-protein-kinase-c%C3%A9-impairing-torc2-dependent-akt-activation
#15
Diana Alcantara, Frances Elmslie, Martine Tetreault, Eric Bareke, Taila Hartley, Jacek Majewski, Kym Boycott, A Micheil Innes, David A Dyment, Mark O'Driscoll
SHORT syndrome is a rare, recognizable syndrome resulting from heterozygous mutations in PIK3R1 encoding a regulatory subunit of phosphoinositide-3-kinase (PI3K). The condition is characterized by short stature, intrauterine growth restriction, lipoatrophy and a facial gestalt involving a triangular face, deep set eyes, low hanging columella and small chin. PIK3R1 mutations in SHORT syndrome result in reduced signaling through the PI3K-AKT-mTOR pathway. We performed whole exome sequencing for an individual with clinical features of SHORT syndrome but negative for PIK3R1 mutation and her parents...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934275/activation-of-phosphatidylinositol-3-kinase-akt-snail-signaling-pathway-contributes-to-epithelial-mesenchymal-transition-induced-multi-drug-resistance-to-sorafenib-in-hepatocellular-carcinoma-cells
#16
Jiejie Dong, Bo Zhai, Weihua Sun, Fengli Hu, Hao Cheng, Jun Xu
Sorafenib, an orally available kinase inhibitor, is the standard first-line systemic drug for advanced hepatocellular carcinoma (HCC), and it exerts potent inhibitory activity against epithelial-mesenchymal transition (EMT) and multidrug resistance (MDR) by inhibiting mitogen-activated protein kinase (MAPK) signaling in HCC. However, after long-term exposure to sorafenib, HCC cells exhibit EMT and resistance to sorafenib. The activation of AKT by sorafenib is thought to be responsible for the development of these characteristics...
2017: PloS One
https://www.readbyqxmd.com/read/28933986/the-antiangiogenesis-effect-of-pirfenidone-in-wound-healing-in-vitro
#17
Xiao'an Liu, Yangfan Yang, Xiujuan Guo, Liling Liu, Kaili Wu, Minbin Yu
Abstracts Background: Pirfenidone is mostly used in antifibrotic and anti-inflammatory therapies. We have previously demonstrated that pirfenidone had antifibrotic and anti-inflammatory effects on the wound healing process after glaucoma filtration surgery in vitro and in vivo. Since the wound healing and reactive scarring process simultaneously involves inflammation, fibrosis, and angiogenesis, and angiogenesis plays a more important role in chronic or prolonged wound healing, we tried to explore the antiangiogenesis effect in pirfenidone and its potential multitarget function in regulating excessive scarring...
September 21, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28932706/global-proteomics-revealed-klebsiella-pneumoniae-induced-autophagy-and-oxidative-stress-in-caenorhabditis-elegans-by-inhibiting-pi3k-akt-mtor-pathway-during-infection
#18
Arumugam Kamaladevi, Krishnaswamy Balamurugan
The enterobacterium, Klebsiella pneumoniae invades the intestinal epithelium of humans by interfering with multiple host cell response. To uncover a system-level overview of host response during infection, we analyzed the global dynamics of protein profiling in Caenorhabditis elegans using quantitative proteomics approach. Comparison of protein samples of nematodes exposed to K. pneumoniae for 12, 24, and 36 h by 2DE revealed several changes in host proteome. A total of 266 host-encoded proteins were identified by 2DE MALDI-MS/MS and LC-MS/MS and the interacting partners of the identified proteins were predicted by STRING 10...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28932550/lncrna260-specific-sirna-targeting-il28ra-gene-inhibit-cardiomyocytes-hypoxic-reoxygenation-injury
#19
Ge Gong, Xin-Xing Yang, Yanyan Li, Hong-Yu Geng, Zhi-Jian Yang, Lian-Sheng Wang, Hyun Jun Kim, Xin-Zheng Lu
BACKGROUND: The interleukin 28 receptor alpha (IL28RA) gene was indicated to be associated with apoptosis. However, it was not clear whether long non-coding RNA 260 (lncRNA 260)-specific siRNA targeting IL28RA gene could inhibit hypoxic reoxygenation (H/R) cardiomyocytes injury or not. To explore the mechanisms underlying the protective effects of lncRNA260-specific siRNA-mediated inhibition of IL28RA from H/R injury in cardiomyocytes, the current research was performed. METHODS: The primary neonatal rat cardiomyocytes were transfected with three different pairs of siRNA specific to lncRNA260 targeting IL28RA gene and then were undergone with the conditions simulating H/R injury...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28932171/the-role-of-ppar%C3%AE-and-autophagy-in-ros-production-lipid-droplets-biogenesis-and-its-involvement-with-colorectal-cancer-cells-modulation
#20
José Antonio Fagundes Assumpção, Kelly Grace Magalhães, José Raimundo Corrêa
BACKGROUND: In cancer cells, autophagy can act as both tumor suppressor, when autophagic event eliminates cellular contends which exceeds the cellular capacity of regenerate promoting cell death, and as a pro-survival agent removing defective organelles and proteins and helping well-established tumors to maintain an accelerated metabolic state while still dealing with harsh conditions, such as inflammation. Many pathways can coordinate the autophagic process and one of them involves the transcription factors called PPARs, which also regulate cellular differentiation, proliferation and survival...
2017: Cancer Cell International
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