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https://www.readbyqxmd.com/read/28811325/ppar%C3%AE-ligand-induced-annexin-a1-expression-determines-chemotherapy-response-via-deubiquitination-of-death-domain-kinase-rip-in-triple-negative-breast-cancers
#1
Luxi Chen, Yi Yuan, Shreya Kar, Madhu M Kanchi, Suruchi Arora, Ji E Kim, Pei F Koh, Einas Yousef, Ramar P Samy, Muthu K Shanmugam, Tuan Z Tan, Sung W Shin, Frank Arfuso, Han M Shen, Henry Yang, Boon C Goh, Joo I Park, Louis Gaboury, Peter E Lobie, Gautam Sethi, Lina Hk Lim, Alan P Kumar
Metastatic breast cancer is still remain incurable so far, new specifically targeted and more effective therapies for triple negative breast cancer (TNBC) are required in the clinic. In this study, our clinical data has established that basal and claudin-low subtypes of breast cancer (TNBC types) express significantly higher levels of Annexin A1 (ANXA1) with poor survival outcomes. Using human cancer cell lines which model the TNBC subtype, we observed a strong positive correlation between expression of ANXA1 and Peroxisome Proliferator-Activated Receptor gamma (PPARγ)...
August 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28811071/biological-evaluation-of-2-pyrazolinyl-1-carbothioamide-derivatives-against-hct116-human-colorectal-cancer-cell-lines-and-elucidation-on-qsar-and-molecular-binding-modes
#2
Beom Soo Kim, Soon Young Shin, Seunghyun Ahn, Dongsoo Koh, Young Han Lee, Yoongho Lim
In the search of compounds exhibiting anticancer activity, 37 derivatives of 2-pyrazolinyl-1-carbothioamide were designed and synthesized. Clonogenic cell survival assays were adapted to measure the cytotoxicities of the synthetic derivatives against HCT116 human colon cancer cell lines. Half-maximal cell growth inhibitory concentrations (GI50) ranged from 0.49 to 41.22µM. The compound with the lowest GI50 value, 3-(2-hydroxy-4,5-dimethoxyphenyl)-5-(naphthalen-1-yl)-N-(3,4,5-trimethoxyphenyl)-pyrazolinyl-1-carbothioamide, was subjected to further biological studies, including cell viability and apoptosis assays to examine levels of annexin-V in the outer plasma membrane layer and poly ADP-ribose polymerase cleavage...
August 4, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28809097/piconewton-scale-analysis-of-ras-braf-signal-transduction-with-single-molecule-force-spectroscopy
#3
Chae-Seok Lim, Cheng Wen, Yanghui Sheng, Guangfu Wang, Zhuan Zhou, Shiqiang Wang, Huaye Zhang, Anpei Ye, J Julius Zhu
Intermolecular interactions dominate the behavior of signal transduction in various physiological and pathological cell processes, yet assessing these interactions remains a challenging task. Here, this study reports a single-molecule force spectroscopic method that enables functional delineation of two interaction sites (≈35 pN and ≈90 pN) between signaling effectors Ras and BRaf in the canonical mitogen-activated protein kinase (MAPK) pathway. This analysis reveals mutations on BRaf at Q257 and A246, two sites frequently linked to cardio-faciocutaneous syndrome, result in ≈10-30 pN alterations in RasBRaf intermolecular binding force...
August 15, 2017: Small
https://www.readbyqxmd.com/read/28794627/in-situ-imaging-of-quantum-dot-azd4547-conjugates-for-tracking-the-dynamic-behavior-of-fibroblast-growth-factor-receptor-3
#4
Gyoyeon Hwang, Hyeonhye Kim, Hojong Yoon, Chiman Song, Dong-Kwon Lim, Taebo Sim, Jiyeon Lee
Fibroblast growth factor receptors (FGFRs) play an important role in determining cell proliferation, differentiation, migration, and survival. Although a variety of small-molecule FGFR inhibitors have been developed for cancer therapeutics, the interaction between FGFRs and FGFR inhibitors has not been well characterized. The FGFR-inhibitor interaction can be characterized using a new imaging probe that has strong, stable signal properties for in situ cellular imaging of the interaction without quenching. We developed a kinase-inhibitor-modified quantum dot (QD) probe to investigate the interaction between FGFR and potential inhibitors...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28791417/diverse-gene-expression-patterns-in-response-to-anticancer-drugs-between-human-and-mouse-cell-lines-revealed-by-a-comparative-transcriptomic-analysis
#5
Yong Guo, Zhuoran Liang, Xiaoliang Hou, Zhi Zhang
The aim of the present study was to perform comparative genomics using gene expression profile datasets of mice and humans who had been treated with anticancer drugs, to determine the similarities and differences in the antitumor mechanisms in the two mammals. This involved data mining of antitumor gene expression regulation, and screening of genetic loci from experimental mouse models of antitumor targets, to provide a theoretical basis of drug design. Subsequently, 9 overlapping genes with opposite expression patterns were identified across mouse and human cell lines that were treated with a specific cyclin‑dependent kinase 4/6 inhibitor, PD0332991...
August 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28791377/c%C3%A2-maf-inducing-protein-inhibits-cofilin%C3%A2-1-activity-and-alters-podocyte-cytoskeleton-organization
#6
Lixia Yu, Jianming Ye, Qifeng Liu, Jianhua Feng, Xiaoxia Gu, Qiang Sun, Guoyuan Lu
The glomerular visceral epithelial cells, also termed podocytes, are key in maintaining the normal renal filtration barrier. Although it has been demonstrated that stimulation of c‑Maf inducing protein (CMIP) expression is involved in podocyte damage, the molecular events during this process remain unclear. In the current study, CMIP‑induced proximal signaling was investigated by focusing on its effect on cofilin‑1 activity in puromycin aminonucleoside (PA)‑damaged podocytes. An obvious elevation of CMIP expression and phosphorylated (p) cofilin‑1 levels was detected in cultured podocytes treated with PA and in glomeruli isolated from PA‑induced nephropathy rats...
August 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28780155/oxyresveratrol-improves-tight-junction-integrity-through-the-pkc-and-mapk-signaling-pathways-in-caco-2%C3%A2-cells
#7
HyunA Jo, Dahyun Hwang, Jeong-Keun Kim, Young-Hee Lim
Strengthening intestinal tight junctions (TJ) provides an effective barrier from the external environment and is important for recovery from inflammatory bowel disease. Oxyresveratrol (OXY), an isomer of hydroxylated resveratrol, is isolated from many plants. The aim of this study was to investigate the effect of OXY on intestinal TJ and to elucidate the mechanism underlying the OXY-mediated increase in TJ integrity in human intestinal Caco-2 cells. OXY-treated Caco-2 cell monolayers showed decreased monolayer permeability as evaluated by paracellular transport assay...
August 2, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28775072/lmo2-lim-domain-only-2-modulates-sphk1-sphingosine-kinase-and-promotes-endothelial-cell-migration
#8
Gianfranco Matrone, Shu Meng, Qilin Gu, Jie Lv, Longhou Fang, Kaifu Chen, John P Cooke
OBJECTIVE: Lmo (LIM-domain-only)2 transcription factor is involved in hematopoiesis and vascular remodeling. Sphk (sphingosine kinase)1 phosphorylates sphingosine to S1P (sphingosine-1-phosphate). We hypothesized that Lmo2 regulates Sphk1 to promote endothelial cell (EC) migration and vascular development. APPROACH AND RESULTS: Lmo2 and Sphk1 knockdown (KD) were performed in Tg(fli1:EGFP) (y1) zebra fish and in human umbilical vein EC. Rescue of phenotypes or overexpression of these factors were achieved using mRNA encoding Lmo2 or Sphk1...
August 3, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28774704/lim-kinase-function-and-renal-growth-potential-role-for-lim-kinases-in-fetal-programming-of-kidney-development
#9
Alexander J Sparrow, Dylan Sweetman, Simon J M Welham
AIMS: Maternal dietary restriction during pregnancy impairs nephron development and results in offspring with fewer nephrons. Cell turnover in the early developing kidney is altered by exposure to maternal dietary restriction and may be regulated by the LIM-kinase family of enzymes. We set out to establish whether disturbance of LIM-kinase activity might play a role in the impairment of nephron formation. MAIN METHODS: E12.5 metanephric kidneys and HK2 cells were grown in culture with the pharmacological LIM-kinase inhibitor BMS5...
July 31, 2017: Life Sciences
https://www.readbyqxmd.com/read/28771227/klotho-enhances-foxo3-mediated-manganese-superoxide-dismutase-expression-by-negatively-regulating-pi3k-akt-pathway-during-tacrolimus-induced-oxidative-stress
#10
Sun Woo Lim, Long Jin, Kang Luo, Jian Jin, Yoo Jin Shin, Sung Yi Hong, Chul Woo Yang
Mammalian members of the forkhead box protein O (FoxO) class of transcription factors are implicated in the regulation of oxidative stress, and FoxO proteins are negatively regulated by the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway. We examined the effect of Klotho on the PI3K/AKT pathway and manganese superoxide dismutase (MnSOD) during tacrolimus (Tac)-induced oxidative stress. Klotho-treated mice showed decreased Tac-induced oxidative stress accompanied by functional and histological improvements...
August 3, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28754884/von-hippel-lindau-regulates-interleukin-32%C3%AE-stability-in-ovarian-cancer-cells
#11
Hyo Jeong Yong, Jeong Su Park, Ae Lee Jeong, Sora Han, Sunyi Lee, Hye In Ka, Buyanravjkh Sumiyasuren, Hyun Jeong Joo, Su Jeong So, Ji Young Park, Do-Young Yoon, Jong Seok Lim, Myeong-Seok Lee, Hee Gu Lee, Young Yang
Hypoxia-induced interleukin-32β (IL-32β) shifts the metabolic program to the enhanced glycolytic pathway. In the present study, the underlying mechanism by which hypoxia-induced IL-32β stability is regulated was investigated in ovarian cancer cells. IL-32β expression increased under hypoxic conditions in ovarian cancer cells as it did in breast cancer cells. The amount of IL-32β was regulated by post-translational control rather than by transcriptional activation. Under normoxic conditions, IL-32β was continuously eliminated through ubiquitin-dependent degradation by the von-Hippel Lindau (VHL) E3 ligase complex...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28751820/cynanchum-wilfordii-polysaccharides-suppress-dextran-sulfate-sodium-induced-acute-colitis-in-mice-and-the-production-of-inflammatory-mediators-from-macrophages
#12
Chang-Won Cho, Sungeun Ahn, Tae-Gyu Lim, Hee-Do Hong, Young Kyoung Rhee, Deok-Chun Yang, Mi Jang
We recently reported the immune-enhancing effects of a high-molecular-weight fraction (HMF) of CW in macrophages and immunosuppressed mice, and this effect was attributed to a crude polysaccharide. As polysaccharides may also have anti-inflammatory functions, we investigated the anti-inflammatory effects and related molecular mechanisms of a crude polysaccharide (HMFO) obtained from HMF of CW in mice with dextran sulfate sodium- (DSS-) induced colitis and in lipopolysaccharide-induced RAW 264.7 macrophages...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28751290/myoadenylate-deaminase-deficiency-a-frequent-cause-of-muscle-pain-a-case-detected-by-exercise-testing
#13
Lydie Lim, Maeva Palayer, Antoine Bruneau, Franck Letournel, Cédric Le Maréchal, Gilles Simard, Pascal Reynier, Chadi Homedan, Aleksandra Nadaj-Pakleza
Myoadenylate deaminase deficit (MAD, MIM#615511) is the most common cause of metabolic myopathies with an estimated prevalence of 1-2% in the general population. We report the case of a 39-year-old man suffering from severe skeletal muscle pain that had developed gradually for 4 years. A moderate increase in creatine kinase (CK) was the only biological sign observed. This study takes a closer look at a common but poorly known pathology and highlights the interest of the dynamic metabolic investigations carried out during exercise stress test with a cycle ergometer...
August 1, 2017: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/28749622/understanding-and-challenges-in-taking-tyrosine-kinase-inhibitors-among-malaysian-chronic-myeloid-leukemia-patients-a-qualitative-study
#14
Yik Ming Lim, Wei Lerk Eng, Huan Keat Chan
Background: In Malaysia, the treatment for chronic myeloid leukemia (CML) has long been delivered under the Malaysian Patient Assistance Program (MYPAP), but research on identifying factors contributing to non-adherence to tyrosine kinase inhibitors (TKIs) is still limited. The current study explored understanding and challenges of Malaysian CML patients in taking imatinib and nilotinib. Methods: Semi-structured, face-to-face interviews were conducted with 13 CML patients receiving treatment at a public tertiary care center, and were analyzed using the content analysis approach...
July 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28745316/elevation-of-adenylate-energy-charge-by-angiopoietin-like-4-enhances-epithelial-mesenchymal-transition-by-inducing-14-3-3%C3%AE-expression
#15
Z Teo, M K Sng, J S K Chan, M M K Lim, Y Li, L Li, T Phua, J Y H Lee, Z W Tan, P Zhu, N S Tan
Metastatic cancer cells acquire energy-intensive processes including increased invasiveness and chemoresistance. However, how the energy demand is met and the molecular drivers that coordinate an increase in cellular metabolic activity to drive epithelial-mesenchymal transition (EMT), the first step of metastasis, remain unclear. Using different in vitro and in vivo EMT models with clinical patient's samples, we showed that EMT is an energy-demanding process fueled by glucose metabolism-derived adenosine triphosphate (ATP)...
July 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28732574/albiflorin-ameliorates-obesity-by-inducing-thermogenic-genes-via-ampk-and-pi3k-akt-in-vivo-and-in-vitro
#16
Mi-Young Jeong, Jinbong Park, Dong-Hyun Youn, Yunu Jung, JongWook Kang, Seona Lim, Min-Woo Kang, Hye-Lin Kim, Hong-Seob So, Raekil Park, Seung-Heon Hong, Jae-Young Um
OBJECTIVE: Brown adipose tissue (BAT) activation has been identified as a possible target to treat obesity and to protect against metabolic diseases by increasing energy consumption. We explored whether albiflorin (AF), a natural compound, could contribute to lowering the high risk of obesity with BAT and primary brown preadipocytes in vivo and in vitro. MATERIALS/METHODS: Human adipose tissue-derived mesenchymal stem cells (hAMSCs) were cultured with adipogenic differentiation media with or without AF...
August 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28732387/the-micrornas-mir-200b-3p-and-mir-429-5p-target-the-limk1-cfl1-pathway-to-inhibit-growth-and-motility-of-breast-cancer-cells
#17
Dengfeng Li, Hong Wang, Hongming Song, Hui Xu, Bingkun Zhao, Chenyang Wu, Jiashu Hu, Tianqi Wu, Dan Xie, Junyong Zhao, Qiang Shen, Lin Fang
Triple-negative breast cancer (TNBC) has the worst prognosis of all subtypes of breast cancer (BC), with limited options for conventional therapy and no targeted therapies. MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression. In this study, we aimed to determine whether two members of the miR-200 family, miR-200b-3p and miR-429-5p, are involved in BC cell proliferation and motility and to elucidate their target genes and pathways. We performed a meta-analysis that reveals down-regulated expression of miR-200b-3p and miR-429-5p in BC tissues and cell lines, consistent with a lower expression of miR-200b-3p and miR-429-5p in MDA-MB-231 and HCC1937 cells than in MCF-7 and MCF-10 cells...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28731589/effects-of-nitric-oxide-on-large-conductance-ca-2-activated-k-currents-in-human-cardiac-fibroblasts-through-pka-and-pkg-related-pathways
#18
Hyemi Bae, Inja Lim
The human cardiac fibroblast (HCF) is the most abundant cell type in the myocardium, and HCFs play critical roles in maintaining normal cardiac function. However, unlike cardiomyocytes, the electrophysiology of HCFs is not well established. In the cardiovascular system, Ca(2+) -activated K(+) (KCa) channels have distinct physiological and pathological functions, and nitric oxide (NO) play key roles. In this study, we investigated the potential effects of NO on KCa channels in HCFs. We recorded strong oscillating, well-maintained outward K(+) currents without marked inactivation throughout the test pulse period and detected outward rectification in the I-V curve; these are all characteristics that are typical of KCa currents...
July 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28724838/csk-regulates-blood-pressure-by-controlling-the-synthetic-pathways-of-aldosterone
#19
Sung-Moon Kim, Ji-One Kang, Ji Eun Lim, Sue-Yun Hwang, Bermseok Oh
BACKGROUND: Blood pressure is regulated by a network of diverse physiological pathways. The C-terminal Src kinase (CSK) locus (15q24) is associated with blood pressure in various ethnic groups. It was recently reported thatCskinsufficiency increases blood pressure through Src. The mechanisms of hypertension inCsk(+/-)mice are examined further in this study.Methods and Results:To identify a causal component responsible for hypertension inCsk(+/-), the heart rate was measured by electrocardiogram and plasma volume by Evans blue dilution...
July 20, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28720775/metformin-ameliorates-the-phenotype-transition-of-peritoneal-mesothelial-cells-and-peritoneal-fibrosis-via-a-modulation-of-oxidative-stress
#20
Hyun-Soo Shin, Jiyeon Ko, Dal-Ah Kim, Eun-Sun Ryu, Hye-Myung Ryu, Sun-Hee Park, Yong-Lim Kim, Eok-Soo Oh, Duk-Hee Kang
Phenotype transition of peritoneum is an early mechanism of peritoneal fibrosis. Metformin, 5'-adenosine monophosphate-activated protein kinase (AMPK) activator, has recently received a new attention due to its preventive effect on organ fibrosis and cancer metastasis by inhibiting epithelial-to-mesenchymal transition (EMT). We investigated the effect of metformin on EMT of human peritoneal mesothelial cells (HPMC) and animal model of peritoneal dialysis (PD). TGF-β1-induced EMT in HPMC was ameliorated by metformin...
July 18, 2017: Scientific Reports
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