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https://www.readbyqxmd.com/read/28928287/hif-3%C3%AE-promotes-metastatic-phenotypes-in-pancreatic-cancer-by-transcriptional-regulation-of-the-rhoc-rock1-signaling-pathway
#1
Xianfei Zhou, Xingjun Guo, Meiyuan Chen, Chencheng Xie, Jianxin Jiang
Hypoxia contributes to pancreatic cancer progression and promotes its growth and invasion. Previous research principally focused on hypoxia-inducible factor-1 alpha and HIF-2α (HIF1A and EPAS1) as the major hypoxia-associated transcription factors in pancreatic cancer. However, the role of HIF-3α (HIF3A) has not been investigated. Therefore, HIF-1α, HIF-2α, and HIF-3α expression levels were measured under normoxic and hypoxic conditions. In addition, HIF-3α expression was measured in human pancreatic cancer tissue specimens and the impact of altered HIF-3α expression on cell invasion and migration was investigated in vitro and in vivo, as well as the underlying mechanisms...
September 19, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28926926/protective-effects-of-aloperin-on-monocroline-induced-pulmonary-hypertension-via-regulation-of-rho-a-rho-kinsase-pathway-in-rats
#2
Fan Wu, Wanxia Yao, Jiamei Yang, Min Zhang, Yanping Xu, Yinju Hao, Lin Yan, Yang Niu, Tao Sun, Jianqiang Yu, Ru Zhou
Pulmonary hypertension (PH) is fatal disease which closely involves Rho A/ Rho kinsase (ROCK) pathway. Aloperine is a main active alkaloid extracted from Sophora alopecuroides, which is a traditional Chinese herbal medicine that has been used widely. However, the effects of this alkaloid on pulmonary hypertension and its mechanisms remain unclear. Therefore, this study is designed to investigate whether aloperine has protective effects on PH induced by monocrotaline, whether these effects may be related to regulation of RhoA/ROCK pathway in rats...
September 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28923399/up-regulation-of-rho-associated-kinase-1-2-by-glucocorticoids-promotes-migration-invasion-and-metastasis-of-melanoma
#3
Gao-Xiang Huang, Yan Wang, Jie Su, Peng Zhou, Bo Li, Li-Juan Yin, Jian Lu
Although glucocorticoids (GCs) regulate proliferation, differentiation and apoptosis of tumor cells, their influence on metastasis of tumor cells is poorly understood. Melanoma is a type of skin cancers with high metastasis. We investigated the effect of GCs on metastasis of melanoma cells and its mechanism. We found that GCs significantly promoted the adhesion, migration, invasion of melanoma cells in vitro and lung metastasis in experimental melanoma metastasis mice. Dexamethasone (Dex), a synthetic GC, did not change the RhoA, RhoB and RhoC signalings, but significantly increased the expression and activity of Rho-associated kinase 1/2 (ROCK1/2)...
September 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28901478/microrna%C3%A2-195-inhibits-cell-proliferation-migration-and-invasion-in-laryngeal-squamous-cell-carcinoma-by-targeting-rock1
#4
Yang Liu, Jixiang Liu, Lin Wang, Xiangli Yang, Xiang Liu
Laryngeal carcinoma is the second most common malignancy of the head and neck cancers. The most common type of laryngeal carcinoma comprises laryngeal squamous cell carcinoma (LSCC), which accounts for ~95% of laryngeal carcinoma cases. Despite great progress in diagnostic and therapeutic techniques over the last few decades, the prognosis for patients with LSCC remains poor. A number of studies reported that various miRNAs are dysregulated in LSCC and serve critical roles in LSCC tumorigenesis and tumor development...
September 11, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28899000/rhoa-rock-signalling-is-necessary-for-lateralization-and-differentiation-of-the-developing-sinoatrial-node
#5
Rebecca Vicente-Steijn, Tim P Kelder, Leon G Tertoolen, Lambertus J Wisse, Daniël A Pijnappels, Robert E Poelmann, Martin J Schalij, Marco C deRuiter, Adriana C Gittenberger-de Groot, Monique R M Jongbloed
Aims: RHOA-ROCK signalling regulates cell migration, proliferation, differentiation, and transcription. RHOA is expressed in the developing cardiac conduction system in chicken and mice. In early development, the entire sinus venosus myocardium, including both the transient left-sided and the definitive sinoatrial node (SAN), has pacemaker potential. Later, pacemaker potential is restricted to the right-sided SAN. Disruption of RHOA expression in adult mice causes arrhythmias including bradycardia and atrial fibrillation, the mechanism of which is unknown but presumed to affect the SAN...
August 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28888686/fibroblast-derived-hgf-drives-acinar-lung-cancer-cell-polarization-through-integrin-dependent-rhoa-rock1-inhibition
#6
Anirban Datta, Emma Sandilands, Keith E Mostov, David M Bryant
The formation of lumens in epithelial tissues requires apical-basal polarization of cells, and the co-ordination of this individual polarity collectively around a contiguous lumen. Signals from the Extracellular Matrix (ECM) instruct epithelia as to the orientation of where basal, and thus consequently apical, surfaces should be formed. We report that this pathway is normally absent in Calu-3 human lung adenocarcinoma cells in 3-Dimensional culture, but that paracrine signals from MRC5 lung fibroblasts can induce correct orientation of polarity and acinar morphogenesis...
September 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28845297/discovery-of-a-rock-inhibitor-fpnd-which-prevents-cerebral-hemorrhage-through-maintaining-vascular-integrity-by-interference-with-ve-cadherin
#7
Shang Li, Nana Ai, Mingyun Shen, Yuanye Dang, Cheong-Meng Chong, Peichen Pan, Yiu Wa Kwan, Shun Wan Chan, George Pak Heng Leung, Maggie Pui Man Hoi, Tingjun Hou, Simon Ming-Yuen Lee
Hemorrhagic stroke occurs when a weakened vessel ruptures and bleeds into the surrounding brain, leading to high rates of death and disability worldwide. A series of complex pathophysiological cascades contribute to the risk of hemorrhagic stroke, and no therapies have proven effective to prevent hemorrhagic stroke. Stabilization of vascular integrity has been considered as a potential therapeutic target for hemorrhagic stroke. ROCKs, which belong to the serine/threonine protein kinase family and participate in the organization of actin cytoskeleton, have become attractive targets for the treatment of strokes...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28841710/inhibition-of-rock1-kinase-modulates-both-tumor-cells-and-stromal-fibroblasts-in-pancreatic-cancer
#8
Clifford J Whatcott, Serina Ng, Michael T Barrett, Galen Hostetter, Daniel D Von Hoff, Haiyong Han
ROCK, or Rho-associated coiled coil-containing protein kinase, is a member of the AGC kinase family and has been shown to play a role in cell migration, ECM synthesis, stress-fiber assembly, and cell contraction. Increased ROCK expression has been reported in multiple pathological conditions, including cancer. Here, we report increased expression of ROCK 1 in pancreatic tumor epithelial cells as well as in cancer associated fibroblasts (CAF). In our analysis, 62% of tumor samples exhibited ≥2+ in staining intensity by IHC analysis, versus 40% of adjacent normal tissue samples (P<0...
2017: PloS One
https://www.readbyqxmd.com/read/28819898/regulation-of-hepatic-na-k-atpase-in-obese-female-and-male-rats-involvement-of-erk1-2-ampk-and-rho-rock
#9
Julijana Stanimirovic, Milan Obradovic, Anastasija Panic, Voin Petrovic, Dragan Alavantic, Irena Melih, Esma R Isenovic
In this study, we assessed whether the disturbed regulation of sodium/potassium-adenosine-triphosphatase (Na(+)/K(+)-ATPase) occurs as a consequence of obesity-induced IR in sex-specific manner. We also assessed whether alterations of IRS/PI3K/Akt, ERK1/2, AMPKα, and RhoA/ROCK signaling cascades have an important role in this pathology. Female and male Wistar rats (150-200 g, 8 weeks old) were fed a standard laboratory diet or a high-fat (HF) diet (42% fat) for 10 weeks. The activity of hepatic Na(+)/K(+)-ATPase and Rho, and the association of IRS-1/p85 were assessed in liver...
August 17, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28818997/ccr2-3-utr-functions-as-a-competing-endogenous-rna-to-inhibit-breast-cancer-metastasis
#10
Jinhang Hu, Xiaoman Li, Xinwei Guo, Qianqian Guo, Chenxi Xiang, Zhiting Zhang, Yingying Xing, Tao Xi, Lufeng Zheng
Diverse RNA transcripts acting as competing endogenous RNAs (ceRNAs) can co-regulate each other's expression by competing for shared microRNAs. CCR2 protein, the receptor of CCL2, is implicated in cancer progression. However, our results showed that higher CCR2 mRNA level was remarkably associated with prolonged survival of breast cancer patients. The conflicting results prompt us to study the non-coding function of CCR2 mRNA. We indicated that CCR2 3'UTR inhibited MDA-MB-231 and MCF-7 cells metastasis by repressing EMT in vitro and suppressed breast cancer metastasis in vivo Mechanistically, CCR2 3'UTR modulated RhoGAP protein STARD13 expression via acting as a STARD13 ceRNA in a microRNA-dependent and protein coding-independent manner...
August 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28804108/effects-of-vitrification-and-a-rho-associated-coiled-coil-containing-protein-kinase-1-inhibitor-on-the-meiotic-and-developmental-competence-of-feline-oocytes
#11
Saengtawan Arayatham, Narong Tiptanavattana, Theerawat Tharasanit
Oocyte cryopreservation is the technique of choice for the long-term storage of female gametes. However, it induces an irreversible loss of oocyte viability and function. We examined the effects of vitrification and a Rho-associated coiled-coil containing protein kinase 1 (ROCK1) inhibitor (ROCKi) on the meiotic and developmental competence of feline oocytes. We examined the expression of LIM kinase (LIMK) 1 and 2, with and without ROCKi treatment. Cumulus oocyte complexes (COCs) were matured in vitro with 0, 10, 20, and 40 µM ROCKi...
August 11, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28800959/mybph-inhibits-vascular-smooth-muscle-cell-migration-and-attenuates-neointimal-hyperplasia-in-a-rat-carotid-balloon-injury-model
#12
Ting Zhu, Yi He, Jue Yang, Weiguo Fu, Xin Xu, Yi Si
Vascular smooth muscle cell (VSMC) migration is implicated in restenosis. Myosin binding protein H (MYBPH) is capable of reducing cell motility and metastasis. In this study, we sought to determine whether MYBPH is involved in VSMC migration and neointima formation in response to vascular injury. To determine the expression of MYBPH in injured artery, we used a standard rat carotid artery balloon-injury model. In vivo studies have demonstrated that MYBPH is upregulated after vascular injury. VSMCs treated with platelet-derived growth factor (PDGF)-BB displayed increased MYBPH mRNA and protein levels...
August 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28761175/rock1-is-a-novel-rac1-effector-to-regulate-tubular-endocytic-membrane-formation-during-clathrin-independent-endocytosis
#13
David Soriano-Castell, Albert Chavero, Carles Rentero, Marta Bosch, Maite Vidal-Quadras, Albert Pol, Carlos Enrich, Francesc Tebar
Clathrin-dependent and -independent pathways contribute for β1-integrin endocytosis. This study defines a tubular membrane clathrin-independent endocytic network, induced with the calmodulin inhibitor W13, for β1-integrin internalization. This pathway is dependent on increased phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) levels and dynamin activity at the plasma membrane. Exogenous addition of PI(4,5)P2 or phosphatidylinositol-4-phosphate 5-kinase (PIP5K) expression mimicked W13-generated-tubules which are inhibited by active Rac1...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28760620/microcontact-printing-of-polydopamine-on-thermally-expandable-hydrogels-for-controlled-cell-adhesion-and-delivery-of-geometrically-defined-microtissues
#14
Yu Bin Lee, Se-Jeong Kim, Eum Mi Kim, Hayeon Byun, Hyung-Kwan Chang, Jungyul Park, Yu Suk Choi, Heungsoo Shin
Scaffold-free harvest of microtissue with a defined structure has received a great deal of interest in cell-based assay and regenerative medicine. In this study, we developed thermally expandable hydrogels with spatially controlled cell adhesive patterns for rapid harvest of geometrically controlled microtissue. We patterned polydopamine (PD) on to the hydrogel via microcontact printing (μCP), in linear shapes with widths of 50, 100 and 200μm. The hydrogels facilitated formation of spatially controlled strip-like microtissue of human dermal fibroblasts (HDFBs)...
July 28, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28751570/association-of-coronary-perivascular-adipose-tissue-inflammation-and-drug-eluting-stent-induced-coronary-hyperconstricting-responses-in-pigs-18-f-fluorodeoxyglucose-positron-emission-tomography-imaging-study
#15
Kazuma Ohyama, Yasuharu Matsumoto, Hirokazu Amamizu, Hironori Uzuka, Kensuke Nishimiya, Susumu Morosawa, Michinori Hirano, Hiroshi Watabe, Yoshihito Funaki, Satoshi Miyata, Jun Takahashi, Kenta Ito, Hiroaki Shimokawa
OBJECTIVE: Although coronary perivascular adipose tissue (PVAT) may play important roles as a source of inflammation, the association of coronary PVAT inflammation and coronary hyperconstricting responses remains to be examined. We addressed this important issue in a porcine model of coronary hyperconstricting responses after drug-eluting stent implantation with (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomographic imaging. APPROACH AND RESULTS: An everolimus-eluting stent (EES) was randomly implanted in pigs into the left anterior descending or the left circumflex coronary artery while nonstented coronary artery was used as a control...
September 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28743511/raf-1-ck2-and-rhoa-rock-signaling-promote-tnf-%C3%AE-mediated-endothelial-apoptosis-via-regulating-vimentin-cytoskeleton
#16
Lifeng Yang, Lian Tang, Fan Dai, Guoliang Meng, Runting Yin, Xiaole Xu, Wenjuan Yao
Both RhoA/ROCK and Raf-1/CK2 pathway play essential roles in cell proliferation, apoptosis, differentiation, and multiple other common cellular functions. We previously reported that vimentin is responsible for TNF-α-induced cell apoptosis. Herein, we investigated the regulation of RhoA/ROCK and Raf-1/CK2 signaling on vimentin filaments and endothelial apoptosis mediated by TNF-α. Treatment with TNF-α significantly induced the activation of RhoA and ROCK, and the expression of ROCK1. RhoA deficiency could obviously inhibit ROCK activation and ROCK1 expression induced by TNF-α...
August 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28729631/therapeutic-effects-of-long-circulating-mir-135a-containing-cationic-immunoliposomes-against-gallbladder-carcinoma
#17
Guanghua Yang, Baobing Yin
Gallbladder carcinoma (GBC) is the most common malignant tumour in the biliary tract, but effective therapeutics are lacking. Based on our previous studies, miR-135a is a potential tool to inhibit GBC proliferation. In this study, we constructed miR-135a-loaded DSPE-PEG2000 liposomes modified with Anti-EGFR antibodies (Anti-EGFR-CIL-miR-135a). The results of an analysis of their physicochemical properties indicated the particle size of it was 222.0 ± 2.1 nm in diameter with an uptake efficiency of 86...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709411/rho-kinase-proteins-display-aberrant-upregulation-in-vascular-tumors-and-contribute-to-vascular-tumor-growth
#18
Clarissa N Amaya, Dianne C Mitchell, Brad A Bryan
BACKGROUND: The serine/threonine protein kinases ROCK1 and 2 are key RhoA-mediated regulators of cell shape and cytoskeletal dynamics. These proteins perform multiple functions in vascular endothelial cell physiology and are attractive targets for cancer therapy based on their roles as oncogenes and metastatic promoters. Given their critical functions in both of these processes, we hypothesized that molecular targeting of ROCK proteins would be exceedingly effective against vascular tumors such as hemangiomas and angiosarcomas, which are neoplasms composed of aberrant endothelial cells...
July 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28684968/effects-of-total-flavone-from-rhododendron-simsii-planch-flower-on-postischemic-cardiac-dysfunction-and-cardiac-remodeling-in-rats
#19
Xinqi Cheng, Jie Zhang, Zhiwu Chen
This study investigated the effect of total flavone from Rhododendron simsii Planch. flower (TFR) on postischemic cardiac dysfunction and ventricular remodeling and was to test the hypothesis that TFR has an antiventricular remodeling effect through inhibition of urotensin-II receptor- (UTR-) mediated activation of RhoA-ROCK pathways. Twenty-four hours after ligation of the left anterior descending coronary artery, male Sprague-Dawley rats were randomized to receive 4-week treatment with saline (model group) or TFR...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28656312/nogo-receptor-knockdown-and-ciliary-neurotrophic-factor-attenuate-diabetic-retinopathy-in-streptozotocin-induced-diabetic-rats
#20
Xiliang Guo, Xuezheng Liu
Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM). We investigated whether Nogo receptor (NgR) knockdown and ciliary neurotrophic factor (CNTF) treatment, either alone or in combination, ameliorated diabetic retinopathy (DR) in diabetic rat model. STZ‑induced diabetic rats were administrated for a total of 12 weeks with 3 µM siRNA (5 µl) once every 6 weeks and/or 1 µg CNTF weekly. The retinal tissues were excised. We measured cell number in ganglion cell layer (GCL) using H&E staining and cell apoptosis using TUNEL assay...
August 2017: Molecular Medicine Reports
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