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https://www.readbyqxmd.com/read/28446017/dexmedetomidine-oral-mucosa-patch-for-sedation-suppresses-apoptosis-in-hippocampus-of-normal-rats
#1
Je Hoon Park, Il Gyu Ko, Sung Eun Kim, Jun Jang Jin, Lakkyong Hwang, Chang Ju Kim, Soo Hwan Yoon, Jongki Hong, Jun Young Chung, Deok Won Lee
PURPOSE: Dexmedetomidine, an α2-adrenergic agonist, provides sedative and analgesic effects without significant respiratory depression. Dexmedetomidine has been suggested to have an antiapoptotic effect in response to various brain insults. We developed an oral mucosa patch using dexmedetomidine for sedation. The effects of the dexmedetomidine oral mucosa patch on cell proliferation and apoptosis in the hippocampus were evaluated. METHODS: A hydrogel oral mucosa patch was adhered onto the oral cavity of physiologically normal rats, and was attached for 2 hours, 6 hours, 12 hours, or 24 hours...
April 2017: International Neurourology Journal
https://www.readbyqxmd.com/read/28445989/tmprss2-erg-gene-fusion-variants-induce-tgf-%C3%AE-signaling-and-epithelial-to-mesenchymal-transition-in-human-prostate-cancer-cells
#2
Leonie Ratz, Mark Laible, Lukasz A Kacprzyk, Stephanie M Wittig-Blaich, Yanis Tolstov, Stefan Duensing, Peter Altevogt, Sabine M Klauck, Holger Sültmann
TMPRSS2:ERG (T/E) gene fusions are present in approximately 50% of all prostate cancer (PCa) cases. The expression of fusion mRNAs from distinct T/E variants is associated with clinicopathological parameters, while the underlying molecular processes remain unclear. We characterized the molecular mechanisms and functional implications caused by doxycycline (Dox)-inducible overexpression of the frequent T/E III and VI fusion variants in LNCaP cells. Induction of T/E expression resulted in increased cellular migratory and invasive potential, and reduced proliferation and accumulation in G1 phase...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445985/interleukin-22-promotes-aerobic-glycolysis-associated-with-tumor-progression-via-targeting-hexokinase-2-in-human-colon-cancer-cells
#3
Yulin Liu, Fan Xiang, Yongming Huang, Liang Shi, Chaojie Hu, Yiming Yang, Di Wang, Nan He, Kaixiong Tao, Ke Wu, Guobin Wang
Interleukin-22 has been explored extensively in human cancer, but its functions and underlying mechanisms are incompletely understood. Here, we show that aberrant interleukin-22 expression facilitates aerobic glycolysis in colon cancer cells. Elevated interleukin-22 mRNA expression was observed and positively correlated with hexokinase-2 in colon cancer tissues. In vitro, interleukin-22 enhanced glucose consumption and lactate production via targeting hexokinase-2 in colon cancer cells. Moreover, the transcriptional factor c-Myc and signal transducer and activator of transcription 3 were involved in interleukin-22-induced up-regulation of hexokinase-2...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445980/the-pp4r1-sub-unit-of-protein-phosphatase-pp4-is-essential-for-inhibition-of-nf-%C3%AE%C2%BAb-by-merkel-polyomavirus-small-tumour-antigen
#4
Hussein Abdul-Sada, Marietta Müller, Rajni Mehta, Rachel Toth, J Simon C Arthur, Adrian Whitehouse, Andrew Macdonald
Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with a high metastatic potential. The majority of MCC cases are caused by the Merkel cell polyomavirus (MCPyV), through expression of the virus-encoded tumour antigens. Whilst mechanisms attributing tumour antigen expression to transformation are being uncovered, little is known of the mechanisms by which MCPyV persists in the host. We previously identified the MCPyV small T antigen (tAg) as a novel inhibitor of nuclear factor kappa B (NF-kB) signalling and a modulator of the host anti-viral response...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445973/plasmodium-parasite-as-an-effective-hepatocellular-carcinoma-antigen-glypican-3-delivery-vector
#5
Quan Liu, Yijun Yang, Xuefang Tan, Zhu Tao, Dickson Adah, Songlin Yu, Junnan Lu, Siting Zhao, Limei Qin, Li Qin, Xiaoping Chen
We have previously demonstrated that malaria parasite infection has an anti-tumor effect in a mouse model. This research aimed to investigate the possibility of using Plasmodium parasite as a novel vaccine vector for hepatocellular carcinoma (HCC) immunotherapy. We constructed a Plasmodium yoelii 17XNL strain (P.y) expressing murine glypican-3 (GPC3) protein (P.y-GPC3), and examined its therapeutic potency in a murine Hepa1-6-induced hepatoma model that highly expressed GPC3 protein. The prerequisites for invoking a CD8+ T cell response were assessed after P...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445967/lactobacillus-casei-zhang-and-vitamin-k2-prevent-intestinal-tumorigenesis-in-mice-via-adiponectin-elevated-different-signaling-pathways
#6
Yong Zhang, Chen Ma, Jie Zhao, Haiyan Xu, Qiangchuan Hou, Heping Zhang
The incidence of colon cancer has increased considerably and the intestinal microbiota participate in the development of colon cancer. We showed that the L. casei Zhang or vitamin K2 (Menaquinone-7) intervention significantly alleviated intestinal tumor burden in mice. This was associated with increased serum adiponectin levels in both treatments. But osteocalcin level was only increased by L. casei Zhang. Furthermore, the anti-carcinogenic actions of L. casei Zhang were mediated by hepatic Chloride channel-3(CLCN3)/Nuclear Factor Kappa B(NF-κB) and intestinal Claudin15/Chloride intracellular channel 4(CLIC4)/Transforming Growth Factor Beta(TGF-β) signaling, while the vitamin K2 effect involved a hepatic Vitamin D Receptor(VDR)-phosphorylated AMPK signaling pathway...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445966/interferon-alpha-antagonizes-the-anti-hepatoma-activity-of-the-oncolytic-virus-m1-by-stimulating-anti-viral-immunity
#7
Liu Ying, Hu Cheng, Xu Wen Xiong, Lin Yuan, Zhang Hai Peng, Zhong Wen Wen, Liang Jian Ka, Xiao Xiao, Cai Jing, Tan Ya Qian, Gao Zhi Liang, Yan Guang Mei, Zhu Wen Bo, Peng Liang
Alpha virus M1 is an oncolytic virus that targets zinc-finger antiviral protein (ZAP)-defective cancer cells, and may be useful for treatment of hepatocellular carcinoma (HCC). Most of HCC patients have hepatitis and need long-term antiviral medication. Thus, it is necessary to clarify whether anti-virus medicines influence oncolytic effect of M1. We examined the effect of drugs used to treat hepatitis B/C on M1-mediated oncolysis in vitro and in vivo. Interferon (IFN)-α induces expression of antiviral IFN-stimulated genes (ISGs) in HCC cells with moderate sensitivity to M1 virus...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445958/repressing-cd147-is-a-novel-therapeutic-strategy-for-malignant-melanoma
#8
REVIEW
Xing Hu, Juan Su, Youyou Zhou, Xiaoyun Xie, Cong Peng, Zhimin Yuan, Xiang Chen
CD147/basigin, a transmembrane protein, is a member of the immunoglobulin super family. Accumulating evidence has revealed the role of CD147 in the development and progression of various cancers, including malignant melanoma (MM). MM is a malignancy of pigment-producing cells that causes the greatest number of skin cancer-related deaths worldwide. CD147 is overexpressed in MM and plays an important role in cell viability, apoptosis, proliferation, invasion, and metastasis, probably by mediating vascular endothelial growth factor (VEGF) production, glycolysis, and multi-drug resistance (MDR)...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445957/peripheral-kynurenine-tryptophan-ratio-is-not-a-reliable-marker-of-systemic-indoleamine-2-3-dioxygenase-a-lesson-drawn-from-patients-on-hemodialysis
#9
Yuanhan Chen, Zhen Xie, Chenggen Xiao, Min Zhang, Zhilian Li, Jianteng Xie, Yusheng Zhang, Xingchen Zhao, Pengfei Zeng, Liyi Mo, Xinling Liang, Wei Shi
Indoleamine 2,3-dioxygenase (IDO) has emerged as a pivotal enzyme for mediating immune tolerance. Because IDO metabolizes tryptophan into kynurenine, the plasma kynurenine/tryptophan (Kyn/Trp) ratio has been widely used as a marker of systemic IDO. Here, we evaluated the clinical value of using the plasma Kyn/Trp ratio to estimate cell-mediated immune responses to tuberculin skin testing and risk of new bacterial infection. We also compared the Kyn/Trp ratio to a novel IDO marker, the IDO median fluorescence index (MFI) of peripheral blood mononuclear cells, which was determined by flow cytometry...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445942/mmp-3-and-mmp-8-single-nucleotide-polymorphisms-are-related-to-alcohol-induced-osteonecrosis-of-the-femoral-head-in-chinese-males
#10
Junyu Chen, Wanlin Liu, Yuju Cao, Xiyang Zhang, Yongchang Guo, Yong Zhu, Jian Li, Jieli Du, Tianbo Jin, Guoqiang Wang, Jianzhong Wang
Our study investigated the association between MMP-3 and MMP-8 single-nucleotide polymorphisms (SNPs) and alcohol-induced osteonecrosis of the femoral head (ONFH) in 695 Chinese males (299 cases and 396 control subjects). The minor allele of MMP-3 rs650108 was associated with a 0.78-fold decrease in alcohol-induced ONFH risk in the allelic model (95% CI = 0.63-0.97, P = 0.026). In the genetic model adjusted for age, rs650108 was associated with decreased risk of alcohol-induced ONFH in the dominant model (OR = 0...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445940/suppression-of-allograft-rejection-by-cd8-cd122-pd-1-tregs-is-dictated-by-their-fas-ligand-initiated-killing-of-effector-t-cells-versus-fas-mediated-own-apoptosis
#11
Huazhen Liu, Yeshu Wang, Qiaohuang Zeng, Yu-Qun Zeng, Chun-Ling Liang, Feifei Qiu, Hong Nie, Zhenhua Dai
Mounting evidence has shown that naturally occurring CD8+CD122+ T cells are regulatory T cells (Tregs) that suppress both autoimmunity and alloimmunity. We have previously shown that CD8+CD122+PD-1+ Tregs not only suppress allograft rejection, but also are more potent in suppression than conventional CD4+CD25+ Tregs. However, the mechanisms underlying their suppression of alloimmunity are not well understood. In an adoptive T-cell transfer model of mice lacking lymphocytes, we found that suppression of skin allograft rejection by CD8+CD122+PD-1+ Tregs was mostly dependent on their expression of Fas ligand as either lacking Fas ligand or blocking it with antibodies largely abolished their suppression of allograft rejection mediated by transferred T cells...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445938/pirfenidone-normalizes-the-tumor-microenvironment-to-improve-chemotherapy
#12
Christiana Polydorou, Fotios Mpekris, Panagiotis Papageorgis, Chrysovalantis Voutouri, Triantafyllos Stylianopoulos
Normalization of the tumor microenvironment by selectively targeting components of the tumor extracellular matrix has been recently proposed to have the potential to decompress tumor blood vessels, increase vessel perfusion and thus, improve drug delivery and the efficacy of cancer therapy. Therefore, we now need to identify safe and well tolerated pharmaceutical agents that are able to remodel the microenvironment of solid tumors and enhance chemotherapy. In this study, we repurposed Pirfenidone, a clinically approved anti-fibrotic drug for the treatment of idiopathic pulmonary fibrosis, to investigate its possible role on tumor microenvironment normalization...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445937/methylation-mediated-silencing-of-microrna-211-promotes-cell-growth-and-epithelial-to-mesenchymal-transition-through-activation-of-the-akt-%C3%AE-catenin-pathway-in-gbm
#13
Weidong Li, Xiaobo Miao, Lingling Liu, Yue Zhang, Xuejun Jin, Xiaojun Luo, Hai Gao, Xubin Deng
Aberrant expression of miR-211 has frequently been reported in cancer studies; however, its role in glioblastoma multiforme (GBM) has not been examined in detail. We investigated the function and the underlying mechanism of miR-211 in GBM. We revealed that miR-211 was downregulated in GBM tissues and cell lines. Restoration of miR-211 inhibited GBM cell growth and invasion both in vitro and in vivo. The epithelial to mesenchymal transition (EMT) phenotype was reversed when miR-211 expression was restored. HMGA2 was identified as a down-stream target of miR-211...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445931/high-glucose-induces-apoptosis-via-upregulation-of-bim-expression-in-proximal-tubule-epithelial-cells
#14
Xiao-Qian Zhang, Jian-Jun Dong, Tian Cai, Xue Shen, Xiao-Jun Zhou, Lin Liao
Diabetic nephropathy is the primary cause of end-stage renal disease. Apoptosis of tubule epithelial cells is a major feature of diabetic nephropathy. The mechanisms of high glucose (HG) induced apoptosis are not fully understood. Here we demonstrated that, HG induced apoptosis via upregulating the expression of proapoptotic Bcl-2 homology domain 3 (BH3)-only protein Bim protein, but not bring a significant change in the baseline level of autophagy in HK2 cells. The increase of Bim expression was caused by the ugregulation of transcription factors, FOXO1 and FOXO3a...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445930/opioids-modulators-of-angiogenesis-in-wound-healing-and-cancer
#15
REVIEW
Martina Ondrovics, Andrea Hoelbl-Kovacic, Daniela Alexandra Fux
Opioids are potent drugs that are widely used to control wound or cancer pain. Increasing evidence suggest that opioids mediate clinically relevant effects that go beyond their classical role as analgesics. Of note, opioids appear to modulate angiogenesis - a process that is critical in wound healing and cancer progression. In this review, we focus on pro- and anti-angiogenic facets of opioids that arise from the activation of individual opioid receptors and the usage of individual concentrations or application routes...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445928/regulation-of-angiogenic-behaviors-by-oxytocin-receptor-through-gli1-indcued-transcription-of-hif-1%C3%AE-in-human-umbilical-vein-endothelial-cells
#16
Ji Zhu, Huiyan Wang, Xiaoyan Zhang, Yin Xie
Angiogenesis is a dynamic hypoxia-stimulated process playing a key role in tissue growth and repair under various pathophysiological circumstances. Abnormal angiogenesis contributes to the pathogenesis of many human diseases. Oxytocin receptor is a classical G-protein-coupled receptor expressed on endothelial cells. The present study was aimed to investigate how oxytocin receptor regulated the angiogenic behaviors of human umbilical vein endothelial cells (HUVECs). We found that oxytocin at 0.1μM significantly increased cell proliferation, upregulated the mRNA and protein expression of CD31 and vWF (two important endothelial markers), and enhanced the tuber formation capacity in HUVECs...
April 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28445868/suppressionof-pyruvate-dehydrogenase-kinase-2-re-sensitizes-paclitaxel-resistant-human-lung-cancer-cells-to-paclitaxel
#17
Hong Sun, Anyou Zhu, Xiang Zhou, Fengchao Wang
Despite impressive initial clinical responses, the majority of lung cancer patients treated with paclitaxel eventually develop resistance to the drug. Pyruvate dehydrogenase kinase-2 (PDK2) is a key regulator of glycolysis and oxidative phosphorylation, and its expression is increased in a variety of tumors. In this study, the role of PDK2 in mediating paclitaxel resistance in lung cancer cells was investigated using biochemical and isotopic tracing methods. Increased expression of PDK2 was observed in paclitaxel-resistant cells ascompared totheir parental cells...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445856/procyanidin-a-kind-of-biological-flavonoid-induces-protective-anti-tumor-immunity-and-protects-mice-from-lethal-b16f10-challenge
#18
Lina Zhang, Shuang Wang, Zeyuan Liu, Li Zhang, Shanzheng Wang, Bin Wang
Recently, increasing evidences show that procyanidin (PC) modulate immune responses in human. To evaluate adjuvant effects of PC on vaccine immune modulation and anti-tumor activity, we formulated PC with B16F10 tumor antigen as tumor vaccine to immune C57BL/6 mice and used intramuscular injection before challenge with tumor B16F10 cells. Our results revealed that PC enhanced T cell-mediated immune responses both in vitro and in vivo. Moreover, the B16F10 tumor vaccine induced some degree of anti-tumor effects as evaluated by the inhibition of tumor growth and the prolongation of survival...
April 23, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28445842/%C3%AE-eta-eudesmol-reduces-stem-cell-factor-induced-mast-cell-migration
#19
Sun-Young Nam, Hee-Yun Kim, Hyung-Min Kim, Hyun-Ja Jeong
Previously, we showed the inhibitory effects of β-eudesmol on mast cell-mediated allergic inflammatory responses. Stem cell factor (SCF) participates in allergic reactions through the differentiation and migration of mast cells. However, the effects of β-eudesmol on SCF-mediated allergic reactions are poorly understood. Herein, we showed that a treatment of rat peritoneal mast cells (RPMCs) with β-eudesmol markedly suppressed SCF-induced mast cell migration and morphological alterations in a concentration-dependent manner...
April 23, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28445841/copper-ii-and-iron-iii-ions-inhibit-respiration-and-increase-free-radical-mediated-phospholipid-peroxidation-in-rat-liver-mitochondria-effect-of-antioxidants
#20
Christian Saporito-Magriñá, Rosario Musacco-Sebio, Juan M Acosta, Sofía Bajicoff, Paola Paredes-Fleitas, Sofia Reynoso, Alberto Boveris, Marisa G Repetto
Rat liver mitochondria (1.5-2.1mg protein·mL(-1)) supplemented with either 25 and 100μM Cu(2+) or 100 and 500μM Fe(3+) show inhibition of active respiration (O2 consumption in state 3) and increased phospholipid peroxidation . Liver mitochondria were supplemented with the antioxidants reduced glutathione, N-acetylcysteine or butylated hydroxitoluene, to evaluate their effects on the above-mentioned alterations. Although the mitochondrial dysfunction is clearly associated to phospholipid peroxidation, the different responses to antioxidant supplementation indicate that the metal ions have differences in their mechanisms of toxicity...
April 19, 2017: Journal of Inorganic Biochemistry
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