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https://www.readbyqxmd.com/read/28445988/specific-up-regulation-of-p21-by-a-small-active-rna-sequence-suppresses-human-colorectal-cancer-growth
#1
Lu-Lu Wang, Hui-Hui Guo, Yun Zhan, Chen-Lin Feng, Shuai Huang, Yan-Xing Han, Wen-Sheng Zheng, Jian-Dong Jiang
The double stranded small active RNA (saRNA)- p21-saRNA-322 inhibits tumor growth by stimulating the p21 gene expression. We focused our research of p21-saRNA-322 on colorectal cancer because 1) p21 down-regulation is a signature abnormality of the cancer, and 2) colorectal cancer might be a suitable target for in situ p21-saRNA-322 delivery. The goal of the present study is to learn the activity of p21-saRNA-322 in colorectal cancer. Three human colorectal cancer cell lines, HCT-116, HCT-116 (p53-/-) and HT-29 were transfected with the p21-saRNA-322...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445970/acid-ceramidase-is-a-novel-drug-target-for-pediatric-brain-tumors
#2
Ninh B Doan, Ha S Nguyen, Andrew Montoure, Mona M Al-Gizawiy, Wade M Mueller, Shekar Kurpad, Scott D Rand, Jennifer M Connelly, Christopher R Chitambar, Kathleen M Schmainda, Shama P Mirza
Pediatric brain tumors are the most common solid tumors in children and are also a leading culprit of cancer-related fatalities in children. Pediatric brain tumors remain hard to treat. In this study, we demonstrated that medulloblastoma, pediatric glioblastoma, and atypical teratoid rhabdoid tumors express significant levels of acid ceramidase, where levels are highest in the radioresistant tumors, suggesting that acid ceramidase may confer radioresistance. More importantly, we also showed that acid ceramidase inhibitors are highly effective at targeting these pediatric brain tumors with low IC50 values (4...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445969/glypican-1-targeted-antibody-based-therapy-induces-preclinical-antitumor-activity-against-esophageal-squamous-cell-carcinoma
#3
Emi Harada, Satoshi Serada, Minoru Fujimoto, Yusuke Takahashi, Tsuyoshi Takahashi, Hisashi Hara, Rie Nakatsuka, Takahito Sugase, Takahiko Nishigaki, Yurina Saito, Kosuke Hiramatsu, Satoshi Nojima, Risa Mitsuo, Tomoharu Ohkawara, Eiichi Morii, Masaki Mori, Yuichiro Doki, Yasufumi Kaneda, Tetsuji Naka
Esophageal squamous cell carcinoma (ESCC) has a poor prognosis despite the development of multimodal therapy. Expression of glypican-1 (GPC1) has been reported to be elevated in a subset of patients with ESCC and associated with chemoresistance. This study aimed to determine the association of GPC1 with ESCC growth and potential usefulness of the GPC1 targeted therapy by monoclonal antibody (mAb) in ESCC. Expression of GPC1 was higher in ESCC tumor tissues than in adjacent non-tumoral tissues and normal tissues...
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
#4
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/28445948/combined-mek-and-pi3-kinase-inhibition-reveals-synergy-in-targeting-thyroid-cancer-in-vitro-and-in-vivo
#5
Oussama ElMokh, Dorothée Ruffieux-Daidié, Matthias A Roelli, Amandine Stooss, Wayne A Phillips, Jürg Gertsch, Matthias S Dettmer, Roch-Philippe Charles
Anaplastic thyroid cancers and radioiodine resistant thyroid cancer are posing a major treat since surgery combined with Iodine131 therapy is ineffective on them. Small-molecule inhibitors are presenting a new hope for patients, but often lead to drug resistance in many cancers. Based on the major mutations found in thyroid cancer, we propose the combination of a MEK inhibitor and a Pi3'-kinase inhibitor in pre-clinical models. We used human thyroid cancer cell lines and genetically engineered double mutant BRAFV600E PIK3CAH1047R mice to evaluate the effect of both inhibitors separately or in combination in terms of proliferation and signaling in vitro; tumor burden, histology, cell death induction and tumor markers expression in vivo...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445944/angiotensin-converting-enzyme-2-overexpression-protects-against-doxorubicin-induced-cardiomyopathy-by-multiple-mechanisms-in-rats
#6
Hui Ma, Jing Kong, Yu-Lin Wang, Jun-Long Li, Nai-Hao Hei, Xin-Ran Cao, Jing-Jing Yang, Wen-Jiang Yan, Wen-Jing Liang, Hong-Yan Dai, Bo Dong
Angiotensin-converting enzyme 2 (ACE2) is considered a potential therapeutic target of the renin-angiotensin system (RAS) for the treatment of cardiovascular diseases. We aimed to explore the effects of ACE2 overexpression on doxorubicin-induced cardiomyopathy in rats. Rats were randomly divided into treatment and control groups. The rats of treatment group were injected intraperitoneally with 6 doses of doxorubicin (2.5 mg/kg) within a period of two weeks. Two weeks after the initial injection of doxorubicin, these rats were randomly divided into Mock, Ad-EGFP, Ad-ACE2, and Cilazapril groups...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445934/jarid2-is-essential-for-the-maintenance-of-tumor-initiating-cells-in-bladder-cancer
#7
Xin-Xing Zhu, Ya-Wei Yan, Chun-Zhi Ai, Shan Jiang, Shan-Shan Xu, Min Niu, Xiang-Zhen Wang, Gen-Shen Zhong, Xi-Feng Lu, Yu Xue, Shaoqi Tian, Guangyao Li, Shaojun Tang, Yi-Zhou Jiang
Bladder cancer is the most common urologic malignancy in China, with an increase of the incidence and mortality rates over past decades. Recent studies suggest that bladder tumors are maintained by a rare fraction of cells with stem cell proprieties. Targeting these bladder tumor initiating cell (TICs) population can overcome the drug-resistance of bladder cancer. However, the molecular and genetic mechanisms regulating TICs in bladder cancer remain poorly defined. Jarid2 is implicated in signaling pathways regulating cancer cell epithelial-mesenchymal transition, and stem cell maintenance...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445871/three-year-clinical-outcome-of-patients-with-coronary-disease-and-increased-event-risk-treated-with-newer-generation-drug-eluting-stents-from-the-randomized-dutch-peers-trial
#8
Liefke C van der Heijden, Marlies M Kok, Marije M Löwik, Peter W Danse, Gillian A J Jessurun, Marc Hartmann, Martin G Stoel, K Gert van Houwelingen, Raymond W M Hautvast, Gerard C Linssen, Carine J M Doggen, Clemens von Birgelen
OBJECTIVE: Limited data is available on the long-term outcome of patients with increased cardiovascular event risk, treated with newer-generation durable polymer drug-eluting stents (DES). METHODS: We therefore assessed 3-year follow-up data of high-risk versus low- to intermediate-risk patients of the randomized DUTCH PEERS trial (NCT01331707). In both risk groups we also compared patients treated with Resolute Integrity versus Promus Element DES. Patients were categorized as "high-risk" if they met ≥1 of the following criteria: (1) diabetes (17...
April 27, 2017: Cardiology
https://www.readbyqxmd.com/read/28445868/suppressionof-pyruvate-dehydrogenase-kinase-2-re-sensitizes-paclitaxel-resistant-human-lung-cancer-cells-to-paclitaxel
#9
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/28445821/the-ampk-mtor-pathway-is-involved-in-d-dopachrome-tautomerase-gene-transcription-in-adipocytes-differentiated-from-sgbs-cells-a-human-preadipocyte-cell-line
#10
Takeo Iwata, Kyoko Kuribayashi, Masahiko Nakasono, Noriko Saito-Tarashima, Noriaki Minakawa, Noriko Mizusawa, Rie Kido, Katsuhiko Yoshimoto
In adipose tissue, D-dopachrome tautomerase (DDT), a cytokine with structural similarity to macrophage migration inhibitory factor, is mainly expressed in adipocytes rather than preadipocytes and acts as an anti-obesity adipokine in an autocrine manner. However, its transcriptional regulation is largely unknown. In order to explore molecules affecting DDT transcription, a chemical library screening using HEK293 cells stably expressing a DDT promoter-reporter construct was performed. Several derivatives of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, were identified as transcriptional activators of the DDT gene...
April 23, 2017: Cytokine
https://www.readbyqxmd.com/read/28445809/inhibition-of-14q32-microrna-mir-495-reduces-lesion-formation-intimal-hyperplasia-and-plasma-cholesterol-levels-in-experimental-restenosis
#11
Sabine M J Welten, Rob C M de Jong, Anouk Wezel, Margreet R de Vries, Martin C Boonstra, Laura Parma, J Wouter Jukema, Tetje C van der Sluis, Ramon Arens, Ilze Bot, Sudhir Agrawal, Paul H A Quax, A Yaël Nossent
BACKGROUND AND AIMS: We aimed at investigating the role of 14q32 microRNAs in intimal hyperplasia and accelerated atherosclerosis; two major contributors to restenosis. Restenosis occurs regularly in patients treated for coronary artery disease and peripheral arterial disease. We have previously shown that inhibition of 14q32 microRNAs leads to increased post-ischemic neovascularization, and microRNA miR-494 also decreased atherosclerosis, while increasing plaque stability. We hypothesized that 14q32 microRNA inhibition has beneficial effects on intimal hyperplasia, as well as accelerated atherosclerosis...
April 13, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28445638/antigenic-gm3-lactone-mimetic-molecule-integrated-mannosylated-glycopeptide-nanofibers-for-the-activation-and-maturation-of-dendritic-cells
#12
Gokhan Gunay, Melis Sardan Ekiz, Xhenti Ferhati, Barbara Richichi, Cristina Nativi, Ayse Begum Tekinay, Mustafa O Guler
The ability of dendritic cells to coordinate innate and adaptive immune responses makes them essential targets for vaccination strategies. Presentation of specific antigens by dendritic cells is required for the activation of the immune system against many pathogens, and nanoscale materials can be functionalized for active targeting of dendritic cells. In this work, we integrated an immunogenic, carbohydrate melanoma-associated antigen-mimetic GM3-lactone molecule into mannosylated peptide amphiphile nanofibers to target dendritic cells through DC-SIGN receptor...
April 26, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28445598/dabigatran-enhances-platelet-reactivity-and-platelet-thrombin-receptor-expression-in-patients-with-atrial-fibrillation-reply
#13
Alina Achilles, Annemarie Mohring, Tobias Zeus, Malte Kelm, Amin Polzin
Firstly, we would like to thank Bonello et al. for their comment on our recent publication. We completely agree that until now, data were contradicting regarding the impact of dabigatran on platelet reactivity. Additionally, we completely agree that during the last year, different groups have clearly shown enhanced platelet aggregation and platelet adhesion in dabigatran treated patients. [1-3] Furthermore, two different mechanisms have been described (enhanced platelet adhesion to the endothelium mediated by GPIb-α by Petzold et al...
April 26, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28445541/iqgap1-is-an-oncogenic-target-in-canine-melanoma
#14
Becky H Lee, Poornima H Neela, Michael S Kent, Ashley M Zehnder
Canine oral mucosal melanoma is an aggressive malignant neoplasm and is characterized by local infiltration and a high metastatic potential. The disease progression is similar to that of human oral melanomas. Whereas human cutaneous melanoma is primarily driven by activating mutations in Braf (60%) or Nras (20%), human mucosal melanoma harbors these mutations much less frequently. This makes therapeutic targeting and research modeling of the oral form potentially different from that of the cutaneous form in humans...
2017: PloS One
https://www.readbyqxmd.com/read/28445439/her2-in-breast-cancer-stemness-a-negative-feedback-loop-towards-trastuzumab-resistance
#15
REVIEW
Babak Nami, Zhixiang Wang
HER2 receptor tyrosine kinase that is overexpressed in approximately 20% of all breast cancers (BCs) is a poor prognosis factor and a precious target for BC therapy. Trastuzumab is approved by FDA to specifically target HER2 for treating HER2+ BC. However, about 60% of patients with HER2+ breast tumor develop de novo resistance to trastuzumab, partially due to the loss of expression of HER2 extracellular domain on their tumor cells. This is due to shedding/cleavage of HER2 by metalloproteinases (ADAMs and MMPs)...
April 26, 2017: Cancers
https://www.readbyqxmd.com/read/28445239/aldosterone-and-vascular-mineralocorticoid-receptors-in-murine-endotoxic-and-human-septic-shock
#16
Fouad Fadel, Gwennan André-Grégoire, Basile Gravez, Brigitte Bauvois, Sandrine Bouchet, Catalina Sierra-Ramos, Andrea Polito, Arnaud Mansart, Diego Alvarez de la Rosa, Djillali Annane, Frédéric Jaisser
OBJECTIVES: Vascular mineralocorticoid receptors play a role in vascular tone and blood pressure regulation, might participate in the pathophysiology of circulatory failure during sepsis, and represent a potential therapeutic target in this disease. We aimed to study the effects of mineralocorticoids and the involvement of vascular mineralocorticoid receptors in murine endotoxic and human septic shock. DESIGN: Experimental study. SETTING: Translational investigation including animal research and in vitro experiments using human vascular cells and plasma from septic patients...
April 25, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28445176/novel-lipid-modifying-drugs-to-lower-ldl-cholesterol
#17
Arjen J Cupido, Laurens F Reeskamp, John J P Kastelein
PURPOSE OF REVIEW: Statins have long been the cornerstone for the prevention of cardiovascular disease (CVD). However, because of perceived adverse effects and insufficient efficacy in certain groups of patients, considerable interest exists in the search for alternatives to lower LDL-cholesterol (LDL-C), and the recent approvals of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors underlines the success of this quest. Here, we give an updated overview on the most recent developments in the area of LDL-C lowering agents...
April 25, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28445161/zerumbone-ameliorates-high-fat-diet-induced-adiposity-by-restoring-ampk-regulated-lipogenesis-and-microrna-146b-sirt1-mediated-adipogenesis
#18
Jiyun Ahn, Hyunjung Lee, Chang Hwa Jung, Won Hee Choi, Tae Youl Ha
Obesity is characterized by increased fat mass, as adipose tissue serves as a storage site for excess energy from food consumption. In obesity, altered lipid metabolism of adipose tissue, characterized by fatty acid uptake, de novo lipogenesis, and lipolysis, are induced. In this study, we examined the effect of zerumbone, a major sesquiterpene from wild ginger, on high-fat diet (HF)-induced obesity and dysregulated lipid metabolism in the white adipose tissues (WAT) of C57BL/6N mice. Dietary supplementation with zerumbone ameliorated HF-induced obesity and improved impaired lipid metabolism in WAT...
April 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445132/targeting-autophagic-cancer-stem-cells-to-reverse-chemoresistance-in-human-triple-negative-breast-cancer
#19
Guilhem Bousquet, Morad El Bouchtaoui, Tan Sophie, Christophe Leboeuf, Cédric de Bazelaire, Philippe Ratajczak, Sylvie Giacchetti, Anne de Roquancourt, Philippe Bertheau, Laurence Verneuil, Jean-Paul Feugeas, Marc Espié, Anne Janin
There is growing evidence for the role of cancer stem-cells in drug resistance, but with few in situ studies on human tumor samples to decipher the mechanisms by which they resist anticancer agents.Triple negative breast cancer (TNBC) is the most severe sub-type of breast cancer, occurring in younger women and associated with poor prognosis even when treated at a localized stage.We investigated here the relationship between complete pathological response after chemotherapy and breast cancer stem-cell characteristics in pre-treatment biopsies of 78 women with triple negative breast carcinoma (TNBC)...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445005/proteomic-based-investigations-on-the-mode-of-action-of-the-marine-anticancer-compound-rhizochalinin
#20
Sergey A Dyshlovoy, Katharina Otte, Simone Venz, Jessica Hauschild, Heike Junker, Tatyana N Makarieva, Stefan Balabanov, Winfried H Alsdorf, Ramin Madanchi, Friedemann Honecker, Carsten Bokemeyer, Valentin A Stonik, Gunhild von Amsberg
Rhizochalinin (Rhiz) is a novel marine natural sphingolipid-like compound which shows promising in vitro and in vivo activity in human castration-resistant prostate cancer (CRPC). In the present study, a global proteome screening approach was applied to investigate molecular targets and biological processes affected by Rhiz in CRPC. Bioinformatical analysis of the data predicted an anti-migratory effect of Rhiz on cancer cells. Validation of proteins involved in the cancer-associated processes, including cell migration and invasion, revealed down-regulation of specific isoforms of stathmin and LASP1, as well as up-regulation of Grp75, keratin 81, and precursor IL-1β by Rhiz...
April 26, 2017: Proteomics
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