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https://www.readbyqxmd.com/read/28076854/open-angle-glaucoma-drug-development-pipeline-during-the-last-20-years-1995-2015
#1
André Vicente, Sylvie Prud'homme, Joana Ferreira, Luís Abegão Pinto, Ingeborg Stalmans
OBJECTIVES: To analyse drug development for open-angle glaucoma during the last 20 years. METHODS: Research was performed by referring to clinical trials registered at the International Clinical Trials Registry Platform (ICTRP). A search for the condition "open-angle glaucoma" with the intervention "drug" was performed. We included trials registered from 01/01/1995 to 01/01/2015, only involving studies in phases 1, 2, and 3. Only studies resorting to novel treatment strategies (either novel drugs or yet-untested fixed associations of approved medication) were considered...
January 12, 2017: Ophthalmic Research
https://www.readbyqxmd.com/read/27984373/hnrnpa1-a-splicing-regulator-is-an-effective-target-protein-for-cervical-cancer-detection-comparison-with-conventional-tumor-markers
#2
Young-Jon Kim, Byoung-Ryun Kim, Jae-Suk Ryu, Gyeong-Ok Lee, Hak-Ryul Kim, Keum-Ha Choi, Jae-Won Ryu, Kyoung-Suk Na, Min-Cheol Park, Hong-Seob So, Ji-Hyun Cho, Do-Sim Park
OBJECTIVE: Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1), serine/arginine-rich splicing factor 1 (SRSF1), and SRSF3 are splicing regulators associated with oncogenesis. However, the alterations of SF proteins and their diagnostic values in cervical cancer are unclear. To apply SFs clinically, effective marker selection and characterization of the target organ properties are essential. MATERIALS AND METHODS: We concurrently analyzed HNRNPA1, SRSF1, SRSF3, and the conventional tumor markers squamous cell carcinoma antigen (SCCA) and carcinoembryonic antigen (CEA) in cervical tissue samples (n = 127) using semiquantitative immunoblotting...
December 15, 2016: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/27973579/knockdown-of-creb3-luman-by-shrna-in-mouse-granulosa-cells-results-in-decreased-estradiol-and-progesterone-synthesis-and-promotes-cell-proliferation
#3
Fan Zhao, Nan Wang, Yanglei Yi, Pengfei Lin, Keqiong Tang, Aihua Wang, Yaping Jin
Luman (also known as LZIP or CREB3) is a transcription factor and a member of the cAMP responsive element-binding (CREB) family proteins. Although Luman has been detected in apoptotic granulosa cells and disorganized atretic bodies, the physiological function of Luman in follicular development has not been reported. Our objective is to determine the role of Luman in folliculogenesis by knocking down Luman expression in mouse GCs (granulosa cells) using shRNA. Luman expression was successfully knocked down in mouse GCs at the mRNA and protein level, as confirmed by real-time quantitative PCR, western blot and immunofluorescence staining, respectively...
2016: PloS One
https://www.readbyqxmd.com/read/27884605/arsenic-induced-activation-of-the-homeodomain-interacting-protein-kinase-2-hipk2-to-camp-response-element-binding-protein-creb-axis
#4
Kazunori Hashimoto, Yoshiaki Tsuji
Cyclic AMP-response element-binding protein (CREB) plays key transcriptional roles in cell metabolism, proliferation, and survival. Ser133 phosphorylation by protein kinase A (PKA) is a well-characterized CREB activation mechanism. Homeodomain-interacting protein kinase (HIPK) 2, a nuclear serine/threonine kinase, activates CREB through Ser271 phosphorylation; however, the regulatory mechanism remains uncharacterized. Transfection of CREB in HEK293 cells together with the kinase demonstrated that HIPK2 phosphorylated CREB at Ser271 but not Ser133; likewise, PKA phosphorylated CREB at Ser133 but not Ser271, suggesting two distinct CREB regulatory mechanisms by HIPK2 and PKA...
January 6, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27880045/koelreuteria-formosana-extract-induces-growth-inhibition-and-cell-death-in-human-colon-carcinoma-cells-via-g2-m-arrest-and-lc3-ii-activation-dependent-autophagy
#5
Chi-Ting Horng, Yueh-Jung Wu, Pei-Ni Chen, Shu-Chen Chu, Chun-Miao Tsai, Yih-Shou Hsieh
Autophagy is a self-destructive process that degrades cytoplasmic constituents. In our previous study, Koelreuteria formosana ethanolic extract (KFEE), which is obtained from natural plants endemic to Taiwan, has inhibited cell metastasis in renal carcinoma cells. However, the anticancer effects of KFEE on colon cancer remain unclear. In this study, KFEE exerted a strong cytotoxic effect on DLD-1 and COLO 205 human colorectal cancer cell lines. KFEE effectively inhibited cancer cell proliferation, induced G2/M-phase arrest associated with downregulaton of cyclin E, cyclin B and cdc25C and upregulation of p21, and induced cell death by activating autophagy but did not cause apoptotic cell death...
January 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/27845389/bafilomycin-a1-induces-caspase-independent-cell-death-in-hepatocellular-carcinoma-cells-via-targeting-of-autophagy-and-mapk-pathways
#6
Yumei Yan, Ke Jiang, Peng Liu, Xianbin Zhang, Xin Dong, Jingchun Gao, Quentin Liu, Martin P Barr, Quan Zhang, Xiukun Hou, Songshu Meng, Peng Gong
Hepatocellular carcinoma (HCC) is refractory to chemotherapies, necessitating novel effective agents. The lysosome inhibitor Bafilomycin A1 (BafA1) at high concentrations displays cytotoxicity in a variety of cancers. Here we show that BafA1 at nanomolar concentrations suppresses HCC cell growth in both 2 dimensional (2D) and 3D cultures. BafA1 induced cell cycle arrest in the G1 phase and triggered Cyclin D1 turnover in HCC cells in a dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) dependent manner...
November 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27792641/lim-domain-only-2-regulates-endothelial-proliferation-angiogenesis-and-tissue-regeneration
#7
Shu Meng, Gianfranco Matrone, Jie Lv, Kaifu Chen, Wing Tak Wong, John P Cooke
BACKGROUND: LIM domain only 2 (LMO2, human gene) is a key transcription factor that regulates hematopoiesis and vascular development. However, its role in adult endothelial function has been incompletely characterized. METHODS AND RESULTS: In vitro loss- and gain-of-function studies on LMO2 were performed in human umbilical vein endothelial cells with lentiviral overexpression or short hairpin RNA knockdown (KD) of LMO2, respectively. LMO2 KD significantly impaired endothelial proliferation...
October 6, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27698802/identification-of-genes-involved-in-epstein-barr-virus-associated-nasopharyngeal-carcinoma
#8
Junguo Wang, Fang Mei, Xia Gao, Shoulin Wang
Nasopharyngeal carcinoma (NPC) is the most common cancer originating from the nasopharynx, and can be induced by infection with Epstein-Barr virus (EBV). To study the mechanisms of EBV-associated NPC, a microarray of the GSE12452 dataset was analyzed. GSE12452 was downloaded from Gene Expression Omnibus and consisted of 31 NPC samples and 10 normal healthy nasopharyngeal tissue samples. The differentially-expressed genes (DEGs) were screened using the linear models for microarray data package in R. Using Database for Annotation, Visualization and Integrated Discovery software, potential functions of the DEGs were predicted by Gene Ontology and pathway enrichment analyses...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27669502/cyclin-a1-expression-and-paclitaxel-resistance-in-human-ovarian-cancer-cells
#9
Kuan-Chun Huang, Junzheng Yang, Michelle C Ng, Shu-Kay Ng, William R Welch, Michael G Muto, Ross S Berkowitz, Shu-Wing Ng
BACKGROUND: The development of intrinsic and acquired resistance to antineoplastic agents is a major obstacle to successful chemotherapy in ovarian cancers. Identification and characterisation of chemoresponse-associated biomarkers are of paramount importance for novel therapeutic development. METHODS: Global RNA expression profiles were obtained by high-throughput microarray analysis. Cell cycle, proliferation rate, and paclitaxel sensitivity of ovarian cancer cells harbouring cyclin A1-inducible expression construct were compared with and without tetracycline induction, as well as when the cyclin A1 expression was suppressed by short inhibiting RNA (siRNA)...
November 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27569210/smyd3-mediated-h2a-z-1-methylation-promotes-cell-cycle-and-cancer-proliferation
#10
Cheng-Hui Tsai, Yun-Ju Chen, Chia-Jung Yu, Shiou-Ru Tzeng, I-Chen Wu, Wen-Hung Kuo, Ming-Chieh Lin, Nei-Li Chan, Kou-Juey Wu, Shu-Chun Teng
SMYD3 methyltransferase is nearly undetectable in normal human tissues but highly expressed in several cancers, including breast cancer, although its contributions to pathogenesis in this setting are unclear. Here we report that histone H2A.Z.1 is a substrate of SMYD3 that supports malignancy. SMYD3-mediated dimethylation of H2A.Z.1 at lysine 101 (H2A.Z.1K101me2) increased stability by preventing binding to the removal chaperone ANP32E and facilitating its interaction with histone H3. Moreover, a microarray analysis identified cyclin A1 as a target coregulated by SMYD3 and H2A...
October 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27551490/sundew-plant-a-potential-source-of-anti-inflammatory-agents-selectively-induces-g2-m-arrest-and-apoptosis-in-mcf-7-cells-through-upregulation-of-p53-and-bax-bcl-2-ratio
#11
N B Ghate, A Das, D Chaudhuri, S Panja, N Mandal
The worldwide cancer incidences are remarkable despite the advancement in cancer drug discovery field, highlighting the need for new therapies focusing on cancer cell and its microenvironment, including inflammation. Several species of Drosera (family: Droseraceae) are used in various traditional as well as homeopathic systems of medicine. Drosera burmannii Vahl. is also enlisted in French Pharmacopoeia in 1965 for the treatment of inflammatory diseases, including chronic bronchitis, asthma and whooping cough...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27460030/endosulfan-inhibiting-the-meiosis-process-via-depressing-expressions-of-regulatory-factors-and-causing-cell-cycle-arrest-in-spermatogenic-cells
#12
Fang-Zi Guo, Lian-Shuang Zhang, Jia-Liu Wei, Li-Hua Ren, Jin Zhang, Li Jing, Man Yang, Ji Wang, Zhi-Wei Sun, Xian-Qing Zhou
Endosulfan is a persistent organic pollutant and widely used in agriculture as a pesticide. It is present in air, water, and soil worldwide; therefore, it is a health risk affecting especially the reproductive system. The aim of this study was to evaluate the toxicity of endosulfan in the reproductive system. To investigate the effect of endosulfan on meiosis process, 32 rats were divided into four groups, treated with 0, 1, 5, and 10 mg/kg/day endosulfan, respectively, and sacrificed after the 21 days of treatments...
July 27, 2016: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/27388959/identification-of-cyclins-a1-e1-and-vimentin-as-downstream-targets-of-heme-oxygenase-1-in-vascular-endothelial-growth-factor-mediated-angiogenesis
#13
Andrea Bauer, Hayley Mylroie, C Clare Thornton, Damien Calay, Graeme M Birdsey, Allan P Kiprianos, Garrick K Wilson, Miguel P Soares, Xiaoke Yin, Manuel Mayr, Anna M Randi, Justin C Mason
Angiogenesis is an essential physiological process and an important factor in disease pathogenesis. However, its exploitation as a clinical target has achieved limited success and novel molecular targets are required. Although heme oxygenase-1 (HO-1) acts downstream of vascular endothelial growth factor (VEGF) to modulate angiogenesis, knowledge of the mechanisms involved remains limited. We set out identify novel HO-1 targets involved in angiogenesis. HO-1 depletion attenuated VEGF-induced human endothelial cell (EC) proliferation and tube formation...
July 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27299463/synergistic-cytotoxicity-of-ampelopsin-sodium-and-carboplatin-in-human-non-small-cell-lung-cancer-cell-line-spc-a1-by-g1-cell-cycle-arrested
#14
Li Lu, Li-Ning Yang, Xue-Xi Wang, Chun-Li Song, Hong Qin, Yong-Jie Wu
OBJECTIVE: To evaluate the cytotoxic effects of ampelopsin sodium (Amp-Na) and carboplatin (CBP) used alone or in combination on human non-small cell lung cancer (NSCLC) cells SPC-A1 in vitro and its related mechanism. METHODS: Cytotoxic effects were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. The synergistic effects of the drugs were calculated with coeffifi cient of drug interaction (CDI). Cell cycle was determined by flfl ow cytometry (FCM)...
June 14, 2016: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/27295628/atheroprotective-laminar-flow-inhibits-hippo-pathway-effector-yap-in-endothelial-cells
#15
Suowen Xu, Marina Koroleva, Meimei Yin, Zheng Gen Jin
Atherosclerosis is a mechanobiology-related disease that preferentially develops in the aortic arch and arterial branches, which are exposed to disturbed/turbulent blood flow but less in thoracic aorta where the flow pattern is steady laminar flow (LF). Increasing evidence supports that steady LF with high shear stress is protective against atherosclerosis. However, the molecular mechanisms of LF-mediated atheroprotection remain incompletely understood. Hippo/YAP (yes-associated protein) pathway senses and effects mechanical cues and has been reported to be a master regulator of cell proliferation, differentiation, and tissue homeostasis...
October 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27226604/mechanistic-target-of-rapamycin-mtor-inhibition-synergizes-with-reduced-internal-ribosome-entry-site-ires-mediated-translation-of-cyclin-d1-and-c-myc-mrnas-to-treat-glioblastoma
#16
Brent Holmes, Jihye Lee, Kenna A Landon, Angelica Benavides-Serrato, Tariq Bashir, Michael E Jung, Alan Lichtenstein, Joseph Gera
Our previous work has demonstrated an intrinsic mRNA-specific protein synthesis salvage pathway operative in glioblastoma (GBM) tumor cells that is resistant to mechanistic target of rapamycin (mTOR) inhibitors. The activation of this internal ribosome entry site (IRES)-dependent mRNA translation initiation pathway results in continued translation of critical transcripts involved in cell cycle progression in the face of global eIF-4E-mediated translation inhibition. Recently we identified compound 11 (C11), a small molecule capable of inhibiting c-MYC IRES translation as a consequence of blocking the interaction of a requisite c-MYC IRES trans-acting factor, heterogeneous nuclear ribonucleoprotein A1, with its IRES...
July 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27110560/proteomic-analysis-of-stage-ii-breast-cancer-from-formalin-fixed-paraffin-embedded-tissues
#17
Naif Abdullah Al-Dhabi, Srisesharam Srigopalram, Soundharrajan Ilavenil, Young Ock Kim, Paul Agastian, Rajasekhar Baaru, Kannan Balamurugan, Ki Choon Choi, Mariadhas Valan Arasu
Breast cancer is the most frequently occurring disease among women worldwide. The early stage of breast cancer identification is the key challenge in cancer control and prevention procedures. Although gene expression profiling helps to understand the molecular mechanism of diseases or disorder in the living system, gene expression pattern alone is not sufficient to predict the exact mechanisms. Current proteomics tools hold great application for analysis of cancerous conditions. Hence, the generation of differential protein expression profiles has been optimized for breast cancer and normal tissue samples in our organization...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27099260/ubiquitin-specific-protease14-interacts-with-ultraviolet-b-insensitive4-to-regulate-endoreduplication-and-cell-and-organ-growth-in-arabidopsis
#18
Yingxiu Xu, Weihuan Jin, Na Li, Wenjuan Zhang, Cuimin Liu, Chuanyou Li, Yunhai Li
Organ growth is determined by a coordinated combination of cell proliferation and cell growth and differentiation. Endoreduplication is often coupled with cell growth and differentiation, but the genetic and molecular mechanisms that link endoreduplication with cell and organ growth are largely unknown. Here, we describe UBIQUITIN-SPECIFIC PROTEASE14 (UBP14), encoded by the DA3 gene, which functions as a negative regulator of endoreduplication. The Arabidopsis thaliana da3-1 mutant shows large cotyledons, leaves, and flowers with higher ploidy levels...
May 2016: Plant Cell
https://www.readbyqxmd.com/read/26921336/cyclin-a1-and-p450-aromatase-promote-metastatic-homing-and-growth-of-stem-like-prostate-cancer-cells-in-the-bone-marrow
#19
Regina Miftakhova, Andreas Hedblom, Julius Semenas, Brian Robinson, Athanasios Simoulis, Johan Malm, Albert Rizvanov, David M Heery, Nigel P Mongan, Norman J Maitland, Cinzia Allegrucci, Jenny L Persson
Bone metastasis is a leading cause of morbidity and mortality in prostate cancer. While cancer stem-like cells have been implicated as a cell of origin for prostate cancer metastasis, the pathways that enable metastatic development at distal sites remain largely unknown. In this study, we illuminate pathways relevant to bone metastasis in this disease. We observed that cyclin A1 (CCNA1) protein expression was relatively higher in prostate cancer metastatic lesions in lymph node, lung, and bone/bone marrow. In both primary and metastatic tissues, cyclin A1 expression was also correlated with aromatase (CYP19A1), a key enzyme that directly regulates the local balance of androgens to estrogens...
15, 2016: Cancer Research
https://www.readbyqxmd.com/read/26875816/the-antineoplastic-drug-flavopiridol-reverses-memory-impairment-induced-by-amyloid-%C3%A3-1-42-oligomers-in-mice
#20
Gian Marco Leggio, Maria Vincenza Catania, Daniela Puzzo, Michela Spatuzza, Rosalia Pellitteri, Walter Gulisano, Sebastiano Alfio Torrisi, Giovanni Giurdanella, Cateno Piazza, Agata Rita Impellizzeri, Lucia Gozzo, Andrea Navarria, Claudio Bucolo, Ferdinando Nicoletti, Agostino Palmeri, Salvatore Salomone, Agata Copani, Filippo Caraci, Filippo Drago
The ectopic re-activation of cell cycle in neurons is an early event in the pathogenesis of Alzheimer's disease (AD), which could lead to synaptic failure and ensuing cognitive deficits before frank neuronal death. Cytostatic drugs that act as cyclin-dependent kinase (CDK) inhibitors have been poorly investigated in animal models of AD. In the present study, we examined the effects of flavopiridol, an inhibitor of CDKs currently used as antineoplastic drug, against cell cycle reactivation and memory loss induced by intracerebroventricular injection of Aß1-42 oligomers in CD1 mice...
April 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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