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https://www.readbyqxmd.com/read/29777202/aberrant-modulation-of-ribosomal-protein-s6-phosphorylation-confers-acquired-resistance-to-mapk-pathway-inhibitors-in-braf-mutant-melanoma
#1
Ming-Zhao Gao, Hong-Bin Wang, Xiang-Ling Chen, Wen-Ting Cao, Li Fu, Yun Li, Hai-Tian Quan, Cheng-Ying Xie, Li-Guang Lou
BRAF and MEK inhibitors have shown remarkable clinical efficacy in BRAF-mutant melanoma; however, most patients develop resistance, which limits the clinical benefit of these agents. In this study, we found that the human melanoma cell clones, A375-DR and A375-TR, with acquired resistance to BRAF inhibitor dabrafenib and MEK inhibitor trametinib, were cross resistant to other MAPK pathway inhibitors. In these resistant cells, phosphorylation of ribosomal protein S6 (rpS6) but not phosphorylation of ERK or p90 ribosomal S6 kinase (RSK) were unable to be inhibited by MAPK pathway inhibitors...
May 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29777201/novel-smoothened-inhibitors-for-therapeutic-targeting-of-na%C3%A3-ve-and-drug-resistant-hedgehog-pathway-driven-cancers
#2
Qing-Rou Li, Hui Zhao, Xue-Sai Zhang, Henk Lang, Ker Yu
The G protein-coupled receptor (GPCR) smoothened (SMO) is a key signaling component of the sonic hedgehog (Hh) pathway and a clinically validated target for cancer treatment. The FDA-approved SMO inhibitors GDC-0449/Vismodegib and LDE225/Sonidegib demonstrated clinical antitumor efficacy. Nevertheless, relatively high percentage of treated patients would eventually develop acquired cross resistance to both drugs. Here, based on published structure and activity of GDC-0449 inhibitor class, we replaced its amide core with benzimidazole which retained bulk of the SMO-targeting activity as measured in our Hh/SMO/Gli1-reporter system...
May 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29773591/t-11-14-positive-mantel-cell-lymphomas-lacking-cyclin-d1-ccnd1-immunostaining-because-of-a-ccnd1-mutation-or-exclusive-expression-of-the-ccnd1b-isoform
#3
Ingram Iaccarino, Lamis Afify, Sietse M Aukema, Katharina Reddemann, Philipp Schütt, Martin Flür, Wolfram Klapper
No abstract text is available yet for this article.
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773108/-adiponectin-inhibits-proliferation-and-induces-apoptosis-in-colorectal-cancer-hct116-cells
#4
Manling Huang, Zhitao Chen, Dan Xu, Heng Zhang, Shengbin Sun, Jie Wu
Objective To investigate the relationship between serum adiponectin level and risk of colorectal cancer, and to explore the effect of recombinant adiponectin on the proliferation and apoptosis of colorectal cancer HCT116 cells. Methods Serum adiponectin levels in patients with colorectal cancer and healthy controls were dectected by ELISA. With the level of adiponectin as a risk factor, ROC curve was acquired using SPSS software. HCT116 cells were treated with recombinant adiponectin (2.5, 5, 10, 20 μg/mL)...
March 2018: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29772436/tanshinone-iia-ameliorates-lipopolysaccharide-induced-inflammatory-response-in-bronchial-epithelium-cell-line-beas-2b-by-down-regulating-mir-27a
#5
Xiuxia Liu, Jie Meng
BACKGROUND: Bronchopneumonia is a common lower respiratory tract inflammatory disease, which is one of main causes of death in infants and young children. Tanshinone IIA (Tan) is a naturally derived anti-inflammatory compound, which has been used for some inflammatory diseases. OBJECTIVE: Tan was expected to inhibit lipopolysaccharide (LPS)-induced inflammatory damage in human bronchial epithelium cell line BEAS-2B. METHODS: BEAS-2B cells were stimulated with LPS to mimic an in vitro model of bronchopneumonia...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29772246/preterm-birth-disrupts-cerebellar-development-by-affecting-granule-cell-proliferation-program-and-bergmann-glia
#6
Igor Y Iskusnykh, Randal K Buddington, Victor V Chizhikov
Preterm birth is a leading cause of long-term motor and cognitive deficits. Clinical studies suggest that some of these deficits result from disruption of cerebellar development, but the mechanisms that mediate cerebellar abnormalities in preterm infants are largely unknown. Furthermore, it remains unclear whether preterm birth and precocious exposure to the ex-utero environment directly disrupt cerebellar development or indirectly by increasing the probability of cerebellar injury, including that resulting from clinical interventions and protocols associated with the care of preterm infants...
May 14, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29770483/melatonin-modulates-dysregulated-circadian-clocks-in-mice-with-diethylnitrosamine-induced-hepatocellular-carcinoma
#7
Diana I Sánchez, Bárbara González-Fernández, Irene Crespo, Beatriz San-Miguel, Marcelino Álvarez, Javier González-Gallego, María Jesús Tuñón
Disruption of circadian rhythms, which are regulated by the circadian clock machinery, plays an important role in different long-term diseases including hepatocellular carcinoma (HCC). Melatonin has been reported to alleviate promotion and progression of HCC, but the potential contribution of circadian clock modulation is unknown. We investigated the effects of melatonin in mice which received diethylnitrosamine (DEN) (35 mg/kg body weight i.p.) once a week for 8 weeks. Melatonin was given at 5 or 10 mg/kg/day i...
May 16, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29769640/hypoxia-induced-microrna-191-contributes-to-hepatic-ischemia-reperfusion-injury-through-the-zonab-cyclin-d1-axis
#8
Wenming Pan, Lin Wang, Xiao-Fei Zhang, Hongji Zhang, Jinxiang Zhang, Guoliang Wang, Peng Xu, Yunwei Zhang, Ping Hu, Xiao-Dong Zhang, Run-Lei Du, Hui Wang
Hepatic ischemia/reperfusion injury (IRI) is a common cause of morbidity and mortality in liver transplantation settings and involves severe cell death and inflammatory responses. MicroRNA-191 has recently been reported to be abnormally expressed in hepatocellular carcinoma and other liver diseases in the regulation of important cellular processes. However, little is known about its function and molecular mechanism in IRI. Here, we demonstrate that miR-191 is significantly upregulated in a cultured cell line during hypoxia/reperfusion (H/R) and in liver tissue during IRI in mice...
May 16, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29769480/5-hydroxy-4-nitro-7-propionyloxy-genistein-inhibited-invasion-and-metastasis-via-inactivating-wnt-b-catenin-signal-pathway-in-human-endometrial-carcinoma-ji-endometrial-cells
#9
Jun Bai, Xin Luo
BACKGROUND Chemotherapy has been assuring more important roles in the treatment of carcinoma. Developing new types of drugs with less adverse effects and low drug resistance has become an important researching focus. The present study aimed to investigate the anticancer effects of 5-hydroxy-4'-nitro-7-propionyloxy-genistein (HNPG) and to elucidate its underlying molecular mechanism. MATERIAL AND METHODS The inhibitory effects of cell viability of HNPG were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flat plate clone formation method, and Transwell assay...
May 17, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29768138/knockdown-of-the-prolyl-isomerase-pin1-inhibits-hep-2-cells-growth-migration-and-invasion-by-targeting-%C3%AE-catenin-signaling-pathway
#10
Guoliang Fan, Lin Wang, Jia Xu, Ping Jiang, Wei Wang, Ying Huang, Minggang Lv, Shaoting Liu
Increasing evidence indicates that peptidylprolyl cis/trans isomerase, NIMA-interacting 1 (Pin1) plays a decisive role in a variety of cancers. Nevertheless, its function in laryngeal squamous cell carcinoma (LSCC) has not been elaborated. The aim of this study is to determine the role of Pin1 in LSCC. Here, we established stably transfected Hep-2 cells with low expression of Pin1. Intriguingly, ability of cell proliferation, migration and invasion was significantly inhibited in Pin1-silenced Hep-2 cells. Similarly, knockdown of Pin1 induced apoptosis of Hep-2 cells, as evidenced by increased expression of cleaved-caspase-3, cleaved-PARP, and bax, and decreased expression of bcl2...
May 16, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29767250/diosmetin-suppresses-human-prostate-cancer-cell-proliferation-through-the-induction-of-apoptosis-and-cell-cycle-arrest
#11
Christine Oak, Ahmad O Khalifa, Ilaha Isali, Natarajan Bhaskaran, Ethan Walker, Sanjeev Shukla
Diosmetin, a plant flavonoid, has been shown to exert promising effects on prostate cancer cells as an anti‑proliferative and anticancer agent. In this study, using western blot analysis for protein expression and flow cytometry for cell cycle analysis, we determined that the treatment of the LNCaP and PC‑3 prostate cancer cells with diosmetin resulted in a marked decrease in cyclin D1, Cdk2 and Cdk4 expression levels (these proteins remain active in the G0‑G1 phases of the cell cycle). These changes were accompanied by a decrease in c-Myc and Bcl-2 expression, and by an increase in Bax, p27Kip1 and FOXO3a protein expression, which suggests the potential modulatory effects of diosmetin on protein transcription...
May 16, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29765996/an-in-vitro-study-on-curcumin-delivery-by-nano-micelles-for-esophageal-squamous-cell-carcinoma-kyse-30
#12
Sare Hosseini, Jamshidkhan Chamani, Hamidreza Rahimi, Navid Azmoodeh, Faezeh Ghasemi, Porya Hassan Abadi
Background: The incidence of esophageal squamous cell carcinoma (ESCC) is increasing, causing catastrophic health burdens on communities. Curcumin has shown promise as a therapeutic agent in the treatment of colon, colorectal, pancreatic, and esophageal cancers but it has very poor bioavailability. The application of nano-carriers as drug delivery systems increases curcumin's bioavailability. Cyclin D1 is overexpressed in ESCC and curcumin may change its expression. Methods: In this study, the effect of SinaCurcumin®, a novel nano-micelle product containing 80 mg curcumin, on the growth of KYSE-30 cells and expression of cyclin D1, was investigated...
April 2018: Reports of Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29764507/aldolase-a-promotes-proliferation-and-g-1-s-transition-via-the-egfr-mapk-pathway-in-non-small-cell-lung-cancer
#13
Hailu Fu, Huijun Gao, Xiaoyu Qi, Lei Zhao, Donghua Wu, Yuxin Bai, Huimin Li, Xuan Liu, Jun Hu, Shujuan Shao
BACKGROUND: Our previous study demonstrated that aldolase A (ALDOA) is overexpressed in clinical human lung squamous cell carcinoma and that ALDOA promotes epithelial-mesenchymal transition and tumorigenesis. The present study aimed to explore the function of ALDOA in the modulation of non-small cell lung cancer (NSCLC) proliferation and cell cycle progression and the potential mechanism. METHODS: ALDOA was knocked down by short hairpin RNA in H520 and H1299 cells...
May 8, 2018: Cancer communications
https://www.readbyqxmd.com/read/29763471/importance-of-extracellular-matrix-and-growth-state-for-the-ea-hy926-endothelial-cell-response-to-polyunsaturated-fatty-acids
#14
Youjia Du, Carla G Taylor, Harold M Aukema, Peter Zahradka
Consumption of different PUFAs (polyunsaturated fatty acids) can induce functional changes in blood vessels via endothelial cells, which interact with dietary factors in the circulation. The basement membrane that separates the endothelium from the smooth muscle cells of the medial layer can also influence the functional state of endothelial cells. However, the effect of basement membrane on the endothelial response to dietary PUFAs in relation to growth state (e.g. proliferation versus quiescence) has never been investigated...
2018: PloS One
https://www.readbyqxmd.com/read/29762880/trim22-knockdown-suppresses-chronic-myeloid-leukemia-via-inhibiting-pi3k-akt-mtor-signaling-pathway
#15
Liyin Li, Yanhua Qi, Xiaobo Ma, Guosheng Xiong, Lijun Wang, Cuixia Bao
Tripartite motif-containing 22 (TRIM22) is reported to participate in numerous cellular activities. Recent studies confirm that TRIM22 is a target gene for P53, and inhibits clonogenic growth of leukemic U-937 cells. The current study aims to discover the effect of TRIM22 in progression of human chronic myeloid leukemia (CML) and explore the related mechanism. TRIM22 was knocked down by siRNA transfection in CML cell K562. We observed that TRIM22 knockdown decreased proliferation and invasion in K562 cells...
May 15, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29755565/-in-vitro-anti-proliferative-and-pro-apoptotic-properties-of-sutureja-khuzestanica-on-human-breast-cancer-cell-line-mcf-7-and-its-synergic-effects-with-anticancer-drug-vincristine
#16
Saeed Esmaeili-Mahani, Mohammad Rasoul Samandari-Bahraseman, Mohammad Mehdi Yaghoobi
Satureja khuzestanica Jamzad (Marzeh Khuzestani in Persian) is an endemic plant that is widely distributed in the southern part of Iran. Despite the number of papers published on this plant, no one has focused on its anticancer effects. Therefore, the present study was designed to investigate the selective cytotoxic and anti-proliferative properties of satureja khuzestanica total extract (SKE). MCF-7 human breast cancer cells were used in this study. Cytotoxicity of the extract was determined using MTT and neutral red assaysafter 24 h treatment period...
2018: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/29754932/mild-hypothermia-inhibits-the-notch-3-and-notch-4-activation-and-seizure-after-stroke-in-the-rat-model
#17
Guo-Shuai Yang, Xiao-Yan Zhou, Xue-Fang An, Xuan-Jun Liu, Yan-Jun Zhang, Dan Yu
Ischemic brain injury is an important cause for seizure. Mild hypothermia of the brain or the whole body is an effective way to remit the post-stroke seizure. Our previous study revealed an implication of Notch 1 and 2 in the post-stroke seizure. This study further investigated the involvement of Notch 3 and 4 in post-stroke seizure and the effect of mild hypothermia on these two factors. A global cerebral ischemia (GCI) model was conducted in Sprague Dawley rats. Seizure activity was evaluated by the frequency of seizure attacks, seizure severity scores, and seizure discharges...
May 4, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29752300/intramyocardial-angiogenetic-stem-cells-and-epicardial-erythropoietin-save-the-acute-ischemic-heart
#18
Christian Klopsch, Anna Skorska, Marion Ludwig, Heiko Lemcke, Gabriela Maass, Ralf Gaebel, Martin Beyer, Cornelia Lux, Anita Toelk, Karina Müller, Christian Maschmeier, Sarah Rohde, Petra Mela, Brigitte Müller-Hilke, Stefan Jockenhoevel, Brigitte Vollmar, Robert Jaster, Robert David, Gustav Steinhoff
Ischemic heart failure still displays the highest mortality. An early boost of intracardiac regenerative key mechanisms and angiogenetic niche signaling in cardiac mesenchymal stem cells (MSCs) could improve myocardial infarction (MI) healing. Epicardial erythropoietin (EPO, 300U kg-1 ) was compared with intraperitoneal and intramyocardial EPO treatments after acute MI in rats (n=156). Real-time PCR and confocal microscopy revealed epicardial EPO treatment enhanced intracardiac regenerative key indicators (SDF-1, CXCR-4, CD34, Bcl-2, Cyclin D1, Cdc2, MMP2), induced TGF-β/WNT signaling in intramyocardial MSC niches through direct activation of AKT, upregulations of upstream signals FOS and Fzd7 and augmented intracardiac mesenchymal proliferation 24 hours after MI...
May 10, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29751783/antiproliferative-and-apoptotic-effect-of-ly2090314-a-gsk-3-inhibitor-in-neuroblastoma-in-vitro
#19
Selvi Kunnimalaiyaan, Victoriana K Schwartz, Iris Alao Jackson, T Clark Gamblin, Muthusamy Kunnimalaiyaan
BACKGROUND: Neuroblastoma (NB) is a devastating disease. Despite recent advances in the treatment of NB, about 60% of high-risk NB will have relapse and therefore long-term event free survival is very minimal. We have reported that targeting glycogen synthase kinase-3 (GSK-3) may be a potential strategy to treat NB. Consequently, investigating LY2090314, a clinically relevant GSK-3 inhibitor, on NB cellular proliferation and may be beneficial for NB treatment. METHODS: The effect of LY2090314 was compared with a previously studied GSK-3 inhibitor, Tideglusib...
May 11, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29750990/streptozotocin-induced-hyperglycemia-stimulates-molecular-signaling-that-promotes-cell-cycle-reentry-in-mouse-hippocampus
#20
Euitaek Yang, Kartheek Gavini, Ami Bhakta, Muralikrishnan Dhanasekaran, Izhar Khan, Kodeeswaran Parameshwaran
AIMS: Cerebral atrophy resulting from neurodegeneration is highly prevalent in individuals with diabetes; however, the underlying mechanisms for diabetic neurodegeneration are not fully understood. Here we hypothesized that hyperglycemia induces molecular signaling that favors induction of proliferation in post mitotic, fully differentiated hippocampal neurons. MATERIALS AND METHODS: Streptozotocin (150 mg/kg) was intraperitoneally injected to four months old male mice to induce diabetes...
May 8, 2018: Life Sciences
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