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Total 66 results found since Jan 2013.

Downregulated DYRK2 expression is associated with poor prognosis and Oxaliplatin resistance in hepatocellular carcinoma
Publication date: Available online 7 January 2016 Source:Pathology - Research and Practice Author(s): Xiubing Zhang, Pan Xu, Wenkai Ni, Hui Fan, Jian Xu, Yongmei Chen, Wei Huang, Shumin Lu, Li Liang, Jinxia Liu, Buyou Chen, Weidong Shi We aimed to investigate the molecular mechanisms of DYRK2 and the HCC sensitivity to Oxaliplatin in DYRK2-depleted HCC cells. HCC tissue specimens were obtained from 86 HCC patients during hepatectomy. We used immunohistochemistry and western blot to analyze DYRK2 expression in HCC tissues and cell lines, and used siRNA transfection to decrease DYRK2 expression in HCC cells. Fl...
Source: Pathology Research and Practice - January 22, 2016 Category: Pathology Source Type: research

Downregulated DYRK2 expression is associated with poor prognosis and Oxaliplatin resistance in hepatocellular carcinoma.
Abstract We aimed to investigate the molecular mechanisms of DYRK2 and the HCC sensitivity to Oxaliplatin in DYRK2-depleted HCC cells. HCC tissue specimens were obtained from 86 HCC patients during hepatectomy. We used immunohistochemistry and western blot to analyze DYRK2 expression in HCC tissues and cell lines, and used siRNA transfection to decrease DYRK2 expression in HCC cells. Flow cytometry and CCK-8 assay were detected in cell cycle progression, cell proliferation and the efficacy of Oxaliplatin, DYRK2 was down-regulated in HCC tissues, compared with adjacent nontumor ones. The significant correlation bet...
Source: Pathology, Research and Practice - January 7, 2016 Category: Pathology Authors: Zhang X, Xu P, Ni W, Fan H, Xu J, Chen Y, Huang W, Lu S, Liang L, Liu J, Chen B, Shi W Tags: Pathol Res Pract Source Type: research

Abstract C5: FLIP protein-protein interaction inhibitors enhance sensitivity of colorectal cancer cells to chemotherapy and TRAIL
ConclusionWe have developed inhibitors of FLIP that decrease its recruitment to the TRAIL-R2 DISC and increase TRAIL-induced caspase activation and apoptosis. Moreover, these inhibitors synergise with 5-Fluorouracil, oxaliplatin and SN38, suggesting that this novel class of agents has therapeutic potential in CRC when used in conjunction with standard-of-care chemotherapeutic agents.AcknowledgementsThis work was supported by a Seeding Drug Discovery award from the Wellcome Trust (reference: 099470).Citation Format: Jennifer P. Fox, Joanna Majkut, Catherine Higgins, Zsuzsanna Nemeth, Adnan Malik, Christopher J. Scott, Peter...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Fox, J. P., Majkut, J., Higgins, C., Nemeth, Z., Malik, A., Scott, C. J., Blurton, P., Boffey, R. J., Perrior, T. R., Harrison, T., Longley, D. B. Tags: Apoptosis, Necrosis, and Autophagy: Poster Presentations - Proffered Abstracts Source Type: research

siRNA-mediated silencing of MDR1 reverses the resistance to oxaliplatin in SW480/OxR colon cancer cells.
Authors: Montazami N, Kheir Andish M, Majidi J, Yousefi M, Yousefi B, Mohamadnejad L, Shanebandi D, Estiar MA, Khaze V, Mansoori B, Baghbani E, Baradaran B Abstract One of the most challenging aspects of colon cancer therapy is rapid acquisition of multidrug resistant phenotype. The multidrug resistance gene 1 (MDR1) product, p—glycoprotein (P—gp), pump out a variety of anticancer agents from the cell, giving rise to a general drug resistance against chemotherapeutic agents. The aim of this study was to investigate the effect of a specific MDR1 small interference RNA (siRNA) on sensitivity of ox...
Source: Cellular and Molecular Biology - December 2, 2015 Category: Molecular Biology Tags: Cell Mol Biol (Noisy-le-grand) Source Type: research

Down-Regulating Receptor Interacting Protein Kinase 1 (RIP1) Promotes Oxaliplatin-Induced Tca8113 Cell Apoptosis.
CONCLUSIONS Down-regulating RIP1 promotes oxaliplatin induced Tca8113 cells apoptosis. PMID: 26460489 [PubMed - in process]
Source: Medical Science Monitor - October 16, 2015 Category: Research Tags: Med Sci Monit Source Type: research

Abstract 4415: Tyrosine phosphorylation is essential for OCT2 function and a target of inhibition by TKIs
Cisplatin and oxaliplatin are among the most widely used anticancer drugs in both children and adults. The clinical use of these agents is associated with dose-limiting damage to kidneys (nephrotoxicity) and peripheral nerves (neurotoxicity). Mechanistic understanding of the underlying etiology remains incomplete and preventive strategies are currently unavailable. We previously reported that cisplatin nephrotoxicity (Filipski et al, CPT 2009) and oxaliplatin neurotoxicity (Sprowl et al, PNAS 2013) are dependent on organic cation transporter-mediated uptake mechanisms and can be reduced by genetic or pharmacological inhibi...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Pabla, N., Sprowl, J. A., Ong, S. S., Gibson, A. A., Du, G., Lin, W., Hu, S., Li, L., Chen, T., Sparreboom, A. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 1656: MK-1775 (WEE1 inhibition) lacks efficacy against DNA repair deficient pancreatic cancer cells
Conclusions: These results support a paradigm in which identified high risk FA/BRCA2-mutated patients would not benefit from WEE1 inhibitor monotherapy; and thus, would most likely respond better to conventional DNA damaging agent-based therapies (e.g., oxaliplatin or MMC).Citation Format: Shruti Lal, Saswati N. Chand, Emanuela Dylgjeri, Charles J. Yeo, Jordan M. Winter, Jonathan R. Brody. MK-1775 (WEE1 inhibition) lacks efficacy against DNA repair deficient pancreatic cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Phi...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Lal, S., Chand, S. N., Dylgjeri, E., Yeo, C. J., Winter, J. M., Brody, J. R. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 1047: A role for the free beta subunit of human chorionic gonadotropin in sensitivity of epithelial ovarian cancer cells to platinum-based chemotherapeutics
Conclusions: These findings suggest that hCG-β may be involved in modulating the sensitivity of some EOCs to platinum based chemotherapy. Suppression of hCG-β may be a strategy to increase the responsiveness of primary EOCs to platinum-based chemotherapeutics.Citation Format: Snega M. Sinnappan, Robert C. Baxter, Deborah J. Marsh. A role for the free beta subunit of human chorionic gonadotropin in sensitivity of epithelial ovarian cancer cells to platinum-based chemotherapeutics. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Phil...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Sinnappan, S. M., Baxter, R. C., Marsh, D. J. Tags: Molecular and Cellular Biology Source Type: research

Resveratrol induces AMPK-dependent MDR1 inhibition in colorectal cancer HCT116/L-OHP cells by preventing activation of NF-κB signaling and suppressing cAMP-responsive element transcriptional activity
In this study, the effects of resveratrol on the expression of P-glycoprotein/multi-drug resistance protein 1 (P-gp/MDR1), and the underlying molecular mechanisms, were investigated in oxaliplatin (L-OHP)-resistant colorectal cancer cells (HCT116/L-OHP). Resveratrol downregulated MDR1 protein and mRNA expression levels and reduced MDR1 promoter activity. It also enhanced the intracellular accumulation of rhodamine 123, suggesting that resveratrol can reverse multi-drug resistance by downregulating MDR1 expression and reducing drug efflux. Resveratrol treatment also reduced nuclear factor-κB (NF-κB) activity, reduced phos...
Source: Tumor Biology - July 1, 2015 Category: Cancer & Oncology Source Type: research

Abstract A71: Post-transcriptional regulation of the proto-oncogene PIM1 by the mRNA stability factor HuR: implications for pancreatic cancer therapeutic response and cell survival
Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignancy characterized by its insidious development and resistance to conventional and targeted therapies. As a result of selective pressures imposed by cytotoxic agents and the tumor microenvironment, PDA cells orchestrate a potent and elusive chemoresistant mechanism. Recently, the serine-threonine kinase PIM1 has emerged as a key regulator of PDA cell survival under cancer-associated stress (e.g: cytotoxic DNA-damaging agents, hypoxia). However, the molecular mechanism behind PIM1 overexpression in PDAs is unknown. Here, we demonstrate that cis-acting AU-rich ele...
Source: Cancer Research - June 30, 2015 Category: Cancer & Oncology Authors: Blanco, F. F., Meisner-Kober, N., Londin, E., Rigoutsos, I., Winter, J., Yeo, C., Brody, J. Tags: Heterogeneity in Tumor Progression Source Type: research

Role of ribophorin II in the response to anticancer drugs in gastric cancer cell lines.
Authors: Yuan TM, Liang RY, Chueh PJ, Chuang SM Abstract The identification of prognostic markers and establishing their value as therapeutic targets improves therapeutic efficacy against human cancers. Ribophorin II (RPN2) has been demonstrated to be a prognostic marker of human cancer, including breast and pancreatic cancers. The present study aimed to evaluate RPN2 expression in gastric cancer and to examine the possible correlation between RPN2 expression and the response of cells to clinical anticancer drugs, which has received little research attention at present. The gastric cancer AGS, TMC-1, SNU-1, TMK-1, ...
Source: Oncology Letters - June 4, 2015 Category: Cancer & Oncology Tags: Oncol Lett Source Type: research

EGCG Synergizes the Therapeutic Effect of Cisplatin and Oxaliplatin through Autophagic Pathway in Human Colorectal Cancer Cells
In this study we used synergistic strategies by combining (-)-Epigallocatechin gallate (EGCG) with cisplatin or oxaliplatin to minimize the ill effects of platinium-based therapy. MTS assay was used to examine the effect of EGCG, cisplatin and oxaliplatin on the proliferation of human colorectal cancer DLD-1 and HT-29 cells. Autophagic process was evaluated by detection of LC3-II protein, autophagosome formation, and quantification of Acidic Vesicular. Treatment of DLD-1 and HT-29 cells with EGCG plus cisplatin or oxaliplatin showed a synergistic effect on inhibition of cell proliferation and induction of cell death. EGCG ...
Source: Journal of Pharmacological Sciences - April 15, 2015 Category: Drugs & Pharmacology Source Type: research

Identification of anti-metastatic drug and natural compound targets in isogenic colorectal cancer cells.
Abstract Therapeutic strategies for cancer treatment often remain challenging due to the cumulative risk derived from metastasis, which has been described as an aggressive state of cancer cell proliferation often resulting in failure of clinical therapy. In the current study, anti-metastatic properties of three chemotherapeutic drugs and three compounds from natural sources were investigated by comparative proteomic analysis. Proteomic profile comparison of the isogenic primary and metastatic colon cancer cell lines SW480 and SW620 identified two potential metastasis related molecular targets: fatty acid synthase ...
Source: Journal of Proteomics - October 23, 2014 Category: Biochemistry Authors: Lee JG, McKinney KQ, Pavlopoulos AJ, Park JH, Hwang S Tags: J Proteomics Source Type: research

Abstract 5267: Pro-inflammatory CXCL8 signaling potentiates survival of K-Ras mutant colorectal cancer cells
Conclusions: CXCL8 signaling is elevated in K-Ras and PI3KCA mutant cancers. The up-regulation of autocrine CXCL8 signaling is linked to the promotion of cell survival, principally mediated through the inhibition of apoptosis and promotion of RTK signaling. The clinical relevance of CXCL8 signaling in modulating outcome of K-Ras mutant CRC to current treatments remains to be determined. However, CXCL8-directed therapies may be relevant as chemo-sensitizing agents in K-Ras and/or PIK3CA mutant tumors. Citation Format: Laura M. Campbell, Olabode Oladipo, Pamela J. Maxwell, Daniel Longley, Richard H. Wilson, David JJ Waugh. P...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Campbell, L. M., Oladipo, O., Maxwell, P. J., Longley, D., Wilson, R. H., Waugh, D. J. Tags: Molecular and Cellular Biology Source Type: research

Abstract 2079: EpHA2 is an essential driver of invasion and a novel target in KRAS mutant colorectal cancer
Conclusion Using our novel comprehensive systems biology approach we have identified novel KRAS synthetic lethal targets and pathways. Combining these findings with targets which are effective against our pre-clinical adjuvant models we have identified EpHA2 as a key driver of invasion and migration and a synthetically lethal target in KRASMT CRC. In addition, we show that EpHA2 is a poor prognostic marker and an important novel target for KRASMT CRC tumors in both the adjuvant and advanced disease setting. Citation Format: Philip D. Dunne, Darragh G. McArt, Jaine K. Blayney, Sonali Dasgupta, Manuel Salto-Tellez, Patrick G...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Dunne, P. D., McArt, D. G., Blayney, J. K., Dasgupta, S., Salto-Tellez, M., Johnston, P. G., Schaeybroeck, S. V. Tags: Tumor Biology Source Type: research