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Source: Cancer Research
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Total 807 results found since Jan 2013.
Abstract 1140: PI3K/Akt inhibition decreases oxygen consumption In tumor cells by phosphorylating and inactivating pyruvate dehydrogenase PDH E1{alpha} subunit
The PI3K/mTOR pathway plays a central role in coupling metabolic processes to the cellular proliferative state. Pharmacologic inhibitors of the PI3K/mTOR pathway or genetic inhibition of Akt/PI3K decreased the oxygen consumption rate (OCR) in transformed cell lines in vitro by 30-40%. Pharmacologic inhibition of this pathway increased phosphorylation of the E1α subunit of the pyruvate dehydrogenase (PDH) complex on Ser293, an inhibitory modification of this critical gatekeeper of mitochondrial respiration. Expressing wild type PTEN in a doxycycline-inducible manner in a glioblastoma cell line with mutant PTEN led to an in...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Cerniglia, G. J., Day, S., Gallagher-Colombo, S. M., Daurio, N., Tuttle, S., Busch, T. M., , Lin, A., Esipova, T. V., Vinogradov, S. A., Koumenis, C., Maity, A. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1142: COP1 functions as a sensor of cellular lipids and regulator of lipogenesis in human cancer cells
ConclusionCOP1 functions as a sensor of cellular lipid state and promoter of lipogenesis, facilitating tumorigenesis.Note: This abstract was not presented at the meeting.Citation Format: Chenfei Huang, Yiwen Bu, Deliang Cao. COP1 functions as a sensor of cellular lipids and regulator of lipogenesis in human cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1142. doi:10.1158/1538-7445.AM2015-1142
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Huang, C., Bu, Y., Cao, D. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1180: Hexokinase II plays a pivotal role in colorectal cancer cell proliferation and survival
The Warburg Effect describes the widely observed metabolic phenotype of cancer cells and their heavy reliance on the glycolytic pathway for energy production regardless of oxygen tension. This is a result of alterations to metabolic signaling pathways leading to an upregulation in key glycolytic enzymes. Hexokinase II (HKII) catalyzes the first irreversible step of glycolysis and is often overexpressed in tumors. 3-bromopyruvate (3BP) has been shown to primarily target HKII, and is a promising anti-cancer compound capable of targeting critical metabolic pathways in cancer cells. Here we examine the importance of HKII to ce...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Ho, N., Coomber, B. L. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1191: The RNA binding protein, HuR, regulates pancreatic cancer cell metabolism
Conclusions: HuR enhances metabolic efficiency in PDA cells by directly regulating multiple metabolic pathways. Ongoing microarray studies will highlight which metabolic transcripts are post-transcriptionally regulated by HuR, resulting in the observed phenotype.canres;75/15_Supplement/1191/table1T1Altered metabolites due to HuR silencing in PDA cells ([1,2-13C2]-D-glucose tracer)PathwayMetabolitesiHuR 25mM glucosesiHuR 5 mM glucoseCorrelation1Myristate (C:14) Intracell13C enrichment70.271.01.02Myristate (C:14) intracellFNS (direct)56.060.41.03Oleate (C:18-1) IntracellIndirect synthes-m187.689.51.04Glutam extracell [C2-C5]...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Blanco, F. F., Zarei, M., Brody, J. R., Boros, L. G., Winter, J. M. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1195: Ethanolamine kinase-1 and phosphoethanolamine are potential diagnostic markers and therapeutic targets in breast cancer
Increased phosphoethanolamine (PE) has been observed in tumors almost as consistently as increased phosphocholine (PC), but the role of PE in cancer is relatively unexplored. Our ongoing studies have shown that choline kinase (ChK)-α, the enzyme that forms PC from choline, has a dual choline/ethanolamine kinase activity but ChK-β has no significant role in maintaining PE levels in vivo. We observed that ethanolamine kinase (EtnK)-1siRNA significantly reduces PE levels in triple negative MDA-MB-231 human breast cancer cells. We further investigated the role of ethanolamine kinase-2 (EtnK-2) in contributing to the increase...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Shah, T., Krishnamachary, B., Wildes, F., Wijnen, J., Glunde, K., Bhujwalla, Z. M. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1199: Systems-based approach identifies altered carbohydrate metabolism as a predictor of a malignant phenotype in ovarian cancer
Conclusions: Here, we present a novel systems-based approach using altered metabolites and genes to predict a malignant phenotype specific to HGSOC patients. Altered metabolism, coupled with genomic analyses, identified the most interconnected gene-biochemical networks that will lead to novel biomarkers and therapeutic targets.Citation Format: Rebecca A. Previs, Tyler J. Moss, Behrouz Zand, Rajesha Rupaimoole, Heather J. Dalton, Jean M. Hansen, Guillermo Armaiz-Pena, Susan Lutgendorf, Robert L. Coleman, Pratip Bhattacharya, Prahlad Ram, Anil K. Sood. Systems-based approach identifies altered carbohydrate metabolism as a pr...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Previs, R. A., Moss, T. J., Zand, B., Rupaimoole, R., Dalton, H. J., Hansen, J. M., Armaiz-Pena, G., Lutgendorf, S., Coleman, R. L., Bhattacharya, P., Ram, P., Sood, A. K. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1212: Mutant p53 stabilizes and protects the transcription factor ETS2 from proteasomal degradation by the ubiquitin ligase COP1/DET1
Genetic mutations of the tumor suppressor gene TP53 contribute to a great majority of human cancers. One mechanism by which mutant TP53 (mtp53) acts is through the interaction with other transcription factors, which can either enhance or repress the transcription of their target genes. Mtp53 preferentially interacts with ETS2, an ETS transcription factor, and increases its stability. This results in an increase of the expression of ETS target genes that are associated with the transition of normal cells into tumor cells. Previous studies have shown that the ubiquitin-proteasomal pathway regulates ETS2 stability. To study t...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Carrero, Z. I., Kollareddy, M., Chauhan, K. M., Ramakrishnan, G., Martinez, L. A. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1214: TP53 affects SOX2 copy number alterations and expression in non-small cell lung cancer
Background: Amplifications of the transcription factor, SRY (sex determining region Y)-box 2 (SOX2), are common in non-small cell lung cancer (NSCLC). SOX2-signaling is important in maintaining the stem cell-like phenotype of cancer cells and contributes to the pathogenesis of lung cancer. TP53 is recognized as a critical regulator of stem cell pluripotency, and it is known that TP53 represses many stem cell associated genes following DNA damage. We hypothesized that SOX2 copy number alterations in lung tumors could be correlated to mutational status of TP53 gene in tumors and that TP53 played a role in regulation of SOX2 ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Samulin-Erdem, J., Skaug, V., Bakke, P., Gulsvik, A., Haugen, A., Zienolddiny, S. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1215: Small molecule Prodigiosin-mediated p53 pathway restoration and inhibition of self-renewal in colorectal cancer involves c-Jun-mediated {Delta}Np73 inhibition and p73 activation
Tumor suppressor p53 is frequently mutated or inactivated in colorectal cancer while p53 family member p73 is rarely mutated in cancer cells. Small molecules that activate p73 can elicit a p53-like tumor suppressive function and represent a novel approach for p53 pathway restoration. Colorectal tumors contain a small population of cancer stem cells (CSCs) capable of self-renewal that contributes to tumor maintenance and resistance to therapy. Targeting CSCs could improve treatment response and prolong patient survival. We have previously shown that small molecule Prodigiosin restores the p53 pathway via activation of p73 a...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Prabhu, V. V., Zhang, S., Hong, B., Allen, J. E., Lulla, A., Dicker, D. T., El-Deiry, W. S. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1019: hnRNPA2/B1 upregulates COX-2 expression and tumor growth and predicts poor prognosis in human lung cancers
In this study, we discovered and identified hnRNPA2/B1 as a novel regulator of COX-2 promoter in non-small cell lung cancer (NSCLC) cells by a DNA probe-biotin-streptavidin-agarose pulldown and proteomic technique. We showed that hnRNPA2/B1 specifically bound to COX-2 core promoter region, activated COX-2 promoter activity and up-regulated COX-2 expression. Knockdown of hnRNPA2/B1 expression by siRNA significantly suppressed tumor cell growth in NSCLC cell lines in vitro and in a animal model in vivo by inhibiting COX-2 expression. In contrast, overexpression of hnRNPA2/B1 promoted COX-2 expression and tumor cell growth in...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Wang, J., Xuan, Y., Guo, W., Du, G., Deng, W. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1021: Superoxide anion (O2.-) mediated activation of mTORC2 by estrogen receptor in breast cancer cells: Role of acetylation dependent inhibition of MnSOD
ConclusionOur findings unravel a new role of MnSOD as an important control-switch through which ER might affect its downstream non-genomic signaling cascades in a redox dependent manner particularly potentiation of mTORC2. We present data in support of MnSOD being responsible for previously reported ER dependent superoxide anion O2.- potentiation in breast-cancer cells following E2 exposure. We showed that MnSOD interacts with ER-alpha leading to its diminished SIRT3 dependent deacetylation, its inhibition and superoxide anion O2.- build up and consequent mTORC2 activation.Citation Format: Mehraj U. lone, Ranjana Km Kancha...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: lone, M. U., Kanchan, R. K., Baghel, K. S., Tripathi, C., Tewari, B. N., Bhadauria, S. Tags: Molecular and Cellular Biology 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
Abstract 1052: Variable expression of 5-alpha reductase 2 in the aging adult prostate is regulated by DNA methylation
BACKGROUND:5-alpha reductase type 2 (SRD5A2), an enzyme that is critical for prostatic development and growth, is utilized as an inhibitory target by finasteride for patients with bladder outlet obstrution secondary to BPH. However, we have found that many aging benign prostate tissues do not express the enzyme. Since the SRD5A2 promoter contains a CpG island, we hypothesized that somatic methylation of the promoter would be regulated by DNA methyltransferases leading to suppression of SRD5A2.METHODS:Benign prostatic tissues from wild-type mice at 3, 6 and 12 months of age were used. In addition, 96 prostate samples from h...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Rongbin, G., Wang, Z., Bechis, S., Otsetov, A., Hua, S., Wu, S., Wu, C.-L., Tabatabaei, S., Olumi, A. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1064: RASSF10 suppresses colorectal cancer growth by activating p53 signaling and sensitizes colorectal cancer cell to docetaxel
RASSF10 has previously been reported to be frequently methylated in a number of malignancies. To understand the importance of RASSF10 inactivation in colorectal carcinogenesis, eight colorectal cancer cell lines, 89 cases of primary colorectal cancer and 5 cases of normal colorectal mucosa were examined. Methylation specific PCR, western blot, siRNA, gene expression array and xenograft mice were employed. The expression of RASSF10 was was regulated by promoter regional methylation in colorectal cancer cells. RASSF10 was methylated in 60.7% (54/89) of primary colorectal cancers and was positively associated with tumor stage (p
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Guo, J., Yang, Y., , Linghu, E., Zhan, Q., Brock, M. V., Herman, J. G., Zhang, B., Guo, M. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1100: Functional genomics to investigate the genetic determinants of cell death induced by oxidative stresses
Increased oxidative stress in the tumor microenvironments is a prominent stress that many tumor cells need to cope with during oncogenesis. The stress depletes intracellular glutathione, increases reactive oxygen species, and finally triggers cell death in tumors. Despite its importance during oncogenesis, the genetic determinants and the cell death mechanisms under oxidative stress remain poorly defined. Here, we applied a genome-wide siRNA screen to oxidative-stress-induced cell death. Candidate genes were identified if the silencing could rescue cell death under oxidative stresses. The identified candidate genes are pri...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Ding, C.-K. C., Tang, X., Kim, S. Y., Chi, J.-T. A. Tags: Molecular and Cellular Biology Source Type: research
