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Source: Cancer Research
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Total 807 results found since Jan 2013.
Abstract 129: RAD17 loss of function is synthetically lethal with the checkpoint kinase inhibitors AZD7762 or MK-1775
Synthetic lethal interactions are a type of genetic interaction in which the simultaneous loss of function of two genes in combination results in cell death. Recently, there has been much interest in the discovery of drugs that are selectively toxic to cancer cells by targeting proteins that form synthetic lethal interactions with tumor specific mutations. He we have identified that RAD17 loss of function is synthetically lethal with AZD7762, an inhibitor of Chk1 and Chk2, and with MK-1775, an inhibitor of Wee1. HeLa or LN428 glioblastoma cells were selectively responsive to AZD7762 or MK-1775 following shRNA-mediated depl...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Shen, J. P., Srivas, R., Bojorquez-Gomez, A., Licon, K., Sivaganesh, V., Xu, J. L., Yeerna, H., Gross, A., Li, J. F., Sobol, R., Ideker, T. Tags: Molecular and Cellular Biology Source Type: research
Abstract LB-136: The role of ER chaperone GRP94 in endometrial cancer progression
This study expands our understanding of GRP94 function in the progression of solid tumors and provides the first evidence that GRP94 could be a target for combating endometrial cancer.Citation Format: Jieli Shen, Yvonne G. Lin, Louis Dubeau, Amy S. Lee. The role of ER chaperone GRP94 in endometrial cancer progression. [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 LB-136. doi:10.1158/1538-7445.AM2015-LB-136
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Shen, J., Lin, Y. G., Dubeau, L., Lee, A. S. Tags: Tumor Biology Source Type: research
Abstract 142: SiRNA therapy against novel lncRNA NRCP: shutting down the fuel for cancer cells
In this study, we report the role of lncRNA NRCP in altering cancer cell metabolism and provide a strategy to target cancer metabolism using siRNAs. Methodology and Results: Using genomic profiling of ovarian tumors (n = 29) and normal ovarian tissues (n = 11) and comparative analyses, we found that NRCP was highly upregulated in ovarian tumors (>100 fold, p80%, p
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Rupaimole, R., Previs, R., Lee, J., Pradeep, S., Wu, S. Y., Ivan, C., Ferracin, M., Dennison, J., Rodriguez-Aguayo, C., Calin, G. A., Mills, G., Zhang, W., Lopez-Berestein, G., Bhattacharya, P., Sood, A. K. Tags: Molecular and Cellular Biology Source Type: research
Abstract 144: CASC15 is a tumor suppressor lncRNA at the 6p22 neuroblastoma susceptibility locus
Background: Neuroblastoma, a clinically heterogeneous childhood tumor, presents as high-risk disease in 40% of diagnoses and is fatal in roughly half of these patients. In an effort to elucidate the genetic basis of high-risk disease, our lab previously undertook a genome-wide association study (2101 cases, 4202 controls), identifying a cluster of single-nucleotide polymorphisms on chromosome 6p associate with an increased risk of developing of high-risk disease (p
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Russell, M. R., Penikis, A., Oldridge, D., Alvarez-Dominguez, J. R., McDaniel, L., Diamond, M., Padovan, O., Raman, P., Li, Y., Wei, J., Zhang, S., Gnanachandran, J., Seeger, R., Asgharzadeh, S., Khan, J., Diskin, S., Maris, J., Cole, K. Tags: Molecular and Cellular Biology Source Type: research
Abstract 146: The long noncoding RNA MALAT1 promotes hypoxia-driven angiogenesis by upregulating pro-angiogenic gene expression in neuroblastoma cells
Neuroblastoma is the most common solid tumour during early childhood, and accounts for 15% of all childhood cancer death. One of the key features of neuroblastoma is aggressive progression due to tumour-driven angiogenesis. However, the mechanism through which neuroblastoma cells drive angiogenesis is unclear. Here we showed that the long noncoding RNA MALAT1 was over-expressed in human neuroblastoma cells under hypoxic condition, the condition which triggers pro-angiogenic switch and angiogenesis. In vitro angiogenesis assays demonstrated that conditioned medium from neuroblastoma cells transfected with MALAT1 siRNAs, com...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Tee, A. E., Liu, P., Maag, J., Song, R., Li, J., Cheung, B. B., Haber, M., Norris, M. D., Marshall, G. M., Dinger, M., Liu, T. Tags: Molecular and Cellular Biology Source Type: research
Abstract 149: Overexpression of the long non-coding RNA PVT1 and its role in cervical carcinogenesis
Although it is becoming increasingly clear that long non-coding RNAs (lncRNAs) are intricately involved in numerous cancer types, the mechanisms by which they influence carcinogenesis remain poorly understood. The plasmacytoma variant translocation 1 gene (PVT1) is a lncRNA that has been designated as an oncogene due to its contribution to the phenotype of multiple cancers. Further, our lab has recently demonstrated that human papillomavirus (HPV) integration, a hallmark of invasive cervical cancer (ICC), into the PVT1 locus occurs in multiple cervical tumors. The present study was designed to investigate the role of PVT1 ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Iden, M., Fye, S., Ramchandran, R., Rader, J. S. Tags: Molecular and Cellular Biology Source Type: research
Abstract 159: LncRNA RoR enhances the c-Myc mRNA stability in colon cancer
Conclusion: It is well known that c-Myc mRNA has a very short half-life and regulation of c-Myc mRNA stability is complex. Our results suggest a novel mechanism of regulation of c-Myc mRNA stability involving lncRNA-RoR, hnRNP U and hnRNP D.Citation Format: Jianguo Huang. LncRNA RoR enhances the c-Myc mRNA stability in colon cancer. [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 159. doi:10.1158/1538-7445.AM2015-159
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Huang, J. Tags: Molecular and Cellular Biology Source Type: research
Abstract 160: ZFAS1, long non-coding RNA with significance in colorectal cancer
Introduction: Colorectal cancer (CRC) is one of the most common cancers in the world. However, the existence of multiple known carcinogens and varying genetic backgrounds makes it difficult to determine which factors are most important in the development of CRC. Therefore, the identification of a bona fide molecule involved in progression of CRC has been greatly sought after. Long noncoding RNAs (lncRNA) are emerging as key molecules in human cancer, and some of them were shown to have potential for cancer diagnosis and prognosis. ZFAS1, an lncRNA, has been recently revealed involving in human breast cancer as putative tum...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Thorenoor, N., Vychytilova, P., Mlcochova, J., Hombach, S., Kretz, M., Sana, J., Slaby, O. Tags: Molecular and Cellular Biology Source Type: research
Abstract 163: Investigation of molecular mechanisms by which PCA3 modulates prostate cancer cell survival
PCA3 is a prostate-specific non coding RNA (ncRNA), involved in the control of prostate cancer (PCa) cell survival, through modulating androgen receptor (AR) signaling. We aimed to investigate whether several cancer related genes, including those involved in epithelial-mesenchymal transition (EMT) and AR co-regulators could modulate LNCaP cell survival in response to PCA3 downregulation. We also aimed to promote PCA3 stable silencing through a lentiviral vector containing a PCA3 short hairpin RNA (shRNA) specific sequence. Small interfering RNA (siRNA) or lentivirus vector-based shRNA were used to downregulate PCA3 express...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Goulart, A. E., Ferreira, L. B., de Freitas, P. P., Batoreu, N., BONAMINO, M. H., Gimba, E. R. P. Tags: Molecular and Cellular Biology Source Type: research
Abstract 191: The role of microRNAs in the epigenetic silencing of CHD5, a tumor suppressor in neuroblastoma
Background: Neuroblastoma (NB) is a tumor of the sympathetic nervous system that is the most common extracranial solid tumor of childhood. NBs show remarkable clinical heterogeneity, and we, along with others, have identified different patterns of genomic change that underlie these diverse clinical behaviors. We first identified 1p deletion as a characteristic change in advanced stage NBs. CHD5, a tumor suppressor gene, was first identified because of its location on 1p36. However, mutation of the remaining allele of CHD5 is rare in these tumors. Therefore, it is likely that epigenetic mechanisms play important roles in CH...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Naraparaju, K., Kolla, V., Zhuang, T., Higashi, M., Blobel, G. A., Brodeur, G. M. Tags: Molecular and Cellular Biology Source Type: research
Abstract 194: Deregulation of miR-222-ABCG2 regulatory module in tongue squamous cell carcinoma contributes to chemoresistance and enhanced metastatic potential
Chemoresistance often associated with other clinical characteristics, such as enhanced metastatic potential. However, the underlying molecular mechanism remains unclear. Our previous studies had revealed that microRNA-222 (miR-222) regulates the cell invasion [Cancer Genomics Proteomics 2009 6:131-138], and plays a role in cell proliferation in tongue squamous cell carcinoma (TSCC) [FEBS Lett. 2010 584(18):4115-20]. The aim of this study is to elucidate the role of miR-222-ABCG2 pathway in the association of cisplatin (cDDP) resistance with enhanced cell migration and invasion ability in TSCC. First, we confirmed the assoc...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Wang, A., Zhao, L., He, Q., Zhao, T., Wang, W., Zhou, X. Tags: Molecular and Cellular Biology Source Type: research
Abstract LB-200: Loss of the scaffold protein Kibra in a mouse model of triple-negative breast cancer
Introduction: Targeted therapies in breast cancer rely on tumor cell expression of Estrogen and/or HER2 receptors. Triple negative breast cancers (TNBCs), lacking these receptors, have no targeted therapies. We have developed a preclinical murine model expressing a naturally occurring oncogenic variant of the Met receptor in the mammary gland combined with loss of function of the tumour suppressor p53 (MMTV-Met;Trp53fl/+;Cre). This model recapitulates many features of TNBC at the level of gene expression, pathological markers and genomic alterations. Notably, this model spontaneously undergoes loss of a genomic region synt...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Knight, J. F., Gruosso, T., de Verteuil, D. A., Saleh, S., Lesurf, R., Zhao, H., Davis, R., Zuo, D., Cardiff, R., Gregg, J., Hallett, M., Park, M. Tags: Tumor Biology Source Type: research
Abstract LB-106: Fusogenic-oligoarginine peptide-mediated silencing of the CIP2A oncogene suppresses oral cancer tumor growth in vivo
Intracellular delivery and endosomal escape of functional small interfering RNAs (siRNAs) remain major barriers limiting the clinical translation of RNA interference (RNAi)-based therapeutics. Recently, we demonstrated that a endosome-disruptive peptide we synthesized termed, 599, could enhance the intracellular delivery and bioavailability of siRNAs designed to target the CIP2A oncoprotein (siCIP2A) into oral cancer cells and consequently inhibit oral cancer cell invasiveness and anchorage-independent growth in vitro. Thus, to further assess the therapeutic potential of the 599 peptide in mediating RNAi-based therapeutics...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Alexander-Bryant, A., Dumitriu, A., Attaway, C., Yu, H., Jakymiw, A. Tags: Cancer Chemistry Source Type: research
Abstract 110: The role of the p53 target Wig-1 in senescence and cancer
The wild type p53-induced gene 1, Wig-1 (also known as Zmat3 or PAG608) binds to AU-rich elements in mRNAs and thereby regulates important tumor associated factors including p53, FAS, and N-Myc.Focusing on normal human diploid fibroblasts (HDF), we are now exploring the role of Wig-1 in senescence. SiRNA-mediated Wig-1 depletion increases senescence markers such as Beta-galactosidase staining, H3K9me3, H4K20me3, and p21. Also, Wig-1 is spontaneously downregulated in cells undergoing replicative senescence.The trimethylation of lysine 9 on histone 3 (H3K9me3) is an established marker of cellular senescence and increases upo...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Jerhammar, F., Bersani, C., Djureinovic, D., Micke, P., Wiman, K. G. Tags: Molecular and Cellular Biology Source Type: research
Abstract LB-218: Protein arginine methyltransferase inhibition of malignant gliomas leads to restored chemokine expression and enhanced immune effector function
Patients with Glioblastoma Multiforme (GBM) face a poor prognosis despite multimodal therapy, thus, there is an unmet need for discovery of novel therapeutic targets and approaches. The immune-privileged nature of the central nervous system and down-modulation of cytokines and chemokines in GBM tumors led us to explore epigenetic approaches to restore expression of immune-relevant genes.PRMT5 is a type II arginine methyltransferase that catalyzes symmetric dimethylation of arginine residues on histone proteins leading to transcriptional repression. Our previous work showed PRMT5 overexpression correlates with poor clinical...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Yan, F., Banasavadi-Siddegowda, Y., Patton, J. T., Lustberg, M., Wu, X., Kaur, B., Baiocchi, R. A. Tags: Immunology Source Type: research
