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Cancers, Vol. 14, Pages 1848: HuR Plays a Role in Double-Strand Break Repair in Pancreatic Cancer Cells and Regulates Functional BRCA1-Associated-Ring-Domain-1(BARD1) Isoforms
Jonathan R. Brody Human Antigen R (HuR/ELAVL1) is known to regulate stability of mRNAs involved in pancreatic ductal adenocarcinoma (PDAC) cell survival. Although several HuR targets are established, it is likely that many remain currently unknown. Here, we identified BARD1 mRNA as a novel target of HuR. Silencing HuR caused a >70% decrease in homologous recombination repair (HRR) efficiency as measured by the double-strand break repair (pDR-GFP reporter) assay. HuR-bound mRNAs extracted from RNP-immunoprecipitation and probed on a microarray, revealed a subset of HRR genes as putative HuR targets, including...
Source: Cancers - April 6, 2022 Category: Cancer & Oncology Authors: Aditi Jain Matthew McCoy Carolyn Coats Samantha Z. Brown Sankar Addya Carl Pelz Rosalie C. Sears Charles J. Yeo Jonathan R. Brody Tags: Article 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 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

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

WEE1 Is Regulated by HuR upon DNA Damage
We describe a novel mechanism that PDA cells use to protect against DNA damage in which HuR posttranscriptionally regulates the expression and downstream function of WEE1 upon exposure to DNA-damaging agents. Cancer Res; 74(4); 1128–40. ©2014 AACR.
Source: Cancer Research - February 16, 2014 Category: Cancer & Oncology Authors: Lal, S., Burkhart, R. A., Beeharry, N., Bhattacharjee, V., Londin, E. R., Cozzitorto, J. A., Romeo, C., Jimbo, M., Norris, Z. A., Yeo, C. J., Sawicki, J. A., Winter, J. M., Rigoutsos, I., Yen, T. J., Brody, J. R. Tags: Molecular and Cellular Pathobiology Source Type: research