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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

Cancers, Vol. 13, Pages 724: SILAC-Based Quantitative Proteomic Analysis of Oxaliplatin-Resistant Pancreatic Cancer Cells
In this study, we performed a stable isotope labelling by amino acids in cell culture (SILAC)-based quantitative proteomics analysis of oxaliplatin-resistant and sensitive pancreatic cancer PANC-1 cells. We identified 107 proteins whose expression levels changed (thresholds of 2-fold changes and p-value ≤ 0.05) between oxaliplatin-resistant and sensitive cells, which were involved in multiple biological processes, including DNA repair, cell cycle process, and type I interferon signaling pathway. Notably, myristoylated alanine-rich C-kinase substrate (MARCKS) and Wntless homolog protein (WLS) were upregulated in oxaliplat...
Source: Cancers - February 10, 2021 Category: Cancer & Oncology Authors: Young Eun Kim Eun-Kyung Kim Min-Jeong Song Tae-Young Kim Ho Hee Jang Dukjin Kang Tags: Article Source Type: research

Effects of taxol resistance gene 1 expression on the chemosensitivity of SGC-7901 cells to oxaliplatin.
Authors: Liu L, Bai Z, Ma X, Wang T, Yang Y, Zhang Z Abstract The present study aimed to evaluate the role of taxol resistance gene 1 (Txr1) in the development of oxaliplatin (L-OHP) resistance in gastric cancer (GC). Using SGC-7901 cells as a model, Txr1 was exogenously expressed or knocked down using small interfering RNA. Quantitative polymerase chain reaction (qPCR) and western blotting were performed to establish whether the Txr1 gene is involved in chemoresistance, and cell proliferation was assessed using an MTS assay. To this end, the mRNA and protein levels of Txr1, thrombospondin-1 and excision repair cro...
Source: Experimental and Therapeutic Medicine - March 23, 2016 Category: Journals (General) Tags: Exp Ther Med 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

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

Gene Expression Profiling for Analysis Acquired Oxaliplatin Resistant Factors in Human Gastric Carcinoma TSGH-S3 Cells: the Role of IL-6 Signaling and Nrf2/AKR1C Axis Identification.
Abstract Oxaliplatin treatment is a mainstay of treatment for advanced gastrointestinal tract cancer, but the underlying mechanisms of acquired oxaliplatin resistance remain largely obscured. We previously demonstrated that increased DNA repair capacity and copper-transporting ATPase 1 (ATP7A) level contributed to oxaliplatin resistance in the human gastric carcinoma cell line TSGH-S3 (S3). In the present study, we applied gene array technology to identify additional resistance factors in S3 cells. We found that interleukin-6 (IL-6), aldo-keto reductase 1C1 (AKR1C1), and AKR1C3 are the top 3 upregulated genes in S...
Source: Biochemical Pharmacology - August 8, 2013 Category: Drugs & Pharmacology Authors: Chen CC, Chu CB, Liu KJ, Huang CY, Chang JY, Pan WY, Chen HH, Cheng YH, Lee KD, Chen MF, Kuo CC, Chen LT Tags: Biochem Pharmacol Source Type: research