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Cancer: Adenocarcinoma
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Total 16 results found since Jan 2013.

Radiosensitivity in Non-Small-Cell Lung Cancer by MMP10 through the DNA Damage Repair Pathway
This study investigated the function and associated mechanism of MMP10 during radiotherapy of NSCLC. MMP10 expression in patients and their overall survival rate were assessed through GEPIA. Protein expression was tested by western blotting. Radioresistance was detected in vitro by apoptosis and clonogenic assay. The extent of DNA damage and repair was revealed by the comet test and γH2AX foci test. High MMP10 levels in specimens of lung adenocarcinoma were related to poor patient outcomes. Clonogenic and apoptosis assays revealed that MMP10 knockdown in A549 cells initiated radiosensitization. Furthermore, MMP10 siRNA in...
Source: Journal of Oncology - March 13, 2023 Category: Cancer & Oncology Authors: Yawei Bi Kun Cao Yuan Wang Wei Yang Na Ma Xiao Lei Yuanyuan Chen Source Type: research

Combination Therapies with CDK4/6 Inhibitors to Treat KRAS-mutant Pancreatic Cancer
Cancer Res. 2022 Nov 8:CAN-22-0391. doi: 10.1158/0008-5472.CAN-22-0391. Online ahead of print.ABSTRACTMutational loss of CDKN2A (encoding p16INK4A) tumor suppressor function is a key genetic step that complements activation of KRAS in promoting the development and malignant growth of pancreatic ductal adenocarcinoma (PDAC). However, pharmacologic restoration of p16INK4A function with inhibitors of CDK4 and CDK6 (CDK4/6) has shown limited clinical efficacy in PDAC. Here, we found that concurrent treatment with both a CDK4/6 inhibitor (CDK4/6i) and an ERK MAPK inhibitor (ERKi) synergistically suppresses the growth of PDAC ce...
Source: Cell Research - November 8, 2022 Category: Cytology Authors: Craig M Goodwin Andrew M Waters Jennifer E Klomp Sehrish Javaid Kirsten L Bryant Clint A Stalnecker Kristina Drizyte-Miller Bjoern Papke Runying Yang Amber M Amparo Irem Ozkan-Dagliyan Elisa Baldelli Valerie Calvert Mariaelena Pierobon Jessica A Sorrentin Source Type: research

Annotation and functional characterization of long noncoding RNAs deregulated in pancreatic adenocarcinoma
ConclusionsOur study expands the repertoire of lncRNAs deregulated in PDAC, thereby revealing novel candidate biomarkers for patient risk stratification. It also provides a roadmap for functional assays aimed to characterize novel mechanisms of action of lncRNAs in pancreatic cancer, which could be explored for therapeutic development.
Source: Cellular Oncology - May 14, 2022 Category: Cancer & Oncology Source Type: research

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

High mobility group box-1 protects against Aflatoxin G1-induced pulmonary epithelial cell damage in the lung inflammatory environment.
Abstract Aflatoxin G1 (AFG1) is a member of the carcinogenic aflatoxin family. Our previous studies indicated that oral administration of AFG1 caused tumor necrosis factor (TNF)-〈-dependent inflammation that enhanced oxidative DNA damage in alveolar epithelial cells, which may be related to AFG1-induced lung carcinogenesis. High mobility group box-1 (HMGB1) is a nuclear DNA-binding protein; the intracellular and extracellular roles of HMGB1 have been shown to contribute to DNA repair and sterile inflammation. The role of HMGB1 in DNA damage in an aflatoxin-induced lung inflammatory environment was investigated i...
Source: Toxicology Letters - May 20, 2020 Category: Toxicology Authors: Kang L, Guo N, Liu X, Wang X, Guo W, Xie SM, Liu C, Lv P, Xing L, Zhang X, Shen H Tags: Toxicol Lett Source Type: research

PCNA and GSK3 β interact with each other to regulate H1299 lung adenocarcinoma cells apoptosis.
PCNA and GSK3β interact with each other to regulate H1299 lung adenocarcinoma cells apoptosis. Neoplasma. 2019 Oct 09;: Authors: Liu XH, Tang DE, Dai Y, Gao XJ, Liu LX Abstract Glycogen synthase kinase beta (GSK3β) is considered as a promising target for lung cancer treatment and its inhibitor lithium chloride (LiCl) is widely regarded as having potent anti-proliferative and apoptosis-modulating activities. Proliferating cell nuclear antigen (PCNA), as an auxiliary protein for DNA polymerase delta which regulates DNA replication and repair, has been reported to play an important role in regulating a...
Source: Neoplasma - October 8, 2019 Category: Cancer & Oncology Authors: Liu XH, Tang DE, Dai Y, Gao XJ, Liu LX Tags: Neoplasma Source Type: research

The JAK/STAT Pathway in Skeletal Muscle Pathophysiology
Conclusion and Perspectives The IL-6/JAK/STAT signaling cascade plays a dominant role in skeletal muscle pathophysiology. IL-6 autocrine, paracrine, and endocrine functions assign to its downstream effectors pivotal importance in skeletal muscle-wasting-associated diseases and other multiple system diseases where muscle acts in communication with other organs. Targeting the components of the JAK/STAT pathway recently emerged as a strategic approach for the treatment of inflammatory diseases and human cancer. This review highlights the opposite outcomes on muscle biology caused by the amount of local and systemic release ...
Source: Frontiers in Physiology - April 29, 2019 Category: Physiology Source Type: research

Complement C5b-9 and Cancer: Mechanisms of Cell Damage, Cancer Counteractions, and Approaches for Intervention
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - April 9, 2019 Category: Allergy & Immunology Source Type: research

PDZ Binding Kinase (PBK) - a Novel Gene Driving Genomic Evolution in Multiple Myeloma
As in all cancers, genomic instability leads to ongoing acquisition of new genetic changes in multiple myeloma (MM). This adaptability underlies the development of drug resistance and progression in MM. This genomic instability is driven by cellular processes, mainly related with DNA repair and perturbed by functional changes in limited number of genes. Since kinases play a critical role in the regulation of biological processes, including DNA damage/repair signaling and are relatively easy to screen for inhibitors, we investigated for novel genes involved in the acquisition of new genomic changes in MM. Using a large geno...
Source: Blood - November 21, 2018 Category: Hematology Authors: Kumar, S., Buon, L., Talluri, S., Shi, J., Avet-Loiseau, H., Samur, M. K., Shammas, M. A., Munshi, N. Tags: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research

P300 inhibition enhances gemcitabine-induced apoptosis of pancreatic cancer.
Authors: Ono H, Basson MD, Ito H Abstract The transcriptional cofactor p300 has histone acetyltransferase activity (HAT) and has been reported to participate in chromatin remodeling and DNA repair. We hypothesized that targeting p300 can enhance the cytotoxicity of gemcitabine, which induces pancreatic cancer cell apoptosis by damaging DNA. Expression of p300 was confirmed in pancreatic cancer cell lines and human pancreatic adenocarcinoma tissues by western blotting and immunohistochemistry. When pancreatic cancer cells were treated with gemcitabine, p300 was recruited to chromatin within 24 hours, indicating the ...
Source: Oncotarget - June 22, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Chemosensitisation of PDAC cell lines by the VCP inhibitor NMS-873
Abstract: Pancreatic ductal adenocarcinoma (PDAC) is often characterized by defective DNA damage repair (DDR), which can be associated with resistance to DNA damaging chemotherapies. We carried out an siRNA screen assessing the potential of 639 DDR genes as therapeutic and chemosensitisation targets for PDAC. We identified several ubiquitin proteasome pathway regulators, including valosin-containing protein/p97 (VCP), whose silencing decreased cell viability and increased caspase 3/7 activities in the PANC-1 cell line.
Source: Pancreatology - May 31, 2016 Category: Gastroenterology Authors: Yuliana Astuti, Euan Stronach, Edward W. Curry, Hani Gabra, Harpreet S. Wasan, Elaina N. Maginn 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 A30: A genome-wide siRNA screen in mammalian cells for regulators of S6 phosphorylation
To identify the cellular components that participate in the regulation of mTOR complex 1 (mTORC1), the amino acid-dependent, rapamycin-inhibitable complex, we carried out a genome-wide RNAi depletion screen. We employed a rabbit monoclonal antibody specific for RPS6 [Ser235P/Ser236P] and high content microscopy to quantify rpS6 phosphorylation in the pancreatic ductal adenocarcinoma cancer cell line (PDAC) MiaPaCa-2. Applying a stringent selection, we retrieved over 600 genes wherein at least two RNAi gave significant reduction in S6 phosphorylation. This cohort is significantly enriched in genes whose depletion affects th...
Source: Molecular Cancer Therapeutics - July 6, 2015 Category: Cancer & Oncology Authors: Papageorgiou, A., Tamayo, P., Mesirov, J., Avruch, J., Rapley, J. Tags: PI3K-mTOR Activation in Human Cancer: Poster Presentations - Proffered Abstracts Source Type: research

Ku80 cooperates with CBP to promote COX-2 expression and tumor growth.
Authors: Xiao Y, Wang J, Qin Y, Xuan Y, Jia Y, Hu W, Yu W, Dai M, Li Z, Yi C, Zhao S, Li M, Du S, Cheng W, Xiao X, Chen Y, Wu T, Meng S, Yuan Y, Liu Q, Huang W, Guo W, Wang S, Deng W Abstract Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku...
Source: Oncotarget - March 24, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Abstract 4911: NSCLC cells demonstrate differential mode of cell death in response to the combined treatment of radiation and a DNA-PKcs inhibitor
Conclusion: Our study clearly shows that NU7441, a novel DNA-PKcs inhibitor, is a potent radio-sensitizer in p53-dificient lung cancer cells and highlights the promise of NU7441 in targeted cancer treatment. Citation Format: Yu Lan, Zengfu Shang, Feng-Ming Hsu, Vasu Tumati, Benjamin P. Chen, Debabrata Saha. NSCLC cells demonstrate differential mode of cell death in response to the combined treatment of radiation and a DNA-PKcs inhibitor. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Lan, Y., Shang, Z., Hsu, F.-M., Tumati, V., Chen, B. P., Saha, D. Tags: Tumor Biology Source Type: research