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Total 151 results found since Jan 2013.

LSC Abstract - Histone deacetylase 7 mediated metabolic remodeling: A new crosslink between pulmonary hypertension and cancer
Pulmonary arterial smooth muscle cells (PASMCs) from Pulmonary Hypertension (PH) patients and several PH animal models are characterized by suppressed mitochondria-dependent apoptosis and hyperpolarization. Similarly to lung cancer (LC) cells, PH-PASMCs have reduced glucose oxidation and increased cytoplasmic glycolysis. Protein acetylation and its enzymes such as histone deacetylases (HDACs) may play a role in the control of metabolism.We assessed the regulation of Class IIa HDACs (HDAC4, 5, 7 and 9) in human and experimental models of PH and lung cancer. By using primary culture of healthy (control-PASMCs), idiopathic de...
Source: European Respiratory Journal - November 7, 2016 Category: Respiratory Medicine Authors: Gamen, E., Chelladurai, P., Grimminger, F., Savai, R., Seeger, W., Savai Pullamsetti, S. Tags: ERS Lung Science Conference 2016 Source Type: research

LSC Abstract - Activation of FGF9 and 18 in idiopathic pulmonary fibrosis promote survival and migration and inhibit myofibroblast differentiation of human lung fibroblasts
Key developmental lung signaling pathways are reactivated in IPF. FGF9 and FGF18 are involved in epithelial–mesenchymal interactions and are critical for lung development.We evaluated the expression of FGF9, FGF18 and FGFR in lung tissue from controls and IPF patients and assessed their effect on proliferation, survival, migration and differentiation of control and IPF human lung fibroblasts (HLF).HLF were cultured with FGF9 and FGF18. FAS-ligand induced apoptosis was assayed by measuring cleaved-PARP expression. Expression of FGFR mRNA, α-smooth muscle actin, collagen I and MMPs was analyzed with qPCR, western...
Source: European Respiratory Journal - November 7, 2016 Category: Respiratory Medicine Authors: Joannes, A., Jaillet, M., Mailleux, A., Crestani, B. Tags: ERS Lung Science Conference 2016 Source Type: research

LSC Abstract - Histone deacetylase 7 mediated metabolic remodeling: A new crosslink between pulmonary hypertension and cancer
Pulmonary arterial smooth muscle cells (PASMCs) from Pulmonary Hypertension (PH) patients and several PH animal models are characterized by suppressed mitochondria-dependent apoptosis and hyperpolarization. Similarly to lung cancer (LC) cells, PH-PASMCs have reduced glucose oxidation and increased cytoplasmic glycolysis. Protein acetylation and its enzymes such as histone deacetylases (HDACs) may play a role in the control of metabolism.We assessed the regulation of Class IIa HDACs (HDAC4, 5, 7 and 9) in human and experimental models of PH and lung cancer. By using primary culture of healthy (control-PASMCs), idiopathic de...
Source: European Respiratory Journal - November 7, 2016 Category: Respiratory Medicine Authors: Gamen, E., Chelladurai, P., Grimminger, F., Savai, R., Seeger, W., Savai Pullamsetti, S. Tags: 4.3 Pulmonary Circulation and Pulmonary Vascular Diseases Source Type: research

Abstract B08: ER chaperone GRP78 increases chemoresistance in pancreatic ductal adenocarcinoma
Conclusions: Collectively, our data show that GRP78 expression promotes chemoresistance in PDAC and therapeutic strategies blocking the activity of GRP78 increase the efficacy of currently available therapies.Citation Format: Jenifer B. Gifford, Wei Huang, Ann E. Zeleniak, Antreas Hindoyan, Hong Wu, Timothy R. Donahue, Reginald Hill.{Authors}. ER chaperone GRP78 increases chemoresistance in pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B08.
Source: Cancer Research - December 13, 2016 Category: Cancer & Oncology Authors: Jenifer B. Gifford, Wei Huang, Ann E. Zeleniak, Antreas Hindoyan, Hong Wu, Timothy R. Donahue, Reginald Hill Tags: Molecular Drivers of Pancreatic Cancer Biology and Metastasis Source Type: research

Abstract B60: Targeting the polyamine addiction of pancreatic cancers: Combination therapies and biomarkers
This project developed a combination therapy which inhibits both polyamine transport and biosynthesis in an effort to target the polyamine addiction of pancreatic cancers. Several parameters were measured in six human pancreatic cell lines (L3.6pl, Panc-1, BxPC3, AsPC-1, Capan-1 and HPNE) and one murine line (Pan02). These included the kinetics of 3H-spermidine uptake (Vmax and Km values), the 72h IC50 value for difluoromethylornithine (DFMO, an inhibitor of polyamine biosynthesis), and the ability of exogenous spermidine to rescue the viability of DFMO-treated cells. DFMO has a mixed clinical history and cancers often esc...
Source: Cancer Research - December 13, 2016 Category: Cancer & Oncology Authors: Otto Phanstiel IV, Meenu Madan, Arjun Patel, Kristen Skruber, Deborah A. Altomare Tags: Molecular Drivers of Pancreatic Cancer Biology and Metastasis Source Type: research

Abstract A67: TFF (Trefoil Factor Family) is a novel tumor suppressor and can be the therapeutic target for pancreatic cancer
Conclusion: TFF1 and TFF2 act as tumor suppressor in pancreatic carcinogenesis in a different manner, and they can be a novel therapeutic target for PDAC.Citation Format: Junpei Yamaguchi, Yukihiro Yokoyama, Toshio Kokuryo, Masato Nagino.{Authors}. TFF (Trefoil Factor Family) is a novel tumor suppressor and can be the therapeutic target for pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A67.
Source: Cancer Research - December 13, 2016 Category: Cancer & Oncology Authors: Junpei Yamaguchi, Yukihiro Yokoyama, Toshio Kokuryo, Masato Nagino Tags: Early Detection Source Type: research

Abstract A30: Characterizing the non-linear dependency of the CDK5-Rb axis in non-small cell lung cancer
In spite of recent therapeutics advances and early detection, lung cancer is still the leading cause of cancer-associated deaths worldwide. The five-year survival rates for its two major subtypes, small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) are estimated to be 6% and 18%, respectively. This high mortality is due to its aggressive nature even when detected at an early stage. Besides its aggressive nature and tendency for early metastasis, another feature of lung cancer is the inactivation of the retinoblastoma protein (Rb) that is observed in both lung cancer subtypes. NSCLC exhibits Rb inactivation...
Source: Cancer Research - January 15, 2017 Category: Cancer & Oncology Authors: Jaileene Perez-Morales, Mauricio Cabrera-Rios, Jonathan Gonzalez-Flores, Pedro Santiago-Cardona Tags: Systems Biology Source Type: research

Abstract B05: The RNA-binding protein HuR enhances exosome secretion in colorectal cancer
Enhanced secretion of exosomes by cancer cells is recognized as a means of transferring oncogenic information within the tumor microenvironment. Through their ability to carry specific RNA and protein cargo, tumor-derived exosomes are now being recognized for their ability to impact the tumor microenvironment and as promising cancer biomarkers. However, our knowledge of the cellular factors that promote increased exosome production from tumor cells and how they impact the loading of specific tumor-promoting RNA cargo is limited. Our prior work has established that colorectal cancer (CRC) cells and tumors overexpress the ke...
Source: Cancer Research - January 30, 2017 Category: Cancer & Oncology Authors: Ranjan Preet, Wei-Ting Hung, Shufei Zhuang, Lane K. Christenson, Dan A. Dixon Tags: Screening and Early Detection Source Type: research

Abstract B16: Activation of NRF2 and adaptive resistance to chemotherapy
Nuclear factor-erythroid-2-related factor 2 (NRF2), a member of the cap ‘n’ collar family of bZIP transcription factors, confers protection against oxidative and electrophilic stress. NRF2 is of great interest in cancer research, due to its role in response to chemotherapy, including the class of drugs targeting thymidylate synthase (TYMS). It has long been known that inhibition of TYMS leads to depletion of thymidine levels and the onset of programmed cell death, deriving from the enzyme's function as the sole de novo source of thymidine for DNA replication and repair. Exposing cells to TYMS inhibitors such as fluorop...
Source: Cancer Research - January 30, 2017 Category: Cancer & Oncology Authors: Sarah A. Clinton, Karen W. Barbour, Franklin G. Berger Tags: New Therapeutic Approaches to Colorectal Cancer Source Type: research

Abstract IA05: Regulation of Ras proteins and their effectors
Ras proteins regulate multiple phenotypes, including proliferation, contact inhibition, cell motility, metabolism, and genome integrity. This range of phenotypes may relate to the number of different effector pathways that Ras activates. The best validated of these is the Raf/MAPK pathway. Ras proteins can activate PI 3-kinase pathways directly, though this seems to vary between tissue types. Ras proteins bind and activate RalGDS, but this pathway is less well understood. In addition to these three major pathways, Ras proteins in their GTP state interact directly with several other potential effectors.Analysis of the contr...
Source: Cancer Research - March 13, 2017 Category: Cancer & Oncology Authors: Tina Yuan, Frank McCormick Tags: Oncogenic Signals Translate the Cancer Genome Source Type: research

Abstract B22: Increased phosphorylation of eIF4E induces resistance to treatment with mTOR inhibitors together with AR antagonists in advanced prostate cancer
The anti-androgen bicalutamide is widely used in the treatment of advanced prostate cancer (CaP) in many countries, but its effect on castration resistant CaP (CRPC) is limited. We previously showed that resistance to bicalutamide results from increased activation of the mechanistic target of rapamycin (mTOR); indicating a role for mTOR inhibitors in CaP treatment. Interestingly, a clinical trial testing combinations of the mTOR inhibitor RAD001 with bicalutamide were initially effective (PSA decline>50%) in 62.5% CRPC patients, but many initial responders later developed resistance. Here we investigate causes for their di...
Source: Cancer Research - March 13, 2017 Category: Cancer & Oncology Authors: Leandro S. D'Abronzo, Michael Crapuchettes, Ryan Beggs, Ruth Vinall, Clifford Tepper, Salma Siddiqui, Maria Mudryj, Frank Melgoza, Blythe Durbin-Johnson, Ralph deVere White, Paramita Ghosh Tags: Small Molecule Drugs Selectively Targeting Translation Specialized for the Cancer Cell Source Type: research

Abstract B21: The selective ATR inhibitor VX-970 enhances the therapeutic effects of standards of care in glioblastoma
Glioblastoma (GBM) represents one of the most aggressive cancer types with the vast majority of patients succumbing to disease within the first five years. This dire prognosis reflects the limited efficacy of our frontline therapies which include radiation therapy and temozolomide (TMZ) chemotherapy. The cellular response to these therapies is critically mediated by DNA damage response signaling networks that are regulated by Ataxia Telangiectasia Mutated (ATM) and Ataxia Telangiectasia And Rad3-Related Protein (ATR). Preliminary studies from our laboratory suggest the ATR inhibitor VX-970 has single agent efficacy in both...
Source: Molecular Cancer Research - April 2, 2017 Category: Cancer & Oncology Authors: Burgenske, D., Mladek, A., Sarkaria, J. Tags: Therapies Targeting Checkpoints and Mismatch Repair: Poster Presentations - Proffered Abstracts Source Type: research

Abstract B45: A genome-scale screen identifies the microcephaly gene, ZNF335, as a regulator of DNA end resection
We examined the recruitment of known resection factors to DSB sites and determined that the localization of CtIP and BLM were impaired in cells depleted of ZNF335. Our data suggests that ZNF335 plays an important role in promoting resection and ATR activation in response to DSBs.Citation Format: Jordan Young, Mikhail Bashkurov, Andrea McEwan, Thomas Sun, Alessandro Datti, Daniel Durocher. A genome-scale screen identifies the microcephaly gene, ZNF335, as a regulator of DNA end resection [abstract]. In: Proceedings of the AACR Special Conference on DNA Repair: Tumor Development and Therapeutic Response; 2016 Nov 2-5; Montre...
Source: Molecular Cancer Research - April 2, 2017 Category: Cancer & Oncology Authors: Young, J., Bashkurov, M., McEwan, A., Sun, T., Datti, A., Durocher, D. Tags: Exploiting Repair Defects in the Tumor Microenvironment: Poster Presentations - Proffered Abstracts Source Type: research

An Ensemble Strategy to Predict Prognosis in Ovarian Cancer Based on Gene Modules
Conclusion Considering the heterogeneity and complexity of ovarian cancer, we demonstrated a new method to predict the prognosis of ovarian cancer based on the clustering information and gene co-expression network in each subtype of cancer patients. We divided the ovarian cancer data into three subtypes by clustering analysis and we found that the survival risks in these three subtypes were significantly different. We mined the important communities based on the co-expression networks in each subtype. There are 50, 73, and 92 communities in the first, second and third subtype, respectively. Next, we constructed a new ense...
Source: Frontiers in Genetics - April 23, 2019 Category: Genetics & Stem Cells Source Type: research