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Source: Cancer Research
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Total 807 results found since Jan 2013.
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 A35: SOX9 induces chemo-resistance in pancreatic cancer cells and its high expression predicts poor prognosis
Conclusions: These data indicate that Sox9 plays an important role in chemo-resistance by the induction of stemness in pancreatic cancer cells.Citation Format: Shingo Kagawa, Taku Higasihara, Hideyuki Yoshitomi, Shigetsugu Takano, Hiroaki Shimizu, Masayuki Ohtsuka, Atsushi Kato, Katsunori Furukawa, Masaru Miyazaki.{Authors}. SOX9 induces chemo-resistance in pancreatic cancer cells and its high expression predicts poor prognosis. [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 S...
Source: Cancer Research - December 13, 2016 Category: Cancer & Oncology Authors: Shingo Kagawa, Taku Higasihara, Hideyuki Yoshitomi, Shigetsugu Takano, Hiroaki Shimizu, Masayuki Ohtsuka, Atsushi Kato, Katsunori Furukawa, Masaru Miyazaki Tags: Early Detection Source Type: research
Abstract A41: GPRC5A acts as a potent oncogene in pancreatic cancer
Conclusions: Our results indicate that GPRC5A acts as an oncogene in pancreatic cancer. Unexpectedly, gemcitabine was found to increase GPRC5A's mRNA and protein levels. We showed that this increase is mediated by HuR, a known enabler of gemcitabine efficacy, through a direct interaction between HuR and GPRC5A’s mRNA. It appears that the sensitivity of pancreatic cancer cells to gemcitabine can be augmented through down-regulation of GPRC5A.Citation Format: Honglei Zhou, Aristeidis Telonis, Yi Jing, Masaya Jimbo, Fernando Blanco, Eric Londin, Jonathan Brody, Isidore Rigoutsos.{Authors}. GPRC5A acts as a potent oncogene i...
Source: Cancer Research - December 13, 2016 Category: Cancer & Oncology Authors: Honglei Zhou, Aristeidis Telonis, Yi Jing, Masaya Jimbo, Fernando Blanco, Eric Londin, Jonathan Brody, Isidore Rigoutsos Tags: Early Detection 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 B71: Resistance to MEK inhibition in pancreatic cancer is associated with amphiregulin mediated EGFR-STAT3 activation
Introduction: Mutations in the KRAS oncogene occur in the majority of pancreatic ductal adenocarcinomas (PDAC), resulting in aberrant activation of the MAPK (RAS-RAF-MEK-ERK) pathway, driving malignant progression. Targeting KRAS has remained an elusive goal. Therefore, efforts have focused on targeting downstream effectors of RAS. The clinical efficacy of MEK inhibitors in other malignancies confirms that targeting the MAPK pathway has therapeutic potential. Unfortunately, clinical trials of MAPK-directed therapies have been unsuccessful in PDAC. Here, we report a novel mechanism of resistance to MAPK-directed therapies, ...
Source: Cancer Research - December 13, 2016 Category: Cancer & Oncology Authors: Nagaraj Nagathihalli, Jason Castellanos, Chanjuan Shi, Casey Roberts, Michael VanSaun, Nipun Merchant Tags: Heterogeneity of Pancreatic Cancer Source Type: research
Transcription Factor ZBP-89 Drives a Feedforward Loop of {beta}-Catenin Expression in Colorectal Cancer
In colorectal cancer, APC-mediated induction of unregulated cell growth involves posttranslational mechanisms that prevent proteasomal degradation of proto-oncogene β-catenin (CTNNB1) and its eventual translocation to the nucleus. However, about 10% of colorectal tumors also exhibit increased CTNNB1 mRNA. Here, we show in colorectal cancer that increased expression of ZNF148, the gene coding for transcription factor ZBP-89, correlated with reduced patient survival. Tissue arrays showed that ZBP-89 protein was overexpressed in the early stages of colorectal cancer. Conditional deletion of Zfp148 in a mouse model of Apc-med...
Source: Cancer Research - November 29, 2016 Category: Cancer & Oncology Authors: Bryan E. Essien, Sinȷu Sundaresan, Ramon Ocadiz–Ruiz, Aaron Chavis, Amy C. Tsao, Arthur J. Tessier, Michael M. Hayes, Amanda Photenhauer, Milena Saqui–Salces, Anthony J. Kang, Yatrik M. Shah, Balazs Győrffy, Juanita L. Merchant Tags: Molecular and Cellular Pathobiology Source Type: research
Role of HO-1-ROS-HDAC4-miR-206 Axis in RMS
Rhabdomyosarcoma (RMS) is an aggressive soft tissue cancer characterized by disturbed myogenic differentiation. Here we report a role for the oxidative stress response factor HO-1 in progression of RMS. We found that HO-1 was elevated and its effector target miR-206 decreased in RMS cell lines and clinical primary tumors of the more aggressive alveolar phenotype (aRMS). In embryonal RMS (eRMS), HO-1 expression was induced by Pax3/7-FoxO1, an aRMS hallmark oncogene, followed by a drop in miR-206 levels. Inhibition of HO-1 by tin protoporphyrin (SnPP) or siRNA downregulated Pax3/7-FoxO1 target genes and induced a myogenic pr...
Source: Cancer Research - October 1, 2016 Category: Cancer & Oncology Authors: Ciesla, M., Marona, P., Kozakowska, M., Jez, M., Seczynska, M., Loboda, A., Bukowska-Strakova, K., Szade, A., Walawender, M., Kusior, M., Stepniewski, J., Szade, K., Krist, B., Yagensky, O., Urbanik, A., Kazanowska, B., Dulak, J., Jozkowicz, A. Tags: Molecular and Cellular Pathobiology Source Type: research
Birinapant and Radiation in HNSCC
Comparison of tumors from The Cancer Genome Atlas (TCGA) reveals that head and neck squamous cell carcinomas (HNSCC) harbor the most frequent genomic amplifications of Fas-associated death domain (FADD), with or without Baculovirus inhibitor of apoptosis repeat containing BIRC2 (cIAP1), affecting about 30% of patients in association with worse prognosis. Here, we identified HNSCC cell lines harboring FADD/BIRC2 amplifications and overexpression by exome sequencing, RT-PCR, and Western blotting. In vitro, FADD or BIRC2 siRNA knockdown inhibited HNSCC displaying amplification and increased expression of these genes, supporti...
Source: Cancer Research - September 14, 2016 Category: Cancer & Oncology Authors: Eytan, D. F., Snow, G. E., Carlson, S., Derakhshan, A., Saleh, A., Schiltz, S., Cheng, H., Mohan, S., Cornelius, S., Coupar, J., Sowers, A. L., Hernandez, L., Mitchell, J. B., Annunziata, C. M., Chen, Z., Van Waes, C. Tags: Therapeutics, Targets, and Chemical Biology Source Type: research
Matrigel Chemoinvasion Assay
Invasive and metastatic cells must cross the basement membrane's extracellular matrix to disseminate to distant sites. Although in the eighties the concept was well established, no easy in vitro functional assay was available. Working in Hynda Kleinman's and George Martin's laboratory at NIH (Bethesda, MD), where the reconstituted basement membrane Matrigel was discovered, I had the intuition that Matrigel coating of migration filters could represent a valid tool to mimic in vitro biological matrix barriers. The “chemoinvasion assay” using Matrigel in Boyden blind-well chambers was developed in 1985–1986 and publishe...
Source: Cancer Research - August 13, 2016 Category: Cancer & Oncology Authors: Albini, A. Tags: Cancer Research 75th Anniversary Commentaries Source Type: research
Abstract C42: DNA methyltransferase 1 (Dnmt1) is a key regulator of TGF{beta}-mediated endothelial-to-mesenchymal transition
Cancer-associated fibroblasts (CAFs) are prominent in the tumor microenvironment and they fuel tumor angiogenesis, tumor growth, and metastasis. CAFs are identified by smooth muscle actin and type collagen 1 expression, they promote intratumoral desmoplasia and fibrosis, and they are derived from multiple cellular precursors including tumor endothelial cells (TECs) through a TGFβ-regulated process termed endothelial-to-mesenchymal transition (EndMT). Recently, we uncovered two distinct TEC populations: TGFβ-responders that undergo rapid EndMT accompanied by CAF marker up-regulation in response to TGFβ and TGFβ non-resp...
Source: Cancer Research - July 27, 2016 Category: Cancer & Oncology Authors: Xiao, L., Dudley, A. C. Tags: Tumor Microenvironment Heterogeneity Source Type: research
Abstract B05: N-Myc downstream regulated gene 2 is a novel regulator of lipid metabolism and ubiquitin-proteasome system in cancer
Conclusion: We demonstrated for the first time that NDRG2 is a critical regulator of lipid metabolism and proteasome activity. NDRG2 inhibits the proteasome activity probably by interacting with Nrf1 and promoting its downregulation.Note: This abstract was not presented at the conference.Citation Format: Libo Yao, Xia Li, Xiping Liu, Yi Ru, Mei Zhang. N-Myc downstream regulated gene 2 is a novel regulator of lipid metabolism and ubiquitin-proteasome system in cancer. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadel...
Source: Cancer Research - July 27, 2016 Category: Cancer & Oncology Authors: Yao, L., Li, X., Liu, X., Ru, Y., Zhang, M. Tags: Metabolism and Tumor Microenvironment Source Type: research
Abstract C05: Pulmonary laminin 332 in tumor cell migration and breast cancer survival
Metastasis to the lung often leads to the demise of the patient, thus a greater understanding of the process might lead to strategies for better cancer control. Tumor cell metastatic ability is determined by both intrinsic properties of tumor cells and contributions from the microenvironment. The goal of this study was to determine the role of the extracellular matrix protein laminin 332 (LN332) in breast cancer progression. Because tumor cell motility is a requirement for metastasis, we hypothesize that lung tissue harbors substances that induce tumor cell migration. In order to better characterize the interaction of brea...
Source: Cancer Research - July 27, 2016 Category: Cancer & Oncology Authors: Carpenter, P. M., Sivadas, P., Ziogas, A., Anton-Culver, H. Tags: Tumor Microenvironment and Metastasis Source Type: research
Abstract B21: Exostosin 1 regulates cancer cell stemness in breast cancer cells
Cancer stem cells (CSCs), a group of cancer cells, are associated with resistance to radiation and chemotherapy and are implicated in recurrent of cancer. Exostosin 1 (EXT1) gene is widely reported as tumor suppressor and its indispensable role in elongation of heparan sulfate (HS) can speculate probable role as tumor promotor. In recent years, a number of tumors are reported to over express EXT1. Here, we investigated the role of EXT1 in the maintenance of cancer cell stemness. MCF7/ADR cells developed by exposing MCF7, breast cancer cells, to doxorubicin for several months in culture, showed high resistance to doxorubici...
Source: Cancer Research - July 27, 2016 Category: Cancer & Oncology Authors: Manandhar, S., Kim, C.-g., Oh, S. Y., Lee, S.-H., Seok, J., Jung, Y.-D., Lee, H.-E., Choi, Y.-S., Lee, Y. M. Tags: Therapeutic Targeting Tumor Microenvironment Source Type: research
Abstract B37: Targeting tumor-stroma metabolic symbiosis for head and neck cancer therapy
Despite aggressive therapies, head and neck squamous cell carcinoma (HNSCC), which affects 50,000 new patients annually in the United States, is associated with less than 50% 5-year survival. HNSCC tumors display increased glycolysis, even in the presence of oxygen. Consequently, there is an increase in lactic acid (LA) production. However, the effect of lactic acid in the tumor microenvironment and the mechanisms whereby HNSCC tumors survive in highly acidic conditions remain unknown. HNSCC consist of up to 80% tumor-associated fibroblasts (TAFs). We previously reported that activation of receptor tyrosine kinase, c-Met, ...
Source: Cancer Research - July 27, 2016 Category: Cancer & Oncology Authors: Kumar, D., Vishwakarma, V., New, J., Gutierrez, W., Chavan, H., Kasturi, P., Tawfik, O., Girod, D., Houten, B. V., Leef, G., Joshi, R., Shelton, S., Straub, J., Shnayder, Y., Kakarala, K., Tsue, T., Lin, F., Dasari, S., Thomas, S. Tags: Tumor Microenvironment and Metabolic Adaptations Source Type: research
