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Source: Cancer Research
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Total 807 results found since Jan 2013.
Abstract 3948: Identification of a new therapeutic target in prostate cancer from siRNA screening in Docetaxel-resistant cells
Conclusion: We identified a new chaperone harbouring an enzymatic activity which could be a relevant therapeutic target in chemoresistant CRPC. We are now focusing on the identification of a specific inhibitor in order to validate the role of this target in two Docetaxel-resistant prostate cancer mice models established within the laboratory.Citation Format: Marine Garrido, Nicolas J-p Martin, Catherine Gaudin, Elaine Del Nery, Jacques Camonis, Franck Perez, Stéphanie Lerondel, Alain Le Pape, Karim Fizazi, Anne Chauchereau. Identification of a new therapeutic target in prostate cancer from siRNA screening in Docetaxel-res...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Garrido, M., Martin, N. J.-p., Gaudin, C., Del Nery, E., Camonis, J., Perez, F., Lerondel, S., Le Pape, A., Fizazi, K., Chauchereau, A. Tags: Molecular and Cellular Biology Source Type: research
Abstract B45: Silencing ss3 integrin by targeted ECO/siRNA nanoparticles inhibits EMT and metastasis of triple-negative breast cancer
Metastatic breast cancer is the second leading cause of cancer-related deaths among women. Triple-negative breast cancer (TNBC) is a highly aggressive subcategory of breast cancer and currently lacks well-defined molecular targets for effective targeted therapies. Disease relapse, metastasis, and drug resistance render standard chemotherapy ineffective in the treatment of TNBC. Because previous studies coupled β3 integrin (ITGB3) to epithelial-mesenchymal transition (EMT) and metastasis, we exploited β3 integrin as a therapeutic target to treat TNBC by delivering β3 integrin siRNA via lipid ECO-based nanoparticles (ECO/...
Source: Cancer Research - January 15, 2017 Category: Cancer & Oncology Authors: Jenny G. Parvani, Maneesh D. Gujrati, Margaret A. Mack, William P. Schiemann, Zheng-Rong Lu Tags: Drug Delivery and Nanomedicine Source Type: research
Abstract 3943: siRNA-mediated HuR silencing sensitizes triple-negative breast cancer cells to radiation therapy
HuR is a ubiquitously expressed member of the Elav/Hu family of RNA-binding proteins which can associate with mRNAs containing AU-rich elements in their 3′-untranslated regions. It is predominantly a nuclear protein that translocates to the cytoplasm in response to stress signals and stabilizes mRNAs encoding proteins implicated in cell proliferation, angiogenesis, apoptosis, and stress response. Studies examining HuR expression in human cancers indicated that elevated cytoplasmic HuR expression is associated with a high histologic grade, large tumor size, and poor survival of patients with cancer, leading to the hypothe...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Basalingappa, K. M., Mehta, M., Griffith, J. N., Muralidharan, R., Gorospe, M., Ramesh, R., Munshi, A. Tags: Tumor Biology Source Type: research
Abstract 4475: IL-4 receptor-targeted delivery of liposomal doxorubicin and siRNA to tumor
Targeted delivery of imaging agents and therapeutics to tumors would provide early detection and increased therapeutic efficacy against cancer. Using phage displayed-random peptide libraries, we have identified IL4RPep-1 (IL-4 receptor-binding peptide-1), CRKRLDRNC, that binds to IL-4 receptor (IL4R). IL4R is over-expressed on many types of cancer cells including lung cancer and breast cancer. Peptides have smaller size and in turn may exert better tissue penetration than bulky antibodies. IL4RPep-1 bound to H226 lung tumor cells that over-express IL4R, while little binding was observed in H460 lung tumor cells that expres...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Murugan, P. V. S., Rangaswamy, G. G., Chi, L., Padmanaban, G., Baek, M.-C., Kim, I.-S., Park, R.-W., Lee, B.-H. Tags: Cancer Chemistry Source Type: research
Abstract A47: IL-4 receptor-targeted delivery of liposomal doxorubicin and siRNA to tumor
Targeted delivery of imaging agents and therapeutics to tumors would provide early detection and increased therapeutic efficacy against cancer. Using phage displayed-random peptide libraries, we have identified IL4RPep-1 (IL-4 receptor-binding peptide-1), CRKRLDRNC, that binds to IL-4 receptor (IL4R). IL4R is over-expressed on many types of cancer cells including lung cancer and breast cancer. Peptides have smaller size and in turn may exert better tissue penetration than bulky antibodies. IL4RPep-1 bound to H226 lung tumor cells that over-express IL4R, while little binding was observed in H460 lung tumor cells that expres...
Source: Cancer Research - January 12, 2015 Category: Cancer & Oncology Authors: Padmanaban, G., Vadevoo, S. M. P., Chi, L., Lee, B.-H. Tags: Translational and Therapeutic Potential of the Tumor Microenvironment Source Type: research
Abstract B31: Combined siRNA and small molecule screening identifies Aurora B kinase as an effective target in MYCN-driven neuroblastoma
Despite advances in multimodal treatment, neuroblastoma (NB) is often fatal for children with high-risk disease and many survivors need to cope with long-term side effects from high-dose chemotherapy and radiation. To identify new therapeutic targets, we performed a siRNA screen of the druggable genome combined with a small molecule screen of 465 compounds targeting 39 different mechanisms of actions in four NB cell lines. We identified 58 genes as targets, including AURKB, in at least one cell line. In the drug screen, aurora kinase inhibitors (nine molecules) and in particular the AURKB-selective compound, barasertib, we...
Source: Cancer Research - April 3, 2016 Category: Cancer & Oncology Authors: Bogen, D., Wei, J. S., Azorsa, D. O., Ormanoglu, P., Buehler, E., Guha, R., Keller, J. M., Griner, L. A. M., Ferrer, M., Song, Y. K., Liao, H., Mendoza, A., Gryder, B. E., Sindri, S., He, J., Wen, X., , Zhang, S., Shern, J. F., Yohe, M. E., Taschner-Mandl Tags: Targeted Therapeutics and Resistance Source Type: research
Effects of DCLK1-siRNA{+/-}Curcumin on Cancer Stem Cells
Curcumin is known to induce apoptosis of cancer cells by different mechanisms, but its effects on cancer stem cells (CSC) have been less investigated. Here, we report that curcumin promotes the survival of DCLK1-positive colon CSCs, potentially confounding application of its anticancer properties. At optimal concentrations, curcumin greatly reduced expression levels of stem cell markers (DCLK1/CD44/ALDHA1/Lgr5/Nanog) in three-dimensional spheroid cultures and tumor xenografts derived from colon cancer cells. However, curcumin unexpectedly induced proliferation and autophagic survival of a subset of DCLK1-positive CSCs. Sph...
Source: Cancer Research - April 30, 2014 Category: Cancer & Oncology Authors: Kantara, C., O'Connell, M., Sarkar, S., Moya, S., Ullrich, R., Singh, P. Tags: Prevention and Epidemiology Source Type: research
Abstract 373: An siRNA screen identifies CHD4 as a target for epigenetic therapy
In this study, we used an unbiased screen to investigate therapeutic targets which might be effective combination with DNMT inhibitors in reactivating hypermethylated genes. Methods: We screened an siRNA library targeting 188 gene predicted as epigenetic regulators using colon cancer cells that harbor a GFP locus stably integrated and silenced by a hypermethylated cytomegalovirus (CMV) promoter. GFP-positive cell percentages were measured using Guava EasyCyte Plus flow analyzer software. For genome wide gene expression analysis, affymetrix microarrays were performed. DNA methylation status was evaluated by pyrosequencing a...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Okamoto, Y., Yamazaki, J., Sato, T., Cesaroni, M., Chung, W., Garriga, J., Jelinek, J., Katz, R. A., Issa, J.-P. Tags: Molecular and Cellular Biology Source Type: research
Abstract 700: Investigating KRAS synthetic lethal/co-dependency interactions using siRNA and CRISPR
No molecularly targeted therapy has yet been identified for KRAS mutant cancers. As oncogenic mutations reduce RAS enzymatic activity, classic small molecule approaches are ineffective, hence most work has focussed on drugging RAS-effector pathways. Multiple inhibitors of MEK, RAF and PI3K have been identified but toxicity issues and pathway adaptation have stymied their success against KRAS-driven cancers. An alternative approach is to exploit “non-oncogene addiction” by identifying targets with synthetic lethal or co-dependence interactions with KRAS.A number of siRNA and shRNA screens have identified targets that ex...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Scrace, S. F., Tsonou, E., Russell, P., Wickenden, J. A., Lawo, S., Scales, T. M., Wiggins, C. M., Moore, J. D. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 3536: Targeting {beta}-catenin with a Dicer-substrate siRNA (DsiRNA) in a sleeping beauty transposon-driven murine hepatoblastoma model
In conclusion, we report a highly relevant modality of RNAi delivery in a mouse model of hepatoblastoma to target a classically-undruggable oncogene.Citation Format: Marc T. Abrams, Junyan Tao, Shanthi Ganesh, Wendy Cyr, Bo Ying, Martin Koser, Rokhand Arvan, Girish Chopda, Hank Dudek, Cheng Lai, Weimin Wang, Bob Brown, Satdarshan Monga. Targeting β-catenin with a Dicer-substrate siRNA (DsiRNA) in a sleeping beauty transposon-driven murine hepatoblastoma model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Abrams, M. T., Tao, J., Ganesh, S., Cyr, W., Ying, B., Koser, M., Arvan, R., Chopda, G., Dudek, H., Lai, C., Wang, W., Brown, B., Monga, S. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 1195: Ethanolamine kinase-1 and phosphoethanolamine are potential diagnostic markers and therapeutic targets in breast cancer
Increased phosphoethanolamine (PE) has been observed in tumors almost as consistently as increased phosphocholine (PC), but the role of PE in cancer is relatively unexplored. Our ongoing studies have shown that choline kinase (ChK)-α, the enzyme that forms PC from choline, has a dual choline/ethanolamine kinase activity but ChK-β has no significant role in maintaining PE levels in vivo. We observed that ethanolamine kinase (EtnK)-1siRNA significantly reduces PE levels in triple negative MDA-MB-231 human breast cancer cells. We further investigated the role of ethanolamine kinase-2 (EtnK-2) in contributing to the increase...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Shah, T., Krishnamachary, B., Wildes, F., Wijnen, J., Glunde, K., Bhujwalla, Z. M. Tags: Molecular and Cellular Biology Source Type: research
Abstract 3892: Inhibitory effects and regulatory mechanism of nestin in pancreatic cancer
Introduction: Nestin, a progenitor/stem cell marker, is expressed in human pancreatic cancer, and we have previously shown that its expression positively correlates with invasiveness and metastasis of the cancer (Cancer Biol Ther, 2011; Am J Pathol. in press). Here, we examined the inhibitory effects of nestin expression using nestin-targeted small interfering RNA (siRNA) in pancreatic cancer cells. We also investigated the regulatory mechanism of nestin expression in pancreatic cancer. Methods: siRNA targeting nestin was transfected to the pancreatic cancer cell lines PANC-1 and PK-45H, and we analyzed the effect on cell ...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Matsuda, Y., Ishiwata, T., Yoshimura, H., Yamashita, S., Ushijima, T., Takubo, K., Arai, T. Tags: Tumor Biology Source Type: research
Abstract 1131: Snail- and ERK2-dependent signaling enhances breast cancer cell resistance to hydroxytamoxifen
Snail transcription factor and MAPK/ERK signaling regulate EMT and chemotherapy resistance in various tumor models by binding to target promoters (i.e., E-cadherin, maspin, ER-α). ERK1 is expressed during embryogenesis and in non-metastatic cells; ERK2 is implicated during vasculogenesis and promotes stem cell phenotype in triple negative breast cancer. Nuclear-localized ERK is associated with more active and potentially metastatic breast and ovarian carcinoma cells; cytoplasmic-localized ERK is a good prognostic factor. The role that Snail plays during the transition from cytoplasmic ERK1 to nuclear ERK2 has not been inv...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Smith, B. N., Nagappan, P., Taliaferro-Smith, L., Mezencev, R., Yates, C., Hinton, C., Odero-Marah, V. Tags: Tumor Biology Source Type: research
Abstract 3668: Multistage delivery of RNA interfering nanotherapeutics targeting the PI3K/Akt/mTOR pathway
An enhanced understanding of underlying processes governing tumorigenesis has led to the identification of several dysregulated pathways in cancer. As an example, the PI3K/Akt/mTOR pathway has recently emerged as one of the most aberrantly activated pathways in cancer, including breast cancer, making several molecular drivers along the cascade viable targets for therapy. However, important targets, such as translation initiation factor 4E (eIF4E), the rate-limiting factor for translation that is overexpressed upon activation of the PI3K/Akt/mTOR pathway, remain “undruggable.” Therefore, specifically targeting the pathw...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Blanco, E., Wu, S., Cara, F., Segura-Ibarra, V., Meric-Bernstam, F., Ferrari, M. Tags: Cancer Chemistry Source Type: research
Abstract 4725: Elevated co-expression of CCL2 and CX3CL1 is associated with apoptosis and good prognosis in soft tissue sarcoma patients
Conclusion: Our findings demonstrate that mRNA expression of CCL2 and CX3CL1 was significantly correlated with prognosis. Interestingly, there was a gender-specific impact of CCL2 on disease-specific survival. A significant decrease in apoptosis induction could be detected when cells were transfected with siRNA targeting CCL2 or CX3CL1 compared to the cells transfected with non-targeting siRNA.
Citation Format: Elke Nolte, Astrid Kehlen, Thomas Greither, Sven Wach, Matthias Kappler, Matthias Bache, Hans-Jürgen Holzhausen, Christine Lautenschläger, Steffen Göbel, Peter Würl, Uta-Dorothee Immel, Abbas Agaimy, Bernd Wulli...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Nolte, E., Kehlen, A., Greither, T., Wach, S., Kappler, M., Bache, M., Holzhausen, H., Lautenschlager, C., Gobel, S., Wurl, P., Immel, U.–D., Agaimy, A., Wullich, B., Taubert, H. Tags: Clinical Research (Excluding Clinical Trials) Source Type: research
