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Total 151 results found since Jan 2013.
Abstract B42: Silencing of DNA repair proteins with ECO/siRNA nanoparticles for the enhancement of radiation response in glioblastoma
In this study we investigate the use of these nanoparticles to deliver siRNA to inhibit ATM and DNApk activity and enhance radiation response in both glioma and glioma stem cell lines.Established glioma (U251) and glioma stem cell (NSC11) lines were used to evaluate the effectiveness of ECO nanoparticle delivery of siRNA in vitro . Cellular uptake of ECO nanoparticles loaded with fluorescent siRNA was assessed using flow cytometry and fluorescent microscopy, demonstrating the rapid uptake of ECO/siRNA nanoparticles in comparison to commercially available transfection agents. Protein and mRNA analyses revealed the kinetics ...
Source: Cancer Research - January 15, 2017 Category: Cancer & Oncology Authors: Jennifer A. Lee, Nadia Ayat, Anita Tandle, Zheng-Rong Lu, Kevin Camphausen Tags: Drug Delivery and Nanomedicine Source Type: research
Abstract B15: In vivo analysis of repeated siRNA silencing on protein expression levels
This study focused on determining the possibility of resistance development against siRNA treatment as a result of repeated exposure to siRNA in vivo. Our preliminary experiments in vitro revealed an unaffected siRNA cellular internalization and reproducible silencing efficiency of selected targets. The expression level of other mediators involved in breast cancer cell survival and proliferation (notably survivin, JUN, JAK2, NFkB and STAT3) were, however, altered in siRNA treated cells. In vivo experiments in a xenograft model demonstrated a similar silencing efficiency at the mRNA level after each repeated dose, with litt...
Source: Molecular Cancer Therapeutics - December 6, 2015 Category: Cancer & Oncology Authors: Aliabadi, H. M., Mahdipoor, P., Uludag, H. Tags: Other Combination Therapies: Poster Presentations - Proffered Abstracts 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 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 B166: A RNA helicase siRNA screen to identify potential therapeutic targets in castration-resistant prostate cancer
Castration-resistant prostate cancers (CRPC) are resistant to androgen-deprivation therapies commonly used to treat carcinoma of the prostate, resulting in death from this disease. CRPC can remain AR-driven through upregulation of the expression of wild-type, mutated or alternatively spliced constitutively active AR. Targeting both full-length AR and AR splice variants may overcome endocrine resistance. Since RNA helicases play crucial roles in various aspects of RNA metabolism including transcription, pre-mRNA splicing, translation, RNA export and RNA decay, we evaluated potentially druggable RNA helicases implicated in t...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Wang, H., de Billy, E., de Bono, J., Workman, P. Tags: Target Identification and Validation: Poster Presentations - Proffered Abstracts 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
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
Abstract C81: Identification of novel synergistic targets for rational drug combinations with PI3 kinase inhibitors using siRNA synthetic lethality screening against GBM
In this study, we performed a synthetic lethality screen to identify genes or pathways whose inactivation, in combination with the PI3K inhibitors PX-866 and NVPBEZ-235, might result in a lethal phenotype in glioblastoma multiforme (GBM) cells. We screened GBM cells (U87, U251, and T98G) with a large-scale, short hairpin RNA library (GeneNet), which contains 43 800 small interfering RNA sequences targeting 8500 well-characterized human genes. To decrease off-target effects, we selected overlapping genes among the 3 cell lines that synergized with PX- 866 to induce cell death. To facilitate the identification of potential t...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Kim, Y.-W. Tags: Drug Resistance and Modifiers: Poster Presentations - Proffered Abstracts Source Type: research
Abstract B47: Therapeutic KRAS silencing in lung and colon cancer models
This study highlights the potential translational impact of therapeutic RNA interference, which may have broad applications in oncology, especially for traditional "undruggable" targets.Citation Format: Chad Pecot, Sherry Wu, Seth Bellister, Rajat Bhattacharya, Anshumaan Maharaj, Cristian Rodriguez-Aguayo, Vianey Gonzalez-Villasana, Rajesha Rupaimoole, Gabriel Lopez-Berestein, Lee M. Ellis, Anil Sood. Therapeutic KRAS silencing in lung and colon cancer models. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR;...
Source: Molecular Cancer Research - February 5, 2015 Category: Cancer & Oncology Authors: Pecot, C., Wu, S., Bellister, S., Bhattacharya, R., Maharaj, A., Rodriguez-Aguayo, C., Gonzalez-Villasana, V., Rupaimoole, R., Lopez-Berestein, G., Ellis, L. M., Sood, A. Tags: RAS Targeting: Poster Presentations - Proffered Abstracts Source Type: research
In vitro evaluation of anti HSV ‐1 siRNAs and in vivo evaluation of electroporation to transfect siRNAs on murine cornea
ConclusionsThese results demonstrate that siRNA directed against HSV‐1 DNA polymerase efficiently inhibits HSV‐1 replication, suggesting that siRNA based antiviral strategy may be a potential therapeutic alternative to treat HSK. Besides, intracorneal penetration may be facilitated by electroporation.
Source: Acta Ophthalmologica - September 13, 2016 Category: Opthalmology Authors: A. Rousseau, V. Escriou, P. Roy, N. Poccardi, J. Takissian, P. Bigey, M. Labetoulle Tags: Abstracts from the 2016 European Association for Vision and Eye Research Conference Source Type: research
Abstract B48: Regulation of mutant KRAS protein stability via SMURF2:UBCH5 complex mediated degradation of beta-TrCP1
Attempts to target mutant KRAS have been unsuccessful. Most of the current therapeutic approaches are indirect, mainly via inhibiting KRAS down-stream signaling, which have been marginally successful. Here we report the identification of Smad ubiquitination regulatory factor 2 (SMURF2), a HECT-type ubiquitin ligase (E3) as a critical regulator of mutant KRAS protein stability. We show that the loss of SMURF2 either by si-/sh-RNA mediated gene silencing or by overexpression of a catalytically inactive SMURF2 Cys716Ala (CA) mutant, can cause lysosome-mediated KRAS degradation; whereas, overexpression of wild type SMURF2 enha...
Source: Molecular Cancer Research - February 5, 2015 Category: Cancer & Oncology Authors: Shukla, S., Allam, U. S., Ahsan, A., Chen, G., Beer, D. G., Lawrence, T. S., Nyati, M. K., Ray, D. Tags: RAS Targeting: Poster Presentations - Proffered Abstracts Source Type: research
Abstract A55: KRAS gene amplification is a distinct molecular subgroup of gastroesophageal adenocarcinoma that may benefit from combined RAS/RAF/MEK/ERK and PI3K/PTEN/AKT/mTOR pathway inhibition
Conclusions: In this series, we observed KRAS wild type gene amp+ to be present in a subset (16%) of GEC patients at diagnosis, correlating with very high protein expression. KRAS amp+ was present after treatment with trastuzumab in HER2+ patients, and also after anti-MET therapy. These data suggest that KRAS amp+ represents a molecular subset with advanced disease at diagnosis. The observation of acquired KRAS amp+ after targeted therapies may be a resistance mechanism to anti-HER and anti-MET inhibitors. Inhibition using combined MEK/AKT pathway inhibitors, and proof-of-principle siRNA, warrants further investigation for...
Source: Molecular Cancer Research - February 5, 2015 Category: Cancer & Oncology Authors: Henderson, L., Xu, P., Rambo, B., Liao, W.-L., Hembrough, T., Catenacci, D. Tags: Role of WT RAS and RAS Isoforms: Poster Presentations - Proffered Abstracts Source Type: research
Abstract A07: Novel effectors of K-Ras-mediated and KSR1 dependent colon tumorigenesis
Conclusion: These results demonstrate the importance of AMPK and its downstream signaling effectors PGC1β and ERRα in maintaining colon tumor cell survival driven by oncogenic Ras and demonstrate the value of using KSR1 as a reference standard to detect genes essential to colon tumor survival.Citation Format: Binita Das, Kurt Fisher, Hyunseok Kim, Deanna J. Volle, Deandra R. Smith, Robert S. Livergood, John MacMillan, Michael White, Robert Lewis. Novel effectors of K-Ras-mediated and KSR1 dependent colon tumorigenesis. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to T...
Source: Molecular Cancer Research - February 5, 2015 Category: Cancer & Oncology Authors: Das, B., Fisher, K., Kim, H., Volle, D. J., Smith, D. R., Livergood, R. S., MacMillan, J., White, M., Lewis, R. Tags: RAS Effectors - Basic Biology: Poster Presentations - Proffered Abstracts Source Type: research
Abstract B114: c-Rel is a critical mediator of NF-{kappa}B dependent TRAIL resistance of pancreatic cancer cells
In conclusion, we were able to delineate a novel c-Rel, NFATc2 and COX-2 dependent anti-apoptotic signalling pathway in PDAC with broad clinical implications for pharmaceutical intervention strategies.Citation Format: Claudia Geismann, Frauke Grohmann, Robert Häsler, Philip Rosenstiel, Günter Schneider, Sebastian Zeissig, Stefan Schreiber, Heiner Schäfer, Alexander Arlt. c-Rel is a critical mediator of NF-κB dependent TRAIL resistance of pancreatic cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Phila...
Source: Cancer Research - June 30, 2015 Category: Cancer & Oncology Authors: Geismann, C., Grohmann, F., Hasler, R., Rosenstiel, P., Schneider, G., Zeissig, S., Schreiber, S., Schafer, H., Arlt, A. Tags: Other Topics Source Type: research
Abstract PR03: Targeting multiple cell cycle regulatory points for the prevention of triple-negative breast cancer
Conclusions: These studies demonstrate that dinaciclib alone or the combination therapy of LG100268 and dinaciclib causes inhibition of premalignant cell growth and delayed ER-negative mammary tumorigenesis in SV40 Tag mice. While an additive effect of dinaciclib and LG100268 was observed in vitro, the in vivo combination therapy was not significantly more effective than dinaciclib treatment alone. Future studies should investigate different combinations of dosages of dinaciclib and LG100268 in vivo. These studies were supported by an NCI/NIH R25T grant (R25CA057730, BL) and Susan G. Komen for the Cure Promise grant (KG081...
Source: Cancer Prevention Research - October 2, 2015 Category: Cancer & Oncology Authors: Litzenburger, B. C., Uray, I. P., Hill, J., Zhang, J., Mazumdar, A., Brown, P. H. Tags: Combinatorial Approaches to Chemoprevention: Oral Presentations - Proffered Abstracts Source Type: research
