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Source: Cancer Research
Therapy: Cancer Therapy
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Total 42 results found since Jan 2013.
Abstract 4966: Identification of deubiquitinating enzyme USP19 as a regulator of EWS/FLI1 protein turnover in Ewing sarcoma
Ewing sarcoma belongs to the family of pediatric tumors which arise most commonly in bone. The majority of Ewing sarcoma is characterized by a balanced translocation between chromosomes 11 and 22 which encodes for the uniquely expressed fusion protein EWS/FLI1. Tumor cells are crucially dependent on expression of the fusion protein. Protein degradation is an important and highly regulated process in all cells and novel insights are beginning to be applied for cancer therapy. We aim to investigate the mechanism of turnover with the goal to diminish EWS/FLI1 protein and thereby identify novel targets for Ewing sarcoma treatm...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Gierisch, M. E., Lopez-Garcia, L. A., Pfistner, F., Niggli, F. K., Schaefer, B. W. Tags: Molecular and Cellular Biology Source Type: research
Abstract 5328: Protein phosphatase 2A activity is a major determinant of therapy response in cancer cells
Protein phosphatase 2A (PP2A) dephosphorylates majority of Ser/Thr phosphorylated proteins. Consequently, PP2A is an antagonist of multiple oncogenic pathways and PP2A reactivation may provide an alternative route to target these pathways. Importantly, because PP2A reactivation would result in simultaneous dephosphorylation of both collateral and downstream effectors of kinase pathways, it might circumvent commonly encountered kinase inhibitor resistance mechanisms.To systematically study the role of PP2A in cancer therapy response we used RNAi targeting against PP2A inhibitor proteins CIP2A, PME-1 and SET (PP2A reactivati...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Kauko, O., Imanishi, S., Kaur, A., Laajala, D., Kulesskiy, E., Jumppanen, M., Corthals, G., Aittokallio, T., Wennerberg, K., Westermarck, J. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 5357: Inhibition of collagen receptor discoidin domain receptor-1 (DDR1) tyrosine kinase enhances cytotoxicity of anti-mesothelin immunotoxin for cancer therapy
In conclusion, we report that collagen protects cells from killing by RITs through DDR1 and that lowering DDR1 protein or inhibiting DDR1 kinase activity enhances the cytotoxic activity of RITs. Our data suggest that the combination of ‘7rh’ and RG7787 represents a novel therapeutic strategy to target mesothelin-expressing cancers. These data also provide insight into how tumor stroma might be protecting cancer cells from therapy.Citation Format: Fatima G. Ali-Rahmani, David Fitzgerald, Scott Martin, Paresma Patel, Craig Thomas, Ira Pastan. Inhibition of collagen receptor discoidin domain receptor-1 (DDR1) tyrosine kin...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Ali-Rahmani, F. G., Fitzgerald, D., Martin, S., Patel, P., Thomas, C., Pastan, I. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract P2-07-04: Treatment of metastatic breast cancer using two nanoparticles combined with siRNA targeting Twist1 to inhibit EMT
Breast cancer is the 2nd leading cause of cancer related deaths among women in the US with over 240,000 diagnoses and 40,000 deaths expected in 2014. Among the more serious and deadly forms of breast cancer are the Triple Negative Breast Cancers (TNBC) (ER-, PR-, HER2-). Mortality rates among patients rise dramatically when these cancers spread beyond the primary tumor site. Therefore reduction of tumor cell dispersion is a key component to minimizing mortality rates. Epithelial-Mesenchymal Transition (EMT) is the process by which cancer cells downregulate proteins associated with cell to cell adhesion (e.g. E-cadherin) re...
Source: Cancer Research - April 30, 2015 Category: Cancer & Oncology Authors: Finlay, J. B., Roberts, C. M., Lowe, G., Peng, L., Zink, J. I., Tamanoi, F., Glackin, C. A. Tags: Poster Session Abstracts Source Type: research
SAT1 Regulates BRCA1 Expression and HR in GBM
Glioblastoma multiforme (GBM) is the most common and severe form of brain cancer. The median survival time of patients is approximately 12 months due to poor responses to surgery and chemoradiation. To understand the mechanisms involved in radioresistance, we conducted a genetic screen using an shRNA library to identify genes in which inhibition would sensitize cells to radiation. The results were cross-referenced with the Oncomine and Rembrandt databases to focus on genes that are highly expressed in GBM tumors and associated with poor patient outcomes. Spermidine/spermine-N1-acetyltransferase 1 (SAT1), an enzyme involved...
Source: Cancer Research - November 30, 2014 Category: Cancer & Oncology Authors: Brett-Morris, A., Wright, B. M., Seo, Y., Pasupuleti, V., Zhang, J., Lu, J., Spina, R., Bar, E. E., Gujrati, M., Schur, R., Lu, Z.-R., Welford, S. M. Tags: Molecular and Cellular Pathobiology Source Type: research
Abstract LB-219: Synthetic lethal screening reveals FGFR as one of combinatorial targets to overcome resistance to Met-targeted therapy
Met is a receptor tyrosine kinase that promotes cancer progression. In addition, Met has been implicated in resistance of tumors to various targeted therapies such as EGFR inhibitors in lung cancers, and has been prioritized as a key molecular target for cancer therapy. However, the underlying mechanism of resistance to Met targeting drugs is poorly understood. Here, we describe screening of 1310 genes to search for key regulators related to drug resistance to an anti-Met therapeutic antibody (SAIT301) by employing a siRNA-based synthetic lethal screening method. We found that knockdown of 69 genes in Met-amplified MKN45 c...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Kim, B. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract LB-103: L1CAM-targeted delivery of siRNA using elastin-like polypeptide (ELP) nanoparticles inhibits the growth of human tumors implanted in mice
Small interfering RNA (siRNA) drugs provide ideal means for perturbing intracellular oncogenic targets. However, specific delivery of siRNA to tumors has proven to be difficult. An ELP was engineered with an N-terminal region that binds to L1 cell adhesion molecule (L1CAM), and a C-terminal region that binds siRNA. Upon binding of siRNA, the L1CAM targeted ELP (ELP-L) spontaneously assembled into a spherical nanocomplex with the siRNA protected within, and the CAM-binding region protruding from the surface. These nanoparticles were used to deliver siRNA to SKOV3 tumors formed following surgical implantation of the cells in...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Primiano, T., Chang, B.-D., Heidel, J. D. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 1155: Chemoresistance acquisition by ovarian adenocarcinoma cells due to microenvironment
Epithelial Ovarian Carcinoma is characterized by high frequency of recurrence (70% of patients) and carboplatin resistance acquisition. We recently showed that Carcinoma-Associated-Mesenchymal Stem Cells (CA-MSC) are involved in ovarian tumor growth via the facilitation of angiogenesis in the tumor site as well as in ovarian cancer chemoresistance acquisition. Our aim is to identify the mechanisms by which CA-MSC activate tumor cells signaling pathway for both effects. First we showed that factors released by CA-MSC are able to induce angiogenic cytokines (IL-6, IL-8 and VEGF) synthesis by tumor cells in a cell line specif...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Thibault, B., Castells, M., Mihas, D., Genre, L., Gandy, C., Mery, E., Delord, J. P., Couderc, B. C. Tags: Tumor Biology Source Type: research
Abstract 1972: The sodium channel auxiliary subunit SCN1B promotes breast tumor growth and metastasis
This study is the first demonstration of a functional role for β1 as a CAM in tumor growth and metastasis. We propose that targeting β1-mediated adhesion interactions may have potential as a novel anti-cancer therapy.
Citation Format: Michaela Nelson, Rebecca Millican-Slater, Lorna C. Forrest, William J. Brackenbury. The sodium channel auxiliary subunit SCN1B promotes breast tumor growth and metastasis. [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):Abstract nr 1972. doi:10.1158/1538-7445.AM2014-1972
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Nelson, M., Millican-Slater, R., Forrest, L. C., Brackenbury, W. J. Tags: Tumor Biology Source Type: research
Abstract 1455: Therapeutic synergy between novel tumor suppressor miR-520d-3p and EphA2-targeting siRNA in ovarian cancer
This study addresses a new concept of RNA inhibition therapy by combining miRNA and siRNA to target oncogenic pathways altered in ovarian cancer.
Citation Format: Maitri Shah, Gabriel Berestein Lopez, Anil Sood, George Calin. Therapeutic synergy between novel tumor suppressor miR-520d-3p and EphA2-targeting siRNA in ovarian cancer. [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):Abstract nr 1455. doi:10.1158/1538-7445.AM2014-1455
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Shah, M., Lopez, G. B., Sood, A., Calin, G. Tags: Molecular and Cellular Biology Source Type: research
Abstract 438: Long non-coding RNA AK023948 enhances breast cancer progression by activating AKT
In this study, using real-time PCR-based lncRNA profiling array, we identified a set of lncRNAs that were differentially expressed in breast cancer tissues of patients as compared to the normal breast tissue. Among them, AK023948 was upregulated in breast cancer; it was also upregulated in breast cancer cell lines (MCF-7 and MDA-MB-231) as compared to human mammary epithelial cells (HMLE). This was further supported by breast cancer tissue microarray by in situ hybridization. Moreover, ectopic expression of AK023948 in MCF-7 cells promoted the proliferation and anchorage independent cell growth, implying its potential onco...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Koirala, P. Tags: Molecular and Cellular Biology Source Type: research
Abstract 707: Tumor-targeted delivery of siRNA using stabilized calcium phosphate nanoparticles based on bio-inspired hyaluronic acid conjugate
Conclusion Considering its biocompatibility, transfection efficacy, and tumor targeting capability, this stabilized organic-inorganic hybrid gene delivery platform should be considered a promising candidate carrier for systemic siRNA delivery and targeted cancer therapy.
Citation Format: Min Sang Lee, Jung Eun Lee, Eunkyoung Byun, Nak Won Kim, Haeshin Lee, Ji Hoon Jeong. Tumor-targeted delivery of siRNA using stabilized calcium phosphate nanoparticles based on bio-inspired hyaluronic acid conjugate. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Di...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Lee, M. S., Lee, J. E., Byun, E., Kim, N. W., Lee, H., Jeong, J. H. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 1750: Combined blockade of Aurora A and JAK2 kinase is highly effective at inhibiting malignant transformation
Our ongoing efforts to validate kinases for cancer therapy led to the novel finding that ectopic expression of JAK2 and Aurora A together is more effective than each alone at inducing normal cells to grow in an anchorage-independent manner and to invade. In addition, siRNA silencing or pharmacological inhibition of JAK2 and Aurora A with Ruxolitinib and Alisertib, respectively, is more effective than blocking each kinase alone at suppressing anchorage-dependent and -independent growth and invasion as well as at inducing apoptosis. This led us to develop dual Aurora and JAK inhibitors, AJI-214 and AJI-100, which potently in...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Sebti, S. M., Yang, H., Lawrence, H., Kazi, A., Gervaria, H., Patel, R., Luo, Y., Rix, U., Schonbrunn, E., Lawrence, N. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 718: Systemic delivery of therapeutic siRNA by multifunctional mesoporous silica-based nanocarrier inhibits lung cancer growth and metastasis
In this study, we developed a novel siRNA delivery vector based on our magnetic mesoporous silica nanoparticles (M-MSNs) platform. This nanocarrier was constructed by loading siRNAs into the mesopores of M-MSNs, followed by polyethylenimine (PEI) capping, PEGylation and fusogenic peptide KALA modification. The resultant functionalized delivery system exhibited prolonged half-life in bloodstream, enhanced cell membrane translocation and endosomal escapablity, and favorable tissue biocompatibility and biosafety. Systemic application of vascular endothelial growth factor (VEGF) siRNA via this nanocarrier resulted in remarkabl...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Chen, Y., Gu, H., Xia, W. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 731: SRI-28731, a highly potent and selective MAP4K4 (HGK) inhibitor for cancer therapy
MAP4K4, a Ser/Thr kinase, was identified as an important pro-migratory kinase in an siRNA screen, targeting 5,234 human genes for modulators of tumor cell motility. MAP4K4 siRNA potently suppressed cell invasion and migration of multiple cancer cell lines, indicating a broad role in cell motility. There are no drugs in the clinic that are known to specifically target MAP4K4 for cancer therapy.
We have successfully developed an orally active, highly effective and selective MAP4K4 inhibitor (SRI-28731) with potent in vitro and in vivo anticancer activity. SRI-28731 is more potent than Paclitaxel (Taxol) against most of the b...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Chang, C.-T., Park, J., Zhou, W., Liu, X., Sato, B., Dinh, D., Furimsky, A., Beviglia, L., Sambucetti, L., Jong, L. Tags: Experimental and Molecular Therapeutics Source Type: research
