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Source: Cancer Research
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Total 807 results found since Jan 2013.
Abstract 3903: A sub-set of DCLK1+ve colon cancer stem cells (CSCs) survive curcumin induced autophagy, while co-treatment with curcumin +DCLK1-siRNA eliminates CSCs: Role of long and short isofoms of DCLK1
Conclusion. Our studies strongly suggest that, 1) DCLK1 represents a functional protein for colon cancers, 2) combination of curcumin+DCLK1-siRNA may target and eradicate colon cancer stem cells., and 3) identifying small molecules that inhibit expression of S-isoform may allow to specifically target cancer stem cells, while sparing normal stem cells for cancer treatment purposes.
This work was supported by NIH Granst to PS (R01CA09795909 and RO1CA0975909-S1).
Citation Format: Shubhashish Sarkar, Malaney O'Connell, Carla, Kantara, Pomila Singh. A sub-set of DCLK1+ve colon cancer stem cells (CSCs) survive curcumin induced a...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Sarkar, S., O'Connell, M., Kantara, C., Singh, P. Tags: Tumor Biology Source Type: research
Abstract 5423: Novel targeted therapy for neuroblastoma: Silencing the MXD3 gene using siRNA
Neuroblastoma is a cancer of the sympathetic nervous system and the most common extracranial solid tumor in children. Almost half of neuroblastoma patients have a high-risk phenotype at diagnosis: metastatic disease. Prognosis of these patients is very poor with only 30% survival despite the most intensive therapies currently available. In addition, patients who respond successfully to treatment suffer from side effects from chemo and radiation therapies, leading to life-long irreversible complications. Therefore, there is a desperate need for a neuroblastoma-targeted therapy that is more effective and has fewer side effec...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Duong, C., Chen, C., Yoshida, S., Barisone, G., Nolta, J., Diaz, E., Nitin, N., Satake, N. Tags: Clinical Research (Excluding Clinical Trials) Source Type: research
Abstract 2958: Discovering therapeutic epigenetic targets using whole genome siRNA screening
Conclusions: A whole genome siRNA screen in combination with the DNMT inhibitor decitabine identified many new target genes that might be epigenetic regulators and potential targets for drug development.Citation Format: Yasuyuki Okamoto, Woonbok Chung, Judith Garriga, Jaroslav Jelinek, Jean-Pierre J. Issa. Discovering therapeutic epigenetic targets using whole genome siRNA screening. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2958. doi:10.1158/1538-7445.AM2015-2958
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Okamoto, Y., Chung, W., Garriga, J., Jelinek, J., Issa, J.-P. J. Tags: Molecular and Cellular Biology Source Type: research
Bifunctional siRNA Against Pancreatic Cancer
In conclusion, combing TGF-β gene silencing with RIG-I signaling confers potent antitumor efficacy against pancreatic cancer by breaking tumor-induced CD8+ T cell suppression. Cancer Res; 73(6); 1709–20. ©2013 AACR.
Source: Cancer Research - March 14, 2013 Category: Cancer & Oncology Authors: Ellermeier, J., Wei, J., Duewell, P., Hoves, S., Stieg, M. R., Adunka, T., Noerenberg, D., Anders, H.-J., Mayr, D., Poeck, H., Hartmann, G., Endres, S., Schnurr, M. Tags: Microenvironment and Immunology Source Type: research
Abstract 3630: Immunoengineering of tumor associated macrophages using targeted, siRNA delivering nanoparticles
Tumor associated macrophages (TAMs) can modify the tumor microenvironment to create a pro-tumor niche. Dysregulation of NF-κB signaling is implicated in creating a pro-tumor phenotype in TAMs. NF-κB signaling consists of a classical pathway and a less understood alternative pathway. Suppression of NF-κB activation in TAMs is predicted to decrease local smoldering inflammation and inhibit the pro-tumor TAM phenotype. However, recent studies have reported anti-tumor macrophage behavior induced by activation of the classical NF-κB pathway. We have successfully used mannosylated polymer nanoparticles (Mn-NP) to deliver siR...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Ortega, R., Barham, W., Tikhomirov, O., Sharman, K., Yull, F., Giorgio, T. Tags: Immunology Source Type: research
Abstract 5323: Integrated computational cell-line modeling of drug sensitivity and high-throughput siRNA screening reveals novel molecular biomarkers for conventional chemotherapy
Conclusions: We present an integrated approach that combines a novel Bayesian multi-task learning model with high-throughput siRNA screens. Our approach aims to uncover sets of important aberrations and allows for the subtyping of drugs based on similarities in targets and mechanisms of action. We integrate our results with high-throughput RNAi experiments to identify synthetic lethal events in specific therapeutic context.
Citation Format: Olga H. Nikolova, Mehmet Gönen, Rodrigo Dienstmann, In Sock Jang, Russell Moser, Silvia Cermelli, Chang Xu, Ryan M. Mitchell, Eduardo Mendez, Carla Grandori, Christopher Kemp, Stephen ...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Nikolova, O. H., Gonen, M., Dienstmann, R., Jang, I. S., Moser, R., Cermelli, S., Xu, C., Mitchell, R. M., Mendez, E., Grandori, C., Kemp, C., Friend, S., Guinney, J., Margolin, A. Tags: Molecular and Cellular Biology Source Type: research
Abstract LB-299: Gene knockdown by EpCAM aptamer-siRNA chimeras suppresses epithelial breast cancers and their tumor-initiating cells
Effective therapeutic strategies for in vivo siRNA delivery to knockdown genes in cells outside the liver are needed to harness RNA interference for treating cancer. EpCAM is a tumor-associated antigen highly expressed on common epithelial cancers and their tumor-initiating cells (T-IC, also known as cancer stem cells). Here we show that aptamer-siRNA chimeras (AsiC, an EpCAM aptamer linked to an siRNA sense strand and annealed to the siRNA antisense strand) are selectively taken up and knockdown gene expression in EpCAM+ cancer cells in vitro and in human cancer biopsy tissues. PLK1 EpCAM-AsiCs inhibit colony and mammosph...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Gilboa-Geffen, A., Hamar, P., Wheeler, L. A., Trifonova, R., Petrocca, F., Wittrup, A., Lieberman, J. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1428: Targeting RRM2 by siRNA inhibits cellular invasion and represents a rational approach for inhibition of metastasis of head and neck and lung cancers
Background: Ribonucleotide reductase subunit M2 (RRM2) has been frequently observed to be aberrantly overexpressed in various tumors. RRM2 is a key enzyme, and essential regulator of balanced deoxyribonucleotides (dNTPs). It is critical for DNA replication and repair, and hence cell survival. In addition to DNA synthesis, it has been reported to modulate cellular invasiveness. However, the mechanisms through which RRM2 affects the invasive phenotype have not been elucidated.Methods: We evaluated the expression of RRM2 protein in metastatic (n = 40) and non-metastatic (n = 40) head and neck squamous cell carcinoma (HNSCC) t...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Rahman, M. A., Amin, A. R. M. R., Zhang, J., Nannapaneni, S., Saba, N. F., Chen, Z. G., Shin, D. M. Tags: Tumor Biology 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 720: Dual MMP-7-proximity-activated and folate-targeted nanoparticles for siRNA delivery
We have developed a dual, folic acid (FA) and matrix metalloproteinase (MMP), proximity-activated targeting (PAT) smart polymeric nanoparticle (SPN) for tumor-specific siRNA delivery. The nanocarrier was designed to expose concealed FA ligands specifically in regions of elevated MMP activity, resulting in targeted uptake by folate receptor-expressing cells.
Site-selective chemistry and reversible addition-fragmentation chain transfer (RAFT) polymerization were used to prepare diblock copolymers {p(DMAEMA)-b-p(DMAEMA-PAA-BMA) (SPN)} terminated with either MMP-7 peptide coupled to a Y-shaped 20 kDa PEG (PAT-SPN) or a 2 kDa l...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Giorgio, T. D., Li, H., Miteva, M., Kirkbride, K. C., Cheng, M., Nelson, C. E., Duvall, C. L. Tags: Experimental and Molecular Therapeutics 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 2598: siRNA silencing of survivin enhances activity of mitomycin C in human bladder RT4 xenografts
For intravesical therapy of nonmuscle-invading bladder cancer, maximizing the mitomycin (MMC) exposure by pharmacokinetic interventions yielded 43% 5-year recurrence-free survival (Au et al., JNCI, 2001). Further improvement requires enhancing chemosensitivity, such as silencing of survivin, an inhibitor of apoptosis and indicator of bladder cancer aggressiveness and recurrence. Survivin is induced by chemotherapy, and its in vitro knockdown by si/shRNA enhances sensitivity to chemotherapy including MMC. As the utility of siRNA has been impeded by lack of activity in vivo, we developed a siRNA carrier that enhances its int...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Cui, M., Wientjes, M. G., Au, J. L.- S., O'Donnell, M., Loughlin, K., Lu, Z. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 2603: Specific growth suppression of wild-type p53 tumor cells by DNA-modified siRNA sequences targeting MDM2
Conclusions: Our 2 newly selected dsRDC-modified siRNAs had high knockdown activity and less nonspecific cytotoxicity. Thus, they represent potent therapeutic agents against cancers carrying wt p53 with MDM2 overexpression.
Citation Format: Mitsuaki Hirose, Kenji Yamato, Rie Saito, Takunori Ueno, Sachiko Hirai, Hideo Suzuki, Shinji Endo, Ichinosuke Hyodo. Specific growth suppression of wild-type p53 tumor cells by DNA-modified siRNA sequences targeting MDM2. [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 R...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Hirose, M., Yamato, K., Saito, R., Ueno, T., Hirai, S., Suzuki, H., Endo, S., Hyodo, I. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 768: A kinome-wide siRNA screen identifies modifiers of sensitivity to the EGFR T790M-targeted tyrosine kinase inhibitor (TKI), AZD9291, in EGFR mutant lung adenocarcinoma
In conclusion, through a kinome wide siRNA screen, we identified that gene products in the MAP kinase signaling pathway modify sensitivity to AZD9291. Such sensitivity may be associated with ERK re-phosphorylation within 96h of drug treatment. Collectively, these data suggest rational drug combinations that could be used to forestall resistance to AZD9291. Additional hits from the screen are currently under investigation.This study is supported by AstraZeneca Oncology Innovative Medicines, National Institutes of Health (NIH) NCI grants R01-CA121210, P01-CA129243, U54-CA143798, and the Uehara Memorial Foundation.Citation Fo...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Ichihara, E., Bauer, J. A., Lu, P., Ye, F., Cross, D., Pao, W., Lovly, C. M. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 3373: Identification of inflammation-related genes that regulate tumor-associated stemness using high-throughput siRNA screening
Cancer associated stem cells (CSCs) are considered to be responsible for tumor recurrence, metastasis as well as chemoresistance. These properties of tumor associated stemness are maintained by specialized microenvironment, including inflammation which is a key component of the tumor microenvironment. To study the relationship between inflammation and stemness of CSCs, here, we established a robust high-throughput RNAi screen platform for a global survey of inflammation-related genes affecting CSCs identity via alteration of Oct4 expression. Consequently, we found 72 novel genes from 1027 inflammation-related genes which c...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Xie, J., He, H., Chen, C., Bai, L., Wang, W., Liu, Y., Guo, J., Wu, P., Xiang, R., Luo, Y. Tags: Tumor Biology Source Type: research
