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Source: Cancer Research
Therapy: Cancer Therapy
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Total 42 results found since Jan 2013.
Abstract B57: RNAi Nanotechnology for Cancer Target Validation and Therapy
RNA interference (RNAi) represents a promising strategy for identification and validation of putative therapeutic targets, and for treatment of a myriad of important human diseases including cancer. The ubiquitous application of RNAi in cancer research and therapy is nevertheless hindered by the challenge of effective systemic in vivo delivery of RNAi agents (e.g., siRNA) to solid tumors, which requires overcoming of multiple physiological barriers, such as enzymatic degradation, rapid elimination by renal excretion or by the mononuclear phagocyte system (MPS), poor tumor penetration, and insufficient cellular uptake and e...
Source: Cancer Research - January 15, 2017 Category: Cancer & Oncology Authors: Jinjun Shi Tags: Tumor Immunology/Immunotherapy Source Type: research
ZIC5 Drives Melanoma Aggressiveness by PDGFD-Mediated Activation of FAK and STAT3
Insights into mechanisms of drug resistance could extend the efficacy of cancer therapy. To probe mechanisms in melanoma, we performed siRNA screening of genes that mediate the development of neural crest cells, from which melanocytes are derived. Here, we report the identification of ZIC5 as a mediator of melanoma drug resistance. ZIC5 is a transcriptional suppressor of E-cadherin expressed highly in human melanoma. ZIC5 enhanced melanoma cell proliferation, survival, drug resistance, in vivo growth and metastasis. Microarray analysis revealed that ZIC5 downstream signaling included PDGFD and FAK activation, which contrib...
Source: Cancer Research - January 15, 2017 Category: Cancer & Oncology Authors: Reiko Satow, Tomomi Nakamura, Chiaki Kato, Miku Endo, Mana Tamura, Ryosuke Batori, Shiori Tomura, Yumi Murayama, Kiyoko Fukami Tags: Molecular and Cellular Pathobiology 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
DDR1 Inhibition Enhances Immunotoxin Therapy
Recombinant immunotoxins (RIT) have been highly successful in cancer therapy due, in part, to the high cancer-specific expression of cell surface antigens such as mesothelin, which is overexpressed in mesothelioma, ovarian, lung, breast, and pancreatic cancers, but is limited in normal cells. RG7787 is a clinically optimized RIT consisting of a humanized anti-mesothelin Fab fused to domain III of Pseudomonas exotoxin A, in which immunogenic B-cell epitopes are silenced. To enhance the therapeutic efficacy of RITs, we conducted a kinome RNAi sensitization screen, which identified discoidin domain receptor 1 (DDR1), a collag...
Source: Cancer Research - March 14, 2016 Category: Cancer & Oncology Authors: Ali-Rahmani, F., FitzGerald, D. J., Martin, S., Patel, P., Prunotto, M., Ormanoglu, P., Thomas, C., Pastan, I. Tags: Therapeutics, Targets, and Chemical Biology Source Type: research
Abstract B37: The histone deacetylase inhibitor panobinostat sensitizes cyclin E-amplified ovarian cancer cells to poly ADP ribose polymerase inhibitors via E2F1 downregulation.
Conclusions: The development of a new PARPi combination therapy with panobinostat has immediate prospects for rapid translation to the clinic and great potential for improving clinical outcomes for non-BRCAness, chemoresistant ovarian cancer.Citation Format: Andrew J. Wilson, Jeanette Saskowski, Dineo Khabele. The histone deacetylase inhibitor panobinostat sensitizes cyclin E-amplified ovarian cancer cells to poly ADP ribose polymerase inhibitors via E2F1 downregulation.. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR;...
Source: Cancer Research - January 14, 2016 Category: Cancer & Oncology Authors: Wilson, A. J., Saskowski, J., Khabele, D. Tags: Epigenetic Cancer Therapies Source Type: research
Abstract B43: Dose and context-dependent roles for Arid1a in liver tumorigenesis
Frequent Arid1a loss-of-function mutations suggest tumor suppressive roles, but the functional impact of Arid1a and SWI/SNF chromatin-remodeling aberrations in human cancer are not clear. Liver-specific Arid1a knockout mice do not develop cancer after 15 months and surprisingly, homozygous mice are potently protected from diethylnitrosamine (DEN) + carbon tetrachloride induced hepatocellular carcinoma (HCC). This is likely due to the fact that Arid1a deficient livers are resistant to chemical damage in a Cytochrome P450 dependent fashion. To determine if genetic drivers of cancer might reveal additional roles for Arid1a, w...
Source: Cancer Research - January 14, 2016 Category: Cancer & Oncology Authors: Sun, X., Wang, S., Nguyen, L., Zhu, H. Tags: Epigenetic Cancer Therapies Source Type: research
Abstract 3669: Engineering the biointerface of synthetic high density lipoprotein nanoparticles enables efficient nucleic acid loading, delivery, and target gene regulation in cancer cells
Local treatment of cancer confined to the primary organ can be curative. However, other than a few success stories, locally advanced and metastatic cancer remains incurable. Ideally, new therapies are needed that specifically target cancer cells and derive efficacy by targeting molecular pathways that are unique to distinct tumor profiles and individual patients. Toward this end, we focus on the use of biomimicry to exploit mechanisms by which cancer cells uptake molecular cargo. Naturally, some cancer cells are dependent upon exogenous cholesterol for cellular signaling, growth, and in some cancers, such as prostate, ster...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: McMahon, K. M., Vander Griend, D., Volpert, O., Thaxton, C. S. Tags: Cancer Chemistry Source Type: research
Abstract 1140: PI3K/Akt inhibition decreases oxygen consumption In tumor cells by phosphorylating and inactivating pyruvate dehydrogenase PDH E1{alpha} subunit
The PI3K/mTOR pathway plays a central role in coupling metabolic processes to the cellular proliferative state. Pharmacologic inhibitors of the PI3K/mTOR pathway or genetic inhibition of Akt/PI3K decreased the oxygen consumption rate (OCR) in transformed cell lines in vitro by 30-40%. Pharmacologic inhibition of this pathway increased phosphorylation of the E1α subunit of the pyruvate dehydrogenase (PDH) complex on Ser293, an inhibitory modification of this critical gatekeeper of mitochondrial respiration. Expressing wild type PTEN in a doxycycline-inducible manner in a glioblastoma cell line with mutant PTEN led to an in...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Cerniglia, G. J., Day, S., Gallagher-Colombo, S. M., Daurio, N., Tuttle, S., Busch, T. M., , Lin, A., Esipova, T. V., Vinogradov, S. A., Koumenis, C., Maity, A. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1180: Hexokinase II plays a pivotal role in colorectal cancer cell proliferation and survival
The Warburg Effect describes the widely observed metabolic phenotype of cancer cells and their heavy reliance on the glycolytic pathway for energy production regardless of oxygen tension. This is a result of alterations to metabolic signaling pathways leading to an upregulation in key glycolytic enzymes. Hexokinase II (HKII) catalyzes the first irreversible step of glycolysis and is often overexpressed in tumors. 3-bromopyruvate (3BP) has been shown to primarily target HKII, and is a promising anti-cancer compound capable of targeting critical metabolic pathways in cancer cells. Here we examine the importance of HKII to ce...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Ho, N., Coomber, B. L. Tags: Molecular and Cellular Biology Source Type: research
Abstract 680: Identification of GLI1 antagonists for breast cancer therapy
Conclusion: Several agents showed efficacy in in vitro BC cancer models demonstrating that GLI inhibitors may be a valid therapeutic approach for targeting GLI-dependent BC cancers.[1] Z. Thomas, W. Gibson, J. Sexton, K. Aird, S. Ingram, A. Aldrich, H. Lyerly, G. Devi, K. Williams, Targeting GLI1 expression in human inflammatory breast cancer cells enhances apoptosis and attenuates migration. British Journal of Cancer 104 (2011) 1575-1586.[2] K.P. Williams, J.L. Allensworth, S.M. Ingram, G.R. Smith, A.J. Aldrich, J. Z Sexton, G. R Devi, Quantitative high-throughput efficacy profiling of approved oncology drugs in inflammat...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Oladapo, H., Fleming, J. M., Addo, K., Tarpley, M., Ehe, B., Ingram, S., Sauer, S., Devi, G., Williams, K. P. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 1992: Evidence for modulation of FoxM1 by p21 in ovarian cancer
The oncogenic transcription factor forkhead box M1 (FoxM1) is overexpressed in many cancers, including 84% of ovarian cancer and plays a role in DNA repair, mitotic checkpoint, cell proliferation, and cancer drug resistance. Similar to Her2 in breast cancer, the constitutive expression of FoxM1 makes it a plausible gene target for novel anti-cancer therapies, but the regulation of FoxM1 has yet to be elucidated. Evidence suggests FoxM1 up-regulation is a result of TP53 mutations, however, no TP53 response element has been found within the FoxM1 promoter, thus there is likely another molecule mediating p53-induced FoxM1 ove...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Madden, J., Chien, J. Tags: Molecular and Cellular Biology Source Type: research
Abstract 287: Specific delivery of immunostimulatory RNA via nanoparticles blocks growth of primary and disseminated ovarian tumors
One important mechanism of immune evasion is the accumulation of tumor-infiltrating regulatory T cells creating an immunosuppressive microenvironment in situ. Many new therapies target immune checkpoint receptors, CTLA-4 and PD-1, on immunosuppressive T-cells to reverse tumor immune evasion. Small interfering RNAs (siRNAs) are double stranded, sequence-specific inhibitors of gene expression. The paradigm for using siRNA to block cancer is to target mRNA sequences of oncogenes. Several limitations have suppressed the use of siRNA in human cancer therapy, such as off-target effects and lack of tumor-specific delivery. Additi...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Primiano, T., Chang, B.-i. Tags: Immunology Source Type: research
Abstract 2561: Contextual combination of PARP inhibitors with p110beta inhibitors: Functional logistics to tame PTEN null tumors
Background: Hyper-activation of the PI3K pathway due to a functional loss of PTEN is a characteristic feature of many tumors including TNBC and GBM. Although p110b rarely undergoes activating mutations in these cancers, loss of PTEN function makes these tumor cells dependent specifically on p110b. In a mechanism-based study we have recently established an integral role of the PI3K pathway in DNA damage repair (DDR)-mediated anti-tumor efficacy of PARP inhibitor wherein we have demonstrated that PTEN-nullness confers in vivo sensitivity to the combination as compared to tumors carrying PTEN WT (De et al., Neoplasia, 2014). ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Carlson, J. H., Sun, Y., Lin, X., De, P., Leyland-Jones, B., Dey, N. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract LB-102: Layer-by-layer engineering of upconversion nanoparticle based siRNA and miRNA delivery system for cancer therapy
Conclusions: In this proof-of-concept study, a layer-by-layer engineered UCNP based siRNA and miRNA delivery system was successfully developed. Our novel delivery system opens up preparation of advanced UCNP based photoresponsive delivery systems that allow remote, precise, and trackable control over therapeutic payload (e.g., drug, gene) release for better cancer theranostics.Citation Format: Lin Min, YAN GAO, Francis J. Hornicek, Mansoor M. Amiji, Zhenfeng Duan. Layer-by-layer engineering of upconversion nanoparticle based siRNA and miRNA delivery system for cancer therapy. [abstract]. In: Proceedings of the 106th Annual...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Min, L., GAO, Y., Hornicek, F. J., Amiji, M. M., Duan, Z. Tags: Cancer Chemistry Source Type: research
Abstract 2640: Small molecule compound NCI-8 induces ERK2-dependent mutant-p53 protein degradation
The tumor suppressor p53 is mutated in over 50% of human cancers leading not only to loss of wild-type p53 function, but also to gain-of-function (GOF) mutant p53 which acts as an oncogene. Mutant p53 is expressed at very high levels and can inhibit residual wild-type p53 activity as well as the function of p53 family member proteins such as p73 or p63. Therefore, targeting mutant p53 by either restoring the p53 pathway or depleting its GOF is an attractive strategy for cancer therapy. NCI-8 is a small molecule compound with dual abilities to induce p53 signal pathway and destabilize mutant p53 protein (deplete GOF) in mut...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Zhang, S., Zhou, L., Dicker, D. T., EL-Deiry, W. S. Tags: Experimental and Molecular Therapeutics Source Type: research
