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Source: Cancer Research
Cancer: Ovarian Cancer
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Total 71 results found since Jan 2013.
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 1434: MDM2 promotes tumor cell migration through the induction of epithelial to mesenchymal transition
Conclusion: In summary, this study explored the molecular mechanisms underlying the role of MDM2 in cancer progression. MDM2 expression has been demonstrated to be closely correlated to human ovarian adenocarcinoma clinical staging, indicating the possible utilization of MDM2 in prognosis. Further study clarified MDM2 promoted tumor cell migration through the induction of EMT, which provides new theoretical evidences for the roles that MDM2 plays in tumor metastasis. Our study implicates that MDM2 may be a potential target for inhibiting metastasis and contributes to the translational research of MDM2 inhibitors as anti-me...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Zheng, L., Wu, Y., Zhou, T., Zhu, H., He, Q., Yang, B. Tags: Tumor Biology Source Type: research
Abstract 142: SiRNA therapy against novel lncRNA NRCP: shutting down the fuel for cancer cells
In this study, we report the role of lncRNA NRCP in altering cancer cell metabolism and provide a strategy to target cancer metabolism using siRNAs. Methodology and Results: Using genomic profiling of ovarian tumors (n = 29) and normal ovarian tissues (n = 11) and comparative analyses, we found that NRCP was highly upregulated in ovarian tumors (>100 fold, p80%, p
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Rupaimole, R., Previs, R., Lee, J., Pradeep, S., Wu, S. Y., Ivan, C., Ferracin, M., Dennison, J., Rodriguez-Aguayo, C., Calin, G. A., Mills, G., Zhang, W., Lopez-Berestein, G., Bhattacharya, P., Sood, A. K. Tags: Molecular and Cellular Biology Source Type: research
Abstract 1199: Systems-based approach identifies altered carbohydrate metabolism as a predictor of a malignant phenotype in ovarian cancer
Conclusions: Here, we present a novel systems-based approach using altered metabolites and genes to predict a malignant phenotype specific to HGSOC patients. Altered metabolism, coupled with genomic analyses, identified the most interconnected gene-biochemical networks that will lead to novel biomarkers and therapeutic targets.Citation Format: Rebecca A. Previs, Tyler J. Moss, Behrouz Zand, Rajesha Rupaimoole, Heather J. Dalton, Jean M. Hansen, Guillermo Armaiz-Pena, Susan Lutgendorf, Robert L. Coleman, Pratip Bhattacharya, Prahlad Ram, Anil K. Sood. Systems-based approach identifies altered carbohydrate metabolism as a pr...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Previs, R. A., Moss, T. J., Zand, B., Rupaimoole, R., Dalton, H. J., Hansen, J. M., Armaiz-Pena, G., Lutgendorf, S., Coleman, R. L., Bhattacharya, P., Ram, P., Sood, A. K. Tags: Molecular and Cellular Biology 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 294: A novel cancer therapeutic strategy: inducing cytotoxic functions in tumor-associated macrophages
Macrophages are recognized as an important component of the tumor microenvironment. Previous studies have shown that they promote tumor growth and participate in the initiation and progression of metastatic spread. Methods are being developed to eliminate macrophages from the tumor, thereby inhibiting their negative effects. However, we believe that the best approach would be to transform the tumor-helping macrophages into tumor-killing macrophages that would both eliminate tumor cells directly and re-invigorate other immune cells around them to better fight the tumor. Our data indicates that we have found a way to induce ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Barham, W., Tikhomirov, O., Ortega, R., Saskowski, J., Thompson, C. S., Wilson, A., Blackwell, T., Mirafzali, Z., Khabele, D., Giorgio, T., Yull, F. E. Tags: Immunology Source Type: research
Abstract 519: V-set and immunoglobulin domain containing 1 (VSIG1) demonstrates a tumor suppressive function in gastric cancer and non-small cell lung cancer
V-set and immunoglobulin domain containing 1 (VSIG1) was recently identified as a novel member of immunoglobulin-like cell-adhesion molecules. In human, VSIG1 has 2 transcript variant forms (variant 1 and variant 2). In normal tissues, VSIG1 was reported to be expressed predominantly in stomach and testis. In cancerous tissues, the expression of VSIG1 was shown to be restricted in a part of gastric, esophageal, and ovarian cancers. However, the role of VSIG1 in cancer progression has not been elucidated.VSIG1 protein expression in human normal tissues obtained at autopsy was detected by western blot analysis. We also analy...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Inoue, Y., Kurabe, N., Matsuura, S., Maeda, M., Kahyo, T., Igarashi, H., Funai, K., Niwa, H., Ogawa, H., Shinmura, K., Konno, H., Suda, T., Sugimura, H. Tags: Tumor Biology Source Type: research
Abstract 1047: A role for the free beta subunit of human chorionic gonadotropin in sensitivity of epithelial ovarian cancer cells to platinum-based chemotherapeutics
Conclusions: These findings suggest that hCG-β may be involved in modulating the sensitivity of some EOCs to platinum based chemotherapy. Suppression of hCG-β may be a strategy to increase the responsiveness of primary EOCs to platinum-based chemotherapeutics.Citation Format: Snega M. Sinnappan, Robert C. Baxter, Deborah J. Marsh. A role for the free beta subunit of human chorionic gonadotropin in sensitivity of epithelial ovarian cancer cells to platinum-based chemotherapeutics. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Phil...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Sinnappan, S. M., Baxter, R. C., Marsh, D. J. Tags: Molecular and Cellular Biology Source Type: research
Abstract 313: Examining the role of ABCA1 cholesterol transporter in ovarian cancer spheroids
Epithelial ovarian cancer (EOC) is a devastating disease which accounts for a large proportion of gynaecological cancer-related deaths. Poor survival is largely due to late diagnosis of the disease which typically presents with peritoneal dissemination. In order to achieve reduced tumor burden and improved survival, it is imperative to identify new prognostic markers and potential therapeutic targets. Recent work by our group identified high ATP- Binding Cassette A1 (ABCA1) transporter expression as being associated with poor outcome in EOC. ABCA1 has been widely studied as a cholesterol transporter, however there is littl...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Williams, R., Russell, A., Bongers, A., Sagnella, S., Fife, C., Jessup, W., DeFazio, A., Chenevix-Trench, G., Haber, M., Norris, M., Henderson, M. Tags: Tumor Biology Source Type: research
Abstract 12: Bclxl is a key regulator of mitochondria-induced apoptosis in ovarian cancer stem cells
Conclusion:Ovarian cancer stem cells have a unique mitochondrial phenotype and Bclxl is a key regulator of its stability and may play a role in resistance to chemotherapy-induced apoptosis. Targeting Bclxl may be an approach to complement current standard of care in ovarian cancer. The demonstration that apoptosis can be fully induced with minimal loss of Bclxl suggests an acceptable therapeutic window for Bclxl inhibitors.Citation Format: Ayesha B. Alvero, Mary Pitruzello, Michele Montagna, Eydis Lima, Gil Mor. Bclxl is a key regulator of mitochondria-induced apoptosis in ovarian cancer stem cells. [abstract]. In: Proceed...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Alvero, A. B., Pitruzello, M., Montagna, M., Lima, E., Mor, G. Tags: Molecular and Cellular Biology Source Type: research
Abstract 2359: Adrenergic regulation of MCP-1 leads to enhanced macrophage recruitment and ovarian carcinoma growth
Increased adrenergic signaling is known to promote tumor progression, but the underlying mechanisms remain poorly understood. Tumor associated macrophages (TAMs) are key components of the tumor microenvironment that contribute to pro-inflammatory processes and tumor growth. Recently, it has been reported that patients with higher levels of adrenergic signaling have higher counts of MMP-9-producing TAMs. Here, we examined factors responsible for stress-mediated effects on monocyte/macrophage recruitment into the tumor microenvironment and the resultant effects on tumor growth. Conditioned media from norepinephrine- or epine...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Armaiz-Pena, G. N., Gonzalez-Villasana, V., Nagaraja, A. S., Rodriguez-Aguayo, C., Dorniak, P., Previs, R., Sadaoui, N., Stone, R., Matsuo, K., Dalton, H. J., Lutgendorf, S. K., Sood, A. K., Lopez-Berestein, G. Tags: Tumor Biology Source Type: research
Abstract 2642: EF2-kinase (EF2K): A novel molecular target in ovarian and pancreatic cancers
Ovarian cancer (OC) and Pancreatic ductal adenocarcinoma (PDAC) are the most aggressive and deadliest cancers and is currently incurable disease with the poorest prognosis and survival rates (4% and 30% 5-year survival rates, respectively). The poor prognosis is attributed to the extensive local tumor invasion and the resistance to existing cancer therapeutics, which are the major characteristics of both cancers and the impediment to effective cure this lethal diseases. Although both cancers have a well-defined spectrum of highly recurrent oncogenic lesions, including p53, c-myc, K-ras, CDKN2A /p16, TP53 and SMAD4/DPC4 eff...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Ashour, A., Erdogan, A., Alpay, S. N., Kahraman, N., Yuka, E., Lopez-Berestein, G., Ozpolat, B. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 2142: Novel oncogenic BRaf deletions functioning as BRaf homodimer and sensitive to inhibition by LY3009120, a pan Raf and Raf dimer inhibitor
In this study, we have identified and characterized novel BRaf aberrant variants, which have in-frame deletions within or adjacent to the L485-P490 region in patient samples and/or cell lines of lung, pancreatic, and ovarian cancers. Tumor cells with these endogenous BRaf deletions are resistant to BRaf monomer inhibitor vemurafenib based on inhibition of phospho-MEK and phospho-ERK, cell proliferation, and cell cycle progression. However, these cells are sensitive to LY3009120, a pan Raf and Raf dimer inhibitor. Further analysis using siRNA showed that the MEK-ERK activity in these cells is mainly dependent on BRaf, not C...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Chen, S.-H., Buchanan, S., Zhang, Y., Van Horn, R., Yin, T., Yadav, V., Wong, S. S., Huber, L., Henry, J., Conti, I., Starling, J. J., Plowman, G. D., Peng, S.-B. Tags: Molecular and Cellular Biology Source Type: research
