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Total 53 results found since Jan 2013.

Abstract P2-12-03: Prospective study of acupuncture in the rehabilitation of women undergoing surgical treatment of breast cancer in relation to the strength and quality of life
Conclusion: DAPK1 is a novel, promising target for the treatment of triple-negative p53-mutant breast cancer. Our studies demonstrate that DAPK1 inhibition sensitizes TNBCs to the cytotoxic effects of cisplatin or the PARP inhibitor. We are now conducting studies to determine whether DAPK1 inhibition will sensitize TNBC tumors and patient-derived TNBC xenografts to the effects of cisplatin and PARP inhibition. These studies suggest that the combination of DAPK1 inhibition with drugs that interfere with DNA repair will be useful for the treatment of the most aggressive form of breast cancer, triple-negative breast cancer.Fu...
Source: Cancer Research - February 13, 2017 Category: Cancer & Oncology Authors: PS Giron, CA Haddad, SL Rizzi, TL Pinheiro, RP Luz, AP Nazario, G Facina Tags: Poster Session Abstracts Source Type: research

Abstract B16: Activation of NRF2 and adaptive resistance to chemotherapy
Nuclear factor-erythroid-2-related factor 2 (NRF2), a member of the cap ‘n’ collar family of bZIP transcription factors, confers protection against oxidative and electrophilic stress. NRF2 is of great interest in cancer research, due to its role in response to chemotherapy, including the class of drugs targeting thymidylate synthase (TYMS). It has long been known that inhibition of TYMS leads to depletion of thymidine levels and the onset of programmed cell death, deriving from the enzyme's function as the sole de novo source of thymidine for DNA replication and repair. Exposing cells to TYMS inhibitors such as fluorop...
Source: Cancer Research - January 30, 2017 Category: Cancer & Oncology Authors: Sarah A. Clinton, Karen W. Barbour, Franklin G. Berger Tags: New Therapeutic Approaches to Colorectal Cancer Source Type: research

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 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 1656: MK-1775 (WEE1 inhibition) lacks efficacy against DNA repair deficient pancreatic cancer cells
Conclusions: These results support a paradigm in which identified high risk FA/BRCA2-mutated patients would not benefit from WEE1 inhibitor monotherapy; and thus, would most likely respond better to conventional DNA damaging agent-based therapies (e.g., oxaliplatin or MMC).Citation Format: Shruti Lal, Saswati N. Chand, Emanuela Dylgjeri, Charles J. Yeo, Jordan M. Winter, Jonathan R. Brody. MK-1775 (WEE1 inhibition) lacks efficacy against DNA repair deficient pancreatic cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Phi...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Lal, S., Chand, S. N., Dylgjeri, E., Yeo, C. J., Winter, J. M., Brody, J. R. Tags: Experimental and Molecular Therapeutics 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 LB-043: Highly specific and sensitive nanoimmunoassay of PARP1 as cell death measurement toolkit
In this study we developed highly sensitive and specific antibodies against PARP1 fragments. Using siRNAs against 18 PARP family members, we validated antibody specificity by western blotting and nanoimmunoassay (NIA). NIA is a highly sensitive platform capable of screening up to 96 cancer samples at sub-microliter volume. Moreover, this platform permits quantitative analysis of non-modified PARP1 as well as post-translational modifications such as PARylation and phosphorylation using a single antibody for the measurement of all species. We anticipate this workflow will be amenable to a wide range of protein targets, usher...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Pontikos, M. A., Zimmermann, A., Moncada, C., Abarca Heidemann, K. V., Miller, J. B., Birabaharan, J., Boyer, M., Zuck, R. M., Lorenzi, P. L., Ascoli, C. 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 2049: Characterization of a novel BRCA1-EGR1 interaction
The tumor suppressor protein BRCA1 orchestrates DNA repair and cell cycle arrest following DNA damage, with transcriptional regulation integral to these processes. We have identified a novel, DNA-damage responsive, interaction between BRCA1 and the zinc-finger transcription factor EGR1. EGR1 is rapidly and transiently expressed in response to a wide variety of stress stimuli and growth factors, and like BRCA1, decreased expression of EGR1 correlates with tumor formation in mammary cell lines and tissues.The stress response gene, NDRG1, was identified as a transcriptional target of BRCA1 by microarray analysis and subsequen...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Dickson, N. A., Crawford, N. T., Mullan, P. B. Tags: Molecular and Cellular 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 2081: The CCCTC-binding factor (CTCF) functions to downregulate the transcription of MGMT gene in human glioblastoma cells
The O6-methylguanine-DNA methyltransferase (MGMT) gene located at chromosome 10q26 encodes a DNA repair protein that abrogates the therapeutic effects of alkylating agents by preventing the formation of mutagenic lesions or cytotoxic DNA crosslinks. MGMT is highly expressed in human gliomas and its transcriptional regulation has emerged as a major translational focal point in neuro-oncology, because the epigenetic silencing of the MGMT gene which occurs in a subset of these malignancies confers improved treatment responses to both chemo and radiation therapies. While the promoter methylation and its contribution to glioma ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Srivenugopal, K. S., Al-Obaide, M. I. Tags: Molecular and Cellular Biology Source Type: research

Abstract 20: Honokiol radiosensitizes squamous cells carcinoma of head and neck by down-regulation of survivin
Conclusions: Survivin is a negative prognostic factor in SCCHN, and is involved in DNA damage response and repair induced by IR in SCCHN cells. Down regulation of survivin by honokiol enhances the efficacy of IR, and may provide a novel therapeutic approach to improve the efficacy of radiotherapy in SCCHN. (This research was supported by the National Cancer Institute award P50 CA128613, and GCC Distinguished Cancer Scholar to Dong M. Shin, Zhuo (Georgia) Chen, and Jonathan J Beitler)Citation Format: Xu Wang, Jonathan J. Beitler, Wen Huang, Guoqing Qian, Kelly Magliocca, Jun Zhang, Sreenivas Nannapaneni, Sungjin Kim, Zhengj...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Wang, X., Beitler, J. J., Huang, W., Qian, G., Magliocca, K., Zhang, J., Nannapaneni, S., Kim, S., Chen, Z., Nabil, S. F., Chen, Z. G., Arbiser, J. L., Shin, D. M. Tags: Molecular and Cellular Biology Source Type: research

Abstract 24: The phosphorylation of p53 at serine 46 is essential to induce cell death through palmdelphin in response to DNA damage
Tumor suppressor p53 plays a pivotal role in cell cycle arrest, DNA repair, and apoptosis in response to DNA damage. Promoter selectivity of p53 depends mainly on post-translational modification. Notably, the apoptotic function of p53 is related to its phosphorylation at serine-46 (ser46) to promote pro-apoptotic genes. However, little is known about the pro-apoptotic genes induced by Ser46 phosphorylation. Our research achieved to investigate the pro-apoptotic genes induced by p53 in a phospho-ser46-specific manner using microarray and ChIP sequencing in human cancer cell lines. As a result, palmdelphin (PALMD), an isofor...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Dashzeveg, N. K., Yoshida, K. Tags: Molecular and Cellular Biology Source Type: research

Abstract 353: Vorinostat enhances anti-tumor effects of cisplatin in head and neck cancer cells by targeting cancer stem cells
Conclusions: Taken together, our results suggest that targeting of HDACs with Vorinostat could be an effective treatment strategy for the treatment of HNSCC patients that do not respond to currently used treatment regimens.Citation Format: Bhavna Kumar, Arti Yadav, Theodoros N. Teknos, Pawan Kumar. Vorinostat enhances anti-tumor effects of cisplatin in head and neck cancer cells by targeting cancer stem cells. [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 353. doi:10...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Kumar, B., Yadav, A., Teknos, T. N., Kumar, P. Tags: Tumor Biology Source Type: research

Abstract 26: Suppression of E-cadherin mediates gallotannin-induced apoptosis in Hep G2 hepatocelluar carcinoma cells
Though gallotannin was known to have anti-oxidant and antitumor activity, the underlying antitumor mechanism of gallotannin still remains unclear. Thus, in the present study, antitumor mechanism of gallotannin was elucidated in hepatocellular carcinoma cells. Gallotannin significantly exerted cytotoxicity against Hep G2 and Chang hepatocellular carcinoma cells with the accumulation of the sub-G1 population and increase of terminal deoxynucleotidyltransferasedUTP nick end labeling (TUNEL) positive cells as an apoptotic feature. Also, gallotannin attenuated the expression of pro-caspase9, pro-caspase3, Bcl2 and integrin β1 ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Kwon, H. Y., Jung, J. H., Lee, H. J., Jeong, M. S., Jung, D.-B., Kim, B., Lee, H., Kim, S.-H. Tags: Molecular and Cellular Biology Source Type: research