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Total 151 results found since Jan 2013.
Abstract A02: Identification of distinct BUB1B-sensitive and -resistant subtypes of glioblastoma with prognostic value
Glioblastoma multiforme is the most aggressive and common form of brain cancer in adults. The combined analysis of functional genetics with glioblastoma (GBM) network modeling identified BUB1B, a critical mitotic spindle checkpoint player, as a new requirement of glioblastoma tumors to suppress lethal consequences of altered kinetochore (KT) (1). Here, we further collected GBM stem-like cells (GSCs) including both BUB1B-sensitive and -resistant isolates, and performed whole-transcriptome sequencing that capture gene expression levels of each GSC. Based on the expression signature associated with BUB1B-sensitiveness from GS...
Source: Cancer Research - December 9, 2015 Category: Cancer & Oncology Authors: Lee, E., Paddison, P. J., Zhu, J. Tags: Computational Genomics and Evolutionary Dynamics Source Type: research
Abstract B12: GABP selectively binds and activates the mutant TERT promoter across multiple cancer types
Reactivation of telomerase reverse transcriptase (TERT) expression enables cells to overcome replicative senescence and escape apoptosis, fundamental steps in the initiation of human cancer. Multiple cancer types, including up to 83% of glioblastomas (GBM), harbor highly recurrent mutations in the TERT promoter specific to two nucleotide positions. The common mutation sites, G228A and G250A, may create de-novo ETS family transcription factor binding sites, but the precise mechanism of how these mutations confer increased TERT expression has been elusive. Here, we demonstrate the de-novo ETS motif to be critical for mutant ...
Source: Cancer Research - December 9, 2015 Category: Cancer & Oncology Authors: Bell, R. J. A., Rube, H. T., Kreig, A., Mancini, A., Fouse, S. F., Nagarajan, R. P., Choi, S., Hong, C., He, D., Pekmezci, M., Wiencke, J. K., Wrensch, M. R., Chang, S. M., Walsh, K. M., Myong, S., Song, J. S., Costello, J. F. Tags: Mutational Landscape in Brain Tumors Source Type: research
Abstract B26: MAPK-interacting kinase inhibition sensitizes glioblastoma and glioma stem cells to arsenic trioxide
In this study, we sought to determine the mechanisms by which MNK signaling regulates arsenic trioxide responses in GBM and glioma stem cells.GBM cell lines were treated with ATO in the presence or absence of MNK inhibitors or siRNA against MNK isoforms. Western blots of treated samples were analyzed with antibodies against phosphorylated eIF4E, the key downstream effector of the MNKs. Following treatment with ATO and MNK inhibitors, proliferation rate and apoptosis were determined by WST-1 assay and Annexin V-FITC/PI staining. GBM cell lines were grown under stem cell conditions and subjected to qPCR and flow cytometry to...
Source: Cancer Research - December 9, 2015 Category: Cancer & Oncology Authors: Bell, J. B., Eckerdt, F., Arslan, A. D., Iqbal, A., Alvarez, A. A., Cheng, S.-Y., Nakano, I., Platanias, L. C. Tags: Preclinical Therapeutics/Trials/Models Source Type: research
Abstract B15: In vivo analysis of repeated siRNA silencing on protein expression levels
This study focused on determining the possibility of resistance development against siRNA treatment as a result of repeated exposure to siRNA in vivo. Our preliminary experiments in vitro revealed an unaffected siRNA cellular internalization and reproducible silencing efficiency of selected targets. The expression level of other mediators involved in breast cancer cell survival and proliferation (notably survivin, JUN, JAK2, NFkB and STAT3) were, however, altered in siRNA treated cells. In vivo experiments in a xenograft model demonstrated a similar silencing efficiency at the mRNA level after each repeated dose, with litt...
Source: Molecular Cancer Therapeutics - December 6, 2015 Category: Cancer & Oncology Authors: Aliabadi, H. M., Mahdipoor, P., Uludag, H. Tags: Other Combination Therapies: Poster Presentations - Proffered Abstracts Source Type: research
Abstract A25: Molecular characterization of cyclin-dependent kinase 1 pathway in newly established epithelial ovarian cancer cell lines
Conclusions: These results suggest that elevated expression of Cdk1/cyclinB1 is important to EOC development and progression, providing new insight into the biology of EOC.Citation Format: Hanbyoul Cho, Assel Sabrgaliyeva, Woo Kyeom Yang, Sol Kim, Ha-Yeon Shin, Eun Ju Lee, Jae-hoon Kim. Molecular characterization of cyclin-dependent kinase 1 pathway in newly established epithelial ovarian cancer cell lines. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 ...
Source: Molecular Cancer Therapeutics - December 6, 2015 Category: Cancer & Oncology Authors: Cho, H., Sabrgaliyeva, A., Yang, W. K., Kim, S., Shin, H.-Y., Lee, E. J., Kim, J.-h. Tags: Biomarkers / Novel Imaging to Assess Response: Poster Presentations - Proffered Abstracts Source Type: research
Abstract A07: Knockdown laminin-511 expression blocked endlthelial cell function in vitro and angiogenesis in vivo knockout skin model
In conclusion, our data suggested a possible involvement of laminin-511 in integrin alphaV and beta3-dependent angiogenesis and blood vessel maturation. Our works revealed the important roles of laminin-511 in endothelial cell activities, which proved its significance for angiogenesis.Citation Format: Jie Li, Tengjiao Cui. Knockdown laminin-511 expression blocked endlthelial cell function in vitro and angiogenesis in vivo knockout skin model. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA...
Source: Molecular Cancer Therapeutics - December 6, 2015 Category: Cancer & Oncology Authors: Li, J., Cui, T. Tags: Antiangiogenic Therapy: Poster Presentations - Proffered Abstracts Source Type: research
Abstract A2-18: The challenges of using large-scale genomics data to identify novel drivers of lung cancer
Lung cancer is one of the major causes of cancer deaths worldwide and only 30% of patients survive the disease for at least one year after diagnosis. Patients are often too frail to receive systemic chemotherapy and there is an urgent need for less toxic, efficacious, targeted therapies. Despite recent efforts with large-scale genomics data we still lack knowledge about driver mutations for the majority of lung cancers.Increasingly, cancer researchers are using online cancer genomic databases to identify novel targets to investigate. A comparison of two prominent databases from different institutes (CCLE and COSMIC) reveal...
Source: Cancer Research - November 15, 2015 Category: Cancer & Oncology Authors: Hudson, A. M., Yates, T., Wirth, C., Li, Y., Trotter, W., Fawdar, S., Miller, C., Brognard, J. Tags: Genomics and Target Discovery Source Type: research
Abstract A1-05: Elucidation of epigenetic driver genes in clear cell renal cell carcinoma using a newly developed assay, AcceSssIble
Conclusions: Our study revealed a vast number of chromatin accessibility and accompanying gene expression changes that occur in gene promoters in the development of ccRCC, both dependent and independent of DNA methylation changes. Each individual tumor has a unique profile of epigenetic alterations. Moreover, almost none of the genes that were found to undergo epigenetic and resulting gene expression changes overlap with TCGA's findings of commonly mutated genes in ccRCC. Overall, these studies represent novel approaches that can help identify new therapeutic target genes and treatment strategies for ccRCC, including perso...
Source: Cancer Research - November 15, 2015 Category: Cancer & Oncology Authors: Becket, E. C., Duymich, C., Chang, Y.-W., Pandiyan, K., Nichols, P., Jones, P., Gill, I., Liang, G. Tags: Cancer Genomics and Epigenomics Source Type: research
Abstract B45: c-MYC is a potential therapeutic target for cisplatin-resistant ovarian cancer
Ovarian cancer accounts for approximately 3% of all cancers in women. However, it is the deadliest cancer of the female reproductive system. Due to its non-specific symptoms, ovarian cancer is diagnosed at advanced stages of the disease. The most common standard treatment for advanced ovarian cancer is the platinum-based drugs such as cisplatin. However, over 70% of women relapse due to chemoresistance. Several mechanisms of cisplatin resistance have been described. However, the exact mechanism is not known. Evidence indicates that activation of the transcription factor c-MYC and its regulated genes could be involved in su...
Source: Molecular Cancer Research - October 18, 2015 Category: Cancer & Oncology Authors: Vivas-Mejia, P. E., Reyes, j., Sood, A. K. Tags: Therapeutic Translation: Poster Presentations - Proffered Abstracts Source Type: research
Abstract PR09: MYCN and is a therapeutic target in neuroblastoma
Neuroblastoma is a childhood cancer of the sympathetic nervous system. Approximately 20% of patients present with an aggressive metastatic disease characterized by amplification of the MYCN locus. However, an additional 30% of patients suffer from an equally aggressive disease, yet there are no unified genetic markers available.To identify potential biomarkers of poor prognosis in neuroblastoma, we conducted unsupervised hierarchical clustering on 649 primary neuroblastoma tumors based on a 51 gene MYC core target signature. This demonstrated strong activation within the MYCN amplified cohort as expected, but surprisingly ...
Source: Molecular Cancer Research - October 18, 2015 Category: Cancer & Oncology Authors: Carter, D. R., Murray, J., Cheung, B. B., Kalla, H., Gamble, L., Tsang, J., Sutton, S., Koach, J., Syed, S., Gifford, A., Issaeva, N., Biktasova, A., Atmadibrata, B., Sun, Y., Sokolowski, N., Ling, D., Kim, P. Y., Webber, H., Clark, A., Ruhle, M., Liu, B. Tags: Targeting Myc-Driven Cancers: Oral Presentations - Proffered Abstracts Source Type: research
Abstract PR15: ERK2 binds to MYC promoter and induces MYC expression
It has been known since 30 years ago that serum and growth factors induce a dramatic upregulation of MYC expression in quiescent cells, but the molecular mechanism for this effect is unknown. It has been reported that ERK can bind to DNA and modify gene expression (Hu et al., Cell, 2009). We have investigated the possibility that ERK directly upregulates MYC at the transcriptional level. We have found that: (i) Bioinformatic analyses reveal the presence of ERK binding sites (ERK boxes) conserved in human, mice and rat MYC promoters, located at -0.3 kbp, -1 kbp and -1.7 kbp from the transcription star site; (ii) ERK binds t...
Source: Molecular Cancer Research - October 18, 2015 Category: Cancer & Oncology Authors: Quintanilla, A., Rodriguez, J., Garcia-Gutierrez, L., Lorena, A., Crespo, P., Leon., J. Tags: Myc Beyond Cancer: Oral Presentations - Proffered Abstracts Source Type: research
Abstract B19: MYC induces PLD6 to suppress YAP/TAZ-dependent self-renewal of mammary stem cells
For the maintenance of a given tissue it is absolutely critical to balance proliferation and differentiation of stem cells, progenitor cells and terminally differentiated cells. Perturbations of these finely tuned processes can lead to various diseases such as cancer.One factor that has been implicated in the transition from a stem cell to a progenitor/ transit-amplifying cell is the oncogenic transcription factor MYC. Paradoxically, despite its strong pro-tumorigenic capabilities it has been shown to promote differentiation in several tissues such as the skin or the hematopoietic system.To identify critical pathways that ...
Source: Molecular Cancer Research - October 18, 2015 Category: Cancer & Oncology Authors: Eyss, B. v., Jaenicke, L. A., Wiese, K., Rosenwald, A., Eilers, M. Tags: Myc Beyond Cancer: Poster Presentations - Proffered Abstracts Source Type: research
Abstract B20: EnCore-LNP mediated tumor delivery of MYC and CTNNB1 Dicer Substrate RNAs (DsiRNAs)
MYC and CTNNB1 are well-characterized drivers of numerous tumor types. Human and preclinical genetic evidence suggest that pharmacological intervention to reduce transactivation of MYC and CTNNB1-regulated genes would yield therapeutic benefit to many cancer patients. Since the proteins encoded by these genes are challenging to target via conventional modalities, progress in new therapeutic agents has been slow despite decades of research. RNA interference technology has enabled the inhibition of previously-undruggable genetic targets at the mRNA level, and has advanced to clinical development for several indications. DCR-...
Source: Molecular Cancer Research - October 18, 2015 Category: Cancer & Oncology Authors: Abrams, M., Ganesh, S., Ying, B., Chopda, G., Saxena, U., Shah, A., Koser, M., Arvan, R., Chen, D., Shui, S., Diwanji, R., Zhou, W., Holmes, B., Kim, B., Yang, H., Patel, M., Cyr, W., Cyr, W., Pursell, N., Avitahl-Curtis, N., Dudek, H., Lai, C., Wang, W., Tags: Therapeutic Translation: Poster Presentations - Proffered Abstracts Source Type: research
Abstract PR03: Targeting multiple cell cycle regulatory points for the prevention of triple-negative breast cancer
Conclusions: These studies demonstrate that dinaciclib alone or the combination therapy of LG100268 and dinaciclib causes inhibition of premalignant cell growth and delayed ER-negative mammary tumorigenesis in SV40 Tag mice. While an additive effect of dinaciclib and LG100268 was observed in vitro, the in vivo combination therapy was not significantly more effective than dinaciclib treatment alone. Future studies should investigate different combinations of dosages of dinaciclib and LG100268 in vivo. These studies were supported by an NCI/NIH R25T grant (R25CA057730, BL) and Susan G. Komen for the Cure Promise grant (KG081...
Source: Cancer Prevention Research - October 2, 2015 Category: Cancer & Oncology Authors: Litzenburger, B. C., Uray, I. P., Hill, J., Zhang, J., Mazumdar, A., Brown, P. H. Tags: Combinatorial Approaches to Chemoprevention: Oral Presentations - Proffered Abstracts Source Type: research
Abstract A74: Differential Wnt signaling in African American and Caucasian women with triple-negative breast cancer
In the U.S., breast cancer (BC) incidences among African American (AA) and Caucasian (CA) women are similar, however, AA have a significantly higher mortality rate (20%). In addition, AA women often present with tumors at a younger age, with a higher grade/later stage, and are more likely to be diagnosed with the highly aggressive triple-negative breast cancer (TNBC) subtype. Although multiple factors may contribute to the observed health disparities in TNBC, it is essential that we identify the molecular characteristics and underlying biological differences between CA and AA TNBC. We initially conducted a gene expression ...
Source: Cancer Epidemiology Biomarkers and Prevention - September 30, 2015 Category: Cancer & Oncology Authors: Getz, J. E., Teoh, D. B., Nasser, S., Waibhav, T., Christophe, L. R., Yellapantula, V., Ahearn, M. E., Gomez, C. R., Jorda, M., Pegram, M. D., Carpten, J. D., Baumbach, L. L. Tags: Cancer Genetics/Gene Expression: Poster Presentations - Proffered Abstracts Source Type: research
