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Total 151 results found since Jan 2013.

Abstract A83: Lentiviral shRNA-mediated knockdown of eosinophilic Galectin-10/Charcot-Leyden crystals: A novel approach to cancer immunotherapy
Conclusion: The creation of galectin-10 knockdown eosinophils provides a useful model for investigating eosinophilic galectin-10's ability to modulate T cell access and homing to tumors, and a putative role, similar to Treg galectin-10, in regulating tumoral T lymphocytic proliferation can certainly be envisioned. The consideration of galectin-10 knockdown eosinophils as a singular approach to cancer immunotherapy, or in combination with other anti-cancer therapies such as adoptive T cell therapies, or therapeutic cancer vaccines, is intriguing.Note: This abstract was not presented at the conference.Citation Format: Christ...
Source: Cancer Epidemiology Biomarkers and Prevention - September 30, 2015 Category: Cancer & Oncology Authors: Clarke, C. A., Lee, C. M., Laniyan, I., Furbert-Harris, P. Tags: Other Topics in Cell, Molecular, and Tumor Biology: 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 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 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 LB-B02: Acquisition of stem cell-like properties accompanying with Src family kinase/Focal adhesion kinase activation contributes to acquired resistance to afatinib in lung cancer cells
Conclusions] Together, our present study presents that increase of cancer stem like cells and SFK/FAK activation could be a mechanism responsible for acquired resistance to afatinib. We would further discuss the association of ALDH1 expression and SFK/FAK activation with afatinib resistance in lung cancer.Citation Format: Yuichi Murakami, Kahori Sonoda, Koichi Azuma, Kosuke Watari, Michihiko Kuwano, Mayumi Ono. Acquisition of stem cell-like properties accompanying with Src family kinase/Focal adhesion kinase activation contributes to acquired resistance to afatinib in lung cancer cells. [abstract]. In: Proceedings of the A...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Murakami, Y., Sonoda, K., Azuma, K., Watari, K., Kuwano, M., Ono, M. Tags: Drug Resistance and Modifiers: Poster Presentations - Proffered Abstracts Source Type: research

Abstract C5: FLIP protein-protein interaction inhibitors enhance sensitivity of colorectal cancer cells to chemotherapy and TRAIL
ConclusionWe have developed inhibitors of FLIP that decrease its recruitment to the TRAIL-R2 DISC and increase TRAIL-induced caspase activation and apoptosis. Moreover, these inhibitors synergise with 5-Fluorouracil, oxaliplatin and SN38, suggesting that this novel class of agents has therapeutic potential in CRC when used in conjunction with standard-of-care chemotherapeutic agents.AcknowledgementsThis work was supported by a Seeding Drug Discovery award from the Wellcome Trust (reference: 099470).Citation Format: Jennifer P. Fox, Joanna Majkut, Catherine Higgins, Zsuzsanna Nemeth, Adnan Malik, Christopher J. Scott, Peter...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Fox, J. P., Majkut, J., Higgins, C., Nemeth, Z., Malik, A., Scott, C. J., Blurton, P., Boffey, R. J., Perrior, T. R., Harrison, T., Longley, D. B. Tags: Apoptosis, Necrosis, and Autophagy: Poster Presentations - Proffered Abstracts Source Type: research

Abstract LB-A12: New target for cancer metabolism : Steroid Sulfatase
In conclusion, STS and the major product DHEA may regulate aerobic glycolysis via HIF1α induction and c-Myc related PKM2 alternative splicing.Citation Format: sangyun shin, Yeo-Jung Kwon, Dong-Jin Ye, Hyoung-Seok Baek, Young-Jin Chun. New target for cancer metabolism : Steroid Sulfatase. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr LB-A12.
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: shin, s., Kwon, Y.-J., Ye, D.-J., Baek, H.-S., Chun, Y.-J. Tags: Signal Transduction Modulators: Poster Presentations - Proffered Abstracts Source Type: research

Abstract LB-A13: Cellular characterization of the selective inhibition of UBA5 by organometallic, adenosine-based inhibitors
Cells that undergo higher protein turnover, such as pancreatic secretory cells and cancerous cells, have the propensity to undergo endoplasmic reticulum (ER) stress. If left uncorrected, ER stress can result in the initiation of apoptosis. To avoid these fates, cells have developed support systems to counteract the apoptotic effects of ER stress, such as conjugation of certain stress-associated proteins with the ubiquitin-fold modifier 1 (UFM1) ubiquitin-like protein. Our research has recently focused on the discovery and in vitro validation of the first selective inhibitor of the UFM1 pathway, 5C-Z, which selectively targ...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: da Silva, S. R., Geletu, M., Javed, F., Paiva, S.-L., Lewis, A. M., Li, H., Gunning, P. T. Tags: Target Identification and Validation: Poster Presentations - Proffered Abstracts Source Type: research

Abstract LB-C22: Acquired resistance to the cMET inhibitor savolitinib in lung cancer models through EGFR/mTOR/MYC deregulation and adoption of PIM signaling
Lung cancer is the most common cause of cancer death globally with a significant, unmet need for more efficacious treatments. Aberrant receptor tyrosine kinase (RTK) signaling is a well-documented driver of disease onset and progression in multiple cancer types, including non-small cell lung cancer (NSCLC), where the cMET RTK contributes to tumor progression, maintenance and resistance to targeted therapies. Here, we explore the therapeutic potential of the potent and selective cMET inhibitor savolitinib (volitinib, AZD6094, HMPL-504) in NSCLC and begin to elucidate mechanisms of acquired savolitinib resistance in preclini...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Henry, R. E., Barry, E. R., Ladd, B., Markovets, A., Beran, G. J., Ren, Y., Zhou, F., Castriotta, L., Adam, A., Qing, W., Su, W., Clark, E., D'Cruz, C. M., Schuller, A. Tags: Drug Resistance and Modifiers: Poster Presentations - Proffered Abstracts Source Type: research

Abstract C25: Targeting cancer stem cells using ALDH-dependent 5-nitrofuran pro-drugs
We hypothesise that cancer stem cells with high aldehyde dehydrogenase (ALDHhigh) activity present a new therapeutic target and will be selectively sensitive to 5-nitrofuran pro-drugs.Cancers are heterogeneous and contain subpopulations of ALDHhigh cells with tumour initiating potential. ALDH enzymes metabolize toxic aldehydes, and are highly expressed in somatic and cancer stem cells (CSCs), although their function in stem cells is not fully understood. In a small molecule screen coupled with target ID, we recently discovered that clinically active 5-nitrofurans (5-NFNs) are substrates of ALDH2 (Zhou et al., 2012). 5-NFNs...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Crispin, R., Spockeli, N., Brunton, V., Carragher, N., Gourley, C., Houston, D., Unciti-Broceta, A., Patton, E. E. Tags: Cancer Stem Cells: Poster Presentations - Proffered Abstracts Source Type: research

Abstract C26: Development of selective MELK kinase inhibitors for breast cancer treatment
In this study, we are reporting development of a series of selective MELK kinase inhibitors. Synthesized compounds exert excellent selectivity and potency in MELK inhibition in a low nanomolar range. Therapeutic effect of the compounds was investigated in the panel of breast cancer cell lines with different genetic background as well as with different MELK kinase levels; it was shown that for some cell lines compounds induced cell death with nanomolar ED50 values. The compound's effect on the proliferation and in the colony formation assay was also investigated. Taken altogether, the presented data supports our rationale o...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Kowalczyk, P., Węgrzyn, P., Prokopowicz, M., Knop, M., Mazur, K., Dziedzic, K., Gluza, K., Knop, M., Dziedzic, K., Mazur, K., Radzimierski, A., Commandeur, C., Zawadzka, M., Bloudoff, K., Vaillancourt, F., Larsen, N., Wang, J., Reynolds, D., Ito, D Tags: Cancer Stem Cells: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A28: NFATC3-PLA2G15 fusion transcript identified by RNA-sequencing promotes tumor progression in colorectal cancer cells
In order to identify novel fusion transcripts in colorectal cancer, we carried out paired-end RNA sequencing in 28 human colorectal cancer cell lines. Fusion transcript candidates were identified using ChimeraScan and FusionMap tools. We obtained 1380 candidates having 4 or more read counts and spanning reads. Among the candidates, we selected 27 candidates for validation which harbors genes related to the Wnt signaling pathway or kinases according to KEGG or DAVID. After the targeted gene filtering step, validation using RT-PCR with fusion specific primers finally resulted in 2 intra- and 1 inter-fusion transcripts. Intra...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Jang, J., Kim, H., Lee, S., Lee, D., Lim, Y., Han, S., Kim, T. Tags: Biomarkers: Poster Presentations - Proffered Abstracts Source Type: research

Abstract A65: A novel regulatory mechanism involving Ras-mediated activation of the zinc-finger transcription factor, SAF-1/MAZ induces EGFR/HER1 expression in breast cancer cells
Tumor microenvironment (TME) plays a critical role in tumor growth, invasion and metastasis. In TME, epidermal growth factor receptor (EGFR) family members, including HER1, HER2, HER3 and HER4, are involved in determining aggressive growth of breast cancer due to their ability to transduce the growth promoting functions of growth factors. This activity is potentiated by the over-expression of these receptor molecules in cancer cells. To reduce the activity of EGFR molecules, various inhibitors have been developed. EGFR/HER1 tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, show antitumor activity but these drugs ...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Ray, A., Havis, B., Ray, B. Tags: EGFR / Her2: Poster Presentations - Proffered Abstracts Source Type: research