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Source: Cancer Research

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Total 807 results found since Jan 2013.

Abstract 4233: Mef2C enhances 1,25-dihydroxyvitamin D3-induced monocytic differentiation of human myeloid leukemia cells by regulating C/EBP{beta} expression
Myogenic enhancer factors 2 (Mef2) are members of the family of MADS (MCM1-agamous-deficiens-serum response factor)-box transcription factors known to have multiple roles in morphogenesis of skeletal, cardiac and smooth muscle cells. Recently, Mef2C was found to be also involved in hematopoiesis. Bone marrow cells isolated from Mef2C knockout mice demonstrated decreased monocytic differentiation in response to cytokine stimulation, whereas constitutive expression of Mef2C promoted monopoiesis. The above findings led us to examine the role of Mef2C in 1,25-dihydroxyvitamin D3 (1,25D)-induced monocytic differentiation. Human...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Zheng, R., Wang, X., Studzinski, G. P. Tags: Molecular and Cellular Biology Source Type: research

Abstract 4455: Targeting a novel kras-integrin-linked kinase regulatory circuitry in pancreatic cancer
In this study, we have identified a novel KRAS-E2F1-ILK-hnRNP A1 regulatory circuitry that governs the expression of oncogenic KRAS. Integrin-linked kinase (ILK) is a serine/threonine kinase that mediates a diversity of cellular functions including cell survival, cell-matrix interactions, angiogenesis and also plays a role in epithelial to mesenchymal transition (EMT) in cancer cells. Dysregulation of ILK expression has been observed in several tumors including breast, ovary, melanoma, lung, prostate and pancreas and reported to be correlated with tumor progression, metastasis and chemoresistance to gemcitabine in pancreat...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Chu, P.-C., Yang, M.-C., Kulp, S. K., Chen, C.-S. Tags: Molecular and Cellular Biology Source Type: research

Abstract 4616: Chemo-sensitisation in epithelial ovarian cancer cell lines by targeting Ankyrin Repeat Domain 1 (ANKRD1)
In this study we showed that ANKRD1 levels decrease in response to cisplatin, in concert with induction of PARP cleavage and apoptosis in human ovarian cancer cell lines, COLO316, PEO14 and OAW42. We showed that decreasing ANKRD1 expression using siRNA (ON-TARGETplus Human ANKRD1 siRNA) increased cisplatin-induced apoptosis. Increased cisplatin sensitivity was associated with endoplasmic reticulum (ER) stress, evidenced by induction of GRP78, GADD153 and increased intracellular Ca2+ release. We have screened drug libraries (Prestwick library) for agents that sensitise ovarian cancer cell lines to platins, via an ANKRD1 rel...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Lei, Y., Henderson, B. R., Emmanuel, C., Harnett, P., Fazio, A. d. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 4618: Therapeutic targeting for sphingosine kinase 1 in epithelial ovarian cancer
This study was designed to investigate the therapeutic potential of SK1 inhibitor in epithelial ovarian carcinoma (EOC). Experimental design: The expression of SK1 protein was evaluated using immunohistochemistry in patients with EOC. EOC cell lines (A2780, SKOV3ip1, A2780-CP20, SKOV3-TR, ES2 and RMG2) were used in this study to test SK1 siRNA or inhibitors. We used two kinds of SK inhibitor including SK inhibitor (for both SK1 and 2) and FTY720 (specifically inhibiting SK1) to check cell proliferation, apoptosis, angiogenesis and invasion using MTT, FACS, ELISA and wound-healing assay, respectively. Furthermore, in vivo e...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Lee, J.-W., Ryu, J. Y., Jeon, H.-K., Park, Y.-A., Cho, Y.-J., Choi, J.-J., Lee, Y.-Y., Kim, T.-J., Choi, C. H., Kim, B.-G., Bae, D.-S. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 4870: Proteomics of phyllodes tumor revealed that decorin increase in the extracellular matrix by periostin deficiency decreased cancer cell motility and invasion
The ability of cancer cells to metastasize is dependent on the interactions of their cell surface molecules with microenvironment. However the tumor microenvironment, especially cancer-associated stroma, is poorly understood. To search for proteins which are present in the stroma, we investigated the phyllodes tumor, which contains breast stromal tissue, specific expression proteins compared with normal tissue by using iTRAQ-based quantitative proteomic approach. Periostin and versican core protein were up-regulated in phyllodes tumor. Decorin, mimecan, hemoglobin subunit alpha, hemoglobin subunit beta and ketatin, type1 c...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Ishiba, T., Nakanishi, A., Sato, T., Nakagawa, T., Nagahara, M., Oono, R., Uetake, H., Sugihara, K., Miki, Y. Tags: Tumor Biology Source Type: research

Abstract 4987: Stathmin regulates cell migration, invasion and transendothelial migration via RhoA activation in neuroblastoma
Neuroblastoma is an aggressive childhood cancer with dismal 5-year survival rates, primarily due to metastatic disease. The microtubule protein stathmin is highly expressed in neuroblastoma, and silencing stathmin decreases metastatic disease in a neuroblastoma orthotopic mouse model1. However, stathmin's role in the metastatic cascade and mechanism of action in this process is unknown. Our aim was to investigate the role of stathmin in neuroblastoma metastasis. Methods: To study the role of stathmin (STMN) in neuroblastoma, siRNA gene knockdown (using two individual siRNAs STMNsiRNA1 and STMNsiRNA2) or a non-targeting con...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Fife, C. M., Byrne, F. L., Sagnella, S. M., Davis, T. P., McCarroll, J. A., Kavallaris, M. Tags: Tumor Biology Source Type: research

Abstract 5124: Identification and characterization of novel regulators of TRAIL-induced apoptosis in breast cancer cells
TNF-related apoptosis inducing ligand (TRAIL) is a member of the tumor necrosis factor super family and can induce apoptotic cell death upon binding to its cognate receptors, TRAIL Receptor 1 (TRAIL-R1) and TRAIL Receptor 2 (TRAIL-R2). TRAIL has been found to induce selectively cell death in triple negative breast cancer (TNBC) cell lines (so called because the breast cancer cells lack estrogen and progesterone receptor expression and Her-2 amplification). Other subtypes of breast cancer are relatively resistant to TRAIL-induced apoptosis. However, the mechanisms that underlie the sensitivity of TNBCs to TRAIL-induced apop...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Dine, J., Garimella, S., Gehlhaus, K., Grandin, M., Caplen, N., Lipkowitz, S. Tags: Molecular and Cellular Biology Source Type: research

Abstract 5203: Long non-coding RNA H19 as a novel therapeutic target for pancreatic cancer
Long non-coding RNAs (lncRNAs), non-protein coding transcripts longer than 200 nucleotides, have been recently reported to play important roles in carcinogenesis and cancer metastasis through epigenetic regulation. In the present study, we examined the expression levels and roles of lncRNA in pancreatic cancer to elucidate whether lncRNA could be a novel candidate for pancreatic cancer therapy. First, we injected PANC-1 and PK-45H, pancreatic ductal adenocarcinoma cells into the spleens of NOD/Shi-scid, IL-2Rγnull (NOG) mice, and then established novel cell lines from liver and lung metastatic nodules. Microarray analysis...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Yoshimura, H., Matsuda, Y., Suzuki, T., Naito, Z., Ishiwata, T. Tags: Molecular and Cellular Biology Source Type: research

Abstract 5289: Role of notch3 in epithelial-to-mesenchymal transition of HCC
Conclusions: NICD3 inhibition significantly reduced the expression of markers of metastasis by increasing E-cadherin and suppressing transcription factors Snail, Slug, and MMPs. These observed change in the protein levels are occurred in the absence of NICD3 protein but the presence of NICD1 protein suggesting that NICD3 may play a role in metastasis. Therefore, targeting NICD3 may be potential strategy for treatment of HCC. Citation Format: Selvi Kunnimalaiyaan, T. Clark Gamblin, Muthusamy Kunnimalaiyaan. Role of notch3 in epithelial-to-mesenchymal transition of HCC. [abstract]. In: Proceedings of the 105th Annual Meeting...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Kunnimalaiyaan, S., Gamblin, T. C., Kunnimalaiyaan, M. Tags: Molecular and Cellular Biology Source Type: research

Abstract 5449A: PI3K and MEK inhibition in intracranial triple negative breast cancer: Efficacy of BKM120 and AZD6244 in preclinical mouse models
Conclusions: BKM120 and AZD6244 both improved survival in an IC TNBC SUM149 mouse model, with single agent AZD6244 being most efficacious. The siRNA screens indicate that combined treatment with BKM120 and AZD6244 should be synthetically lethal, suggesting that combination therapy may have underperformed due to toxicity. Ongoing in vitro and in vivo studies (including dosing schedules) will further characterize the effects of these drugs in intracranial TNBC. Citation Format: Amanda E.D. Van Swearingen, Marni B. Siegel, Ryan Bash, Brian Golitz, Charlene Santos, David Darr, Joel Parker, Gary L. Johnson, C. Ryan Miller, Care...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Swearingen, A. E. D. V., Siegel, M. B., Bash, R., Golitz, B., Santos, C., Darr, D., Parker, J., Johnson, G. L., Miller, C. R., Anders, C. K. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 5455: Resistance to a MEK inhibitor (AZD6244): Its association with increased expression of transcription factor 4
The important role of Ras/Raf/MEK/ERK pathway in carcinogenesis has led to clinical development of MEK inhibitors for treatment of various cancers. Although recent studies have demonstrated impressive antitumor activities of the agents, many tumors show intrinsic and acquired resistance to MEK inhibitors. We tried to find biomarkers that were associated with intrinsic or acquired resistance to a MEK inhibitor (AZD6244) by public microarray data acquisition and development of AZD6244-resistance cell lines. First, we analyzed a set of genome-wide gene expression profiling data from 6 sensitive and 6 resistant cell lines of v...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Goo, B.-K., Hur, E.-H., Choi, Y., Kim, S.-D., Hwang, J. J., Kim, C.-S., Bae, K. S., Choi, J., Cho, S. Y., Yang, S.-H., Lee, J.-H. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 5469: Trastuzumab resistant HER2+ breast cancer cells retain sensitivity to poly (ADP-ribose) polymerase (PARP) inhibition
Conclusions: HER2+ breast cancer cells resistant to trastuzumab continue to be sensitive to PARP inhibition through attenuation of the NF-κB signaling pathway. These results support the use of PARPi as part of a therapeutic strategy for patients with HER2+ breast cancer. Citation Format: Monica E. Wielgos, Tiffiny Cooper, Andres Forero, James A. Bonner, Francisco J. Esteva, C K. Osborne, Rachel Schiff, Albert F. LoBuglio, Eddy S. Yang. Trastuzumab resistant HER2+ breast cancer cells retain sensitivity to poly (ADP-ribose) polymerase (PARP) inhibition. [abstract]. In: Proceedings of the 105th Annual Meeting of the American...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Wielgos, M. E., Cooper, T., Forero, A., Bonner, J. A., Esteva, F. J., Osborne, C. K., Schiff, R., LoBuglio, A. F., Yang, E. S. Tags: Experimental and Molecular Therapeutics Source Type: research

Combinations of Topoisomerase I and ATR Inhibitors
Camptothecin and its derivatives, topotecan and irinotecan, are specific topoisomerase I (Top1) inhibitors and potent anticancer drugs killing cancer cells by producing replication-associated DNA double-strand breaks, and the indenoisoquinoline LMP-400 (indotecan) is a novel Top1 inhibitor in clinical trial. To develop novel drug combinations, we conducted a synthetic lethal siRNA screen using a library that targets nearly 7,000 human genes. Depletion of ATR, the main transducer of replication stress, came as a top candidate gene for camptothecin synthetic lethality. Validation studies using ATR siRNA and the ATR inhibitor...
Source: Cancer Research - November 30, 2014 Category: Cancer & Oncology Authors: Josse, R., Martin, S. E., Guha, R., Ormanoglu, P., Pfister, T. D., Reaper, P. M., Barnes, C. S., Jones, J., Charlton, P., Pollard, J. R., Morris, J., Doroshow, J. H., Pommier, Y. Tags: Therapeutics, Targets, and Chemical Biology Source Type: research

In Vivo Silencing of {beta}3 Integrin Inhibits TNBC Metastasis
Metastatic breast cancer is the second leading cause of cancer-related deaths among women. Triple-negative breast cancer (TNBC) is a highly aggressive subcategory of breast cancer and currently lacks well-defined molecular targets for effective targeted therapies. Disease relapse, metastasis, and drug resistance render standard chemotherapy ineffective in the treatment of TNBC. Because previous studies coupled β3 integrin (ITGB3) to epithelial–mesenchymal transition (EMT) and metastasis, we exploited β3 integrin as a therapeutic target to treat TNBC by delivering β3 integrin siRNA via lipid ECO-based nanoparticles (EC...
Source: Cancer Research - May 31, 2015 Category: Cancer & Oncology Authors: Parvani, J. G., Gujrati, M. D., Mack, M. A., Schiemann, W. P., Lu, Z.-R. Tags: Therapeutics, Targets, and Chemical Biology Source Type: research

Abstract B19: Redox factor 1 (Ref-1) signaling in the interaction between pancreatic tumor cells and cancer-associated fibroblasts
The objective of this work is to determine the outcome of inhibiting Ref-1 in CAFs and the effects of that inhibition on proliferation and migration in PDAC. The central hypothesis of the proposed work is that Ref-1 redox activity plays a critical role in the signaling within the TME between tumor and CAFs. We are using several innovative methods to probe the tumor-CAF interaction including: 1) co-culture 2D and 3D models; 2) genetic approach via redox inactive-Ref-1 constructs and siRNA to Ref-1; 3) pharmacologic approach via a well-established small molecule inhibitor of Ref-1 redox activity, E3330; 4) quantitation of Re...
Source: Cancer Research - June 30, 2015 Category: Cancer & Oncology Authors: Fishel, M. L., Cheng, H., Korc, M., Kelley, M. R. Tags: Inflammation/Stroma Source Type: research