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Source: Cancer Research
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Total 807 results found since Jan 2013.
Abstract 663: Targeting autophagy potentiates the anti-tumoral action of crizotinib in ALK-positive anaplastic large cell lymphoma
ALK (Anaplastic Lymphoma Kinase)-positive Anaplastic Large Cell Lymphoma (ALCL) occurs predominantly in children and young adults. Their chemotherapeutic treatment leads to a 5-year overall survival amounted to 70-80%. The tumor relapses are often very aggressive and lethal and their underlying mechanisms are unknown. Therefore, there is still a need to improve current therapy. Crizotinib is the most advanced ALK tyrosine kinase inhibitor already used in clinics for ALK-associated lung cancers. However, mechanisms of escape to crizotinib have been reported in cell lines and patients submitted to continuous crizotinib treat...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: MITOU, G., FRENTZEL, J., LAMANT, L., MEGGETTO, F., ESPINOS, E., CODOGNO, P., BROUSSET, P., GIURIATO, S. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 680: Identification of GLI1 antagonists for breast cancer therapy
Conclusion: Several agents showed efficacy in in vitro BC cancer models demonstrating that GLI inhibitors may be a valid therapeutic approach for targeting GLI-dependent BC cancers.[1] Z. Thomas, W. Gibson, J. Sexton, K. Aird, S. Ingram, A. Aldrich, H. Lyerly, G. Devi, K. Williams, Targeting GLI1 expression in human inflammatory breast cancer cells enhances apoptosis and attenuates migration. British Journal of Cancer 104 (2011) 1575-1586.[2] K.P. Williams, J.L. Allensworth, S.M. Ingram, G.R. Smith, A.J. Aldrich, J. Z Sexton, G. R Devi, Quantitative high-throughput efficacy profiling of approved oncology drugs in inflammat...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Oladapo, H., Fleming, J. M., Addo, K., Tarpley, M., Ehe, B., Ingram, S., Sauer, S., Devi, G., Williams, K. P. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 694: Structure-function analysis of RPL18A, a putative binding target of rigosertib
Rigosertib (ON 01910.Na; RGS) is a clinical stage anticancer agent that causes spindle abnormalities and mitotic arrest in neoplastic cells. The drug inhibits PI3K and PLK1 signaling pathways, down regulates cyclin D1 expression and induces apoptosis. Previously, we reported identification of RPL18A (L18A), a protein from the large ribosomal subunit, as a putative binding target of RGS [Proc. AACR 2014, #4595]. Knock-down of L18A with siRNA caused apoptosis in cancer cell lines. Role of L18A in the function of the ribosome is not known. Goal of this study was to conduct structure-function analysis of L18A and create defici...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Oussenko, I. A., Gupta, Y. K., Vasquez-Del Carpio, R., Ramana-Reddy, M. V., Aggarwal, A. K., Reddy, E. P., Holland, J. F., Ohnuma, T. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 696: Comprehensive genomic analysis identifies frequent MET juxtamembrane domain deletions as an actionable genomic alteration in pulmonary sacromatoid carcinoma
Conclusions:Our study finds an unprecedently high frequency of exon 14 skipping MET mutations in pulmonary SC and suggests that MET activation might contribute to the mesenchymal differentiation and aggressive biology and defines MET inhibition as a promising novel therapeutic strategy for MET-mutated pulmonary SC.Citation Format: Xuewen Liu, Yuxia Jia, Yufeng Shen, Haiying Cheng, Sanjay Koul, Alain C. Borczuk, Balazs Halmos. Comprehensive genomic analysis identifies frequent MET juxtamembrane domain deletions as an actionable genomic alteration in pulmonary sacromatoid carcinoma. [abstract]. In: Proceedings of the 106th A...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Liu, X., Jia, Y., Shen, Y., Cheng, H., Koul, S., Borczuk, A. C., Halmos, B. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 700: Investigating KRAS synthetic lethal/co-dependency interactions using siRNA and CRISPR
No molecularly targeted therapy has yet been identified for KRAS mutant cancers. As oncogenic mutations reduce RAS enzymatic activity, classic small molecule approaches are ineffective, hence most work has focussed on drugging RAS-effector pathways. Multiple inhibitors of MEK, RAF and PI3K have been identified but toxicity issues and pathway adaptation have stymied their success against KRAS-driven cancers. An alternative approach is to exploit “non-oncogene addiction” by identifying targets with synthetic lethal or co-dependence interactions with KRAS.A number of siRNA and shRNA screens have identified targets that ex...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Scrace, S. F., Tsonou, E., Russell, P., Wickenden, J. A., Lawo, S., Scales, T. M., Wiggins, C. M., Moore, J. D. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 730: The role of ZEB1/ZEB2 and {beta}III-tubulin in mediating docetaxel-resistant prostate cancer
Docetaxel therapy is the gold standard treatment for advanced castrate-resistant prostate cancer (CRPC). However, patients either do not respond or develop resistance over time. Transcriptomic and proteomic analysis of docetaxel-resistant prostate cancer sub-lines developed by our group revealed multiple mechanisms of resistance in line with advanced disease, including over-expression of anti-apoptotic proteins and alterations of NF-KB activation. The sub-lines also demonstrated a coordinated loss and gain of epithelial and mesenchymal markers respectively; a process characteristic of Epithelial-Mesenchymal Transition (EMT...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Hanrahan, K., Prencipe, M., Bugler, J., Murphy, L., O'Neill, A., Watson, R. W. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 478: EWS/FLI1 transcription is modulated by the PI3K pathway via SP1 in Ewing sarcoma
Ewing sarcoma (ES) is the second most frequent bone cancer in childhood and it is characterized by the presence of the balanced t(11;22)(q24;q12) translocation in more than 85% of cases, generating a dysregulated transcription factor EWS/FLI1. ES belongs to small-round-blue-cell tumors and it is a very aggressive osteolytic cancer with early tendency for development of metastasis. Mostly it affects bones such as pelvis, femour and ribs but can also arise in soft tissues, mainly in adults. EWS/FLI1 is an essential oncogenic component of ES development which is necessary for tumor cell maintenance, through inappropriate regu...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Giorgi, C., Boro, A., Lopez-Garcia, L. A., Schaefer, B. W., Niggli, F. K. Tags: Tumor Biology Source Type: research
Abstract 479: Inhibition of the splicing of the EWS-FLI1 fusion transcript reverses EWS-FLI1 driven oncogenic expression in Ewing sarcoma
This study has implications for the treatment of ES through inhibition of proteins required for expression of the EWS-FLI1 transcript and identifies a candidate lead compound for further clinical development. Our findings may also open up strategies for treatment of other cancers driven by fusion oncogenes.Citation Format: Patrick J. Grohar, Suntae Kim, Sara Haddock, Guillermo Rangel Rivera, Matt Harlow, Nichole K. Maloney, Konrad Huppi, Kristen Gehlhaus, Magdalena Grandin, Carleen Klumpp-Thomas, Eugen Buehler, Lee J. Helman, Scott E. Martin, Natasha J. Caplen. Inhibition of the splicing of the EWS-FLI1 fusion transcript r...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Grohar, P. J., Kim, S., Haddock, S., Rangel Rivera, G., Harlow, M., Maloney, N. K., Huppi, K., Gehlhaus, K., Grandin, M., Klumpp-Thomas, C., Buehler, E., Helman, L. J., Martin, S. E., Caplen, N. J. Tags: Tumor Biology Source Type: research
Abstract 737: Clonal evolution of the HER2 L755S mutation as a mechanism of acquired HER-targeted therapy resistance
Conclusion: Acquired L/LT resistance in the two BT474 R lines is due to selection of HER2 L755S subclones present in parental cells. The higher HER2 L755S levels in BT474 parentals compared with other parentals, and detection of its subclonal presence in a pre-treatment HER2+ BC patient, suggest that sensitive mutation detection methods will be needed to identify patients with potentially actionable HER family mutations in primary tumor. Treating this patient group with an irreversible TKI like Afa may prevent resistance and improve clinical outcome of this subset of HER2+ BC.Citation Format: Xiaowei Xu, Agostina Nardone, ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Xu, X., Nardone, A., Hu, H., Qin, L., Nanda, S., Heiser, L., Wang, N., Covington, K., Chen, E., Renwick, A., Mitchell, T., Shea, M., Wang, T., De Angelis, C., Contreras, A., Gutierrez, C., Fuqua, S., Chamness, G., Shaw, C., Li, M., Wheeler, D., Hilsenbeck Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 487: Whole genome screen to identify genes targeting MYCN-driven embryonal tumors
MYCN is a driver of neuroblastoma (NB) tumorigenesis and is over-expressed in a number of tumors of embryonal origin, including rhabdomyosarcoma, medulloblastoma and diffuse intrinsic pontine gliomas. We sought to identify regulators of MYCN transcription by performing a whole genome screen (WGS) for regulators of MYCN promoter activity using a NB cell model. A plasmid containing the MYCN promoter (1.3kb upstream of MYCN TSS) fused to luciferase and stably integrated into the genome of NGP NB cells was the readout system. NGP-MYCNpluc, was selected based on MYCN luciferase activity inhibition by ATRA and HDAC inhibitors to...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Thiele, C. J., Liu, Z., Veschi, V., Buehler, E., Martin, S. Tags: Tumor Biology Source Type: research
Abstract 509: MicroRNA-140 suppresses the migration and invasion of colorectal cancer cell possibly through targeting Smad3
Conclusions miR-140 directly targets Smad3 in the post-transcriptional level. miR-140 suppresses the migrating and invasive potentials of CRC cell, possibly through down-regulating Smad3. The findings of this study suggest that miR-140 may have a unique potential as a possible biomarker candidate for tumor metastasis diagnosis and therapy.[Keywords] Colon neoplasms; microRNA-140; SMAD family member 3; Cell migration; Cell invasionCitation Format: Bo Song, Wenyue Zhao, Lianhong Li. MicroRNA-140 suppresses the migration and invasion of colorectal cancer cell possibly through targeting Smad3. [abstract]. In: Proceedings of th...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Song, B., Zhao, W., Li, L. Tags: Tumor Biology 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 522: Involvement of Zyxin in aggressiveness of human prostate cancer
In this study, Phospho-peptide in DU145 cells cultured in CM was analyzed using Liquid chromatography-tandem mass spectrometry (LC-MS/MS). Zyxin was identified as a CM-related phosphor-peptide. Zyxin is a conserved protein that has two major domains, an N-terminal half containing proline-rich sequences and a C-terminal LIM domain region. Its functions are involved in regulation of cell adhesion and motility. This protein also appears to have tumor suppressor activity with a few reports, however in dispute. We analyzed the involvement of Zyxin in behavior of DU145 cells. Functional analysis of Zyxin in cell migration, invas...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Yamamoto, K., Hori, Y., Seo, J., Hashimoto, S., Endo, Y., Nittami, T., Ito, Y., Ishiguro, H., Uemura, H., Watanabe, M. Tags: Tumor Biology Source Type: research
Abstract 568: Fibroblast growth factor receptors 2 is a novel therapeutic target in esophagogastric junction adenocarcinoma
In this study, we confirmed that FGFR2 can be a therapeutic target for EGJ adenocarcinoma.Methods: Utilizing 200 cases with EGJ adenocarcinoma (Siewert types I-III), FGFR2 copy number was assayed by Real-time PCR (using RNaseP as a referent), and FGFR2 expression was detected by immunohistochemistry. We examined whether FGFR2 amplification correlates with FGFR2 expression. The associations between FGFR2 expression and clinicopathological factors, and prognostic impact of FGFR2 expression were examined. We investigated the role of FGFR2 in cell proliferation, invasion, apoptosis and cell cycle, using OACM 5.1C (FGFR2 overex...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Tokunaga, R., Imamura, Y., Nakamura, K., Ishimoto, T., Iwagami, S., Kurashige, J., Izumi, D., Kosumi, K., Higashi, T., Taki, K., Hiyoshi, Y., Baba, Y., Sakamoto, Y., Miyamoto, Y., Yoshida, N., Hiroshi, S., Oki, E., Maehara, Y., Baba, H. Tags: Clinical Research (Excluding Clinical Trials) Source Type: research
Abstract 585: Elevated levels of CD24 in head and neck squamous carcinoma cells: A potential marker for unfavorable cisplatin response
Conclusion: Our work thus far, indicates that higher expression of CD24 in head and neck tumors result in a cisplatin resistant population that may well be the cause of unfavorable response to cisplatin treatment. Overall, CD24 has the potential to be a valuable predictor of response to cisplatin in HNSCC patients as well as a therapeutic target.Citation Format: Vishnu Modur. Elevated levels of CD24 in head and neck squamous carcinoma cells: A potential marker for unfavorable cisplatin response. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadel...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Modur, V. Tags: Clinical Research (Excluding Clinical Trials) Source Type: research
