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Source: Cancer Research

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Total 807 results found since Jan 2013.

Abstract 1388A: Assessment of the anti-angiogenic effect of VEGFR2 siRNA in HUVEC using the Lonza 4D-Nucleofecto system
Angiogenesis is a hallmark of most cancers, and is thus an attractive target for the treatment of cancer. One of the easiest screening and target validation strategies for anti-angiogenic target identification involves knocking down targets in Human Umbilical Vein Endothelial Cells (HUVEC) and assessing subsequent effects on tube formation in Corning's Matrigel product.The usage of small interfering RNA (siRNA) is one of the strategies to knock-down RNA, and thereby protein expression within cells. siRNA can be delivered within cells using either chemical transfection or electroporation-based strategies such as the one off...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Kokatam, S., Tiwari, K., Schroeder, J., Toell, A., Hussain, L., Kapoor, P. Tags: Tumor Biology Source Type: research

Abstract 1405: Novel biomarkers for gastric cancer stem cells utilizing comparative proteomics analysis
Conclusion: The eight proteins, RBBP6, GLG1, VPS13A, DCTPP1, HSPA9, HSPA4, ALDOA, and KRT18, utilizing comparative proteomics analysis, were perceived to be potential CSC markers of gastric cancer. Of the eight candidate proteins, RBBP6 was suggested to be a promising prognostic biomarker and a therapeutic target for gastric cancer.Citation Format: Masakazu Yashiro, Tamami Morisaki, Tsuyoshi Hasegawa, Anna Kakehashi, Haruhito Kinoshita, Tatsunari Fukuoka, Hiroaki Kasashima, Go Masuda, Katsunobu Sakurai, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Hideki Wanibuchi, Kosei Hirakawa. Novel biomarkers for gast...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Yashiro, M., Morisaki, T., Hasegawa, T., Kakehashi, A., Kinoshita, H., Fukuoka, T., Kasashima, H., Masuda, G., Sakurai, K., Kubo, N., Tanaka, H., Muguruma, K., Ohira, M., Wanibuchi, H., Hirakawa, K. Tags: Tumor Biology Source Type: research

Abstract 1419: Glypican-3 (GPC3) inhibits metastatic dissemination in a preclinical human breast cancer model
Although GPC3 has been linked to cancer, its role during mammary tumor progression is barely known. With the aim to develop a pre-clinical breast cancer model, we genetically modified MCF-7 (poorly-metastatic, GPC3 +) and MDA-MB231 (metastatic, GPC3 -) cell lines. GPC3 expression was blocked in MCF-7 by siRNA (generating MCF-7-shGPC3 sublines), while it was overexpressed in MDA-MB231 by viral infection (producing MDA-MB231-GPC3 sublines).First, we analyzed the in vivo tumor growth by s.c. inoculation of MCF-7 and MDA-MB231 engineered cells into nude mice. Silencing GPC3 stimulated tumorigenicity, while its overexpression i...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Castillo, L. F., Tascon, R., Bal de Kier Joffe, E., Peters, M. G. Tags: Tumor Biology Source Type: research

Abstract 1424: F-box protein fbxl5 nuclear retention by specific inhibitors of nuclear export induces snail ubiquitination leading to reversal of EMT
Background: FBXL5 belonging to SKP1-cullin 1-F-box protein E3 ligase complexes (F-BOX) been shown to promote snail nuclear ubiquitination thereby regulating snail induced epithelial-to-mesenchymal transition (EMT) processes. However, cancer associated enhancement in the nuclear exporter Exportin1 (Xpo1) expression results in nuclear expulsion of FBXL5 causing snail stability and EMT. Here we demonstrate that Xpo1 inhibition by specific inhibitors of nuclear export (SINEs) results in nuclear retention FBXL5, causing nuclear degradation of SNAIL leading to reversal of mesenchymal phenotype to epithelial in HMLE-SNAIL models....
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Muqbil, I., Aboukameel, A., Landesman, Y., Kauffman, M., Shacham, S., Mohammad, R. M., Azmi, A. S. Tags: Tumor Biology Source Type: research

Abstract 1427: Embigin is overexpressed in pancreatic ductal adenocarcinoma and regulates cell motility through epithelial to mesenchymal transition via the TGF-{beta} pathway
Embigin is a member of the immunoglobulin superfamily and encodes a transmembrane glycoprotein. Strong expression of Embigin has been observed in the mouse endoderm during early postimplantation embryogenesis and in the gut and visceral endoderm at the somite stage. There have been reports of Embigin involvement in neuromuscular junction formation and plasticity; however, the molecular functions of Embigin in other organs are unknown. Pancreatic cancer is an extremely aggressive malignancy, and it is necessary to understand the biology of pancreatic cancer to better detect and treat this disease. Our aim was to investigate...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Jung, D. E., Kim, J. M., Kim, C., Song, S. Y. Tags: Tumor Biology 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 1429: Contribution of membrane-bound carboxypeptidase M to tumor growth and metastasis by regulating epithelial mesenchymal transition in esophageal squamous carcinoma
In this study, we examined the properties of CPM for tumor growth and metastasis in human esophageal carcinoma cells. In order to investigate the expression of CPM on human tumor cells, we established the monoclonal antibody specific for human CPM and found the constitutive expression of CPM on various human carcinomas by flow cytometry and confocal laser microscopy. Treatment of cancer cells with EMT-mediated cytokines, including TGF-beta, IL-6 and OSM, increased CPM expression on their cell surface followed by enhancement of cell migration and change of cell shapes from epithelial to mesenchymal type. Silencing CPM expre...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Kudo, Y., Fukuda, J., Harigai, R., Kato, K. Tags: Tumor Biology Source Type: research

Abstract 1228: Identification of a novel p53 target regulating p53-induced apoptotic pathway
In response to various cellular stresses, p53 induces its target genes and suppresses tumor development. However, the anti-tumor function of p53 has not been fully elucidated. The purpose of our study is the identification and functional analysis of novel p53 downstream targets. We conducted cDNA microarray analysis by using Hct116p53+/+ and p53-/- cells treated with adriamycin and identified p53 inducible protein (p53IP) as a novel p53 downstream target. Induction of p53IP mRNA was confirmed by qRT-PCR. We also found that p53IP protein was increased only in Hct116p53+/+ cells by adriamycin treatment. The result of reporte...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Mori, J., Lo, P., Tanikawa, C., Nakamura, Y., Matsuda, K. Tags: Molecular and Cellular Biology Source Type: research

Abstract 1233: Impairment of TFF3 induces cellular apoptosis in prostate cancer cell lines and overexpression of TFF3 may be a prognostic biomarker in human prostate cancers
Background: Human trefoil factor 3(TFF3)/ Intestinal trefoil factor(ITF) is originally known well as an essential regulator for epithelial restitution in gastrointestinal tract and also suggested as a potential cancer marker in serum. Furthermore, the aberrant overexpression of TFF3 has been reported in various human cancers, majorly colorectal cancers, suggesting that TFF3 may play a critical role in tumor growth. However, its molecular signaling pathway remains unclear.Objective: To clarify whether TFF3 is related to survival/anti-apoptotic cell signaling pathways, and to determine that tff3 could be a molecular marker i...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Kim, S.-Y., Liu, J.-Y., Chung, Y.-J. Tags: Molecular and Cellular Biology Source Type: research

Abstract 1245: Peroxiredoxin induction in breast cancer
Cancer cells possess elevated levels of reactive oxygen species (ROS) that can enhance genomic instability and alter redox signaling. Aberrant antioxidant expression has also been recognized in many cancers, suggesting an adaptive response to the cancerous state. Breast cancers express significantly elevated levels of Peroxiredoxins (Prdxs), a family of thiol-specific antioxidant proteins involved in regulating cell growth and proliferation in many cell types. We previously reported overexpression of many Prdx proteins in the MCF-7 breast cancer line, as well as their importance in doxorubicin-resistance in this line. In t...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Buurma, V., Freeman, B., Adzenyah, A., Pettit, G., Heinen, F., Muhlbauer, J., Phelan, S. A. Tags: Molecular and Cellular Biology Source Type: research

Abstract 1246: c-Myc is critical for apoptosis in 4-hyroxynonenal-treated colorectal cancer cells
The transcription factor c-myc has an important role in the control of cell proliferation, differentiation and apoptosis. The dysregulation of c-myc activity is a feature of many cancers. Although it enhances proliferation, the overexpression of c-myc also sensitizes cells to a variety of pro-apoptotic stimuli. 4-hydroxynonenal (HNE) is a reactive lipid that is generated as a consequence of oxidative stress, and is found to be elevated in many solid lesions. HNE is known to promote apoptosis in various cancer cell types, including colorectal cancer cells. We therefore decided to investigate whether c-myc has a role in HNE-...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Wales, C. T., Gristock, R., So, N., Jacobs, A. T. Tags: Molecular and Cellular Biology Source Type: research

Abstract 1265: LAMP2 overexpression in the plasma membrane of breast cancer cells in response of chronic acidosis as a new imaging and therapeutic target
A combination of poor vasculature perfusion, hypoxia, and increased flux of carbons through fermentative glycolysis lead to extracellular acidosis in solid tumors; with extracellular pH values as low as 6.5. The proton concentration increases within the lumen due to diffusion limitations and increased production of acid from hypoxic-glycolytic cells, causing the interior of the lumen to become highly acidic. The glycolytic phenotype can become “hardwired” as Warburg proposed, leading to the continued generation of metabolic acids even in well-oxygenated conditions. This acidified habitat is constant and imparts a Darwi...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Damaghi, M., Sprung, R., Tafreshi, N., Estrella, V., Koomen, J., Morse, D., Gillies, R. Tags: Molecular and Cellular Biology Source Type: research

Abstract 1346: Immunotherapy against breast cancer based on Stat3 blockade
In this study our objectives were to study whether immunization with supernatants (SN) produced by Stat3-blocked cells induces an antitumor immune response and to explore the contribution of senescence phenotype in this response. For that purpose we used BC models of ErbB-2-positive, JIMT-1 and KPL-4 cells (human) and C4HD cells (murine), and of triple negative, MDA-MB231 cells (human) and 4T1 cell (murine). Knockdown of Stat3 with siRNA in these cells, induced senescence (assessed by acidic β-galactosidase staining). In human BC cells the senescent phenotype was accompanied by up-regulation of p21cip1 and downregulation ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: De Martino, M., Mercogliano, M. F., Tkach, M., Venturutti, L., Elizalde, P. V., Schillaci, R. Tags: Immunology Source Type: research

Abstract 1371: Systems biology analysis to identify biomarkers for lenvatinib in the preclinical cancer cell line panels
Objectives: Lenvatinib mesilate (lenvatinib) is the selective inhibitor of VEGFR1-3, and other proangiogenic and oncogenic pathway-related RTKs including fibroblast growth factor receptors (FGFR1-4), the platelet-derived growth factor receptor (PDGFR) α, KIT, and RET. Lenvatinib have been tested in several clinical trials, such as thyroid cancer and hepatocellular carcinoma in Ph3, but biomarkers to predict lenvatinib activity were not established. We performed a preclinical systems biology approach to identify biomarkers predictive of lenvatinib sensitivity in endometrial cell lines.Methods: We performed gene expression ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Dezso, Z., Ino, M., Minoshima, Y., Tohyama, O., Sugi, N. H., Agoulnik, S., Oda, Y., Funahashi, Y. Tags: Tumor Biology Source Type: research

Abstract 1379: IKK{beta} is a potential anti-angiogenic therapeutic target in KRAS-induced lung cancer
Activating mutations in KRAS are prevalent in cancer, but therapies targeted to oncogenic RAS have been ineffective to date. An alternative route for blocking RAS-driven oncogenic pathways is to target downstream effectors of RAS involved in promoting the oncogenic phenotype. One of the critical characteristics required for tumors to grow and progress is the ability of tumor cells to drive angiogenesis. Interestingly, oncogenic RAS promotes angiogenesis by upregulating the proangiogenic IL-8 cytokine, an NF-kB target gene; and recent studies have shown that oncogenic RAS also activates the NF-κB transcription factor pathw...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Lobo, T. C., Magalhaes, L., Cardeal, L., Giordano, R., Baldwin, A., Basseres, D. Tags: Tumor Biology Source Type: research