bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2248: The Y-box-binding protein 1 is associated with breast cancer progression and metastasis
Authors: Yu Yingnan , Yip George Wai-Cheong , Tan Puay-Hoon , Matsumoto Ken , Tsujimoto Masafumi , Bay Boon-Huat 
Published: February 2011

Abstract
The Y-box-binding protein 1 (YB-1) which belongs to the RNA- and DNA-binding protein family with a conserved cold-shock domain, is known to regulate transcription and translation. Extensive studies carried out on the multi-functional YB-1 protein have implicated its role in tumor growth and drug resistance. However, the association between YB-1 and breast cancer metastasis has not been fully investigated. To determine if YB-1 expression is correlated with breast cancer progression, we evaluated protein expression analysis in breast cancer tissue microarrays from the Singapore General Hospital by immunohistochemistry using an N-terminal YB-1 antibody and gene expression analysis in a TissueScan breast cancer tissue qPCR array (a rapid-scan cDNA panel of 48 breast cancer tissues representing breast cancer in different tumor stages) by real time RT-PCR. Next, we down-regulated the expression of the YB-1 protein in MDA-MB-231 breast cancer cells by si-RNA mediated silencing of the YB-1 gene and performed migration assays (using polycarbonate membranes of transwells separating the upper and lower chambers in 24-well plates) and invasion assays (using Matrigel-coated transwell chambers). The results show that 88.7% of breast cancer tissues were positively immunostained for the YB-1 protein and a higher YB-1 expression level was associated with axillary lymph node spread. YB-1 gene expression level in the breast cancer tissues was also higher in the advance stages of breast cancer as compared to the early stage of the tumor. In the in vitro experiments, the silencing efficiency of the YB-1 siRNA was around 90% and significant down-regulation of the YB-1 protein was verified by Western blot analysis and immunostaining of the MDA-MB-231 cells. Furthermore, siYB-1 mediated knockdown of YB-1 expression significantly reduced the migration ability and invasive potential of MDA-MB-231 cells as compared to the control group. Collectively, the data obtained from breast cancer tissues and in vitro experiments has provided evidence that YB-1 expression is associated with aggressive behavior in breast cancer. It would seem that YB-1 is a potential biomarker of metastasis in breast cancer and a promising molecular target in breast cancer therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2248.
Abstract 2249: Slug Expression is predictive marker of lymph node metastasis and prognosis in colorectal carcinoma
Authors: Toiyama Yuji , Yasuda Hiromi , Saigusa Susumu , Inoue Yasuhiro , Miki Chikao , Hori Hiroki , Kusunoki Masato 
Published: February 2011

Abstract
Purpose: Slug is a member of the snail family of transcription factors, plays a crucial role in the regulation of epithelisal-mesenchymal transition(EMT) by suppressing several epithelial markers. In this study, we investigated the clinical significance of Slug expression in colorectal cancer and identified the function of Slug gene in vitro.
Methods: Slug gene expression in surgically resected colorectal carcinoma of 184 patients were quantified by real-time quantative reverse transcription-PCR to assess the association between Slug expression and clinicopathologic factors and survival. To identify the function of Slug RNA interference (RNAi) was used to inactivate this gene in the colon cancer cell line SW480. Immunohistochemical analysis was performed to characterize the pattern of Slug expression in colorectal cancer.
Results: Slug expression in cancer tissue was significantly higher than that in normal tissue and significantly higher in patients with invasive tumor stage, lymphatic invasion, lymph node involvement, liver metastasis and advanced TNM stage. Increased Slug expression demonstrated a significantly associated with poor prognosis and independent prognostic factor not only in all colorectal cancer patients but also in patients with curative intent. Furthermore, increased Slug expression was an independent marker for predicting lymph node metastasis. Function of Slug gene investigated by RNAi have ability of cell proliferation and invasive ability to basal membrane in cancer cell line and this protein was mainly expressed in the invasive front of the tumor.
Conclusions: Slug is up-regulated in human colon cancer and seems to play a role in cancer invasion from primary lesion. Our present data might be suggested that quantification of slug gene in colorectal cancer could be useful marker to identify the patients with lymph node positive or with poor prognosis in curative intent.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2249.
Abstract 2251: Functional significance of prostate derived ETs factor in detection of highgrade prostate cancer
Authors: Koul Sweaty , Kumar Binod , Maroni Paul D. , Meacham randall B. , Koul Hari K. 
Published: February 2011

Abstract
INTRODUCTION AND OBJECTIVES: Conventional therapies produce a high rate of cure for patients with localized prostate cancer, but there is, at present, no effective treatment for intervention in metastatic prostate cancer. These facts underline the need to develop new approaches for early diagnosis of aggressive prostate cancer patients, and mechanism based anti-metastasis therapies that will improve the outlook for hormone-refractory prostate cancer. In this study we evaluated role of prostate-derived Ets factor (PDEF) in prostate cancer.
METHODS: PDEF and MMP9 expression was assayed by Immuno-histochemical methods in Prostate Cancer tissue microarrays. PDEF expression in cell lines was investigated using Western Blot analysis. We constructed cells with stable expression of PDEF using a retroviral vector or knocked down PDEF in cells using PDEF specific SiRNA. Cell migration, invasion and clonogenic activity were monitored using scratch assays, Matrigel invasion assays and growth in soft agar respectively.
RESULTS: We observed decrease of PDEF expression in prostate cancer cell lines correlated with increased aggressive phenotype, and complete loss of PDEF protein in metastatic prostate cancer cell lines. Loss of PDEF expression was confirmed in high Gleason Grade prostate cancer samples by immunohistochemical methods. Our results also demonstrated that PDEF down regulated MMP-9 promoter activity, suppressed MMP9 mRNA expression, and resulted in loss of MMP9 activity in prostate cancer cells. These results suggested that loss of PDEF might be associated with increased MMP9 expression and activity in aggressive prostate cancer. To confirm results we investigated MMP9 expression in clinical samples of prostate cancer. Results of these studies show increased MMP9 expression correlated with advanced Gleason grade. Taken together our results demonstrate that decreased PDEF expression and increased MMP-9 expression during the transition to aggressive prostate cancer.
CONCLUSIONS: These studies demonstrate for the first time negative regulation of MMP9 expression by PDEF, that PDEF expression was lost in aggressive prostate cancer and was inversely associated with MMP-9 expression in clinical samples of prostate cancer. Based on these exciting results we propose that loss of PDEF along with increased MMP9 expression should serve as novel markers for early detection of aggressive prostate cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2251.
Abstract 2256: Identifying the molecular signature of melanoma metastasis via a personalized quantitative proteomics approach
Authors: Eissa Azza , Cho Chan-Kyung J. , Diamandis Eleftherios P.D. 
Published: February 2011

Abstract
Melanoma metastasis is the primary cause of skin cancer deaths. Unfortunately, the biology of melanoma metastasis remains elusive, although several pathways, including epithelial-to-mesenchymal transition (EMT), have been suggested as underlying mechanisms of tumor progression and immunosuppression. No reliable single or multiple prognostic markers currently exist in the clinic to predict chances of melanoma metastasis, resistance to therapy, and recurrence after treatment. Microarrays have been the primary means for large-scale expression analyses of genes implicated in cancer progression. However, recent advents in high throughput mass spectrometry allow for investigating cancer development directly at the protein level. In this study, we applied a quantitative proteomics technique, Stable Isotope Labeling with Amino acids in Cell culture (SILAC), to compare the proteomes of primary and metastatic cancer cells derived from the same melanoma patient. We hypothesized that quantitative proteomic profiling of primary and metastatic cell lines from the same patient will: 1) reflect differences in their metastatic potential by identifying differentially expressed proteins and pathways, 2) uncover new protein candidates involved in cancer progression-related processes, such as EMT, and 3) yield promising prognostic biomarkers and therapuetic targets. A “bottom-up” proteomics approach and a two-dimensional (strong cation exchange followed by reversed-phase) LC-MS/MS strategy on an LTQ-Orbitrap were utilized to perform 3 different pair-wise comparisons of the expressions of extracellular and membrane-bound proteins in the conditioned media of melanoma cell lines from 3 different patients (3 primary cells labelled with ‘light’ arginine and lysine and their corresponding ‘heavy’- labelled metastatic counterparts). We identified over 1000 proteins from each pair of primary and metastatic cell conditioned media, several of which were previously reported as either up-regulated or down-regulated in melanoma, confirming the validity of our approach. In addition, we identified candidate proteins that have not been correlated previously with melanoma metastasis. Candidate proteins were selected based on the quantification ratio (&gt;2-fold change) between the two conditions and the consistency among triplicates within each condition. Many of the identified proteins may shed light on the molecular mechanisms underlying melanoma metastasis and may open novel areas for further research geared towards finding effective personalized prognostic and therapeutic approaches to manage this devastating cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2256.
Abstract 2260: Modulation of P-glycoprotein expression by a novel nutrient mixture in multidrug-resistant human uterine sarcoma cell line MES-SA/Dx5 but not in drug-sensitive MES-SA cell line
Authors: Roomi M. Waheed , Roomi Nusrath W. , Rath Matthias , Niedzwiecki Aleksandra 
Published: February 2011

Abstract
Introduction: We have characterized a nutrient mixture containing lysine, proline, ascorbic acid and green tea extract as a novel antineoplastic agent with a broad spectrum of antitumor activity against a number of cancer cell lines.
Objective: We investigated the effect of NM on modulation of P-glycoprotein (Pgp) in the drug-resistant human uterine sarcoma cell line MES-SA/Dx5 and compared it with the effect on drug-sensitive cell line MES-SA. In addition we also studied the effect of NM on MMP expression and Rhodamine-123 accumulation and efflux.
Material and Methods: Human drug insensitive uterine sarcoma cell line MES-SA/Dx5 and drug sensitive cell line MES-SA (ATCC) were grown in RPMI 1640 medium supplemented with fetal bovine serum and antibiotics. At near confluence, the cells were tested with NM at 0, 50, 100, 250, 500 and 1000 mcg/ml, in triplicate at each dose. Cell proliferation was evaluated by MTT assay, MMPs by gelatinase zymography, and Pgp expression by Western blot and immunodetection using FITC-conjugated antibody and rhodamine-123 (Rh-123) accumulation and efflux assays.
Results: NM exhibited antiproliferative effect on MES-SA/Dx5, by 20% at 50 and 100 mcg/ml and by 40% at 25, 500 and 1000 mcg/ml, whereas in MES-SA cell line, NM showed dose-response toxicity of 40% at 50 and 30% at 1000 mcg/ml. In both cell lines, zymography demonstrated a band corresponding to MMP-2 in normal cells and MMP-9 with PMA treatment. Both MMPs showed dose-response inhibition by NM. NM treatment also showed diminished dose-dependent Pgp expression by MES-SA/Dx5 cell line by Western blot and by immunodetection, whereas MES-SA did not exhibit Pgp by Western blot or by immunostaining. NM enhanced the accumulation and efflux of Pgp substrate Rh-123 in MES-SA/Dx5 uterine sarcoma cell line but not in the drug-sensitive cell line MES-SA.
Conclusions: In summary, this study demonstrated that Pgp is modulated by NM, which may be an attractive potential agent for therapeutic use in cancer treatment
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2260.
Abstract 2264: Lumican as a new target to develop molecularly-targeted drugs for pancreatic cancer
Authors: Yamamoto Tetsushi , Ishiwata Toshiyuki , Matsuda Yoko , Onda Munehiko , Yamahatsu Kazuya , Kawahara Kiyoko , Kawamoto Yoko , Uchida Eiji , Naito Zenya 
Published: February 2011

Abstract
Background: Lumican is a member of a small leucine-rich proteoglycan family and its overexpression has been reported in breast, colorectal, neuroendocrine cell, uterine cervical and pancreatic cancers. The expression of lumican in stromal tissues in breast cancer is associated with a high tumor grade, a low estrogen receptor expression level, and young age. Lumican expression in the cytoplasm in advanced colorectal cancer is correlated with a poor prognosis. Lumican expression was previously reported in pancreatic cancer, but the role of lumican in pancreatic cancer is still not well understood. In this study, we clarified the role of lumican in pancreatic cancer. Methods: Immunohistochemical analysis using anti-lumican antibody was performed in 65 pancreatic cancer patients. Lumican mRNA and protein were examined in pancreatic cancer cell lines (i.e. PANC-1, MIA PaCa-2, KLM-1) by real-time PCR and western blot. Lumican stably transfected PANC-1 cells were prepared. Then, the growth rates in vitro and in vivo were compared with mock cells. The lumican expression of PANC-1 cell was knocked down using siRNA. Then, the growth rate in vitro was compared with the control cell. Results: Immunohistochemically, lumican was localized in the cytoplasm of cancer cells in 33 of 65 patients (51%). Lumican expression in cancer cells did not correlated with clinicopathological factors. However, the survival rate of patients with lumican-positive cancer cells was significantly lower than those with lumican-negative cancer cells in the surgery-only group. Lumican mRNA and the protein were detected in all pancreatic cancer cell lines and PANC-1 cells expressed median level of lumican in the cancer cell lines examined. The growth rate of lumican-transfected PANC-1 cells was significantly higher than that of mock cells both in vitro and in vivo. Moreover, the growth rate of lumican-knocked down PANC-1 cell was significantly lower than that of the control cell. Conclusion: Lumican might regulate pancreatic cancer cell growth and become a new target to develop anti-cancer drug for pancreatic cancer patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2264.
Abstract 2266: Pioglitazone increases tumor progression and metastasis in an orthotopic mouse model of non-small cell lung cancer
Authors: Li Howard Y. , Sorenson Amber , Amin Jay , Middleton Deryck , Weiser-Evans Mary , Nemenoff Raphael A. 
Published: February 2011

Abstract
RATIONALE: Pathways regulating lung cancer metastasis are not well understood. As with most cancers, metastasis depends on critical interactions between tumor cells and the surrounding tumor microenvironment. Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. In humans, a retrospective study of patients treated with thiazolidinediones (TZDs), which are ligands for PPARγ, demonstrated a 33% reduction in risk of developing lung cancer. However, the effect of PPARγ activation on progression and metastasis of established lung tumors has not been clearly established. Our laboratory has developed a mouse model in which murine lung cancer cells directly injected into the lung of syngeneic mice develop secondary pulmonary tumors and metastasize to the mediastinal lymph nodes, the liver, and the brain. The goal of this study was to assess the effects of the TZD pioglitazone on lung cancer progression using this model.
METHODS: Murine non-small cell lung cancer cells stably transfected with firefly luciferase were implanted in the left lung of C57BL/6 wild-type mice. Mice were fed either chow impregnated with pioglitazone (0.05%) or control chow. At various time points following injection, animals were sacrificed and organs were assessed for tumors using ex vivo bioluminescence imaging. Primary tumors were measured with digital calipers, and the number of secondary tumors in the other lung lobes, liver and brain were quantified.
RESULTS: There was no significant difference in the size of the primary tumor between pioglitazone-treated and control mice at one week. However, primary tumors were significantly larger in pioglitazone-treated animals both 16 and 22 days after implantation of cancer cells. The differences in pulmonary metastases were even more impressive. At both 7 and 16 days, pioglitazone-treated mice showed 2-3 times more secondary pulmonary tumors compared to control animals. By day 25-30, 37.5% of mice fed pioglitazone-impregnated chow developed liver metastases, whereas only 17.6% of mice fed normal chow developed liver metastases. Brain metastases were only detected in mice fed chow impregnated with pioglitazone.
CONCLUSION: Treatment of mice with the PPARγ activator pioglitazone unexpectedly accelerates metastasis of established pulmonary tumors. Since selective activation of PPARγ in tumor cells has been shown to inhibit transformed growth and invasiveness, we hypothesize that the metastasis-promoting effects of pioglitazone are mediated through effects on the tumor microenvironment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2266.
Abstract 2267: Inhibition of extracellular sulfatase 2 as a possible mechanism to partially explain the anticancer activity of the nitrone OKN007
Authors: Chandru Hema K. , Towner Rheal A. , Floyd Robert A. 
Published: February 2011

Abstract
Sulfatase 2 (Sulf2) is an extracellular enzyme that has endosulfatase activity and catalyzes the removal of 6-O-sulfate groups on glucosamine from subregions of the glycosaminoglycans heparin sulfate. The action of Sulf2 has been shown to alter the binding of protein ligands to heparin which is involved in the binding of growth factors such as VEGF, FGF-2 and TGF to cellular receptors. Studies in experimental models have shown that fully active Sulf2 is important in the development of breast cancer and pancreatic cancer. Several tumors have been shown to be enriched in Sulf2 in comparison to the normal tissues where its level is either absent or present at very low levels. Sulf2 acts as a potentiator for the Wnt signaling and this is considered important in cancer stem cell growth.
We have shown that PBN (alpha-phenyl-tert-butylnitrone) has anti-cancer activity in three experimental models, A) the choline deficiency induced liver cancer model, B) the APCmin model of colon cancer and C) the rat C6 glioma model. We have also shown that 2,4-disulfonyl-alpha-phenyl-tert-butylnitrone (OKN007) has potent anti-cancer activity in the rat C6 glioma model. We considered based on the presence of phenyl sulfonyl groups that the nitrone 2,4-disulfonyl-alpha-phenyl-tert-butylnitrone (OKN007) may act as a competitive inhibitor of Sulf2.
We have found that Sulf2 is secreted into the media of Sulf2 transfected Hek-293 cells as well as several cancer cells, including from the highest to lower levels; MCF-7 breast cancer cells, Hek-293 cells, C6 glioma cells and BxPc-3 pancreatic cancer cells. Utilizing the concentrated media of these cells we have shown that Sulf2 has aryl sulfatase activity against the sulfate ester of 4-methylumbelliferone. We have shown that phenyl sulfonyl compounds suppress Sulf2 activity in an apparent competitive action. For instance, we found that the polysulfonated compound suramin potently suppressed the Sulf2 aryl sulfatase activity and that 2,4-disulfonylphenyl-tert-butylnitrone inhibited Sulf2 activity but less so than suramin. Utilizing concentrated extracellular media of several human cancer cell lines we have shown that Sulf2 activity is decreased by incubation with H2O2. Our results suggest that the anti-cancer activity of OKN007 may in part be explained by its inhibitory action against Sulf1. Research to test this concept is now underway.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2267.