bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1727: Interleukin-6 and intracrine androgens in prostate cancer cells
Authors: Chun Yae Yeon , Nadiminty Nagalakshmi , Lou Wei , Yang Joy , Evans Christopher P. , Kung Hsing-Jien , Gao Allen C. 
Published: February 2011

Abstract
INTRODUCTION AND OBJECTIVES: The standard systemic treatment for prostate cancer patients is androgen deprivation therapy. Although serum testosterone concentrations were significantly reduced after androgen deprivation therapy, levels of intraprostatic androgens are reproducibly measured at concentrations sufficient to activate androgen receptor (AR) and stimulate tumor growth, suggesting that prostate cancer cells may survive androgen deprivation therapies by increasing intracrine androgen synthesis within the prostate. However, factors that regulate de novo intracrine androgen synthesis have not been identified. Interleukin-6 (IL-6) has been implicated in the modulation of AR activation and growth and differentiation in prostate cancer. In this study, we investigate whether IL-6 regulates intraprostatic androgen synthesis in prostate cancer cells.
METHODS: Quantitative reverse transcription-PCR and western blot were performed to detect expression levels of steroidogenic enzymes. AKR1C3 promoter reporter was constructed and analyzed for IL-6-mediated AKR1C3 transcriptional activity. IL-6-mediated signaling was knocked down using siRNAs specific to IL-6R and gp130 and the effect on AKR1C3 expression was examined. To measure intraprostatic androgen levels, IL-6 overexpressing LNCaP-IL6+ cells were inoculated orthotopically into the prostate of castrated male nude mice and generated tumors. Intraprostatic androgen levels were measured by an enzyme immunoassay (Testosterone EIA kit) based on the competition between testosterone and a testosterone-acetylcholinesterase (AChE) conjugate (testosterone tracer) for a limited amount of testosterone in the sample.
RESULTS: We found that IL-6 increases the expression of genes encoding many steroidogenic enzymes including HSD3B2 and AKR1C3 involved in androgen biosynthesis. Down regulation of IL-6 receptor and gp130 expression using specific siRNA abolished IL-6 mediated AKR1C3 expression, suggesting that IL-6 signaling is responsible for AKR1C3 expression. IL-6 increases AKR1C3 promoter activity, indicating that the increase in IL-6-mediated AKR1C3 expression is in part at the transcriptional level. Treatment of IL-6 increased testosterone level in LNCaP cells. The tumor testosterone levels were detected at 378 pg/g in tumors generated from IL-6 overexpressing LNCaP-IL6+ cells inoculated orthotopically into the prostates of castrated male nude mice.
CONCLUSIONS: These results suggest that IL-6 increases levels of intracrine androgens through enhanced expression of genes mediating androgen metabolism in prostate cancer cells during androgen deprivation 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 1727.
Abstract 1729: Cytoplasmic expression of survivin is an independent predictor of poor prognosis in patients with salivary gland cancer
Authors: Klussmann Jens P. , Stenner Markus , Weinell Antje , Ponert Tobias , Hardt Aline , Hahn Moritz , Preuss Simon , Speel Ernst J. 
Published: February 2011

Abstract
Background: The expression of the inhibitor of apoptosis protein survivin is shown to be a significant prognostic indicator in various human cancers. Its role in cancer of the major salivary glands remains unclear.
Methods: We analysed the survivin expression in 171 patients with malignant parotid gland cancer (12 different histological subtypes) by means of immunohistochemistry. The experimental findings were correlated with clinicopathological and survival parameters. The mean follow-up time was 42 months.
Results: There was no significant correlation of cytoplasmic survivin expression levels with the patients’ clinicopathological characteristics. A strong cytoplasmic expression of survivin was found in 25% of the examined tumors. High cytoplasmic survivin expression was an independent prognostic indicator for a significant poorer 5-year disease-free survival rate (31% versus 67%, p&lt;0.0005) and overall survival (45% versus 62%, p=0.048). In the multivariate analysis survivn expression and distant metastasis were significant predictors for patient outcome (p=0.001, p&lt;0.0005).
Conclusions: The correlation between cytoplasmic survivin expression and survival probabilities of salivary gland malignancies might make this an effective tool in patient follow-up, prognosis and targeted therapy in future.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
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 1729.
Abstract 174: Characterization of methylation-controlled DnaJD1 in Hep3B hepatoma cell line
Authors: Lai Yi-Wen , Tsai Meng-Feng , Chen Chuan-Mu 
Published: February 2011

Abstract
The development of hepatocllular carcinoma (HCC) is a multistep process with accumulation of genetic and epigenetic alternations in regulatory genes, leading to activation of oncogenes and inactivation of tumor suppressor genes. For genome-wide DNA methylation study, we used homemade MCGI (mouse CpG islands) microarray to identify many genes that were hypermethylation in the liver tumor tissues of HBx-overexpressd transgenic mice. These selected hypermethylation genes were also confirmed in human hepatocellular carcinoma cell (HCC) lines. In this study, we focused on a methylation-controlled DNAJ family (MCJ) gene, DnaJD1. It has been observed highly frequent DnaJD1 gene methylation and silencing in ovarian cancer, and associated with increased resistance to chemotherapeutic. The DnaJD1 was found hypermethylation in the promoter region and followed reduced mRNA expression in Hep3B hepatoma cells, which contain HBV genome. After treated by 5-aza-2’-deoxycytidine (DAC) in Hep3B cells, the methylation level of DnaJD1 could be reduced and mRNA re-expressed. We over-expressed DnaJD1 in Hep3B cells to study the physiologic effects of DnaJD1 in cell proliferation, cell migration, and invasion ability in vitro. The tumorgenesis in xenotransplanted nude mice were also examined. Data suggested that DnaJD1 re-expressed in Hep3B cells that could affect the cell morphology and lost cell contact insensitive. In these results, we concluded that DnaJD1 could be the one of main role of HCC progression.
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 174.
Abstract 1740: Over-expression of gelsolin protein in human cervical carcinoma associate with cell migration in vitro and recurrence-free survival in vivo
Authors: Wu Tzu-I , Liao Chia-Jung , Chang Ting-Chang , Lin Kwang Huei 
Published: February 2011

Abstract
Introduction:
The global yearly incidence and mortality of cervical cancer are 471,000 annual new cases and 233,000 deaths. Almost 80% cases occur in less developed countries, where it accounts for 15% of cancer in women. Cervical carcinoma ranks as the leading malignancy of genital tract malignancy in the developing countries. The recurrence indicate poor prognosis while the clinicopathological risk factors exist. In order to identify the potential molecular biomarker, proteomic analysis was performed and gesolin protein was selected.
Materials and Methods:
The plasma from normal healthy and cervical cancer, and tissue of cervical cancer plus adjacent normal tissue were collected for Western blotting assay, enzyme-linked immunosorbent assay (ELISA) or immunohistochemical stain (IHC). One hundred and twenty four patients with cervical cancers underwent surgical management were enrolled to evaluate IHC Histoscore of gesolin according to the multiply of immunoreactivity and involved percentage. The Transwell assay was conducted for cell migration analysis in HeLa cell line. The statistical analysis include independent t tests, Kaplan-Meier method using the log-rank test and the Cox proportional hazard model Receiver operating characteristics (ROC) curve analysis was used to determine cut-off points of the predictive parameters in univariate analysis.
Results:
The Western blot and ELISA assay both demonstrated the overexpression of plasma gelsolin in cases with cervical cancer rather than normal population, and with staged III/IV rather than stage I/II cases, In addition, gelsolin protein level also increased in conditional medium of cultured HeLa cell. Thus in vitro cell migration assay revealed decreased cell numbers while adding the gelsolin neutralizing antibody or small interference RNA compared with adding mock, non-specific antibody or Luciferase-shRNA. The other clinical parameters including stage, tumor size and lymph node status also put into consideration. The best cut-off point of gesolin Histosore to clarify the recurrence by ROC curve analysis is 115. The gelsolin Histosore (≤ 115 vs &gt; 115, P= 0.018) and lymph node metastasis (no vs yes, P&lt;0.001) play important prognostic role in recurrence by multivariate analysis.
Conclusion:
Overexpression of plasma and cytoplasmic gelsolin protein in cervical cancer promote cell migration by binding to actin cytoskeleton for rearrangement and cell motility. Among the clinicopathological parameters, the gelsolin overexpression and lymph node metastasis disclosed the recurrence-free survival impact by multivariate analysis.
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 1740.
Abstract 1741: Quantitative Real-Time PCR analysis of SPARCL1 and SPARC expression in colorectal cancer tissues
Authors: Georges Rania , Adwan Hassan , Schimanski Carl C. , Berger Martin R. 
Published: February 2011

Abstract
The SPARC family of proteins comprises 10 members, which share structural similarities in one or more protein domains. SPARC-like protein 1 (SPARCL1; also known as hevin) and SPARC are two important family members, which have been found to be involved in various tumors.
The relationship between these two molecules and colorectal cancer and its liver metastasis has not yet been fully studied and understood.
cDNA microarray was used to analyze the expression profiles of 22523 genes in CC531 rat colon adenocarcinoma cells. Briefly, 2 × 106 CC531 were injected into the portal vein of male Wag/Rij rats to grow in the liver. The tumor cells were then re-isolated from rat livers at different time points (after 3, 6, 9, 14 and 21 days). SPARCL 1 and SPARC were among the genes, which were up-regulated in the re-isolated metastatic cells as compared to control CC531 cells grown in vitro, especially on days 3 (two- and nine-fold for SPARCL1 and SPARC) and 6 (four- and eleven-fold for SPARCL1 and SPARC) following tumor implantation.
These results motivated us to analyze the expression of these two genes in 65 colorectal cancer tissues taken from patients in different UICC tumor stages (I, n=11; II, n=23; III, n=17; IV, n=14). A mixture of 10 mucosa samples was taken for comparison as normal control.
Quantitative real time-PCR results showed that SPARCL1 mRNA was significantly down-regulated in 44 samples (68%) with these levels being on average fourfold lower (0.24 ± 0.21) than those in normal mucosa. Normal levels were found in 18 samples (28%), and up-regulated levels were detected in only 3 samples (4%) with these levels being on average threefold higher than those in normal mucosa (3.0 ± 1.1). No correlation between this down- or up-regulation and tumor stage could be found.
In contrast to the results for SPARCL1, SPARC showed an almost consistent up-regulation in 60 of the tumor samples (92%). The average level of SPARC up-regulation was higher than that of SPARCL1 (6.5 fold higher than in normal mucosa). It is worth noting here that in those 21 samples, in which SPARCL1 mRNA was not down-regulated, SPARC expression was on average twofold higher (13fold higher than in normal mucosa) than the average expression level of all samples.
These results suggest a relationship between the two family members, but it is still not clear, whether they have opposing or complementary functions in the context of tumor initiation and progression. More studies should be performed to uncover the possible role of these proteins in the course of colorectal cancer and its liver metastasis.
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 1741.
Abstract 1745: Foxp3 expression and prognosis in early stage non-small cell lung cancer
Authors: Tao Hiroyuki 
Published: February 2011

Abstract
Foxp3 is a transcription factor that specifically characterizes regulatory T cells (Tregs). Increased number of tumor-infiltrating Tregs has been reported to be related to poor prognosis. Recently, it has been demonstrated that cancer cells also can express foxp3 and its expression level correlates with unfavorable prognosis in several types of malignant tumors. In non-small cell lung cancer (NSCLC), prognostic impact of foxp3 expressing cancer cells is not yet determined. We examined foxp3 expression in resected NSCLC and investigated its association with recurrence.
Methods: Foxp3 expressing cancer cells were detected by immunohistochemical staining from surgically removed specimens of the 59 patients with NSCLC that were pathologically diagnosed with Stage Ia or Ib. Prognostic value of foxp3 was evaluated by Kaplan-Meier analysis and log-rank test.
Results: Male/female: 41/19, p-stage Ia/Ib: 39/20, squamous(sq)/adeno(ad)/adenosquamous(adsq)/large and LCNEC: 16/36/3/4. Foxp3 positive cancer cells were observed in 17 of 59 patients (28.8%, male/female: 9/8, p-stage Ia/Ib: 10/7, sq/ad/adsq/large and LCNEC: 2/12/1/2). Of the 59 patients examined, recurrent tumors were seen in 12 within two years. Of the 12 patients who experienced recurrence, foxp3 expression in cancer cells were detected in 4 (33.3%). Of the 47 patients without relapse within five years, foxp3 positive tumor cells were observed in 13 (27.7%). Kaplan-Meier analysis and log-rank test showed no significant difference between the presence or absence of the foxp3 positive cancer cells both in overall and relapse free survival.
Conclusions: In our study, foxp3 expressing tumor cells were seen in 28.8% of the patients with node-negative NSCLC. Prognositic value of foxp3 positive cancer cells in p-Stage I NSCLC was not determined.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
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 1745.
Abstract 1746: Expression of the translation regulatory protein RBM3 is associated with a favourable prognosis in epithelial ovarian cancer
Authors: Åsa Ehlén , Brennan Donal J , Alvarado-Kristensson María , Nodin Björn , O'Connor Darran J , Uhlén Mathias , Pontén Fredrik , Jirström Karin 
Published: February 2011

Abstract
Background: RNA binding proteins are important regulators of gene expression involved in various post-transcriptional processes like mRNA stability and translation. We have recently demonstrated that high expression of RBM3 is associated with a favourable prognosis in breast cancer.
Aims and Methods: The aim of the present investigation was to examine the prognostic value of RBM3 in epithelial ovarian cancer (EOC). For this purpose, protein expression of RBM3 was examined by immunohistochemistry in tumour samples from 154 prospectively collected EOC cases (Cohort I). In addition, RBM3 gene expression was examined in an independent cohort with 282 EOC cases (Cohort II).
Results: No significant correlation was seen between RBM3 protein expression and any established prognostic clinicopathological parameters. However, survival analysis revealed a significant association between RBM3 nuclear expression and prolonged survival (HR=0.633, 95% CI=0.421-0.952, p=0.028) in cohort I. This association did not remain significant in multivariate analysis. In line with the IHC data, high RBM3 mRNA levels were associated with prolonged survival in Cohort II in both univariate (HR=0.671, 95% CI=0.504-0.894, p=0.006) and multivariate (HR=0.751, 95% CI=0.562-1.004, p=0.053) analysis.
Conclusion: In accordance with our previously studies of breast and colon cancer, high nuclear expression of RBM3 was associated with improved survival in patients with ovarian cancer. Further investigations are needed in order to understand the role of RBM3 in tumour progression and to confirm the utility of RBM3 as a prognostic biomarker in various cancer forms. We are currently investigating the role of RBM3 in cisplatin response in ovarian cancer cell lines.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
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 1746.
Abstract 1747: Helicobacter pylori-positive diffuse large b-cell lymphoma: a distinct clinicopathologic entity
Authors: Kuo Sung-Hsin , Lin Chung-Wu , Chen Li-Tzong , Hsu Ping-Ning , Hsu Chiun , Wu Ming-Shiang , Yeh Kun-Huei , Tzeng Yi-Shin , Yeh Pei -Yen , Wang Hsiu-Po , Cheng Ann-Lii 
Published: February 2011

Abstract
Background
We previously reported that H. pylori-positive gastric DLBCL, with or without evidence of MALT origin, may respond to H. pylori eradication therapy. In this study, we further investigated the clinicopathologic features of H. pylori-positive DLBCL without histologic evidence of MALT origin.
Methods
We reviewed consecutive cases of gastric DLBCL without histologic evidence of MALT origin. H. pylori infection was documented by histologic examination, a urease test or bacterial culture. H. pylori-positive cases were further examined for CagA protein expression.
Results
A group of 45 patients positive for H. pylori were not histomorphologically different from a group of 48 patients negative for H. pylori. However, patients with H. pylori infection had a better International Prognostic Index score (0-1, 70% vs 30%, P = ·001), a lower clinical stage (I-IIE1, 73% vs 33%, P &lt; [[Unable to Display Character: &#8729;]]001), a better tumor response to chemotherapy (complete response, 80% vs 50%, P = .01), and significantly better 5-year event-free survival (EFS) (71% vs 24%, P &lt; [[Unable to Display Character: &#8729;]]001) and overall survival (OS) (73% vs 30%, P &lt; [[Unable to Display Character: &#8729;]]001). CagA expression, as defined by more than 5% of tumor cells with CagA staining, was identified in 23 (68%) of 34 H. pylori-positive tumors. Compared with the 11 H. pylori-positive but CagA-negative cases, the 23 H. pylori-positive, CagA-positive cases were associated with significantly better 5-year EFS (73% vs 15%, P = [[Unable to Display Character: &#8729;]]002) and OS (91% vs 27%, P = [[Unable to Display Character: &#8729;]]001).
Conclusion
H. pylori-positive gastric DLBCL, particularly with CagA expression in tumor cells, appears to be a distinct tumor entity, sharing some key clinicopathologic features with H. pylori-associated gastric MALT lymphoma.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
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 1747.
Abstract 175: Lack of rDNA promoter hypomethylation in clinical prostate cancer specimens and cell lines
Authors: Uemura Motohide , Zheng Qizhi , Nelson William G. , Yegnasubramanian Srinivasan , De Marzo Angelo M. 
Published: February 2011

Abstract
INTRODUCTION
Alterations in the structure of nucleoli are hallmarks of prostate cancer cells. However, the molecular mechanisms that result in enlarged nucleoli in prostate cancer are unclear. The nucleolus is formed around tandem repeats (n=∼400) of the ribosomal RNA genes (18S, 5.8S and 28S) each of which contains an upstream promoter region. Only a limited number of repeat units are activated at any one time, and the inactive silent repeat units are characterized by dense methylation of the CpG island of the upstream promoter. While a previous study in liver cancer indicated that tumor cells contained hypomethylated CpG islands in the rDNA promoter, there are no prior studies in prostate cancer. Since MYC is overexpressed in most human PIN and prostate cancers, can affect nucleolar structure and activates rRNA transcription, we also addressed whether MYC levels affect rDNA promoter methylation.
METHODS
Genomic DNA was extracted from clinical samples of ten fresh frozen matched pairs of tumor and normal tissues obtained from radical prostatectomies, as well as, from 7 prostate cancer cell lines. Isolated DNA was subjected to sodium bisulfite sequencing of a region of the rDNA promoter, as well as, real-time methylation specific PCR. The functional role of MYC was explored by siRNA mediated knockdown in cell lines.
RESULTS
Most prostate cancer cell lines showed two roughly equal populations of the rDNA promoter region repeat units consisting of those that were densely methylated and those that were largely unmethylated. All clinical specimens were similar to the cell lines showing 2 populations with no changes in cancer compared to normal. After MYC knockdown in PC3 cells, there was an unexpected marked reduction in methylation of the rDNA promoter, despite decreased rRNA transcription. Chromatin immunoprecipitation (ChIP) followed by bisulfite sequencing revealed that MYC was bound nearly exclusively to the fully unmethylated promoters.
CONCLUSIONS
Clinical prostate cancer specimens, as well as most prostate cancer cell lines, do not show rDNA promoter hypomethylation. Thus, hypomethylation of the rDNA promoter does not explain why tumor nucleoli are enlarged. While MYC can activate transcription from unmethylated rDNA promoters, we show for the first time that it is unexpectedly required to maintain proper rDNA promoter methylation levels in the inactive repeat units.
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 175.