bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4668: Pro-inflammatory lipid PAF may induce malignant potential via PAFR and phospho-FAK/STAT pathway in BRCA1-positive tubo-ovarian epithelial cells
Authors: Zhang LiFang , Wang Dan , Edwards Dale , Aponte Margarita , Qiu Weiliang , Jin LianJin , Seethapan Vanitha , Vitonis Allison , Wang Jian Liu , Mok Samuel , Crum Christopher , Cramer Daniel W. , Ye Bin 
Published: February 2011

Abstract
The loss of BRCA1 function may induce profound transcriptional changes, phenotypic reprogramming and ultimately, generate genetically unstable tumor-initiating cells, which significantly increase the risk of breast and ovarian cancer. The molecular targets and pathways involved in early events of malignant transformation of at-risk epithelium has not been well investigated, particularly the effects of chronic inflammation. In an earlier study, we demonstrated that platelet activating factor (PAF), a potent pro-inflammatory mediator, plays a significant role in ovarian cancer progression and invasion (Cancer Research, 68:5839, 2008). Here, we extend our finding to show that PAF receptor is over expressed in BRCA1-mutated (BRCA1+) human ovarian surface epithelial cells (HOSE) by western blot and in distal fallopian tube (fimbria) epithelial cells by immunohistochemistry. In addition, PAF induced cell apoptosis only in wild type HOSE cells, and anti-apoptosis in BRCA1+ ovarian surface epithelial cells. A kinase microarray revealed that phosphor-STAT1/3/4/6 was simultaneously activated by 100 nM PAF treatment in BRCA1+ ovarian cancer cells. Induction of phosphor-STAT1 associated with PAFR and BRCA1-mutation was further confirmed in three BRCA1+ HOSE cell lines, but not in normal (HOSEE6E7) or malignant (OVCA429) ovarian epithelial cells. Co-immune precipitation revealed that PAF/PAFR coordinately activates FAK through dephosphorylation and STAT1 through phosphorylation only in BRCA1+ ovarian epithelial cells. These findings strongly suggest that potent inflammatory mediators (i.e. PAF) may play a significant role to induce malignant transformation in BRCA1-mutant ovarian epithelial cells through the FAK-STAT pathway.
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 4668.
Abstract 467: Effects of Monascus-fermented rice extract on malignant cell associated neovascularization and intravasation by chicken embryo chorioallantoic membrane model
Authors: Ho Bing-Ying , Wu Yao-Ming , Hsu Ya-Wen , Hsu Li-Chuan , Kuo Yao-Haur , Chang King-Jen , Pan Tzu-Ming 
Published: February 2011

Abstract
The traditional Chinese medicine, “Hong-Qu”, also call “red mold rice” in the United States and Europe, has been identified and used for the treatment of blood stasis, a disorder related to hyperlipidemia and atherosclerosis. In addition to its value in improving metabolism syndrome, extracts from Monascus fermented rice inhibited proliferation of various cancer cells in vitro and in vivo have demonstrated previously. The objective of the current study was to examine correlation of red mold rice ethanol extract (RMRE) on the process of angiogenesis, invasion and metastasis during tumor progression. In the current study, we examined the inhibitory effects of SW480 and SW620 human colorectal carcinoma cells by RMRE using in vitro MTT assay. RMRE significantly inhibited the proliferation of SW480 and SW620 cells in dose- and time-dependent manner. However, human umbilical vein endothelial cells (HUVECs) showed a minor reduction effect of cell viability up to 20 µg/mL of RMRE for 48 hours using crystal violet staining assay. The capillary-like network morphology was observed following 20 ng/mL VEGF or SW620 culture-conditional medium (CM) addition. Nevertheless, capillary-like tube formation have failed to show when RMRE participation. Moreover, SW620 cells could growth in Matrigel grafts and spontaneously intravasation from the upper to the lower of chick embryo chorioallantoic membrane (CAM) model, which detected human Alu genomic DNA by PCR amplification from the lower CAMs at RMRE-untreated group. The percentage of neovascularization was increased 75.3±11.6% by SW620 cells onplant with Matrigel grafts on the CAM model. However, addition of RMRE significantly reduced CAM neovascularization in dose-dependent effect. Finally, we have finding that RMRE effectively decreased activity of matrix metalloproteinase (MMP)-7 determined by RT-PCR, Western blotting, and casein zymography assays. In summary Monascus fermented products exerted a potent effect on tumor growth and activation, suggesting that it may useful serves as a supplementary agent in adjuvant 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 467.
Abstract 4671: Tumor Suppressive Role of HOP (homeobox only protein) Gene in Gastric Cancer
Authors: Yamashita Keishi , Ooki Akira , Katoh Hiroshi , Sidransky David , Watanabe Masahiko 
Published: February 2011

Abstract
Background: Homeobox only protein (HOP) is an unusual homeobox gene encoding the 3 spliced transcript variants, among which the only HOP-β promoter harbors CpG islands and inactivated by methylation in esophageal and gastric cancer (Yamashita K et al., Cancer Cell, 2002, Kim MS and Yamashita K et al., Cancer Res., 2006, Yamashita K et al., Mol. Cancer Res., 2009). HOP acts as a novel tumor suppressor gene, but remains elusive for functional role in human cancer.
Methods: Using bisulfite sequencing analysis and quantitative-methylation specific PCR (Q-MSP), HOP-β methylation status was evaluated in 80 pairs of gastric cancer and the corresponding normal tissues, further validated in 90 advanced gastric cancer. Transfection of HOP into gastric cancer cell line GCIY was done to examine whether it actually has a tumor suppressive function.
Results: By Q-MSP, HOP-β hypermethylation was found in 84% (67/80) primary tumor tissues and 10% (8/80) corresponding normal tissues. When the cut-off value was set at 11.28, the HOP-β methylation was a potent prognostic factor (P=0.0006), which was further validated in the independent 90 advanced gastric cancer (P=0.009). Multivariate analysis revealed that HOP-β methylation could be independent prognostic factors. HOP-β expression was silenced by the promoter methylation in all gastric cancer cell lines tested; expression could be restored by treatment with methyltransferase inhibitor. Moreover, reintroduction of HOP-β gene repressed cell growth and invasion.
Conclusion: HOP-β promoter methylation is a frequent and cancer-specific event in gastric cancer. Quantitative assessment of HOP-β methylation has great clinical potential as a marker of tumor aggressiveness and may thus facilitate treatment planning in patients with advanced gastric 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 4671.
Abstract 4673: Myopodin methylation is a prognostic marker in patients with T1G3 bladder cancer
Authors: Alvarez Miguel , Cebrian Virginia , Fernandez Jesus , Fresno Florentino , Escaf Safwan , Sanchez-Carbayo Marta 
Published: February 2011

Abstract
BACKGROUND: Urothelial carcinomas presenting T1G3 non muscle-invasive lesions are high-risk tumors because of the high recurrence and progression to muscle invasive disease rates. The Bacillus of Calmette-Guérin (BCG) is a standard treatment to reduce tumor recurrence and delay progression of high-risk non-muscle invasive bladder tumors. However, it is not clear yet which T1G3 patients are more prone to display a more aggressive clinical behavior or be susceptible to respond to BCG.
OBJECTIVE: The aim of this study was to evaluate the role of myopodin methylation as a clinical outcome prognosticator and predictive biomarker for BCG response in patients with T1G3 bladder tumors.
DESIGN, SETTING, AND PARTICIPANTS: The methylation status of myopodin was analyzed on tumor specimens belonging to 170 patients with T1G3 non-muscle invasive bladder cancer, being a subset of them undergoing BCG treatment (n=108).
MEASUREMENTS: Myopodin methylation was assessed by methylation-specific polymerase chain reactions. Recurrence, progression into muscle invasive tumors and disease-specific overall survival rates were analyzed using competing risks regression analysis.
RESULTS: Among the 170 cases analyzed, 72 of them recurred (42.4%), 36 progressed (21.2%), and 24 died of the disease (14.1%). Univariate and multivariate survival analyses revealed that myopodin methylation was significantly associated with an increased recurrence rate (p=0.004), progression (p=0.002), and shorter disease-specific overall survival (p=0.020). Interestingly, in a subset of cases treated with BCG, myopodin methylation was also related to an increased recurrence rate (p=0.011), progression (p=0.030), and a shorter disease-specific overall survival (p=0.028).
CONCLUSIONS: Epigenetic analyses revealed that myopodin methylation was associated with the clinical outcome of patients with T1G3 tumors. Myopodin methylation was related to tumor aggressiveness in patients with T1G3 disease undergoing BCG treatment. Myopodin methylation distinguished patients responding to BCG from those who may require a more aggressive therapeutic approach.
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 4673.
Abstract 4674: Receptor for advanced glycation endproducts (RAGE) regulates ß-catenin function and chemosensitivity in pancreatic cancer cells
Authors: Kang Rui , Tang Daolin , Lotze Michael T. , Zeh Herbert J. 
Published: February 2011

Abstract
β-catenin is a key downstream effector in the Wnt signaling pathway. It is implicated in two major biological processes in vertebrates: early embryonic development and tumorigenesis. The receptor for advanced glycation endproducts (RAGE), a member of the immunoglobulin superfamily of cell membrane receptors, is encoded within the MHC Class III Region. It interacts with various ligands including high mobility group protein 1 [HMGB1], certain S100 protein family members, and advanced glycation endproducts and is involved in cancer, inflammation, diabetes and Alzheimer disease. To evaluate whether treatment with RAGE short hairpin RNA (shRNA) increases chemosensitivity in pancreatic cancers involves β-catenin signaling, we first examined the expression level of β-catenin and its target genes. In normal states, β-catenin and its target genes cyclinD1, c-myc, and Nr-CAM but not L1CAM were decreased when RAGE was depleted in the murine Panc02 cell line by western blot and immunofluorescence analysis. Importantly, RAGE deletion enhanced the suppressive effects of chemotherapy on the expression of β-catenin and its target genes. To evaluate the effects of β-catenin on chemosensitivity in pancreatic cancer cells, we used cells in which the expression of RAGE and/or β-catenin was suppressed by shRNA. Knockdown of β-catenin increased chemosensitivity in pancreatic cancer cells and these effects were enhanced when both β-catenin and RAGE were knocked down. Notably, knockdown of β-catenin had no effect on the commitment of cells to enhanced autophagic flux when assessed by evaluation of microtubule-associated protein 1 light chain 3 (LC3) punctae formation. However, knockdown of β-catenin did significantly increase apoptosis when assayed by increased activity of caspase 3 and cleavage of caspase3. Taken together, these results suggest that RAGE regulates β-catenin transcription function and chemosensitivity in pancreatic 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 4674.
Abstract 4675: Lack of evidence for XMRV infection in German prostate cancer patients
Authors: Krause Hans , Hohn Oliver , Miller Kurt , Kurth Reinhard , Bannert Norbert 
Published: February 2011

Abstract
A novel gammaretrovirus named xenotropic MuLV-related retrovirus (XMRV) has been recently identified with 40 % prevalence in prostate tumor samples from US American patients carrying a homozygous R462Q mutation in the RNASEL gene. This mutation impairs the function of the innate antiviral type I interferon pathway and is a known susceptibility factor for prostate cancer. In subsequent studies, analyzing small European cohorts of prostate cancer patients a less significant prevalence and correlation of the QQ-phenotype with XMRV has been found or even a complete absence of viral traces was reported. A second independent report from the US found XMRV DNA in 6% and XMRV protein expression in 23% of prostate cancers. Contrary to the initial report the XMRV infection was not associated with this common variant of RNASEL and predominantly observed in malignant epithelial cells.
We aimed to determine the prevalence of XMRV in prostate cancer patients who had undergone radical prostatectomy at the Charité hospital in Berlin, Germany between 2000 and 2006. To validate the association of the XMRV infection with the R462Q polymorphism, we first genotyped our 589 prostate tumour samples for the G-to-A transition at nt1385 of the RNASEL gene. Using nested PCR and RT-PCR approaches, DNA and RNA samples of prostate cancer (PCa) patients with varying degrees of malignancy were screened for the presence of XMRV specific gag sequences. Furthermore 146 sera samples from PCa patients were tested for XMRV Gag and Env antibodies with a newly developed ELISA assay.
Genotyping our patients revealed the presence of the minor allele (QQ genotype) in 76 samples (12.9 %). Although using highly sensitive PCR-based detection methods we could not detect XMRV specific sequences either at the DNA or RNA level. Consistent with this result, all analysed sera from prostate cancer patients did not contain XMRV specific antibodies.
Our results indicate a complete absence or at least a much lower prevalence of XMRV in prostate tumour patients in Germany.
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 4675.
Abstract 4677: Irinotecan plus anthracycline - based combination chemotherapy in advanced solid tumors
Authors: Rebollo Joseba , Sureda Manuel , Gonzalez-Manzano Ramon , Balenzuela Belen , Brugarolas Antonio 
Published: February 2011

Abstract
Irinotecan and Anthracyclines (Topoisomerase I and II inhibitors, respectively) are widely used as antitumoral agents in cancer treatment. However, no data have been reported when used in combination.
In this study we report the activity of biweekly Irinotecan (150 mg/m2) plus Anthracycline (Doxorrubicin 30 mg/m2 or Pegylated Doxorrubicin 20 mg/m2) - based combination chemotherapy in some previously treated advanced solid tumours.
From June ’04 to June ’09, eighteen patients (pt) have been treated. Median age has been 64 y (range 28-84 y). Eight pt had ovarian cancer, 8 pt non-small-cell lung cancer (NSCLC) and 2 pt gastric cancer. Therapy has been administered as a second line treatment in 11 pt and as a third and further treatment in 7 pt. Four pt have received radiotherapy previously.
Toxicities have been leucopenia (3 pt grade III-IV, 6 pt grade I-II), mucositis (6 pt grade III-IV, 5 pt grade I-II), diarrhea (2 pt grade III) and hand-foot syndrome (2 pt grade II). One pt died of neutropenic sepsis after the first dose of chemotherapy.
Seven out of 16 (44%) pt presented objective response: 4/7 ovarian cancer pt, 2/7 NSCLC pt and 1/2 gastric cancer pt. Two pt are not evaluable for response (one pt without evaluable disease and 1 pt early toxic death). Median Progression Free Survival has been 4 mo (range 1-13 mo).
Irinotecan plus Anthracycline - based combination chemotherapy is an active treatment in some solid tumours and it is well tolerated. Most of the toxic events were related to heavily pre-treated pt. It is infrequent to observe objective good quality responses in first line therapy resistant tumours. For this reason, we purpose there is a synergistic effect based on the known mechanisms of both drugs (Topoisomerase I and II inhibition) and an early-use first line therapy is recommended with this combination. This combination should be tested in larger trials to confirm antineoplastic activity.
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 4677.
Abstract 4680: Correlation between Wnt pathway and colorectal cancer recurrence using protein, mRNA and microRNA analysis
Authors: Coudry Renata A. , Martins Mila O. , Coutinho Cláudia M C , Buim Marcilei , Carvalo Kátia C. , Santos Erika M. , Brentani Helena 
Published: February 2011

Abstract
BACKGROUND: Wnt signaling pathway has a fundamental role in colorectal carcinogenesis. However, few studies have focused in the association of this pathway and the risk of postoperative recurrence. Besides microRNAs repress protein translation through binding to targets mRNAs and have shown association with specific targets. The main goal of this study was to evaluate several members of Wnt signaling pathway (Wnt protein family, proteins from β-catenin/APC complex, transcription factors and target proteins) and CRC recurrence. We also would like to assess association of microRNAs with specific Wnt targets or the direct implication of those small non coding RNAs with CRC recurrence. METHODS: The expression of Wnt proteins and mRNAs were assessed using immunohistochemistry and Real Time-PCR techniques, respectively. We also studied 381 microRNAs using Low Density TaqMan Array. This study was performed in samples from patients presenting stages I and II CRC and comparing those who had recurrence to those who did not. All patients undergone surgery with curative intention from 2000 to 2006 in A. C. Camargo Hospital. Statistical analyses used in this study were Chi-square, exact Fisher's test and T Paired. RESULTS: Regarding the protein expression and gene expression of Wnt signaling members only c-Myc showed statistically significant association with recurrence (p=0,001 and p=0,048, respectively). Regarding the analysis of 381 microRNAs, a statistically significant association was observed for miR-197 (p=0,03), where the group of patients who did not had recurrence demonstrated higher expression levels of this microRNA when compared to the group of patients who developed tumor recurrence. CONLUSION: Increased levels of c-Myc expression and low levels of miR-197 in the tumor may be used at the time of primary removal for defining patients at risk for tumor recurrence. miR-197 may regulate indirectly the expression of c-Myc. However, further experiments will be required to better evaluate this hypothesis.
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 4680.
Abstract 4685: Multiplexed methylation profiles of urinary DNA for non-invasive bladder cancer diagnostics
Authors: Cabello Maria Jose , Grau Laura , Orenes-Piñero Esteban , Franco Noreli , Alvarez Miguel , Blanca-Pedregosa Ana , Heredero Oscar , Fernandez Jesus , Palacios Alberto , Lopez-Beltran Antonio , Sanchez-Carbayo Marta 
Published: February 2011

Abstract
Changes in DNA methylation of crucial cancer genes including tumor suppressors can occur early in carcinogenesis, being potentially important early indicators of cancer. The objective of this study was to examine a multiplexed approach to assess the methylation of tumor suppressor genes as urinary diagnostic markers for bladder cancer. A multicandidate probe panel interrogated DNA for aberrant methylation status in 25 tumor suppressor genes using a methylation-specific multiplex ligation-dependent probe amplification assay (MS-MLPA). Initial analyses in bladder cancer cell lines (n=14), and fresh-frozen primary bladder tumor specimens (n=31) supported the panel of genes selected to be altered in bladder cancer. MS-MLPA was then optimized for its application in body fluids using two sets of urinary specimens (n=146) including bladder cancer patients (n=96) and controls (n=50). Genes previously reported to be methylated such as BRCA1, CDH13 and RARB, were confirmed to be methylated in the three types of samples analyzed. WT1 and PAX5A were identified as novel tumor suppressor candidates methylated in bladder cancer specimens. The most frequently methylated genes in the bladder tumors analyzed were BRCA1 (71.0%), WT1 (38.7%), and RARB (38.7%), being WT1 methylation significantly associated with tumor stage (p=0.011). BRCA1, WT1 and RARB were also as the most frequently methylated genes in two independent training and validation sets of urinary specimens (n=146). ROC curves analyses revealed significant diagnostic accuracies over 70% in both sets of urinary specimens for BRCA1, RARB, WT1, PAX5A and CDH13. In summary, the novelty of this report deals with applying a multiplexed methylation technique for bladder cancer, and also in body fluids. MS-MLPA represents a promising methylation profiling tool for histopathologic stratification of bladder tumors, and diagnosis using urinary samples. This latter is clinically relevant by offering a non-invasive strategy for the clinical management of patients affected with uroepithelial neoplasias
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 4685.