bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3639: Systemic inflammation and survival of patients with prostate cancer: Evidence from the Glasgow Inflammation Outcome Study.
Authors: Shafique Kashif , Proctor Michael , McMillan Donald , Qureshi Khaver , Leung Hing , Morrison David 
Published: August 2012

Abstract
Background: There is some evidence that pre-treatment systemic inflammation may be associated with survival in patients with prostate cancer; however, it is unclear whether this is independent of grade and stage of cancer. We therefore investigated the role of inflammation-based prognostic scores, the modified Glasgow Prognostic Score (mGPS) and Neutrophil Lymphocyte Ratio (NLR), and their associations with Gleason grade and socioeconomic circumstances in patients with prostate cancer. Methods: Patients from a cohort, the Glasgow Inflammation Outcome Study, who had diagnosis of prostate cancer, were included in this study. The mGPS was constructed by combining C-reactive protein and albumin while NLR by calculating the ratio of neutrophils to lymphocytes. We estimated five-year relative survival using the age, gender and deprivation specific life tables and relative excess risk of death by mGPS and NLR categories after adjusting for age, socioeconomic circumstances and Gleason grade. Results: Eight hundred and ninety seven prostate cancer patients were identified; of those 422 (47%) died during a maximum follow up of 6.2 years. Systemic inflammation appeared to have significant prognostic value. The mGPS predicted poorer 5-year overall and relative survival independent of age, socioeconomic circumstances, disease grade and NLR. Raised mGPS also had a significant association with excess risk of death (mGPS 2: Relative Excess Risk = 2.41, 95% CI 1.37-4.23) among aggressive, clinically significant prostate cancer (Gleason grades 8-10). Similarly, age-specific analyses were also carried out and raised mGPS showed significantly higher risk of death among those with age &lt;65 and 65-74 years at diagnosis. However, a non-significant increased risk of death was also observed among those age &gt;75 years. Conclusions: The mGPS is a strong measure of systemic inflammation, when compared to NLR. Prostate cancer patients with a raised mGPS had significantly higher risk of death for overall as well high grade disease. Inflammation-based prognostic scores predict outcome in patients with prostate cancer and should be added to their routine clinical assessment. Keywords: mGPS, NLR, prostate cancer, prognosis, Gleason grade, systemic inflammation
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3639. doi:1538-7445.AM2012-3639
Abstract 3648: Nanofluidic technologies to define biological and response profile in neoadjuvant patients with ovarian cancer
Authors: Mariani Marisa , Ferlini Cristiano , Wilmot Amanda , Shahabi Shohreh 
Published: August 2012

Abstract
Objectives: Neoadjuvant chemotherapy is used in the treatment of advanced ovarian cancer. In this study, we determined the impact of chemotherapy on gene and microRNA (miRNA), expression in ovarian cancer specimens using nanofluidic technology. We performed the validation of this technique by using RNA extraction from archival formalin-fixed paraffin-embedded tissue. Molecular pathways involved in prediction of the outcome in neoadjuvant patients were analyzed. Methods: Seventy-eight patients with advanced ovarian cancer who were treated with primary surgical debulking versus neoadjuvant chemotherapy (15/78) were investigated. All patients were treated with Paclitaxel and Carboplatin. A chip 48.48 served to analyze a panel of 96 potential predictors of the outcome and response to chemotherapy. All the samples were normalized for multiple housekeeping genes and as consistent reference the ovarian cancer cell line A2780 was used. When needed for the analysis each factor was then categorized as high and low expression using the mean value as cutoff. Overall survival was analyzed using the methods of Kaplan and Meier and comparisons between groups by log-rank and Wilcoxon test. Results: We assessed the impact of neoadjuvant chemotherapy on the selected genes and microRNAs. Among the cell growth and proliferation genes MKI67, PLK1, PBK were reduced. Deactivation of the TUBB3 survival pathway, which was reduced while its negative regulator GNAI1 was increased. ERBB2 resulted downregulated in the neoadjuvant setting, while HGF and PTEN were increased. MicroRNAs expression broadly increased, with the only exception of miR-20a and miR-141. Patients exhibiting high levels of COL11A1 and PLK1 were poor performers, while the opposite occurred for GLI1. At the micro-RNA level the best predictors were miR-193a-5p, miR-375 and miR-20a. The poor performers (miR-193a-5p, miR-375) were featured by high levels of the micro-RNA while the opposite was evident for miR-20a. Conclusions: Use of the nanofluidic technology provides deeper insight into the specific roles of clinically relevant major molecular networks. Chemotherapy induced modification of genes and microRNA expression can be used as a model to develop future prognostic biomarkers and therapeutic modalities. Moreover, our findings suggest that neoadjuvant patients with ovarian cancer may benefit from biologic agent targeting HGF treatment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3648. doi:1538-7445.AM2012-3648
Abstract 3649: Expression of CXCR5 and its natural ligand CXCL13 in ovarian cancer
Authors: Singh Rajesh , Grizzle William E. , Singh Shailesh , Lillard James W. 
Published: August 2012

Abstract
Ovarian carcinoma (OvCa) is the most lethal gynecological malignancy among women and its poor prognosis is mainly due to metastasis. Chemokines and their corresponding receptors play an important role in metastasis and organ specific homing of cancer cells including OvCa. CXCL13 is a homeostatic chemokine for lymphocyte- and prostate cancer cell-homing and -positioning within secondary lymphoid tissues. This important chemokine acts through its only known receptor, CXCR5. In this study, we provide the first evidence that in OvCa CXCR5 and CXCL13 are highly elevated in OvCa cell lines and clinical samples. Flow cytometry analysis of OvCa cell lines (OVCAR-3 and SK-OV-3) show significantly higher expression of CXCR5 in comparison to normal adult ovarian epithelial cells. To determine the clinical significance of CXCR5 expressed by OvCa cell lines, ovarian cancer tissue microarrays were stained for CXCR5 and CXCL13. Aperio ScanScope scanning system was used to quantify the immuno-histochemical staining of CXCR5 and CXCL13. Our results show significantly higher expression of CXCR5 and CXCL13 (p &lt; 0.001) in cancerous tissue than compared to non-neoplastic ovarian tissue. Among cancerous tissues, CXCR5 and CXCL13 expression was highest in serous adenocarcinoma followed by serous papillary cystadenoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, cystadenoma, mucinous boderline adenocarcinoma, clear cell carcinoma, granulosa cell tumor, dysgerminoma, transitional cell carcinoma, brenner tumor, yolk sac tumor, adenocarcinoma and fibroma. These data demonstrate biological and clinical significance of CXCR5 and CXCL13 as an OvCa biomarker.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3649. doi:1538-7445.AM2012-3649
Abstract 3654: Prognostic role of androgen receptor in bladder cancer
Authors: Hartmann Arndt , Bertz Simone , Keck Bastian , Dyrskjot Lars , Orntoft Torben , Wullich Bernd , Hake Roland , Eidt Sebastian , Wirtz Ralph 
Published: August 2012

Abstract
Aims: Hormone receptors are the prototype predictive marker in breast and prostate cancer. Hormone receptor positive cancers have a better prognosis, increased tropism to metastasize into the bones and respond to endocrine treatment options. The prognostic value of hormone receptor in urothelial carcinoma of the bladder (UCB) is less established. This may in part result from technical limitations of immunhistochemical detection methods. Interestingly, female gender has recently been identified as strong adverse factor in advanced UCB (May et al., 2011). By analyzing whole genome expression data from non-muscle invasive bladder cancer patients, we have evaluated the potential of top candidate genes (ESR1, PGR, AR, CYP19, HER2, RACGAP1) commonly used to stratify breast cancer patients to predict bladder cancer progression. In view of the gender specific effects, we have focused on the prognostic role of androgen receptor expression on tumor invasion, disease progression and survival. Methods: Affymetrix microarray data from 41 non-metastatic bladder cancer patients undergoing curative surgery were analyzed. Prognostic value of androgen receptor mRNA expression was analyzed by unsupervised Cluster analysis, partitioning tests, Mann Whitney tests and Kaplan Meier estimates of cancer specific survival. Results: Cluster analysis in the microarray date of the superficial UCB cohort identified a hormone receptor positive subtype and a proliferation dominated subtype of equal size. Androgen receptor expression was negatively associated with cancer specific death (r=−0,42; p=0,005), while proliferation correlated with increased risk of cancer specific death (r=0,46; p=0,003). In addition, low androgen receptor expression was associated with higher tumor stage (pTa vs pT1-4; p=0,017). In Kaplan Meier analysis, the cancer specific survival was significantly better in tumors exhibiting high androgen receptor levels (80% vs. 20 %; p&lt;0,0001). Discussion: Resembling to some extent the situation in other cancer types, hormone receptors are prognostic factors in early stage bladder cancer. These results may also explain the recently described gender specific effects in bladder cancer. Moreover, these results raise the possibility, that UCB patients may be stratified according to their androgen receptor status in view of prognosis and putative endocrine therapy options.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3654. doi:1538-7445.AM2012-3654
Abstract 3655: Stem cell-associated gene Lin-28B genotype and phenotype in epithelial ovarian cancer and their associations with disease survival outcomes
Authors: Lu Lingeng , Katsaros Dionyssios , Risch Harvey , Yu Herbert 
Published: August 2012

Abstract
Several single nucleotide polymorphisms (SNPs) in lin-28B, a gene encoding RNA binding protein that represses miRNA let-7 maturation and acts as an oncogene, were found in the genome-wide association studies (GWAS), to be associated with the risk of ovarian cancer and cancer-related risk factors such as age at menarche, body mass index (BMI) and height. However, whether these SNPs are functionally important and can serve as prognostic markers in ovarian cancer remain unknown. The purposes of this study were to investigate the genotype-phenotype relationship in lin-28B and their associations with patient survivals in epithelial ovarian cancer. To achieve these purposes, we analyzed five lin-28B SNPs using Taqman® assays and lin-28B expression using SYBR green-based qPCR in tumor samples collected from 211 patients diagnosed with primary epithelial ovarian cancer. Wilcoxon rank sum test was performed to analyze cis-regulatory eQTL; Kaplan-Meir survival curves and Cox proportional hazards regression models were used to assess the associations of lin-28B SNPs and expression with the risks of relapse and death. The results showed that three SNPs (rs314276, rs314277 and rs7759938) were associated with lin-28B mRNA levels. Using mfold, rs314276 and rs314277 were predicted to affect the secondary structures of lin-28B mRNA. SNP rs7759938 is located at the 500 bp downstream of the region with H3K4Me1 (an enhancer marker) enrichment restricted to stem cells. However, these SNPs were not significantly associated with clinical and pathological parameters including disease stage, tumor grade, histological types, residual tumor size, and debulking results. No SNPs alone were related to patient survivals. Among patients initially responding to chemotherapy, those with high lin-28B expression had higher risks of death (hazard ratio (HR)=3.27, 95% CI: 1.63-6.56), and relapse (HR=2.53, 95% CI: 1.41-4.54) than those with low one. After adjustment for patient age at surgery, disease stage, tumor grade, histological types and residual tumor size, the associations were still statistically significant. These findings suggest that 3 of the GWAS-hit SNPs in lin-28B may affect gene expression, but these SNPs are not associated with ovarian cancer survival. The results also indicate that lin-28B may affect the outcome of chemotherapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3655. doi:1538-7445.AM2012-3655
Abstract 3658: The association of mitochondrial DNA content with bladder cancer risk and outcome
Authors: Ye Yuanqing , Dinney Colin P. , Kamat Ashish M. , Wu Xifeng 
Published: August 2012

Abstract
Mitochondrion plays essential role in energy production and apoptosis process from the initiation to regulation of apoptosis. Many studies have showed the association of dys-regulated mitochondrial DNA (mtDNA) with the development and progression of cancer, aging and longevity, and neurodegenerative diseases. In this study, we will test the hypothesis that variation in mtDNA content (also called mtDNA copy number) may be associated with individual's bladder cancer risk and clinical outcome in a case-control study of 1026 bladder cancer patients and 980 healthy-controls. We will also assess the association of mtDNA content with progression/recurrence in non-muscle invasive bladder cancer (NMIBC) patients and overall survival in muscle invasive and metastatic bladder cancer (MIMBC) patients. Quantitative real-time polymerase chain reaction in peripheral blood lymphocytes was used to measure mtDNA content. We observed significantly lower mtDNA content in bladder cancer patients (mean = 1.05, SD = 0.36) than controls (mean = 1.11, SD = 0.39) with P value &lt; 0.001. When we categorized the mtDNA content using the quartile distribution in controls, Lower mtDNA content (less than 1st quantile) was associated with 1.69-fold increased risk of bladder cancer (95% confidence interval [CI] = 1.17 to 1.68), compared to those who have higher mtDNA content (greater than 4th quartile). In patients with MIMBC, we also observed the significant association of lower mtDNA content with poor survival. After categorizing the mtDNA content using quartile distribution in patients who were alive, there is a significantly increased risk of death for patients with lower mtDNA content (hazard ratio = 1.75, 95% CI = 1.11 to 2.77). There is also a significantly reduced median survival time (44.5 months vs 25.4 months, log-rank P = 0.004). However, there is no significant association of mtDNA content with progression/recurrence in NMIBC patients. In conclusion, low mtDNA content is associated with significantly increased risk of bladder cancer risk and poor survival. The resulted from our study will contribute to personalized risk prediction and may also become potential molecular targets for prevention.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3658. doi:1538-7445.AM2012-3658
Abstract 3663: A gene signature for predicting outcome in patients with basal-like breast cancer
Authors: Hallett Robin M. , Dvorkin-Gheva Anna , Bane Anita , Hassell John A. 
Published: August 2012

Abstract
Basal-like breast cancer is a molecular subtype of breast cancer generally thought to have a universally poor prognosis. Subsequent studies examining the long-term outcome in thousands of patients with basal-like breast cancer have shown that these patients can be separated into two clinically distinct groups: those likely to experience a systemic recurrence and succumb to their disease within the first 5 years and those expected to show excellent long term survival. The ability to distinguish between these two sub-groups (good and poor prognosis) of basal-like breast cancer patients at the time of initial diagnosis would permit tailoring more aggressive therapeutic regimens to those patients with an inherently poorer prognosis and conversely to avoid such therapy in patients with a more indolent course. We aimed to identify a gene signature that could predict the clinical outcome of basal-like breast cancer patients. To this end we mined publicly available human breast tumor gene expression profiling data and identified patients with basal-like breast cancer. We divided these patients into training and validation sets to identify and confirm the accuracy of a prognostic signature. We identified 137 basal-like breast tumors among 995 breast tumor gene expression profiles. We used 85 of these samples as a training group and identified an optimal 14-gene signature, which accurately identified patients that experienced poor and good long-term survival. We confirmed the accuracy of our gene signature on a 49 patient independent validation set. Importantly, we also confirmed the capacity of our signature to predict outcome in a chemotherapy naïve 27 patient sub-set of the 49 patients validation set.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3663. doi:1538-7445.AM2012-3663
Abstract 367: Imaging and diagnostic potentials of a novel cancer targeting peptide on bladder cancer in vitro and in vivo
Authors: Trehan Siddharth , Lin Tzu-yin , Liu Ruiwu , Zhang Hong-Yong , Pan Chong-Xian 
Published: August 2012

Abstract
Background: We have previously identified a cyclic peptide PLZ4 through screening of “one bead one compound”(OBOC), that specifically binds to bladder urothelial carcinoma cells. The main objective of this study is: 1) to optimize the binding and diagnostic potential of PLZ4 on cancer cells in urine, 2) to determine the imaging potential in xenograft mouse model. Methods: PLZ4 peptide was conjugated to the fluorescent dye Alexa 488 to determine the binding affinity toward several human and canine clinical biopsy smears and paraffin-fixed bladder tumor sections. It was also tested for in vitro diagnostic efficiency with human and dog bladder cancer cell lines treated with urine for 2 and 4 hours. To determine the in vivo targeting and imaging efficacy, PLZ4 was labeled with 64Cu through the chelator DOTA or near-infrared dye DiD loaded in nanocarriers. Mice carrying subcutaneous human or dog bladder cancer xenografts generated from cell lines or clinical specimens were used for in vivo imaging. Results: Our results indicated that PLZ4-Alexa 488 bound to primary bladder cancer obtained from dog and human patients and had higher affinity in paraffin-fixed bladder tumor sections compared to H232A lung cancer xenograft tissue sections. PLZ4 also retained its affinity toward both human and dog bladder cancer cells in the presence of urine for 2 and 4 hours. Positron emission tomography (PET) imaging displayed the accumulation of PLZ4-DOTA-64Cu conjugate at human xenograft bladder cancer sites, while liver and kidney were also found to have high uptake. DiD-loaded nanomicelles decorated with PLZ4 showed a better homing property than non-targeting nanomicelles in both human and canine xenograft bladder cancers. Conclusion: PLZ4 has high imaging, diagnostic and therapeutic potential both in vitro and in vivo. It can possibly be developed for targeted delivery of radionuclides or chemotherapeutic nanoformulations in the management of bladder cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 367. doi:1538-7445.AM2012-367
Abstract 368: Development of a highly potent and non-invasive optical imaging agent for glioblastoma
Authors: Liu Ruiwu , Xiao Wenwu , Bononi Fernanda C. , Sanchez Eduardo , Liu Yanlei , Mazloom Anisha , Tseng Harry , Lam Kit S. 
Published: August 2012

Abstract
Using the “one-bead one-compound” (OBOC) combinatorial library approach, we have previously identified a peptide ligand LXY1, cyclic c-d-G-L-G-Hyp-N-c, that targets the α3β1 integrin of U87MG glioblastoma cells. Very recently, we have further optimized LXY1 using the OBOC focused library approach, and subsequently traditional medicinal chemistry. Three focused OBOC peptide libraries have been designed by fixing the motif c-d-G_G_ _c, randomizing the other positions with a large number of D- and other unnatural amino acids, and extending with 1-2 random amino acids at the N-terminus and/or C-terminus of LXY1. The bead libraries have been screened against U87MG cells using an on-bead cell binding assay. Three out of the twelve positive ligands have an additional L-amino acid at the C-terminus of LXY1. However, none of the positive beads has an extension of additional residues at the N-terminus. A series of new ligands has been designed based on the screening results, and extensive structure-activity relationship (SAR) studies have been performed. Several ligands have shown more potent in vitro binding to U87MG cells, and better in vivo tumor uptake than LXY1. Among them, LXY30 [cyclic c-d-G-Phe(3,5-diF)-G-Hyp-N-c-R] is the most promising ligand. Optical imaging of LXY30, using LXY30-biotin/streptavidin-Cy5.5 conjugate, in both subcutaneous and orthotopic U87MG glioblastoma mouse models, will be presented. LXY30 could be used as an efficient vehicle for the delivery of imaging probes and therapeutic agents against glioblastoma and other tumors with a high expression of the α3β1 integrin.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 368. doi:1538-7445.AM2012-368