bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B22: Is there a role of estrogen and progesterone receptors in differentiating primary neuroendocrinal lung tumors from metastatic adenocarcinoma?
Authors: Hassan Wafaa , Darwish Atef , Darwish Abeer 
Published: January 2011

Abstract
Background: The distinction between primary lung carcinoma and metastatic tumors is essential for patient management and treatment. However for metastatic tumors, a wedge resection is often the procedure of choice, whereas for primary pulmonary neoplasms the standard treatment is to perform at least a lobectomy with mediastinal lymph node sampling. Computed tomography scans, histology and immunohistochemical stains still have some limitations in differentiating primary neuroendocrinal lung tumors and metastatic adenocarcinoma. Estrogen and progesterone receptors, although more frequently immunoreactive in breast carcinomas and gynecologic tumors than in primary lung tumors, can be positive in metastatic pulmonary adenocarcinoma.
Objective: To assess estrogen and progesterone receptor expression in primary pulmonary neuroendocrine tumors.
Design: Fifty seven neuroendocrine lung neoplasms including small cell carcinomas (25), carcinoids (19), large cell neuroendocrine carcinomas (6), and combined small cell carcinomas (7) were evaluated in this cross-sectional study for estrogen and progesterone receptors. Lung metastasis from gynecologic tumors (27) and non-small cell lung carcinomas (30) were also stained for comparison.
Settings: Chest and gynecology departments of Assuit and Woman's Health University hospitals.
Results: Neuroendocrine primary lung neoplasm demonstrated focal to diffuse estrogen and progesterone expression. There was no correlation with the size of the tumor, the sex or the age of the patients. In comparison with neuroendocrine lung carcinomas, lung metastasis from gynecologic adenocarcinomas (20 endocervical cancer, 7 endometrial cancer) expressed estrogen and progesterone receptors more frequently (p&lt;0.7). Non-small cell carcinomas had less immunoreactivity for estrogen and progesterone than primary neuroendocrinal lung tumors and gynelogic lung metastasis (p&lt;0.4).
Conclusions: Although estrogen and progesterone receptor staining is frequently associated with gynecologic tumors, it can also be observed in “nontarget” organs. Therefore, presence of estrogen and progesterone expression in lung metastasis from gynecologic adenocarcinomas should not exclude a primary pulmonary neoplasm.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B22.
Abstract B29: Role of inflammatory-related gene expression in clear cell renal cell carcinoma
Authors: Tan Weiqi , Hildebrandt Michelle AT , Pu Xia , Huang Maosheng , Tamboli Pheroze , Wood Christopher G. , Wu Xifeng 
Published: January 2011

Abstract
Renal cell carcinoma (RCC) is the 10th most common cancer in United States with clear-cell renal carcinoma (ccRCC) being the most common. Many genes and signaling pathways have been implicated in ccRCC development, including the inflammation pathway. However, less is known about how gene expression variation within this pathway influences ccRCC development and clinical outcomes. Gene expression in tumor and adjacent normal tissues from 93 patients with ccRCC was detected using a genome-wide expression array and a panel of 661 inflammation-related genes was then analyzed. Differential expression patterns between tumor and adjacent normal tissue were observed. Association between expression and recurrence or survival was evaluated with those genes showing significant association further tested in a validation set of 258 ccRCC tumor samples. A total of 151 genes with at least a 2-fold change in gene expression between adjacent normal and tumor were identified, with a majority of the genes being upregulated in the tumors. Eleven inflammation-related genes (BLNK, APP, IL8, CARD9, SOD2, IL10RA, GADD45G, ADORA3, CXCL1, CIITA, and NCF2) were found to be significantly associated with recurrence and/or overall survival in 93 ccRCC tumors and selected for further validation. Expression of CIITA and NCF2 was significantly associated with overall survival in the replication dataset with high expression levels associated with significant 2.65-fold (95% CI=1.28-5.49, P=0.0088) and a 2.26-fold (95% CI=1.12-4.58, P=0.023) increased risk of dying, respectively. Our results suggest expression of CIITA and NCF2 genes may be significant prognostic biomarkers for risk of dying in patients with ccRCC.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B29.
Abstract B30: Susceptibility loci for lung cancer: Are COPD genes the missing link?
Authors: Young Robert P. , Hopkins Raewyn J. , Hay Bryan A. , Whittington Christopher F. , Gamble Gregory D. 
Published: January 2011

Abstract
Epidemiological studies show COPD, characterized by reduced FEV1, is the most important independent risk factor for susceptibility to lung cancer. When spirometry is routinely measured, co-existing COPD is found in 50-80% of lung cancer cases compared to only 15-20% of randomly selected matched smokers. Recent GWA studies have identified a number of susceptibility loci for COPD, lung function and lung cancer. Several of these loci overlap suggesting that the gene conferring susceptibility to lung cancer might include COPD-related genes.
In this case control study of Caucasian smokers matched for smoking exposure with COPD (n=458), lung cancer (N=454) and healthy smoker status (n=488) we compared the genotype frequencies of 12 loci on chromosomes 1q23, 4q22-24, 4q31, 5p15, 5q33, 6p21, 6q24 and 15q25. All subjects underwent spirometry, completed a modified ATS respiratory questionnaire and gave blood for DNA. Genotyping was done using Taqman real-time PCR (ABI 7900).
We found (1) the AA genotype of CHRNA3/5 (previously associated with lung cancer) conferred susceptibility to lung cancer (OR=1.76, P=0.005) and COPD (OR-1.47, P=0.06), (2) the GG genotype of HHIP (previously associated with reduced risk of COPD) conferred protection from COPD (OR=0.59, P=0.006) and lung cancer (OR=0.70, P=0.05) and the CC genotype of FAM13A (previously associated with reduced risk of COPD) conferred protection from COPD (OR=0.71, P=0.02) and lung cancer (OR=0.64, P=0.003). These overlapping effects in lung cancer were independent of co-existing COPD.
We conclude the genes conferring susceptibility to lung cancer overlap with those of COPD. Such an observation requires healthy smokers with normal lung function to be used as controls to best identify these COPD-related genes affecting the susceptibility of smokers to lung cancer.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B30.
Abstract B31: Gene-based lung cancer risk test (Respiragene), identifies high-risk smokers for early detection of lung cancer
Authors: Young Robert P. , Hopkins Raewyn J. , Field John , Zulueta Javier , Hay Bryan A. 
Published: January 2011

Abstract
Lung cancer results from the combined effects of smoking and genetic susceptibility. Recent studies show that between 50-90% of lung cancer cases have preexisting COPD and reduced FEV1 has been shown to be the single most important risk factor for lung cancer among smokers. Given the heritability for COPD and lung cancer is 40-75% and 15-25% respectively, it is clear genes conferring risk of COPD also underlies lung cancer susceptibility. In a study of 930 subjects, we have developed a gene-based lung cancer susceptibility model that combines genetic markers (SNPs) associated with COPD and lung cancer, with non-genetic variables (age and family history), to derive a score that helps to distinguish those smokers (and ex-smokers) at greatest risk of lung cancer. The panel includes SNPs validated in candidate and GWAS studies. In a prospective study of 1212 smokers we identified 52 new lung cancers and show their lung cancer scores are very similar to that of the original lung cancer cases (n=446). In a 2nd cross-sectional study of 606 lung cancer cases from the United Kingdom, the lung cancer score was also similarly distributed and showed similar performance in an ROC analysis. In a CT study of 25 lung cancer detected through CT screening in Spain, a similar high score was shown. Current CT screening programs for lung cancer generally target smokers over 50 years with a minimum 20 pack year history and achieve pick up rates of 1%. Using our gene-based model, where age, family history, COPD and genetic variants are combined, lung cancer detection rates maybe even higher.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B31.
Abstract B34: Association of endogenous oxidative and aldehyde stress: Implications for studies of colon carcinogenesis
Authors: Bruce W. Robert , Cani Patrice D. , Cirocco Maria , DaCosta Ralph S. , Giacca Adria , Kim Young-In , Lee Owen , Liu Zhen , Ma David W.L. , Marcon Norman , Minkin Salomon , O'Brien Peter J. 
Published: January 2011

Abstract
The results of a small pilot study provided new insights into the process of colon carcinogenesis.
Background: The known risk factors for colorectal cancer (CRC) suggested that CRC resulted from the interaction of exposure to energy excess and to oxidative stress [McKeown-Eyssen G et al. pp 673-693 in “Endogenous Toxins” Wiley, 2010]. The suggestion was supported by: cellular studies that demonstrated the cytotoxicity and genotoxicity of excess energy substrate (fructose) with oxidative stress (H2O2); animal studies that showed a wide range of pathology associated with fructose-based diets when combined with oxidative stress; and clinical studies that described the association of advanced glycation end-products (AGEs) with chronic diseases associated with the Western lifestyle.
Methods: A pilot case-control study at a hospital-based gastroenterology clinic was conducted to assess methods for future tests of the hypothesis. It was based on an analysis of plasma samples collected from patients with (n = 20) or without (n = 21) colonoscopy-demonstrated polyps.
Results: Although as anticipated none of the differences between polyp and non-polyp plasma samples achieved statistical significance, there were unexpectedly strong associations of the concentrations of the endogenous plasma aldehydes, glyoxal and methylglyoxal (r = 0.92), and glyoxal and 4-hydroxynonenal (r = 0.52) across the collected samples.
Conclusions: The associations were likely a consequence of the known interaction of endogenous aldehydes with oxidative stress: endogenous aldehydes increased oxidative stress; oxidative stress increased the formation of endogenous aldehydes [e.g. Vander Jagt DL. Drug Metab Drug Interact 2008;23:93-124]. The products of such interactions, AGEs and advanced lipid oxidation endproducts (ALEs), could explain the known accumulation of fluorescent lipofuscin observed with dysplastic adenomas.
Impact: Exposure to endogenous aldehydes and oxidation products is complex. Endogenous aldehyde derived — AGEs could provide robust biomarkers of this exposure including information relating to the tissues, cells and cellular organelles affected.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B34.
Abstract B37: Relationship of human rectal aberrant crypt foci and formation of colorectal polyp
Authors: Takahashi Hirokazu , Sakai Eiji , Uchiyama Takashi , Sugiyama Michiko , Hosono Kunihiro , Endo Hiroki , Nakajima Atsushi 
Published: January 2011

Abstract
In experimental models of colonic carcinogenesis, aberrant crypt foci (ACF) are the earliest detectable abnormality and precede adenomas. Herein, we wanted to determine the adenoma incidence over a 1-year period after polypectomy. Eighty-nine subjects were recruited from the population of Japanese individuals who underwent polypectomy at Yokohama City University Hospital. All patients had baseline adenomas (&gt; 6mm) removed at year 0 colonoscopy. ACF were defined as lesions in which the crypts were more darkly stained with methylene blue than normal crypts and had larger diameters, often with oval or slit-like lumens and a thicker epithelial lining. A total of 366 ACFs were identified in 89 patients; all had baseline adenomas (&gt; 6mm) removed at the first examination (year 0) colonoscopy and returned for the second (year 1). ACF in the lower rectum were assessed at year 0 and study group were divided into two groups depend on ACF numbers, 0-3 or over 4. All participants were examined in the number and maximum size of adenoma. There was no statistical difference in number and maximum size of ACF at year 0, however, maximum size of adenoma was larger in over 4 group than 0-3 group at year 1. The meaning of the number of ACF is not elucidated; however, the number of ACF may be a predictive factor of relatively large adenoma incidence in the pilot phase study.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B37.
Abstract B42: Cell-based, genome-wide assessment of chromosome-specific telomere length by quantitative fluorescent in situ hybridization in esophageal adenocarcinoma patients
Authors: Gong Yilei , Gu Jian , Ajani Jaffer , Luo Sherri , Hawk Ernest , Wu Xifeng 
Published: January 2011

Abstract
Chromosomal instability is one of the early hallmarks of human carcinogenesis. Shortened telomeres may predispose to chromosomal instability leading to the development of some cancers, including esophageal adenocarcinoma (EAC). However, whether the telomere changes associated with cancer risk occur at the global or chromosome-specific level remain largely unknown. Here, we developed a novel two-step quantitative fluorescent in situ hybridization (FISH) assay to measure the overall and genome-wide chromosome-specific telomere length in peripheral blood lymphocytes (PBLs). In this assay, overall telomere FISH is first carried out using peptide-coupled nucleic acid (PNA) probe. The relative intensity of each telomere signal is obtained by digital capture of the microscopic image and quantified. Then we perform the second FISH with centromere and subtelomere probes on the same slide to label each chromosome. Therefore, we can identify and quantify the telomere length for the p arm or q arm of each chromosome. We next used this assay to measure the overall and chromosome specific telomere length in a pilot case-control study of 31 EAC cases and 31 matched controls. We found EAC patients had significantly shorter overall telomere lengths in PBLs compared with controls (P = 0.039). Notably, the chromosome-specific telomeres of 8, 10, 14, 16, 17, and 22 were significantly shorter in cases than in controls (P &lt; 0.05). Analysis of chromosome arm-specific telomeres indicated that the telomere lengths of 17p, 17q, 16q, Xp, and 10q, and 13p were shorter in cases than controls (P &lt; 0.04). Cumulative analysis of these six significant telomeres showed that the total length for cases was significantly shorter than controls (P &lt; 0.001). Using median expression as cutoff, we found that patients with short telomeres on chromosome 17, 13p, 22q, or Xp had 4.4-fold increased risk of EAC (P for trend &lt; 0.001). Taken together, our study provides the first epidemiologic evidence that cancer cases have generally short telomeres across all chromosome arms and suggests that short telomeres in specific chromosome arms may exhibit stronger cancer predisposing effects than others depending on cancer types.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B42.
Abstract B43: Identification of prognostic markers for prostate cancer by serum profiling with a carbohydrate antigen microarray
Authors: Gildersleeve Jeff , Campbell Chris , Schlom Jeff , Gulley James 
Published: January 2011

Abstract
Purpose: The purpose of this study was to evaluate carbohydrate antigen array technology as a tool for identifying anti-glycan antibodies in human sera with potential as prognostic markers for prostate cancer.
Methods: A carbohydrate antigen array, or glycan array, containing 220 different glycans and glycoproteins was used to profile the anti-glycan antibody repertoire in sera from 29 prostate cancer patients. The Halabi nomogram was used to predict the survival for each patient. Relationships between antibody levels and the Halabi predicted survival were evaluated as a means to identify potential prognostic markers.
Results: A number of anti-glycan antibodies found in sera showed statistically significant correlations with the predicted survival for prostate cancer patients. Some examples include fucose-alpha (p = 0.009), fucosebeta (p = 0.023), Sialyl Lewis X (p = 0.014), and the Tn antigen (p = 0.022). For each of these antigens, higher antibody levels were associated with shorter predicted survival.
Conclusions: Anti-glycan antibodies have potential as prognostic markers for prostate cancer, and, based on the preliminary data, larger and more detailed studies are warranted.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B43.
Abstract B44: Reproducibility and short-term intraindividual variability of telomere length measurement using a monochrome multiplexing quantitative PCR
Authors: Kim Sangmi , Sandler Dale , Carswell Gleta , Cawthon Richard , Weinberg Clarice , Taylor Jack 
Published: January 2011

Abstract
Background: Telomeres are repetitive DNA structure at the end of chromosomes that are required for genomic integrity and stability. Numerous epidemiologic studies have examined telomere length in peripheral blood in relation to cancer and other aging-related diseases. In many of these studies, a measurement of telomere length from a single blood draw is quantified using a real-time PCR technique, and assumed to reflect a replicative history of hematopoietic stem cells in individuals. We examined the reproducibility of telomere length measurement and the relative magnitudes of sources of variation using sequential samples collected over a 9-month period.
Methods: Relative telomere length in peripheral blood was estimated using a single tube monochrome multiplex quantitative PCR assay in blood DNA samples from 27 non-pregnant adult women (aged 35 to 74 years) collected in 7 visits over a 9-month period. Each specimen was assayed in triplicate on each of two plates. Reproducibility of the technical triplicates within a plate was assessed using the coefficient of variation (%CV). A linear mixed model was used to estimate the components of variance for telomere length measurements attributed to variation among women and variation between time points within women.
Results: Within-plate technical replicate variability ranged from 8.5 to 15% (mean %CV=12.9). Plates had a significant systematic influence on telomere length measurements, explaining 16% of the variance; however, telomere length measurements between different plates were highly correlated (Pearson's correlation coefficient r=0.93, p&lt;0.01). After controlling for plate effects, 64% of the remaining variance was estimated to be accounted for by variance due to subject. Variance explained by date of collection within a subject was minor, contributing 5% of the remaining variance. Compared to classification into quartiles based on all 7 time point measures and all six technical replicates for each time point, using the six technical replicates from a single time point resulted in the same quartile classification for 73%. Using a single time point and only 3 technical replicates decreased that agreement to 64%. These differences in quartile assignment were almost always only across neighboring quartile categories.
Conclusion: Our data demonstrate good reproducibility of telomere length measurement using blood from a single draw. However, the existence of technical variability, particularly plate effects, reinforces the need for technical replicates and balancing of case and control samples across plates.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B44.
Abstract B46: The effect of sulforaphane on protein expression in benign prostatic hyperplasia tissue
Authors: McCall Rosemary , Traka Maria , Mithen Richard 
Published: January 2011

Abstract
Background: Benign prostatic hyperplasia (BPH) is a common condition that occurs in over 25% of men aged 50+, increasing to 50% amongst those over 80. Although the etiology of the condition has not been ascertained, the majority of BPH specimens contain inflammatory infiltrates indicating inflammation plays an important role in the progression of the disease. Furthermore, a role for inflammation has also been suggested in prostate cancer (PCa). BPH is not a pre-cursor of PCa but using BPH as a model of inflammation could result in findings that may apply and add to our understanding of PCa. Previous work has demonstrated that the consumption of broccoli can alter inflammatory pathways in the human prostate, and this may be due to the action of the isothiocyanate sulforaphane (SF), a phytochemical derived from broccoli. This dietary compound has a range of biological activities, including reducing inflammation.
Hypothesis: Sulforaphane reduces inflammatory pathways and beneficially alters protein expression in BPH tissue.
Methods: We obtained and cultured human BPH tissue for 24 hours with or without 10µM SF and collected tissue and media for further analysis using two distinct approaches. Firstly, in a targeted approach, known inflammatory markers were measured in the media of five tissue samples by commercially available ELISA. Secondly, a global proteomic analysis was carried out to give an unbiased view of the effect of SF on the protein expression within the tissue. Initially, protein was extracted from the tissue of three individuals, run on 2D gels and spots of interest excised from the gel and in-gel trypsin digested. The resulting peptides were analyzed on an LTQ-Orbitrap Mass Spectrometer and the proteins identified by Mascot. Selected proteins were then further quantified in additional tissue samples.
Results: Analysis of the effect of SF on inflammatory markers revealed that SF significantly reduced levels of secreted IL-6 and to a lesser extent IL-8 and FGF-2. Global proteomic analysis demonstrated that there was, as expected, considerable variation between individuals, and that SF altered expression of several proteins in BPH tissue. Reduction of GRP94, an endoplasmic reticulum chaperone protein observed in one individual, was further verified in independent BPH samples. Initial immunohistochemistry in sections of BPH tissue suggests that SF reduces the nuclear localization of this protein. Further experiments are currently ongoing to investigate these effects in more individuals and also to look at the biological consequences.
Conclusion: Natural variation present within humans highlights the need to use a larger number of samples in order to understand the complex effects of SF on prostate tissue. The results suggest that SF can reduce inflammatory markers and alter proteins within the human prostate indicating a possible protective role for SF in pathogenesis of the prostate.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B46.