bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum Concentrations of Insulin-Like Growth Factor and Insulin-Like Growth Factor Binding Protein 3 and Recurrent Colorectal Adenomas
Authors: Flood Andrew , Mai Volker , Pfeiffer Ruth , Kahle Lisa , Rosen Clifford J. , Lanza Elaine , Schatzkin Arthur 
Published: June 2008

Abstract
Insulin-like growth factor I (IGF-I) and its primary binding protein, IGFBP-3, have been associated with colorectal cancer incidence in prior epidemiologic studies. High concentrations of IGF-I generally result in increasing risk and high concentrations of IGFBP-3 in decreasing risk. Only one prior study of IGF-I and IGFBP-3 and adenoma recurrence has been reported. We assayed fasting serum from 375 subjects with and 375 subjects without a recurrent adenoma during the course of the Polyp Prevention Trial to determine baseline concentrations of IGF-I and IGFBP-3. To estimate relative risk of adenoma recurrence over the course of 4 years of follow-up for each of these serum measures, we calculated odds ratios (OR) and 95% confidence intervals (CI) using multivariable logistic regression models adjusting for age, gender, body mass index, intervention group, aspirin, smoking, ethnicity, and education. For both IGF-I and IGFBP-3, we found trends indicating decreased risk for subjects in the high compared with the low quartile (for IGF-I: OR, 0.65; 95% CI 0.41-1.01; for IGFBP-3: OR, 0.66; 95% CI, 0.42-1.05). The associations were even greater for advanced adenomas (for IGF-I: OR, 0.51; 95% CI, 0.21-1.29; for IGFBP-3: OR, 0.32; 95% CI, 0.13-0.82). These results showed an unexpected null association, or even the suggestion of a reduction in risk for recurrent adenoma, with not just high IGFBP-3 concentration but also with high levels of IGF-I. Why IGF-I would decrease risk of recurrent adenoma (as distinct from incident adenoma or colorectal cancer) is not clear. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1493–8)
Informed Consent for Biorepositories: Assessing Prospective Participants' Understanding and Opinions
Authors: Beskow Laura M. , Dean Elizabeth 
Published: June 2008

Abstract
Purpose: Obtaining informed consent for the collection, storage, and future research use of biospecimens is challenging, as potentially complex and controversial information must be communicated clearly. We gathered input on a consent template developed for the Duke Biorepository from individuals representative of those who might one day consider contributing specimens.
Methods: Forty subjects were recruited from the Durham, NC area and screened to achieve diversity by race/ethnicity, education, age, and sex. Cognitive interviews assessed participants' (a) understanding of information in the template, and (b) opinions about that information. Participants also completed a survey assessing trust in medical researchers.
Results: Interviewees seemed to understand the template. Although responses were diverse, majority views emerged: more than half were comfortable with indefinite biospecimen storage, periodic contact to update information and to inform participants of additional research opportunities, the prospect that commercial products could be developed, and the fact that profits would not be shared. More than half were willing to provide medical record access, although this was a primary concern for others. More than two thirds were comfortable with not receiving individual research results as a matter of routine, but many thought they should be informed of findings with serious health implications. Lack of trust in researchers was associated with declining certain consent options.
Conclusions: Protecting and promoting trust in research is essential to fostering widespread participation in biorepositories. Biorepositories should also devise ways to communicate clearly about the research being conducted and what is being learned.(Cancer Epidemiol Biomarkers Prev 2008;17(6)1440:–51)
Infant Feeding and the Incidence of Endometrial Cancer
Authors: Xue Fei , Hilakivi-Clarke Leena A. , Maxwell G. Larry , Hankinson Susan E. , Michels Karin B. 
Published: June 2008

AbstractBiological mechanisms could support both an inverse and a direct association between exposure to breast milk in infancy and the risk of cancer. Having been breast-fed has been investigated in relation to the risk of breast and other cancer sites, and conflicting results have been reported. The association between infant feeding and the risk of endometrial cancer has not been explored. From 1976 to 2004, we followed 74,757 cancer-free participants in the Nurses' Health Study who had not undergone hysterectomy. Information on infant feeding was self-reported by study participants. A total of 708 incident cases of endometrial cancer were diagnosed during follow-up. After adjusting for age, family history of endometrial cancer, birth weight, premature birth, and birth order, the incidence of endometrial cancer was not associated with ever having been breast-fed (hazards ratio, 0.94; 95% confidence interval, 0.79-1.11) or duration of having been breast-fed [hazards ratio (95% confidence interval): 1.11 (0.80-1.54), 0.84 (0.62-1.13), 1.02 (0.79-1.31), respectively, for ≤3, 4-8, and ≥9 months of having been breastfed; P for trend = 0.88]. There was no significant effect modification by menopausal status, anthropometric factors (somatotype at age 5 or 10 years, body mass index at age 18 years, or current body mass index), or by other early-life exposures (birth weight, premature birth or exposure to parental smoking in childhood). Additional adjustment for adulthood risk factors of endometrial cancer did not materially change the results. Having been breast-fed was not associated with the incidence of endometrial cancer in this cohort, but statistical power for analyses restricted to premenopausal women was limited. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1316–21)
Association betweenGSTGenetic Polymorphism and Dose-Related Production of Urinary Benzene Metabolite Markers,trans, trans-Muconic Acid andS-Phenylmercapturic Acid
Authors: Lin Lung-Cheng , Chen Wan-Jou , Chiung Yin-Mei , Shih Tung-Sheng , Liao Pao-Chi 
Published: June 2008

AbstractThe urinary benzene metabolites, trans, trans-muconic acid (ttMA) and S-phenylmercapturic acid (SPMA), are widely used as benzene exposure biomarkers. The influence of the glutathione S-transferase (GST) genetic polymorphism on the excretion levels of urinary ttMA and/or SPMA has been investigated. The association between dose-related production of urinary benzene metabolites and benzene exposure level was also reported. However, the association between the dose-related productions of urinary benzene metabolites and GST genetic polymorphism was not described in the literature. The purpose of this study was to investigate the association between the GST genetic polymorphism and dose-related production of the two widely used biomarkers, urinary ttMA and SPMA. Seventy male workers in a chemical factory were measured for their benzene exposure levels and provided blood and urine specimens at the end of work-shift. The atmospheric benzene exposure levels of these workers were determined by passive samplers with gas chromatograph mass spectrometer. The urinary ttMA and SPMA levels were quantitated by an online dual-loop cleanup device with an electrospray ionization tandem mass spectrometer. The analyses of GST genotypes, including M1, T1, and P1, were done using PCR. Mean (± SD) of benzene exposure levels in participants was 7.2 ± 15 ppm. The ttMA and SPMA levels in the high benzene exposure group (≧1 ppm) were higher than those in the low benzene exposure group (&lt;1 ppm; P &lt; 0.001). Among the GST genotypes investigated in this study, the results showed that only the GSTT1 genotype was related to the level and dose-related production of SPMA. Using SPMA for evaluating benzene exposure, the results suggest that the GSTT1 genetic polymorphism, especially in a comparison study between two populations with different GSTT1 genotype frequencies, should be considered. Additionally, the biological exposure index value of SPMA should be set based on the levels of subjects with GSTT1-deficient genotypes for protection of all subjects.(Cancer Epidemiol Biomarkers Prev 2008;17(6):1460–9)
TheGc2Allele of the Vitamin D Binding Protein Is Associated with a Decreased Postmenopausal Breast Cancer Risk, Independent of the Vitamin D Status
Authors: Abbas Sascha , Linseisen Jakob , Slanger Tracy , Kropp Silke , Mutschelknauss Elke Jonny , Flesch-Janys Dieter , Chang-Claude Jenny 
Published: June 2008

AbstractVitamin D pathway gene polymorphisms may influence breast cancer risk by altering potential anticarcinogenic effects of vitamin D. The association between polymorphisms in the vitamin D binding protein (Gc) and postmenopausal breast cancer risk, with additional focus on the influence of serum 25-hydroxyvitamin D [25(OH)D], the biomarker for vitamin D status in humans, has not been examined thus far. We assessed the combined effects of two known functional polymorphisms in the Gc gene (rs4588 and rs7041), composing the phenotypic alleles Gc1s, Gc1f (combined: Gc1), and Gc2, on postmenopausal breast cancer risk and potential effect modification by 25(OH)D status in a population-based case-control study including 1,402 cases and 2,608 matched controls. Odds ratios (OR) for breast cancer risk adjusted for potential confounders were calculated for Gc genotypes. ANOVA was used to compare geometric means of serum 25(OH)D across Gc genotypes. Serum 25(OH)D concentrations in the control group significantly differed by Gc genotype, being lowest in Gc2 allele carriers. The geometric means of 25(OH)D were 53.0, 47.8, and 40.4 nmol/L for Gc1-1, Gc2-1, and Gc2-2 genotypes, respectively (Ptrend &lt; 0.0001). Gc2-2 genotype was associated with a significantly decreased risk of postmenopausal breast cancer with an odds ratio (95% confidence interval) of 0.72 (0.54-0.96), compared with homozygote Gc1s allele carriers. No interaction between 25(OH)D status and Gc genotype was observed, nor did the association change considerably after adjustment for 25(OH)D status. Our results provide evidence for a serum 25(OH)D-independent effect of Gc2 allele carrier status in postmenopausal breast cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1339–43)
Stability of the Nicotine Metabolite Ratio inad Libitumand Reducing Smokers
Authors: Mooney Marc E. , Li Zhong-ze , Murphy Sharon E. , Pentel Paul R. , Le Chap , Hatsukami Dorothy K. 
Published: June 2008

AbstractBackground: The ratio of two nicotine metabolites, cotinine and trans-3′-hydroxycotinine (3-HC), has been validated as a method of phenotyping the activity of the liver enzyme cytochrome P450 (CYP) 2A6 and, thus, the rate of nicotine metabolism. Our objective was to evaluate the correlates and stability of the 3-HC to cotinine ratio in ad libitum and reducing smokers, using nicotine replacement therapy (NRT), over a period of months.Methods: Smokers (n = 123, 94% Caucasian) participated in a smoking reduction study, where one-third of the sample smoked ad libitum for 8 weeks (Waitlist phase), before joining the rest of the participants for 12 weeks of cigarette reduction (Reduction phase) using NRT. Urinary nicotine, cotinine, and 3-HC were measured at each visit.Results: The baseline 3-HC to cotinine ratio was significantly but weakly correlated with cigarettes per day (r = 0.19), BMI (r = −0.27), and waking at night to smoke (r = 0.23). As assessed by repeated measure ANOVA, the 3-HC to cotinine ratio was stable in the Waitlist phase [coefficient of variation for 3 to 4 measurements, 38% (range, 5-110%)], whereas minor variation was noted in the Reduction phase [coefficient of variation for 3-5 measurements, 35% (range, 10-107%)].Conclusions: In nonreducing ad libitum smokers, the 3-HC to cotinine ratio was generally stable, whereas during smoking reduction using NRT, some small variation was detected. Although the current findings are suggestive of the stability of the 3-HC to cotinine ratio in a predominantly Caucasian sample smoking freely or reducing smoking with NRT, additional research is needed in more diverse populations. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1396–400)
Down-Regulation of Hedgehog-Interacting Protein through Genetic and Epigenetic Alterations in Human Hepatocellular Carcinoma
Authors: Tada Motohisa , Kanai Fumihiko , Tanaka Yasuo , Tateishi Keisuke , Ohta Miki , Asaoka Yoshinari , Seto Motoko , Muroyama Ryosuke , Fukai Kenichi , Imazeki Fumio , Kawabe Takao , Yokosuka Osamu , Omata Masao 
Published: June 2008

Abstract
Purpose: Hedgehog (Hh) signaling is activated in several cancers. However, the mechanisms of Hh signaling activation in hepatocellular carcinoma (HCC) have not been fully elucidated. We analyzed the involvement of Hh-interacting protein (HHIP) gene, a negative regulator of Hh signaling, in HCC.
Experimental Design: Glioma-associated oncogene homologue (Gli) reporter assay, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, and quantitative real-time reverse transcription–PCR for the target genes of the Hh signals were performed in HHIP stably expressing hepatoma cells. Quantitative real-time PCR for HHIP was performed in hepatoma cells and 36 HCC tissues. The methylation status of hepatoma cells and HCC tissues was also analyzed by sodium bisulfite sequencing, demethylation assay, and quantitative real-time methylation-specific PCR. Loss of heterozygosity (LOH) analysis was also performed in HCC tissues.
Results: HHIP overexpression induced significant reductions of Gli reporter activity, cell viability, and transcription of the target genes of the Hh signals. HHIP was hypermethylated and transcriptionally down-regulated in a subset of hepatoma cells. Treatment with a demethylating agent led to the HHIP DNA demethylation and restoration of HHIP transcription. HHIP transcription was also down-regulated in the majority of HCC tissues, and more than half of HCC tissues exhibited HHIP hypermethylation. The HHIP transcription level in HHIP-methylated HCC tissues was significantly lower than in HHIP-unmethylated HCC tissues. More than 30% of HCC tissues showed LOH at the HHIP locus.
Conclusions: The down-regulation of HHIP transcription is due to DNA hypermethylation and/or LOH, and Hh signal activation through the inactivation of HHIP may be implicated in the pathogenesis of human HCC.
Increase in Brain Tumor Permeability in Glioma-Bearing Rats with Nitric Oxide Donors
Authors: Yin Dali , Wang Xiao , Konda Bindu M. , Ong John M. , Hu Jinwei , Sacapano Manuel R. , Ko MinHee K. , Espinoza Andres J. , Irvin Dwain K. , Shu Yan , Black Keith L. 
Published: June 2008

AbstractPurpose: The blood-brain tumor barrier (BTB) significantly limits the delivery of chemotherapeutics to brain tumors. Nitric oxide (NO) is involved in the regulation of cerebral vascular permeability. We investigated the effects of NO donors, l-arginine and hydroxyurea, on BTB permeability in 9L gliosarcoma-bearing Fischer rats.Experimental Design: The rats implanted with 9L gliosarcoma were dosed orally with hydroxyurea and l-arginine. BTB permeability, defined by the unidirectional transport constant, Ki, for [14C]sucrose was measured. The expression of neural and endothelial NO synthase (NOS) in tumors and normal brain tissue was examined. Further, the levels of NO, l-citrulline, and cGMP in the tumor and normal brain tissue were measured.Results: Oral administration of l-arginine or hydroxyurea significantly increased BTB permeability when compared with the nontreated control. The selective effects were abolished by iberiotoxin, an antagonist of calcium-dependent potassium (KCa) channel that is a cGMP pathway effector. The expression of endothelial NOS, but not neural NOS, was higher in tumor vessels than in those of normal brain. Moreover, the levels of NO, l-citrulline, a byproduct of NO formation from l-arginine, and cGMP were enhanced in the tumor tissue by oral administration of l-arginine and/or hydroxyurea.Conclusions: Oral administration of l-arginine or hydroxyurea selectively increased tumor permeability, which is likely mediated by alteration in cGMP levels. The findings suggest that use of oral NO donors may be a strategy to enhance the delivery of chemotherapeutics to malignant brain tumors.
Affibody Molecules for In vivo Characterization of HER2-Positive Tumors by Near-Infrared Imaging
Authors: Lee Sang Bong , Hassan Moinuddin , Fisher Robert , Chertov Oleg , Chernomordik Victor , Kramer-Marek Gabriela , Gandjbakhche Amir , Capala Jacek 
Published: June 2008

Abstract
Purpose: HER2 overexpression has been associated with a poor prognosis and resistance to therapy in breast cancer patients. We are developing molecular probes for in vivo quantitative imaging of HER2 receptors using near-infrared (NIR) optical imaging. The goal is to provide probes that will minimally interfere with the studied system, that is, whose binding does not interfere with the binding of the therapeutic agents and whose effect on the target cells is minimal.
Experimental Design: We used three different types of HER2-specific Affibody molecules [monomer ZHER2:342, dimer (ZHER2:477)2, and albumin-binding domain-fused-(ZHER2:342)2] as targeting agents and labeled them with Alexa Fluor dyes. Trastuzumab was also conjugated, using commercially available kits, as a standard control. The resulting conjugates were characterized in vitro by toxicity assays, Biacore affinity measurements, flow cytometry, and confocal microscopy. Semiquantitative in vivo NIR optical imaging studies were carried out using mice with s.c. xenografts of HER2-positive tumors.
Results: The HER2-specific Affibody molecules were not toxic to HER2-overexpressing cells and their binding to HER2 did interfere with neither binding nor effectives of trastuzumab. The binding affinities and specificities of the Affibody-Alexa Fluor fluorescent conjugates to HER2 were unchanged or minimally affected by the modifications. Pharmacokinetics and biodistribution studies showed the albumin-binding domain-fused-(ZHER2:342)2-Alexa Fluor 750 conjugate to be an optimal probe for optical imaging of HER2 in vivo.
Conclusion: Our results suggest that Affibody-Alexa Fluor conjugates may be used as a specific NIR probe for the noninvasive semiquantitative imaging of HER2 expression in vivo.
CIP2A Is Overexpressed in Gastric Cancer and Its Depletion Leads to Impaired Clonogenicity, Senescence, or Differentiation of Tumor Cells
Authors: Li Wenjuan , Ge Zheng , Liu Cheng , Liu Zhifang , Björkholm Magnus , Jia Jihui , Xu Dawei 
Published: June 2008

Abstract
Purpose: Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogenic factor stabilizing c-MYC protein and driving cellular transformation. We determine whether CIP2A expression can serve as marker for gastric cancer and investigate the mechanism underlying CIP2A-mediated transformation and cell proliferation.
Experimental Design: Normal and malignant gastric tissues derived from 37 patients with gastric cancer were analyzed for CIP2A expression using reverse transcription-PCR and immunohistochemical staining. Gastric and other cell lines with different p53 and pRB backgrounds were used to inhibit CIP2A expression using small interfering RNA and then examined for clonogenic potentials, senescence, or differentiation.
Results: CIP2A mRNA was present in 34 of 37 (90%) of tumor specimens but absent in 27 of 37 (73%) of matched normal gastric mucosa. In 10 adjacent normal tissues with detectable CIP2A mRNA, 6 of them exhibited much weaker levels of CIP2A compared with their corresponding tumors. Thus, a total of 32 (87%) gastric cancer samples overexpressed CIP2A. CIP2A protein expression was readily detectable in the tumor tissues but absent in normal gastric mucosa. Depleting CIP2A expression substantially inhibited growth and clonogenic capabilities of tumor cell lines independently of p53 and pRB pathways. Gastric cancer–derived AGS cells underwent senescence following the inhibition of CIP2A expression. Moreover, CIP2A depletion triggered partial differentiation of leukemic HL60 cells.
Conclusion: CIP2A in tumor cells is required for sustained proliferation by preventing cell growth arrest, senescence, or differentiation and its expression is significantly (P &lt; 0.001) discriminatory between normal and cancerous gastric tissue.
Intraoperative 186Re-Liposome Radionuclide Therapy in a Head and Neck Squamous Cell Carcinoma Xenograft Positive Surgical Margin Model
Authors: Wang Sean X. , Bao Ande , Herrera Stephanie J. , Phillips William T. , Goins Beth , Santoyo Cristina , Miller Frank R. , Otto Randal A. 
Published: June 2008

Abstract
Purpose: Positive surgical margins in advanced head and neck squamous cell carcinoma (HNSCC) have a well-documented association with an increased risk of locoregional recurrence and significantly poorer survival. Traditionally, unresectable tumor is treated with postoperative radiotherapy and/or chemotherapy. However, these therapeutic options can delay treatment and increase toxicity. The potential value of intraoperative injection of liposomal therapeutic radionuclides as a locoregional, targeted therapy in unresectable advanced HNSCC was assessed in a nude rat xenograft positive surgical margin model.
Experimental Design: The therapeutic effects of β-emission rhenium-186 (186Re) carried by liposomes into the tumor remnants in a nude rat squamous cell carcinoma xenograft model were studied. Following the partial resection of tumor xenografts, the animals were intratumorally injected with 186Re-labeled or unlabeled (control) neutrally charged or positively charged 100-nm-diameter liposomes. Tumor size, body weight, hematology, and toxicity were monitored for 35 days posttherapy.
Results: The neutral (n = 4) and cationic (n = 4) liposome control groups showed an increase in tumor growth of 288.0 ± 37.3% and 292.2 ± 133.7%, respectively, by day 15. The 186Re-neutral-liposome group (n = 8) and the 186Re-cationic-liposome group (n = 8) presented with an average final tumor volume of 25.6 ± 21.8% and 28.5 ± 32.2%, respectively, at the end of the study (day 35). All groups showed consistent increases in body weight. No significant systemic toxicity was observed in any of the animals.
Conclusions: With excellent tumor suppression and minimal side-effect profile, the intraoperative use of liposomal therapeutic radionuclides may play a role in the management of positive surgical margins in advanced HNSCC.