bluuebunny/crossref_metadata_2025_split huggingface dataset:
Down-regulation of p57Kip2 Induces Prostate Cancer in the Mouse
Authors: Jin Ren Jie , Lho Yongsoo , Wang Yongqing , Ao Mingfang , Revelo Monica Patricia , Hayward Simon W. , Wills Marcia L. , Logan Susan K. , Zhang Pumin , Matusik Robert J. 
Published: May 2008

Abstract
p57Kip2 has been considered a candidate tumor suppressor gene because of its location in the genome, biochemical activities, and imprinting status. However, little is known about the role of p57Kip2 in tumorigenesis and cancer progression. Here, we show that the expression of p57Kip2 is significantly decreased in human prostate cancer, and the overexpression of p57Kip2 in prostate cancer cells significantly suppressed cell proliferation and reduced invasive ability. In addition, overexpression of p57Kip2 in LNCaP cells inhibited tumor formation in nude mice, resulting in well-differentiated squamous tumors rather than adenocarcinoma. Furthermore, the prostates of p57Kip2 knockout mice developed prostatic intraepithelial neoplasia and adenocarcinoma. Remarkably, this mouse prostate cancer is pathologically identical to human prostate adenocarcinoma. Therefore, these results strongly suggest that p57Kip2 is an important gene in prostate cancer tumorigenesis, and the p57Kip2 pathway may be a potential target for prostate cancer prevention and therapy. [Cancer Res 2008;68(10):3601–8]
OSU-HDAC42, a Histone Deacetylase Inhibitor, Blocks Prostate Tumor Progression in the Transgenic Adenocarcinoma of the Mouse Prostate Model
Authors: Sargeant Aaron M. , Rengel Robert C. , Kulp Samuel K. , Klein Russell D. , Clinton Steven K. , Wang Yu-Chieh , Chen Ching-Shih 
Published: May 2008

Abstract
Histone deacetylase (HDAC) inhibitors suppress tumor cell growth via a broad spectrum of mechanisms, which should prove advantageous in the context of cancer prevention. Here, we examined the effect of dietary administration of OSU-HDAC42, a novel HDAC inhibitor, on prostate tumor progression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Based on a series of pilot studies, an AIN-76A diet was formulated containing 208 ppm OSU-HDAC42, which was estimated to deliver ∼25 mg/kg of drug per day to each mouse and found to cause a suppression of PC-3 xenograft tumor growth equivalent to that achieved by gavage administration of a similar dose. At 6 weeks of age, TRAMP mice received this drug-containing or control diet for 4 or 18 weeks and were evaluated for prostatic intraepithelial neoplasia (PIN) and carcinoma development, respectively. OSU-HDAC42 not only decreased the severity of PIN and completely prevented its progression to poorly differentiated carcinoma (74% incidence in controls versus none in drug-treated mice), but also shifted tumorigenesis to a more differentiated phenotype, suppressing absolute and relative urogenital tract weights by 86% and 85%, respectively, at 24 weeks of age. This tumor suppression was associated with the modulation of intraprostatic biomarkers, including those indicative of HDAC inhibition, increased apoptosis and differentiation, and decreased proliferation. With the exception of completely reversible hematologic alterations and testicular degeneration, no significant changes in body weight or other indicators of general health were observed in drug-treated mice. These results suggest that OSU-HDAC42 has value in prostate cancer prevention. [Cancer Res 2008;68(10):3999–4009]
Differences in Baseline Characteristics and Outcomes at 1- and 2-Year Follow-up of Cancer Survivors Accrued via Self-Referral versus Cancer Registry in the FRESH START Diet and Exercise Trial
Authors: Snyder Denise Clutter , Sloane Richard , Lobach David , Lipkus Isaac M. , Peterson Bercedis , Kraus William , Demark-Wahnefried Wendy 
Published: May 2008

Abstract
Participant accrual to research studies is a challenge; oftentimes, advertisements are used to supplement cases ascertained through clinic caseloads and cancer registries. It is unknown, however, if cases ascertained through these two sources differ. In this study, we compared self-referred (n = 209) and registry-ascertained (n = 334) participants enrolled in FRESH START, a randomized controlled trial promoting a healthy diet and increased exercise among breast and prostate cancer survivors. The two groups were compared on baseline characteristics, adherence, attrition, and outcomes by study arm. Compared with participants enrolled from registries, self-referrals were significantly younger (54.1 ± 10.4 versus 58.7 ± 10.7 years), more likely to have later-stage disease and to have received chemotherapy (40% versus 19%), and more likely to report “fighting spirit” coping styles (50% versus 30%), lower quality-of-life (88.2 ± 15.1 versus 92.0 ± 12.9), fewer comorbid conditions (1.87 ± 1.60 versus 2.24 ± 1.78), and lower consumption of five or more daily servings of fruits and vegetables (35% versus 45%; P values &lt;0.05). Although no differences in behavior change were observed between self-referred and registry-ascertained cases assigned to the tailored intervention arm, this was not the case within the attention control arm. Among those who received the attention control intervention of standardized materials in the public domain, self-referred versus registry-ascertained participants showed significantly greater increases in exercise at 1-year follow-up and significantly greater increases in fruit and vegetable consumption at both 1- and 2-year follow-up (P values &lt;0.05). Several differences exist between self-referred and registry-ascertained participants, including motivation to respond to standardized educational materials, which appears significantly greater in self-referred populations. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1288–94)
Long-term Anti-inflammatory and Antihistamine Medication Use and Adult Glioma Risk
Authors: Scheurer Michael E. , El-Zein Randa , Thompson Patricia A. , Aldape Kenneth D. , Levin Victor A. , Gilbert Mark R. , Weinberg Jeffrey S. , Bondy Melissa L. 
Published: May 2008

Abstract
A personal history of asthma or allergy has been associated with a reduced risk for adult malignant gliomas. Recent reports on the use of nonsteroidal anti-inflammatory drugs (NSAID) and the presence of risk alleles in asthma susceptibility genes showed similar inverse associations. To further explore the relationship between immune mediators and gliomas, we examined the use of NSAID and antihistamines, history of asthma or allergy, and infection in 325 glioma cases and 600 frequency-matched controls from the metropolitan area of Houston, TX (2001-2006). The regular use of NSAID was associated with a 33% reduction in the risk for glioma, suggestive of possible antitumor activity. Surprisingly, regular long-term antihistamine use among those reporting a history of asthma or allergies was significantly associated with a 3.5-fold increase in the risk for glioma. Similar to previous reports, cases in our study were less likely to have reported asthma, allergy, or a history of a number of viral infections (chickenpox or shingles, oral herpes, and mononucleosis) than controls. We therefore speculate that the observed positive association with antihistamine use may reflect an alteration of protective immune factors in susceptible individuals. Our results lend additional support for an important but unknown link between malignant brain tumors and immune mediators. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1277–81)
Evaluating the Effectiveness of Using Standard Mammogram Form to Predict Breast Cancer Risk: Case-Control Study
Authors: Ding Jane , Warren Ruth , Warsi Iqbal , Day Nick , Thompson Deborah , Brady Michael , Tromans Christopher , Highnam Ralph , Easton Douglas 
Published: May 2008

Abstract
Breast density is a well-known breast cancer risk factor. Most current methods of measuring breast density are area based and subjective. Standard mammogram form (SMF) is a computer program using a volumetric approach to estimate the percent density in the breast. The aim of this study is to evaluate the current implementation of SMF as a predictor of breast cancer risk by comparing it with other widely used density measurement methods. The case-control study comprised 634 cancers with 1,880 age-matched controls combined from the Cambridge and Norwich Breast Screening Programs. Data collection involved assessing the films based both on Wolfe's parenchymal patterns and on visual estimation of percent density and then digitizing the films for computer analysis (interactive threshold technique and SMF). Logistic regression was used to produce odds ratios associated with increasing categories of breast density. Density measures from all four methods were strongly associated with breast cancer risk in the overall population. The stepwise rises in risk associated with increasing density as measured by the threshold method were 1.37 [95% confidence interval (95% CI), 1.03-1.82], 1.80 (95% CI, 1.36-2.37), and 2.45 (95% CI, 1.86-3.23). For each increasing quartile of SMF density measures, the risks were 1.11 (95% CI, 0.85-1.46), 1.31 (95% CI, 1.00-1.71), and 1.92 (95% CI, 1.47-2.51). After the model was adjusted for SMF results, the threshold readings maintained the same strong stepwise increase in density-risk relationship. On the contrary, once the model was adjusted for threshold readings, SMF outcome was no longer related to cancer risk. The available implementation of SMF is not a better cancer risk predictor compared with the thresholding method. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1074–81)
Vitamin D Receptor Expression in Normal, Premalignant, and Malignant Human Lung Tissue
Authors: Menezes Ravi J. , Cheney Richard T. , Husain Aliya , Tretiakova Maria , Loewen Gregory , Johnson Candace S. , Jayaprakash Vijay , Moysich Kirsten B. , Salgia Ravi , Reid Mary E. 
Published: May 2008

Abstract
Background: There is a strong interest in identifying chemopreventive agents that might help decrease the burden of lung cancer. The active metabolite of vitamin D, 1,25-dihydroxycholecalciferol (calcitriol), has been shown to have antiproliferative effects in several tumor types, mediated by the vitamin D receptor (VDR). This is the first comprehensive survey of VDR expression in a series of human lung tissues, including normal and premalignant central airway biopsies and lung tumors.
Methods: Immunohistochemical expression of nuclear and cytoplasmic VDR was examined in 180 premalignant or malignant bronchial biopsies from bronchoscopy of 78 high-risk individuals at the Roswell Park Cancer Institute and also in 63 tumor samples from 35 lung cancer patients from the University of Chicago Hospitals. Associations between clinicopathologic data and VDR expression were examined.
Results: VDR expression was present in many samples. In biopsies, VDR was commonly detected throughout the full epithelial layer. Most histologically normal (60%, 53 of 88) and metaplastic (61%, 39 of 64) samples had moderate to high nuclear intensity; dysplastic samples mostly had low nuclear intensity (10 of 18, 55%). In tumor samples, 62% (38 of 61) were lacking cytoplasmic VDR, with nuclear expression present in 79%(49 of 62). Analysis of all samples revealed a positive linear trend between proportion of samples with greater nuclear than cytoplasmic intensity and increasing histologic grade (P &lt; 0.01).
Conclusions: VDR expression spanned the lung carcinogenesis spectrum. Nuclear expression was similar across various histologies, whereas cytoplasmic expression decreased with increasing histologic grade. These results indicate that there is potential for the use of calcitriol as a chemopreventive agent against the development of lung cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1104–10)
Matrix Metalloproteinase 1 (MMP1) Is Associated with Early-Onset Lung Cancer
Authors: Sauter Wiebke , Rosenberger Albert , Beckmann Lars , Kropp Silke , Mittelstrass Kirstin , Timofeeva Maria , Wölke Gabi , Steinwachs Angelika , Scheiner Daniela , Meese Eckart , Sybrecht Gerhard , Kronenberg Florian , Dienemann Hendrik ,   The LUCY-Consortium, Chang-Claude Jenny , Illig Thomas , Wichmann Heinz-Erich , Bickeböller Heike , Risch Angela 
Published: May 2008

Abstract
Matrix metalloproteinases (MMP) play a key role in the breakdown of extracellular matrix and in inflammatory processes. MMP1 is the most highly expressed interstitial collagenase degrading fibrillar collagens. Overexpression of MMP1 has been shown in tumor tissues and has been suggested to be associated with tumor invasion and metastasis. Nine haplotype tagging and additional two intronic single nucleotide polymorphisms (SNP) of MMP1 were genotyped in a case control sample, consisting of 635 lung cancer cases with onset of disease below 51 years of age and 1,300 age- and sex-matched cancer-free controls. Two regions of linkage disequilibrium (LD) of MMP1 could be observed: a region of low LD comprising the 5′ region including the promoter and a region of high LD starting from exon 1 to the end of the gene and including the 3′ flanking region. Several SNPs were identified to be individually significantly associated with risk of early-onset lung cancer. The most significant effect was seen for rs1938901 (P = 0.0089), rs193008 (P = 0.0108), and rs996999 (P = 0.0459). For rs996999, significance vanished after correction for multiple testing. For each of these SNPs, the major allele was associated with an increase in risk with an odds ratio between 1.2 and 1.3 (95% confidence interval, 1.0-1.5). The haplotype analysis supported these findings, especially for subgroups with high smoking intensity. In summary, we identified MMP1 to be associated with an increased risk for lung cancer, which was modified by smoking. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1127–35)
Body Mass Index, Physical Activity, and Bladder Cancer in a Large Prospective Study
Authors: Koebnick Corinna , Michaud Dominique , Moore Steven C. , Park Yikyung , Hollenbeck Albert , Ballard-Barbash Rachel , Schatzkin Arthur , Leitzmann Michael F. 
Published: May 2008

Abstract
Increased body size and lack of physical activity are associated with increased risk of several cancers, but the relations of body mass index (BMI) and physical activity to bladder cancer are poorly understood. We investigated the associations between BMI, physical activity, and bladder cancer in the NIH-AARP Diet and Health Study, a prospective cohort of 471,760 U.S. men and women, followed from 1995 to 2003. During 3,404,642 person-years of follow-up, we documented 1,719 incident cases of bladder cancer. Compared with normal weight, obesity was associated with an up to 28% increased risk for bladder cancer. The multivariate relative risks of bladder cancer for BMI values of 18.5 to 24.9 (reference), 25.0 to 29.9, 30.0 to 34.9, and ≥35 kg/m2 were 1.0, 1.15, 1.22, and 1.28 (95% confidence interval, 1.02-1.61; Ptrend = 0.028). The association between BMI and bladder cancer was consistent among subgroups defined by gender, education, smoking status, and other potential effect modifiers. In contrast, physical activity showed no statistically significant relation with bladder cancer. After multivariate adjustment, including BMI, the relative risks of bladder cancer for increasing frequency of physical activity [0 (reference), &lt;1, 1-2, 3-4, and ≥5 times a week] were 1.0, 0.85, 0.89, 0.91, and 0.87 (95% confidence interval, 0.74-1.02; Ptrend = 0.358), respectively. In conclusion, these findings provide support for a modest adverse effect of adiposity on risk for bladder cancer. In contrast, our results do not suggest a relation between physical activity and bladder cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1214–21)
Effects of Baseline Comorbidities on Cancer Screening Trial Adherence among Older African American Men
Authors: Ford Marvella E. , Havstad Suzanne L. , Fields Maya E. , Manigo Brandy , McClary Beth , Lamerato Lois 
Published: May 2008

AbstractBackground: The purpose of this study was to examine the effects of baseline comorbidities on screening adherence in a sample of older African American men (ages ≥55 years) enrolled in a case management intervention in a cancer screening trial.Methods: Baseline comorbidity data were obtained from 683 African American men who were randomly assigned to a case management intervention group (n = 344) or to a case management control group (n = 339). The effects of comorbidities on the screening adherence rates of each group were then assessed.Results: No statistically significant interactions were found between each health history characteristic and the intervention. Therefore, analyses were not stratified by intervention status. In general, participants with comorbidities were no less likely to adhere to trial screening than participants without comorbidities. Exceptions were current smokers and participants with chronic bronchitis. Current smokers were less likely than others to adhere to the prostate-specific antigen test (P = 0.02) and the digital rectal examination for prostate cancer screening (P = 0.01), to the chest X-ray for lung cancer screening (P &lt; 0.01), and to the flexible sigmoidoscopy for colorectal cancer screening (P = 0.04). Participants with chronic bronchitis had lower rates of adherence to the chest X-ray (P = 0.06). Having a relative with cancer positively influenced adherence to the digital rectal examination (P = 0.05).Conclusions: Overall, older African American men with comorbidities appear to be very good candidates for participation in longitudinal cancer screening trials. However, smoking had a statistically significant and deleterious effect on adherence to all types of screening. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1234–9)
Mechanisms of Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer
Authors: Engelman Jeffrey A. , Jänne Pasi A. 
Published: May 2008

AbstractEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors gefitinib and erlotinib are effective therapies for non–small cell lung cancer patients whose tumors harbor somatic mutations in EGFR. All patients, however, ultimately develop resistance to these agents. Thus, there is a great need to understand how patients become resistant to develop effective therapies for these cancers. Studies over the last few years have identified two different EGFR tyrosine kinase inhibitor resistance mechanisms, a secondary mutation in EGFR, EGFR 790M, and amplification of the MET oncogene. These findings have led to clinical trials using newly designed targeted therapies that can overcome these resistance mechanisms and have shown promise in laboratory studies. Ongoing research efforts will likely continue to identify additional resistance mechanisms, and these findings will hopefully translate into effective therapies for non–small cell lung cancer patients.
Detection of Copy Number Alterations in Metastatic Melanoma by a DNA FluorescenceIn situHybridization Probe Panel and Array Comparative Genomic Hybridization: A Southwest Oncology Group Study (S9431)
Authors: Moore Stephen R. , Persons Diane L. , Sosman Jeffrey A. , Bobadilla Dolores , Bedell Victoria , Smith David D. , Wolman Sandra R. , Tuthill Ralph J. , Moon Jim , Sondak Vernon K. , Slovak Marilyn L. 
Published: May 2008

AbstractPurpose: Gene copy number alteration (CNA) is common in malignant melanoma and is associated with tumor development and progression. The concordance between molecular cytogenetic techniques used to determine CNA has not been evaluated on a large set of loci in malignant melanoma.Experimental Design: A panel of 16 locus-specific fluorescence in situ hybridization (FISH) probes located on eight chromosomes was used to identify CNA in touch preparations of frozen tissue samples from 19 patients with metastatic melanoma (SWOG-9431). A subset (n = 11) was analyzed using bacterial artificial chromosome (BAC) array comparative genomic hybridization (aCGH) of DNA isolated directly from touch-preparation slides.Results: By FISH, most samples showed loss near or at WISP3/6p21, CCND3/6q22, and CDKN2A/9p21 (&gt;75% of samples tested). More than one third of CDKN2A/9p21 losses were biallelic. Gains of NEDD9/6p24, MET/7q31, and MYC/8q24 were common (57%, 47%, and 41%, respectively) and CNA events involving 9p21/7p12.3 and MET were frequently coincident, suggesting gain of the whole chromosome 7. Changes were confirmed by aCGH, which also uncovered many discreet regions of change, larger than a single BAC. Overlapping segments observed in &gt;45% of samples included many of the loci analyzed in the FISH study, in addition to other WNT pathway members, and genes associated with TP53 pathways and DNA damage response, repair, and stability.Conclusions: This study outlines a set of CNAs at the gene and regional level, using FISH and aCGH, which may provide a benchmark for future studies and may be important in selection of individual therapy for patients with metastatic malignant melanoma.
Phase I Safety and Pharmacokinetic Study of CT-011, a Humanized Antibody Interacting with PD-1, in Patients with Advanced Hematologic Malignancies
Authors: Berger Raanan , Rotem-Yehudar Rinat , Slama Gideon , Landes Shimon , Kneller Abraham , Leiba Merav , Koren-Michowitz Maya , Shimoni Avichai , Nagler Arnon 
Published: May 2008

Abstract
Purpose: CT-011 is a humanized IgG1 monoclonal antibody that modulates the immune response through interaction with PD-1, a protein belonging to the B7 receptor family present on lymphocytes. The objectives of this phase I study were to assess the dose-limiting toxicities, to determine the maximum tolerated dose, and to study the pharmacokinetics of CT-011 administered once to patients with advanced hematologic malignancies.
Experimental Design: Seventeen patients were treated with escalating doses of CT-011 ranging from 0.2 to 6 mg/kg. For pharmacokinetic analysis, blood samples were withdrawn from the patients before and immediately after treatment and at 24 hours, 48 hours, and on days 7, 14, and 21. CT-011 blood levels were assessed with a specific ELISA and derived concentrations were used to calculate pharmacokinetic parameters. Activation of the immune system was assessed by measuring peripheral blood CD4+, CD8+, and CD69+ lymphocytes.
Results: The study showed the antibody to be safe and well tolerated in this patient population. No single maximum tolerated dose was defined in this study. Clinical benefit was observed in 33% of the patients with one complete remission. Pharmacokinetic analyses show that serum Cmax and the AUC of CT-011 increased proportionally with dose. The median t1/2 of CT-011 ranged from 217 to 410 hours. Sustained elevation in the percentage of peripheral blood CD4+ lymphocytes was observed up to 21 days following CT-011 treatment.
Conclusions: A single administration of 0.2 to 6.0 mg/kg of CT-011 is safe and well tolerated in patients with advanced hematologic malignancies.