bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age of Diagnosis of Squamous Cell Cervical Carcinoma and Early Sexual Experience
Authors: Edelstein Zoe R. , Madeleine Margaret M. , Hughes James P. , Johnson Lisa G. , Schwartz Stephen M. , Galloway Denise A. , Carter Joseph J. , Koutsky Laura A. 
Published: April 2009

Abstract
Background: Given the established links among young age at first intercourse (AFI), number of sex partners, high-risk human papillomavirus infection, and squamous cell cervical cancer (SCC), we hypothesized that women diagnosed with SCC at younger ages would be more likely to report young AFI than women diagnosed later in life.
Methods: We performed a population-based investigation among invasive SCC cases who were diagnosed between 1986 and 2004, were ages 22 to 53 years, and lived in the metropolitan Seattle-Puget Sound region (n = 333). Using multivariate linear regression, we estimated coefficients and 95% confidence intervals (95% CI) to assess the association between age at SCC diagnosis and AFI (&lt;15, 15-18, ≥19 years) and number of sex partners at age &lt;20 years (0, 1, 2-4, 5-14, ≥15), accounting for birth year and other factors. Interactions were assessed using the likelihood ratio test.
Results: The interval between AFI and SCC diagnosis ranged from 4 to 35 years. In a multivariate model, compared with SCC cases reporting AFI ≥19, the mean age of diagnosis was 3.1 years younger for SCC cases reporting AFI &lt;15 (95% CI, -5.8 to -0.5) and 2.6 years younger for SCC cases reporting AFI 15 to 18 (95% CI, -4.6 to -0.6). Although number of sex partners at age &lt;20 years was associated with age at SCC diagnosis in a crude analysis, the association was not independent of AFI. However, in the AFI ≥19 and &lt;15 groups, differences in effect were seen by number of sex partners at age &lt;20 years (Pinteraction = 0.08), with the association remaining strong and significant only in the AFI &lt;15 group that had ≥2 partners at age &lt;20 years (coefficient, -4.2; 95% CI, -6.3 to -2.1).
Conclusion: Among younger and middle-aged women with SCC, early age of diagnosis was associated with early AFI, although the effect appeared to be modified by number of sex partners at age &lt;20 years. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1070–6)
Gender is an Age-Specific Effect Modifier for Papillary Cancers of the Thyroid Gland
Authors: Kilfoy Briseis A. , Devesa Susan S. , Ward Mary H. , Zhang Yawei , Rosenberg Philip S. , Holford Theodore R. , Anderson William F. 
Published: April 2009

Abstract
Background: Thyroid cancer incidence rates have increased worldwide for decades, although more for papillary carcinomas than other types and more for females than males. There are few known thyroid cancer risk factors except female gender, and the reasons for the increasing incidence and gender differences are unknown.
Methods: We used the National Cancer Institute's Surveillance, Epidemiology, and End Results 9 Registries Database for cases diagnosed during 1976-2005 to develop etiological clues regarding gender-related differences in papillary thyroid cancer incidence. Standard descriptive epidemiology was supplemented with age-period-cohort (APC) models, simultaneously adjusted for age, calendar-period and birth-cohort effects.
Results: The papillary thyroid cancer incidence rate among females was 2.6 times that among males (9.2 versus 3.6 per 100,000 person-years, respectively), with a widening gender gap over time. Age-specific rates were higher among women than men across all age groups, and the female-to-male rate ratio declined quite consistently from more than five at ages 20-24 to 3.4 at ages 35-44 and approached one at ages 80+. APC models for papillary thyroid cancers confirmed statistically different age-specific effects among women and men (P &lt; 0.001 for the null hypothesis of no difference by gender), adjusted for calendar-period and birth-cohort effects.
Conclusion: Gender was an age-specific effect modifier for papillary thyroid cancer incidence. Future analytic studies attempting to identify the risk factors responsible for rising papillary thyroid cancer incidence should be designed with adequate power to assess this age-specific interaction among females and males. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1092–100)
Components of Metabolic Syndrome and Metachronous Colorectal Neoplasia
Authors: Ashbeck Erin L. , Jacobs Elizabeth T. , Martínez María Elena , Gerner Eugene W. , Lance Peter , Thompson Patricia A. 
Published: April 2009

Abstract
Background: The consistent association between obesity and colorectal cancer is thought to be explained by metabolic disturbances common, but not exclusive, to the obese.
Methods: We assessed the relation between metachronous neoplasia and the components of metabolic syndrome (MetS) as defined by the National Cholesterol Education Program's Adult Treatment Panel III in 2,392 participants of two previously conducted chemoprevention trials. Waist circumference, fasting plasma glucose, trigylcerides, high-density lipoprotein, and systolic and diastolic blood pressure were measured at baseline.
Results: MetS classification was associated with increased odds of metachronous neoplasia among women [odds ratio (OR), 1.37; 95% confidence interval (95% CI), 1.01-1.85] but not among men (OR, 0.99; 95% CI, 0.81-1.21). High waist circumference in men (OR, 1.41; 95% CI, 1.15-1.72) and women (OR, 1.41; 95% CI, 1.05-1.90) and elevated fasting glucose in women (OR, 1.46; 95% CI, 1.09-1.96), as defined by Adult Treatment Panel III cutpoints, were associated with increased odds, whereas none of the other criteria were independently associated with metachronous neoplasia. When each trait was evaluated using quartiles, elevated glucose among women and large waist circumference among men were significantly associated with metachronous lesions. Exploratory analysis of waist circumference and fasting glucose suggested an interaction, where only the combination of large waist circumference and elevated glucose conferred significant increased odds of metachronous neoplasia among both men (OR, 1.36; 95% CI, 1.04-1.78; Pinteraction = 0.08) and women (OR, 1.83; 95% CI, 1.26-2.67; Pinteraction = 0.12).
Conclusions: These results suggest that, of the specific components of MetS, those that capture impaired glucose uptake increased the odds of metachronous neoplasia. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1134–43)
Associations between Polymorphisms in DNA Repair Genes and Glioblastoma
Authors: McKean-Cowdin Roberta , Barnholtz-Sloan Jill , Inskip Peter D. , Ruder Avima M. , Butler MaryAnn , Rajaraman Preetha , Razavi Pedram , Patoka Joe , Wiencke John K. , Bondy Melissa L. , Wrensch Margaret 
Published: April 2009

AbstractA pooled analysis was conducted to examine the association between select variants in DNA repair genes and glioblastoma multiforme, the most common and deadliest form of adult brain tumors. Genetic data for ∼1,000 glioblastoma multiforme cases and 2,000 controls were combined from four centers in the United States that have conducted case-control studies on adult glioblastoma multiforme, including the National Cancer Institute, the National Institute for Occupational Safety and Health, the University of Texas M. D. Anderson Cancer Center, and the University of California at San Francisco. Twelve DNA repair single-nucleotide polymorphisms were selected for investigation in the pilot collaborative project. The C allele of the PARP1 rs1136410 variant was associated with a 20% reduction in risk for glioblastoma multiforme (odds ratioCT or CC, 0.80; 95% confidence interval, 0.67-0.95). A 44% increase in risk for glioblastoma multiforme was found for individuals homozygous for the G allele of the PRKDC rs7003908 variant (odds ratioGG, 1.44; 95% confidence interval, 1.13-1.84); there was a statistically significant trend (P = 0.009) with increasing number of G alleles. A significant, protective effect was found when three single-nucleotide polymorphisms (ERCC2 rs13181, ERCC1 rs3212986, and GLTSCR1 rs1035938) located near each other on chromosome 19 were modeled as a haplotype. The most common haplotype (AGC) was associated with a 23% reduction in risk (P = 0.03) compared with all other haplotypes combined. Few studies have reported on the associations between variants in DNA repair genes and brain tumors, and few specifically have examined their impact on glioblastoma multiforme. Our results suggest that common variation in DNA repair genes may be associated with risk for glioblastoma multiforme. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1118–26)
Association of Nonsteroidal Anti-Inflammatory Drugs with Lung Cancer: Results from a Large Cohort Study
Authors: Slatore Christopher G. , Au David H. , Littman Alyson J. , Satia Jessie A. , White Emily 
Published: April 2009

Abstract
Background: Lung cancer is the most common cause of cancer-related mortality. Smoking cessation is crucial to decrease risk, but additional prevention modalities are needed. The use of nonsteroidal anti-inflammatory drugs (NSAID) may be promising.
Methods: The study was a prospective cohort of 77,125 men and women, ages 50 to 76 years, from Washington state recruited in 2000 to 2002 (the VITamin And Lifestyle study). Lung cancer cases were identified through the Seattle-Puget Sound Surveillance, Epidemiology and End Results cancer registry during 5 years of follow-up. Hazard ratios (HR) associated with 10-year average use of total NSAIDs (excluding low-dose aspirin) and specific categories of NSAIDs were calculated for total incident lung cancer and specific morphologies.
Results: A total of 665 lung cancer cases were identified. After adjusting for smoking, age, gender, and acetaminophen use, there was a borderline-significant inverse trend with total NSAID use [&gt;4.2 d/wk for &gt;10 years versus none: HR, 0.82; 95% confidence interval (95% CI), 0.64-1.04; P for trend = 0.05]. The association was strongest for adenocarcinoma (HR, 0.59; 95% CI, 0.37-0.94; P for trend = 0.01) and seemed to be limited to men (HR, 0.66; 95% CI, 0.47-0.92; P for trend = 0.01) and to long-term (≥10 years) former smokers (HR, 0.65; 95% CI, 0.44-0.96; P for trend = 0.04). There were no appreciable differences by NSAID type.
Conclusions: Total NSAID use was associated with a small reduced risk of lung cancer, which was strongest for adenocarcinoma, men, and long-term former smokers. These findings are supported by known lung carcinogenesis mechanisms and suggest that NSAIDS may be useful for chemoprevention. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1203–7)
Role of Eotaxin-1 Signaling in Ovarian Cancer
Authors: Levina Vera , Nolen Brian M. , Marrangoni Adele M. , Cheng Peng , Marks Jeffrey R. , Szczepanski Miroslaw J. , Szajnik Marta E. , Gorelik Elieser , Lokshin Anna E. 
Published: April 2009

AbstractPurpose: Tumor cell growth and migration can be directly regulated by chemokines. In the present study, the association of CCL11 with ovarian cancer has been investigated.Experimental Design and Results: Circulating levels of CCL11 in sera of patients with ovarian cancer were significantly lower than those in healthy women or women with breast, lung, liver, pancreatic, or colon cancer. Cultured ovarian carcinoma cells absorbed soluble CCL11, indicating that absorption by tumor cells could be responsible for the observed reduction of serum level of CCL11 in ovarian cancer. Postoperative CCL11 levels in women with ovarian cancer negatively correlated with relapse-free survival. Ovarian tumors overexpressed three known cognate receptors of CCL11, CC chemokine receptors (CCR) 2, 3, and 5. Strong positive correlation was observed between expression of individual receptors and tumor grade. CCL11 potently stimulated proliferation and migration/invasion of ovarian carcinoma cell lines, and these effects were inhibited by neutralizing antibodies against CCR2, CCR3, and CCR5. The growth-stimulatory effects of CCL11 were likely associated with activation of extracellular signal-regulated kinase 1/2, MEK1, and STAT3 phosphoproteins and with increased production of multiple cytokines, growth factors, and angiogenic factors. Inhibition of CCL11 signaling by the combination of neutralizing antibodies against the ligand and its receptors significantly increased sensitivity to cisplatin in ovarian carcinoma cells.Conclusion: We conclude that CCL11 signaling plays an important role in proliferation and invasion of ovarian carcinoma cells and CCL11 pathway could be targeted for therapy in ovarian cancer. Furthermore, CCL11 could be used as a biomarker and a prognostic factor of relapse-free survival in ovarian cancer.
RhoGDI2 Expression Is Associated with Tumor Growth and Malignant Progression of Gastric Cancer
Authors: Cho Hee Jun , Baek Kyoung Eun , Park Sun-Mi , Kim In-Kyu , Choi Yeong-Lim , Cho Hye-Jung , Nam In-Koo , Hwang Eun Mi , Park Jae-Yong , Han Jae Yoon , Kang Sang Soo , Kim Dong Chul , Lee Won Sup , Lee Mi-Ni , Oh Goo Taeg , Kim Jae Won , Lee Chang Won , Yoo Jiyun 
Published: April 2009

Abstract
Purpose: Rho GDP dissociation inhibitor 2 (RhoGDI2) has been identified as a regulator of Rho family GTPase. However, there is currently no direct evidence suggesting whether RhoGDI2 activates or inhibits Rho family GTPase in vivo (and which type), and the role of RhoGDI2 in tumor remains controversial. Here, we assessed the effects of RhoGDI2 expression on gastric tumor growth and metastasis progression.
Experimental Design: Proteomic analysis was done to investigate the tumor-specific protein expression in gastric cancer and RhoGDI2 was selected for further study. Immunohistochemistry was used to detect RhoGDI2 expression in clinical samples of primary gastric tumor tissues which have different pathologic stages. Gain-of-function and loss-of-function approaches were done to examine the malignant phenotypes of the RhoGDI2-expressing or RhoGDI2-depleting cells.
Results: RhoGDI2 expression was correlated positively with tumor progression and metastasis potential in human gastric tumor tissues, as well as cell lines. The forced expression of RhoGDI2 caused a significant increase in gastric cancer cell invasion in vitro, and tumor growth, angiogenesis, and metastasis in vivo, whereas RhoGDI2 depletion evidenced opposite effects.
Conclusion: Our findings indicate that RhoGDI2 is involved in gastric tumor growth and metastasis, and that RhoGDI2 may be a useful marker for tumor progression of human gastric cancer.
Fine Mapping of Chromosome 6q23-25 Region in Familial Lung Cancer Families Reveals RGS17 as a Likely Candidate Gene
Authors: You Ming , Wang Daolong , Liu Pengyuan , Vikis Haris , James Michael , Lu Yan , Wang Yian , Wang Min , Chen Qiong , Jia Dongmei , Liu Yan , Wen Weidong , Yang Ping , Sun Zhifu , Pinney Susan M. , Zheng Wei , Shu Xiao-Ou , Long Jirong , Gao Yu-Tang , Xiang Yong-Bing , Chow Wong-Ho , Rothman Nat , Petersen Gloria M. , de Andrade Mariza , Wu Yanhong , Cunningham Julie M. , Wiest Jonathan S. , Fain Pamela R. , Schwartz Ann G. , Girard Luc , Gazdar Adi , Gaba Colette , Rothschild Henry , Mandal Diptasri , Coons Teresa , Lee Juwon , Kupert Elena , Seminara Daniela , Minna John , Bailey-Wilson Joan E. , Amos Christopher I. , Anderson Marshall W. 
Published: April 2009

Abstract
Purpose: We have previously mapped a major susceptibility locus influencing familial lung cancer risk to chromosome 6q23-25. However, the causal gene at this locus remains undetermined. In this study, we further refined this locus to identify a single candidate gene, by fine mapping using microsatellite markers and association studies using high-density single nucleotide polymorphisms (SNP).
Experimental Design: Six multigenerational families with five or more affected members were chosen for fine-mapping the 6q linkage region using microsatellite markers. For association mapping, we genotyped 24 6q-linked cases and 72 unrelated noncancer controls from the Genetic Epidemiology of Lung Cancer Consortium resources using the Affymetrix 500K chipset. Significant associations were validated in two independent familial lung cancer populations: 226 familial lung cases and 313 controls from the Genetic Epidemiology of Lung Cancer Consortium, and 154 familial cases and 325 controls from Mayo Clinic. Each familial case was chosen from one high-risk lung cancer family that has three or more affected members.
Results: A region-wide scan across 6q23-25 found significant association between lung cancer susceptibility and three single nucleotide polymorphisms in the first intron of the RGS17 gene. This association was further confirmed in two independent familial lung cancer populations. By quantitative real-time PCR analysis of matched tumor and normal human tissues, we found that RGS17 transcript accumulation is highly and consistently increased in sporadic lung cancers. Human lung tumor cell proliferation and tumorigenesis in nude mice are inhibited upon knockdown of RGS17 levels.
Conclusion: RGS17 is a major candidate for the familial lung cancer susceptibility locus on chromosome 6q23-25.
Increased Vascular Endothelial Growth Factor-C Expression Is Insufficient to Induce Lymphatic Metastasis in Human Soft-Tissue Sarcomas
Authors: Lahat Guy , Lazar Alexander , Wang Xuemei , Wang Wei-Lien , Zhu Quan-Sheng , Hunt Kelly K. , Pollock Raphael E. , Lev Dina 
Published: April 2009

Abstract
Purpose: Unlike carcinomas, soft-tissue sarcoma (STS) rarely exhibit lymphatic spread. Consequently, we examined expression and function of vascular endothelial growth factor (VEGF)-C and STS-associated lymphatic vessel density (LVD) components of this process.
Experimental Design: VEGF-C and VEGF-A mRNA and VEGF-C protein expression were evaluated in STS, STS cell lines, and breast cancers (reverse transcription-PCR, quantitative reverse transcription-PCR, and ELISA). STS cell conditioned medium after VEGF-C knockdown was examined for endothelial cell proliferation and migration effects (MTS and migration assays). Paraffin-embedded human lymph node-negative and lymph node-positive STS and lymph node-negative and lymph node-positive breast cancers were examined for VEGF-C, D2-40, and CD31 expression (immunohistochemistry). LVD differences were analyzed by Wilcoxon rank-sum tests.
Results: STS and breast cancer VEGF-C expression was comparable and higher than normal tissue levels. STS cells secreted functional VEGF-C: STS conditioned medium induced lymphatic endothelial cell proliferation and migration, which was abrogated by STS cell VEGF-C knockdown. STS and breast cancer intratumoral LVD was similar. STS peritumoral LVD (PT-LVD) was reduced versus breast cancer PT-LVD (P &lt; 0.001). Significantly higher PT-LVD was observed in lymph node-positive versus lymph node-negative STS; lymphatic spreading STS subtypes also had higher LVD. STS VEGF-C expression and PT-LVD lacked correlation, and many lymph node-negative STS had high PT-LVD, suggesting complexity in this metastatic process.
Conclusions: Compared with breast cancers, STS exhibited lower PT-LVD independent of VEGF-C expression, which may underlie STS lymph node metastasis rarity. Moreover, lymphatic vessels appear necessary but not sufficient to sustain STS lymphatic spread. Examining STS “nonlymphatic” dissemination may help elucidate mechanisms of lymphatic spread, insights critically important to cancer metastasis control.
Surgical Stress Promotes Tumor Growth in Ovarian Carcinoma
Authors: Lee Jeong-Won , Shahzad Mian M.K. , Lin Yvonne G. , Armaiz-Pena Guillermo , Mangala Lingegowda S. , Han Hee-Dong , Kim Hye-Sun , Nam Eun Ji , Jennings Nicholas B. , Halder Jyotsnabaran , Nick Alpa M. , Stone Rebecca L. , Lu Chunhua , Lutgendorf Susan K. , Cole Steve W. , Lokshin Anna E. , Sood Anil K. 
Published: April 2009

AbstractPurpose: Surgical stress has been suggested to facilitate the growth of preexisting micrometastases as well as small residual tumor postoperatively. The purpose of this study was to examine the effects of surgical stress on ovarian cancer growth and to determine underlying mechanisms responsible for increased growth.Experimental Design: To mimic the effects of surgery, we did a laparotomy or mastectomy under isoflurane inhalation on athymic nude mice 4 days after i.p. tumor cell injection. Propranolol infusion via Alzet pumps was used to block the influence of sympathetic nervous system activation by surgical stress.Results: In both HeyA8 and SKOV3ip1 models, the mice in the laparotomy and mastectomy groups had significantly greater tumor weight (P &lt; 0.05) and nodules (P &lt; 0.05) compared with anesthesia only controls. There was no increase in tumor weight following surgery in the β-adrenergic receptor–negative RMG-II model. Propranolol completely blocked the effects of surgical stress on tumor growth, indicating a critical role for β-adrenergic receptor signaling in mediating the effects of surgical stress on tumor growth. In the HeyA8 and SKOV3ip1 models, surgery significantly increased microvessel density (CD31) and vascular endothelial growth factor expression, which were blocked by propranolol treatment.Conclusion: These results indicate that surgical stress could enhance tumor growth and angiogenesis, and β-blockade might be effective in preventing such effects.
Effects on sleep stages and microarchitecture of caffeine and its combination with zolpidem or trazodone in healthy volunteers
Authors: Paterson LM , Nutt DJ , Ivarsson M , Hutson PH , Wilson SJ 
Published: April 2009

AbstractCaffeine is the world’s most popular stimulant and is known to disrupt sleep. Administration of caffeine can therefore be used in healthy volunteers to mimic the effects of insomnia and thus to test the hypnotic effects of medication. This study assessed the effects of caffeine on sleep architecture and electroencephalography (EEG) spectrum alone and in combination with two different sleep-promoting medications. Home polysomnography was performed in 12 healthy male volunteers in a double-blind study whereby subjects received placebo, caffeine (150 mg), caffeine plus zolpidem (10 mg) and caffeine plus trazodone (100 mg) at bedtime in a randomised crossover design. In addition to delaying sleep onset, caffeine decreased total sleep time (TST), sleep efficiency (SE) and stage 2 sleep without significantly altering wake after sleep onset or the number of awakenings. Zolpidem attenuated the caffeine-induced decrease in SE and increased spindle density in the caffeine plus zolpidem combination compared with placebo. Trazodone attenuated the decrease in SE and TST, and it also increased stage 3 sleep, decreased the number of awakenings and decreased the spindle density. No significant changes in rapid eye movement (REM) sleep were observed, neither was any significant alteration in slow wave activity nor other EEG spectral measures, although the direction of change was similar to that previously reported for caffeine and appeared to ‘normalise’ after trazodone. These data suggest that caffeine mimics some, but not all of the sleep disruption seen in insomnia and that its disruptive effects are differentially attenuated by the actions of sleep-promoting compounds with distinct mechanisms of action.
Commentary on STAR*D: a summary and UK perspective
Authors: Hawley CJ , Fineberg NA 
Published: April 2009

Abstract The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) program attempted to determine whether some treatment sequences are better than others in the management of depression. Application of the findings to UK treatment settings is difficult because depression is an inhomogeneous condition and to regard it as a unitary entity, to which a unitary stratagem can be applied, is possibly misguided.