bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reliability of Serum Biomarkers of Inflammation from Repeated Measures in Healthy Individuals
Authors: Navarro Sandi L. , Brasky Theodore M. , Schwarz Yvonne , Song Xiaoling , Wang C.Y. , Kristal Alan R. , Kratz Mario , White Emily , Lampe Johanna W. 
Published: July 2012

Abstract
Background: Biomarkers of low-grade systemic inflammation are used to study the associations of inflammation with chronic diseases, including cancer. However, relatively little is known about the intraindividual variability of most of these measures.
Methods: Fasting serum samples, collected at baseline and the end of ≥3-week washout periods in a four-diet crossover feeding trial, were used to measure the inflammatory markers high sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-8, and soluble TNF receptor (sTNFR) I and II. Participants included 62 men and women for analyses of IL-6 and CRP and 56 for analyses of IL-8, TNF-α, and sTNFRs, aged 20 to 40, who were free of factors known to influence inflammation, for example, chronic disease, medication use, heavy alcohol use, smoking, and obesity (body mass index &gt;30 kg/m2). Intraclass correlations (ICC) were estimated using random effects ANOVA, across all four time points (∼6 weeks apart).
Results: ICCs for TNF-α and sTNFR I and II were very high: ICC = 0.92 [95% confidence interval (CI), 0.89–0.96], 0.92 (95% CI, 0.88–0.95), and 0.90 (95% CI, 0.85–0.94), respectively. ICCs for IL-8 and hsCRP were 0.73 (95% CI, 0.63–0.83) and 0.62 (95% CI, 0.49–0.75), respectively. The ICC for IL-6 was considerably lower, ICC = 0.48 (95% CI, 0.36–0.62). Three measures of IL-6 would be needed to achieve a reliability coefficient (Cronbach α) of 0.75.
Conclusions: With the exception of IL-6, reliability of all inflammatory markers in our panel was high.
Impact: This suggests that a single measure accurately captures the short-term (e.g., 4–6 months) variability within an individual. Cancer Epidemiol Biomarkers Prev; 21(7); 1167–70. ©2012 AACR.
Circadian Disruption, Sleep Loss, and Prostate Cancer Risk: A Systematic Review of Epidemiologic Studies
Authors: Sigurdardottir Lara G. , Valdimarsdottir Unnur A. , Fall Katja , Rider Jennifer R. , Lockley Steven W. , Schernhammer Eva , Mucci Lorelei A. 
Published: July 2012

Abstract
Disruption of the circadian system has been hypothesized to increase cancer risk, either because of direct disruption of the molecular machinery generating circadian rhythms or because of disruption of parameters controlled by the clock such as melatonin levels or sleep duration. This hypothesis has been studied in hormone-dependent cancers among women, but data are sparse about potential effects of circadian disruption on the risk of prostate cancer. This review systematically examines available data evaluating the effects of light at night, sleep patterns, and night shift work on prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 21(7); 1002–11. ©2012 AACR.
A Simulation Model to Predict the Impact of Prophylactic Surgery and Screening on the Life Expectancy of BRCA1 and BRCA2 Mutation Carriers
Authors: Sigal Bronislava M. , Munoz Diego F. , Kurian Allison W. , Plevritis Sylvia K. 
Published: July 2012

Abstract
Background: Women with inherited mutations in the BRCA1 or BRCA2 (BRCA1/2) genes are recommended to undergo a number of intensive cancer risk-reducing strategies, including prophylactic mastectomy, prophylactic oophorectomy, and screening. We estimate the impact of different risk-reducing options at various ages on life expectancy.
Methods: We apply our previously developed Monte Carlo simulation model of screening and prophylactic surgery in BRCA1/2 mutation carriers. Here, we present the mathematical formulation to compute age-specific breast cancer incidence in the absence of prophylactic oophorectomy, which is an input to the simulation model, and provide sensitivity analysis on related model parameters.
Results: The greatest gains in life expectancy result from conducting prophylactic mastectomy and prophylactic oophorectomy immediately after BRCA1/2 mutation testing; these gains vary with age at testing, from 6.8 to 10.3 years for BRCA1 and 3.4 to 4.4 years for BRCA2 mutation carriers. Life expectancy gains from delaying prophylactic surgery by 5 to 10 years range from 1 to 9.9 years for BRCA1 and 0.5 to 4.2 years for BRCA2 mutation carriers. Adding annual breast screening provides gains of 2.0 to 9.9 years for BRCA1 and 1.5 to 4.3 years for BRCA2. Results were most sensitive to variations in our assumptions about the magnitude and duration of breast cancer risk reduction due to prophylactic oophorectomy.
Conclusions: Life expectancy gains depend on the type of BRCA mutation and age at interventions. Sensitivity analysis identifies the degree of breast cancer risk reduction due to prophylactic oophorectomy as a key determinant of life expectancy gain.
Impact: Further study of the impact of prophylactic oophorectomy on breast cancer risk in BRCA1/2 mutation carriers is warranted. Cancer Epidemiol Biomarkers Prev; 21(7); 1066–77. ©2012 AACR.
Parental Age, Family Size, and Offspring's Risk of Childhood and Adult Acute Leukemia
Authors: Larfors Gunnar , Hallböök Helene , Simonsson Bengt 
Published: July 2012

Abstract
Background: An association between childhood acute leukemia and advanced parental age was observed more than 50 years ago, and the association has been repeated in several, but not all, subsequent studies. In contrast to the many studies addressing childhood leukemia, few have included adult patients.
Methods: In this register-based case–control study, we examined the association between parental age and incidence of acute leukemia in 2,660 childhood cases and 4,412 adult cases of acute leukemia, compared with 28,288 age-matched controls selected from a population-based register. Relative risks were estimated with conditional logistic regression.
Results: We found a small increased risk of childhood acute lymphoblastic leukemia with increasing paternal age (adjusted OR, 1.05 per 5-year increase in age). Risk estimates were similar for childhood acute myeloid leukemia (AML), whereas no association was found with adult leukemia. Meanwhile, we observed a decreased risk of adult AML with increasing number of siblings, both older and younger.
Conclusions: The results support the idea of a prenatal etiology of leukemia but indicate that parental age effects are limited to childhood cases.
Impact: This is the first large study on parental age and leukemia risk, which includes adult cases. The finding on family size and risk of adult AML needs to be validated in future studies. Cancer Epidemiol Biomarkers Prev; 21(7); 1185–90. ©2012 AACR.
Reproducibility of the Nicotine Metabolite Ratio in Cigarette Smokers
Authors: St.Helen Gideon , Novalen Maria , Heitjan Daniel F. , Dempsey Delia , Jacob Peyton , Aziziyeh Adel , Wing Victoria C. , George Tony P. , Tyndale Rachel F. , Benowitz Neal L. 
Published: July 2012

Abstract
Background: The nicotine metabolite ratio (NMR or 3-hydroxycotinine/cotinine) has been used to phenotype CYP2A6-mediated nicotine metabolism. Our objectives were to analyze (i) the stability of NMR in plasma, saliva, and blood in various storage conditions, (ii) the relationship between NMRs derived from blood, plasma, saliva, and urine, and (iii) the reproducibility of plasma NMR in ad libitum cigarette smokers.
Methods: We analyzed data from four clinical studies. In studies 1 and 2, we assessed NMR stability in saliva and plasma samples at room temperature (∼22°C) over 14 days and in blood at 4°C for up to 72 hours. In studies 2 and 3, we used Bland–Altman analysis to assess agreement between blood, plasma, saliva, and urine NMRs. In study 4, plasma NMR was measured on six occasions over 44 weeks in 43 ad libitum smokers.
Results: Reliability coefficients for stability tests of NMR in plasma and saliva at room temperature were 0.97 and 0.98, respectively, and 0.92 for blood at 4°C. Blood NMR agreed consistently with saliva and plasma NMRs but showed more variability in relation to urine NMR. The reliability coefficient for repeated plasma NMR measurements in smokers was 0.85.
Conclusion: The NMR is stable in blood, plasma, and saliva at the conditions tested. Blood, plasma, and saliva NMRs are similar whereas urine NMR is a good proxy for these NMR measures. Plasma NMR was reproducible over time in smokers.
Impact: One measurement may reliably estimate a smoker's NMR for use as an estimate of the rate of nicotine metabolism. Cancer Epidemiol Biomarkers Prev; 21(7); 1105–14. ©2012 AACR.
Quantifying Mediating Effects of Endogenous Estrogen and Insulin in the Relation between Obesity, Alcohol Consumption, and Breast Cancer
Authors: Hvidtfeldt Ulla A. , Gunter Marc J. , Lange Theis , Chlebowski Rowan T. , Lane Dorothy , Farhat Ghada N. , Freiberg Matthew S. , Keiding Niels , Lee Jennifer S. , Prentice Ross , Tjønneland Anne , Vitolins Mara Z. , Wassertheil-Smoller Silvia , Strickler Howard D. , Rod Naja H. 
Published: July 2012

Abstract
Background: Increased exposure to endogenous estrogen and/or insulin may partly explain the relationship of obesity, physical inactivity, and alcohol consumption and postmenopausal breast cancer. However, these potential mediating effects have not been formally quantified in a survival analysis setting.
Methods: We combined data from two case–cohort studies based in the Women's Health Initiative-Observational Study with serum estradiol levels, one of which also had insulin levels. A total of 1,601 women (601 cases) aged 50 to 79 years who were not using hormone therapy at enrollment were included. Mediating effects were estimated by applying a new method based on the additive hazard model.
Results: A five-unit increase in body mass index (BMI) was associated with 50.0 [95% confidence interval (CI), 23.2–76.6] extra cases per 100,000 women at-risk per year. Of these, 23.8% (95% CI, 2.9–68.4) could be attributed to estradiol and 65.8% (95% CI, 13.6–273.3) through insulin pathways. The mediating effect of estradiol was greater (48.8%; 95% CI, 18.8–161.1) for BMI when restricted to estrogen receptor positive (ER+) cases. Consuming 7+ drinks/wk compared with abstinence was associated with 164.9 (95% CI, 45.8–284.9) breast cancer cases per 100,000, but no significant contribution from estradiol was found. The effect of alcohol on breast cancer was restricted to ER+ breast cancers.
Conclusions: The relation of BMI with breast cancer was partly mediated through estradiol and, to a greater extent, through insulin.
Impact: The findings provide support for evaluation of interventions to lower insulin and estrogen levels in overweight and obese postmenopausal women to reduce breast cancer risk. Cancer Epidemiol Biomarkers Prev; 21(7); 1203–12. ©2012 AACR.
Use of Lung Cancer Screening Tests in the United States: Results from the 2010 National Health Interview Survey
Authors: Doria-Rose V. Paul , White Mary C. , Klabunde Carrie N. , Nadel Marion R. , Richards Thomas B. , McNeel Timothy S. , Rodriguez Juan L. , Marcus Pamela M. 
Published: July 2012

Abstract
Background: Before evidence of efficacy, lung cancer screening was being ordered by many physicians. The National Lung Screening Trial (NLST), which showed a 20% reduction in lung cancer mortality among those randomized to receive low-dose computed tomography (LDCT), will likely lead to increased screening use.
Methods: We estimated the prevalence of chest X-ray and CT use in the United States using data from the 2010 National Health Interview Survey (NHIS). Subjects included 15,537 NHIS respondents aged ≥40 years without prior diagnosis of lung cancer. Estimates of the size of the U. S. population by age and smoking status were calculated. Multivariate logistic regression examined predictors of test use adjusting for potential confounders.
Results: Twenty-three percent of adults reported chest X-ray in the previous year and 2.5% reported chest X-ray specifically to check for lung cancer; corresponding numbers for chest CT were 7.5% and 1.3%. Older age, black race, male gender, smoking, respiratory disease, personal history of cancer, and having health insurance were associated with test use. Approximately, 8.7 million adults in the United States would be eligible for LDCT screening according to NLST eligibility criteria.
Conclusions and Impact: Monitoring of trends in the use of lung screening tests will be vital to assess the impact of NLST and possible changes in lung cancer screening recommendations and insurance coverage in the future. Education of patients by their physicians, and of the general public, may help ensure that screening is used appropriately, in those most likely to benefit. Cancer Epidemiol Biomarkers Prev; 21(7); 1049–59. ©2012 AACR.
Frontiers in Cancer Epidemiology: A Challenge to the Research Community from the Epidemiology and Genomics Research Program at the National Cancer Institute
Authors: Khoury Muin J. , Freedman Andrew N. , Gillanders Elizabeth M. , Harvey Chinonye E. , Kaefer Christie , Reid Britt C. , Rogers Scott , Schully Sheri D. , Seminara Daniela , Verma Mukesh 
Published: July 2012

Abstract
The Epidemiology and Genomics Research Program (EGRP) at the National Cancer Institute (NCI) is developing scientific priorities for cancer epidemiology research in the next decade. We would like to engage the research community and other stakeholders in a planning effort that will include a workshop in December 2012 to help shape new foci for cancer epidemiology research. To facilitate the process of defining the future of cancer epidemiology, we invite the research community to join in an ongoing web-based conversation at http://blog-epi.grants.cancer.gov/ to develop priorities and the next generation of high-impact studies. Cancer Epidemiol Biomarkers Prev; 21(7); 999–1001. ©2012 AACR.
A Phase I First-in-Human Study of TRC105 (Anti-Endoglin Antibody) in Patients with Advanced Cancer
Authors: Rosen Lee S. , Hurwitz Herbert I. , Wong Michael K. , Goldman Jonathan , Mendelson David S. , Figg William D. , Spencer Shawn , Adams Bonne J. , Alvarez Delia , Seon Ben K. , Theuer Charles P. , Leigh Bryan R. , Gordon Michael S. 
Published: July 2012

AbstractPurpose: TRC105 is a chimeric IgG1 monoclonal antibody that binds CD105 (endoglin). This first-in-human, phase I, open-label study assessed safety, pharmacokinetics, and antitumor activity of TRC105 in patients with advanced refractory solid tumors.Patients and Methods: Patients received escalating doses of intravenous TRC105 until disease progression or unacceptable toxicity using a standard 3 + 3 phase I design.Results: Fifty patients were treated with escalating doses of TRC105. The maximum tolerated dose (MTD) was exceeded at 15 mg/kg every week because of dose-limiting hypoproliferative anemia. TRC105 exposure increased with increasing dose, and continuous serum concentrations that saturate CD105 receptors were maintained at 10 mg/kg weekly (the MTD) and 15 mg/kg every 2 weeks. Common adverse events including anemia, telangiectasias, and infusion reactions reflected the mechanism of action of the drug. Antibodies to TRC105 were not detected in patients treated with TRC105 from Chinese hamster ovary cells being used in ongoing phase Ib and phase II studies. Stable disease or better was achieved in 21 of 45 evaluable patients (47%), including two ongoing responses at 48 and 18 months.Conclusion: TRC105 was tolerated at 10 mg/kg every week and 15 mg/kg every 2 weeks, with a safety profile that was distinct from that of VEGF inhibitors. Evidence of clinical activity was seen in a refractory patient population. Ongoing clinical trials are testing TRC105 in combination with chemotherapy and VEGF inhibitors and as a single agent in prostate, ovarian, bladder, breast, and hepatocellular cancer. Clin Cancer Res; 18(17); 4820–9. ©2012 AACR.
Phase I Study of Aurora A Kinase Inhibitor MLN8237 in Advanced Solid Tumors: Safety, Pharmacokinetics, Pharmacodynamics, and Bioavailability of Two Oral Formulations
Authors: Dees E. Claire , Cohen Roger B. , von Mehren Margaret , Stinchcombe Thomas E. , Liu Hua , Venkatakrishnan Karthik , Manfredi Mark , Fingert Howard , Burris Howard A. , Infante Jeffrey R. 
Published: July 2012

AbstractPurpose: This phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of the investigational oral drug MLN8237 (alisertib), a small-molecule Aurora A kinase (AAK) inhibitor, in 87 adult patients with advanced solid tumors.Experimental Design: Sequential cohorts of patients received MLN8237 5 to 150 mg orally once daily or twice daily for 7, 14, or 21 days, followed by 14 days' rest per cycle. MLN8237 pharmacokinetics was characterized, and the relative bioavailability of an enteric-coated tablet (ECT) formulation was evaluated in reference to the original powder-in-capsule (PIC) formulation. Pharmacodynamic effects of MLN8237 on inhibition of AAK activity were evaluated in skin biopsies. Tolerability and response to treatment were assessed.Results: Common toxicities included fatigue, nausea, and neutropenia. Plasma exposures increased dose proportionally (5–150 mg/d), and were similar for PIC and ECT. The terminal half-life was 23 hours. At the maximum tolerated dose of 50 mg twice daily on the 7-day schedule, the mitotic index of the skin basal epithelium was increased within 24 hours after MLN8237 administration on days 1 and 7, a finding consistent with AAK inhibition. One (1%) patient achieved a partial response lasting for more than 1 year and received MLN8237 for 51 cycles; 20 (23%) patients achieved stable disease for ≥3 months.Conclusions: This first-in-human trial of MLN8237 showed tolerability and favorable pharmacokinetics in this patient population. The recommended phase II dose of MLN8237 is 50 mg twice daily orally for 7 days in 21-day cycles, which is being evaluated further in the treatment of various solid tumors and hematologic malignancies. Clin Cancer Res; 18(17); 4775–84. ©2012 AACR.
Phase I Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of the MEK Inhibitor RO4987655 (CH4987655) in Patients with Advanced Solid Tumors
Authors: Leijen Suzanne , Middleton Mark R. , Tresca Patricia , Kraeber-Bodéré Françoise , Dieras Veronique , Scheulen Max E. , Gupta Avinash , Lopez-Valverde Vanesa , Xu Zhi-Xin , Rueger Ruediger , Tessier Jean J.L. , Shochat Eliezer , Blotner Steve , Naegelen Valerie Meresse , Schellens Jan H.M. , Eberhardt Wilfried Ernst Erich 
Published: July 2012

Abstract
Purpose: This phase I study of the mitogen-activated protein/extracellular signal–regulated kinase inhibitor RO4987655 (CH4987655) assessed its maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety, pharmacokinetic/pharmacodynamic profile, and antitumor activity in patients with advanced solid tumors.
Patients and Methods: An initial dose escalation was conducted using a once-daily dosing schedule, with oral RO4987655 administered at doses of 1.0 to 2.5 mg once daily over 28 consecutive days in 4-week cycles. Doses were then escalated from 3.0 to 21.0 mg [total daily dose (TDD)] using a twice-daily dosing schedule.
Results: Forty-nine patients were enrolled. DLTs were blurred vision (n = 1) and elevated creatine phosphokinase (n = 3). The MTD was 8.5 mg twice daily (TDD, 17.0 mg). Rash-related toxicity (91.8%) and gastrointestinal disorders (69.4%) were the most frequent adverse events. The pharmacokinetic profile of RO4987655 showed dose linearity and a half-life of approximately 4 hours. At the MTD, target inhibition, assessed by suppression of extracellular signal–regulated kinase phosphorylation in peripheral blood mononuclear cells, was high (mean 75%) and sustained (90% of time &gt;IC50). Of the patients evaluable for response, clinical benefit was seen in 21.1%, including two partial responses (one confirmed and one unconfirmed). 79.4% of patients showed a reduction in fluorodeoxyglucose uptake by positron emission tomography between baseline and day 15.
Conclusion: In this population of heavily pretreated patients, oral RO4987655 showed manageable toxicity, a favorable pharmacokinetics/pharmacodynamics profile, and promising preliminary antitumor activity, which has been further investigated in specific populations of patients with RAS and/or RAF mutation driven tumors. Clin Cancer Res; 18(17); 4794–805. ©2012 AACR.
Topical TLR7 Agonist Imiquimod Can Induce Immune-Mediated Rejection of Skin Metastases in Patients with Breast Cancer
Authors: Adams Sylvia , Kozhaya Lina , Martiniuk Frank , Meng Tze-Chiang , Chiriboga Luis , Liebes Leonard , Hochman Tsivia , Shuman Nicholas , Axelrod Deborah , Speyer James , Novik Yelena , Tiersten Amy , Goldberg Judith D. , Formenti Silvia C. , Bhardwaj Nina , Unutmaz Derya , Demaria Sandra 
Published: July 2012

AbstractPurpose: Skin metastases of breast cancer remain a therapeutic challenge. Toll-like receptor 7 agonist imiquimod is an immune response modifier and can induce immune-mediated rejection of primary skin malignancies when topically applied. Here we tested the hypothesis that topical imiquimod stimulates local antitumor immunity and induces the regression of breast cancer skin metastases.Experimental Design: A prospective clinical trial was designed to evaluate the local tumor response rate of breast cancer skin metastases treated with topical imiquimod, applied 5 d/wk for 8 weeks. Safety and immunologic correlates were secondary objectives.Results: Ten patients were enrolled and completed the study. Imiquimod treatment was well tolerated, with only grade 1 to 2 transient local and systemic side effects consistent with imiquimod's immunomodulatory effects. Two patients achieved a partial response [20%; 95% confidence interval (CI), 3%–56%]. Responders showed histologic tumor regression with evidence of an immune-mediated response, showed by changes in the tumor lymphocytic infiltrate and locally produced cytokines.Conclusion: Topical imiquimod is a beneficial treatment modality for breast cancer metastatic to skin/chest wall and is well tolerated. Importantly, imiquimod can promote a proimmunogenic tumor microenvironment in breast cancer. Preclinical data generated by our group suggest superior results with a combination of imiquimod and ionizing radiation and we are currently testing in patients whether the combination can further improve antitumor immune and clinical responses. Clin Cancer Res; 18(24); 6748–57. ©2012 AACR.