bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promoter Methylation in APC, RUNX3, and GSTP1 and Mortality in Prostate Cancer Patients
Authors: Richiardi Lorenzo , Fiano Valentina , Vizzini Loredana , De Marco Laura , Delsedime Luisa , Akre Olof , Tos Anna Gillio , Merletti Franco 
Published: May 2009

Purpose There is a need to better understand prostate cancer progression and identify new prognostic markers for this tumor. We investigated the association between promoter methylation in a priori selected genes and survival in two independent large series of prostate cancer patients. Methods We followed up with two cohorts of patients (216 patients diagnosed in 1982 to 1988 and 243 patients diagnosed in 1993 to 1996) diagnosed at one hospital pathology ward in Turin, Italy. DNA was obtained from paraffin-embedded tumor tissues and evaluated for promoter methylation status in glutathione S-transferase (GSTP1), adenomatous polyposis coli (APC), and runt-related transcription factor 3 (RUNX3). Results The two cohorts had different prevalences of methylation in APC (P = .047), GSTP1 (P = .002), and RUNX3 (P < .001). Methylation in APC was associated with an increased risk of prostate cancer–specific mortality (hazard ratio [HR] = 1.42; 95% CI, 0.98 to 2.07 in the 1980s cohort; HR = 1.57; 95% CI, 0.95 to 2.62 in the 1990s cohort; HR = 1.49; 95% CI, 1.11 to 2.00 in the two cohorts combined). In subgroup analyses, the HRs were higher among patients with a Gleason score less than 8 (HR = 1.52; 95% CI, 0.85 to 2.73 in the 1980s cohort; HR = 2.09; 95% CI, 1.02 to 4.28 in the 1990s cohort). Methylation in RUNX3 was associated with prostate cancer mortality only in the 1990s cohort, and methylation in GSTP1 did not predict mortality in either cohort. Conclusion The pattern of hypermethylation may have changed after the introduction of prostate-specific antigen testing in the beginning of the 1990s. Promoter methylation in APC was identified as a marker for prostate cancer progression.
MDM2 and Ki-67 Predict for Distant Metastasis and Mortality in Men Treated With Radiotherapy and Androgen Deprivation for Prostate Cancer: RTOG 92-02
Authors: Khor Li-Yan , Bae Kyounghwa , Paulus Rebecca , Al-Saleem Tahseen , Hammond M. Elizabeth , Grignon David J. , Che Mingxin , Venkatesan Varagur , Byhardt Roger W. , Rotman Marvin , Hanks Gerald E. , Sandler Howard M. , Pollack Alan 
Published: May 2009

Purpose MDM2 regulates p53, which controls cell cycle arrest and apoptosis. Both proteins, along with Ki-67, which is an established strong determinant of metastasis, have shown promise in predicting the outcome of men treated with radiation therapy (RT) with or without short-term androgen deprivation (STAD). This report compares the utility of abnormal expression of these biomarkers in estimating progression in a cohort of men treated on RTOG 92-02. Patients and Methods Adequate tissue for immunohistochemistry was available for p53, Ki-67, and MDM2 analyses in 478 patient cases. The percentage of tumor nuclei staining positive (PSP) was quantified manually or by image analysis, and the per-sample mean intensity score (MIS) was quantified by image analysis. Cox regression models were used to estimate overall mortality (OM), and Fine and Gray's regressions were applied to the end points of distant metastasis (DM) and cause-specific mortality (CSM). Results In multivariate analyses that adjusted for all markers and treatment covariates, MDM2 overexpression was significantly related to DM (P = .02) and OM (P = .003), and Ki-67 overexpression was significantly related to DM (P < .0001), CSM (P = .0007), and OM (P = .01). P53 overexpression was significantly related to OM (P = .02). When considered in combination, the overexpression of both Ki-67 and MDM2 at high levels was associated with significantly increased failure rates for all end points (P < .001 for DM, CSM, and OM). Conclusion Combined MDM2 and Ki-67 expression levels were independently related to distant metastasis and mortality and, if validated, could be considered for risk stratification of patients with prostate cancer in clinical trials.
Conversion to Resectability Using Hepatic Artery Infusion Plus Systemic Chemotherapy for the Treatment of Unresectable Liver Metastases From Colorectal Carcinoma
Authors: Kemeny Nancy E. , Melendez Fidel D. Huitzil , Capanu Marinela , Paty Philip B. , Fong Yuman , Schwartz Lawrence H. , Jarnagin William R. , Patel Dina , D'Angelica Michael 
Published: May 2009

Purpose To determine the conversion to resectability in patients with unresectable liver metastases from colorectal cancer treated with hepatic arterial infusion (HAI) plus systemic oxaliplatin and irinotecan (CPT-11). Patients and Methods Forty-nine patients with unresectable liver metastases (53% previously treated with chemotherapy) were enrolled onto a phase I protocol with HAI floxuridine and dexamethasone plus systemic chemotherapy with oxaliplatin and irinotecan. Results Ninety-two percent of the 49 patients had complete (8%) or partial (84%) response, and 23 (47%) of the 49 patients were able to undergo resection in a group of patients with extensive disease (73% with > five liver lesions, 98% with bilobar disease, 86% with ≥ six segments involved). For chemotherapy-naïve and previously treated patients, the median survival from the start of HAI therapy was 50.8 and 35 months, respectively. The only baseline variable significantly associated with a higher resection rate was female sex. Variables reflecting extensive anatomic disease, such as number of lesions or number of vessels involved, were not significantly associated with the probability of resection. Conclusion The combination of regional HAI floxuridine/dexamethasone and systemic oxaliplatin and irinotecan is an effective regimen for the treatment of patients with unresectable liver metastases from colorectal cancer, demonstrating a 47% conversion to resection (57% in chemotherapy-naïve patients). Future randomized trials should compare HAI plus systemic chemotherapy with systemic therapy alone to assess the additional value of HAI therapy in converting patients with hepatic metastases to resectability.
American Society of Clinical Oncology Clinical Practice Guideline Update on the Use of Pharmacologic Interventions Including Tamoxifen, Raloxifene, and Aromatase Inhibition for Breast Cancer Risk Reduction
Authors: Visvanathan Kala , Chlebowski Rowan T. , Hurley Patricia , Col Nananda F. , Ropka Mary , Collyar Deborah , Morrow Monica , Runowicz Carolyn , Pritchard Kathleen I. , Hagerty Karen , Arun Banu , Garber Judy , Vogel Victor G. , Wade James L. , Brown Powel , Cuzick Jack , Kramer Barnett S. , Lippman Scott M. 
Published: May 2009

Purpose To update the 2002 American Society of Clinical Oncology guideline on pharmacologic interventions for breast cancer (BC) risk reduction. Methods A literature search identified relevant randomized trials published since 2002. Primary outcome of interest was BC incidence (invasive and noninvasive). Secondary outcomes included BC mortality, adverse events, and net health benefits. An expert panel reviewed the literature and developed updated consensus guidelines. Results Seventeen articles met inclusion criteria. In premenopausal women, tamoxifen for 5 years reduces the risk of BC for at least 10 years, particularly estrogen receptor (ER) –positive invasive tumors. Women ≤ 50 years of age experience fewer serious side effects. Vascular and vasomotor events do not persist post-treatment across all ages. In postmenopausal women, raloxifene and tamoxifen reduce the risk of ER-positive invasive BC with equal efficacy. Raloxifene is associated with a lower risk of thromboembolic disease, benign uterine conditions, and cataracts than tamoxifen in postmenopausal women. No evidence exists establishing whether a reduction in BC risk from either agent translates into reduced BC mortality. Recommendations In women at increased risk for BC, tamoxifen (20 mg/d for 5 years) may be offered to reduce the risk of invasive ER-positive BC, with benefits for at least 10 years. In postmenopausal women, raloxifene (60 mg/d for 5 years) may also be considered. Use of aromatase inhibitors, fenretinide, or other selective estrogen receptor modulators to lower BC risk is not recommended outside of a clinical trial. Discussion of risks and benefits of preventive agents by health providers is critical to patient decision making.
Cognitive Rehabilitation in Patients With Gliomas: A Randomized, Controlled Trial
Authors: Gehring Karin , Sitskoorn Margriet M. , Gundy Chad M. , Sikkes Sietske A.M. , Klein Martin , Postma Tjeerd J. , van den Bent Martin J. , Beute Guus N. , Enting Roelien H. , Kappelle Arnoud C. , Boogerd Willem , Veninga Theo , Twijnstra Albert , Boerman Dolf H. , Taphoorn Martin J.B. , Aaronson Neil K. 
Published: May 2009

Purpose Patients with gliomas often experience cognitive deficits, including problems with attention and memory. This randomized, controlled trial evaluated the effects of a multifaceted cognitive rehabilitation program (CRP) on cognitive functioning and selected quality-of-life domains in patients with gliomas. Patients and Methods One hundred forty adult patients with low-grade and anaplastic gliomas, favorable prognostic factors, and both subjective cognitive symptoms and objective cognitive deficits were recruited from 11 hospitals in the Netherlands. Patients were randomly assigned to an intervention group or to a waiting-list control group. The intervention incorporated both computer-based attention retraining and compensatory skills training of attention, memory, and executive functioning. Participants completed a battery of neuropsychological (NP) tests and self-report questionnaires on cognitive functioning, fatigue, mental health–related quality of life, and community integration at baseline, after completion of the CRP, and at 6-month follow-up. Results At the immediate post-treatment evaluation, statistically significant intervention effects were observed for measures of subjective cognitive functioning and its perceived burden but not for the objective NP outcomes or for any of the other self-report measures. At the 6-month follow-up, the CRP group performed significantly better than the control group on NP tests of attention and verbal memory and reported less mental fatigue. Group differences in other subjective outcomes were not significant at 6 months. Conclusion The CRP has a salutary effect on short-term cognitive complaints and on longer-term cognitive performance and mental fatigue. Additional research is needed to identify which elements of the intervention are most effective.
Hospital Factors and Racial Disparities in Mortality After Surgery for Breast and Colon Cancer
Authors: Breslin Tara M. , Morris Arden M. , Gu Niya , Wong Sandra L. , Finlayson Emily V. , Banerjee Mousumi , Birkmeyer John D. 
Published: May 2009

Purpose Black patients have worse prognoses than whites with breast or colorectal cancer. Mechanisms underlying such disparities have not been fully explored. We examined the role of hospital factors in racial differences in late mortality after surgery for breast or colon cancer. Methods Patients undergoing surgery after new diagnosis of breast or colon cancer were identified using the Surveillance Epidemiology and End Results–Medicare linked database (1995 to 2005). The main outcome measure was mortality at 5 years. Proportional hazards models were used to assess relationships between race and late mortality, accounting for patient factors, socioeconomic measures, and hospital factors. Fixed and random effects models were used to account for quality differences across hospitals. Results Black patients, compared with white patients, had lower 5-year overall survival rates after surgery for breast (62.1% v 70.4%, respectively; P < .001) and colon cancer (41.3% v 45.4%, respectively; P < .001). After controlling for age, comorbidity, and stage, black race remained an independent predictor of mortality for breast (adjusted hazard ratio [HR] = 1.25; 95% CI, 1.16 to 1.34) and colon cancer (adjusted HR = 1.13; 95% CI, 1.07 to 1.19). After risk adjustment, hospital factors explained 36% and 54% of the excess mortality for black patients with breast cancer and colon cancer, respectively. Hospitals with large minority populations had higher late mortality rates independent of race. Conclusion Hospital factors, including quality, are important mediators of the association between race and mortality for breast and colon cancer. Hospital-level quality improvement should be a major component of efforts to reduce disparities in cancer outcomes.
The Pattern of Growth Hormone Delivery to Peripheral Tissues Determines Insulin-Like Growth Factor-1 and Lipolytic Responses in Obese Subjects
Authors: Surya Sowmya , Horowitz Jeffrey F. , Goldenberg Naila , Sakharova Alla , Harber Matthew , Cornford Andrea S. , Symons Kathy , Barkan Ariel L. 
Published: May 2009

Context: It is unclear whether the pattern of GH delivery to peripheral tissues has important effects.
Objective: The aim of the study was to compare the effects of pulsatile vs. continuous administration of GH upon metabolic and IGF-I parameters in obese subjects.
Setting: The study was conducted at the General Clinical Research Center at the University of Michigan Medical Center.
Participants: Four men and five women with abdominal obesity (body mass index, 33 ± 3 kg/m2; body fat, 40 ± 3%) participated in the study.
Intervention: GH (0.5 mg/m2 · d) was given iv for 3 d as: 1) continuous infusion (C); and 2) pulsatile boluses (P) (15% of the dose at 0700, 1300, and 1800 h and 55% at 2400 h). These trials were preceded by a basal period (B) when subjects received normal saline.
Main Outcome Measures: Rate of lipolysis and hepatic glucose production were evaluated using stable isotope tracer techniques. The composite index of insulin sensitivity (Matsuda index) was assessed using oral glucose tolerance test.
Results: The increase in plasma IGF-I concentrations was greater (P &lt; 0.05) with continuous GH infusion (211 ± 31, 423 ± 38, and 309 ± 34 μg/liter for B, C, and P, respectively). Muscle IGF-I mRNA was significantly increased (P &lt; 0.05) only after the continuous GH infusion (1.2 ± 0.4, 4.4 ± 1.3, and 2.3 ± 0.6 arbitrary units, for B, C, and P, respectively). Only pulsatile GH augmented the rate of lipolysis (4.1 ± 0.3, 4.8 ± 0.7, and 7.1 ± 1.1 μmol/kg · min for B, C, and P, respectively). GH had no effect on hepatic glucose production, but both modes of GH administration were equally effective in impairing insulin sensitivity.
Conclusion: These findings indicate that, in obese subjects, discrete components of GH secretory pattern may differentially affect IGF-I generation and lipolytic responses.
Dissecting the roles of Raf- and PI3K-signalling pathways in melanoma formation and progression in a zebrafish model
Authors: Michailidou Christina , Jones Mary , Walker Paul , Kamarashev Jivko , Kelly Amanda , Hurlstone Adam F. L. 
Published: May 2009

SUMMARYDeregulated Ras signalling is implicated in most human neoplasia, exemplified by melanoma. Whereas Raf activation occurs almost ubiquitously in benign and malignant melanocytic neoplasms, implying an involvement in tumour initiation, phosphoinositide 3-kinase (PI3K) activation occurs predominantly in malignant neoplasms, implying an involvement in malignant progression. Here, we dissect the contributions of these two pathways to tumourigenesis in vivo, by modulating their activities in zebrafish melanocytes. Misexpression of oncogenic Ras (V12RAS) in founder fish induced frequent melanoma, beginning at larval stages, with concomitant activation of Raf-Mek-Erk and PI3K-Akt signalling. Misexpression of effector-domain mutants of V12RAS, or of various downstream effectors, confirmed a selective role for the Raf-Mek-Erk pathway in initiating neoplasia, but highlighted the requirement for additional Ras effector pathways for malignancy. The phenotype of animals with germ-line transmission of V12RAS resembled familial atypical mole and melanoma (FAMM) syndrome: melanocytes displayed hyperplasia, dysplasia, altered terminal differentiation and spontaneously progressed to invasive melanoma. Co-expressing a dominant-interfering form of PI3K abolished V12RAS-induced malignancy, demonstrating a direct role for PI3K signalling in the malignant progression of melanoma in vivo, and highlighting PI3K as a promising target for melanoma therapy.
“But Doctors do it…”: Nurses' Views of Gifts and Information from the Pharmaceutical Industry
Authors: Jutel Annemarie , Menkes David B 
Published: May 2009

Background Most nurses, like their physician counterparts, lack education regarding pharmaceutical marketing strategies, and little is known of their beliefs and practices regarding this industry. Nurses are increasingly targeted by pharmaceutical companies as they become more involved in prescription and as policies restrict pharmaceutical companies' contact with physicians. Objective To assess nurses' beliefs and reported practices concerning pharmaceutical marketing and sponsorship strategies. Methods We conducted parallel Web- and paper-based surveys of a sample of senior registered nurses employed by government-funded health boards in 2 regions of New Zealand to explore their contact with the pharmaceutical industry as well as their beliefs and practices regarding information, gifts, and sponsorship provided by pharmaceutical companies. Returns were tested using Fisher's exact test to determine consistency in response between regions. Results for key outcome variables, including attitude toward the value of industry-derived information, were analyzed by region and in aggregate. Results Most nurses had contact with pharmaceutical sales representatives (69/106), accepted gifts from representatives (79/105), and believed information from the pharmaceutical industry probably improved their practice (71/106). Half believed that they would be able to detect misleading information if it were present, and 35% believed that accepting gifts and sponsorship was ethically acceptable. We found positive associations between the belief that information from the industry improved practice and reported acceptance of conference funding (OR 3.63; 95% CI 1.41 to 11.55), free food (OR 3.24; 95% CI 2.03 to 7.55), or gifts (OR 3.52; 95% CI 1.38 to 8.95). Nurses generally acknowledge the presence of pharmaceutical marketing in the hospital and the ethical challenges it presents; nonetheless, they also generally accept marketing gifts and may underestimate both the ethical challenges and their own susceptibility to persuasion. Conclusions Given the increasing role that nurses may play in pharmaceutical marketing strategy, the profession should consider its position vis-à-vis the industry.
Evaluating the Power to Detect Temporal Trends in Fishery-Independent Surveys: A Case Study Based on Gill Nets Set in the Ohio Waters of Lake Erie for Walleyes
Authors: Wagner Tyler , Vandergoot Christopher S. , Tyson Jeff 
Published: May 2009

Abstract
Fishery-independent (FI) surveys provide critical information used for the sustainable management and conservation of fish populations. Because fisheries management often requires the effects of management actions to be evaluated and detected within a relatively short time frame, it is important that research be directed toward FI survey evaluation, especially with respect to the ability to detect temporal trends. Using annual FI gill-net survey data for Lake Erie walleyes Sander vitreus collected from 1978 to 2006 as a case study, our goals were to (1) highlight the usefulness of hierarchical models for estimating spatial and temporal sources of variation in catch per effort (CPE); (2) demonstrate how the resulting variance estimates can be used to examine the statistical power to detect temporal trends in CPE in relation to sample size, duration of sampling, and decisions regarding what data are most appropriate for analysis; and (3) discuss recommendations for evaluating FI surveys and analyzing the resulting data to support fisheries management. This case study illustrated that the statistical power to detect temporal trends was low over relatively short sampling periods (e.g., 5–10 years) unless the annual decline in CPE reached 10–20%. For example, if 50 sites were sampled each year, a 10% annual decline in CPE would not be detected with more than 0.80 power until 15 years of sampling, and a 5% annual decline would not be detected with more than 0.8 power for approximately 22 years. Because the evaluation of FI surveys is essential for ensuring that trends in fish populations can be detected over management-relevant time periods, we suggest using a meta-analysis–type approach across systems to quantify sources of spatial and temporal variation. This approach can be used to evaluate and identify sampling designs that increase the ability of managers to make inferences about trends in fish stocks.
Effects of temperature on ventilatory behavior of fish exposed to sublethal concentrations of endosulfan and chlorpyrifos
Authors: Patra Ronald W. , Chapman John C. , Lim Richard P. , Gehrke Peter C. , Sunderam Ramasamy M. 
Published: May 2009

Abstract
The ventilation amplitude and frequency of silver perch Bidyanus bidyanus, and the ventilation frequency of rainbow fish Melanotaenia duboulayi and rainbow trout Oncorhynchus mykiss, were determined at different temperatures upon exposure to endosulfan and chlorpyrifos, respectively. Silver perch and rainbow fish were tested at 15, 20, 25, 30, and 35°C, while rainbow trout was tested at 10, 15, 20, and 25°C. Although some trend of increasing amplitudes with increasing temperature was evident; there was no significant temperature response of ventilation frequency rates over time in silver perch pre-exposed to 10 μg L−1 endosulfan for 18 h. The rate of ventilation frequency of rainbow fish pre-exposed to 200 μg L−1 of chlorpyrifos for 96 h was lower in treatments than in the control at 15°C. However, between 20 and 35°C, rates were significantly higher in the treatments than those of the control. In rainbow trout pre-exposed to 100 μg L−1 of chlorpyrifos, the rates of frequency were significantly lower than those of controls in temperatures between 10 and 20°C but higher at 25°C. The amplitude of silver perch seemed to increase with the increase in temperature; however, the corresponding temperature quotient values at various temperature regimes and over exposure time showed no significant differences. The ventilation frequency of rainbow fish and rainbow trout significantly increased at the higher test temperatures, and their corresponding temperature quotient values for both fish also increased at the elevated temperatures.