bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiorespiratory Fitness and Digestive Cancer Mortality: Findings from the Aerobics Center Longitudinal Study
Authors: Peel J. Brent , Sui Xuemei , Matthews Charles E. , Adams Swann A. , Hébert James R. , Hardin James W. , Church Timothy S. , Blair Steven N. 
Published: April 2009

Abstract
Although higher levels of physical activity are inversely associated with risk of colon cancer, few prospective studies have evaluated overall digestive system cancer mortality in relation to cardiorespiratory fitness (CRF). The authors examined this association among 38,801 men ages 20 to 88 years who performed a maximal treadmill exercise test at baseline in the Aerobics Center Longitudinal Study (Dallas, TX) during 1974 to 2003. Mortality was assessed over 29 years of follow-up (1974-2003). Two hundred eighty-three digestive system cancer deaths occurred during a mean 17 years of observation. Age-adjusted mortality rates per 10,000 person-years according to low, moderate, and high CRF groups were 6.8, 4.0, and 3.3 for digestive system cancer (Ptrend &lt; 0.001). After adjustment for age, examination year, body mass index, smoking, drinking, family history of cancer, personal history of diabetes, hazard ratios (95% confidence intervals) for overall digestive cancer deaths for those in the middle and upper 40% of the distribution of CRF relative to those in the lowest 20% were 0.66 (0.49-0.88) and 0.56 (0.40-0.80), respectively. Being fit (the upper 80% of CRF) was associated with a lower risk of mortality from colon [0.61 (0.37-1.00)], colorectal [0.58 (0.37-0.92)], and liver cancer [0.28 (0.11-0.72)] compared with being unfit (the lowest 20% of CRF). These findings support a protective role of CRF against total digestive tract, colorectal, and liver cancer deaths in men. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1111–7)
Association of CYP1B1 Haplotypes and Breast Cancer Risk in Caucasian Women
Authors: Huang Yifan , Trentham-Dietz Amy , García-Closas Montserrat , Newcomb Polly A. , Titus-Ernstoff Linda , Hampton John M. , Chanock Stephen J. , Haines Jonathan L. , Egan Kathleen M. 
Published: April 2009

Abstract
CYP1B1 is a key enzyme involved in estrogen metabolism and may play an important role in the development and progression of breast cancer. In a population-based case-control study, we examined eight CYP1B1 haplotype-tagging single nucleotide polymorphisms in relation to invasive breast cancer risk. Analyses were based on 1,655 cases and 1,470 controls; all women were Caucasian. Among the individual single nucleotide polymorphisms, one (rs9341266) was associated with increased risk of breast cancer (Ptrend = 0.021), although the association was no longer significant after adjusting for multiple tests. A marginally significant haplotype effect was identified (Pglobal = 0.015), with significant associations identified for 2 uncommon haplotypes comprising 4% of the controls. Results suggest that genetic variation in CYP1B1 has at most a minor influence on breast cancer susceptibility among Caucasian women. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1321–3)
Prospective Study of Plasma Vitamin B6 and Risk of Colorectal Cancer in Men
Authors: Lee Jung Eun , Li Haojie , Giovannucci Edward , Lee I-Min , Selhub Jacob , Stampfer Meir , Ma Jing 
Published: April 2009

Abstract
Vitamin B6 may lower risk of colorectal cancer by preventing aberrations in one-carbon metabolism or by anti-inflammatory effects. We prospectively evaluated the association between plasma levels of pyridoxal 5′-phosphate (PLP; the active form of vitamin B6) and risk of colorectal cancer in a nested case-control study within the Physicians' Health Study. Among 14,916 men who provided blood specimens in 1982 to 1984, we identified 197 incident colorectal cancer cases through 2000 and individually matched them to 371 controls by age and smoking status. Plasma PLP levels were positively correlated with cold cereal intake and plasma levels of folate and vitamin B12 (age- and smoking-adjusted partial correction r = 0.28-0.48) and slightly inversely correlated with body mass index (r = −0.11) and plasma levels of homocysteine, C-reactive protein, tumor necrosis factor-α receptor 2, and interleukin-6 (r = −0.23 to −0.14). With control for these factors and known risk factors for colorectal cancer, plasma PLP levels were significantly inversely associated with risk of colorectal cancer; compared with men in the lowest quartile, those with PLP in quartiles 2 to 4 had relative risks (95% confidence interval) of 0.92 (0.55-1.56), 0.42 (0.23-0.75), and 0.49 (0.26-0.92; Ptrend = 0.01), respectively. In conclusion, vitamin B6 may protect against colorectal cancer independent of other one-carbon metabolites and inflammatory biomarkers. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1197–202)
Heritable Variation ofERBB2and Breast Cancer Risk
Authors: Breyer Joan P. , Sanders Melinda E. , Airey David C. , Cai Qiuyin , Yaspan Brian L. , Schuyler Peggy A. , Dai Qi , Boulos Fouad , Olivares Maria G. , Bradley Kevin M. , Gao Yu-Tang , Page David L. , Dupont William D. , Zheng Wei , Smith Jeffrey R. 
Published: April 2009

AbstractAmplification of the epithelial growth factor receptor gene ERBB2 (HER2, NEU) in breast cancer is associated with a poor clinical prognosis. In mammary gland development, this receptor plays a role in ductal and lobuloalveolar differentiation. We conducted a systematic investigation of the role of genetic variation of the ERBB2 gene in breast cancer risk in a study of 842 histologically confirmed invasive breast cancer cases and 1,108 controls from the Shanghai Breast Cancer Study. We observed that the ERBB2 gene resides within a locus of high linkage disequilibrium, composed of three major ancestral haplotypes in the study population. These haplotypes are marked by simple tandem repeat and single nucleotide polymorphisms, including the missense variants I655V and P1170A. We observed a risk-modifying effect of a highly polymorphic simple tandem repeat within an evolutionarily conserved region, 4.4 kb upstream from the ERBB2 transcription start site. Under a dominant genetic model, the age-adjusted odds ratio was 1.74 (95% confidence interval, 1.27-2.37). Its association with breast cancer, and with breast cancer stratified by histology, by histologic grade, and by stage, remained significant after correction for multiple comparisons. In contrast, we observed no association of ERBB2 single nucleotide polymorphism haplotypes with breast cancer predisposition. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1252–8)
Serum Antioxidants and Skin Cancer Risk: An 8-Year Community-Based Follow-up Study
Authors: van der Pols Jolieke C. , Heinen Mirjam M. , Hughes Maria Celia , Ibiebele Torukiri I. , Marks Geoffrey C. , Green Adèle C. 
Published: April 2009

AbstractBackground: Antioxidant nutrients can help prevent skin damage caused by ultraviolet radiation from sunlight, but it is not clear whether serum concentrations of such nutrients influence skin cancer risk.Methods: We carried out a prospective study of the associations between serum concentrations of antioxidant nutrients and incidence (person-based and tumor-based) of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin among a random subsample of 485 adults from an Australian community. Participants were divided into thirds, ranked according to their serum concentrations of carotenoids, α-tocopherol, and selenium measured in 1996 and were monitored for incident, histologically confirmed BCC and SCC tumors until 2004.Results: Although there were no associations between baseline serum carotenoids or α-tocopherol concentrations and incidence of BCC or SCC, baseline serum selenium concentrations showed strong inverse associations with both BCC and SCC tumor incidence. Compared with participants with lowest selenium concentrations at baseline (0.4-1.0 μmol/L), those with the highest serum selenium concentrations (1.3-2.8 μmol/L) had a decreased incidence of BCC tumors (multivariate relative risk, 0.43; 95% confidence interval, 0.21-0.86; Ptrend = 0.02) and SCC tumors (multivariate relative risk, 0.36; 95% confidence interval, 0.15-0.82; Ptrend = 0.02).Conclusion: Relatively high serum selenium concentrations are associated with an ∼60% decrease in subsequent tumor incidence of both BCC and SCC, whereas serum concentrations of carotenoids or α-tocopherol are not associated with later skin cancer incidence. A possible U-shaped association between serum selenium concentrations and SCC of the skin needs confirmation. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1167–73)
Sequencing of Type I Insulin-Like Growth Factor Receptor Inhibition Affects Chemotherapy Response In vitro and In vivo
Authors: Zeng Xianke , Sachdev Deepali , Zhang Hua , Gaillard-Kelly Martine , Yee Douglas 
Published: April 2009

Abstract
Purpose: The aim of this study was to determine the optimal sequence of combining anti-type I insulin-like growth factor receptor (IGF1R) antibodies with chemotherapeutic drugs in cancer cells in vitro and in vivo.
Experimental Design: MCF-7 and LCC6 cells were treated with subcytotoxic concentrations of doxorubicin with or without anti-IGF1R antibodies (scFv-Fc or EM164 and its humanized version AVE1642). Treatments were given simultaneously, doxorubicin followed by anti-IGF1R antibody, or anti-IGF1R antibody followed by doxorubicin, with measurement of in vitro proliferation, apoptosis, and anchorage-independent growth. The effects of sequencing on LCC6 xenograft growth and metastasis were studied.
Results: Doxorubicin followed by anti-IGF1R antibody (scFv-Fc or EM164) was the most effective combination strategy to inhibit cell monolayer growth and anchorage-independent growth. This sequential combination triggered increased poly (ADP-ribose) polymerase cleavage compared with other treatment sequences. The reverse sequence, antibody followed by doxorubicin treatment, protected cells from chemotherapy by decreasing apoptosis, arresting cells in S phase, and inhibiting the level and activity of topoisomerase IIα. Finally, our in vivo data show that recovery of IGF1R prior to doxorubicin therapy resulted in the best therapeutic responses. Low doses of AVE1642 that allowed IGF1R expression to recover at one week were more effective in combination with doxorubicin than higher antibody doses.
Conclusion: The timing of IGF1R inhibition affects responses to chemotherapy. The optimal sequence was doxorubicin followed by anti-IGF1R antibody, whereas the opposite sequence inhibited doxorubicin effects. Thus, the dose and sequencing of anti-IGF1R therapies should be considered in the design of future clinical trials.
Valproate, in Combination with Pemetrexed and Cisplatin, Provides Additional Efficacy to the Treatment of Malignant Mesothelioma
Authors: Vandermeers Fabian , Hubert Pascale , Delvenne Philippe , Mascaux Céline , Grigoriu Bogdan , Burny Arsène , Scherpereel Arnaud , Willems Luc 
Published: April 2009

Abstract
Purpose: Present chemotherapeutic regimens are marginally efficient in tumor cells being particularly resistant to radiotherapy and/or chemotherapy. We hypothesized that unresponsiveness of tumors to conventional therapeutic agents might be due to inappropriate gene expression resulting from epigenetic modifications and leading to transcriptional silencing. The goal of this study was to evaluate the anticancer effect of a histone deacetylase inhibitor, valproate, on mesothelioma cells in combination with pemetrexed and cisplatin, the usual first-line regimen of chemotherapy for this tumor.
Experimental Design and Results: We show that valproate augments apoptosis induced by pemetrexed and cisplatin in mesothelioma cell lines and in tumor cells from patient's biopsies. Onset of apoptosis involves both extrinsic and intrinsic pathways requiring enzymatic activities of caspases 8 and 9, respectively. Valproate but not suberoylanilide hydroxamic acid efficiently stimulates the production of reactive oxygen species. The free radical scavenger N-acetylcysteine inhibits apoptosis, indicating that reactive oxygen species are major mediators of valproate activity. As expected, valproate alone or combined with pemetrexed and cisplatin triggers hyperacetylation of histone H3. Bid protein processing in truncated t-Bid and cytochrome c release from mitochondria are significantly increased in the presence of valproate, providing a mechanistic rationale for improvement of the proapoptotic efficacy of cisplatin and pemetrexed. Finally, valproate when combined with pemetrexed and cisplatin prevents tumor growth in mouse models of epithelioid mesothelioma.
Conclusions: These observations support the potential additional efficacy of valproate in combination with pemetrexed and cisplatin for treatment of malignant mesothelioma.
A Phase I Study of a Combination of Yttrium-90–Labeled Anti–Carcinoembryonic Antigen (CEA) Antibody and Gemcitabine in Patients with CEA-Producing Advanced Malignancies
Authors: Shibata Stephen , Raubitschek Andrew , Leong Lucille , Koczywas Marianna , Williams Lawrence , Zhan Jiping , Wong Jeffrey Y.C. 
Published: April 2009

Abstract
Purpose: To determine the maximum tolerated dose of combined therapy using an yttrium-90–labeled anti–carcinoembryonic antigen (CEA) antibody with gemcitabine in patients with advanced CEA-producing solid tumors.
Experimental Design: The chimeric human/murine cT84.66 is an anti-CEA intact IgG1, with high affinity and specificity to CEA. This was given at a fixed yttrium-90–labeled dose of 16.6 mCi/m2 to subjects who had and an elevated CEA in serum or in tumor by immunohistochemistry. Also required was a tumor that imaged with an 111In-labeled cT84.66 antibody. Patients were treated with escalating doses of gemcitabine given i.v. over 30 minutes on day 1 and 3 after the infusion of the yttrium-90–labeled antibody. Patients were treated in cohorts of 3. The maximum tolerated dose was determined as the highest level at which no &gt;1 of 6 patients experienced a dose limiting toxicity.
Results: A total of 36 patients were enrolled, and all but one had prior systemic therapy. The maximum tolerated dose of gemcitabine in this combination was 150 mg/m2. Dose limiting toxicities at a gemcitabine dose of 165 mg/m2 included a grade 3 rash and grade 4 neutropenia. One partial response was seen in a patient with colorectal cancer, and 4 patients had a &gt;50% decrease in baseline CEA levels associated with stable disease. Human antichimeric antibody responses were the primary reason for stopping treatment in 12 patients.
Conclusions: Feasibility of combining gemcitabine with an yttrium-90–labeled anti-CEA antibody is shown with preliminary evidence of clinical response.
Resource utilisation and costs of palliative cancer care in an interdisciplinary health care model
Authors: Johnson AP , Abernathy T , Howell D , Brazil K , Scott S 
Published: April 2009

This paper presents a detailed description of health care resource utilisation and costs of a pilot interdisciplinary health care model of palliative home care in Ontario, Canada. The descriptive evaluation entailed examining the use of services and costs of the pilot program: patient demographics, length of stay broken down by disposition (discharged, alive, death), access to services/resources, use of family physician and specialist services, and drug use. There were 434 patients included in the pilot program. Total costs were approximately CAN$2.4 million, and the cost per person amounted to approximately CAN$5586.33 with average length of stay equal to over 2 months (64.22 days). One may assume that length of stay would be influenced by the amount of service and support available. Future research might investigate whether in-home palliative home care is the most cost effective and suitable care setting for those patients requiring home care services for expected periods of time.
Accessibility and partner number of protein residues, their relationship and a webserver, ContPlot for their display
Authors: Pal Arumay , Bahadur Ranjit Prasad , Ray Partha Sarathi , Chakrabarti Pinak 
Published: April 2009

Abstract

Background
Depending on chemical features residues have preferred locations – interior or exterior – in protein structures, which also determine how many other residues are found around them. The close packing of residues is the hallmark of protein interior and protein-protein interaction sites.

Results
The average values of accessible surface area (ASA) and partner number (PN, the number of other residues within a distance of 4.5 Å from any atom of a given residue) of different residues have been determined and a webserver, ContPlot has been designed to display these values (relative to the average values) along the protein sequence. This would be useful to visually identify residues that are densely packed, or those involved in protein-protein interactions. The skewness observed in the distribution of PNs is indicative of the hydrophobic or hydrophilic nature of the residue. The variation of ASA with PN can be analytically expressed in terms of a cubic equation. These equations (one for each residue) can be used to estimate the ASA of a polypeptide chain using the PNs of the individual residues in the structure.

Conclusion
The atom-based PNs (obtained by counting surrounding atoms) are highly correlated to the residue-based PN, indicating that the latter can adequately capture the atomic details of packing. The average values of ASA and PN associated with each residue should be useful in protein structure prediction or fold-recognition algorithm. ContPlot would provide a handy tool to assess the importance of a residue in the protein structure or interaction site.
ProtSA: a web application for calculating sequence specific protein solvent accessibilities in the unfolded ensemble
Authors: Estrada Jorge , Bernadó Pau , Blackledge Martin , Sancho Javier 
Published: April 2009

Abstract

Background
The stability of proteins is governed by the heat capacity, enthalpy and entropy changes of folding, which are strongly correlated to the change in solvent accessible surface area experienced by the polypeptide. While the surface exposed in the folded state can be easily determined, accessibilities for the unfolded state at the atomic level cannot be obtained experimentally and are typically estimated using simplistic models of the unfolded ensemble. A web application providing realistic accessibilities of the unfolded ensemble of a given protein at the atomic level will prove useful.

Results
ProtSA, a web application that calculates sequence-specific solvent accessibilities of the unfolded state ensembles of proteins has been developed and made freely available to the scientific community. The input is the amino acid sequence of the protein of interest. ProtSA follows a previously published calculation protocol which uses the Flexible-Meccano algorithm to generate unfolded conformations representative of the unfolded ensemble of the protein, and uses the exact analytical software ALPHASURF to calculate atom solvent accessibilities, which are averaged on the ensemble.

Conclusion
ProtSA is a novel tool for the researcher investigating protein folding energetics. The sequence specific atom accessibilities provided by ProtSA will allow obtaining better estimates of the contribution of the hydrophobic effect to the free energy of folding, will help to refine existing parameterizations of protein folding energetics, and will be useful to understand the influence of point mutations on protein stability.
Norepinephrine transport-mediated gene expression in noradrenergic neurogenesis
Authors: Hu Yao Fei , Caron Marc G , Sieber-Blum Maya 
Published: April 2009

AbstractBackgroundWe have identified a differential gene expression profile in neural crest stem cells that is due to deletion of the norepinephrine transporter (NET) gene. NET is the target of psychotropic substances, such as tricyclic antidepressants and the drug of abuse, cocaine. NET mutations have been implicated in depression, anxiety, orthostatic intolerance and attention deficit hyperactivity disorder (ADHD). NET function in adult noradrenergic neurons of the peripheral and central nervous systems is to internalize norepinephrine from the synaptic cleft. By contrast, during embryogenesis norepinephrine (NE) transport promotes differentiation of neural crest stem cells and locus ceruleus progenitors into noradrenergic neurons, whereas NET inhibitors block noradrenergic differentiation. While the structure of NET und the regulation of NET function are well described, little is known about downstream target genes of norepinephrine (NE) transport.ResultsWe have prepared gene expression profiles of in vitro differentiating wild type and norepinephrine transporter-deficient (NETKO) mouse neural crest cells using long serial analysis of gene expression (LongSAGE). Comparison analyses have identified a number of important differentially expressed genes, including genes relevant to neural crest formation, noradrenergic neuron differentiation and the phenotype of NETKO mice. Examples of differentially expressed genes that affect noradrenergic cell differentiation include genes in the bone morphogenetic protein (BMP) signaling pathway, thePhox2bbinding partnerTlx2, the ubiquitin ligasePraja2, and the inhibitor of Notch signaling,Numbl. Differentially expressed genes that are likely to contribute to the NETKO phenotype include dopamine-β-hydroxylase (Dbh), tyrosine hydroxylase (Th), the peptide transmitter 'cocaine and amphetamine regulated transcript' (Cart), and the serotonin receptor subunitHtr3a. Real-time PCR confirmed differential expression of key genes not only in neural crest cells, but also in the adult superior cervical ganglion and locus ceruleus. In addition to known genes we have identified novel differentially expressed genes and thus provide a valuable database for future studies.ConclusionLoss of NET function during embryonic development in the mouse deregulates signaling pathways that are critically involved in neural crest formation and noradrenergic cell differentiation. The data further suggest deregulation of signaling pathways in the development and/or function of the NET-deficient peripheral, central and enteric nervous systems.