bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma Vitamins B2, B6, and B12, and Related Genetic Variants as Predictors of Colorectal Cancer Risk
Authors: Eussen Simone J.P.M. , Vollset Stein Emil , Hustad Steinar , Midttun Øivind , Meyer Klaus , Fredriksen Åse , Ueland Per Magne , Jenab Mazda , Slimani Nadia , Boffetta Paolo , Overvad Kim , Thorlacius-Ussing Ole , Tjønneland Anne , Olsen Anja , Clavel-Chapelon Françoise , Boutron-Ruault Marie-Christine , Morois Sophie , Weikert Cornelia , Pischon Tobias , Linseisen Jakob , Kaaks Rudolf , Trichopoulou Antonia , Zilis Demosthenes , Katsoulis Michael , Palli Domenico , Pala Valeria , Vineis Paolo , Tumino Rosario , Panico Salvatore , Peeters Petra H.M. , Bueno-de-Mesquita H. Bas , van Duijnhoven Fränzel J.B. , Skeie Guri , Muñoz Xavier , Martínez Carmen , Dorronsoro Miren , Ardanaz Eva , Navarro Carmen , Rodríguez Laudina , VanGuelpen Bethany , Palmqvist Richard , Manjer Jonas , Ericson Ulrika , Bingham Sheila , Khaw Kay-Tee , Norat Teresa , Riboli Elio 
Published: October 2010

AbstractBackground: B-vitamins are essential for one-carbon metabolism and have been linked to colorectal cancer. Although associations with folate have frequently been studied, studies on other plasma vitamins B2, B6, and B12 and colorectal cancer are scarce or inconclusive.Methods: We carried out a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, including 1,365 incident colorectal cancer cases and 2,319 controls matched for study center, age, and sex. We measured the sum of B2 species riboflavin and flavin mononucleotide, and the sum of B6 species pyridoxal 5′-phosphate, pyridoxal, and 4-pyridoxic acid as indicators for vitamin B2 and B6 status, as well as vitamin B12 in plasma samples collected at baseline. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for colorectal cancer were estimated using conditional logistic regression, adjusted for smoking, education, physical activity, body mass index, alcohol consumption, and intakes of fiber and red and processed meat.Results: The relative risks comparing highest to lowest quintile were 0.71 [95% confidence interval (95% CI), 0.56-0.91; Ptrend = 0.02] for vitamin B2, 0.68 (95% CI, 0.53-0.87; Ptrend &lt;0.001) for vitamin B6, and 1.02 (95% CI, 0.80-1.29; Ptrend = 0.19) for vitamin B12. The associations for vitamin B6 were stronger in males who consumed ≥30 g alcohol/day. The polymorphisms were not associated with colorectal cancer.Conclusions: Higher plasma concentrations of vitamins B2 and B6 are associated with a lower colorectal cancer risk.Impact: This European population-based study is the first to indicate that vitamin B2 is inversely associated with colorectal cancer, and is in agreement with previously suggested inverse associations of vitamin B6 with colorectal cancer. Cancer Epidemiol Biomarkers Prev; 19(10); 2549–61. ©2010 AACR.
Complement Factor H Is Elevated in Bronchoalveolar Lavage Fluid and Sputum from Patients with Lung Cancer
Authors: Pio Ruben , Garcia Javier , Corrales Leticia , Ajona Daniel , Fleischhacker Michael , Pajares Maria J. , Cardenal Felipe , Seijo Luis , Zulueta Javier J. , Nadal Ernest , Witt Christian , Lozano Maria D. , Schmidt Bernd , Montuenga Luis M. 
Published: October 2010

Abstract
Background: Cytologic examination of specimens obtained from the respiratory tract is a lung cancer diagnostic procedure with high specificity but moderate sensitivity. The use of molecular biomarkers may enhance the sensitivity of cytologic examination in the detection of lung cancer.
Methods: Complement factor H, a protein secreted by lung cancer cells, was quantified in a series of bronchoalveolar lavage supernatants from lung cancer patients and patients with nonmalignant respiratory diseases. Albumin, total protein content, and hemoglobin were also analyzed. Results were validated in independent sets of bronchoalveolar lavage and sputum supernatants.
Results: There was a significantly higher concentration of factor H in bronchoalveolar lavage samples from lung cancer patients. The sensitivity and specificity of the factor H test was 82% and 77%, respectively. These results were validated in an independent set of patients with nearly identical results. Furthermore, 70% and 45% of bronchoalveolar lavage fluids from central and peripheral tumors, respectively, reported as cytologically negative, were classified as positive using this marker. Finally, the test was evaluated in a series of sputum supernatants from lung cancer patients and controls. The sensitivity and specificity of the factor H test in this series was 80% and 88%, respectively.
Conclusion: Factor H is elevated in bronchoalveolar lavage and sputum from lung cancer patients.
Impact: Measurement of molecular biomarkers, such as complement factor H, may be used in the future as an adjunct to cytology in the diagnosis of malignant pulmonary diseases. Cancer Epidemiol Biomarkers Prev; 19(10); 2665–72. ©2010 AACR.
Alcohol-Folate Interactions in the Risk of Oral Cancer in Women: A Prospective Cohort Study
Authors: Shanmugham Jayapriyaa R. , Zavras Athanasios I. , Rosner Bernard A. , Giovannucci Edward L. 
Published: October 2010

Abstract
Background: The aim of this cohort study was to quantify the effect of alcohol on the risk of oral cancer in different strata of folate intake, controlling for known confounders.
Methods: A cohort of 87,621 women in the Nurses' Health Study was followed up from 1980 to 2006, and 147 incident oral cancer cases were reported and confirmed. Data on alcohol intake and diet were obtained through self-reported food frequency questionnaires every 4 years. Cox proportional regression analysis was conducted to estimate the adjusted risk ratios (RR) and 95% confidence intervals (95% CI).
Results: When compared with nondrinkers, the adjusted RRs (95% CIs) for alcohol intake were 0.59 (0.39-0.87) for 0.1-14.9 g/d, 1.15 (0.67-1.97) for 15-29.9 g/d, and 1.92 (1.08-3.40) for ≥30 g/d. We observed a significant interaction between alcohol and folate intakes (P = 0.02). The cancer risk for subjects with high alcohol (≥30 g/d) and low folate (&lt;350 μg/d) intakes was significantly elevated (RR, 3.36; 95% CI, 1.57-7.20) as compared with nondrinkers with low folate intake. The risk associated with high alcohol intake (≥30 g/d) was reduced to 0.98 (0.35-2.70) in the high-folate (≥350 μg/d) group as compared with nondrinkers with high folate intake.
Conclusions: High alcohol intake is associated with significantly increased oral cancer risk, especially in women with low folate intake.
Impact: A significant interaction between alcohol and folate intakes seems to affect oral cancer risk in women, a finding with potential public health utility. Cancer Epidemiol Biomarkers Prev; 19(10); 2516–24. ©2010 AACR.
Influence of Obesity on the Serum Carcinoembryonic Antigen Value in Patients with Colorectal Cancer
Authors: Park Jun Seok , Choi Gyu-Seog , Jang You Seok , Jun Soo Han , Kang Hyun 
Published: October 2010

Abstract
Background: Prior studies suggest that obesity is inversely associated with tumor marker concentration and may reduce diagnostic precision. This study was undertaken to evaluate the association between body mass index (BMI) and serum carcinoembryonic antigen (CEA) concentrations in colorectal cancer patients.
Methods: We analyzed the association between BMI and CEA concentration in a group of 2,845 patients who underwent surgical treatment for colorectal adenocarcinoma from 1995 to 2009. Multivariate linear regression analysis was applied to adjust for clinicopathologic confounding factors to analyze main outcome measures. The association of BMI with plasma volume, CEA concentration, and total circulating CEA mass was assessed by determining P values for trends. We also developed a regression formula to calculate the effect of obesity on the serum CEA levels.
Results: Increased BMI was linearly correlated with higher plasma volume (P &lt; 0.001 for trend) and lower adjusted CEA concentrations after controlling for potentially confounding factors (P ≤ 0.005 for trend in stage II and III tumors). Our theoretical model suggests that a CEA value of 7.0 ng/mL in patients of normal weight corresponds to 6.1 ng/mL in obese patients.
Conclusions: The hemodilution effect from increased plasma volume may account for the decreased CEA concentrations observed in patients with higher BMI.
Impact: Obesity might be one of the factors that affect CEA value, leading to loss of sensitivity and diagnostic accuracy in the CEA test. The BMI status of patients should be taken into account during assessment of serum CEA during the surveillance of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 19(10); 2461–8. ©2010 AACR.
Do Steroid Hormones Play a Role in the Etiology of Glioma?
Authors: Kabat Geoffrey C. , Etgen Anne M. , Rohan Thomas E. 
Published: October 2010

AbstractGliomas are the most common type of primary malignant brain tumor and have a very poor prognosis. Little is known, however, about the etiology of these tumors. Evidence from a number of sources suggests that endogenous steroid hormones may play a role in the development of gliomas. First, the descriptive epidemiology of glioma suggests a relative protection of females compared with males, particularly during the premenopausal years. Second, some gliomas and glioblastomas express estrogen receptors (ER), especially ERβ, as well as aromatase, the enzyme responsible for the conversion of testosterone to estradiol, and possibly other steroid hormone receptors. Third, experimental studies indicate that glioblastomas transplanted into animals grow at a slower rate in females compared with males. Finally, experimental studies show that estradiol, 2-methoxyestradiol, and a number of selective estrogen receptor modulators inhibit proliferation of gliomas and induce cell death. These hormonal agonists and antagonists may act either through classical steroid hormone receptors or independently of such receptors. In view of these findings, further clinical, experimental, and epidemiologic studies are needed to elucidate the role of steroid hormone agonists and antagonists in the development and proliferation of glioma. If hormonal pathways are involved in gliomagenesis, this could eventually lead to the design of preventive strategies. Cancer Epidemiol Biomarkers Prev; 19(10); 2421–7. ©2010 AACR.
Expression of the Tumor Suppressor Krüppel-Like Factor 4 as a Prognostic Predictor for Colon Cancer
Authors: Patel Nilesh V. , Ghaleb Amr M. , Nandan Mandayam O. , Yang Vincent W. 
Published: October 2010

Abstract
Background: The zinc finger transcription factor Krüppel-like factor 4 (KLF4) regulates numerous physiologic processes, including proliferation, differentiation, and development. Studies also showed that KLF4 is involved in tumorigenesis and somatic cell reprogramming. Here, we aimed to assess whether KLF4 is a prognostic indicator for colon cancer.
Methods: Levels of KLF4 were measured by immunohistochemical analysis of a tissue microarray containing 367 independent colon cancer sections. Univariate data analysis was done in addition to construction of multivariate models with several clinicopathologic factors to evaluate KLF4 as an independent predictor of survival and cancer recurrence (disease-free survival).
Results: Colon cancer tissues had significantly overall lower KLF4 levels compared with noncancer tissues (P &lt; 0.0001). Using logistic regression, a trend was noted for decreased odds of KLF4 expression in higher stages of tumors. In univariate and multivariate analyses, KLF4 was a significant predictor of survival and recurrence.
Conclusions: KLF4 expression is significantly downregulated in colon cancer, and loss of KLF4 is an independent predictor of survival and recurrence.
Impact: These findings suggest that KLF4 may serve as a prognostic biomarker for colon cancer. Cancer Epidemiol Biomarkers Prev; 19(10); 2631–8. ©2010 AACR.
Oral Contraceptive Use and Breast Cancer: A Prospective Study of Young Women
Authors: Hunter David J. , Colditz Graham A. , Hankinson Susan E. , Malspeis Susan , Spiegelman Donna , Chen Wendy , Stampfer Meir J. , Willett Walter C. 
Published: October 2010

Abstract
Background: Previous studies convincingly showed an increase in risk of breast cancer associated with current or recent use of oral contraceptives from the 1960s to 1980s. The relation of contemporary oral contraceptive formulations to breast cancer risk is less clear.
Methods: We assessed lifetime oral contraceptive use and the specific formulations used among 116,608 female nurses ages 25 to 42 years at enrollment in 1989, and subsequently updated this information every 2 years. We related this information to risk of breast cancer up to June 1, 2001.
Results: During 1,246,967 person-years of follow-up, 1,344 cases of invasive breast cancer were diagnosed. Past use of any oral contraceptive was not related to breast cancer risk [multivariate relative risk (RR), 1.12; 95% confidence interval 0.95-1.33]. Current use of any oral contraceptive was related to a marginally significant higher risk (multivariate RR, 1.33; 95% CI, 1.03-1.73). One specific formulation substantially accounted for the excess risk: the RR for current use of triphasic preparations with levonorgestrel as the progestin was 3.05 (95% CI, 2.00-4.66; P &lt; 0.0001).
Conclusions: Current use of oral contraceptives carries an excess risk of breast cancer. Levonorgestrel used in triphasic preparations may account for much of this elevation in risk.
Impact: Different oral contraceptive formulations might convey different risks of breast cancer; ongoing monitoring of these associations is necessary as oral contraceptive formulations change. Cancer Epidemiol Biomarkers Prev; 19(10); 2496–502. ©2010 AACR.
Development of a Validated Immunofluorescence Assay for γH2AX as a Pharmacodynamic Marker of Topoisomerase I Inhibitor Activity
Authors: Kinders Robert J. , Hollingshead Melinda , Lawrence Scott , Ji Jiuping , Tabb Brian , Bonner William M. , Pommier Yves , Rubinstein Larry , Evrard Yvonne A. , Parchment Ralph E. , Tomaszewski Joseph , Doroshow James H. 
Published: October 2010

Abstract
Purpose: Phosphorylated histone H2AX (γH2AX) serves as a biomarker for formation of DNA double-strand break repair complexes. A quantitative pharmacodynamic immunofluorescence assay for γH2AX was developed, validated, and tested in human tumor xenograft models with the use of clinically relevant procedures.
Experimental Design: The γH2AX immunofluorescence assay uses a novel data quantitation and image processing algorithm to determine the extent of nuclear-specific γH2AX staining in tumor needle biopsies and hair follicles collected from mice bearing topotecan-responsive A375 xenografts. After method validation with the topoisomerase I (Top1) inhibitor topotecan, the assay was used to compare pharmacodynamic properties of three structurally related indenoisoquinoline Top1 inhibitors.
Results: γH2AX response to topotecan was quantified over a 60-fold dose range (0.016-1.0 times the murine single-dose maximum tolerated dose), and significant pharmacodynamic response was measured at the mouse equivalent of the 1.5 mg/m2 clinical dose as well as the lowest dose tested. Responses were within a time window amenable for biopsy collection in clinical trials. These studies enabled characterization of dose and time responses for three indenoisoquinolines, resulting in selection of two for clinical evaluation. γH2AX response to Top1 inhibitors in hair follicles was also observable above a minimal dose threshold.
Conclusions: Our γH2AX assay is sufficiently accurate and sensitive to quantify γH2AX in tumor samples and will be used in correlative studies of two indenoisoquinolines in a phase I clinical trial at the National Cancer Institute. Data suggest that hair follicles may potentially serve as a surrogate tissue to evaluate tumor γH2AX response to Top1 inhibitors. Clin Cancer Res; 16(22); 5447–57. ©2010 AACR.
REO-10: A Phase I Study of Intravenous Reovirus and Docetaxel in Patients with Advanced Cancer
Authors: Comins Charles , Spicer James , Protheroe Andrew , Roulstone Victoria , Twigger Katie , White Christine M. , Vile Richard , Melcher Alan , Coffey Matt C. , Mettinger Karl L. , Nuovo Gerard , Cohn David E. , Phelps Mitch , Harrington Kevin J. , Pandha Hardev S. 
Published: October 2010

Abstract
Purpose: REOLYSIN (Oncolytics Biotech) consists of a wild-type oncolytic reovirus, which has selective cytotoxicity for tumor cells while sparing normal cells. In a phase I study as a single agent, repeated infusions of reovirus were safe with evidence of antitumor activity. Preclinical studies indicate potential for synergy between reovirus and chemotherapeutic agents. A multicenter, phase I dose escalation study was designed to assess the safety of combining reovirus with docetaxel chemotherapy in patients with advanced cancer.
Experimental Design: Patients received 75 mg/m2 docetaxel (day 1) and escalating doses of reovirus up to 3 × 1010 TCID50 (days 1-5) every 3 weeks.
Results: Twenty-five patients were enrolled, and 24 patients were exposed to treatment, with 23 completing at least one cycle and 16 suitable for response assessment. Dose-limiting toxicity of grade 4 neutropenia was seen in one patient, but the maximum tolerated dose was not reached. Antitumor activity was seen with one complete response and three partial responses. A disease control rate (combined complete response, partial response, and stable disease) of 88% was observed. Immunohistochemical analysis of reovirus protein expression was observed in posttreatment tumor biopsies from three patients.
Conclusion: The combination of reovirus and docetaxel is safe, with evidence of objective disease response, and warrants further evaluation in a phase II study at a recommended schedule of docetaxel (75 mg/m2, three times weekly) and reovirus (3 × 1010 TCID50, days 1-5, every 3 weeks). Clin Cancer Res; 16(22); 5564–72. ©2010 AACR.
Compensatory Insulin Receptor (IR) Activation on Inhibition of Insulin-Like Growth Factor-1 Receptor (IGF-1R): Rationale for Cotargeting IGF-1R and IR in Cancer
Authors: Buck Elizabeth , Gokhale Prafulla C. , Koujak Susan , Brown Eric , Eyzaguirre Alexandra , Tao Nianjun , Rosenfeld-Franklin Maryland , Lerner Lorena , Chiu M. Isabel , Wild Robert , Epstein David , Pachter Jonathan A. , Miglarese Mark R. 
Published: October 2010

Abstract
Insulin-like growth factor-1 receptor (IGF-1R) is a receptor tyrosine kinase (RTK) and critical activator of the phosphatidylinositol 3-kinase–AKT pathway. IGF-1R is required for oncogenic transformation and tumorigenesis. These observations have spurred anticancer drug discovery and development efforts for both biological and small-molecule IGF-1R inhibitors. The ability for one RTK to compensate for another to maintain tumor cell viability is emerging as a common resistance mechanism to antitumor agents targeting individual RTKs. As IGF-1R is structurally and functionally related to the insulin receptor (IR), we asked whether IR is tumorigenic and whether IR-AKT signaling contributes to resistance to IGF-1R inhibition. Both IGF-1R and IR(A) are tumorigenic in a mouse mammary tumor model. In human tumor cells coexpressing IGF-1R and IR, bidirectional cross talk was observed following either knockdown of IR expression or treatment with a selective anti–IGF-1R antibody, MAB391. MAB391 treatment resulted in a compensatory increase in phospho-IR, which was associated with resistance to inhibition of IRS1 and AKT. In contrast, treatment with OSI-906, a small-molecule dual inhibitor of IGF-1R/IR, resulted in enhanced reduction in phospho-IRS1/phospho-AKT relative to MAB391. Insulin or IGF-2 activated the IR-AKT pathway and decreased sensitivity to MAB391 but not to OSI-906. In tumor cells with an autocrine IGF-2 loop, both OSI-906 and an anti–IGF-2 antibody reduced phospho-IR/phospho-AKT, whereas MAB391 was ineffective. Finally, OSI-906 showed superior efficacy compared with MAB391 in human tumor xenograft models in which both IGF-1R and IR were phosphorylated. Collectively, these data indicate that cotargeting IGF-1R and IR may provide superior antitumor efficacy compared with targeting IGF-1R alone. Mol Cancer Ther; 9(10); 2652–64. ©2010 AACR.
Toxic encephalopathy in elderly patients during treatment with capecitabine: literature review and a case report
Authors: Fantini Manuela , Gianni Lorenzo , Tassinari Davide , Nicoletti Stefania , Possenti Cinzia , Drudi Fabrizio , Sintini Michele , Bagli Laura , Tamburini Emiliano , Ravaioli Alberto 
Published: October 2010

Capecitabine is now-a-days rapidly replacing 5-Fluorouracil in daily clinical practice. Neurologic toxicity during a treatment with fluoropyrimidines, as 5-fluorouracil, represents a well-known side-effect, largely described in literature. Central nervous system (CNS) toxicity, mainly encephalopathy with or without seizures, occurs occasionally even when conventional doses are used. CNS toxicity incidence increases markedly when the blood-brain barrier is either overwhelmed or bypassed (Hildebrand J. Neurological complications of cancer chemotherapy. Curr Opin Oncol 2006; 18: 321—324). Peripheral nervous system (PNS) toxicity is more common because proximal and distal extremities of the peripheral nerves are not protected by a blood-brain like barrier and peripheral neuropathy remains a major limiting factor for the administration of conventional doses of several agents (Saif W, Wood TE, McGee PJ and Diasio RB. Peripheral neuropathy associated with capecitabine, Anticancer Drugs 2004;15: 767—771). Capecitabine is a prodrug of 5-fluorouracil, more easily administered by mouth; its transformation in 5-fluorouracil is performed in the liver. There are only a few reports on the toxic neurological side-effects of capecitabine. We describe in our report a rare case of toxic encephalopathy in a 82-year-old female, with a brief review of literature. In the literature reviewed, we found 12 neurologic episodes due to capecitabine lasting between a few days till some months. All clinical symptoms of the cases described in literature, obtained a complete regression with the discontinuation of capecitabine. A relation was not found with dihydropyrimidine dehydrogenase (DPD) mutation, also if pharmacologic and pharmacogenetic assessment should be done for this drug, especially in old patients. Toxic encephalopathy represents a rare event during capecitabine treatment and on the bases of the data found, is fairly managed in the clinical setting. The knowledge of the natural history of the toxic effect allows the use of the drug also in old patients.
Stability of unused reconstituted bortezomib in original manufacturer vials
Authors: Vanderloo Joshua P , Pomplun Marcia L , Vermeulen Lee C , Kolesar Jill M 
Published: October 2010

Background. Bortezomib is a modified dipeptidyl boronic acid analogue used to treat multiple myeloma, mantle cell lymphoma, and, more recently, renal transplantation graft rejection. As per manufacturer recommendations, bortezomib is to be administered within 8 h of preparation or may be stored for up to 8 h in the vial or a syringe following reconstitution. Preserving unused reconstituted bortezomib beyond these 8 h may allow for cost savings. This study aims to examine the stability of unused reconstituted bortezomib when stored at 4°C for up to 15 days. Methods. Using an LC-MS/MS assay, the concentration of reconstituted bortezomib was measured at predetermined time points following storage at 4°C in the manufacturer vial. Percent bortezomib remaining at a time point was calculated versus initial bortezomib concentration. Results. The concentrations of bortezomib were found to be 51.93 ng/mL ± 4.60 after 1 day of storage, 57.40 ng/mL ± 4.77 after 8 days of storage, and 49.43 ng/mL ± 2.85 after 15 days of storage. The percent of bortezomib remaining was 110.53% and 95.19% after 8 days and 15 days, respectively. Conclusion. Unused reconstituted bortezomib is stable for up to 15 days stored at 4°C in the original manufacturer vial. Such use of bortezomib may improve cost efficiency by reducing bortezomib waste.