bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcoholic Beverage Intake and Risk of Lung Cancer: The California Men's Health Study
Authors: Chao Chun , Slezak Jeff M. , Caan Bette J. , Quinn Virginia P. 
Published: October 2008

Abstract
We investigated the effect of alcoholic beverage consumption on the risk of lung cancer using the California Men's Health Study.
Methods: The California Men's Health Study is a multiethnic cohort of 84,170 men ages 45 to 69 years who are members of the Kaiser Permanente California health plans. Demographics and detailed lifestyle characteristics were collected from surveys mailed between 2000 and 2003. Incident lung cancer cases were identified by health plan cancer registries through December 2006 (n = 210). Multivariable Cox's regression was used to examine the effects of beer, red wine, white wine (including rosé), and liquor consumption on risk of lung cancer adjusting for age, race/ethnicity, education, income, body mass index, history of chronic obstructive pulmonary disease/emphysema, and smoking history.
Results: There was a significant linear decrease in risk of lung cancer associated with consumption of red wine among ever-smokers: hazard ratio (HR), 0.98; 95% confidence interval (95% CI), 0.96-1.00 for increase of 1 drink per month. This relationship was slightly stronger among heavy smokers (≥20 pack-years): HR, 0.96; 95% CI, 0.93-1.00. When alcoholic beverage consumption was examined by frequency of intake, consumption of ≥1 drink of red wine per day was associated with an approximately 60% reduced lung cancer risk in ever-smokers: HR, 0.39; 95% CI, 0.14-1.08. No clear associations with lung cancer were seen for intake of white wine, beer, or liquor.
Conclusion: Moderate red wine consumption was inversely associated with lung cancer risk after adjusting for confounders. Our results should not be extrapolated to heavy alcohol consumption. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2692–9)
A Population-Based, Descriptive Analysis of Malignant Intraductal Papillary Mucinous Neoplasms of the Pancreas
Authors: Le Hoa , Ziogas Argyrios , Rhee Jessica M. , Lee John G. , Lipkin Steven M. , Zell Jason A. 
Published: October 2008

Abstract
Background: Intraductal papillary mucinous neoplasms (IPMN) are distinct precursor lesions that can progress to pancreatic adenocarcinoma; thus, it has been of particular interest to cancer prevention researchers. We set out to do a population-based analysis of malignant IPMNs compared with other pancreatic subtypes to better delineate its characteristics and explore implications for prevention and management.
Methods: We conducted a case-only analysis of California Cancer Registry data (2000-2007), including descriptive analysis of relevant clinical variables. Overall survival univariate analyses were conducted using the Kaplan-Meier method. Multivariate survival analyses were done using Cox proportional hazards ratios.
Results: Overall, 15,296 pancreatic cancer cases were identified, including incident cases of 10,186 adenocarcinomas, 880 mucinous tumors, 568 endocrine tumors, 3,619 carcinoma not otherwise specified tumors, and 43 malignant IPMNs. Thirty-three (80.5%) IPMN cases had localized disease at presentation, eight had regional disease (19.5%), and no IPMNs were identified with distant disease (two were unstaged). Five-year overall survival was better for malignant IPMN cases (65%) compared with pancreatic endocrine tumors (30%), mucinous tumors (5%), carcinoma not otherwise specified (2%), and adenocarcinoma cases (2%). Compared with adenocarcinoma cases, malignant IPMN cases (hazard ratio = 0.19; 95% CI, 0.10-0.35), endocrine tumors (hazard ratio = 0.28; 95% CI, 0.25-0.32), and mucinous tumors (hazard ratio = 0.84; 95% CI, 0.77-0.90) had higher overall survival in a multivariate survival analysis after adjustment for age, gender, stage, race, socioeconomic status, surgery, chemotherapy, and radiation therapy.
Conclusions: Pancreatic malignant IPMNs represent an uncommon pancreatic tumor subtype, uniquely characterized by early stage at presentation and better survival. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2737–41)
Multianalyte Profiling of Serum Antigens and Autoimmune and Infectious Disease Molecules to Identify Biomarkers Dysregulated in Epithelial Ovarian Cancer
Authors: Bertenshaw Greg P. , Yip Ping , Seshaiah Partha , Zhao Jinghua , Chen Tzong-Hao , Wiggins Wesley S. , Mapes James P. , Mansfield Brian C. 
Published: October 2008

Abstract
Ovarian cancer is the deadliest gynecologic cancer in the United States. When detected early, the 5-year survival rate is 92%, although most cases remain undetected until the late stages where 5-year survival rates are 30%. Serum biomarkers may hold promise. Although many markers have been proposed and multivariate diagnostic models were built to fit the data on small, disparate sample sets, there has been no systematic evaluation of these markers on a single, large, well-defined sample set. To address this, we evaluated the dysregulation of 204 molecules in a sample set consisting of serum from 294 patients, collected from multiple collection sites, under a well-defined Gynecologic Oncology Group protocol. The population, weighted with early-stage cancers to assess biomarker value for early detection, contained all stages of ovarian cancer and common benign gynecologic conditions. The panel of serum molecules was assayed using rigorously qualified, high-throughput, multiplexed immunoassays and evaluated for their independent ovarian cancer diagnostic potential. Seventy-seven biomarkers were dysregulated in the ovarian cancer samples, although cancer antigen 125, C-reactive protein, epidermal growth factor receptor, interleukin 10, interleukin 8, connective tissue growth factor, haptoglobin, and tissue inhibitor of metalloproteinase 1 stood out as the most informative. When analyzed by cancer subtype and stage, there were differences in the relative value of biomarkers. In this study, using a large sample cohort, we show that some of the reported ovarian cancer biomarkers are more robust than others, and we identify additional informative candidates. These findings may guide the development of multivariate diagnostic models, which should be tested on additional, prospectively collected samples. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2872–81)
Alcohol Drinking and One-Carbon Metabolism-Related Gene Polymorphisms on Pancreatic Cancer Risk
Authors: Suzuki Takeshi , Matsuo Keitaro , Sawaki Akira , Mizuno Nobumasa , Hiraki Akio , Kawase Takakazu , Watanabe Miki , Nakamura Tsuneya , Yamao Kenji , Tajima Kazuo , Tanaka Hideo 
Published: October 2008

Abstract
Effect of alcohol consumption on pancreatic cancer risk has been investigated in many studies, but results have been inconsistent. We conducted a case-control study to assess the effect of alcohol on pancreatic cancer in conjunction with polymorphisms in one-carbon metabolism enzymes, methylenetetrahydrofolate reductase (MTHFR C677T), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G), and thymidylate synthase (TS) variable number of tandem repeat. A total of 157 pancreatic cancer patients and 785 age- and sex- matched control subjects were genotyped for polymorphisms. Odds ratios (OR) with 95% confidence intervals (95% CI) were estimated using unconditional logistic models adjusted for potential confounders. Heavy alcohol drinking was marginally associated with an increased risk of pancreatic cancer (OR, 1.90; 95% CI, 1.00-3.62). None of the polymorphisms showed any significant effect on pancreatic cancer risk by genotype alone. In stratified analysis, effect of alcohol consumption on pancreatic cancer was observed in individuals with the MTHFR 667 CC, MTR 2756 AA, or MTRR 66 G allele. OR (95% CI) of pancreatic cancer for heavy drinkers compared with never drinkers was 4.50 (1.44-14.05) in the MTHFR 667 CC genotype, 2.65 (1.17-6.00) in the MTR 2756 AA genotype, and 3.35 (1.34-8.36) in the MTRR 66 G allele carriers. These results suggest that the folate-related enzyme polymorphism modifies the association between drinking habit and pancreatic cancer risk. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2742–7)
Differences in Estrogen Receptor Subtype According to Family History of Breast Cancer among Hispanic, but not Non-Hispanic White Women
Authors: Hines Lisa M. , Risendal Betsy , Slattery Martha L. , Baumgartner Kathy B. , Giuliano Anna R. , Byers Tim 
Published: October 2008

Abstract
Background: Pathologic differences have been reported among breast tumors when comparing ethnic populations. Limited research has been done to evaluate the ethnic-specific relationships between breast cancer risk factors and the pathologic features of breast tumors.
Methods: Given that genetic variation may contribute to ethnic-related etiologic differences in breast cancer, we hypothesized that tumor characteristics differ according to family history of breast cancer among Hispanic and non-Hispanic White (NHW) women. Logistic regression models were used to compute odds ratios (OR) and 95% confidence intervals (95% CI) to assess this relationship in the population-based, case-control 4-Corners Breast Cancer Study (1,537 cases and 2,452 controls).
Results: Among Hispanic women, having a family history was associated with a 2.7-fold increased risk of estrogen receptor (ER) negative (95% CI, 1.59-4.44), but not ER positive tumors (OR, 1.04; 95% CI, 0.71-1.54) when compared with women without breast cancer. In contrast, there was an increased risk for ER positive (OR, 1.89; 95% CI, 1.50-2.38) and a marginally significant increased risk for ER negative tumors (OR, 1.41; 95% CI, 0.92-2.17) among NHW women. When comparing tumor characteristics among invasive cases, those with a family history also had a significantly higher proportion of ER negative tumors among Hispanics (39.2% versus 25.8%; P = 0.02), but not among NHWs (16.3% versus 21.1%; P = 0.13).
Conclusions: These results may reflect ethnic-specific predisposing genetic factors that promote the development of specific breast tumor subtypes, and emphasize the importance of evaluating the relationship between breast cancer risk factors and breast tumor subtypes among different ethnic populations. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2700–6)
Single-Dose Pharmacokinetics and Tolerability of Absorption-Enhanced 3,3′-Diindolylmethane in Healthy Subjects
Authors: Reed Gregory A. , Sunega Jean M. , Sullivan Debra K. , Gray John C. , Mayo Matthew S. , Crowell James A. , Hurwitz Aryeh 
Published: October 2008

Abstract
We have completed a single ascending dose clinical study of the proposed chemopreventive agent 3,3′-diindolylmethane (DIM). The study agent was nutritional-grade, absorption-enhanced BioResponse 3,3′-diindolylmethane (BR-DIM). We determined the safety, tolerability, and pharmacokinetics of single doses of BR-DIM in drug-free, non-smoking, healthy men and women. Groups of four subjects were enrolled for each dose level. After randomization, one subject in each group received placebo whereas three received active BR-DIM. The doses administered were 50, 100, 150, 200, and 300 mg, with the 300-mg dose repeated in an additional group. No BR-DIM–related adverse effects were reported at doses up to 200 mg. At the 300-mg dose, one of six subjects reported mild nausea and headache and one also reported vomiting. Only the latter effect was judged as probably related to the study agent. Analysis of serial plasma samples showed that only one subject at the 50-mg dose had detectable concentrations of DIM. The single 100-mg dose of BR-DIM resulted in a mean maximum plasma concentration (Cmax) of 32 ng/mL and a mean area under the curve (AUC) of 128 h ng/mL, and a single 200-mg dose produced a mean Cmax of 104 ng/mL and a mean AUC of 553 h ng/mL. The single 300-mg dose of BR-DIM resulted in a mean Cmax of 108 ng/mL and a mean AUC of 532 h ng/mL. We conclude that BR-DIM is well tolerated at single doses of up to 200 mg, and that increasing the dose to 300 mg did not result in an increase in Cmax. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2619–24)
A Prospective Study of Dietary Folate and Vitamin B and Colon Cancer According to Microsatellite Instability and KRAS Mutational Status
Authors: Schernhammer Eva S. , Giovannuccci Edward , Fuchs Charles S. , Ogino Shuji 
Published: October 2008

Abstract
Sporadic microsatellite instability (MSI)-high colon cancers are positively associated with MLH1 promoter methylation and inversely with KRAS mutation. One-carbon metabolism is critical for methylation reactions and nucleotide biosynthesis, but the influence of dietary one-carbon nutrients such as folate and B vitamins on molecular changes in colon cancer is not known. Using the database of two independent prospective cohort studies (88,691 women and 47,371 men), we examined the relation between dietary intake of one-carbon nutrients and the incidence of microsatellite instability and KRAS mutation in 669 incident colon cancers. The overall inverse association between folate and colon cancer did not differ significantly according to MSI status [relative ratio (RR), 0.79; 95% confidence interval (95% CI), 0.60-1.03 for microsatellite stable/MSI-low colon cancers; and RR, 0.61, 95% CI, 0.37-1.02 for MSI-high colon cancers; Pheterogeneity = 0.53] or KRAS status (RR, 0.66; 95% CI, 0.49-0.87 for KRAS wild-type colon cancers; and RR, 1.05; 95% CI, 0.68-1.61 for KRAS mutated colon cancers; Pheterogeneity = 0.12), although our analyses had limited power to preclude an effect of folate on KRAS wild-type colon cancers. Similarly, high vitamin B6 or B12 intake was inversely associated with colon cancers, regardless of MSI or KRAS status. No significant effect of methionine intake or alcohol consumption was observed for colon cancers with MSI high or KRAS mutation. In conclusion, the influence of dietary one-carbon nutrient intake on colon cancer risk does not seem to differ according to MSI or KRAS mutational status. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2895–8)
Experimental studies on the bone metabolism of male rats chronically exposed to cadmium intoxication using dual-energy X-ray absorptiometry
Authors: Yokota H , Tonami H 
Published: October 2008

Cadmium (Cd) has been identified as the etiologic agent of itai-itai disease. The purpose of this study was to investigate whether chronic Cd exposure affects bone metabolism in a male rat model and to estimate the bone mineral density (BMD) differences in lumbar and femoral bone because of Cd exposure. Six-week-old male Hos Donryu rats were used in this experiment. Cadmium was administered at a dose of 200 ppm to rats in the diet to produce experimental chronic Cd poisoning. Bone mineral density was measured using dual-energy X-ray absorptiometry (DEXA) with a high-resolution scan collimator (0.25 mm diameter) (Hologic QDR-2000). The Cd content in renal tissue reached a critical concentration of 128.42 ± 14.38 μg/g 10 months after the administration of the element (Table 3). The average blood urea nitrogen (BUN) value was increased throughout the period of the experiment, and the serum creatinine value of the experimental group showed an increase after 2 months of Cd administration (0.46 ± 0.09 mg/dL). The concentration of urinary calcium changed in the experimental group after exposure to Cd for 12 months (15.4 ± 0.13 mg/dL). DEXA showed a greater reduction in the bone mineral density of the 5th vertebral body (L5) in rats that had ingested Cd for 4 months (0.359 ± 0.013 g/cm2) than in control rats (0.372 ± 0.012 g/cm2, P < 0.01). On the contrary, the difference in bone mineral content between rats ingesting Cd for 6–8 months and control rats was not significant. However, significant reductions in bone mineral content were again noted in rats that had ingested Cd for 12 months (0.339 ± 0.023 g/cm2) compared with the control group (0.385 ± 0.012 g/cm2, P < 0.01). The bone mineral density of the right femoral bone in control rats was 0.328 ± 0.018 g/cm2 and that in experimental rats was 0.306 ± 0.012 g/cm2, and a meaningful difference was recognized ( P < 0.05). Histological examination of the rats exposed to Cd for 12 months showed that the 5th lumbar vertebral body (L5) exhibited osteomalacia. The results of our studies show that Cd stimulated a loss of bone mineral at an early stage to a great extent in male rats. In the examination of male rats, bone injury and renal functional disorder were encountered simultaneously. This study suggested that osteomalacia was induced by a direct action of Cd on the bone through abnormal calcium homeostasis at an early stage in male rats.
Neuropathological changes induced by neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in male Swiss albino mice
Authors: Rajeswari A , Sabesan M 
Published: October 2008

We investigated the level of dopamine in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated male Swiss albino mice (40 mg/kg), after 7 days, we measured the levels of non-enzymatic antioxidants, the reduced glutothione (GSH), enzymatic anti-oxidants such as superoxide dismulase (SOD), cataloes (CAT) and also observed the histopathology of the mesencephalic areas after MPTP treatment by transmission electron microscopy (EM). We found that the MPTP treatment in mice caused a significant depletion of GSH, increased the specific activity of SOD, CAT, and thiobarbituric acid–reactive substances (TBARS) in mesencephalic region after 7 days of treatment, and decreased the striatal dopamine level to 75% by 7 days of MPTP treatment. The EM results also suggested that the mitochondrial alternation, nuclear membrane invagination, condensation of cytoplasm, vacuoles and perinuclear inclusion in the cytoplasm, and nuclear membrane disappearance were observed in MPTP-treated mice.
Metabolic activation of retronecine and retronecine N-oxide – formation of DHP-derived DNA adducts
Authors: Yan J , Xia Q , Chou MW , Fu PP 
Published: October 2008

We have previously reported that metabolism of a series of pyrrolizidine alkaloids in vitro and in vivo generated a set of (+/−)6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts. It has also been shown that the levels of the DHP-derived DNA adduct formation correlated closely with the tumorigenic potencies of the mice fed with different doses of riddelliine. Retronecine is the necine base and the structurally smallest chemical of the retronecine-type pyrrolizidine alkaloids. Although it has been reported that microsomal metabolism of retronecine generated DHP as a metabolite, it was yet not known whether metabolism of retronecine in vivo could generate DHP-derived DNA adducts and if formed, whether or not the levels of DNA adducts were comparable with those formed from the other tumorigenic retronecine-type pyrrolizidine alkaloids, such as riddelliine, retrorsine, and monocrotaline. In this investigation, the in-vitro and in-vivo metabolic activation of retronecine was studied. Rat liver microsomal metabolism of retronecine in the presence of calf thymus DNA resulted in the formation of a set of DHP–DNA adducts. The metabolism of retronecine N-oxide under similar conditions also formed the similar set of DHP–DNA adducts. The level of DNA adducts from retronecine was enhanced when metabolism by liver microsomes from phenobarbital (PB)-induced rats were used. The DHP–DNA adducts were also found in the liver DNA of female F344 rats treated with retronecine or retronecine N-oxide. The highest level of the total DHP–DNA adducts was found in liver DNA from the rats treated with dehydroretronecine (DHR). The order of the levels of DNA adducts in the liver DNA samples from rats treated with various pyrrolizidine alkaloids was: DHR > riddelliine > riddelliine N-oxide >> retronecine > retronecine N-oxide. The results indicate that 1) retronecine can be metabolized to form DHP by rat liver microsomal enzymes and interacts with DNA to produce DHP–DNA adducts and 2) retronecine N-oxide undergoes the biotransformation to the parent compound, retronecine. The results from this and our previous findings strongly suggest that formation of DHP–DNA adducts may be a potential biomarker for pyrrolizidine alkaloid carcinogenesis.
GATA-2 regulates granulocyte-macrophage progenitor cell function
Authors: Rodrigues Neil P. , Boyd Ashleigh S. , Fugazza Cristina , May Gillian E. , Guo YanPing , Tipping Alex J. , Scadden David T. , Vyas Paresh , Enver Tariq 
Published: October 2008

Abstract
The zinc finger transcription factor GATA-2 has been implicated in the regulation of hematopoietic stem cells. Herein, we explored the role of GATA-2 as a candidate regulator of the hematopoietic progenitor cell compartment. We showed that bone marrow from GATA-2 heterozygote (GATA-2+/−) mice displayed attenuated granulocyte-macrophage progenitor function in colony-forming cell (CFC) and serial replating CFC assays. This defect was mapped to the Lin−CD117+Sca-1−CD34+CD16/32high granulocyte-macrophage progenitor (GMP) compartment of GATA-2+/− marrow, which was reduced in size and functionally impaired in CFC assays and competitive transplantation. Similar functional impairments were obtained using a RNA interference approach to stably knockdown GATA-2 in wild-type GMP. Although apoptosis and cell-cycle distribution remained unperturbed in GATA-2+/− GMP, quiescent cells from GATA-2+/− GMP exhibited altered functionality. Gene expression analysis showed attenuated expression of HES-1 mRNA in GATA-2–deficient GMP. Binding of GATA-2 to the HES-1 locus was detected in the myeloid progenitor cell line 32Dcl3, and enforced expression of HES-1 expression in GATA-2+/− GMP rectified the functional defect, suggesting that GATA-2 regulates myeloid progenitor function through HES-1. These data collectively point to GATA-2 as a novel, pivotal determinant of GMP cell fate.
Extracellular ligation-dependent CD45RB enzymatic activity negatively regulates lipid raft signal transduction
Authors: Parikh Kaushal , Poppema Sibrand , Peppelenbosch Maikel P. , Visser Lydia 
Published: October 2008

AbstractCD45 is the most prominent membrane protein on lymphocytes. The function and regulation of this protein tyrosine phosphatase remain largely obscure, mainly because of the lack of a known ligand, and it still remains unknown whether such tyrosine phosphatases are subject to extracellular control at all. We report that an anti-CD45RB antibody (Ab) that prevents rejection and induces tolerance activates CD45RB tyrosine phosphatase enzymatic activity in T lymphocytes, allowing us to directly monitor the effects of increased CD45RB activity on signal transduction. Using both kinase substrate peptide arrays as well as conventional biochemistry, we also provide evidence of the various kinases involved in bringing about the inhibitory effect of this Ab on CD3-induced T-cell receptor signaling. Furthermore, we report that activated CD45RB translocates to lipid rafts and interferes with lipid raft localization and activation state of CD45 substrate Lck. Thus, these findings indeed prove that CD45 is subject to extracellular control and also define a novel mechanism by which receptor tyrosine phosphatases control lymphocyte biology and provide further insight into the intracellular signaling pathways effected by anti-CD45RB monoclonal Ab treatment.