bluuebunny/crossref_metadata_2025_split huggingface dataset:
HER-2/neu-Mediated Regulation of Components of the MHC Class I Antigen-Processing Pathway
Authors: Herrmann Felix , Lehr Hans-Anton , Drexler Ingo , Sutter Gerd , Hengstler Jan , Wollscheid Ursula , Seliger Barbara 
Published: September 2005

Abstract
Because of its amplification and/or overexpression in many human tumors, the HER-2/neu proto-oncogene represents an attractive target for T-cell-mediated vaccination strategies. However, overexpression of oncogenes is often associated with defective expression of components of the MHC class I antigen-processing machinery (APM), thereby resulting in an immune escape phenotype of oncogene-transformed cells. To determine whether HER-2/neu influences the MHC class I antigen-processing pathway, the expression pattern of different APM components was examined in murine in vitro models of constitutive and tetracycline-controlled HER-2/neu expression. In comparison with HER-2/neu− control cells, HER-2/neu+ fibroblasts exhibit reduced levels of MHC class I surface antigens that were associated with impaired expression and/or function of the peptide transporter associated with antigen processing, the proteasome subunits low molecular weight protein 2 and low molecular weight protein 10, the proteasome activators PA28α and PA28β, and tapasin. These APM abnormalities resulted in reduced sensitivity to lysis by CTLs. The HER-2/neu-mediated immune escape phenotype could be corrected by IFN-γ treatment. The clinical relevance of this finding was supported by an inverse correlation between HER-2/neu and the peptide transporter associated with antigen-processing protein expression as determined by immunhistochemical analysis of a series of HER-2/neu− and HER-2/neu+ breast cancer specimens. Thus, a functional link between deficient APM component expression and HER-2/neu overexpression is proposed that might influence the design of HER-2/neu-targeted T-cell-based immunotherapeutic strategies.
Alteration in Copy Numbers of Genes as a Mechanism for Acquired Drug Resistance
Authors: Yasui Kohichiroh , Mihara Saori , Zhao Chen , Okamoto Hiroyuki , Saito-Ohara Fumiko , Tomida Akihiro , Funato Tadao , Yokomizo Akira , Naito Seiji , Imoto Issei , Tsuruo Takashi , Inazawa Johji 
Published: September 2005

Abstract
Chemoresistance is a major obstacle for successful treatment of cancer. To identify regions of the genome associated with acquired resistance to therapeutic drugs, we conducted molecular cytogenetic analyses of 23 cancer-cell lines, each resistant to either camptothecin, cisplatin, etoposide (VP-16), Adriamycin, or 1-β-d-arabinofuranosylcytosine, although the parental tumor lines were not. Subtractive comparative genomic hybridization studies revealed regions of gain or loss in DNA-copy numbers that were characteristic of drug-resistant cell lines; i.e., differences from their drug-sensitive parental cell lines. Thirteen ATP-binding cassette (ABC) transporter genes [ABCA3, ABCB1 (MDR1), ABCB6, ABCB8, ABCB10, ABCB11, ABCC1 (MRP1), ABCC4, ABCC9, ABCD3, ABCD4, ABCE1, and ABCF2] were amplified among 19 of the resistant cell lines examined. Three genes encoding antiapoptotic BCL-2 proteins (BCL2L2, MCL1, and BCL2L10) were also amplified and consequently overexpressed in three of the derivative lines. Down-regulation of BCL2L2 with an antisense oligonucleotide sensitized a VP-16 resistant ovarian-cancer cell line (SKOV3/VP) to VP-16. A decrease in copy numbers of genes encoding deoxycytidine kinase, DNA topoisomerase I, and DNA topoisomerase II α reduced their expression levels in one cytosine arabinoside-resistant line, two of three camptothecin-resistant lines, and two of five VP-16-resistant cell lines, respectively. Our results indicated that changes in DNA-copy numbers of the genes mentioned can activate or down-regulate them in drug-resistant cell lines, and that such genomic alterations might be implicated in acquired chemoresistance.
Antitumor Efficacy of Intermittent Treatment Schedules with the Rapamycin Derivative RAD001 Correlates with Prolonged Inactivation of Ribosomal Protein S6 Kinase 1 in Peripheral Blood Mononuclear Cells
Authors: Boulay Anne , Zumstein-Mecker Sabine , Stephan Christine , Beuvink Iwan , Zilbermann Frederic , Haller Roland , Tobler Sonja , Heusser Christoph , O’Reilly Terence , Stolz Barbara , Marti Andreas , Thomas George , Lane Heidi A. 
Published: September 2005

Abstract
The orally bioavailable rapamycin derivative RAD001 (everolimus) targets the mammalian target of rapamycin pathway and possesses potent immunosuppressive and anticancer activities. Here, the antitumor activity of RAD001 was evaluated in the CA20948 syngeneic rat pancreatic tumor model. RAD001 demonstrated dose-dependent antitumor activity with daily and weekly administration schedules; statistically significant antitumor effects were observed with 2.5 and 0.5 mg/kg RAD001 administered daily [treated tumor versus control tumor size (T/C), 23% and 23–30%, respectively], with 3–5 mg/kg RAD001 administered once weekly (T/C, 14–36%), or with 5 mg/kg RAD001 administered twice weekly (T/C, 36%). These schedules were well tolerated and exhibited antitumor potency similar to that of the cytotoxic agent 5-fluorouracil (T/C, 23%). Moreover, the efficacy of intermittent treatment schedules suggests a therapeutic window allowing differentiation of antitumor activity from the immunosuppressive properties of this agent. Detailed biochemical profiling of mammalian target of rapamycin signaling in tumors, skin, and peripheral blood mononuclear cells (PBMCs), after a single administration of 5 mg/kg RAD001, indicated that RAD001 treatment blocked phosphorylation of the translational repressor eukaryotic initiation factor 4E-binding protein 1 and inactivated the translational activator ribosomal protein S6 kinase 1 (S6K1). The efficacy of intermittent treatment schedules was associated with prolonged inactivation of S6K1 in tumors and surrogate tissues (≥72 h). Furthermore, detailed analysis of the dose dependency of weekly treatment schedules demonstrated a correlation between antitumor efficacy and prolonged effects (≥7 days) on PBMC-derived S6K1 activity. Analysis of human PBMCs revealed that S6K1 also underwent a concentration-dependent inactivation after RAD001 treatment ex vivo (&gt;95% inactivation with 20 nm RAD001). In contrast, human PBMC-derived eukaryotic initiation factor 4E-binding protein 1 was present predominantly in the hypophosphorylated form and was unaffected by RAD001 treatment. Taken together, these results demonstrate a correlation between the antitumor efficacy of intermittent RAD001 treatment schedules and prolonged S6K1 inactivation in PBMCs and suggest that long-term monitoring of PBMC-derived S6K1 activity levels could be used for assessing RAD001 treatment schedules in cancer patients.
Plasma and Dietary Carotenoids, and the Risk of Prostate Cancer
Authors: Wu Kana , Erdman John W. , Schwartz Steven J. , Platz Elizabeth A. , Leitzmann Michael , Clinton Steven K. , DeGroff Valerie , Willett Walter C. , Giovannucci Edward 
Published: September 2005

Abstract
The association between plasma carotenoids and prostate cancer risk was investigated in a case-control study nested within the prospective Health Professionals Follow-up Study. We matched 450 incident prostate cancer cases diagnosed from 1993–1998 to 450 controls by age, time, month, and year of blood donation.
Modest inverse, but not statistically significant, associations were observed among plasma α-carotene, β-carotene, and lycopene concentrations, and overall risk of prostate cancer diagnosis {odds ratio (highest versus lowest quintile; OR), α-carotene: OR, 0.67 [95% confidence interval (CI), −0.40–1.09]; β-carotene: OR, 0.78 (95% CI, 0.48–1.25); lycopene: OR, 0.66 (95% CI, 0.38–1.13)}. The inverse association between plasma lycopene concentrations and prostate cancer risk was limited to participants who were 65 years or older (OR, 0.47; 95% CI, 0.23–0.98) and without a family history of prostate cancer (OR, 0.48; 95% CI, 0.26–0.89). Combining, older age and a negative family history provided similar results (OR, 0.43; 95% CI, 0.18–1.02). Inverse associations between β-carotene and prostate cancer risk were also found among younger participants (&lt;65 years of age; OR, 0.36; 95% CI, 0.14–0.91; Ptrend = 0.03). Combining dietary intake and plasma data confirmed our results.
We found a statistically significant inverse association between higher plasma lycopene concentrations and lower risk of prostate cancer, which was restricted to older participants and those without a family history of prostate cancer. This observation suggests that tomato products may exhibit more potent protection against sporadic prostate cancer rather than those with a stronger familial or hereditary component. In addition, our findings also suggest that among younger men, diets rich in β-carotene may also play a protective role in prostate carcinogenesis.
Reported Use of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Was Not Associated with Reduced Recurrence of Colorectal Adenomas
Authors: Wei Jeffrey T. , Mott Leila A. , Baron John A. , Sandler Robert S. ,   for the Polyp Prevention Study Group
Published: September 2005

Abstract
We did a secondary analysis of data from three large colorectal adenoma chemoprevention trials to assess the association between 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor use and reduced risk of recurrent colorectal adenomas. Reported use of HMG-CoA reductase inhibitors was not associated with a reduced recurrence of colorectal adenomas, multiple adenomas, or advanced adenomas. Lack of statistical power from limited exposure to HMG-CoA reductase inhibitors might be responsible for the lack of association.
Seroreactivity to Human Papillomavirus (HPV) Types 16, 18, or 31 and Risk of Subsequent HPV Infection
Authors: Viscidi Raphael P. , Schiffman Mark , Hildesheim Allan , Herrero Rolando , Castle Philip E. , Bratti Maria C. , Rodriguez Ana Cecilia , Sherman Mark E. , Wang Sophia , Clayman Barbara , Burk Robert D. 
Published: September 2005

Abstract
Whether antibodies to human papillomavirus (HPV) capsids, elicited by natural infection, are protective is unknown. This question was addressed in a population-based cohort of 7046 women in Costa Rica by examining the association between baseline seroreactivity to HPV-16, HPV-18, or HPV-31 virus-like particles and the risk of subsequent HPV infection at a follow-up visit 5–7 years after enrollment. Seropositivity to HPV-16, HPV-18, or HPV-31 was not associated with a statistically significant decreased risk of infection with the homologous HPV type [relative risk (RR) and [95% confidence interval (CI)], 0.74 (0.45–1.2), 1.5 (0.83–2.7), and 0.94 (0.48–1.8), respectively]. Seropositivity to HPV-16 or HPV-31 was not associated with a decreased risk of infection with HPV-16 or its genetically related types [RR (95% CI), 0.82 (0.61–1.1) and 0.93 (0.68–1.2), respectively]. Seropositivity to HPV-18 was not associated with a decreased risk of infection with HPV-18 or its genetically related types (RR 1.3; 95% CI 1.0–1.8). Thus, we did not observe immunity, although a protective effect from natural infection cannot be excluded because of the limits of available assays and study designs.
Peptic Ulcer Disease and the Risk of Bladder Cancer in a Prospective Study of Male Health Professionals
Authors: Michaud Dominique S. , Mysliwiec Pauline A. , Aldoori Walid , Willett Walter C. , Giovannucci Edward 
Published: September 2005

Abstract
Helicobacter pylori is a risk factor for gastric and duodenal ulcers, but gastric ulcers generally occur in individuals who have low acid production and diffuse gastritis, whereas duodenal ulcers are more likely to occur with high acid output and antrum-predominant gastritis. Low acid production, gastritis, and ulcer healing each contribute to poor antioxidant absorption, oxidative stress, and elevated nitrite levels in the stomach. N-Nitrosamines are known carcinogens, and nitrate ingestion has been related to bladder cancer risk. Consequently, we hypothesized that the gastric conditions associated with gastric ulcers may contribute to elevated bladder cancer risk. We thus examined the association between self-reported history of peptic ulcer disease and the risk of bladder cancer (414 cases) over 14 years of follow-up in the Health Professional Follow-Up Study. Cox proportional hazards models were performed to adjust for known risk factors of bladder cancer. Men who reported a gastric ulcer before 1986 had a significantly higher risk of bladder cancer compared with those with no history of gastric ulcer (relative risk = 1.55, 95% confidence interval = 1.03–2.33, controlling for smoking and other potential confounders). No association was observed for duodenal ulcers (multivariate relative risk = 0.97, 95% confidence interval = 0.68–1.38). The ulcers in this study were based solely on self-report and not medical records; consequently, misclassification of ulcers may have occurred. Although intriguing, these findings need to be replicated.
Increased Prevalence of theHFE C282YHemochromatosis Allele in Women with Breast Cancer
Authors: Kallianpur Asha R. , Hall Lynn D. , Yadav Meeta , Christman Brian W. , Dittus Robert S. , Haines Jonathan L. , Parl Fritz F. , Summar Marshall L. 
Published: September 2005

AbstractIndividuals with the major hemochromatosis (HFE) allele C282Y and iron overload develop hepatocellular and some extrahepatic malignancies at increased rates. No association has been previously reported between the C282Y allele and breast cancer. We hypothesized that due to the pro-oxidant properties of iron, altered iron metabolism in C282Y carriers may promote breast carcinogenesis. Because 1 in 10 Caucasians of Northern European ancestry carries this allele, any impact it may have on breast cancer burden is potentially great. We determined C282Y genotypes in 168 patients who underwent high-dose chemotherapy and blood cell transplantation for cancer: 41 with breast cancer and 127 with predominantly hematological cancers (transplant cohort). Demographic, clinical, and tumor characteristics were reviewed in breast cancer patients. The frequency of C282Y genotypes in breast cancers was compared with the frequency in nonbreast cancers, an outpatient sample from Tennessee (n = 169), and a published United States national sample. The frequency of at least one C282Y allele in breast cancers was higher (36.6%, 5 homozygotes/10 heterozygotes) than frequencies in Tennessee (12.7%, P &lt; 0.001), the general population (12.4%, P &lt; 0.001), and similarly selected nonbreast cancers (17.0%, P = 0.008). The likelihood of breast cancer in the transplant cohort increased with C282Y allele dose (Ptrend = 0.010). These results were supported by the finding in a nontransplant cohort of a higher frequency of C282Y mutations in Caucasian (18.4%, P = 0.039) and African-American (8.5%, P = 0.005) women with breast cancer than race-specific national frequency estimates. A high prevalence of C282Y alleles in women with breast cancer with and without poor risk features suggests that altered iron metabolism in C282Y carriers may promote the development of breast cancer and/or more aggressive forms of the disease.
MTHFR
Polymorphisms, Dietary Folate Intake, and Breast Cancer Risk
Authors: Shrubsole Martha J. , Gao Yu-Tang , Cai Qiuyin , Shu Xiao Ou , Dai Qi , Hébert James R. , Jin Fan , Zheng Wei 
Published: September 2005

Abstract
Folate plays an important role in DNA methylation, synthesis, and repair; intake has been associated with breast cancer. The folate-metabolizing enzyme, methylenetetrahydrofolate reductase (MTHFR) is polymorphic at nucleotides 677 (C→T) and 1298 (A→C), resulting in allozymes with decreased activity. We evaluated these two common polymorphisms and their effects on the folate intake and breast cancer risk association in a population-based case-control study of 1144 breast cancer cases and 1236 controls using a PCR-RFLP-based assay. All subjects completed in-person interviews, which included a food frequency questionnaire. Unconditional logistic regression models were used to calculate odds ratios and their 95% confidence intervals, after adjusting for potential confounding factors. Cases and controls were similar in the distribution of MTHFR polymorphisms at codons 677 (41.4% cases and 41.8% controls carried the T allele) and 1298 (17.6% cases and 17.5% controls carried the C allele). An inverse association of breast cancer risk with folate intake was observed in all genotype groups, particularly among subjects with the 677TT genotype. Compared with those with the 677CC genotype and high folate, the adjusted odds ratios (95% confidence intervals) associated with low folate intake were 1.94 (1.15–3.26), 2.17 (1.34–3.51), and 2.51 (1.37–4.60) for subjects who had CC, CT, and TT genotypes (p for interaction, 0.05). No modifying effect of A1298C genotypes on the association of folate intake with breast cancer risk was observed. Results of this study suggest that the MTHFR C677T polymorphisms may modify the association between dietary folate intake and breast cancer risk.
Genetic Polymorphisms in
GSTM1
,
GSTP1
, and
GSTT1
and the Risk for Breast Cancer
Authors: Egan Kathleen M. , Cai Qiuyin , Shu Xiao-Ou , Jin Fan , Zhu Tian-Li , Dai Qi , Gao Yu-Tang , Zheng Wei 
Published: September 2005

Abstract
Purpose: We studied the relation of breast cancer to common deletion mutations in GSTM1 and GSTT1 and the functional Ile105Val polymorphism in GSTP1 in a large, population-based case-control study conducted in China and performed a meta-analysis to summarize the literature.
Experimental Design: In the case-control study, a total of 1144 breast cancer cases and 1221 community controls were genotyped for GSTM1, GSTP1, and GSTT1 using PCR-based methods. Associations of genotypes and breast cancer were evaluated in logistic regression models. Meta-analysis odds ratios (ORs) were estimated using a fixed effects model.
Results: In the case-control study, associations were null for GSTM1 [age-adjusted OR 0.97, 95% confidence interval (CI): 0.82–1.14] and GSTT1 (OR 0.97, 95% CI: 0.83–1.15). A significant increase in risk was observed among homozygotes for the variant Ile105Val polymorphism (OR 1.92, 95% CI: 1.21–3.04). No combined effects of GSTM1, GSTP1, and GSTT1 genotypes or interactions with potential effect modifiers were detected. All results were similar in pre- and postmenopausal women and for early versus advanced stage breast cancer. The meta-analysis, based predominately on Caucasian women, supported null results for the homozygous deletion variant in GSTM1 (summary OR 1.05; combining 19 studies) and GSTT1 (summary OR 1.11; 15 studies). Meta-analysis results for the homozygous GSTP1 variant indicated no overall association (summary OR 1.04; 10 studies), although results varied significantly across studies (P = 0.009).
Conclusions: This large case-control study provides strong support for earlier studies showing no overall association of the GSTM1 and GSTT1 deletion polymorphisms with breast cancer risk. The GSTP1 variant may be relevant to breast cancer risk in Asian populations.
Chlamydial Antibodies and Risk of Prostate Cancer
Authors: Anttila Tarja , Tenkanen Leena , Lumme Sonja , Leinonen Maija , Gislefoss Randi Elin , Hallmans Göran , Thoresen Steinar , Hakulinen Timo , Luostarinen Tapio , Stattin Pär , Saikku Pekka , Dillner Joakim , Lehtinen Matti , Hakama Matti 
Published: September 2005

Abstract
Objective: We assessed the risk of prostate cancer by exposure to Chlamydia trachomatis.
Method: Seven hundred thirty eight cases of prostate cancer and 2,271 matched controls were identified from three serum sample banks in Finland, Norway, and Sweden by linkage to the population based cancer registries.
Results: A statistically significant inverse association (odds ratio, 0.69; 95% confidence interval, 0.51-0.94) was found. It was consistent by different serotypes and there was a consistent dose-response relationship.
Conclusion: C. trachomatis infection is not likely to increase the risk of prostate cancer. Whether the inverse relationship is true or due to difficulties in measuring the true exposure in prostatic tissue by serology, confounders or other sources of error remain open.
Association of Gain and Loss of Weight before and after Menopause with Risk of Postmenopausal Breast Cancer in the Iowa Women's Health Study
Authors: Harvie Michelle , Howell Anthony , Vierkant Robert A. , Kumar Nagi , Cerhan James R. , Kelemen Linda E. , Folsom Aaron R. , Sellers Thomas A. 
Published: September 2005

Abstract
Obesity and adult weight gain are well-established risk factors for postmenopausal breast cancer. Although there are a few studies demonstrating the contribution of adult weight gain to breast cancer risk, whether weight gain during a critical time period is specifically associated with risk, or whether subsequent weight loss among women who have gained weight will reduce the excess risk, is not firmly established. We investigated the association of changes in weight (loss or gain in excess of 5% of body weight) using two risk factor models: (a) age 18 to 30 years and age 30 years to menopause and (b) age 30 years to menopause and after the menopause to the baseline study in 1986 on risk of postmenopausal breast cancer in a prospective cohort of 33,660 postmenopausal women in Iowa. Over 15 years of follow-up, 1,987 cases of breast cancer occurred. Data were analyzed using proportional hazards regression models adjusted for established breast cancer risk factors. The most frequently observed pattern of body weight over time was a consistent increase; these women were observed to have the highest rates of breast cancer and served as the reference category for all comparisons. The lowest-risk groups were (a) women who maintained or lost weight from age 18 to 30 years and then lost weight from age 30 years to menopause [risk ratio (RR), 0.36; 95% confidence interval (95% CI), 0.22-0.60] and (b) women who maintained or lost weight from age 30 years to menopause and then lost weight after the menopause (RR, 0.48; 95% CI, 0.22-0.65). Women who gained weight from age 30 years to menopause but then lost weight after the menopause experienced risk reductions (RR, 0.77; 95% CI, 0.64-0.92) although perhaps slightly smaller in magnitude than women who maintained their weight in both time intervals (RR, 0.63; 95% CI, 0.55-0.73). Women who gained weight from age 18 to 30 years and then lost weight from age 30 years to menopause had comparable risk reductions (RR, 0.61; 95% CI, 0.46-0.8) with women who maintained their weight in both time intervals (RR, 0.73; 95% CI, 0.64-0.84). Women who gained weight during the period from age 30 years to menopause but who had stable weight after menopause had rates similar to the reference group. These data suggest prevention of weight gain between age 18 years and menopause or weight loss and maintenance during these years reduces risk of postmenopausal breast cancer.