bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective Depletion of Foxp3+ Regulatory T Cells Improves Effective Therapeutic Vaccination against Established Melanoma
Authors: Klages Katjana , Mayer Christian T. , Lahl Katharina , Loddenkemper Christoph , Teng Michele W.L. , Ngiow Shin Foong , Smyth Mark J. , Hamann Alf , Huehn Jochen , Sparwasser Tim 
Published: October 2010

AbstractTumor-bearing individuals have been reported to harbor increased numbers of Foxp3+ regulatory T cells (Treg), which prevent the development of efficient antitumor immune responses. Thus, Treg depletion has already been tested as a promising therapeutic approach in various animal models and entered clinical trials. However, the use of nonspecific Treg targeting agents such as CD25 depleting antibodies, which in addition to CD25+ Tregs also deplete recently activated CD25+ effector T cells, potentially masked the tremendous potential of this therapeutic strategy. To avoid such nonspecific effects, we used transgenic DEREG (depletion of regulatory T cells) mice, which express a diphtheria toxin receptor under control of the Foxp3 locus, allowing selective depletion of Foxp3+ Tregs even during ongoing immune responses. We showed that Foxp3+ Treg depletion induced partial regression of established ovalbumin (OVA)-expressing B16 melanoma, which was associated with an increased intratumoral accumulation of activated CD8+ cytotoxic T cells. The antitumor effect could be significantly enhanced when Treg depletion was combined with vaccination against OVA. To further assess whether this therapeutic approach would break self-tolerance, we crossed DEREG mice with RipOVAlow mice, expressing OVA as neo–self-antigen under control of the rat insulin promoter. In these mice, combined Treg depletion and vaccination also induced tumor regression without the onset of diabetes. Together, our data suggest that selective Treg targeting strategies combined with vaccinations against tumor-associated (self) antigens have the potential to evoke efficient antitumor responses without inducing overt autoimmunity. These findings might have implications for future therapeutic interventions in cancer patients. Cancer Res; 70(20); 7788–99. ©2010 AACR.
A Population-based Study on the Risks of Cervical Lesion and Human Papillomavirus Infection among Women in Beijing, People's Republic of China
Authors: Li Changdong , Wu Minghui , Wang Jiandong , Zhang Songwen , Zhu Li , Pan Jing , Zhang Weiyuan 
Published: October 2010

AbstractBackground: Few population-based studies have investigated premalignant and malignant cervical abnormalities in Beijing.Methods: A total of 6,385 randomly selected sexually active women were interviewed and examined. Cervical lesion was diagnosed using cytology and histology. High-risk human papillomavirus (HPV) was detected by the second-generation hybrid capture test and typed by gene chip of DNA from paraffin-embedded tissue.Results: The cervical lesion prevalence diagnosed by histology was 5.8%. High-risk HPV overall prevalence was 9.9%, 50.5% with cervical lesion and 7.4% without cervical lesion. High-risk HPV DNA load increased with increasing degree of lesions. HPV 16 was the most common type (26.5%) among women with cervical lesion, followed by HPV 58 (8.8%), HPV 33 (7.8%), and HPV 56 (5.3%). Women under 50 years of age, married status, pregnancy and delivery status, couple's sexual behavior, contraceptive history, columnar ectopy, and bacterial vaginosis or trichomonas vaginitis history were more risk factors for HPV infection. Factors for cervical lesion were similar, but in comparison with HPV infection, all associations were weakened. Only middle-aged women, husband's sexual partners, oral contraceptives, columnar ectopy, and history of trichomonas vaginitis remained associated with cervical lesion.Conclusion: In Beijing, the prevalence of cervical lesion and high-risk HPV is higher than estimated in previous reports. HPV 16, 58, and 33 were the most prevalent types. This is relevant for work related to cervical cancer vaccination.Impact: The study was conducted to understand the current status and epidemiologic characteristics of women with cervical lesion and HPV infection in Beijing. Cancer Epidemiol Biomarkers Prev; 19(10); 2655–64. ©2010 AACR.
Adherence to a Breast Cancer Screening Program and Its Predictors in Underserved Women in Southern Brazil
Authors: Caleffi Maira , Ribeiro Rodrigo A. , Bedin Ademar J. , Viegas-Butzke Júlia M.P. , Baldisserotto Fernanda D.G. , Skonieski Giovana P. , Giacomazzi Juliana , Camey Suzi A. , Ashton-Prolla Patrícia 
Published: October 2010

AbstractBackground: Adherence to breast cancer screening is a key element to ensure effectiveness of programs aiming at downstaging of breast cancer. In this study, we evaluated adherence to a screening program and its predictors in underserved women in southern Brazil.Methods: Attendance to the program, which is based on yearly mammogram and clinical examination, was evaluated prospectively. Mean time frames between visits were calculated. Possible predictors of adherence (defined as mean intervals ≤18 mo), such as socioeconomic indicators and health/lifestyle behaviors, were investigated.Results: A total of 3,749 women (age 51 ± 8 y, illiteracy rate of 6.8%, 57.4% with parity ≥3) were analyzed. Median time between screening rounds was 16.5 months (interquartile range, 13.1-25.7), and median number of rounds attended was 3 (interquartile range, 2-4); 57.6% had mean intervals ≤18, and 71% ≤24 months. The most important independent predictors of adherence were high genetic risk [relative risk (RR), 1.25; 95% confidence interval (95% CI), 1.11-1.40], illiteracy (RR, 0.77; 95% CI, 0.67-0.90), parity ≥5 (RR, 0.89; 95% CI, 0.83-0.96), and smoking (RR, 0.82; 95% CI, 0.77-0.88).Conclusions: Although the proposed screening interval was 1 year, compliance to biannual screening (accepted in several international programs) was high, especially when considering the low socioeconomic level of the sample.Impact: This project aims to test a breast cancer screening model for underserved populations in limited-resource countries where adherence is an issue. The identification of worst adherence predictors can point to interventions to improve outcomes of similar public health screening strategies. Cancer Epidemiol Biomarkers Prev; 19(10); 2673–9. ©2010 AACR.
A Prospective Study on Dietary Acrylamide Intake and the Risk for Breast, Endometrial, and Ovarian Cancers
Authors: Wilson Kathryn M. , Mucci Lorelei A. , Rosner Bernard A. , Willett Walter C. 
Published: October 2010

Abstract
Background: Acrylamide is a probable human carcinogen formed during cooking of many common foods. Epidemiologic studies on acrylamide and breast cancer risk have been null; however, positive associations with ovarian and endometrial cancers have been reported. We studied acrylamide intake and risk for breast, endometrial, and ovarian cancers in a prospective cohort study.
Methods: We assessed acrylamide intake among 88,672 women in the Nurses' Health Study using food frequency questionnaires administered every 4 years. Between 1980 and 2006, we identified 6,301 cases of invasive breast cancer, 484 cases of invasive endometrial adenocarcinoma, and 416 cases of epithelial ovarian cancer. We used Cox proportional hazards models to study the association between acrylamide and cancer risk.
Results: We found no association between acrylamide intake and breast cancer overall or according to estrogen and progesterone receptor status. We found an increased risk for endometrial cancer among high acrylamide consumers (adjusted relative risk for highest versus lowest quintile = 1.41; 95% CI, 1.01-1.97; P for trend = 0.03). We observed a nonsignificant suggestion of increased risk for ovarian cancer overall (relative risk, 1.25; 95% CI, 0.88-1.77; P trend = 0.12), with a significantly increased risk for serous tumors (relative risk, 1.58; 95% CI, 0.99-2.52; P trend = 0.04). Associations did not differ by smoking status.
Conclusions: We observed no association between acrylamide and breast cancer. Risk for endometrial cancer and possibly ovarian cancer was greater among high acrylamide consumers.
Impact: This is the second prospective study to report positive associations with endometrial and ovarian cancers. These associations should be further evaluated to inform public health policy. Cancer Epidemiol Biomarkers Prev; 19(10); 2503–15. ©2010 AACR.
Prospective Study of Human Papillomavirus (HPV) Types, HPV Persistence, and Risk of Squamous Cell Carcinoma of the Cervix
Authors: Sundström Karin , Eloranta Sandra , Sparén Pär , Arnheim Dahlström Lisen , Gunnell Anthony , Lindgren Anders , Palmgren Juni , Ploner Alexander , Sanjeevi Carani B. , Melbye Mads , Dillner Joakim , Adami Hans-Olov , Ylitalo Nathalie 
Published: October 2010

Abstract
Background: The link between squamous cell cervical carcinoma and human papillomavirus (HPV) 16/18 is well established, but the magnitude of the risk association is uncertain and the importance of other high-risk HPV (HRHPV) types is unclear.
Methods: In two prospective nested case-control series among women participating in cytologic screening in Sweden, we collected 2,772 cervical smears from 515 women with cancer in situ (CIS), 315 with invasive squamous cell carcinoma (SCC), and individually matched controls. All smears were tested for HPV with PCR assays, and the median follow-up until diagnosis was 5 to 7 years. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (95% CI).
Results: The presence of HPV16/18 in the first smear was associated with 8.5-fold (95% CI, 5.3-13.7) and 18.6-fold (95% CI, 9.0-38.9) increased risks of CIS and SCC, respectively, compared with women negative for HPV. Infection with other HRHPV types in the first smear was also associated with significantly increased risks for both CIS and SCC. Persistence of HPV16 infection conferred a RR of 18.5 (95% CI, 6.5-52.9) for CIS and 19.5 (95% CI, 4.7-81.7) for SCC. The HPV16/18 attributable risk proportion was estimated at 30% to 50% for CIS, and 41% to 47% for SCC. Other HRHPV types also conferred significant proportions.
Conclusions: Our large population-based study provides quantification of risks for different HPV types and prospective evidence that non-16/18 HRHPV types increase the risk for future cervical cancer.
Impact: This study gives further insights into cervical cancer risk stratification with implications for HPV-based prevention strategies. Cancer Epidemiol Biomarkers Prev; 19(10); 2469–78. ©2010 AACR.
A Common Prostate Cancer Risk Variant 5′ of Microseminoprotein-β (MSMB) Is a Strong Predictor of Circulating β-Microseminoprotein (MSP) Levels in Multiple Populations
Authors: Waters Kevin M. , Stram Daniel O. , Le Marchand Loic , Klein Robert J. , Valtonen-André Camilla , Peltola Mari T. , Kolonel Laurence N. , Henderson Brian E. , Lilja Hans , Haiman Christopher A. 
Published: October 2010

Abstract
Background: β-Microseminoprotein (MSP) is one of the three most abundantly secreted proteins of the prostate and has been suggested as a biomarker for prostate cancer risk. A common variant, rs10993994, in the 5′ region of the gene that encodes MSP (MSMB) has recently been identified as a risk factor for prostate cancer.
Methods: We examined the association between rs10993994 genotype and MSP levels in a sample of 500 prostate cancer–free men from four racial/ethnic populations in the Multiethnic Cohort (European Americans, African Americans, Latinos, and Japanese Americans). Generalized linear models were used to estimate the association between rs10993994 genotype and MSP levels.
Results: We observed robust associations between rs10994994 genotype and MSP levels in each racial/ethnic population (all P &lt; 10−8), with carriers of the C allele having lower geometric mean MSP levels (ng/mL; CC/CT/TT genotypes: European Americans, 28.8/20.9/10.0; African Americans, 29.0/21.9/10.9; Latinos, 29.2/17.1/8.3; and Japanese Americans, 25.8/16.4/6.7). We estimated the variant accounts for 30% to 50% of the variation in MSP levels in each population. We also observed significant differences in MSP levels between populations (P = 3.5 × 10−6), with MSP levels observed to be highest in African Americans and lowest in Japanese Americans.
Conclusions: Rs10993994 genotype is strongly associated with plasma MSP levels in multiple racial/ethnic populations.
Impact: This supports the hypothesis that rs10993994 may be the biologically functional allele. Cancer Epidemiol Biomarkers Prev; 19(10); 2639–46. ©2010 AACR.
Comparison Study on the Complete Sequence of Hepatitis B Virus Identifies New Mutations in Core Gene Associated with Hepatocellular Carcinoma
Authors: Zhu Yu , Jin Yan , Guo Xia , Bai Xin , Chen Taoyang , Wang Jinbing , Qian Gengsun , Groopman John D. , Gu Jianren , Li Jinjun , Tu Hong 
Published: October 2010

Abstract
Background: Mutations in the hepatitis B virus (HBV) genome may influence the activity of liver disease. The aim of this study was to identify new viral variations associated with hepatocellular carcinoma (HCC).
Methods: We carried out a comparison study on the complete sequence of HBV isolated from 20 HCC and 35 non-HCC patients in Qidong, China, an area with a high incidence of HCC. We compared the HBV sequences in a consecutive series of plasma samples from four HCC cases before and after the occurrence of HCC. In addition, we selected four mutations in the HBV core (C) gene to verify their relationships to HCC in an independent set of 103 HCC cases and 103 sex- and age-matched non-HCC controls.
Results: The pre-S deletion and 12 point mutations, namely, the pre-S2 start codon mutation, T53C in the pre-S2 gene, T766A in the S gene, G1613A, C1653T, A1762T, G1764A in the X gene, and G1899A, C2002T, A2159G, A2189C, and G2203W (A or T) in the pre-C/C gene, showed close associations with HCC. In the validation study, A2159G, A2189C, and G2203W showed consistent associations with HCC by univariate analysis. Multivariate analysis showed that A2189C and G2203W were independent risk factors for HCC. The odds ratios (95% confidence interval) were 3.99 (1.61-9.92) and 9.70 (1.17-80.58), respectively, for A2189C and G2203W.
Conclusions: These results implicate A2189C and G2203W as new predictive markers for HCC.
Impact: The complete genome analysis of HBV provided pilot data for the identification of novel mutations that could serve as markers for HCC. Cancer Epidemiol Biomarkers Prev; 19(10); 2623–30. ©2010 AACR.
Lipophilic Statin Use and Risk of Breast Cancer Subtypes
Authors: Woditschka Stephan , Habel Laurel A. , Udaltsova Natalia , Friedman Gary D. , Sieh Weiva 
Published: October 2010

Abstract
Background/Aims: Statins are widely used and of high interest as potential chemopreventive agents for cancer. Preclinical studies suggest that lipophilic statins have anticancer properties targeting hormone receptor (HR)-negative breast cancer. Few epidemiologic studies have investigated the relationship between lipophilic statin use and risk for breast cancer, stratified by HR status. We conducted a large case-control study within Kaiser Permanente of Northern California (KPNC) to determine whether chronic use of lipophilic statins is associated with decreased risk of HR-negative breast cancer or other breast cancer subtypes.
Methods: We identified 22,488 breast cancer cases diagnosed from 1997 to 2007, and 224,860 controls matched to cases based upon birth year and duration of KPNC pharmacy coverage. Use of lipophilic statins was ascertained using the comprehensive electronic pharmacy records of KPNC.
Results: We found no association between lipophilic statin use (≥2 y versus never) and overall breast cancer risk (odds ratioadj, 1.02; 95% CI, 0.97-1.08) in conditional logistic regression models adjusted for oral contraceptive and hormone therapy use. Women who used lipophilic statins did not have a decreased risk of HR-negative breast cancer (odds ratioadj, 0.98; 95% CI, 0.84-1.14) nor altered risk of HR-positive disease (odds ratioadj, 1.03; 95% CI, 0.97-1.10). Furthermore, lipophilic statin use was not associated with risk of any of the intrinsic subtypes, luminal A, luminal B, human epidermal growth factor receptor 2 positive/estrogen receptor negative, or triple negative.
Conclusions: Our results do not support an association of lipophilic statin use with the risk for breast cancer in general or with risks of HR-negative or other breast cancer subtypes specifically.
Impact: These findings do not confirm previous reports of a possible preventive association. Cancer Epidemiol Biomarkers Prev; 19(10); 2479–87. ©2010 AACR.
Mammographic Density and Risk of Second Breast Cancer after Ductal Carcinoma In situ
Authors: Habel Laurel A. , Capra Angela M. , Achacoso Ninah S. , Janga Aradhana , Acton Luana , Puligandla Balaram , Quesenberry Charles P. 
Published: October 2010

Abstract
Background: We examined whether mammographic density predicts risk of second breast cancers among patients with ductal carcinoma in situ (DCIS).
Methods: The study included DCIS patients diagnosed during 1990 to 1997 and treated with breast-conserving surgery at Kaiser Permanente Northern California. Medical records were reviewed for clinical factors and subsequent breast cancers (DCIS and invasive). Ipsilateral mammograms from the index DCIS were assessed for density without knowledge of subsequent cancer status. Cox regression modeling was used to examine the association between mammographic density and risk of breast cancer events.
Results: Of the 935 eligible DCIS patients, 164 (18%) had a subsequent ipsilateral breast cancer, and 59 (6%) had a new primary cancer in the contralateral breast during follow-up (median, 103 mo). Those with the greatest total area of density (upper 20% of values) were at increased risk for invasive disease in either breast [hazard ratio (HR), 2.1; 95% confidence interval (95% CI), 1.2-3.8] or any cancer (DCIS or invasive) in the ipsilateral (HR, 1.7; 95% CI, 1.0-2.9) or contralateral (HR, 3.0; 95% CI, 1.3-6.9) breast compared with those with the smallest area of density (bottom 20%). HRs for these same end points comparing those in the highest with those in the lowest American College of Radiology Breast Imaging Reporting and Data System category were 1.6 (95% CI, 0.7-3.6), 1.3 (95% CI, 0.7-2.6), and 5.0 (95% CI, 1.4-17.9), respectively. There was a suggestion of increasing risk of contralateral, but not ipsilateral, cancer with increasing percent density.
Conclusions: Women with mammographically dense breasts may be at higher risk of subsequent breast cancer, especially in the contralateral breast.
Impact: Information about mammographic density may help with DCIS treatment decisions. Cancer Epidemiol Biomarkers Prev; 19(10); 2488–95. ©2010 AACR.
MSH6 and MUTYH Deficiency Is a Frequent Event in Early-Onset Colorectal Cancer
Authors: Giráldez María Dolores , Balaguer Francesc , Bujanda Luis , Cuatrecasas Miriam , Muñoz Jenifer , Alonso-Espinaco Virginia , Larzabal Mikel , Petit Anna , Gonzalo Victoria , Ocaña Teresa , Moreira Leticia , Enríquez-Navascués José María , Boland C. Richard , Goel Ajay , Castells Antoni , Castellví-Bel Sergi 
Published: October 2010

AbstractPurpose: Early-onset colorectal cancer (CRC) is suggestive of a hereditary predisposition. Lynch syndrome is the most frequent CRC hereditary cause. The MUTYH gene has also been related to hereditary CRC. A systematic characterization of these two diseases has not been reported previously in this population.Experimental Design: We studied a retrospectively collected series of 140 patients ≤50 years old diagnosed with nonpolyposis CRC. Demographic, clinical, and familial features were obtained. Mismatch repair (MMR) deficiency was determined by microsatellite instability (MSI) analysis, and immunostaining for MLH1, MSH2, MSH6, and PMS2 proteins. Germline MMR mutations were evaluated in all MMR-deficient cases. Tumor samples with loss of MLH1 or MSH2 protein expression were analyzed for somatic methylation. Germline MUTYH mutations were evaluated in all cases. BRAF V600E and KRAS somatic mutational status was also determined.Results: Fifteen tumors (11.4%) were MSI, and 20 (14.3%) showed loss of protein expression (7 for MLH1/PMS2, 2 for isolated MLH1, 3 for MSH2/MSH6, 7 for isolated MSH6, and 1 for MSH6/PMS2). We identified 11 (7.8%) germline MMR mutations, 4 in MLH1, 1 in MSH2, and 6 in MSH6. Methylation analysis revealed one case with somatic MLH1 methylation. Biallelic MUTYH mutations were detected in four (2.8%) cases. KRAS and BRAF V600E mutations were present in 39 (27.9%) and 5 (3.6%) cases, respectively.Conclusions: Loss of MSH6 expression is the predominant cause of MMR deficiency in early-onset CRC. Our findings prompt the inclusion of MSH6 and MUTYH screening as part of the genetic counseling of these patients and their relatives. Clin Cancer Res; 16(22); 5402–13. ©2010 AACR.
Immunomodulatory impact of a synbiotic in Th1 and Th2 models of infection
Authors: Cazzola Mario , Tompkins Thomas A. , Matera Maria G. 
Published: October 2010

Background and methods: The immunomodulatory activity of a synbiotic combination containing three bacterial strains (Lactobacillus helveticus R0052, Bifidobacterium longum subsp. infantis R0033 and Bifidobacterium bifidum R0071) and short-chain fructooligosaccharide was examined in two distinct infectious rat models. In the Th1 model, Wistar rats were administered the synbiotic combination for 2 weeks prior to challenge with a single oral dose of enterotoxigenic Escherichia coli or vehicle. In the Th2 model, pretreated rats were challenged with a single subcutaneous dose of hook worm, Nippostrongylus brasiliensis. Blood samples were collected 3 hours or 4 days postchallenge and serum levels of pro- and anti-inflammatory cytokines were measured. Results: Significant reductions in pro-inflammatory cytokines interleukin (IL)-1α, IL-1β, IL-6, and tumour necrosis factor (TNF)-α were observed in both models suggesting a single, unifying mode of action on an upstream regulator. The N. brasiliensis study also compared the effect of the individual strains to synbiotic. For most of cytokines the combination appeared to average the effect of the individual strains with the exception of IL-4 and IL-10 where there was apparent synergy for the combination. Furthermore, the cytokine response varied by strain. Conclusions: It was concluded that this synbiotic combination of these three microbes could be beneficial in both Th1 and Th2 diseases.
High doses of mother's lymphocyte infusion to treat EBV-positive T-cell lymphoproliferative disorders in childhood
Authors: Wang Qian , Liu Hongxing , Zhang Xian , Liu Qian , Xing Yanping , Zhou Xiaoge , Tong Chunrong , Zhu Ping 
Published: October 2010

Abstract
Donor lymphocyte infusion is an alternative treatment for Epstein-Barr virus (EBV)–associated lymphoproliferative disorders (LPDs) but with risk of graft-versus-host diseases (GVHDs). According to the fetal-maternal microchimerism tolerance, we assumed that maternal lymphocyte infusion may be effective without causing GVHD. In 54 cases when a child required cytotherapy or hematopoietic stem cell transplantation, we studied the mother for child-mother microchimerism with use of insertion-deletion polymorphisms as allogeneic markers and a combination of nested polymerase chain reaction (PCR) and real-time quantitative PCR. Thirteen mothers were child-microchimerism–positive at the ratio of 10−5-10−3. Among them, 5 children had non–transplant-associated, EBV+ T-cell LPD. In these 5 cases, high doses of human leukocyte antigen–haploidentical maternal peripheral blood mononuclear cells (> 108/kg/infusion) were infused 1-4 times. Symptoms of all 5 patients improved between 3 and 10 days after the infusion; thereafter, 3 cases showed complete remission for 6-18 months without further therapy and 2 had partial remission. During the period of observation, none developed obvious GVHD. By quantitative PCR, in some patients maternal cells were found to be eliminated or decreased after infusions, indicating existence of host-versus-graft reaction. We suggest that high doses of mother's lymphocyte infusion may be an effective and safe treatment for non–transplant-associated EBV+ T-cell LPD.