bluuebunny/crossref_metadata_2025_split huggingface dataset:
Male circumcision and anatomic sites of penile high‐risk human papillomavirus in Rakai, Uganda
Authors: Tobian Aaron A.R. , Kong Xiangrong , Gravitt Patti E. , Eaton Kevin P. , Kigozi Godfrey , Serwadda David , Oliver Amy E. , Nalugoda Fred , Makumbi Frederick , Chen Michael Z. , Wawer Maria J. , Quinn Thomas C. , Gray Ronald H. 
Published: February 2011

AbstractMale circumcision (MC) reduces penile high‐risk human papillomavirus (HR‐HPV) on the coronal sulcus and urethra. HR‐HPV varies by anatomic site, and it is unknown whether MC decreases HR‐HPV on the penile shaft. We assessed the efficacy of MC to reduce HR‐HPV on the penile shaft and compared it to known efficacy of MC to reduce HR‐HPV on the coronal sulcus. HIV‐negative men randomized to receive immediate circumcision (intervention) or circumcision delayed for 24 months (control) were evaluated for HR‐HPV at 12 months postenrollment using the Roche HPV Linear Array assay. Among swabs with detectable β‐globin or HPV, year 1 HR‐HPV prevalence on the coronal sulcus was 21.5% in the intervention arm and 36.3% in the control arm men [adjusted prevalence risk ratios (PRRs) = 0.57, 95% CI 0.39–0.84, p = 0.005]. On the shaft, year 1 HR‐HPV prevalence was 15.5% in the intervention and 23.8% in the control arm (adjusted PRR = 0.66, 95% CI 0.39–1.12, p = 0.12). Efficacy of MC to reduce HR‐HPV on the shaft was similar to efficacy on the coronal sulcus (p = 0.52). In a sensitivity analysis in which swabs without detectable β‐globin or HPV were included as HPV negative, prevalence of HR‐HPV on the shaft was lower in the intervention arm (7.8%) than control arm (13.6%; PRR 0.57, 95% CI 0.33–0.99, p < 0.05). HR‐HPV was more frequently detected on the coronal sulcus than penile shaft among uncircumcised men (36.3% vs. 23.8%, respectively, p = 0.02) and circumcised men (21.5% vs. 15.5%, respectively, p = 0.24). MC reduced HR‐HPV prevalence on both the coronal sulcus and shaft.
Downregulation of breast cancer resistance protein in colon adenomas reduces cellular xenobiotic resistance and leads to accumulation of a food‐derived carcinogen
Authors: Dietrich Christoph G. , Vehr Ann‐Kathrin , Martin Ina V. , Gaßler Nikolaus , Rath Timo , Roeb Elke , Schmitt Johannes , Trautwein Christian , Geier Andreas 
Published: February 2011

AbstractSeveral molecular changes in colorectal adenomas provide the basis of the adenoma–carcinoma sequence. We investigated the expression of xenobiotic ATP‐binding cassette (ABC) transporters in humans and in ApcMin mice and conducted functional studies estimating the importance of the expression changes. Twenty‐nine adenomas from 21 patients and eight adenomas from four ApcMin mice were analyzed using Western blotting and quantitative Real‐time polymerase chain reaction (RT‐PCR). Adjacent healthy tissue served as control for each polyp. Breast cancer resistance protein (BCRP) was significantly downregulated in human colorectal adenomas (to 28 ± 35% of adjacent healthy tissue). This was in line with data from ApcMin mice adenomas, where downregulation was significant as well (to 58 ± 34%). In parallel, quantitative RT‐PCR showed BCRP mRNA downregulation in human adenomas (to 17 ± 31%). Basal multidrug resistance‐associated protein 2 expression was low and did not change in adenomas; multidrug resistance transporter 1 expression also did not differ between adenomas and healthy tissue. In a functional study, ApcMin mice received radioactively labelled 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐β] pyridine (PhIP), a food colon carcinogen and substrate of BCRP, by oral gavage with analysis of PhIP accumulation and DNA adduct formation 48 hr later. In this setting, we could demonstrate a higher carcinogen concentration in adenomas of ApcMin mice (181 ± 113% of normal tissue) including immunohistochemical detection of PhIP–DNA adducts. We conclude that significant transcriptional downregulation of BCRP/Bcrp leads to higher carcinogen concentrations in colorectal adenomas of mice and men. This might promote the adenoma–carcinoma sequence by higher genotoxic effects. The results indicate a possible role of transporter deficiencies in susceptibility for colon carcinoma.
Body mass index and body size in early adulthood and risk of pancreatic cancer in a central European multicenter case–control study
Authors: Urayama Kevin Y. , Holcatova Ivana , Janout Vladimir , Foretova Lenka , Fabianova Eleonora , Adamcakova Zora , Ryska Miroslav , Martinek Arnost , Shonova Olga , Brennan Paul , Scélo Ghislaine 
Published: February 2011

AbstractThe relationship between two measures of excess body weight, body mass index (BMI) and body size score, and risk of pancreatic cancer was examined among 574 pancreatic cancer cases and 596 frequency‐matched controls from the Czech Republic and Slovakia enrolled between 2004 and 2009. Analyses using multivariable logistic regression showed an increased risk of pancreatic cancer associated with elevated quartiles of BMI at ages 20 [fourth quartile: odds ratio (OR) = 1.79, 95% confidence interval (CI): 1.23, 2.61] and 40 (fourth quartile: OR = 1.57, 95% CI: 1.09, 2.27) compared to the lowest quartile. Consistent results were observed for body size score at ages 20 (high versus low: OR = 1.66, 95% CI: 1.08, 2.57) and 40 (medium versus low: OR = 1.36, 95% CI: 1.00, 1.86), but no association was found for BMI and body size score at 2 years before the interview. Stronger risk estimates for BMI were observed in males than females, particularly at age 20, but the analysis of body size yielded similar estimates by sex. When considering excess body weight at both ages 20 and 40 jointly, the highest risk estimates were observed among subjects with elevated levels at both time periods in the analysis of BMI (OR = 1.86, 95% CI: 1.32, 2.62) and body size (OR = 1.53, 95% CI: 1.09, 2.13). These findings, based on two different measures, provide strong support for an increased risk of pancreatic cancer associated with excess body weight, possibly strongest during early adulthood.
Costimulation by chimeric antigen receptors revisited the T cell antitumor response benefits from combined CD28‐OX40 signalling
Authors: Hombach Andreas A. , Abken Hinrich 
Published: February 2011

AbstractThe therapeutic success of adoptive therapy with chimeric antigen receptor (CAR) engineered T cells depends on the appropriate costimulation of CD3ζ to induce full T cell activation. Costimulatory endodomains of the CD28 family are therefore fused with CD3ζ in a dual signalling CAR. Serious adverse events in two most recent trials; however, highlight the need to analyse in more detail the impact of each costimulatory endodomain on individual effector functions of redirected T cells. We therefore performed a thoroughly controlled side‐by‐side comparison of the most frequently used endodomains with respect to their impact on CD4+ and CD8+ T cell effector functions. CD28 reinforced T cell proliferation and is mandatory to induce IL‐2. In the absence of added IL‐2, CD28 and OX40 (CD137) but not 4‐1BB (CD134) enhanced specific cytolysis. While CD28, 4‐1BB and OX40 similarly improved pro‐inflammatory cytokine secretion, OX40 most efficiently prevented activation induced cell death of CD62L− effector memory T cells. CD28 was superior to initiate the T cell response, OX40 and 4‐1BB sustained the response in long term with OX40 being most effective. We consequently combined the beneficial functions in a 3rd generation CD28‐OX40 CAR which substantially improved the antitumor response without loosing specificity.
The activated transforming growth factor‐beta signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer
Authors: Yamamura Shogo , Matsumura Noriomi , Mandai Masaki , Huang Zhiqing , Oura Tomonori , Baba Tsukasa , Hamanishi Junzo , Yamaguchi Ken , Kang Hyun Sook , Okamoto Takako , Abiko Kaoru , Mori Seiichi , Murphy Susan K. , Konishi Ikuo 
Published: February 2011

AbstractPeritoneal dissemination including omental metastasis is the most frequent route of metastasis and an important prognostic factor in advanced ovarian cancer. We analyzed the publicly available microarray dataset (GSE2109) using binary regression and found that the transforming growth factor (TGF)‐beta signaling pathway was activated in omental metastases as compared to primary sites of disease. Immunohistochemical analysis of TGF‐beta receptor type 2 and phosphorylated SMAD2 indicated that both were upregulated in omental metastases as compared to primary disease sites. Treatment of the mouse ovarian cancer cell line HM‐1 with recombinant TGF‐β1 promoted invasiveness, cell motility and cell attachment while these were suppressed by treatment with A‐83‐01, an inhibitor of the TGF‐β signaling pathway. Microarray analysis of HM‐1 cells treated with TGF‐β1 and/or A‐83‐01 revealed that A‐83‐01 efficiently inhibited transcriptional changes that are induced by TGF‐β1. Using gene set enrichment analysis, we found that genes upregulated by TGF‐β1 in HM‐1 cells were also significantly upregulated in omental metastases compared to primary sites in the human ovarian cancer dataset, GSE2109 (false discovery rate (FDR) q = 0.086). Therapeutic effects of A‐83‐01 in a mouse model of peritoneal dissemination were examined. Intraperitoneal injection of A‐83‐01 (150 μg given three times weekly) significantly improved survival (p = 0.015). In summary, these results show that the activated TGF‐β signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer.
VEGFR‐2 expression in human melanoma: Revised assessment
Authors: Molhoek Kerrington R. , Erdag Gulsun , Rasamny Jk , Murphy Cheryl , Deacon Donna , Patterson James W. , Slingluff Craig L. , Brautigan David L. 
Published: February 2011

AbstractVascular endothelial growth factor (VEGF) is an angiogenic factor that also functions as an autocrine growth factor for VEGF receptor (VEGFR)‐2+ melanomas. In multiple studies, VEGFR‐2 was detected by immunostaining in 78–89% of human melanoma cells, suggesting that most patients with melanoma would benefit from anti‐VEGF therapy. Here, we evaluated 167 human melanoma specimens in a tissue microarray to verify the presence of VEGFR‐2, but found disparities in staining with commercial antibodies A‐3 and 55B11. Antibody A‐3 stained melanoma cells in 79% of specimens, consistent with published results; however, we noted extensive nonspecific staining of other cells such as smooth muscle and histiocytes. In contrast, antibody 55B11 stained melanoma cells in only 7% (95% confidence interval: 3.3–11.5) of specimens. As an internal positive control for VEGFR‐2 detection, vascular endothelial cells were stained with antibody 55B11 in all specimens. We compared VEGFR‐2+ and VEGFR‐2− melanoma cell lines by immunoblotting and immunohistochemistry after small interfering RNA (siRNA) knockdown and transient overexpression of VEGFR‐2 to validate antibody specificity. Immunoblotting revealed that A‐3 primarily cross‐reacted with several proteins in both cell lines and these were unaffected by siRNA knockdown of VEGFR‐2. In contrast, 55B11 staining of VEGFR‐2+ cells was mostly eliminated by siRNA knockdown of VEGFR‐2 and increased in VEGFR‐2− melanoma cell lines following transfection to express ectopic VEGFR‐2. Our results show that relatively few melanoma cells (<10%) express detectable levels of VEGFR‐2, and therefore, the majority of patients with melanoma are unlikely to benefit from antiproliferative effects of anti‐VEGF therapy.
Functional interrelationship between the WASF3 and KISS1 metastasis‐associated genes in breast cancer cells
Authors: Teng Yong , Liu Mingyao , Cowell John K. 
Published: February 2011

AbstractLoss of WASF3 function in breast cancer cells results in loss of invasion phenotypes and reduced metastatic potential. By using oligonucleotide arrays, we now demonstrate that knockdown of WASF3 leads to the upregulation of the KISS1 metastasis suppressor gene with concomitant reduced invasion and loss of matrix metalloproteinases (MMP)‐9 activity. Using a luciferase reporter, KISS1 transcription is significantly increased in the absence of WASF3. Knockdown of KISS1 in WASF3‐silenced cells resulted in the recovery of the invasion phenotype. WASF3 knockdown also resulted in elevated IκBα levels in the cytoplasm and reduced levels of nuclear factor‐kappa‐B (NF‐κB) p65/50 subunits in the nucleus. Tumor necrosis factor‐alpha (TNF‐α) has been associated with cell invasion through induction of MMP‐9 production via KISS1 regulation of the NF‐κB pathway. When WASF3 knockdown cells are treated with TNF‐α, no effect is seen on invasion or nuclear translocation of NF‐κB. Thus, coordinated expression patterns of the WASF3 metastasis promoter gene and the KISS1 metastasis suppressor gene appear to exert their influence through inhibition of NF‐κB signaling, which in turn regulates MMP‐9 production facilitating invasion.
Bezielle (BZL101)‐induced oxidative stress damage followed by redistribution of metabolic fluxes in breast cancer cells: A combined proteomic and metabolomic study
Authors: Klawitter Jelena , Klawitter Jost , Gurshtein Jennifer , Corby Kyler , Fong Sylvia , Tagliaferri Mary , Quattrochi Linda , Cohen Isaac , Shtivelman Emma , Christians Uwe 
Published: February 2011

AbstractBezielle is an orally administered aqueous extract of Scutellaria barbata for treatment of advanced and metastatic breast cancer. Phase I trials showed promising tolerability and efficacy. In our study, we used a combined proteomic–metabolomic approach to investigate the molecular pathways affected by Bezielle in ER‐positive BT474 and ER‐negative SKBR3 cell lines. In both, Bezielle inhibited cell proliferation, induced cell death and G2 cycle arrest by regulating the mediator proteins Jab1, p27Kip1 and p21Cip1. In addition, it stimulated reactive oxygen species production, hyperactivation of PARP and inhibition of glycolysis. Bezielle's ability to induce oxidative stress was associated with the changes in expression of redox potential maintaining enzymes: glutathione‐ and thioredoxin‐related proteins and peroxiredoxins. In regards to cell metabolism, decreased expression of α‐enolase was associated with a reduction of de novo
13C‐lactate formation. Reduced Krebs cycle activity as evidenced by the reduced expression of α‐ketoglutarate dehydrogenase and succinyl‐CoA synthetase led to decreased intracellular succinate concentrations. By inhibiting glucose metabolism, cells reacted by lowering the expression of glucose transporters and resulting in decreased intracellular glucose concentration. Decreased expression of fatty acid synthase and reduced concentration of phosphocholine indicated considerable changes in phospholipid metabolism. Ultimately, by inhibiting the major energy‐producing pathways, Bezielle caused depletion of ATP and NAD(H). Both cell lines were responsive, thus suggesting that Bezielle has the potential to be effective against ER‐negative breast cancers. In conclusion, Bezielle's cytotoxicity toward cancer cells is primarily based on inhibition of metabolic pathways that are preferentially activated in tumor cells thus explaining its specificity for cancer cells.
Comparison of visual inspection with acetic acid and cervical cytology to detect high‐grade cervical neoplasia among HIV‐infected women in India
Authors: Sahasrabuddhe Vikrant V. , Bhosale Ramesh A. , Kavatkar Anita N. , Nagwanshi Chandraprabha A. , Joshi Smita N. , Jenkins Cathy A. , Shepherd Bryan E. , Kelkar Rohini S. , Sahay Seema , Risbud Arun R. , Vermund Sten H. , Mehendale Sanjay M. 
Published: February 2011

AbstractHuman immunodeficiency virus (HIV)‐infected women in India and other developing country settings are living longer on antiretroviral therapy, yet their risk for human papillomavirus (HPV)‐induced cervical cancer remains unabated because of lack of cost‐effective and accurate secondary prevention methods. Visual inspection after application of dilute acetic acid on the cervix (VIA) has not been adequately studied against the current standard: conventional cervical cytology (Pap smears) among HIV‐infected women. We evaluated 303 nonpregnant HIV‐infected women in Pune, India, by simultaneous and independent screening with VIA and cervical cytology with disease ascertainment by colposcopy and histopathology. At the cervical intraepithelial neoplasia (CIN2+) disease threshold, the sensitivity, specificity and positive and negative predictive value estimates of VIA were 80, 82.6, 47.6 and 95.4% respectively, compared to 60.5, 59.6, 22.4 and 88.7% for the atypical squamous cells of undetermined significance or severe (ASCUS+) cutoff on cytology, 60.5, 64.6, 24.8 and 89.4% for the low‐grade squamous intraepithelial cells or severe (LSIL+) cutoff on cytology and 20.9, 96.0, 50.0 and 86.3% for high‐grade squamous intraepithelial lesion or severe (HSIL+) cutoff on cytology. A similar pattern of results was found for women with the presence of carcinogenic HPV‐positive CIN2+ disease, as well as for women with CD4+ cell counts <200 and <350 μL−1. Overall, VIA performed better than cytology in this study with biologically rigorous endpoints and without verification bias, suggesting that VIA is a practical and useful alternative or adjunctive screening test for HIV‐infected women. Implementing VIA‐based screening within HIV/acquired immunodeficiency syndrome care programs may provide an easy and practical means of complementing the highly anticipated low‐cost HPV‐based rapid screening tests in the near future, thereby contributing to improve program effectiveness of screening.
Induction of autophagy promotes differentiation of glioma‐initiating cells and their radiosensitivity
Authors: Zhuang Wenzhuo , Li Bingzong , Long Linmei , Chen Liesong , Huang Qiang , Liang Zhongqin 
Published: February 2011

AbstractGlioblastoma (GBM) is a highly aggressive brain tumor characterized by increased proliferation and resistance to chemotherapy and radiotherapy. Recently, the identification of tumor‐initiating cells with stem‐like properties in diverse human cancers including GBM represents an important conceptual advance in cancer biology with therapeutic implications. However, the factors determining the differential development and radiosensitization of glioma‐initiating cells (GICs) remain poorly defined. Here, we report that rapamycin induced differentiation of GICs and increased their sensitivity to radiation by activating autophagy. Transient in vitro exposure to rapamycin and radiation abolished the capacity of transplanted GICs to establish intracerebral GBMs. Most importantly, in vivo combination of rapamycin and radiation effectively blocked the tumor growth and associated mortality that occurs in mice after intracerebral grafting of human GICs. We demonstrate that rapamycin activated their autophagy and triggers the differentiation cascade in GICs isolated from human GBMs. This was followed by a reduction in proliferation, cell viability, clonogenic ability and increased expression of neural differentiation markers after radiation. Our results suggest that autophagy plays an essential role in the regulation of self‐renewal, differentiation, tumorigenic potential and radiosensitization of GICs, suggesting autophagy could be a promising therapeutic target in a subset of GBMs. We propose that autophagy defect in GICs contributes to radioresistance of GICs by desensitizing GICs to normal differentiation cues. Activating autophagy may abrogate the resistance of GICs to radiation and could lead to the development of novel therapeutic approaches for the treatment of GBMs.
Fetal exposure to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin induces expression of the chemokine genes Cxcl4 and Cxcl7 in the perinatal mouse brain
Authors: Mitsui Tetsuo , Taniguchi Naofumi , Kawasaki Nobuchika , Kagami Yoshihiro , Arita Jun 
Published: February 2011

AbstractFetal exposure to dioxins affects brain development and influences behaviors in human and laboratory animals. However, the cellular target and mechanisms of the neurotoxic action of dioxins are largely unknown. To investigate the molecular basis for the neurotoxicity of dioxins, pregnant C57BL/6 mice were exposed to 5 µg kg−1 body weight of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) by a single gavage on gestational day 12.5 (GD 12.5), and gene expression of the whole fetal brain at GD 18.5 was profiled by DNA microarray analysis. The analysis revealed that the expression of two chemokine genes, Cxcl4 and Cxcl7, was up‐regulated by TCDD exposure. Real‐time PCR analysis verified that they were up‐regulated by TCDD in both male and female brains, while the mRNA levels of a majority of other chemokines and their receptor genes were not affected. The up‐regulation was TCDD dose‐dependent and peaked at GD 15.5–18.5. In situ hybridization analysis showed that the Cxcl4 mRNA expression was localized in part of the surface of cerebral cortex and that the level was increased by TCDD treatment. These results suggest that Cxcl4 and Cxcl7 play a role in the development of neurobehavioral alterations that are triggered by in utero TCDD exposure and later surface in adults. Copyright © 2011 John Wiley & Sons, Ltd.
A tabular source approach to modelling and simulating device and circuit noise in the time domain
Authors: Brinson M. E. , Jahn S. , Nabijou H. 
Published: February 2011

AbstractSimulation of device and circuit noise at low frequencies is often carried out as part of a small‐signal ac analysis. Moreover, circuit simulators with rf analysis capabilities usually specify circuit performance in terms of S parameters and model high‐frequency noise in terms of noise waves and correlation matrices. It is also unusual to find circuit simulators that extend noise simulation to the time domain. This is particularly true for software packages developed from SPICE 2g6 or 3f5. This paper introduces a simple tabular noise source technique, which adds time‐domain noise to semiconductor device models and integrated circuit macromodels. The proposed technique is suitable for use with any general purpose circuit simulator. To demonstrate the power of the suggested approach the text describes time‐domain noise extensions to the SPICE diode, BJT, JFET, MOSFET and MESFET models. These noise extensions have been implemented and tested with the ‘Quite universal circuit simulator’ (Qucs). Copyright © 2011 John Wiley & Sons, Ltd.
Promoting group potency in project teams: The importance of group identification
Authors: Lee Cynthia , Farh Jiing‐Lih , Chen Zhi‐Jun 
Published: February 2011

AbstractWe examined the antecedents and consequences of group potency in 71 multinational project teams in the Greater China region. We extended the theoretical basis of group potency by employing group identification theory. Results showed that group identification was one of the key factors in developing group potency. Further, fostering the acceptance of group goals that are interdependent was important for increasing group identification. We discuss the implications of our findings for future research. Copyright © 2011 John Wiley & Sons, Ltd.