bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case‐control study of familial lung cancer risks in UK women
Authors: Matakidou Athena , Eisen Tim , Bridle Helen , O'Brien Mary , Mutch Rosalind , Houlston Richard S. ,   Members of the GELCAPS Consortium
Published: March 2005

AbstractFamily history data from a case‐control study of lung cancer conducted in the United Kingdom between 1999 and 2004 were analysed to estimate familial risks of the disease. Comparison of lung cancer prevalence in first‐degree relatives of 1,482 female lung cancer cases and 1,079 female controls was undertaken using logistic regression adjusting for age and tobacco exposure. Overall, lung cancer in a first‐degree relative was associated with a significant increase in the risk of lung cancer [odds ratio (OR) 1.49; 95% confidence interval (CI), 1.13–1.96]. For cases with early onset of the disease (< 60 years), the OR of lung cancer was 2.02 (95% CI, 1.22–3.34). Having 2 or more affected relatives was associated with an OR of 2.68 (95% CI, 1.29–5.55), with a significant trend in risk according to the number of relatives affected (p = 0.001). An increased risk of lung cancer associated with family history of the disease was observed when analysis was restricted to lifetime nonsmokers, although this did not reach significance (OR 1.23; 95% CI, 0.65–2.31). Results confirm previous findings and support the role of a familial predisposition to lung cancer. © 2005 Wiley‐Liss, Inc.
Induction of autoantibodies to syngeneic prostate‐specific membrane antigen by xenogeneic vaccination
Authors: Gregor Polly D. , Wolchok Jedd D. , Turaga Vandana , Latouche Jean‐Baptiste , Sadelain Michel , Bacich Dean , Heston Warren D.W. , Houghton Alan N. , Scher Howard I. 
Published: March 2005

AbstractProstate‐specific membrane antigen (PSMA) is a prototypical differentiation antigen expressed on normal and neoplastic prostate epithelial cells, and on the neovasculature of many solid tumors. Monoclonal antibodies specific for PSMA are in development as therapeutic agents. Methodologies to actively immunize against PSMA may be limited by immunologic ignorance and/or tolerance that restrict the response to self‐antigens. Our studies have previously shown that xenogeneic immunization with DNA vaccines encoding melanosomal differentiation antigens induces immunity in a mouse melanoma model. Here we apply this approach to PSMA to establish proof of principle in a mouse model. Immunization with xenogeneic human PSMA protein or DNA induced antibodies to both human and mouse PSMA in mice. Monoclonal antibodies specific for mouse PSMA were generated to analyze antibody isotypes and specificity for native and denatured PSMA at the clonal level. Most antibodies recognized denatured PSMA, but C57BL/6 mice immunized with xenogeneic PSMA DNA followed by a final boost with xenogeneic PSMA protein yielded autoantibodies that reacted with native folded mouse PSMA. Monoclonal antibodies were used to confirm the expression of PSMA protein in normal mouse kidney. These results establish the basis for clinical trials to test PSMA DNA vaccines in patients with solid tumors that either express PSMA directly or that depend on normal endothelial cells expressing PSMA for their continued growth. © 2005 Wiley‐Liss, Inc.
Ethnic group‐related differences in CpG hypermethylation of the GSTP1 gene promoter among African‐American, Caucasian and Asian patients with prostate cancer
Authors: Enokida Hideki , Shiina Hiroaki , Urakami Shinji , Igawa Mikio , Ogishima Tatsuya , Pookot Deepa , Li Long‐Cheng , Tabatabai Z. Laura , Kawahara Motoshi , Nakagawa Masayuki , Kane Christopher J. , Carroll Peter R. , Dahiya Rajvir 
Published: March 2005

AbstractThe incidence and mortality of prostate cancer (PC) is approximately 2‐fold higher among African‐Americans as compared to Caucasians and very low in Asian. We hypothesize that inactivation of GSTP1 genes through CpG methylation plays a role in the pathogenesis of PC, and its ability to serve as a diagnostic marker that differs among ethnic groups. GSTP1 promoter hypermethylation and its correlation with clinico‐pathological findings were evaluated in 291 PC (Asian = 170; African‐American = 44; Caucasian = 77) and 172 benign prostate hypertrophy samples (BPH) (Asian = 96; African‐American = 38; Caucasian = 38) using methylation‐specific PCR. In PC cells, 5‐aza‐dC treatment increased expression of GSTP1 mRNA transcripts. The methylation of all CpG sites was found in 191 of 291 PC (65.6%), but only in 34 of 139 BPH (24.5%). The GSTP1 hypermethylation was significantly higher in PC as compared to BPH in each ethnic group (p < 0.0001). Logistic regression analysis (PC vs. BPH) showed that African‐Americans had a higher hazard ratio (HR) (13.361) compared to Caucasians (3.829) and Asian (8.603). Chi‐square analysis showed correlation of GSTP1 hypermethylation with pathological findings (pT categories and higher Gleason sum) in Asian PC (p < 0.0001) but not in African‐Americans and Caucasian PC. Our results suggest that GSTP1 hypermethylation is a sensitive biomarker in African‐Americans as compared to that in Caucasians or Asian, and that it strongly influences tumor progression in Asian PC. Ours is the first study investigating GSTP1 methylation differences in PC among African‐American, Caucasian and Asian. © 2005 Wiley‐Liss, Inc.
Connexin43 is overexpressed in ApcMin/+‐mice adenomas and colocalises with COX‐2 in myofibroblasts
Authors: Husøy Trine , Knutsen Helle K. , Cruciani Véronique , Ølstørn Hege B. , Mikalsen Svein‐Ole , Løberg Else Marit , Alexander Jan 
Published: March 2005

AbstractThe expression of gap junction proteins, connexins, in the intestine and their role in tumorigenesis are poorly characterised. Truncating mutations in the tumour suppressor gene adenomatous polyposis coli (APC) are early and important events, both in inheritable (familial adenomatous polyposis, FAP) and spontaneous forms of intestinal cancer. Multiple intestinal neoplasia (Min) mice, a FAP model with inherited heterozygous mutation in Apc, spontaneously develop numerous intestinal adenomas. We recently reported reduced expression of connexin32 in Paneth cells of Min‐mice. We further examine the expression of connexin43 (Cx43) and other connexins as a function of heterozygous and homozygous Apc mutation in normal intestinal tissues and adenomas of Min‐mice. Qualitative analysis of connexin mRNA in intestine revealed a similar expression pattern in Min‐ and wild‐type (wt) mice. Connexin26 and connexin40 proteins were found in equal amounts in Min and wt epithelia of large and small intestine, respectively. Interestingly, the connexin43 level was increased in the stroma of Min‐mice adenomas, in close proximity to epithelial cells with nuclear β‐catenin staining. Cx43 and COX‐2 were located to the same areas of the adenomas, and immunostaining exhibited coexpression in the myofibroblasts. Prostaglandin E2 induces Cx43 expression and COX‐2 is the rate‐limiting enzyme in the prostaglandin synthesis. However, the COX‐2‐specific inhibitor, celecoxib, did not reduce Cx43 expression. Although both Cx43 and COX‐2 are target genes for β‐catenin, they were overexpressed in stromal cells but not in epithelial tumour cells. We hypothesise that gap junctions may be of importance in the transfer of signals between epithelium and stroma. © 2005 Wiley‐Liss, Inc.
Overexpression of S100A2 protein as a prognostic marker for patients with stage I non small cell lung cancer
Authors: Wang Huijun , Zhang Zhengdong , Li Ruiyun , Ang K. Kian , Zhang Huazhong , Caraway Nancy P. , Katz Ruth L. , Jiang Feng 
Published: March 2005

AbstractS100A2, a calcium‐binding protein, recently became of major interest because of its differential expression during transformation and metastasis in various tumors. The purpose of this study was to investigate the prognostic significance of S100A2 expression in the early‐stage non small lung cancer (NSCLC). Immunohistochemical analysis to determine the percentage of cells staining positive for S100A2 was performed on 11 NSCLC tissue microarray slides containing samples from 113 patients with pathologic stage I NSCLC who had undergone curative surgery. S100A2 was expressed in samples from 79 patients (69.9%). Kaplan‐Meier analysis showed that patients whose tumors had positive S100A2 expression had a significantly lower overall survival and disease‐specific survival rate at 5 years after surgery than did patients with negative S100A2 expression (p < 0.001 and p < 0.001, respectively). Age at diagnosis, histologic type of cancer, degree of differentiation and smoking history did not have a statistically significant effect on survival. Multivariate analysis confirmed that S100A2 expression is a better predictor for disease‐specific survival than were other clinical and histologic variables tested. Our results suggested that the expression of the S100A2 protein in stage I NSCLC indicates poor prognosis and may be used to identify patients with early‐stage NSCLC who might benefit from adjuvant treatment. © 2005 Wiley‐Liss, Inc.
Serum cytochrome c indicates in vivo apoptosis and can serve as a prognostic marker during cancer therapy
Authors: Barczyk Katarzyna , Kreuter Michael , Pryjma Juliusz , Booy Evan P. , Maddika Subbareddy , Ghavami Saeid , Berdel Wolfgang E. , Roth Johannes , Los Marek 
Published: March 2005

AbstractDespite significant progress in cancer therapy, the outcome of the treatment is often unfavorable. Better treatment monitoring would not only allow an individual more effective, patient‐adjusted therapy, but also it would eliminate some of the side effects. Using a cytochrome c ELISA that was modified to increase sensitivity, we demonstrate that serum cytochrome c is a sensitive apoptotic marker in vivo reflecting therapy‐induced cell death burden. Furthermore, increased serum cytochrome c level is a negative prognostic marker. Cancer patients whose serum cytochrome c level was normal 3 years ago have a twice as high probability to be still alive, as judged from sera samples collected for 3 years, analyzed recently and matched with survival data. Moreover, we show that serum cytochrome c and serum LDH‐activity reflect different stages and different forms of cell death. Cellular cytochrome c release is specific for apoptosis, whereas increased LDH activity is an indicator of (secondary) necrosis. Whereas serum LDH activity reflects the “global” degree of cell death over a period of time, the sensitive cytochrome c‐based method allows confirmation of the individual cancer therapy‐induced and spontaneous cell death events. The combination of cytochrome c with tissue‐specific markers may provide the foundation for precise monitoring of apoptosis in vivo, by “lab‐on‐the‐chip” technology. © 2005 Wiley‐Liss, Inc.
Pharmaceutical‐mediated inactivation of p53 sensitizes U87MG glioma cells to BCNU and temozolomide
Authors: Xu G. Wei , Mymryk Joe S. , Cairncross J. Gregory 
Published: March 2005

AbstractPifithrin‐α (PFTα) is a small molecule inhibitor of p53. By reversibly blocking apoptosis in response to DNA damage, PFTα protects normal cells from lethal doses of γ‐radiation (Komarov et al., Science, 1999;285:1733–7). We examined the effect of PFTα on the chemosensitivity of a human cancer in which cell cycle arrest, not apoptosis, is the principle cellular consequence of p53 activation. This was of interest because E6 silencing of p53 sensitizes U87MG astrocytic glioma cells to BCNU and temozolomide (TMZ), cytotoxic drugs that are modestly helpful in the treatment of aggressive astrocytic gliomas. We observed that exposure of U87MG cells to PFTα before cytotoxic chemotherapy attenuated p53‐mediated induction of p21WAF1 protein levels, sensitizing U87MG cells to BCNU and TMZ. Sensitization of U87MG cells was associated with G1 arrest, delayed entry into S‐phase and decreased repair of DNA damage by BCNU. Our findings suggest that in addition to protecting normal cells from the toxic effects of radiation and chemotherapy, small molecule inhibitors of p53, like PFTα, might play a role in clinical oncology by sensitizing certain resistant cancers to cytotoxic chemotherapies. © 2005 Wiley‐Liss, Inc.
A forecast comparison of volatility models: does anything beat a GARCH(1,1)?
Authors: Hansen Peter R. , Lunde Asger 
Published: March 2005

AbstractWe compare 330 ARCH‐type models in terms of their ability to describe the conditional variance. The models are compared out‐of‐sample using DM–$ exchange rate data and IBM return data, where the latter is based on a new data set of realized variance. We find no evidence that a GARCH(1,1) is outperformed by more sophisticated models in our analysis of exchange rates, whereas the GARCH(1,1) is clearly inferior to models that can accommodate a leverage effect in our analysis of IBM returns. The models are compared with the test for superior predictive ability (SPA) and the reality check for data snooping (RC). Our empirical results show that the RC lacks power to an extent that makes it unable to distinguish ‘good’ and ‘bad’ models in our analysis. Copyright © 2005 John Wiley & Sons, Ltd.
Phospholipid polymer surfaces reduce bacteria and leukocyte adhesion under dynamic flow conditions
Authors: Patel Jasmine D. , Iwasaki Yasuhiko , Ishihara Kazuhiko , Anderson James M. 
Published: March 2005

AbstractPersistence of infection can occur when the host immune response is compromised because of the presence of a foreign implant. Surface modification of biomaterials with phospholipid polymers may enhance biocompatibility and reduce incidence of infection by impeding bacterial and leukocyte adhesion. A rotating disk model, which generates shear stress from 0 to 18 dynes/cm2, was used to characterize adhesion of neutrophils, monocytes, and bacteria in phosphate‐buffered saline (PBS) or 25% human serum on polyethylene terephthalate surfaces coated with a phospholipid polymer, poly[ω‐methacryloyloxyalkyl phosphorylcholine (MAPC)‐co‐n‐butyl methacrylate (BMA)]. The material designated PMB30 contains a methylene chain length, (CH2)n, of n = 2, whereas PMHB30 contains a chain length of n = 6. In PBS, bacterial adhesion was shear stress dependent with the lowest bacterial density observed on PMB30. However, the presence of serum proteins eliminated shear stress and surface chemistry effects in addition to bacterial adhesion reduced to <10% of adhesion in PBS. Trends for leukocyte adhesion in serum demonstrated shear dependence with PMB30 exhibiting the lowest cell density throughout the range of shear stresses. In conclusion, modification of the polyethylene terephthalate surfaces with phospholipid polymers resulted in reduced bacterial and leukocyte adhesion. Furthermore, shortening the methylene chain length of the MAPC copolymer most effectively reduced adhesion. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res 73A: 359–366, 2005
Pexiganan‐incorporated collagen matrices for infected wound‐healing processes in rat
Authors: Gopinath D. , Kumar M. Senthil , Selvaraj D. , Jayakumar R. 
Published: March 2005

AbstractThe use of peptide‐based drugs is limited by their rapid degradability and toxicity at high concentration during their therapeutic application. These problems could be managed by the use of a peptide delivery agent for sustained release in the site of action. Collagen is one of the most proven biomaterials of good biocompatibility with an exceptional ligand encapsulating property. In this work, we have shown that pexiganan, an antimicrobial, 22‐amino‐acid peptide could be incorporated and delivered to the wound‐healing site against bacterial strains Pseudomonas aeruginosa and Staphylococcus aureus. The release profiles of pexiganan collagen films with different collagen concentration were studied. The release of pexiganan from 2.5% w/w of collagen film showed a sustainable activity over 72 h with effective antimicrobial concentrations. Pexiganan‐incorporated collagen (PIC)‐treated groups were compared with open wound (OW)‐ and collagen film (CF)‐treated rats. PIC‐treated animals showed a diminishing level of bacterial growth as compared with OW‐ and CF‐treated animals. The biochemical parameters such as hydroxyproline, protein, DNA, uronic acid, hexosamine, SOD, and catalase content in the granulation tissue of the healing wound revealed increased proliferation of cells involved in tissue reconstruction in PIC‐treated groups when compared with OW‐ and CF‐treated groups. Furthermore, spectroscopic studies suggested that collagen structure is not perturbed by pexiganan incorporation. This study provides rationale for application of collagen membrane for antimicrobial peptide delivery in infected wounds. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res 73A: 320–331, 2005
Effects of amphotericin B on ion transport proteins in airway epithelial cells
Authors: Jornot Lan , Rochat Thierry , Caruso Assunta , Lacroix Jean‐Silvain 
Published: March 2005

AbstractTopical intranasal application of the antifungal Amphotericin B (AmphoB) has been shown as an effective medical treatment of chronic rhinosinusitis. Because this antibiotic forms channels in lipid membranes, we considered the possibility that it affects the properties and/or cell surface expression of ion channels/pumps, and consequently transepithelial ion transport. Human nasal epithelial cells were exposed apically to AmphoB (50 μM) for 4 h, 5 days (4 h daily), and 4 weeks (4 h daily, 5 days weekly) and allowed to recover for 18–48 h. AmphoB significantly reduced transepithelial potential difference, short‐circuit current, and the amiloride‐sensitive current. This was not due to generalized cellular toxicity as judged from normal transepithelial resistance and mitochondrial activity, but was related to inhibitory effects of AmphoB on ion transport proteins. Thus, cells exposed to AmphoB for 4 h showed decreased apical epithelial sodium channels (ENaC) activity with no change in basolateral Na+K+‐ATPase activity and K+ conductance, and reduced amount of αENaC, α1‐Na+K+‐ATPase, and NKCC1 proteins at the cell membrane, but no change in mRNA levels. After a 5‐day treatment, there was a significant decrease in Na+K+‐ATPase activity. After a 4‐week treatment, a decrease in basolateral K+ conductance and in αENaC and α1‐Na+K+‐ATPase mRNA levels was also observed. These findings may reflect a feedback mechanism aimed to limit cellular Na+ overload and K+ depletion subsequently to formation of AmphoB pores in the cell membrane. Thus, the decreased Na+ absorption induced by AmphoB resulted from reduced cell surface expression of the ENaC, Na+K+‐ATPase pump and NKCC1 and not from direct inhibition of their activities. © 2005 Wiley‐Liss, Inc.
Group III metabotropic glutamate receptor activation inhibits Ca2+ influx and nitric oxide synthase activity in bone marrow stromal cells
Authors: Foreman Megan A. , Gu Yuchun , Howl John D. , Jones Sarah , Publicover Stephen J. 
Published: March 2005

AbstractNitric oxide (NO) is pivotal to bone physiology. In the central nervous system constitutive, Ca2+‐calmodulin regulated NO synthase activity and glutamate signalling are intimately linked. Since L‐glutamate signalling occurs in bone and is implicated in bone regulation, we have investigated the effect of L‐glutamate on NO synthase in bone‐derived cells. Treatment of marrow stromal cells with L‐glutamate reduced basal NO synthase activity by 40%. Imaging showed that L‐glutamate caused a rapid, usually localised and slowly‐reversible fall in [Ca2+]i. This effect was resistant to disruption of intracellular Ca2+ stores but sensitive to extracellular La3+ or omission of extracellular Ca2+, demonstrating that glutamate acts by inhibition of membrane Ca2+ influx. The only previous description of such an effect of L‐glutamate is via activation of the group III receptor, mGluR6, in the retina. Using Western blotting and RT‐PCR we detected mGluR6 protein and transcripts in marrow stromal cells. The effects of L‐glutamate on NOS activity and [Ca2+]i in marrow stromal cells were abolished by a group III mGluR inhibitor, (S)‐2‐amino‐2‐methyl‐4‐phosphonobutyric acid. Recording of membrane potential showed that, similarly to the effects of retinal mGluR6 activation, L‐glutamate induced membrane hyperpolarisation (−16 ± 2 mV), which was also sensitive to group III mGluR inhibition. L‐glutamate had no effect on cAMP levels. We conclude that activation of a group III mGluR in bone marrow stromal cells inhibits a Ca2+‐permeable plasma membrane channel, reducing [Ca2+]i and suppressing generation of NO. These observations directly link bone L‐glutamate signalling to processes central to bone growth and regulation. © 2005 Wiley‐Liss, Inc.
Osteoprotegerin (OPG) is localized to the Weibel‐Palade bodies of human vascular endothelial cells and is physically associated with von Willebrand factor
Authors: Zannettino A.C.W. , Holding C.A. , Diamond P. , Atkins G.J. , Kostakis P. , Farrugia A. , Gamble J. , To L.B. , Findlay D.M. , Haynes D.R. 
Published: March 2005

AbstractRecent studies demonstrate roles for osteoprotegerin (OPG) in both skeletal and extra‐skeletal tissues. Although its role in preventing osteoclast (OC) formation and activity is well documented, emerging evidence suggests a role of OPG in endothelial cell survival and the prevention of arterial calcification. In this communication, we show that vascular endothelial cells in situ, and human umbilical vein endothelial cells (HUVEC) in vitro, express abundant OPG. In HUVEC, OPG co‐localizes with P‐selectin and von Willebrand factor (vWF), within the Weibel‐Palade bodies (WPB). Treatment of HUVEC with the pro‐inflammatory cytokines, tumor necrosis factor (TNF)‐α and IL‐1β, resulted in mobilization from the WPBs and subsequent secretion of OPG protein into the culture supernatant. Furthermore, TNF‐α treatment of HUVEC resulted in a sustained increase in OPG mRNA levels and protein secretion over the 24‐h treatment period. Reciprocal immunoprecipitation experiments revealed that while not associated with P‐Selectin, OPG is physically complexed with vWF both within the WPB and following secretion from endothelial cells. Interestingly, this association was also identified in human peripheral blood plasma. In addition to its interaction with vWF, we show that OPG also binds with high avidity to the vWF reductase, thrombospondin (TSP‐1), raising the intriguing possibility that OPG may provide a link between TSP‐1 and vWF. In summary, the intracellular localization of OPG in HUVEC, in association with vWF, together with its rapid and sustained secretory response to inflammatory stimuli, strongly support a modulatory role in vascular injury, inflammation and hemostasis. © 2005 Wiley‐Liss, Inc.