bluuebunny/crossref_metadata_2025_split huggingface dataset:
High frequency of HPV16‐associated head and neck squamous cell carcinoma in the Puerto Rican population
Authors: Báez Adriana , Almodóvar José I. , Cantor Alan , Celestin Frederic , Cruz‐Cruz Luis , Fonseca Sharon , Trinidad‐Pinedo Juan , Vega William 
Published: June 2004

AbstractBackground.Recent evidence has accumulated suggesting that human papillomavirus (HPV) plays a role in the development of head and neck squamous cell carcinoma (HNSCC). HPV16 is the most common of the HPV subtypes associated with oral and laryngeal malignancies. This study estimated the prevalence of HPV16 DNA in Puerto Rican patients with HNSCC.Methods.DNA was extracted from frozen tissue of 118 HNSCCs. Genomic DNA was screened for the presence of HPV16 DNA with E6‐specific and E7‐specific primers.Results.HPV16 was detected in tumor tissue of 52 patients (44%) with HNSCC. The oropharynx had a slightly higher incidence of HPV16 DNA. Fifteen of 66 patients with HPV16‐negative HNSCC later had recurrences. Positivity for HPV16 was independent of the tumor grade, tumor stage, nodal status, and tobacco or alcohol use. The 3‐year survival rate was higher in HPV16‐positive patients than in HPV16‐negative patients (36% vs 21%).Conclusions.Our findings suggest that HPV16 may play a role in the etiology of a subgroup of HNSCC in Puerto Ricans. Overall survival times of the HPV16‐positive patients were not significantly different from those of HPV16‐negative patients. Increasing our understanding of the role of HPV16 in the etiology of HNSCC might facilitate the development of new treatment modalities for this subgroup of HNSCC. © 2004 Wiley Periodicals, Inc. Head Neck 26: 778–784, 2004
Expression of tumor necrosis factor receptor–associated factor 1 in nasopharyngeal carcinoma: Possible upregulation by Epstein‐Barr virus latent membrane protein 1
Authors: Siegler Gabriele , Meyer Birgit , Dawson Chris , Brachtel Elena , Lennerz Jochen , Koch Claudia , Kremmer Elisabeth , Niedobitek Edith , Gonnella Roberta , Pilch Ben Z. , Young Lawrence S. , Niedobitek Gerald 
Published: June 2004

AbstractEBV infection is associated with virtually all cases of undifferentiated NPC, and the EBV‐encoded LMP1 is expressed in a proportion of cases. LMP1 has transforming functions similar to members of the TNF receptor family and activates intracellular signaling cascades through interaction with TRAFs. In B cells, expression of TRAF1 is in turn upregulated by LMP1. LMP1 signaling in epithelial cells may be affected by the presence or absence of TRAF1. By immunohistochemistry, we detected TRAF1 expression in 17 of 42 (40%) EBV+ undifferentiated NPCs. All 7 LMP1+ NPC biopsies were also TRAF1+. Using an RNAse protection assay, high‐level TRAF1 expression was detected in an LMP1‐expressing NPC‐derived cell line (C15) and expression was weaker in 2 LMP1− cell lines (C17, C19). Finally, LMP1 upregulated TRAF1 expression in an EBV− keratinocyte cell line. Our results demonstrate that TRAF1 is expressed in NPC tumor cells in vivo and suggest that TRAF1 expression may be upregulated by LMP1 in NPC. An antiapoptotic function has been proposed for TRAF1, and this may be relevant for the pathogenesis of NPC. © 2004 Wiley‐Liss, Inc.
Histone deacetylase inhibitors: Understanding a new wave of anticancer agents
Authors: Villar‐Garea Ana , Esteller Manel 
Published: June 2004

AbstractCancer is as much an epigenetic disease as it is a genetic and cytogenetic disease. The discovery that drastic changes in DNA methylation and histone modifications are commonly found in human tumors has inspired various laboratories and pharmaceutical companies to develop and study epigenetic drugs. One of the most promising groups of agents is the inhibitors of histone deacetylases (HDACs), which have different biochemical and biologic properties but have a single common activity: induction of acetylation in histones, the key proteins in nucleosome and chromatin structure. One of the main mechanisms of action of HDAC inhibitors is the transcriptional reactivation of dormant tumor‐suppressor genes, such as p21WAF1. However, their pleiotropic nature leaves open the possibility that their well‐known differentiation, cell‐cycle arrest and apoptotic properties are also involved in other functions associated with HDAC inhibition. Many phase I clinical trials indicate that HDAC inhibitors appear to be well‐tolerated drugs. Thus, the field is ready for rigorous biologic and clinical scrutiny to validate the therapeutic potential of these drugs. Our current data indicate that the use of HDAC inhibitors, probably in association with classical chemotherapy drugs or in combination with DNA‐demethylating agents, could be promising for cancer patients. © 2004 Wiley‐Liss, Inc.
Dietary soy and increased risk of bladder cancer: A prospective cohort study of men in Shanghai, China
Authors: Sun Can‐Lan , Yuan Jian‐Min , Wang Xue‐Li , Gao Yu‐Tang , Ross Ronald K. , Yu Mimi C. 
Published: June 2004

AbstractTo verify our previous finding of a positive association between dietary soy and bladder cancer risk, we examined the association in a second, geographically distinct prospective cohort of Chinese subjects, the Shanghai Cohort Study. Briefly, 18,244 men aged 45–64 years were recruited between January 1986 and September 1989. As of December 31, 2002, 61 incident bladder cancer cases were identified. Information on soy consumption was obtained through in‐person interviews at baseline using a food frequency questionnaire. Cox proportional hazard regression methods were used to estimate relative risks (RR) and their corresponding 95% confidence intervals (CI), with adjustment for age (years) at baseline interview, level of education and other potential confounders. Compared to men consuming soy less than once a week, the RR (95% CI) for those who consumed soy 1–<3 times per week, 3–<7 times a week and daily were 2.05 (0.80–5.29), 2.45 (0.89–6.76) and 4.61 (1.57–13.51), respectively (pfor trend = 0.004), after adjustment for age, cigarette smoking and level of education. The soy–bladder cancer risk associations in smokers and non‐smokers were comparable. The soy–bladder cancer relationship became stronger when the analysis was restricted to subjects with 2 or more years of follow‐up. © 2004 Wiley‐Liss, Inc.
Enhanced cathepsin L expression is mediated by different Ras effector pathways in fibroblasts and epithelial cells
Authors: Collette John , Ulku Aylin S. , Der Channing J. , Jones Anta'Sha , Erickson Ann H. 
Published: June 2004

AbstractRas expression induces increased expression and altered targeting of lysosomal proteases in multiple cell types, but the specific downstream cytoplasmic signaling pathways mediating these changes have not been identified. In this study, we compared the involvement of 3 major Ras effectors, Raf, phosphatidylinositol 3‐kinase (PI3K) and Ral guanine nucleotide exchange factor (RalGEF) in the Ras‐mediated alteration of lysosomal protease protein expression and targeting in rat 208F fibroblasts and rat ovarian surface epithelial (ROSE) cells. Effector domain mutants of Ras, constitutively activated variants of Raf, PI3K and RalGEF and pharmacologic inhibitors of MEK and PI3K were utilized to determine the role of these downstream pathways in mediating fibroblast transformation and lysosomal protease regulation in the fibroblasts and epithelial cells. We found that Raf activation of the ERK mitogen‐activated protein kinase pathway alone was sufficient to cause morphologic and growth transformation of the fibroblasts and was necessary and sufficient to alter cathepsin L expression and targeting. In contrast, transformation and upregulation of cathepsin L expression in the epithelial cells required the activity of all 3 Ras effectors. Increased protease secretion from the epithelial cells was not observed on ectopic expression of Ras, as it was from the fibroblasts, consistent with the utilization of different signaling pathways in the 2 cell types. In neither cell type did Ras expression increase the expression, processing or secretion of 2 other major lysosomal proteases, cathepsin B and cathepsin D. Thus, Ras utilizes different effectors to mediate transformation and to deregulate cathepsin L expression and secretion in fibroblast and epithelial cells. © 2004 Wiley‐Liss, Inc.
First pregnancy characteristics and subsequent breast cancer risk among young women
Authors: Innes Kim E. , Byers Tim E. 
Published: June 2004

AbstractThere is growing evidence that perinatal factors associated with altered gestational hormones may influence subsequent breast cancer risk in the mother. Events occurring during the first pregnancy may be particularly important. In this matched case‐control study, we investigated the relation between characteristics of a woman's first pregnancy and her later breast cancer risk using linked records from the New York State birth and tumor registries. Cases were 2,522 women aged 22 to 55 diagnosed with breast cancer between 1978 and 1995 and who had also completed a first pregnancy in New York State (NY) at least 1 year prior to diagnosis. Controls were 10,052 primiparous women not diagnosed with breast or endometrial cancer in NY and matched to cases on county of residence and date of delivery. Information on factors characterizing the woman's first pregnancy was obtained from the pregnancy record of each subject. The association of these factors to breast cancer risk was assessed using conditional logistic regression. Extreme prematurity (< 32 weeks gestational age) was associated with elevated maternal breast cancer risk [adjusted odds ratio (OR)=2.1, 95% confidence interval (CI) 1.2,3.9], as were abruptio placentae (OR = 1.8, CI 1.1,3.0) and multifetal gestation (OR=1.8, CI 1.1,3.0). Preeclampsia was associated with a marked reduction in breast cancer risk among women who bore their first child after age 30 (OR=0.3, CI 0.2,0.7) and in the first 3 years after delivery (OR=0.2 (0.1–0.9). These findings suggest that certain perinatal factors influence maternal breast cancer risk and offer indirect support for a role of gestational hormones, and particularly gestational estrogens, in the etiology of breast cancer. © 2004 Wiley‐Liss, Inc.
Endogenous sex hormones and subsequent breast cancer in premenopausal women
Authors: Micheli Andrea , Muti Paola , Secreto Giorgio , Krogh Vittorio , Meneghini Elisabetta , Venturelli Elisabetta , Sieri Sabina , Pala Valeria , Berrino Franco 
Published: June 2004

AbstractBecause of large intra‐individual variation in hormone levels, few studies have investigated the relation of serum sex hormones to breast cancer (BC) in premenopausal women. We prospectively studied this relation, adjusting for timing of blood sampling within menstrual cycle. Premenopausal women (5,963), recruited to the Hormones and Diet in the Etiology of Breast Tumors (ORDET) cohort study, provided a blood sample in the 20–24th day of their menstrual cycle. After 5.2 years of follow‐up, 65 histologically confirmed BC cases were identified and matched individually to 4 randomly selected controls. Sera, stored at −80°C, were assayed blindly for dehydroepiandrosterone sulfate, total and free testosterone (FT), androstenedione, androstanediol‐glucoronide, progesterone, 17‐OH‐progesterone, sex hormone‐binding globulin, follicle‐stimulating hormone (FSH) and luteinizing hormone (LH). Fifty‐five cases had information for multivariate analyses. Compared to controls, BC cases had shorter cycles and intervals between blood sampling and bleeding, and lower LH and FSH. FT was significantly associated with BC risk: relative risk (RR; adjusted for age, body mass index and ovarian cycle variables) of highest vs. lowest tertile was 2.85 [95% confidence interval (CI) = 1.11–7.33, p for trend = 0.030]. Progesterone was inversely associated with adjusted RR for highest vs. lowest tertile of 0.40 (95% CI = 0.15–1.08, p for trend = 0.077), significantly so in women with regular menses, where adjusted RR was 0.12 (95% CI = 0.03–0.52, p for trend = 0.005). These findings support the hypothesis that ovarian hyperandrogenism associated with luteal insufficiency increases the risk of BC in premenopausal women. © 2004 Wiley‐Liss, Inc.
Smoking is associated with postmenopausal breast cancer in women with high levels of estrogens
Authors: Manjer Jonas , Johansson Robert , Lenner Per 
Published: June 2004

AbstractWe investigated the association between smoking and risk of postmenopausal breast cancer in groups defined by high levels of estrogens, a factor known to enhance tumour progression. Two prospective cohorts of Swedish women provided 260 postmenopausal breast cancer cases and 514 controls. Blood samples were collected at baseline, and anthropometry, life‐style factors and reproductive history had been assessed. Subjects were classified into quartiles with regard to the level of estrone, and into three categories with regard to estradiol. All analyses of the relation between smoking and breast cancer were repeated in different categories of these hormones. Logistic regression analysis, adjusted for matching factors, i.e., age at baseline, storage time and sub‐cohort, yielded odds ratios (OR) with 95% confidence intervals (CI). Ever‐smoking was associated with breast cancer in the top category of estrone, 2.02 (1.17–3.49). The highest risk was seen among ex‐smokers, 2.96 (1.53–5.75). The pattern was similar for estradiol. Recent smoking cessation was associated with a high OR in top categories of estrone, 4.38 (1.27–15.2) and estradiol 10.0 (1.14–88.7). Smoking initiation before the age of 20 was associated with breast cancer in the top category of estrone, 2.73 (1.27–5.91). Several potential confounders were introduced into the statistical model, but none remained using backward selection. We conclude that ever‐smoking was associated with the risk of breast cancer in women with high levels of estrone, and that ex‐smoking was associated with breast cancer in women with high levels of estrone or estradiol. © 2004 Wiley‐Liss, Inc.
Induction of a metastatogenic tumor cell type by neurotransmitters and its pharmacological inhibition by established drugs
Authors: Lang Kerstin , Drell Theodore L. , Lindecke Antje , Niggemann Bernd , Kaltschmidt Christian , Zaenker Kurt S. , Entschladen Frank 
Published: June 2004

AbstractThe active migration of tumor cells, a crucial requirement for metastasis development and cancer progression, is regulated by signal substances including neurotransmitters. We investigated the migration of tumor cells within a three‐dimensional collagen matrix using time‐lapse videomicroscopy and computer‐assisted analysis of the migration path. Tumor cell migration is induced by norepinephrine, dopamine and substance P. We show that this induced migration, using MDA‐MB‐468 breast and PC‐3 prostate carcinoma cells, can be inhibited by using specific, clinically established receptor antagonists to the β2‐adrenoceptor, the D2 receptor, or the neurokinin‐1 receptor, respectively. All of the investigated neurotransmitters significantly activated the cyclic adenosine‐monophosphate response element binding protein (CREB). Furthermore, microarray analysis revealed changes of gene expression toward a highly motile tumor cell type, including an upregulation of the α2 integrin, which is an essential adhesion receptor for collagen in migration. The gene for the tumor suppressor gelsolin was downregulated. These 2 critical alterations were confirmed on the protein level by flow‐cytometry and immunoblotting, respectively. Neurotransmitters thus induce a metastatogenic tumor cell type by directly regulating gene expression and increased migratory activity, which can be prevented by established neurotransmitter antagonists. © 2004 Wiley‐Liss, Inc.
Fenretinide induces sustained‐activation of JNK/p38 MAPK and apoptosis in a reactive oxygen species‐dependent manner in neuroblastoma cells
Authors: Osone Shinya , Hosoi Hajime , Kuwahara Yasumichi , Matsumoto Yoshifumi , Iehara Tomoko , Sugimoto Tohru 
Published: June 2004

AbstractFenretinide, which mediates apoptosis in neuroblastoma cells, is being considered as a novel therapeutic for neuroblastoma. The cytotoxic mechanisms of fenretinide, however, have not been fully elucidated. Sustained‐activation of JNK and p38 MAPK signaling has been shown recently to have a pivotal role in stress‐induced apoptosis. Whether fenretinide activates the signaling in neuroblastoma cells is not known. In the present study, fenretinide induced sustained‐activation of both JNK and p38 MAPK in neuroblastoma cells. Pretreatment with the antioxidant L‐ascorbic acid almost completely inhibited the accumulation of fenretinide‐induced intracellular reactive oxygen species (ROS), activation of JNK and p38 MAPK and apoptosis. Intracellular ROS production and activation of stress signaling was not altered by fenretinide in resistant neuroblastoma cells. Our study demonstrates that in neuroblastoma cells, fenretinide induces sustained‐activation of JNK and p38 MAPK in an ROS‐dependent manner and indicates that JNK and p38 MAPK signaling might mediate fenretinide‐induced apoptosis. Our results also indicate that suppression of the fenretinide‐induced ROS productive system and the downstream JNK and p38 MAPK signaling pathways causes neuroblastoma cells to become resistant to fenretinide. © 2004 Wiley‐Liss, Inc.
In vitro tobramycin elution analysis from a novel β‐tricalcium phosphate–silicate‐xerogel biodegradable drug‐delivery system
Authors: DiCicco Michael , Goldfinger Aaron , Guirand Felix , Abdullah Aquill , Jansen Susan A. 
Published: June 2004

AbstractThis in vitro research analyzed local tobramycin elution characteristics from a novel, biodegradable drug delivery system, consisting of a β‐TCP bone substitute, VITOSS™, encapsulated with silicate xerogel prepared by the sol‐gel process. Tobramycin elution from silicate‐xerogel‐encapsulated VITOSS was compared directly with non‐silicate‐xerogel‐encapsulated VITOSS to assess whether xerogels are effective in delivering greater tobramycin quantities in a controllable, sustained manner crucial for microbial inhibition. Tobramycin elution characteristics indicate an initial release maximum during the first 24 h that diminishes gradually several days after impregnation. The copious tobramycin quantity eluted from the VITOSS/silicate‐xerogel systems is attributed to various factors: the intrinsic ultraporosity and hydrophilicity of VITOSS, the ability of tobramycin to completely dissolve in aqueous media, tobramycin complexation with highly polar SO salts that further assist dissolution, and ionic exchanges between VITOSS and the environment. Silicate‐xerogel–encapsulated VITOSS eluted 60.65 and 61.31% of impregnated tobramycin, whereas non‐silicate‐xerogel–encapsulated VITOSS eluted approximately one‐third less impregnated tobramycin, at 21.53 and 23.60%. These results suggest that silicate xerogel optimizes tobramycin elution because of its apparent biodegradability. This mechanism occurs through xerogel superficial acidic sites undergoing exchanges with various ions present in the leaching buffer. Tobramycin elution kinetics were evaluated, and demonstrate that first‐order elution rate constants are considerably less when silicate xerogels are employed, following a more uniform exponential decay‐type mechanism, thus bolstering controlled release. Overall, tobramycin elution rates adhere to linear‐type Higuchi release profiles. Elution rate constants are initially first order, and taper into zero‐order elution kinetics in the latter stages of release. Because VITOSS and silicate xerogel are completely biodegradable, essentially all impregnated tobramycin will be delivered to the surgical site after implantation. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 70B: 1–20, 2004
The effects of curing history on residual stresses in bone cement during hip arthroplasty
Authors: Li Chaodi , Wang Ying , Mason James 
Published: June 2004

AbstractDuring cement curing in total hip arthroplasty, residual stresses are introduced in the cement mantle as a result of curing shrinkage, thermal shrinkage, and geometrical constraints. These high residual stresses are capable of initiating cracks in the mantle of cemented hip replacements. The purpose of this study was to determine the residual stresses in the cemented hip replacements. The finite element method was developed to predict the residual stresses built up in joint arthroplasties. Experimental tests were then performed to validate the numerical methodology. Then the effects of curing history on the residual stress distribution were investigated with finite element simulations. Results showed that the predictions of the thermal shrinkage residual stresses by the developed method agreed with the experimental tests very well. The residual stress buildup was shown to depend on the curing history. By preheating the prosthesis stem prior to implantation, a desired low‐level residual stress at the critical prosthesis–cement interface was obtained. As a result, this article provides a numerical tool for the quantitative simulation of residual stress and for examining and refining new designs computationally. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 70B: 30–36, 2004
Design of braided composite cardiovascular catheters based on required axial, flexural, and torsional rigidities
Authors: Carey Jason , Fahim Atef , Munro Michael 
Published: June 2004

AbstractCardiovascular catheterization is a common medical procedure. A single braided catheter with different rigidities at the proximal and distal ends can, if properly designed, provide the necessary control and flexibility and thus replace the current two‐piece (external catheter/internal guidewire) system. An analytical model based on classical laminate plate theory was developed in order to predict the elastic properties of angle‐plied, single‐overlap two‐dimensional fiber composite tubular braids, which are required for the determination of the axial, flexural, and torsional rigidities. In this work the analytical model has been used to design one‐piece cardiovascular catheters with axial, flexural, and torsional rigidities similar to those values for existing two‐piece catheters, thus validating the model as a tool for designing braided cardiovascular catheters. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 70B: 73–81, 2004
Retardation of setting of plaster of Paris by organic acids: Understanding the mechanism through molecular modeling
Authors: Hill Jörg‐Rüdiger , Plank Johann 
Published: June 2004

AbstractTo develop an understanding of the action of specific formulations, the growth of gypsum crystals under the influence of retardation agents (tartaric and citric acid) has been studied using molecular modeling. Surface energies of gypsum and plaster crystal faces were calculated using established protocols. The crystal morphology predicted for gypsum crystals in the absence of retardation agents is in excellent agreement with experiment. The simulations show that only in an alkaline environment is the crystal morphology of gypsum changed by retardation agents. The simulations provide a detailed description of retardation, for example, the specific mechanisms by which tartaric and citric acid retard setting of gypsum and how they differ. At high pH meso, D(−), and L(+) tartaric acid inhibit both the growth of gypsum and the dissolution of plaster while at low pH tartaric acid and citric acid will principally inhibit the growth of gypsum. The simulations provide a molecular rationalization for a range of experimental observations and a basis for the selection of alternate retardation agents. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1438–1448, 2004