bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemotherapeutic efficacy of topical celecoxib in a murine model of ultraviolet light B–induced skin cancer
Authors: Wilgus Traci A. , Koki Alane T. , Zweifel Ben S. , Rubal Patricia A. , Oberyszyn Tatiana M. 
Published: August 2003

AbstractOver a million nonmelanoma skin cancer cases will be reported in the United States this year alone. Currently the primary form of treatment for these types of skin tumors is excision. However, excision of the initial lesion may not be curative because almost 50% of patients with one nonmelanoma skin cancer lesion develop another tumor within the next 5 yr at the site or adjacent to the site of excision. As with other types of epithelial based cancers, there is mounting evidence for the role of cyclooxygenase‐2 (COX‐2) and its products, particularly prostaglandin E2 (PGE2), in the development of nonmelanoma skin cancer. To avoid the excision process, the present study was designed to evaluate the possible chemotherapeutic effect of directly treating established tumors with a topical formulation of the specific COX‐2 inhibitor celecoxib. Skh/hr hairless mice were irradiated three times per wk for 16 wk to induce tumor formation. The mice were then divided into two groups and treated topically with either 500 μg celecoxib or the vehicle for 6 wk. Our results demonstrated that although topical treatment with celecoxib was not able to induce regression of established tumors, it did prevent new tumor formation after the onset of photocarcinogenesis. Although further studies are warranted, these data suggest that topical celecoxib treatment may prove to be effective in preventing the recurrence of tumors at the site of nonmelanoma skin cancer excision. © 2003 Wiley‐Liss, Inc.
Promyelocytic leukaemia (PML) protein expression in human placenta and choriocarcinoma
Authors: Kim Chong Jai , Yoon Bo Hyun , Jun Jong Kwan , Park Jung Ok , Cho So Young , Romero Roberto , Kim Yeon Mee , Yu Eun‐Sil 
Published: August 2003

AbstractPromyelocytic leukaemia (PML) protein, the product of the pml gene, is heterogeneously expressed in various normal and neoplastic tissues, and the fusion of the pml gene with retinoic acid receptor‐α is believed to be a central mechanism in acute PML tumourigenesis. As PML is important for controlling major cellular processes, such as growth and differentiation, it is believed that it plays an important role during human gestation. The human placenta is a critical organ for the maintenance of gestation, but the expression pattern and functional significance of PML in the placenta have not been documented. The present study has therefore investigated the expression of PML in the human placenta and in choriocarcinoma, and has observed the biological effects following the overexpression of PML in choriocarcinoma cell lines (BeWo and JEG‐3). In the human placenta, PML expression was readily found in villous stromal fibroblasts, capillary endothelial cells, Hofbauer cells, and occasionally in amnion cells. Moreover, immunoblotting of placental lysates demonstrated increased PML expression with increasing gestation. Interestingly, PML expression was confined to intermediate trophoblasts and syncytiotrophoblastic giant cells at the placental site (placental site giant cells) in the trophoblastic cell population. Intermediate trophoblasts at non‐placental sites, and villous cytotrophoblasts and syncytiotrophoblasts consistently did not express PML. Further screening of PML expression in hydatidiform moles (n = 4) and choriocarcinomas (n = 7) also revealed selective PML expression in intermediate trophoblastic cells and syncytiotrophoblastic cells, but not in the cytotrophoblastic populations, which corresponds well with observations in the placental bed. Adenoviral transduction of PML resulted in a marked reduction in cell growth in both choriocarcinoma cell lines, which was associated with increased apoptosis. The findings of the present study strongly suggest that PML plays an important role in human placental development and growth, and in the pathobiology of trophoblasts and trophoblastic neoplasia. Copyright © 2003 John Wiley & Sons, Ltd.
Differential expression of telomerase activity in neuroendocrine lung tumours: correlation with gene product immunophenotyping
Authors: Zaffaroni Nadia , De Polo Daniela , Villa Raffaella , Della Porta Chiara , Collini Paola , Fabbri Alessandra , Pilotti Silvana , Daidone Maria Grazia 
Published: August 2003

AbstractTelomerase activity was examined by the telomeric repeat amplification protocol (TRAP) assay in 38 neuroendocrine (NE) lung tumours. A significantly (p = 0.001) different frequency of telomerase positivity was observed among different histological tumour types. Specifically, a positive TRAP signal was observed in 14 of 15 (93%) small cell lung cancers (SCLCs), 7 of 8 (87%) large‐cell NE carcinomas (LCNECs), and only 1 of 15 (7%) typical carcinoid tumours. When telomerase activity was correlated with the gene product‐based immunophenotypic profile of individual tumours, it was found that the absence of telomerase activity was associated with a lack of bcl‐2, p53, and c‐kit expression, and characterized by a low proliferation index consistent with the absence of cdk‐4 expression and the presence of the cdk inhibitor Rb. Such a phenotype was appreciable in most of the carcinoid tumours. Conversely, telomerase‐positive tumours generally showed an immunophenotype consistent with gene product alterations (including high expression of bcl‐2, p53, and c‐kit, and loss of Rb) and were characterized by a high proliferation index. These telomerase data support the previously reported evidence for two genetically unrelated groups of NE lung tumours (SCLC, and to some extent LCNEC, versus carcinoid tumours) that have distinct phenotypic profiles. Copyright © 2003 John Wiley & Sons, Ltd.
Imbalanced secondary mucosal antioxidant response in inflammatory bowel disease
Authors: Kruidenier Laurens , Kuiper Ineke , van Duijn Wim , Mieremet‐Ooms Marij AC , van Hogezand Ruud A , Lamers Cornelis BHW , Verspaget Hein W 
Published: August 2003

AbstractIntestinal mucosal damage in the inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC) involves reactive oxygen metabolites (ROMs). ROMs are neutralized by endogenous antioxidant enzymes in a carefully balanced two‐step pathway. Superoxide dismutases (SODs) convert superoxide anion to hydrogen peroxide (H2O2), which is subsequently neutralized to water by catalase (CAT) or glutathione peroxidase (GPO). Remarkably changed expression levels of the three isoforms of SOD in paired non‐inflamed and inflamed mucosae from CD and UC patients have been previously reported in comparison to normal control mucosa. Most notable was the strong up‐regulation of Mn‐SOD in inflamed epithelium. It was hypothesized that in order to provide optimal protection against ROM‐mediated damage, these changes should be coordinately counterbalanced by an increased H2O2‐neutralizing capacity. Therefore, the same tissue samples were used to assess the levels, activities, and/or localization of the most prominent mucosal H2O2‐related antioxidants CAT, GPO, glutathione (GSH), myeloperoxidase (MPO), and metallothionein (MT). Quantitative measurements showed that in both CD and UC patients, intestinal inflammation was associated with increased activities of CAT, GPO, and MPO, whereas the mucosal GSH content was unaffected and the concentration of MT was decreased. Despite this overall increase in mucosal H2O2‐metabolizing enzyme capacity, immunohistochemical analysis revealed a differentially disturbed antioxidant balance in IBD epithelium and lamina propria. In the lamina propria, the risk of direct H2O2‐mediated damage seemed to be restrained by the increasing numbers of CAT‐ and MPO‐positive monocytes/macrophages and neutrophils that infiltrated the inflamed areas. On the other hand, MPO overexpression might increase the lamina propria levels of hypochlorous acid, a stable ROM with multiple pro‐inflammatory effects. In the epithelium, the number of cells that expressed CAT remained unchanged during inflammation and GPO was found in only a very low and constant number of epithelial cells. In addition, the inflamed epithelium displayed decreased expression of the hydroxyl radical (OH•) scavenger MT. In view of the high epithelial SOD levels in inflamed IBD epithelium, it is speculated that the efficient removal of excess H2O2 is hampered in these cells, thereby increasing not only the risk of detrimental effects of H2O2 directly, but also those of its extremely reactive derivatives such as OH•. Taken together, the results suggest an imbalanced and inefficient endogenous antioxidant response in the intestinal mucosa of IBD patients, which may contribute to both the pathogenesis and the perpetuation of the inflammatory processes. Copyright © 2003 John Wiley & Sons, Ltd.
Respective roles of porto‐septal fibrosis and centrilobular fibrosis in alcoholic liver disease
Authors: Michalak Sophie , Rousselet Marie‐Christine , Bedossa Pierre , Pilette Christophe , Chappard Daniel , Oberti Frédéric , Gallois Yves , Calès Paul 
Published: August 2003

AbstractIn alcoholic liver disease, fibrosis classically begins around the centrilobular veins, while portal tract fibrosis is described as inconstant and septal fibrosis is a late event. The aim of this study was to compare the roles of centrilobular fibrosis (CLF) and portal tract/septal fibrosis (PTF) especially in alcoholic chronic liver disease. One hundred and sixty patients with alcoholic chronic liver disease and 83 controls with viral chronic hepatitis were included. The PTF score, derived from the Metavir score, CLF and the area of fibrosis, assessed by image analysis, were evaluated on liver biopsies in addition to blood markers of fibrosis. The correlation between the PTF score and the area of fibrosis was higher in alcoholic liver disease (r = 0.87, p < 10−4) than in viral chronic hepatitis (r = 0.66, p < 10−4). The PTF score correlated with the CLF score (r = 0.92, p < 10−4), serum hyaluronate (r = 0.76, p < 10−4), and the prothrombin index (r = −0.77, p < 10−4). Multiple regression analyses showed that the area of fibrosis was explained only by the PTF score and not by the CLF score. PTF appears more frequent than CLF in alcoholic chronic liver disease, suggesting that PTF may precede CLF. PTF is more responsible for the amount of fibrosis than CLF. The results of this study also validate the use of the Metavir fibrosis score in alcoholic chronic liver disease. Copyright © 2003 John Wiley & Sons, Ltd.
Platelet‐derived growth factor and its receptors are related to the progression of human muscular dystrophy: an immunohistochemical study
Authors: Zhao Yajuan , Haginoya Kazuhiro , Sun Guilian , Dai Hongmei , Onuma Akira , Iinuma Kazuie 
Published: August 2003

AbstractThis study has examined the immunological localization of platelet‐derived growth factor (PDGF)‐A, PDGF‐B, and PDGF receptor (PDGFR) alpha and beta to clarify their role in the progression of muscular dystrophy. Biopsied frozen muscles from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and congenital muscular dystrophy (CMD) were analysed immunohistochemically using antibodies raised against PDGF‐A, PDGF‐B, and PDGFR alpha and beta. Muscles from two dystrophic mouse models (dy and mdx mice) were also immunostained with antibodies raised against PDGFR alpha and beta. In normal human control muscle, neuromuscular junctions and vessels were positively stained with antibodies against PDGF‐A, PDGF‐B, PDGFR alpha and PDGFR beta. In human dystrophic muscles, PDGF‐A, PDGF‐B, PDGFR alpha and PDGFR beta were strongly immunolocalized in regenerating muscle fibres and infiltrating macrophages. PDGFR alpha was also immunolocalized to the muscle fibre sarcolemma and necrotic fibres. The most significant finding in this study was a remarkable overexpression of PDGFR beta and, to a lesser extent, PDGFR alpha in the endomysium of DMD and CMD muscles. PDGFR was also overexpressed in the interstitium of muscles from dystrophic mice, particularly dy mice. Double immunolabelling revealed that activated interstitial fibroblasts were clearly positive for PDGFR alpha and beta. However, DMD and CMD muscles with advanced fibrosis showed very poor reactivity against PDGF and PDGFR. Those findings were confirmed by immunoblotting with PDGFR beta. These findings indicate that PDGF and its receptors are significantly involved in the active stage of tissue destruction and are associated with the initiation or promotion of muscle fibrosis. They also have roles in muscle fibre regeneration and signalling at neuromuscular junctions in both normal and diseased muscle. Copyright © 2003 John Wiley & Sons, Ltd.
Molecular alterations in pancreatic carcinoma: expression profiling shows that dysregulated expression of S100 genes is highly prevalent
Authors: Crnogorac‐Jurcevic Tatjana , Missiaglia Edoardo , Blaveri Ekaterina , Gangeswaran Rathi , Jones Melanie , Terris Benoit , Costello Eithne , Neoptolemos John P , Lemoine Nicholas R 
Published: August 2003

AbstractIn order to expand our understanding of the molecular changes underlying the complex pathology of pancreatic malignancy, global gene expression profiling of pancreatic adenocarcinoma compared with normal pancreatic tissue was performed. Human cDNA arrays comprising 9932 elements were interrogated with fluorescence‐labelled normal and adenocarcinoma samples (nine tumours, three normal pancreata, and three cell lines). The data were analysed for differential gene expression, which was confirmed by serial analysis of gene expression (SAGE), digital differential display (DDD) analysis, and immunohistochemistry for selected cases. The array data were filtered to produce lists of a total of 75 genes significantly up‐regulated or down‐regulated in pancreatic adenocarcinoma. Two of those showing the highest differential were members of the S100 family of Ca‐binding proteins, namely S100P and S100A6, and therefore the S100 genes were studied in more detail. By immunohistochemical analysis of custom‐built, pancreas‐specific tissue arrays and commercially available, normal/cancer tissue arrays that included a wide variety of different tumour types, differential expression of S100P protein was found to be almost exclusive to pancreatic cancer. S100P could therefore represent a useful biomarker for pancreatic adenocarcinomas. Copyright © 2003 John Wiley & Sons, Ltd.
Consulting about lifestyle change: Evaluation of a training course for specialist diabetes nurses
Authors: Lane C , Johnson S , Rollnick S , Edwards K , Lyons M 
Published: August 2003

AbstractThe National Service Framework (NSF) for Diabetes highlights the importance of sharing decision making with patients when helping them to adopt and maintain a healthy lifestyle. It was felt that this shift in focus with the development of a more patient‐centred approach would require the teaching of new skills to health care professionals. The Communication Skills Unit in Cardiff worked with the local Diabetes Unit to design a training programme that allows professionals to develop their skills in behaviour change counselling. The nurse specialists in the Diabetes Unit were very involved in talking to patients about lifestyle issues, and yet they had little or no previous communication skills training.A pilot course was designed, in which four audiotaped simulated consultations were conducted before and after two seminars led by an expert in behaviour change counselling. The consultations were carried out in six nurses' normal clinical settings to ensure a truer representation of a normal consultation. The results showed that initially most participants were using a didactic and nurse‐centred approach when offering lifestyle advice. Following the course, all the nurses were using skills that were more aligned with behaviour change counselling, and interviews afterwards revealed that the course was acceptable and enjoyable. This pilot study provides the rationale for paying closer attention to practitioner skill acquisition before examining the efficacy of behaviour change counselling for improving lifestyles among those with chronic diseases like diabetes. Copyright © 2003 John Wiley & Sons, Ltd.
The adherence of type 2 diabetes patients to their therapeutic regimens: a qualitative study from the patient's perspective
Authors: Vermeire E , Van Royen P , Coenen S , Wens J , Denekens J 
Published: August 2003

AbstractIn chronic diseases such as type 2 diabetes, adherence to treatment is a major public health problem, seriously undercutting the benefits of medical care. Many studies have assessed factors associated with compliance, but the patient perspective is remarkably absent. From these studies, it seems that the patient's role in the process of adhering was to be passive and since the prescriber's view was rational and based on scientific research, it may have been assumed to be superior to the patient's beliefs and wishes. This paper reports on type 2 diabetes patients' health beliefs in relation to their illness, their communication with caregivers and the problems encountered in adhering to treatment regimens.Seven focus groups were held for type 2 diabetes patients recruited by pharmacists in primary care in Flanders, Belgium. These groups focussed on participants' experience of their treatment. Possible explanatory models were generated by qualitative content analysis of the focus group discussions.Forty‐six patients recruited from primary care participated in six semi‐structured group discussions. The data demonstrate that health beliefs, the quality of doctor/patient communication, and the quality of the information patients receive are important factors for patient adherence to treatment. Possible explanatory models for adherence emerged, relating to knowledge of the illness, body awareness and the doctor/patient relationship.This qualitative research identified explanatory models for adhering to medical treatment from the patient's perspective. Interventions designed to enhance adherence should address the patient perspective using these models in order to maximise effectiveness. Copyright © 2003 John Wiley & Sons, Ltd.
Advantages of training Asian diabetes support workers for Asian families and diabetes health care professionals
Authors: Curtis S , Beirne J , Jude E 
Published: August 2003

AbstractLocal consultation with Asian groups and community members in Tameside, Greater Manchester during 1999 on issues around diabetes identified barriers towards optimal self‐care. Six local Asian trainees were recruited in male and female cultural pairs (Bangladeshi, Indian and Pakistani) to participate in a modular Asian Diabetes Support Worker training programme. The training was accredited with Greater Manchester Open College Network, in association with Tameside College, at NVQ Levels 2 and 3. The Asian Diabetes Support Worker Service was evaluated from patient/family and health professional perspectives 12 months after referrals began to be accepted by the team. This article describes the process and outcomes of the service and discusses plans to improve its utilisation. Copyright © 2003 John Wiley & Sons, Ltd.
Positive correlation between single or combined genotypes of CYP1A1 and GSTM1 in relation to prostate cancer in Chilean people
Authors: Acevedo Cristian , Opazo Jose Luis , Huidobro Christian , Cabezas Juan , Iturrieta Jeannette , Quiñones Sepúlveda Luis 
Published: August 2003

AbstractBACKGROUNDThe prostate cancer is a slowly progressing disease that begins decades prior to diagnosis. It has been suggested that there might be differences in susceptibility due to genetic polymorphisms in biotransformation enzyme genes. In the present work, associations between CYP1A1(Msp1), GSTM1(−/−) polymorphisms, and prostate cancer were analyzed in a case‐control study.METHODSGenomic DNA was isolated from peripheral blood samples, collected on EDTA. PCR‐RFLP was used to determine simultaneously Msp1 and GSTM1(−/−) polymorphisms.RESULTSIn cancer patients, frequency of m2 variant allele (0.377) and GSTM1(−/−) (0.362) showed statistically significant increases compared to the control group (0.262 and 0.227, respectively). The estimate relative risks (OR) were higher for individuals carrying combined CYP1A1 and GSTM1 rare genotypes, in relation to individuals carrying CYP1A1 or GSTM1 alone. Multivariate logistic regression analysis including confounding factors (age, digital examination, and PSA antigen) showed even higher risk for individuals carrying m2m2 genotype (OR = 3.99; 95% CI, 1.27–12.54), GST(−/−) genotype (OR = 2.75; 95% CI, 1.31–5.79), and m2m2/GST(−) genotype (OR = 16.63; 95% CI, 1.67–165.48).CONCLUSIONSTaken together, these findings suggest that Chilean people carrying single or combined GSTM1 and CYP1A1 polymorphisms are more susceptible to prostate cancer. Prostate 57: 111–117, 2003. © 2003 Wiley‐Liss, Inc.
Adrenergic regulation of the intracellular [Ca2+] and voltage‐operated Ca2+ channel currents in the rat prostate neuroendocrine cells
Authors: Kim Jun Hee , Shin Sun Young , Nam Joo Hyun , Hong Eun‐Kyung , Chung Young‐Shin , Jeong Jeong Yun , Kang Jeongyoon , Uhm Dae‐Yong , Kim Sung Joon 
Published: August 2003

AbstractBACKGROUNDThe prostate gland contains numerous neuroendocrine cells (PNECs) innervated by adrenergic neurons. PNECs are believed to influence the growth and physiological function of the prostate gland via paracrine release of hormones.MATERIALS AND METHODSUsing fura‐2 fluorescence measurement and patch‐clamp techniques, we investigated the effects of adrenergic stimulation on cytosolic concentration of Ca2+ ([Ca2+]c) and high voltage‐activated Ca2+ channel currents (HVA‐ICa) of the putative rat prostate neuroendocrine cells (RPNECs) freshly isolated by an enzymic digestion.RESULTSNoradrenaline (NA, 1 μM) induced a sharp, transient increase of [Ca2+]c measured by the fura‐2 fluorescence. Pharmacological studies showed that α1‐adrenoceptors (α1‐ARs) coupled with PLC/IP3 signaling pathway induce the release of stored Ca2+, which subsequently recruits store‐operated Ca2+ entry pathways. In the whole‐cell voltage clamp experiment, NA decreased the amplitude of HVA‐ICa by 40%, which was mimicked by an α2‐AR agonist (UK14304) but not by an α1‐AR agonist (phenyleprine). After selective blockade of N‐type Ca2+ channels by ω‐conotoxin GVIA, the addition of NA showed no further inhibition on the remaining L‐type Ca2+ channel currents. The adrenergic inhibition of HVA‐ICa was partially prevented by the pretreatment with pertussis toxin (PTX) (5 μg/ml, 4 hr, 37°C).CONCLUSIONSRPNECs express both α1‐ and α2‐ARs, signaling the release of stored Ca2+ and the inhibition of N‐type Ca2+ channels, respectively. Prostate 57: 99–110, 2003. © 2003 Wiley‐Liss, Inc.