bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression and mutation analyses of P53R2, a newly identified p53 target for DNA repair in human gastric carcinoma
Authors: Byun Do‐Sun , Chae Kwon‐Seok , Ryu Byung‐Kyu , Lee Min‐Goo , Chi Sung‐Gil 
Published: August 2002

Abstractp53R2, a recently identified putative tumor suppressor located at 8q23.1, encodes a protein with striking similarity to a small subunit of ribonucleotide reductase. p53R2 is directly induced by wild‐type p53 and involved in the p53 checkpoint for repair of damaged DNA, raising the possibility that mutational inactivation of p53R2 may contribute to the development and progression of human malignancies. To explore the p53R2's candidacy for a suppressor in gastric tumorigenesis, we examined the expression and mutation status of p53R2 in 166 gastric specimens including 90 primary adenocarcinomas and 15 cell lines. In response to genotoxic damages, p53R2 transcription was clearly activated in wild‐type but not mutant‐type p53‐carrying cells while basal expression of p53R2 in undamaged cells showed no association with the mutational status of p53. Host cell reactivation assay revealed that p53R2 enhances DNA repair efficiency and plays a role in the p53‐mediated repair of damaged DNA, whereas no significant effect of p53R2 on cell growth and apoptosis was detected in flow cytometry and [3H]thymidine incorporation assays. p53R2 transcript was expressed in all normal and tumor tissues and its expression levels were not significantly different between normal and malignant carcinoma tissues. p53R2 expression showed no correlation with stage, grade and histological types of tumors. Moreover, no tumor‐specific reduction of p53R2 was detected in 30 matched sets. Mutational analysis of p53R2 in 105 carcinomas including 15 cell lines also failed to detect any evidences for genomic deletion or somatic mutations leading to amino acid substitutions or frameshift whereas 31% (28 of 90) of the same primary tumors showed p53 alterations. Whereas 82% (23 of 28) of the mutant p53‐carrying primary tumors expressed abnormally low p21Waf1, no association of p53R2 expression with the p53 status was recognized, suggesting that basal transcription of p53R2 is regulated through the p53‐independent mechanism. Collectively, our study indicates that although p53R2 is induced in a p53‐dependent manner and involved the p53‐mediated DNA repair in gastric epithelial cells, it is not a critical target of genetic inactivation in gastric tumorigenesis. © 2002 Wiley‐Liss, Inc.
Blocking a novel 55 kDa melanoma‐associated cell surface antigen inhibits the development of spontaneous metastases and interactions with frozen lung section
Authors: Baril Patrick , Nejjari Mimoun , Scoazek Jean‐Yves , Boukerche Habib 
Published: August 2002

AbstractWe recently identified a novel 55‐kDa cell‐cell adhesion protein (p55) whose expression is upregulated in primary melanomas in the transition from radial growth phase to vertical growth phase. However, the functional role of p55 in various steps of the metastatic process had not been investigated. We provide evidence that subcutaneous injection of metastatic melanoma variant T1P26 in immunosuppressed newborn rats rapidly caused spontaneous metastatic lung lesions that could be readily detected by histochemical analysis with the anti‐p55 monoclonal antibody (MAb) LY1. Subsequently, we were able to demonstrate that multiple subcutaneous injections of the LY1 MAb starting on the same day after tumor cell inoculation of T1P26 cells specifically blocked the formation of spontaneous lung metastases, yet had no effects on primary tumor growth, suggesting a critical role of p55 in the earlier steps of the intravasation process. To study later stages in spontaneous metastasis, we investigated the role of p55 in organ‐specific cell adhesion of tumor cells in vitro. We showed that the T1P26 variant attached preferentially to lung frozen sections compared with other organs, reflecting the pattern of organ involvement of metastasis in vivo and that LY1 significantly blocked this interaction. However, no significant differences in attachment to lung sections were observed between the parental melanoma cell line M4Beu and its derived variant, although cellular topography analysis indicated a preferential attachment of a T1P26 variant on specific compartments of the lungs such as the perialveolar components, the endothelium and the vessel lumen of pulmonary venules. Attachment of the T1P26 variant to lung sections is not due to alterations of tumor cell adherence to basement membrane matrix by the LY1 MAb, suggesting that p55 is involved in cellular adhesion with cellular elements of the lung. p55 could represent a new functional constituent that contributes to the metastatic spread of melanoma cells by promoting the intravasation process and subsequent specific interactions between tumor cells and the target lung organ. © 2002 Wiley‐Liss, Inc.
Grade of malignancy of cervical cancer in regions of Uganda with varying malarial endemicity
Authors: Odida Michael , Schmauz Rolf , Lwanga Stephen K. 
Published: August 2002

AbstractAs in a prior study on malignant lymphomas, 3 and 6 areas of Uganda showing low and high malarial endemicity, respectively, were selected for analysis and the data retrieved from the Kampala Cancer Registry, which in the 1960s and 1970s collected cases of cancer through a widely used free biopsy service from the whole country. Overall incidence rates were derived from 924 cases from the 12‐year period 1964–1975. For reasons of economy, grade of tumour was determined only in cases pertaining to the 6‐year period 1968–1973. Of 457 cases, 304 could be reviewed histologically. Only the group of squamous cell carcinomas (84.9%, 258 cases) was large enough for subsequent geographic analysis. High incidence rates of CC were found in areas with high malarial endemicity, whereas low incidence rates occurred where malaria was either frequent or rare. A correlate to malarial infection was the proportion of high‐grade carcinomas irrespective of the overall incidence of CC. With high prevalence of malaria and high CPRs of 35–74%, the relative share of high‐grade cancer amounted to 50–67%. Where malaria was rare with low CPRs of 8–11%, these values were lower and varied only from 25–39% with a similar range of 14%. Geographic agreement between malarial endemicity and the PI of high‐grade cancer was high in the 9 study areas and only slightly lower than for BL, for which the association with malaria is beyond doubt. Compared to areas with little malaria, the RR for the incidence of high‐grade carcinomas in areas with severe malaria was increased. The value was 2.04 with a 95% confidence interval of 1.37–3.04. Attributable to secondary immunodeficiency, lifelong exposure to malaria may result in excess frequency of high‐grade malignant tumours not only in the group of malignant lymphomas but also in CC. © 2002 Wiley‐Liss, Inc.
Effect of type of screening laboratory on population‐based occurrence of cervical lesions in Finland
Authors: Nieminen Pekka , Hakama Matti , Tarkkanen Jussi , Anttila Ahti 
Published: August 2002

AbstractThe incidence of cervical cancer decreased in Finland over a 30‐year period because of an effective screening program, but in the beginning of the 1990s it began to increase. Reasons for such an increase are variable: changes in sexual habits, shortcomings in attendance for screening and possibly variation in laboratory quality. We evaluated the impact of 3 laboratories in the greater Helsinki area on screening performance and on the incidence of invasive cervical cancer and preinvasive cervical lesions in the target population. We studied time trends, geographic differences in attendance and detection rates from screening and the incidence of invasive cancer in the greater Helsinki area (population about 1 million) during the 1990s, when screening was reorganized from the Cancer Society of Finland laboratory to the municipal one (Helsinki) and to a private laboratory (Espoo), while in Vantaa screening remained with the same Cancer Society laboratory. The attendance rate for screening increased during the study period in all 3 cities. The numbers of cytologically suspected and histologically confirmed precancerous lesions found, including severe lesions, decreased significantly with the change of laboratory in Espoo; but in Helsinki and Vantaa, they increased. The overall incidence of invasive cervical cancer increased in all cities in the age groups screened but mostly in Espoo. The rather rapid changes and variation in trends in the number of screening findings cannot be explained by changes in etiologic factors or attendance. They may be related more to the quality of the laboratory performance and perhaps to the criteria used in cytology and colposcopy. A well‐organized auditing system is proposed to maintain high quality in screening. © 2002 Wiley‐Liss, Inc.
VEGF expression and enhanced production by gonadotropins in ovarian epithelial tumors
Authors: Wang Jun , Luo Feng , Lu Jean J. , Chen Peter K. , Liu Paul , Zheng Wenxin 
Published: August 2002

AbstractVascular endothelial growth factor (VEGF) is a heparin‐binding, dimeric polypeptide with potent mitogenic effects on endothelial cells. VEGF expression has also been reported in ovarian epithelial tumors (OETs), which may be associated with gonadotropin stimulatioin. We recently reported that most OETs, including OET cell lines, express gonadotropin receptors. Here we studied VEGF mRNA expression in 141 OET and 35 benign ovarian samples using reverse transcriptase polymerase chain reaction and in situ hybridization (ISH). We also studied VEGF production by OET cell lines under stimulation of gonadotropins. AO (serous carcinoma), low malignant potential (LMP; SV40‐transformed borderline tumor) and ML‐5 (SV40‐transformed cystadenoma) cells were examined for VEGF protein production under the regulation of gonadotropins in vitro. The biologic function of VEGF was confirmed by using bovine endothelial growth assay. Whereas VEGF was not detected in benign ovarian surface epithelium or in ovarian epithelial inclusions, it was detected in both epithelial and stromal compartments of OETs. For VEGF epithelial expression, only 5% of ovarian cystadenomas and 30% of borderline tumors were positive for VEGF detection by ISH, whereas VEGF mRNA signal was detected in 80% of ovarian carcinoma cases. This increment of VEGF expression in ovarian carcinomas was statistically significant compared with benign and borderline tumors. Within ovarian carcinomas, the percentage of VEGF‐positive cells was significantly associated with the grade of cancer but not with cancer cell types or cancer stages. Both follicle‐stimulating hormone (FSH) and luteinizing hormone (LH) stimulated the expression of VEFG165 in AO cells in a dose‐dependent manner. Maximal induction was obtained for FSH at dose of 40 mIU/ml and for LH at 50 mIU/ml after 48 hr of culture. Compared with the nonstimulated cells, VEGF level was significantly elevated in both LMP and AO cells after stimulation of gonadotropins. Furthermore, the induction of VEGF expression was significantly stronger in carcinoma cells than in borderline OET cells. These observations suggest that VEGF may play a role in the development of ovarian cancer and that the elevated gonadotropins, as found in menopause and in most ovarian cancer patients after surgery, could accelerate tumor growth and tumor recurrence by inducing VEGF expression in OETs. © 2002 Wiley‐Liss, Inc.
Involvement of nucleophosmin/B23 in the response of HeLa cells to UV irradiation
Authors: Wu Ming H. , Chang Jei H. , Chou Chih C. , Yung Benjamin Y.M. 
Published: August 2002

AbstractThe steady‐state mRNA level of nucleophosmin/B23 in HeLa cells increased after UV irradiation. Nucleophosmin/B23 antisense transfection potentiated ultraviolet (UV)‐induced cell killing. A block in G2/M phase, larger peak of apoptotic cells and higher caspase‐3 in vitro activity were noted in nucleophosmin/B23 antisense‐transfected cells compared with vector‐transfected cells after UV treatment. Irradiated cells that received vector plasmid exhibited increased levels of [3H]thymidine incorporation due to DNA repair synthesis. In contrast, irradiated cells that received nucleophosmin/B23 antisense plasmid exhibited no such increase of [3H]thymidine incorporation, indicating inhibition of DNA repair. Cotransfection of cells with vector allowed repair of the damaged chloramphenicol acetyl transferase (CAT) reporter and rescue of CAT activity by host repair machinery. CAT activity in cells cotransfected with nucleophosmin/B23 antisense was less (<50%) than that of vector‐transfected cells, indicating reduction of host nucleotide excision repair activity. Lower protein expressions of nucleophosmin/B23 and proliferating cell nuclear antigen (PCNA) were observed in nucleophosmin/B23 antisense‐transfected cells compared with vector‐transfected cells with or without UV treatment. Cotransfection of nucleophosmin/B23 antisense‐transfected HeLa cells with PCNA construct made the cells less susceptible to UV‐induced cell killing. Our results indicate that nucleophosmin/B23 correlates with PCNA and DNA repair capacity in cellular sensitivity to UV. © 2001 Wiley‐Liss, Inc.
Mammographic mass detection by adaptive thresholding and region growing
Authors: Lee Yong Jin , Park Jeong Mi , Park Hyun Wook 
Published: August 2002

AbstractWe present an efficient method to detect mass lesions on digitized mammograms, which consists of breast region extraction, region partitioning, automatic seed selection, segmentation by region growing, feature extraction, and neural network classification. The method partitions the breast region into a fat region, a fatty and glandular region, and a dense region, so that different threshold values can be applied to each partitioned region during processes of the seed selection and segmentation. The mammographic masses are classified by using four features representing shape, density, and margin of the segmented regions. The method detects subtle mass lesions with various contrast ranges and can facilitate a procedure of mass detection in computer‐aided diagnosis systems. © 2001 John Wiley & Sons, Inc. Int J Imaging Syst Technol, 11, 340–346, 2000
Dams and development – an insight to the report of the World Commission on Dams1
Authors: Bird Jeremy , Wallace Pamela 
Published: August 2002

AbstractThe World Commission on Dams was initiated as a new form of global policy making to find a way beyond the intensifying conflicts over dam projects. It was established by diverse groups to conduct an independent global review of the performance and impacts of large dams and develop internationally acceptable criteria and guidelines for the future.The Commission's Report, Dams and Development: a New Framework for Decision Making, presents an integrated assessment of how large dams have performed against their development targets and what the costs and impacts have been. Performance was highly variable, with a considerable portion of those studied falling short of physical targets, while many continue to generate benefits beyond their projected economic life. Many were less profitable in economic terms than expected, indicating that there is considerable scope for improving performance of existing projects. The Commission considered the adverse impacts on ecosystems and people's livelihoods to be unacceptable and unnecessary.To move forward beyond conflict, the Commission presents a new framework for decision‐making. It rejects the notion of trading one person's gain against another's loss and proposes an approach based on recognising rights and assessing risks for identifying legitimate stakeholders and negotiating development outcomes. Seven strategic priorities and corresponding policy principles for water and energy resources development were derived from this approach and a series of practical criteria and guidelines are presented.The Commission's recommendations require more attention to be paid to the preliminary stages of planning. This has time and cost implications, but in the long run, the Commission's Report offers the opportunity to reduce conflict, reduce delays and lower overall costs to the operator, the government and to society in general. Copyright © 2001 John Wiley & Sons Ltd.
Linear models for minimizing misclassification costs in bankruptcy prediction
Authors: Nanda Sudhir , Pendharkar Parag 
Published: August 2002

AbstractThis paper illustrates how a misclassification cost matrix can be incorporated into an evolutionary classification system for bankruptcy prediction. Most classification systems for predicting bankruptcy have attempted to minimize misclassifications. The minimizing misclassification approach assumes that Type I and Type II error costs for misclassifications are equal. There is evidence that these costs are not equal and incorporating costs into the classification systems can lead to better and more desirable results. In this paper, we use the principles of evolution to develop and test a genetic algorithm (GA) based approach that incorporates the asymmetric Type I and Type II error costs. Using simulated and real‐life bankruptcy data, we compare the results of our proposed approach with three linear approaches: statistical linear discriminant analysis (LDA), a goal programming approach, and a GA‐based classification approach that does not incorporate the asymmetric misclassification costs. Our results indicate that the proposed approach, incorporating Type I and Type II error costs, results in lower misclassification costs when compared to LDA and GA approaches that do not incorporate misclassification costs. Copyright © 2001 John Wiley & Sons, Ltd.
Immunogenicity of polymeric implants: Long‐term antibody response against polyester (Dacron) following the implantation of vascular prostheses into LEW.1A rats
Authors: Schlosser M. , Wilhelm L. , Urban G. , Ziegler B. , Ziegler M. , Zippel R. 
Published: August 2002

AbstractImplanted biomaterials trigger acute and chronic inflammatory responses directly correlated to the central role of phagocytic cells at the host–implant interface. This study was designed to evaluate specific humoral immune responses following repeated intraperitoneal implantations of collagen‐impregnated polyester (Dacron) prosthetic segments into LEWIS rats. Serum antibody detection was performed by enzyme immunoassay with the prosthetic segments as a target. Cutoff values for antibody positivity were greater than or equal to the 99th percentile for control rats. Polymer immunoglobiulin G (IgG) antibodies were significantly increased (p < 0.05) by repeated implantation and were subsequently followed until experimental day 293. Antibody formation was significantly enhanced through the application of complete Freund's adjuvant in combination with the first implantation. All rats within this group were antibody‐positive on day 53, but only 6 of 10 animals that received the prosthesis without the adjuvant were. After preincubation of sera with bovine collagen type I (solid phase adsorbed or in solution), polymer antibody binding was discovered not to be diminished, indicating that the IgG antibodies detected were not directed against the prosthesis impregnation. Furthermore, a significant correlation was obtained between polymer antibody binding to collagen‐impregnated and nonimpregnated prostheses (rs = 0.797, p < 0.001). There was no substantiated correlation between antibody binding to polyester and to an irrelevant polymer (Tecoflex EG 80). We conclude that specific polymer antibodies may indeed provide an additional parameter for biocompatibility testing as well as a possible serological marker of an inflammatory response to implants. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 450–457, 2002
Nanoscale modifications of PET polymer surfaces via oxygen‐plasma discharge yield minimal changes in attachment and growth of mammalian epithelial and mesenchymal cells in vitro
Authors: Xie Yubing , Sproule Taryn , Li Yan , Powell Heather , Lannutti John J. , Kniss Douglas A. 
Published: August 2002

AbstractSurface topography is believed to be a factor affecting cellular morphology, proliferation, and differentiation. The effect of surface roughness in the micron to supramicron range has been investigated previously. In the current study, the influence of nanoscale surface roughness was examined in terms of its effects on morphology, cytoskeleton expression, proliferation, differentiation, and apoptosis of three model cell types. Polyethylene terephthalate (PET) disks were etched using oxygen plasma to produce uniform and decidedly nanoscale levels of surface roughness. Three distinct types of cell lines—mouse 3T3‐L1 preadipocytes, human JEG‐3 choriocarcinoma cells, and human MCF‐7 breast adenocarcinoma cells—were cultured on the plasma‐treated disks. Untreated PET disks were used as a control. Cytoskeletal proteins (F‐actin and cytokeratin) exhibited similar patterns of expression. Cell morphology also was similar on both surfaces. Cell growth kinetics for the three types of cells and hormone secretion from the JEG‐3 cells were not significantly different from that of the controls (p > 0.05). However, the differentiation of preadipocyte 3T3‐L1 cells into lipid‐laden fat cells was modestly affected by nanoscale surface topography. In addition, 15‐deoxy‐Δ12,14‐prostaglandin J2 (15dPGJ2)‐induced apoptosis of the JEG‐3 and MCF‐7 cells revealed differences between the two surfaces. Plasma‐treated surfaces showed more differentiated and apoptotic cells, respectively, compared to the controls. These results indicate that nanoscale roughness contributes in only moderate ways to cellular adhesion, proliferation, and differentiation in the cell lines tested. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 234–245, 2002
Increase in gap‐junctional intercellular communications (GJIC) of normal human dermal fibroblasts (NHDF) on surfaces coated with high‐molecular‐weight hyaluronic acid (HMW HA)
Authors: Park Jeong Ung , Tsuchiya Toshie 
Published: August 2002

AbstractNormal human dermal fibroblast (NHDF) cells were used to detect differences in gap‐junctional intercellular communication (GJIC) by hyaluronic acid (HA), a linear polymer built from repeating disaccharide units that consist of N‐acetyl‐D‐glucosamine (GlcNa) and D‐glucuronic acid (GlcA) linked by a β1‐4 glycosidic bond. The NHDF cells were cultured with different molecular weights (MW) of HA for 4 days. The rates of cell attachment in dishes coated with high‐molecular‐weight (HMW; 310 kDa or 800 kDa) HA at 2 mg/dish were significantly reduced at an early time point compared with low‐molecular‐weight (LMW; 4.8 kDa or 48 kDa) HA with the same coating amounts. HA‐coated surfaces were observed by atomic force microscopy (AFM) under air and showed that HA molecules ran parallel in the dish coated with LMW HA and had an aggregated island structure in the dish coated with HMW HA surfaces. The cell functions of GJIC were assayed by a scrape‐loading dye transfer (SLDT) method using a dye solution of Lucifer yellow. Promotion of the dye transfer was clearly obtained in the cell monolayer grown on the surface coated with HMW HA. These results suggest that HMW HA promotes the function of GJIC in NHDF cells. In contrast, when HMW HA was added to the monolayer of NHDF cells, the functions of GJIC clearly were lowered in comparison with the cells grown in the control dish or with those grown on the surface of HMW HA. Therefore it is concluded that the MW size of HA and its application method are important factors for generating biocompatible tissue‐engineered products because of the manner in which the GJIC participates in cell differentiation and cell growth rate. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 541–547, 2002