bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathogenetic significance of p53 and c‐Ki‐ras gene mutations and human papillomavirus dna integration in adenocarcinoma of the uterine cervix and uterine isthmus
Authors: Jiko Kumiko , Tsuda Hitoshi , Sato Shinji , Hirohashi Setsuo 
Published: February 2007

AbstractThe pathogenetic significance of p53 and c‐Ki‐ras gene mutations and genomic integration of human papillomavirus (HPV) DNA was examined in surgically resected specimens of adenocarcinomas of the uterine cervix and isthmus using polymerase chain reaction (PCR), single‐strand‐conformation polymorphism and Southern blotting analysis. Among 25 cervical adeno‐carcinomas, p53 gene mutations between exons 5 and 8 were detected in 32%, and the incidence of these mutations was higher in cases at advanced clinical stages and with high grades of nuclear and structural atypia both in endocervical and in endometrioid types. HPV DNA type 16 or 18 in cervical adenocarcinomas was detected in 35% of cases by PCR and in 29% by Southern blotting, and, in contrast to the p53 mutations, the majority of cases with the HPV DNA were at a relatively early clinical stage with low‐grade histological atypia. c‐Ki‐ras gene mutation was detected in only 4% of cervical adenocarcinomas. Among 8 isthmus adenocarcinomas, the incidence of p53 and c‐Ki‐ras gene mutations, and the presence and integration of HPV DNA type 16 or 18 were 38%, 50%, 57% and 25% respectively. The pattern of p53 mutations differed between isthmus and cervical adenocarcinomas: all of the mutations in the former were one‐base substitutions of the transition type, whereas in the latter nearly half of the mutations were of the transversion type. Among cervical adenocarcinomas, p53 mutations between exons 5 and 8 were indicated as being mostly involved in the pathogenesis and development of biologically aggressive tumors, whereas HPV type 16 or 18 infection appeared to be involved in less aggressive cases. In isthmus adenocarcinoma, c‐Ki‐ras gene mutation, apart from p53 mutation and HPV‐type‐16 or −18 infection, appeared to be involved frequently in cancer development.
Oncogene amplifications in early‐stage human prostate carcinomas
Authors: Latil Alain , Baron Jean‐Christophe , Cussenot Olivier , Fournier Georges , Boccon‐Gibod Laurent , Le Duc Alain , Lidereau Rosette 
Published: February 2007

AbstractOncogene amplifications are frequently found in solid tumours and are often associated with more aggressively growing forms of human cancer. The proto‐oncogenes c‐myc, c‐erbB2/neu and the IIq13 band are the most frequently amplified regions in adenocarcinomas of various origins. The present study was undertaken to define whether c‐myc, int2/FGF3 (11q13 region) and c‐erbB2/neu genes are involved in prostate tumorigenesis. Tumours and peripheral lymphocyte DNA from 21 localized early‐stage prostatic carcinomas were analysed by Southern‐blot electrophoresis for amplification of the c‐myc and c‐erbB2/neu genes and the 11q13 region (int2/FGF3). We detected no amplification of these 3 oncogenes in our panel.
A HLA class I cis‐regulatory element whose activity can be modulated by hormones
Authors: Sim Bee C. , Hui Kam M. 
Published: February 2007

AbstractTo elucidate the basis of the down‐regulation in major histocompatibility complex (MHC) class I gene expression and to identify possible DNA‐binding regulatory elements that have the potential to interact with class I MHC genes, we have studied the transcriptional regulation of class I HLA genes in human breast carcinoma cells. A 9 base pair (bp) negative cis‐regulatory element (NRE) has been identified using band‐shift assays employing DNA sequences derived from the 5′‐flanking region of HLA class I genes. This 9‐bp element, GTCATGGCG, located within exon I of the HLA class I gene, can potently inhibit the expressior of a heterologous thymidine kinase (TK) gene promoter and the HLA enhancer element. Furthermore, this regulatory element can exert its suppressive function in either the sense or anti‐sense orientation. More interstingly, NRE can suppress dexamethasone‐mediated gene activation in the context of the reported glucocorticoidresponsive element (GRE) in MCF‐7 cells but has no influence on the estrogen‐mediated transcriptional activation of MCF‐7 cells in the context of the reported estrogen‐responsice element (ERE). Furthermore, the presence of such a regulatory element within the HLA class I gene whose activity can be modulated by hormones correlates well with our observation that the level of HLA class I gene expression can be down‐regulated by hormones in human breast carcinoma cells. Such interactions between negative regulatory elements and specific hormone trans‐activators are novel and suggest a versatile form of transcriptional control.
Intrinsic MDR‐1 gene and P‐glycoprotein expression in human melanoma cell lines
Authors: Berger Walter , Elbling Leonilla , Minai‐Pour Michael , Vetterlein Monika , Pirker Robert , Kokoschka Eva‐Maria , Micksche Michael 
Published: February 2007

AbstractMetastatic malignant melanoma is considered a chemotherapy‐refractory malignancy. A few previous studies have delivered contradictory results regarding the presence and functionality of P‐glycoprotein (P‐gp), a transmembranous protein associated with the classical multidrug resistance (cMDR), in malignant melanoma. Therefore we have investigated this issue on 33 cell lines established from primary and metastatic lesions of human malignant melanoma, comparing different cMDR detection methods. Immunocytochemically 33% of the cell lines stained positive for P‐gp. The data correlated with those of a P‐gp‐radioimmunometric (antibody‐binding) assay. When RT‐PCR was used for MDR‐I mRNA determination, 76% of the melanoma cell lines scored positive. Slot‐blot analysis was seen to be less sensitive than RT‐PCR. Results from the functional P‐gp assays, using daunomycin (DM) as MDR‐substrate, showed no influence of P‐gp expression on drug accumulation and cytotoxicity. However, the cMDR‐modifier verapamil (VP) significantly increased both parameters in those melanoma cells with the highest P‐gp levels. We conclude that cMDR is apparently not the decisive but probably a complementary protective mechanism against toxic agents in malignant melanoma.
Genotypic analysis of epstein‐barr virus isolates associated with nasopharyngeal carcinoma in chinese immigrants to the united states
Authors: Li Lung Maria , Chang Garrick C. , Miller Theodore R. , Wara William M. , Phillips Theodore L. 
Published: February 2007

AbstractEBV genotypes of first‐ and second‐generation Chinese diagnosed with nasopharyngeal carcinoma in the United States were analyzed by PCR techniques. Previous studies showed a geographical distribution of genotypically distinct sub‐types of EBV. Viruses detected at a higher frequency among Chinese NPC patients (Cf) were distinguished from those found in the majority of Caucasian NPC patients (DF) in the United States by polymorphisms in the BamHI F and I regions. Exploiting this distinction, we analyzed the biopsies of Chinese immigrants in the United States for their C/D and F/f genotypes to evaluate the importance of retention of the Cf virus among Chinese NPC patients in a geographical area where the DF virus prevails. This study shows that approximately 45.5 to 50% of first‐ and second‐generation Chinese NPC patients in California harbor the Cf virus, which is present in only 8% of Caucasian NPC patients in California. It is interesting that, while only 48% of the viral isolates from immigrant Chinese to California harbor the “f” variant, 96% harbor the type‐C viruses.
The common molecular genetic alterations in Dukes' B and C colorectal carcinomas are not short‐term prognostic indicators of survival
Authors: Dix Brett R. , Robbins Peter , Soong Richie , Jenner Deborah , House Anthony K. , Iacopetta Barry J. 
Published: February 2007

AbstractOur study was undertaken to determine the prognostic significance of several common genetic alterations observed in colorectal carcinomas. We have previously analysed loss of heterozygosity of the MCC, APC, p53 and DCC tumour suppressor gene loci as well as p53 gene mutations and protein over‐expression in a series of 100 Dukes' stage B and C colorectal tumours obtained at surgery. To extend our observations of alterations that may occur in these tumours, mutations to the c‐Ki‐ras oncogene and APC tumour suppressor gene were detected by PCR single‐strand conformation polymorphism analysis. Short‐term follow‐up revealed no significant association between overall patient survival and any single, or combination of, genetic alteration(s). Surprisingly, patients whose tumours showed evidence of p53 protein over‐expression/ accumulation by immunocytochemistry (ICC) had a significantly better prognosis (p = 0.039) than those whose tumours had no p53 ICC reactivity.
Intake of fried meat and risk of cancer: A follow‐up study in finland
Authors: Knekt Paul , Steineck Gunnar , Järvinen Ritva , Hakulinen Timo , Aromaa Arpo 
Published: February 2007

AbstractIt has been suggested that mutagens in fried meat may be involved in the cancer process. Therefore the relationships between intake of fried meat and subsequent risk of cancers at different sites were studied among 9,990 Finnish men and women, 15–99 years of age and initially free of cancer. The baseline study was carried out in 1966–1972, and cases of cancer were identified through data linkage with the Finnish Cancer Registry. During a 24‐year follow‐up, 853 cancer cases were diagnosed. The intake of fried meat was estimated from a dietary history interview covering the total diet of the participants during the previous year. There was a positive association between fried meat intake and the risk of female‐hormone‐related cancers, i.e., cancer of the breast, endometrium and ovary combined. The relative risk of these cancers combined between persons in the highest and lowest tertiles of daily intake of fried meat adjusted for age, personal characteristics and intake of other main food groups was 1.77 (95% confidence interval = 1.11–2.84). Pancreatic and nervous system cancers also presented non‐significant suggestive associations. No associations were observed with respect to other single cancer sites studied or to all sites of cancer combined. Further epidemiological efforts are needed to ascertain the potential link between fried‐food mutagens and cancer risk.
Incidence and risk factors for childhood brain tumors in the ILE DE France
Authors: Cordier Sylvaine , Iglesias Maria‐José , Le Goaster Corinne , Guyot Marie‐Madeleine , Mandereau Laurence , Hemon Denis 
Published: February 2007

AbstractA case‐control study investigating risk factors for childhood brain tumors was conducted in the lle de France (Paris region). During a 2‐year period (1985–1987) 109 newly diagnosed cases were identified and, of these, 75 could be interviewed. In the same region, 113 population controls, frequency‐matched for year of birth, were interviewed. Odds ratios adjusted for child's age and sex and for maternal age were estimated for each risk factor present in utero or during childhood by conditional logistic regression. Statistically significant associations were found for the following risk factors: farm residence, cat scratches, home treated with pesticides, passive smoking, family history of cancer, antihistamine intake. Intake of vitamin supplements during childhood was associated with a decrease in risk. This study is part of a multicentric case‐control study coordinated by the International Agency for Research on Cancer and its results will be compared for consistency, and pooled with those of other centers using the same protocol.
Effective anti‐metastatic melanoma vaccination with tumor cells transfected with MHC genes and/or infected with newcastle disease virus (NDV)
Authors: Plaksin Daniel , Porgador Angel , Vadai Ezra , Feldman Michael , Schirrmacher Volker , Eisenbach Lea 
Published: February 2007

AbstractThe therapeutic efficacy of active immunization with B16‐F10.9 melanoma cells transfected with syngeneic major histocompatibility complex (MHC) class‐l genes, modified by infection with Newcastle Disease virus (NDV) or modified by both treatments, was compared. B16‐F10.9 tumor‐bearing mice were treated at various stages of tumor growth and metastasis with irradiated, modified tumor‐cell vaccines. Irradiated tumor cells and H‐2Db transfectants did not stimulate anti‐tumor immunity while H‐2Kb transfectants and NDV‐modified F10.9 cells showing low and high expression of MHC class‐l genes efficiently prevented metastasis of small established tumors. NDV‐modified parental‐cell vaccines functioned optimally and improved overall survival by about 60%, also at early stages of metastasis establishment. A synergistic effect of H‐2Kb expression and virus modification on rejection of micrometastases was observed in mice bearing advanced tumors. Postoperative vaccination of mice carrying multiple metastases with NDV‐modified vaccines caused significant, but incomplete, reduction of metastatic tumor load. The therapeutic effect of NDV‐modified tumor vaccines was dependent on multiple immune mechanisms. Depletion of CD8, CD4 or NK cells by in vivo treatment with monoclonal antibodies reversed the immunotherapeutic effects of the vaccine. Thus, tumor xenogenization and gene modification may act synergistically to vaccinate against advanced tumors, while single modalities can effectively vaccinate against metastasis at early stages of tumor growth.
Lysosomes as photochemical targets
Authors: Berg Kristian , Moan Johan 
Published: February 2007

AbstractSulfonated tetraphenyl porphines (TPPSn) are photosensitizing dyes that localize in lysosomes of NHIK 3025 cells. In order to elucidate the mechanisms of cell inactivation by photochemical treatment with TPPSn, lysosomal enzyme inactivation and release of lysosomal contents were examined after treatment. In cells treated with TPPS4, and light, the lysosomal enzymes β‐N‐acetyl‐D‐glucosaminidase (β‐AGA) and cathepsin(L + B) were almost completely inactivated and no enzyme activities were released from the lysosomes. In contrast, a maximum of 30 and 50% of the initial β‐AGA activity was released from lysosomes after treatment with TPPS1and TPPS2a, respectively. Forty per cent of the initial β‐AGA activity was released after treatment with TPPS2aand a non‐cytotoxic dose of light. After such a treatment only approximately 10% of the initial cathepsin activity was found in the cytosol fraction and in all other cases no cathepsin activity was recovered in the cytosol fraction after photochemical treatment. It was found that the constituents of the cytosol partly inhibited cathepsin activity. This inhibitory effect was not influenced by the photochemical treatment, neither was the colony‐forming ability of photochemically treated cells influenced by pre‐treatment with the cathepsin inhibitor E64. The present results indicate that NHIK 3025 cells are not killed by lysosomal disruption after photochemical treatment. This is partly due to photochemical inactivation of the lysosomal enzymes and to the action of cytosolic cysteine cathepsin inhibitors. The present results also indicate that cells can survive a partial lysosomal disruption.
The evaluation of screening for gastric cancer in miyagi prefecture, Japan: A population‐based case‐control study
Authors: Fukao Akira , Tsubono Yoshitaka , Tsuji Ichiro , Hisamichi Shigeru , Sugahara Nobuyuki , Takano Akira 
Published: February 2007

AbstractAlthough a screening program for gastric cancer, using barium X‐ray examination, has been carried out widely in Japan for the past 3 decades, there is insufficient evidence to confirm its effectiveness in terms of reducing mortality. To evaluate the effectiveness of the screening, a population‐based case‐control study was carried out in Miyagi Prefecture, japan. Case subjects, who had died from gastric cancer (198) and control subjects matched in age, sex and residence (577) were selected from among members of the National Health Insurance. Their screening histories during 5 years before the cases were diagnosed were surveyed on the basis of records of the regional cancer registry and the cancer‐detection center. The odds ratio (OR) of death from gastric cancer for the persons who participated in the screening at least once during 5 years was 0.41. For those who participated only once during 5 years the OR was 0.43, and for those whose last participation was 5 years earlier it was 0.30. Our data suggest that screening for gastric cancer at 5‐year intervals might reduce mortality by 60%, and that the effect might remain for at least 5 years. © 1995 Wiley‐Liss, Inc.
Altered intracellular processing and enhanced secretion of procathepsin D in a highly deviated rat hepatoma
Authors: Isidoro Ciro , Demoz Marina , De Stefanis Daniela , Mainferme Francis , Wattiaux Robert , Baccino Francesco M. 
Published: February 2007

AbstractBoth freshly‐isolated rat hepatocytes and Morris hepatoma 7777 cells synthesized cathepsin D as a precursor that was either processed intracellulary to smaller mature forms or secreted into the medium. The pattern of mature enzyme forms was different in the 2 cell types. In addition, the relative amount of precursor secreted was much higher for hepatoma cells. Monensin strongly enhanced the secretion and also impaired the intracellular transport‐linked maturation of procathepsin D in hepatocytes, while it markedly inhibited intracellular maturation and only slightly increased secretion of the pro‐enzyme in hepatoma cells. Ammonium chloride influenced the intralyso‐somal segregation and maturation of procathepsin D in hepatocytes but not in hepatoma cells. Our observations indicate that (i) the lysosomal segregation of cathepsin D was less efficient and its fractional secretion higher in hepatoma cells than in hepatocytes; (ii) in the 2 cell types, delivery to lysosomes and processing of procathepsin D were differently sensitive to increases in the vacuolar pH. © 1995 Wiley‐Liss, Inc.
Burkitt's lymphoma cells are resistant to programmed cell death in the presence of the epstein‐barr virus latent antigen EBNA‐4
Authors: Silins Sharon L. , Sculley Tom B. 
Published: February 2007

AbstractGroup I Epstein‐Barr virus (EBV)‐positive Burkitt's lymphoma (BL) cells display a surface phenotype characteristic of germinal centre B cells and readily undergo apoptosis in response to a variety of stimuli, including serum deprivation. Activation of EBV latent gene expression has been shown to increase the survival of these tumour cells by blocking programmed cell death. To investigate the nature of this protection, we assessed the function of the EBV latent EBNA‐4 gene in a group 1 lymphoma line, dG75. Group I BL cells induced to undergo apoptosis in response to serum starvation were protected in the presence of EBNA‐4 protein. A possible factor underlying this EBNA‐4‐associated survival was increased expression of the oncoprotein bcl‐2, a known repressor of cell death. Together these data suggest that EBNA‐4 plays an important role in the regulation of programmed cell death in BL tumour cells. © 1995 Wiley‐Liss, Inc.
New short‐chain analogs of a substance‐P antagonist inhibit proliferation of human small‐cell lung‐cancer cells in vitro and in vivo
Authors: Orosz Antal , Schrett János , Nagy Józscf , Bartha László , Schön István , Nyéki Olga 
Published: February 2007

AbstractHuman small‐cell lung‐cancer cells (SCLC) produce and secrete gastrin‐releasing peptide (GRP), the mammalian equivalent of bombesin (BN). There is some evidence to suggest that GRP is an autocrine regulator of SCLC cell growth. In the search for potent BN antagonists, several substance‐P (SP) analogs were found to inhibit the growth of SCLC cells. We found that a known short‐chain SP antagonist, pHOPA‐DTrp‐Phe‐DTrp‐Leu‐Leu‐NH2 (NY3238), inhibits the binding of 125l‐Tyr4‐BN on Swiss 3T3 cell line expressing BN receptors, as well as the proliferation of NCI‐H69 SCLC cells. In this study we tested several analogs of NY3238 and we found that NY3521 and NY3460 are more effective in inhibition of proliferation of SCLC cells but less potent in inhibition of binding of 125l‐Tyr4‐BN on Swiss 3T3 cells than NY3238. Furthermore, we detected specific binding of radiotabelled NY3238 even below I nM on NCI‐H69 cells that could have been inhibited by SP and NY3460 rather than by BN. In addition to these in vitro studies, NY3460 proved to be effective in inhibiting the growth of NCI‐H69 SCLC xenografts in nude mice in vivo. These analogs of NY3238 could be promising therapeutic agents in the treatment of SCLC. © 1995 Wiley‐Liss, Inc.
Transformation of human keratinocytes is characterized by quantitative and qualitative alterations of the T‐16 antigen (Trop‐2, MOv‐16)
Authors: Schön Michael P. , Orfanos Constantin E. 
Published: February 2007

AbstractThe regulation of synthesis and post‐translational processing of the T‐16 antigen, a human cell‐surface glycoprotein of 50 to 60 kDa, was investigated in normal and transformed human keratinocytes in vitro. Normal keratinocytes of interfollicular and follicular origin were compared with squamous‐cell‐carcinoma lines, spontaneously immortalized keratinocytes, and SV‐40 transformed keratinocytes. FACS analysis and radio‐immunoprecipitation showed that the synthesis and expression of T‐16 was 3‐ to 4‐fold higher in transformed keratinocytes than in their normal counterparts. In normal keratinocytes, no quantitative differences were observed among freshly prepared cells, primary cultures and sub‐cultures. In SDS‐PAGE, a single broad band at 50 to 60 kDa was observed in normal keratinocytes, whereas 2 bands at 42 and 45 to 55 kDa were detected after transformation. Tunicamycin treatment of living cells and glycosidase digestion of immunopurified T‐16 antigen revealed this molecular heterogeneity to be due to different N‐glycosylation in normal and transformed keratinocytes. In pulse‐chase experiments, 2 distinct precursor proteins at 38 and 42 kDa were detected in transformed keratinocytes, whereas in normal cells the 38‐kDa signal was dramatically decreased. These findings indicate that quantitative and qualitative changes of T‐16 mark the transformation process of human keratinocytes, showing similar post‐translational alterations in all transformed populations investigated. © 1995 Wiley‐Liss, Inc.
Characterisation of four merkel cell carcinoma adherent cell lines
Authors: Leonard J. Helen , Dash Peter , Holland Peter , Kearsley John H. , Bell John R. 
Published: February 2007

AbstractWe have previously described the establishment of a number of cell lines from Merkel cell carcinoma (MCC), also known as small cell cancer of the skin or neuroendocrine carcinoma of the skin. These cells, all of which grew as suspension cultures, were found to resemble small cell lung cancer (SCLC) lines types 1, 2 and 3 by their morphology and growth characteristics. We now report 4 more MCC cell lines which resemble the SCLC type 4 cell lines in that they grow as adherent monolayers. These MCC lines would belong to the variant subgroup as they no longer express most neuroendocrine markers, grow at low cell density and have population doubling times of 1–5 days in contrast to the MCC suspension lines which have doubling times of 6–12 days. MCC 14/1 and MCC 14/2 were established from the same metastatic node and would appear to represent 2 clones of the tumour which differ in morphology, histochemical markers and DNA content. We present details of the morphology, DNA content and immunohistochemistry of these 4 lines and com‐pare their growth patterns with those of SCLC and MCC lines which grow in suspension. © 1995 Wiley‐Liss, Inc.