bluuebunny/crossref_metadata_2025_split huggingface dataset:
K‐ras point mutations in human colorectal carcinomas: Relation to aneuploidy and metastasis
Authors: Suchy Bernhard , Zietz Christian , Rabes Hartmut M. 
Published: February 2007

AbstractMaterial from paraffin sections of 109 human colorectal carcinomas, mostly obtained at autopsy, was analyzed for the presence of K‐ras point mutations at codon 12, position 2. Mutations at this position were found in 23 cases (21.1%). Aneuploid colorectal carcinomas showed a significantly higher prevalence of K‐ras point mutations than diploid tumors, suggesting an involvement of ras mutations in the development of aneuploidy. No differences in the prevalence of K‐ras mutations were observed with respect to the patients' age, sex and tumor type. In metastases, the type of ras gene mutation was always identical to that of the respective primary tumor. Mutations were not found in metastases from primary tumors devoid of ras mutations. This renders a clonal selection of K‐ras mutated cells from a wild‐type primary tumor during the metastatic process unlikely. However, nearly twice as many ras gene mutations were seen in metastatic than in non‐metastatic primary tumors. © 1992 Wiley‐Liss, Inc.
Detection of distinct Epstein‐Barr virus genotypes in NPC biopsies from Southern Chinese and Caucasians
Authors: Lung Maria Li , Chang Garrick C. 
Published: February 2007

AbstractUsing the polymerase chain reaction (PCR) to analyze paraffin sections from 12 Caucasian patients, we detected only the prototype F Epstein‐Barr virus (EBV) in 10 specimens from patients with nasopharyngeal carcinoma (NPC). This is in contrast to the higher frequency of association of “f” variants in NPC biopsies from Southern Chinese. The results of EBV genotyping support evidence that the EBV strains associated with NPC in the Southern Chinese population differ from those found in Caucasians. DNA sequencing confirmed that a simple point mutation is responsible for the restriction‐fragment‐ length polymorphism which distinguishes the prototype F virus from the “f” variant. © 1992 Wiley‐Liss, Inc.
Micronuclei in bronchial biopsy specimens from heavy smokers: Characterization of an intermediate marker of lung carcinogenesis
Authors: Benner Steven E. , Lippman Scott M. , Wargovich Michael J. , Velasco Marco , Peters Edward J. , Morice Rodolfo C. , Hong Waun K. 
Published: February 2007

AbstractBronchial micronuclei, small fragments of extra‐nuclear DNA formed during cell division, provide a non‐specific but quantifiable marker of DNA damage. Micronuclei have been used to assess carcinogen exposure and as an intermediate endpoint in chemoprevention trials. As part of an ongoing chemoprevention trial, heavy smokers underwent screening bronchoscopy, with biopsies taken at 6 standardized sites. Micronuclei counts were obtained for each site in each of the 40 volunteers found to have squamous metaplasia. Unlike squamous metaplasia, the average micronuclei counts among these heavy smokers were not associated with smoking history. Micronuclei counts were also not associated with the presence or extent of metaplasia. A striking degree of intra‐individual variability was observed by comparing the micronuclei counts from different biopsy sites within individuals. The findings suggest that use of micronuclei from single sites may be misleading as a marker of carcinogen exposure or as an estimate of cancer risk. Serial measurements in individuals may provide the most useful information concerning carcinogenic exposure and the impact of chemopreventive agents. © 1992 Wiley‐Liss, Inc.
Distribution of autologous tumor‐specific cytotoxic T lymphocytes in human metastatic melanoma
Authors: Itoh K. , Salmeron M. A. , Morita T. , Seito D. , Mansfield P. P. , Ross M. I. , Balch C. M. , Augustus L. B. 
Published: February 2007

AbstractThe study of specific immunity in human cancers has been hampered by the elusive distribution and heterogeneity of effector cells. In this study, we have investigated the distribution of autologous melanoma‐specific cytotoxic T lymphocytes (CTLs) in 18 different distant metastases from melanomas (9 non‐ visceral and 9 visceral metastases). Uncultured cells from tumors were provided directly for the establishment of T‐cell clones using limiting dilution analysis to avoid any possible effects of in vitro sensitization of T cells to coexisting tumor cells. Autologous tumor‐specific CTL, clones were detected in 6 of 18 tumors (33%, 4 non‐visceral and 2 visceral metastases). The majority of GTL clones (35 of 46 and 17 of 19) in 2 patients with HLA class‐1 A2 haplotype failed to lyse either A2+ or A2− allogeneic melanoma cells, although anti‐class‐1 (monomorphic) MAb inhibited their cytotoxicity. The remaining 11 of 46 and 2 of 19 CTL clones showed A2‐restricted cytotoxicity. Autologous tumor‐specific cytotoxicity was also detected after polyclonal culture of these tumor‐infiltrating lymphocytes (TILs) in 8 of 16 tumors (50%, 5 non‐visceral and 3 visceral metastases). These results suggest that tumor‐specific T cells exist at tumor sites in at least one‐third of distant metastases of melanomas and could be induced by the addition of IL‐2 in at least half of the tumors. Tumor‐specific T cells were detectable more often in non‐ visceral than in visceral metastases. © 1992 Wiley‐Liss, Inc.
Single‐step transformation of human breast epithelial cells by SV40 large T oncogene
Authors: Berthon Philippe , Goubin Gérard , Dutrillaux Bernard , Degeorges Armelle , Faille Annick , Gespach Christian , Calvo Fabien 
Published: February 2007

AbstractNormal human mammary epithelial cell (HMEC) cultures originating from 2 mammoplasty reduction surgical samples were transfected with replication‐defective SV 40 DMA. Two independent cell lines designated as S2T2 and S1T3, selected for their increased proliferation potential and lifespan, were propagated for >22 months in culture. They maintained a near‐diploid karyotype with few chromosomal markers such as trisomy 1q (SITS) and trisonny 8q (S2T2), which are most common in breast cancer in vivo. Immortalized S1T3 cells were not tumorigenic, whereas S2T2 cells produced slowly growing tumors in nude mice. One tumor was propagated in vitro and the transformed NS2T2 cell line subsequently raised 100% large tumors in the nude mouse. Rearrangement of the SV40 genome was observed in NS2T2 cells, which was not associated with increased expression of large T antigen. S1T3, S2T2 and transformed NS2T2 cell lines expressed cytokeratins CK18, CK19, the mammary‐specific antigen DF3, and functional EGF receptors. Single‐step immortalization and malignant transformation of human breast epithelial cells can thus occur upon transfection with SV40 large T oncogene. The chromosomal abnormalities observed in these cell lines suggest that they could offer a model for the study of breast‐tumor progression in vitro. © 1992 Wiley‐Liss, Inc.
Effects of light exposure on the uptake of photofrin II in tumors and normal tissues
Authors: Ma L. W. , Moan J. , Peng Q. 
Published: February 2007

AbstractDBA mice bearing CaD2mammary carcinomas were used to determine the effect of giving small doses of light to the tumor area 1.5 hr after injecting Photofrin II (PII). The smallest light dose applied (12.5 J/cm2) had no effect on the uptake of Pll in the tumor and its surrounding tissues, as measured 24 hr after the i.p. injection. However, several higher light doses increased the uptake of PII in the tumor significantly, the uptake in skin slightly, while the uptake in muscle tissue was decreased rather than increased. Thus, the PII concentration ratio between the tumor and the surrounding normal tissues was significantly improved. The rates of clearance of PII from irradiated tissues and non‐irradiated tissues were not significantly different. Most likely, the present observations are due to transient pH lowering in the tumor resulting from vascular damage. © 1992 Wiley‐Liss, Inc.
Enhancement of hepatitis‐B surface‐antigen expression by 5‐azacytidine in a hepatitis‐B‐virus‐transfected cell line
Authors: Miyoshi Eiji , Fujii Junichi , Hayashi Norio , Ueda Keiji , Towata Takahiro , Fusamoto Hideyuki , Kamada Takenobu , Taniguchi Naoyuki 
Published: February 2007

AbstractThe human hepatoblastoma‐derived cell line HB611 secretes hepatitis‐B surface antigen (HBsAg) and hepatitis‐B e antigen (HBeAg) into the medium. Hepatitis‐B‐virus(HBV) DNA integrated into the cellular genome was found to be hypermethylated. When the cells were treated with 5‐azacytidine for 3 days, the level of HBsAg in the medium increased, while the level of HBeAg remained constant. The level of alphafetoprotein (AFP) decreased with the 5‐azacytidine treatment. Southern blot analysis of DNA digested with Hpall or Mspl showed that 5‐azacytidine treatment resulted in hypomethylation of the integrated HBV DNA, suggesting that 5‐azacytidine increased HBsAg production in the cells through hypomethylation of the HBV genomic DNA. © 1992 Wiley‐Liss, Inc.
P‐glycoprotein transports corticosterone and is photoaffinity‐labeled by the steroid
Authors: Wolf David C. , Horwitz Susan Band 
Published: February 2007

AbstractMulti‐drug‐resistant cells overproduce a 130–180‐kDa integral membrane phosphoglycoprotein known as P‐glycoprotein which acts as an energy‐dependent drug efflux pump. While P‐glycoprotein has been shown to transport hydrophobic anti tumor drugs out of multi‐drug‐resistant cells in tissue culture, its endogenous substrates remain unknown. This report shows that 3H‐corticosterone can specifically photoaffinity label P‐glycoprotein. Furthermore, corticosterone is effluxed from multidrug‐resistant cells by P‐glycoprotein. These data suggest that corticosterone may be an endogenous substrate for P‐glycoprotein. © 1992 Wiley‐Liss, Inc.
Direct detection of Epstein‐Barr virus in peripheral blood and comparison of Epstein‐Barr virus genotypes present in direct specimens and lymphoblastoid cell lines established from nasopharyngeal carcinoma patients and healthy carriers in Hong Kong
Authors: Lung Maria Li , Lam Wai Pang , Chan Kwok Hung , Li Shaobing , Sham Jonathan , Choy Damon 
Published: February 2007

AbstractBy means of a PCR assay, EBV was demonstrated directly in peripheral blood of previously infected individuals. The virus was detected in approximately 80% of specimens from EBV‐seropositive individuals, but not in cord‐blood lymphocytes by this method. When virus present in peripheral blood was compared to that observed directly in NPC biopsies or throat washings, it was distinct from that seen in biopsies in 4/15 cases (17%) and from that seen in throat washes in 1/22 cases (5%). The throat‐wash virus differed from the biopsy virus in 3/20 cases (15%). The prototype F virus was found in 7/10 LCLs (70%) established from NPC patients' peripheral blood, but was only detected in 2/9 specimens (22%) directly analyzed by the PCR assay. This finding suggests selective isolation of prototype F EBV in spontaneous LCLs established from NPC patients. © 1992 Wiley‐Liss, Inc.
The study of markers of biological effect in cancer prevention research trials
Authors: Greenwald Peter , Witkin Karen M. , Malone Winfred F. , Byar David P. , Freedman Laurence S. , Stern Harriet R. 
Published: February 2007

AbstractBiological markers may provide a valuable tool for the development of cancer prevention agents, for monitoring patient compliance to a selected intervention, or for further defining the carcinogenic process. This discussion focuses on markers of biological effect and the rationale for their use in cancer prevention trials. Recent studies with biological markers are investigating their incorporation into phase‐I, ‐II, and ‐III chemoprevention clinical trial designs. Their use in clinical studies is expected to increase the number of agents that may be evaluated and to provide valuable information on the biological effectiveness of agents, doses, and schedules. Markers may also provide information to help in selecting high‐risk groups for prevention research, and to indicate the pathways inhibited and the stage of carcinogenesis affected. Such information may prove of crucial importance in strengthening the rationale for long‐term trials and other ancillary research. Biomarker research for colon carcinogenesis is discussed, including examples of a number of recent trials that may influence future progress in this area of prevention research. A crucial step in this process is marker validation as an aspect of major prospective observational and intervention studies where cancer incidence is the endpoint. We cannot be fully confident of markers as intermediate endpoints until the evidence from clinical trials is sufficiently strong to support major public health initiatives for prevention. © 1992 Wiley‐Liss, Inc.
The effect of endocrine therapy with medroxyprogesterone acetate, 4‐hydroxyandrostenedione or tamoxifen on plasma concentrations of insulin‐like growth factor (IGF)‐I, IGF‐II and IGFBP‐1 in women with advanced breast cancer
Authors: Reed M. J. , Christodoulides A. , Koistinen R. , Seppälä M. , Teale J. D. , Ghilchik M. W. 
Published: February 2007

AbstractTamoxifen treatment of women with advanced breast cancer has previously been reported to reduce plasma insulin‐like growth factor‐type I (IGF‐I) concentrations. In this study we have examined the effect of treatment with Tamoxifen, medroxyprogesterone acetate (MPA) or 4‐hydroxyandrostenedione (4‐OHA) on plasma IGF‐I and IGF‐II concentrations. As IGF‐binding proteins (IGFBPs) can modulate the biological effects of IGF‐I, plasma IGFBP‐I levels were also measured. Treatment with Tamoxifen for 2 weeks resulted in a small, but significant, decrease in IGF‐I levels, but increase in the plasma concentration of IGFBP‐I. In contrast, treatment with MPA increased levels of IGF‐I, but significantly reduced plasma IGFBP‐I concentrations. Treatment with 4‐OHA had no significant overall effect on plasma IGF‐I or IGFBP‐I levels, although changes were detected for some subjects. Plasma IGF‐II concentrations were not altered by treatment with Tamoxifen, MPA or 4‐OHA. It is concluded that although treatment with Tamoxifen or MPA produced significant changes in plasma IGF‐I concentrations, any physiological effects of such changes are likely to be modulated by the corresponding alterations in plasma IGFBP‐I concentrations. © 1992 Wiley‐Liss, Inc.
Effects of short‐chain fatty acids on growth and differentiation of the human colon‐cancer cell line HT29
Authors: Gamet Laurence , Daviaud Danièle , Denis‐Pouxviel Colette , Remesy Christian , Murat Jean‐Claude 
Published: February 2007

AbstractShort‐chain fatty acids (SCFAs), namely butyrate, acetate and propionate, originate from the bacterial fermentation of dietaiy fibers and are the predominant anions present in the large bowel. Our study was carried out to investigate the effects of SCFAs on growth of the human adenocarcinoma cell line, HT29. The results show that, under our culture conditions, both propionate and butyrate inhibit growth of HT29 cells, whereas acetate has no significant effect. The antiproliferative effect of propionate or butyrate is associated with an inhibition of FCS‐induced activation of ornithine decarboxylase (ODC), a key enzyme of polyamine metabolism. Inhibition of growth induced by either propionate or butyrate is not reversed by the addition of putrescine, which reveals that these SCFAs are not acting solely on the ODC/polyamine system. Our data show that propionate and butyrate, unlike acetate, induce an increase in alkaline phosphatase activity, which reflects a more differentiated phenotype than that of untreated control cells. Taken together, our results suggest that propionate, like butyrate, may play an important role in the physiology of the colon and could partially account for the protective effect of dietary fibers with respect to colon carcinogenesis. © 1992 Wiley‐Liss, Inc.
Clonal variation of expression of the genes coding for plasminogen activators, their inhibitors and the urokinase receptor in HT1080 sarcoma cells
Authors: Laug Walter E. , Wang Kai , Mundi Rita , Rideout William , Kruithof Egbert K. O. , Bogenmann Emil 
Published: February 2007

AbstractThe human sarcoma cell line HT1080 was found, by in situ hybridization, to consist of cells expressing various levels of urokinase (uPA) and tissue type (tPA) plasminogen activator (PA) suggesting clonal variation of expression of these genes. Colonies originating from single HT1080 cells were, therefore, established and screened for PA activity using a fibrin agarose overlay. Colonies inducing lysis (clone C+ and H+) or no lysis (clones B− and M−) were isolated and tested for mRNA levels of uPA, tPA, uPA receptor (uPAR) and the 3 PA inhibitors (PAI), PAI‐1, PAI‐2 and protease‐nexin I. The different clones revealed considerable variation of expression of the different PA and PAI genes, with lysis‐inducing clones expressing mainly the PA genes, whereas non‐lysing clones demonstrated higher expression of the PAI genes. Amplification or loss of specific genes was excluded by Southern blotting. The protein levels of cellular and secreted PA and PAI determined by ELISA and Western blots demonstrated a pattern similar to that observed for PA and PAI mRNA concentrations, suggesting clonal differences either on the level of transcription or in RNA processing and/or stability. Due to complex interactions between PA and PAI, neither mRNA nor protein levels of the different genes were predictive for the amount of functional PA activity present in the supernatant or on the cell surface of the different clones. Receptor‐bound uPA activity was found to be considerably higher in lysis‐inducing than in non‐lysing clones and the activity was dependent on neutralization by PAI‐1 rather than on the level of uPAR mRNA. © 1992 Wiley‐Liss, Inc.
Effects of areca nut on growth, differentiation and formation of DNA damage in cultured human buccal epithelial cells
Authors: Sundqvist Kristina , Grafström Roland C. 
Published: February 2007

AbstractBecause the high incidence of oral cancers in South‐East Asia is causally linked to the common habit of betel quid chewing, the effects of an aqueous extract of areca nut, one of the main ingredients of the quid, on growth, differentiation, morphology and DNA damage were studied in cultured human buccal epithelial cells. An acute exposure (3 hr) of the cells to the extract altered their morphology and induced ridges in the plasma membrane, with indications of internalization of extract particles. Such exposure also caused formation of DNA single‐strand breaks which accumulated during post‐treatment culture, indicating continuous exposure to residual particles and/or the possibility of inhibited DNA repair. The extract accelerated terminal differentiation of the cells, measured as involucrin expression at relatively non‐toxic levels. The extract caused similar loss of colony‐forming efficiency in normal cells and in a buccal carcinoma cell line (SqCC/YI) which was defective in its ability to undergo differentiation, indicating that extract toxicity could occur independently from this response. Finally, the genotoxicity of the salivary areca‐nut‐specific carcinogen 3‐(N‐nitrosomethyl‐amino)propionaldehyde, was demonstrated by the formation of DNA protein cross‐links and DNA single‐strand breaks in normal buccal epithelial cells. These findings in vitro suggest that betel quid carcinogenesis in the human oral cavity may involve cytopathic alterations of normal cell morphology, growth and differentiation, as well as formation of DNA damage by areca‐nut‐related agents extracted or formed in saliva. © 1992 Wiley‐Liss, Inc.
Schedule‐dependent effects of two consecutive, divided, low doses of actinomycin D on translocation of protein B23, inhibition of cell growth and RNA synthesis in hela cells
Authors: Yung Benjamin Yat‐Ming , Chang Fu‐Jung , Bor Amy Meei‐Shuu , Lee Edith Siew‐Teh 
Published: February 2007

AbstractThe effects of 2 consecutive, divided, low doses of actinomycin‐D (Act‐D) on cellular localization of protein B23, inhibition of cell growth, RNA synthesis and colony formation were studied in HeLa cells. The second dose of Act‐D was administered at various times after removal of the first dose. One short exposure of HeLa cells to Act‐D had previously been shown to induce “resversible” translocation of protein B23, inhibition of cell growth, and RNA synthesis. Relocalization of protein B23 from the nucleoplasm to nucleoli as well as “reversible” inhibition of cell growth and RNA synthesis were still observed in cells that had been treated with a second dose of Act‐D administered as early as 0–2 hr or as late as 30 hr after removal of the first dose of Act‐D. In contrast, no relocalization of protein B23 from the nucleoplasm to nucleoli was observed in cells that had been treated with a second dose of Act‐D administered 9 hr after removal of the first dose. A second exposure to Act‐D, administered 9 hr after removal of the first dose, caused irreversible inhibition of cell growth and RNA synthesis; a significant inhibitory effect on colony formation was also observed. RNA synthesis in HeLa cells after 2 sequential exposures to Act‐D was further analyzed by 1 % agarose gel electrophoresis. There were higher‐molecular‐weight bands above 28S RNA, which may be the 45S and 32S RNA, observed in the controls and in the cells that had been exposed to Act‐D treatment once or in the cells that underwent Act‐D exposure twice, in which the second dose was administered as early as 0–2 hr or as late as 30 hr after removal of the first dose. These high‐molecular‐weight bands were not observed in the cells that underwent Act‐D exposure twice, in which the second dose was administered 9 hr after removal of the first. These results indicated that cells at different stages of inhibition or that have recovered from the first exposure to Act‐D respond differently to the second short Act‐D exposure. © 1992 Wiley‐Liss, Inc.
Reproductive factors and the risk of hepatocellular carcinoma in women
Authors: La Vecchia Carlo , Negri Eva , Franceschi Silvia , D'Avanzo Barbara 
Published: February 2007

AbstractThe relationship between reproductive factors and the risk of primary liver cancer was analyzed using data of a case‐control study conducted in Northern Italy between 1984 and 1991 on 79 women with histologically or serologically confirmed hepatocellular carcinoma and 344 controls in hospital for a wide spectrum of acute, non‐neoplastic diseases. The multivariate relative risk (RR) for parous vs. nulliparous women was 2.6 (95% confidence interval (CI) 1.2 to 5.8), and the risk increased with parity from 2.1 for 1, to 2.6 for 2, to 3.2 for 3, to 3.5 for 4 or more births (x trend = 6.49, p = 0.01). The relative risks were above unity, though not significantly, in women reporting spontaneous (RR = 1.3) and induced (RR = 1.6) abortions, and there was a significant trend in risk with total number of abortions. An apparent inverse trend in risk with age and first birth was accounted for by parity. No relationship emerged with age at menarche, at menopause or other menstrual factors. The association between parity and hepatocellular carcinoma was, if anything, more marked at older ages, since the RR was 1.6 (95% CI 0.5 to 4.6) below age 60, and 4.8 (95% CI 1.3 to 18.1) at age 60 or over. This observation has relevant public‐health implications, since in developed countries primary liver cancer is extremely rare among young women, but not at older ages. The association between parity and hepatocellular carcinoma is similar to that described for combined oral contraceptives, again confirming that the impact of contraceptives on the risk of several neoplasms is similar to that of pregnancy. © 1992 Wiley‐Liss, Inc.