bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of the estrous cycle at gamma‐ray exposure on radiation‐induced mammary tumorigenesis in virgin rats
Authors: Inano Hiroshi , Ishii‐Ohba Hiroko , Suzuki Keiko , Yamanouchi Hiroshi 
Published: February 2007

AbstractWistar rats received whole body irradiation with 260 cGy gamma‐rays at 10 a.m. of individual phases of their estrous cycle and then had diethylstilbestrol pellets implanted for 1 year. When the radiation was given during di‐estrus II, the highest incidence (73.3%) of mammary tumorigenesis was observed, and mean latency until the first tumor appearance was 8.5 × 0.7 months. Also, rats irradiated on estrus had significantly lower incidence (35.3%) of mammary tumors than those irradiated on pro‐estrus and di‐estrus II, but there was no significant difference in latency period, Iball's indices of total mammary tumors, fibroadenoma plus adenocarcinoma, were 14.3 × 0.9, 28.8 × 2.1, 23.3 × 0.8 and 12.2 × 0.2 in rats irradiated during di‐estrus I, di‐estrus II, pro‐estrus and estrus respectively. The percentage of adenocarcinomas was comparatively uniform (25.0 to 34.8%) throughout the various phases of the estrous cycles. Also, Iball's indices calculated from adenocarcinoma indicated no significant differences between all groups. From our results, the highest incidence of mammary tumors arose in rats after irradiation at di‐estrus II with minimum level of prolactin in serum. We discuss different mechanisms of radiation‐induced and chemical‐carcinogen‐induced tumorigenesis of mammary glands. © 1992 Wiley‐Liss, Inc.
Strong induction of ICAM‐1 in human T cells transformed by human T‐cell‐leukemia virus type 1 and depression of ICAM‐1 or LFA‐1 in adult T‐cell‐leukemia‐derived cell lines
Authors: Fukudome Kenji , Furuse Mikio , Fukuhara Norio , Orita Satoshi , Imai Toshio , Takagi Shin , Nagira Morio , Hinuma Yorio , Yoshie Osamu 
Published: February 2007

AbstractSixteen human T‐cell lines were studied for the expression of a cell‐adhesion molecule ICAM‐1 and its counter‐receptor LFA‐1. The cell lines included 3 human T‐cell‐leukemia‐virus‐type‐1 (HTLV‐1)‐negative cell lines derived from acute lymphoblastic leukemia (ALL) and 13 HTLV‐1‐positive cell lines, 7 of them established from cord‐ or peripheral‐blood T cells by in vitro transformation with HTLV‐1, 2 derived from HTLV‐1 carriers, and 4 derived from patients with adult T‐cell leukemia (ATL). In sharp contrast to a basal level of ICAM‐1 in 3 HTLV‐1‐negative ALL cell lines, strong induction of ICAM‐1 was seen in all HTLV‐1‐positive T‐cell lines except for MT‐1, one of the 4 ATL cell lines used in the present study. On the other hand, the expression of LFA‐1 (CD11a and CD18) was more or less similar among the cell lines with and without HTLV‐1. Interestingly, however, 3 out of 4 ATL cell lines (TL‐Oml, H582, HUT102) revealed striking depression of LFA‐1 expression. Several lines of evidence strongly argued against direct involvement of the viral transactivator p40tax or some autocrine cytokines in the induction of ICAM‐1 in HTLV‐1‐positive T‐cell lines. It was also found that ICAM‐1 and LFA‐1 were involved in syncytium formation induced in the co‐culture of HTLV‐1‐positive and HTLV‐1‐negative human T‐cell lines. Implications of constitutive expression of ICAM‐1 for certain clinical manifestations of ATL and of depression of either ICAM‐1 or LFA‐1 during progression of ATL are discussed. © 1992 Wiley‐Liss, Inc.
Bile acids, non‐phorbol‐ester‐type tumor promoters, stimulate the phosphorylation of protein kinase C substrates in human platelets and colon cell line HT29
Authors: Huang X. P. , Fan X. T. , Desjeux J. F. , Castagna M. 
Published: February 2007

AbstractProtein kinase C (PKC) is the target for a number of tumor promoters. The mechanism underlying the promoting effects of bile acids in colorectal cancer is not understood. We report that sodium deoxycholate (DOC) triggered activation of PKC in physiological conditions. The biphasic effects of DOC upon PKC activation were Ca2+‐stimulated and did not require phosphatidylserine (PtdSer) as phospholipid co‐factor. The optimal rate of activation was obtained at 0.4 mM DOC and reached approximately half the maximal rate of activation obtained in the presence of PtdSer. Similarly to PtdSer, DOC supported diacylglycerol‐as well as phorbol‐ester‐mediated PKC activation. The reciprocal effects of PtdSer and DOC upon PKC in either 0.5 mM CaCl2 or 0.5 mM EGTA suggest that DOC interacts with the phospholipid‐binding domain to elicit PKC activation. DOC‐supported enzyme activation exhibited substrate specificity different from that of PtdSer‐supported enzyme activation. All tested primary and secondary bile acids activated PKC to various extents, with DOC being the most potent. We suggest that amphipathic bile acids acting in a PtdSer‐like manner provide the hydrophobic environment required for PKC activation. Treatment of 32P‐labeled platelets and colonic cells HT29 C1. 19A with DOC enhanced the phosphorylation of endogenous substrates for PKC. Colonic cells responsive at 50 μM DOC, appeared to be 10‐fold more sensitive than platelets. We suggest that direct or indirect activation of PKC by bile acids may account for the promoting effects of these non‐phorbol‐ester‐type tumor promoters. © 1992 Wiley‐Liss, Inc.
Insertion of SMRV‐H viral DNA at the c‐myc gene locus of a BL cell line and presence in established cell lines
Authors: Middleton P. G. , Miller S. , Ross J. A. , Steel C. M. , Guy K. 
Published: February 2007

AbstractMutation of the c‐myc gene locus has occurred during in vitro culture of the Burkitt lymphoma cell line Namalwa. Gene cloning and sequencing of this c‐myc gene locus has revealed the insertion of incomplete copies of the Squirrel Monkey Retrovirus‐Human (SMRV‐H) proviral genome. Insertions of the SMRV‐H genome were seen in all Namalwa cell lines tested, with multiple insertions being seen in some sublines. Viral particles with the morphology of type‐D retrovirus, budding from these cells, were seen by transmission EM. New insertions of the genome were produced spontaneously in these cells. The origins of the type‐D retrovirus and its implications for workers in the field are discussed. © 1992 Wiley‐Liss, Inc.
Progressive abrogation of TGF‐β‐1 and EGF growth control is associated with tumour progression in ras‐transfected human keratinocytes
Authors: Game S. M. , Huelsen A. , Patel V. , Donnelly M. , Yeudall W. A. , Stone A. , Fusenig N. E. , Prime S. S. 
Published: February 2007

AbstractThis study examined the response of human keratinocytes in different stages of transformation to exogenous TGF‐β 1 and EGF as well as their receptor and growth‐factor expression. Cells of the spontaneously immortalized HaCaT cell line and c‐Ha‐ras transfected clones (1–6, 1–7, 11–3, 11–4) exhibited different tumorigenic potentials when transplanted to athymic mice. HaCaT‐ and 1–6 cells were non‐tumorigenic, 1–7 cells formed persisting epidermal cysts (benign tumours) and 11‐3 and 11‐4 cells developed into invasive squamous‐cell carcinomas. TGF‐β 1 inhibited thymidine uptake in a dose‐dependent manner, a progressive decrease in response being associated with an increasing malignant potential (HaCaT > 1–6 > 1–7 = 11‐4). HaCaT‐cells and ras‐clones expressed TGF‐β I mRNA at similar levels, but cells of increasing malignant potential secreted markedly less receptor‐binding TGF‐P (HaCaT > 1–6 = 1–7 > 11‐3 > 11‐4) into the culture medium. Whilst ras‐transfected cells expressed fewer TGF‐P receptors than HaCaT cells, there was little difference between TGF‐p receptor number or affinity between the 4 transfected cell clones. The same was true for the TGF‐p receptor types, but Type‐11 receptors were expressed at lower levels by the malignant clones 11‐3 and 11‐4. When HaCaT and ras‐transfected cells were investigated for their response to exogenous EGF, cells were refractory (1–7, 11‐4), partially stimulated (1–6) or fully stimulated (HaCaT). Cells with increasing malignant potential produced increasing amounts of endogenous TGF‐α (11‐4 = 11‐3 > 1–7 = 1–6 > HaCaT). All tumorigenic ras clones expressed higher mRNA levels than HaCaT‐cells. Ras‐transfected clones expressed fewer high‐ and low‐affinity EGF receptors than HaCaT cells with a tendency toward increased numbers of high‐affinity EGF receptors associated with increasing malignant potential (11‐4 = 11‐3 > 1–7 > 1–6) but these changes were associated with a progressive decrease in receptor affinity. The results indicate that tumour progression in human epidermal keratinocytes transfected with c‐Ha‐ras is associated with a progressive abrogation of TGF‐β 1 and EGF growth control. They suggest that the increased autonomous growth potential associated with advanced stages of epithelial tumour progression can be defined more closely using a cellular profile of TGF‐β and EGF. © 1992 Wiley‐Liss, Inc.
TGF‐α production correlates with tumorigenicity in clones of the SW613‐S human colon carcinoma cell line
Authors: Modjtahedi Nazanine , Haddada Hedi , Lamonerie Thomas , Lazar Eliane , Lavialle Christian , Brison Olivier 
Published: February 2007

AbstractThe c‐myc gene is amplified and the c‐Ki‐ras gene is mutated in the SW613‐S human colon carcinoma cell line. Two cell types with different levels of c‐myc amplification are present in the SW613‐S cell population and representative cell clones can be isolated. The clones with a high level of amplification and expression of the c‐myc gene are tumorigenic in nude mice whereas those with a low level are not. The tumorigenic clones secrete transforming growth factor a (TGF‐α) in the culture medium whereas the non‐tumorigenic clones do not produce any detectable amount. Accordingly the level of TGF‐α mRNA is higher and the transcription rate of the gene is increased in the tumorigenic clones. The acquisition of the tumorigenic pheno‐type by cells of non‐tumorigenic clones, following introduction of c‐myc gene copies by transfection, is accompanied by an increase in the steady‐state level of TGF‐α mRNA. These findings suggest a role for an elevated level of TGF‐α production in the tumorigenic phenotype of SW613‐S cells. The possibility that this role is indirect is discussed. © 1992 Wiley‐Liss, Inc.
HLA‐B5‐restricted auto‐tumor‐specific cytotoxic T cells generated in mixed lymphocyte‐tumor‐cell culture
Authors: Wang P. , Végh Zs. , Vánky F. , Klein E. 
Published: February 2007

AbstractT‐cell‐enriched lymphocyte populations derived from the malignant exudate of a patient with ovarian carcinoma were exposed to autologous tumor cells in the mixed lymphocyte‐tumor‐cell culture (MLTC) and propagated for 42 days. Proliferation of lymphocytes depended on exposures to autologous tumor cells and on the presence of IL‐2. After 7 days, the MLTC‐lymphocytes lysed K562 and the autologous tumor cells. The latter effect was not inhibited by monoclonal antibodies (MAbs) reactive with MHC class‐1 antigens or with CD3. After 7 restimulations, the culture was enriched in CD8+ cells (92%) and showed selective lytic activity against the autologous tumor. This function was inhibited by the α‐class 1 or α‐CD3 MAbs, and also by antibodies reactive with the HLA B locus or B5 allele products. The antibodies reactive with HLA A molecules had no such effect. It seems therefore that the function of the CTLs was restricted by HLA B5. Analysis of the TCRβ genes indicated clonal T‐cell expansion in this culture. This MLTC was I of 21 initiated with 11 blood‐and 10 tumor‐derived lymphocyte (TIL) populations prepared from the malignant effusions of ovarian carcinoma patients. None of these ex‐vivo lymphocytes lysed autologous tumor cells. In 17 MLTCs the lymphocytes did not proliferate, and in 3 cultures the proliferation was maintained only for 2–3 weeks. In 3 of 4 cultures auto‐tumor cytotoxicity was induced. © 1992 Wiley‐Liss, Inc.
Effect of smoking on folate levels in buccal mucosal cells
Authors: Piyathilake C. J. , Hine R. J. , Dasanayake A. P. , Richards E. W. , Freeberg L. E. , Vaughn W. H. , Krumdieck C. L. 
Published: February 2007

AbstractThe objective of the study was to document the existence of localized deficiency of folate in a tissue exposed to cigarette smoke, by analysis of oral and circulatory levels of this vitamin in smokers and non‐smokers. Buccal mucosal cells and blood samples were collected from 25 smokers and 34 non‐smokers. The Health Habits and History Questionnaire was completed by each subject. A 96‐well plate L. casei assay, along with preincubation with a folate‐free chick pancreas pteroyl‐gamma‐glutamyl hydrolase, was used to quantitate total buccal mucosal cell folates. The reproducibility (CV 5 to 7%) and recovery (95 to 106%) of the folate assay were satisfactory. Smokers had significantly lower buccal mucosal cell folate levels than did non‐smokers. The mean plasma folate level of smokers although within normal limits, was also significantly lower than that of non‐smokers. There were no significant differences in mean dietary folate intake or in alcohol consumption between the 2 groups. The strength of the positive association between smoking and plasma and buccal mucosal cell folate deficiency (by any definition) was moderate to strong and statistically significant. Our results indicate that cigarette smoking may result in a localized folate deficiency in buccal mucosal cells, independent of the plasma folate levels. © 1992 Wiley‐Liss, Inc.
Lung cancers associated with thorotrast exposure: High incidence of small‐cell carcinoma and implications for estimation of radon risk
Authors: Ishikawa Yuichi , Mori Takesaburo , Kato Yoshio , Tsuchiya Eiju , Machinami Rikuo , Sugano Haruo , Kitagawa Tomoyuki 
Published: February 2007

AbstractThe widely accepted concept that the alpha‐emitting radionuclide radon (222Rn,220Rn) induces lung cancers in humans has been based on the excess of lung tumours observed in underground miners extracting uranium or other substances. However, this poses the important question of whether radon is the only carcinogenic factor because such miners are also heavily exposed to mine dusts including silicates, diesel exhaust, etc. in their working environment. Patients to whom Thorotrast was administered continuously exhale radon (220Rn) derived from232Th deposits in the body and therefore provide a good model for lung carcinogenesis by radon without concomitant dust exposure. We therefore investigated lung‐cancer incidence in our epidemiological follow‐up series, analysing the histological types of 11 lung cancers which were found among 359 Thorotrast autopsy cases and measuring radioactivity in the breath of living Thorotrast patients. The study revealed that, while the proportion of small‐cell lung cancers considered to be related to alpha‐particles was significantly increased, the overall lung cancer incidence was not significantly higher than in controls, in spite of the high level of220Rn in the patients' breath. This result suggests that radon in the lung does induce cancers (particularly small‐cell carcinomas) but that the induction rate is not as high as expected from risk factors associated with mining. Thus, excess lung cancers among the miners might be related to the combined effects of exposure to radon and mine dusts, and not solely to radon. © 1992 Wiley‐Liss, Inc.
The gene encoding for MC56 determinant (drug‐sensitivity marker) is located on the short arm of human chromosome 11
Authors: Cianfriglia M. , Viora M. , Tombesi M. , Merendino N. , Esposito G. , Samoggia P. , Forsberg U. H. , Schröder J. 
Published: February 2007

AbstractA panel of mouse × human B‐and T‐cell hybrids was analyzed for the expression of MC56 determinant which marks the drug‐sensitive state of CEM cells. Karyotypic and phenotypic analyses of the tested clones showed that the expression of MC56 determinant correlated to the presence of human chromosome 11 and segregated concordantly to the epitopes recognized by monoclonal antibodies in the CD44 cluster. By using a particular class of interspecific rodent × human‐cell hybrids in which the human genome counterpart is represented in the different clones only by human chromosome 11 or its fragments, we showed that the gene encoding for MC56 determinant is located on the region p 13‐pter of the short arm of chromosome 11. Therefore, the hypothesized homology between the drug‐sensitivity marker MC56 and the CD44 determinant is supported also by gene mapping studies. © 1992 Wiley‐Liss, Inc.
The lipoxygenase metabolite 12(S)‐hete promotes αllbβ3integrin‐mediated tumor‐cell spreading on fibronectin
Authors: Timar Jozsef , Chen Yong Q. , Liu Bin , Bazaz Rajesh , Taylor John D. , Honn Kenneth V. 
Published: February 2007

AbstractTumor‐cell interaction with the vessel wall during metastasis involves adhesion, induction of endothelial‐cell retraction and spreading on the exposed sub‐endothelial matrix. The signals for initiation of tumor‐cell spreading and the receptors involved are unknown. A protocol was developed to distinguish between initial tumor‐cell (B16 amelanotic melanoma; B16a) adhesion to and spreading on fibronectin. The time for maximum spreading was 50 min. Treatment with a lipoxygenase metabolite of arachidonic acid [12(S)‐HETE] resulted in maximum spreading in 15 min (max. effect approx. O.1 μM). Other lipoxygenase metabolites were ineffective. 12(S)‐HETE treatment induced a rearrangement of F‐actin, vinculin, vimentin intermediate filaments and integrin α11bβ3, but not integrin α5β1. Antibodies to α11bβ3 but not α5β1 blocked the 12(S)‐HETE effect on B16a spreading. B16a‐cell attachment to fibronectin resulted in increased metabolism of arachidonic acid to 12(S)‐HETE, which was inhibited by lipoxygenase but not by cyclo‐oxygenase inhibitors. Accordingly, lipoxygenase inhibitors but not cyclo‐oxygenase inhibitors blocked spontaneous B16a‐cell spreading. The protein‐kinase‐C inhibitors calphostin C, H7 and staurosporine also inhibited spreading, while the protein‐kinase‐A inhibitor H8 was ineffective. These data suggest that B16a‐cell spreading on fibronectin is initiated by a lipoxygenase metabolite [12(S)‐HETE] of arachidonic acid and is mediated by protein kinase C. © 1992 Wiley‐Liss, Inc.
An anti‐mucin immunotoxin BrE‐3‐ricin A‐chain is potently and selectively toxic to human small‐cell lung cancer
Authors: Derbyshire Elaine J. , Wawrzynczak Edward J. 
Published: February 2007

AbstractMonoclonal antibodies (MAbs) known to recognize epithelial mucin or defined carbohydrate structures present on mucin molecules were screened for their ability to form cytotoxic agents with ricin A‐chain active against human small‐cell lung cancer (SCLC) in an indirect assay of immunotoxin cytotoxicity. Anti‐X hapten and anti‐Y hapten antibodies binding to a high proportion of SCLC cells mediated only weak to moderate effects on 3H‐leucine incorporation in combination with the screening agent, sheep anti‐mouse IgG F'ab‐ricin A‐chain. In contrast, the mouse MAb BrE‐3, recognizing the polypeptide core of the MUCI mucin gene product, exerted potent and selective cytotoxic effects in the assay. An immunotoxin made by the direct attachment of ricin A‐chain to BrE‐3 was selectively toxic to SCLC cell lines in tissue culture. The cytotoxic activity of BrE‐3‐ricin A‐chain was enhanced 100‐fold in the presence of monensin but not by lysosomotropic amines or calcium antagonists. Our findings suggest that anti‐mucin immunotoxins may have a therapeutic role to play in the treatment of SCLC. © 1992 Wiley‐Liss, Inc.
Immunotoxins directed against the high‐molecular‐weight melanoma‐associated antigen. Identification of potent antibody‐toxin combinations
Authors: Godal Aslak , Kumle Brita , Pihl Alexander , Juell Siri , Fodstad Øystein 
Published: February 2007

AbstractTo study factors influencing the cytotoxicity of immunotoxins (ITs), we compared the in vitro cytotoxicity of conjugates in which the plant toxin abrin and the bacterial toxin Pseudomonas exotoxin A (PE) were coupled by 2 different procedures to 2 MAbs, 9.2.27 and NR‐ML‐05, which bind to different epitopes on the melanoma‐associated antigen p250. The individual target cell lines differed widely in sensitivity to the different ITs, as assessed by measurement of protein synthesis inhibition. The action of the ITs was highly specific, as the toxicity of abrin and PE conjugates was respectively 20–540 and 2,200–550,000 times higher in antigen‐positive cell lines (FEMX, SESX, OHS) than in the antigen‐negative line KPDX. The PE conjugates prepared with the 2 different MAbs differed in potency by factors of 16–126 in the target‐cell lines, but were consistently more toxic than the abrin ITs. The results demonstrate that the cytotoxicity of ITs varies with the nature of both of its moieties and that optimal results require that toxins and MAbs be matched. Moreover, the 2 coupling procedures affected differentially the binding and potency of some ITs. Each of the 2 toxins was conjugated to a sheep anti‐mouse antibody (SAM) and the toxicity of these 2 conjugates was tested in an indirect approach using 9.2.27 and NR‐ML‐05 as primary MAbs. The results showed that the indirect procedure would have correctly predicted the most potent antibody‐toxin pair, indicating that the approach may be valid for selecting suitable combinations of MAbs and toxins for use as direct ITs. © 1992 Wiley‐Liss, Inc.
Prevention of programmed cell death in burkitt lymphoma cell lines by bcl‐2‐dependent and ‐independent mechanisms
Authors: Milner Anne E. , Johnson Gerald D. , Gregory Christopher D. 
Published: February 2007

AbstractBurkitt lymphoma (BL) cell lines which retain the phenotypic characteristics of the freshly‐isolated tumour cells (group I cells) readily enter programmed cell death (apoptosis) in response to a variety of triggers. By contrast, isogenic BL cells which are phenotypically altered as a result of activation of their resident EBV genome (group‐III cells) are highly protected from apoptosis. Phenotypic changes in group‐III cells include the up‐regulation of the oncogene, bcl‐2. Expression of the 26‐kDa bcl‐2 protein in group‐1 BL cells following gene transfer was found to afford protection from apoptosis: the degree of protection was proportional to the amount of bcl‐2 protein expressed. When group‐1 bcl‐2 transfectants were compared with their group‐III counterparts it was found that, whilst bcl‐2 made a significant contribution in protecting from entry into apoptosis, hyper‐expression of bcl‐2 protein in group‐1 cells (well beyond that of group‐III cells) was necessary to attain the high levels of protection observed in group‐III cells. These results suggested that additional, bcl‐2‐independent, survival mechanisms could operate in BL cells. In support of this notion it was also found that: (I) prolonged culture of group‐1 lines in vitro resulted in enhanced survival in the absence of bcl‐2 up‐regulation, and (2) exposure of group‐1 cells to interferon‐α triggered a bcl‐2‐independent protective response. The molecular mechanisms of both the bcl‐2‐dependent and ‐independent survival pathways remain to be determined. © 1992 Wiley‐Liss, Inc.