bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of LY‐6.2 and Thy‐1 antigens on NIH 3T3 cells suppressed after transformation with activated human ras‐oncogenes
Authors: Ivanyi Dagmar , Janssen Johannes W. G. , Collard John G. 
Published: February 2007

AbstractWe have studied the expression of several cell surface antigens in NIH 3T3 cells after neoplastic transformation with activated human ras and myc oncogenes. The binding of monoclonal antibodies (MAbs), specific for mouse differentiation antigens Ly‐6.2, Thy‐1 and 9F3, to normal and transformed cells was assessed using a fluorescence‐activated cell sorter (FACS IV). Significant reduction of Ly‐6.2 and Thy‐1 antigen expression was detected in cells transformed with either the N‐ras, Ki‐ras or H‐ras oncogenes but not in c‐myc transfected cells. 9F3 antigen expression remained at the original high level in all transfectants studied. Normal levels of Ly‐6.2 and Thy‐1 expression reappeared in revertants derived from: unstable ras‐transfectants. These data indicate that ras sequences did not preferentially transform cells that were deficient in Ly‐6.2 and Thy‐l antigens. It was also shown that the reduced binding of anti‐Ly‐6.2 antibodies to ras‐transfectants was not due to a masking effect of increased cell‐surface sialylation occurring in ras‐transfected cell lines. Other possible explanations of the detected phenotypic changes are discussed. The results extend the range of tumor‐associated membrane alterations in NIH 3T3 cells following transfection with human tumor DNA containing activated ras oncogenes by a hitherto unreported alteration in the expression of Ly‐6 and Thy‐1 antigens.
Development of quantitative liquid competition radioimmunoassays for the ras oncogene and proto‐oncogene p21 products
Authors: Caruso Arnaldo , Schlom Jeffrey , Vilasi Vincent , Weeks Maureen O. , Hand Patricia Horan 
Published: February 2007

AbstractThe ras gene family of rodents and humans is highly conserved and consists of several distinct genes, i.e., rodent Harvey and Kirsten, and human Harvey, Kirsten and neuroblastoma. This gene family mediates transformation via (1) a point‐mutation resulting in the change of one amino acid in the 21 kDA ras gene product (p21) or (2) increased expression of ras p21. Group‐specific, type‐selective and interspecies indirect binding liquid competition radioimmunoassays (RIAs), capable of providing truly quantitative analyses of the 21 ras oncogene and protp‐oncogene products, have been developed. Using purified recombinant ras p21 from Escherichla coli expressing the full‐length T24 mutant human Harvey‐ras gene protein product as a standard in these RIAs, we have defined the absolute numbers of pg, fM and molecules of ras p21 in: (1) E. coli expressing the point‐mutated or proto‐ras p21 and (2) mammalian cell lines of human and murine origin. Two of the RIAs developed can be termed group‐specific in that they have the ability to detect the point‐mutated and proto forms of all 3 human ras genes (Harvey, Kirsten, and neuroblastoma), while the third RIA is type‐selective, since it detects an antigenic determinant located primarily on the Harvey ras p21. All 3 RIAs are interspecies‐specific since they are able to detect ras p21 in rodent as well as human cells. The adaptability of the RIAs to various assay conditions and ease of methodology make these immunoassays applicable to the study of several parameters associated with ras p21 expression. These assays, used in conjunction with specific cDNA probes to identify specific ras proto‐oncogenes or point‐mutated oncogenes being expressed, now provide truly quantitative analysis of ras p21 in mammalian cells to further the study of the association between ras p21 expression and transformation.
Binding of oestradiol to blood proteins and aetiology of breast cancer
Authors: Moore J. W. , Clark G. M. G. , Hoare S. A. , Millis R. R. , Hayward J. L. , Quinlan M. K. , Wang D. Y. , Bulbrook R. D. 
Published: February 2007

AbstractA prospective study of 5,000 women has shown that, compared to controls, those who subsequently developed breast cancer had a higher proportion of their blood oestradiol in the non‐protein‐bound and albumin‐bound fractions (the bio‐available fraction) and a lower proportion in the sex‐hormone‐bound fraction. The increased proportion of bio‐available oestradiol was partly due to a lower concentration of sex‐hormone‐binding globulin. Weight was excluded as a confounding factor.
Characterization and chromosomal assignment of a human cell surface antigen defined by the monoclonal antibody AUAI
Authors: Spurr N. K. , Durbin H. , Sheer D. , Parkar M. , Bobrow L. , Bodmer W. F. 
Published: February 2007

AbstractWe describe the chromosomal assignment and biochemical characterization of the genetic locus controlled by a human cell surface antigen which is defined by the monoclonal antibody (MAb) AUAI. This gene product is only expressed on epithelial cells. Therefore, human‐mouse somatic cell hybrids of epithelial origin were used to assign this gene to chromosome 2. Cell surface iodination of the hybrids and parental cells followed by immunoprecipitation and polyacrylamide gel electrophoresis showed that AUAI detected a single 35‐kDa protein. The MAb AUAI reacted on tissue sections with a subset of normal epithelial cells, but in tumours it showed a much wider distribution, though still only on epithelium‐derived tumours.
Androgen, estrogen, and progesterone receptor levels in malignant and benign breast tumors: A multivariate analysis approach
Authors: Brentani Maria Mitzi , Franco Eduardo Luis , Oshima Celina Tizuko F. , Pacheco Mercia Medeiros 
Published: February 2007

AbstractAndrogens have been frequently used in the treatment of breast cancer. However, objective responses seem to vary according to the steroid hormone receptor expression of the tumor. We have studied the relationship between concentrations of androgen receptors (AR) and those of estrogen (ER) and progesterone (PR) receptors by multiple regression and stratified analysis techniques in 154 cases of primary breast carcinomas and 39 cases of benign tumors. Both the proportion of AR‐positive tumors and the concentration of AR were dependent upon the coexpression of ER and PR by the specimens. This association was evident for malignant tumors with predominance of the positive correlation between AR and ER over that of AR and PR in post‐menopausal patients. In premenopausal women, ER and PR concentrations were similarly correlated with AR levels. The PR, but not the ER concentration, was positively correlated to AR levels in benign breast tumors. These findings were confirmed by multiple regression, taking into consideration additional information about the patients to build statistical models allowing prediction of AR. Among the other variables considered in building these models—age, menopausal status, weight, height, and clinical stage—only height (using data from all patients) and age (data from post‐menopausal women) emerged in addition to ER and PR as significantly explaining the variability of AR as the dependent variable.
Evidence for HTLV‐III/LAV expression by primary cultures of T8 cells
Authors: Fouchard M. , Reveil B. , Mbayo K. , Lurhuma A. , Sarin P. S. , Gallo R. C. , Zagury D. 
Published: February 2007

AbstractThe selective targets for HTLV‐III/LAV, the causal infectious agent of AIDS and AIDS‐related complex (ARC), are T4 cells, apparently because the virus receptor is associated with T4 antigen determinants. This accounts for T4 cell depletion in AIDS and for a decrease of IL‐2 production by AIDS peripheral blood lymphocytes (PBL) after in vitro PHA activation. By contrast, T8 cells are not targets for HTLV‐III/LAV, since T8 cells from PBL and from long‐term cultured T cells (CTC) could not be infected by the virus. We describe 2 samples of PBL from Zairian patients with HTLV‐III infection in which HTLV‐III was expressed by T8 cells. Evidence that T8 cells were expressing virus was obtained by complement cytotoxicity experiments performed in the presence of OKT8 monoclonal antibody (MAb), which removed HTLV‐III‐positive cells from cultured T cells producing the virus, and by double labelling experiments, in which some cells exhibit both T8 antigens detected either by IFA (rhodamine) or by rosetting in presence of OKT8 MAbs and HTLV‐III antigens detected by IFA (fluorescein) with of anti‐HTLV‐III p24 and p15 MAbs. Since normal T cells have previously been shown to undergo antigenic diversity, we think these results can be explained by HTLV‐III infection of T4 cells which later lost T4 antigens and acquired the T8 phenotype.
Immunoresistant metastatic tumor variants can re‐express their tumor antigen after treatment with DNA methylation‐inhibiting agents
Authors: Altevogt P. , von Hoegen P. , Schirrmacher V. 
Published: February 2007

AbstractImmuno‐escaping variants which arise during metastasis of ESb lymphoma cells in syngeneic DBA/2 mice have been shown to exhibit selective resistance to lysis by ESb‐specific cytotoxic T‐lymphocytes (CTL). The immuno‐resistant variants present no changes in the expression of H‐2Kd molecules which appear to be the restricting elements for ESb‐specific CTL. We now show that treatment of clonal immuno‐resistant ESb variant cells with MNNG or 5′azacytidine can restore the sensitivity to tumor‐specific CTL lysis in a high percentage of cloned progenitor cells. The acquisition of susceptibility to lysis by these clones is most likely due to re‐expression of ESb‐type tumor antigens because such cells (i) regain the capacity to compete with original 51Cr‐labelled ESb cells for lysis by ESb‐specific CTL, and (ii) regain the capacity to induce ESb‐specific CTL in vivo. Our data suggest that the immuno‐resistant variants are not cellular mutants but rather gene regulatory variants. This could explain: (i) their high frequency of occurrence during metastasis; (ii) the relative stability of the variant phenotype; and (iii) the reversibility observed after the use of DNA‐demethy‐lating and gene‐activating drugs like 5′‐azacytidine or MNNG.
Relationship between cellular levels of beta‐carotene and sensitivity to genotoxic agents
Authors: Stick Hans F. , Dunn Bruce P. 
Published: February 2007

AbstractThe usefulness of an in vitro test system to predict the inhibitory effect of beta‐carotene on the genotoxic activity of carcinogens/mutagens was explored. To facilitate the comparison of data obtained from cultured cells (CHO) and from exfoliated human cells, end‐points were used which can be quantitated in both cell systems: the frequency of micronuclei for estimating the effect of genotoxic agents, and cellular levels of beta‐carotene as a protective agent. In CHO cells, beta‐carotene inhibited the clastogenic and micronu‐cleus‐forming effect of methyl methanesulfonate (MMS) and 4‐nitroquinoline‐l‐oxide (4NQO), but had no protective action against gallic acid, tannic acid, an aqueous extract of areca nut or H2O2. The extent of inhibition depended on the ratio of beta‐carotene to MMS. Doses of beta‐carotene which exerted a protective effect in vitro ranged from approximately 2 to 5 ng per 106 CHO cells. Comparable levels of beta‐carotene were previously found to reduce the frequency of micronucleated exfoliated cells from the buccal mu‐cosa of tobacco and areca‐nut chewers (Stich et al., 1984b).
Rearrangement of c‐myc, pim‐1 and Mlvi‐1 and trisomy of chromosome 15 in MCF‐ and moloney‐MuLV‐induced murine T‐cell leukemias
Authors: Wirschubsky Zvi , Tsichlis Philip , Klein George , Sumegi Janos 
Published: February 2007

AbstractProvirus insertion near the c‐myc, pim‐1 or MIvi‐I genes occurred in 7 out of 59 virally induced T‐cell leukemias. C‐myc was exclusively rearranged in approximately 10% of MCF 247‐induced tumors while MIvi‐I was rearranged to a similar frequency in Molo‐ney‐virus‐induced lymphomas. Out of 25 karyotyped tumors, 9 (36%) showed trisomy of chromosome 15. Provirus insertion near c‐myc, pim‐I or MIvi‐I occurred both in diploid lymphomas and in tumors with trisomy 15. These results suggest that the molecular and cytogenetic changes observed in murine T‐cell leukemias are independent tumor‐associated events and that trisomy of chromosome 15 is a common tumor‐progression‐related event.
In vivo anti‐tumour activity of recombinant human and murine TNF, alone and in combination with murine IFN‐γ, on a syngeneic murine melanoma
Authors: Brouckaert Peter G. G. , Leroux‐Roels Geert G. , Guisez Yves , Tavernier Jan , Fiers Walter 
Published: February 2007

AbstractTNF, a protein released by induced macrophages, is believed to mediate, at least in part, the tumoritoxic effects of activated macrophages. In vitro, it has cyto‐toxic effects on transformed cells but not on normal cells, and in vivo it causes necrosis of tumours. Recently, both human and murine TNF became available as pure recombinant proteins. Subsequent work confirmed its in vitro cytotoxic activity, selective for transformed cells, and revealed other, non‐cytotoxic effects on some normal cells. In vitro, the B16BL6 melanoma cells, syngeneic with C57BL6 mice, are resistant to the cytotoxic effects of rTNF but become sensitive when they are also treated with rIFN‐γ. We report that established, s.c. B16BL6 tumours in vivo can be induced to necrotize and regress by a combined systemic treatment with rTNF and murine rIFN‐γ. Although TNF is not species‐specific in vitro, the effects of treatment with human and murine rTNF in vivo are different: with murine rTNF, the synergism with rIFN‐γ is relatively less clear, the addition of IFN‐γ is not necessary to induce regression, toxicity is more pronounced and additional mechanisms of tu‐moritoxicity could be involved. Relapses are frequent but complete cures have been observed. These results give further evidence in favour of a potential clinical use of TNF in combination therapy, e.g. with IFN‐γ. However, there is still a need to develop better regimens, especially for consolidation, and to continue research in order to understand and limit the toxicity, which could be mediated by the activating effects of TNF on some normal cell types.
Ethnic composition, age and sex, together with location and standard of housing as determinants of HLTV‐I infection in an urban trinidadian community
Authors: Miller George J. , Pegram Susan M. , Kirkwood Betty R. , Beckles Gloria L. A. , Byam Neville T. A. , Clayden Susan A. , Kinlen Leo J. , Chan Li C. , Carson Deborah C. , Greaves Melvyn F. 
Published: February 2007

AbstractThe presence of antibody to human T‐cell leukaemia virus (HLTV‐I) has been assessed in 2,143 men and women who represent 83% of all adults aged 35 to 69 years resident in a defined urban community in Trinidad. Individuals of African descent had a higher sero‐positivity rate (7.0%) than those originating from India (1.4%), Europe (0%) or of mixed descent (2.7%). Women were infected more frequently than men, and the prevalence of infection increased with age in both sexes. Sero‐positivity rates were significantly increased in adults who lived in housing of poor quality (p<0.001) or close to water courses (p< 0.025). These data and others raise the possibility that one route of HLTV‐I transmission may be via insect vectors under particular domestic circumstances.
Unsuitability of monoclonal antibodies to oncogene proteins for anti‐tumour drug‐targeting
Authors: Embleton M. J. , Habib N. A. , Garnett M. C. , Wood C. 
Published: February 2007

AbstractMonoclonal antibodies (MAbs) to ras, sis, erb‐B, src, myb and myc oncoproteins were evaluated for their potential to target anti‐cancer drugs to malignant cells. Each antibody was tested for reactivity against both fixed and viable cultured human tumour cells by immunofluorescence, and all reacted against a variety of fixed tumour cell preparations. Reactions were also observed against fixed non‐malignant cells. None, however, reacted significantly with viable cells. Two antibodies (against ras and myc proteins) were tested for their ability to localize to tumour xenografts in nude mice, and conjugates were constructed by linking these antibodies to methotrexate using human serum albumin as an intermediate carrier. Neither antibody localized to tumour in vivo, and the methotrexate conjugates were not significantly cytotoxic for tumour cells in vitro, in contrast to similar conjugates simultaneously prepared with a proven anti‐tumour MAb (791T/36). It was concluded that currently available MAbs to oncogene proteins are not suitable vectors for targeting cytotoxic agents to tumour cells.
A t(8;14)(q24;q11) translocation in a T‐cell leukemia (L1‐all) with c‐myc and TcR‐alpha chain locus rearrangements
Authors: Mathieu‐Mahul Danièle , Sigaux François , Zhu Chen , Bernheim Alain , Mauchauffe Martine , Daniel Marie‐Thérèse , Berger Roland , Larsen Christian‐Jacques 
Published: February 2007

AbstractCell lines established from T‐cell leukemias have recently been reported to exhibit a chromosome translocation t(8;14) involving proto‐oncogene c‐myc and the gene of the T‐cell receptor α‐chain(TcR‐α). In this work, we have studied a case of T‐cell leukemia presenting a t(8;14)(q24;q11) translocation that was found in fresh Jeukemic cells taken during relapse, but was absent in cells collected at diagnosis. Hybridization analysis showed that the breakpoint on chromosome 8 was located 3′ to the c‐myc exon 3. A TcR‐α‐specific original probe (D14S7, Mathieu‐Mahul et al., 1985) revealed two differently rearranged patterns in DNA from leukemic cells obtained at diagnosis and during relapse. In contrast, the rearranged TcR‐β‐gene DNA pattern did not change during the course of the disease, indicating that leukemic cells were clonally related. These data indicate that the chromosome breakpoint in 14q11 is situated in the TcR‐α locus. These results suggest that translocations t(8;14) involving TcR‐α and c‐myc genes in T‐cell malignancies are analogous to variant t(2;8) and t(8;22) translocations observed in Burkitt lymphoma. They also establish that the same types of molecular rearrangements due to a t(8;14) (q24;q11) translocation, at first described in T‐cell lines established in culture, also exist in vivo and may play a role in the evolution of the leukemic process.
Tissue expression of the tumor marker CA 50 in benign and malignant pancreatic lesions. A comparison with CA 19‐9
Authors: Haglund Caj , Lindgren Jan , Roberts Peter J. , Nordling Stig 
Published: February 2007

AbstractThe expression of the tumor marker antigen CA 50, defined by the monoclonal antibody (MAb) C 50, was studied by the immunoperoxidase technique in formalin‐fixed, paraffin‐embedded tissue sections from normal pancreata, from pancreata with pancreatitis and from benign and malignant pancreatic neoplasms. The results were compared with those obtained with MAb 1116 NS 19‐9. The C 50 antibody reacts, like the 1116 NS 19‐9 antibody, with sialosylfucosyllactotetraose (corresponding to sialylated blood group antigen Lewisa), but also with another sugar moiety, sialosyl‐lactotetraose. Thirty‐two of 37 well‐to moderately‐differentiated adenocarcinomas and all cystadenocarcinomas were positive for CA 50. The staining was most intense in the apical border of the cells, and in the intraluminal mucus. The number of positive cells was smaller in poorly differentiated adenocarcinomas and only occasional cells were stained in anaplastic carcinomas. In acute and chronic pancreatitis small terminal ducts, centro‐acinar cells and some large ducts stained for CA 50. In normal pancreas only a few small terminal ducts were CA‐19‐9‐positive, whereas both ducts and centro‐acinar cells were C‐50‐positive. Normal pancreatic tissue adjacent to carcinoma usually stained more strongly for CA 50 than the carcinoma, whereas the opposite was true for CA 19‐9. Eight out of 11 CA‐19‐9‐negative carcinomas were CA‐50‐positive. Serous cystadenomas and malignant islet‐cell tumors were focally positive for CA 50, but negative for CA 19‐9. It seems apparent that the C 50 antibody reacts with another determinant than sialylated Lewis3 in CA‐19‐9‐negative specimens, serous cystadenomas and malignant islet‐cell tumors. Serum CA 50 and CA 19‐9 levels were determined in 29 patients with pancreatic cancer. The sensitivity was similar for both markers (76%), and there was a positive correlation between the serum levels. However, there was no correlation between the serum levels and the histological expression of the CA 50 and CA 19‐9 antigens.
Unusual cytogenetic findings in two patients with t(4;11) acute leukemia
Authors: Testa Joseph R. , Misawa Shinichi , Pollak Avrom , Leavitt Richard 
Published: February 2007

AbstractUnusual cytogenetic findings are described in two patients with acute leukemia and rearrangements involving chromosomes 4 and 11. Both patients had clinical and phenotypic features often found in leukemia with t(4;11)(q21;q23). At initial diagnosis, one patient showed a standard t(4;11) with duplication of the 4q‐translocation derivative. The latter finding has been described previously in a few patients with t(4;11) in association with disease progression. By analogy with the Ph1 chromosome in chronic myelogenous leukemia, duplication of the 4q‐suggests that this derivative is the critical recombinant in the t(4;11). The second patient has a novel complex translocation, t(4;11;15)(q21;q23;q21). Analysis of this variant trans‐location implies that the 11 q + is the consistent chromosome rearrangement in this type of leukemia. The apparent contradiction of the findings in these and other relevant reported cases reviewed here suggests that genes on both the 11q+ and 4q‐recombinant chromosomes are important, in either the etiology or the progression of this disease.
Experimental inoculation of monkeys with autologous lymphoid cell lines immortalized by and producing human T‐cell leukemia virus type‐I
Authors: Nakamura Hideo , Tanaka Yuetsu , Komuro‐Tsujimoto Atsumi , Ishikawa Kohichi , Takadaya Kumiko Iijima , Tozawa Hideki , Tsujimoto Hajime , Honjo Shigeo , Hayami Masanori 
Published: February 2007

AbstractCynomolgus monkeys and squirrel monkeys were inoculated with autologous lymphoid cell lines immortalized by and producing human T‐cell leukemia virus type‐1 (HTLV‐I) in order to serve as an animal model of adult T‐cell leukemia (ATL). The autologous cell tines were established from peripheral blood mononuclear cells (PBMC) from each monkey by co‐cultivation with lethally irradiated MT‐2 cells producing HTLV‐I. All of these cell lines, which had monkey karyotypes, grew continuously without addition of interleukin‐2 (IL‐2) and expressed virus‐specific proteins of HTLV‐I and IL‐2 receptor. After inoculation with the autologous cell lines, specific antibodies against HTLV‐I proteins could be detected in their plasma, and transformed HTLV‐I‐infected cells could be recovered from their peripheral blood for at least 6 months. However, no signs of ATL have been observed to date, i.e. 2 years after inoculation.