bluuebunny/crossref_metadata_2025 huggingface dataset:
Precision in the first stage of the gastric carcinoma mass survey
Authors: Yoshida Yuji , Yamaguchi Yumiko , Tebayashi Akio , Arisue Taro , Tamura Koichi , Ichikawa Heizaburo
Published: February 2007

A new method of estimating false‐negative rate (FNR) in gastric carcinoma mass surveys is reported. It is called the “ADC method”, since estimation of FNR is based on “Accidentally Detected Carcinoma”. ADC is a carcinoma detected by chance upon close examination because of abnormalities falsely pointed out in the first stage of the mass survey (mass screening) in a region other than the one in which carcinoma is located. This method was tested in the gastric carcinoma mass survey program conducted by the Hokkaido Anti‐cancer Association. Overall FNR was estimated at 28.3%. The FNRs estimated by the ADC method appear more reasonable and reliable indicators of precision of the mass survey program. The ADC method is discussed in comparison with the previously used “follow‐up study” and several advantages of this new method are presented.
Effect of hormones on the expression of proviral genes Mtv‐2 and Mtv‐3 in mouse mammary gland
Authors: Sluyser Mels , Verstraeten Rob A. , Van Hie Roberta
Published: February 2007

We have investigated the expression of the Mtv‐2 and Mtv‐3 proviral genes in mouse mammary glands by examining the effect of hormones on levels of mammary tumor virus (MTV)3 proteins p27 (gag) and gp52 (env) in mouse mammary explants. We also investigated the effect of the hormones on DNA synthesis in the explants. The mammary glands were derived from inbred GR and 020 mice, and from the respective congenic mouse strains GR/Mtv‐2− and 020/Mtv‐2+. The addition of insulin to the culture medium caused increases in p27 and gp52 levels in GR and 020/Mtv‐2+ glands; a further increase in the viral proteins was obtained by also adding dexamethasone. Prolactin in combination with progesterone enhanced p27 and gp52 levels, but to a lesser extent than did dexamethasone. Dexamethasone caused a slight but significant increase in p27 protein in mammary explants from GR/Mtv‐2− mice. Our data indicate that the Mtv‐2 locus and the Mtv‐3 locus in mouse mammary gland are under separate glucocorticoid control, and that Mtv‐2 expression is also stimulated by the prolactin and progesterone combination. Whereas dexamethasone enhances MTV protein levels in mouse mammary explants, it inhibits DNA synthesis in the explants.
Effect of treatment with interferon and cyclophosphamide on the growth of a spontaneous liposarcoma in rats
Authors: Marquet R. L. , Schellekens H. , Westbroek D. L. , Jeekel J.
Published: February 2007

A spontaneous non‐immunogenic transplantable liposarcoma in BN rats was found to be sensitive to the antitumor effects of rat fibroblast interferon (RIF) when it was administered from the day of tumor implantation onwards. Treatment with RIF starting at 7 days after implantation was not effective. Tumor growth was markedly inhibited by cyclophosphamide (Cyclo). At the time and dose schedules used, Cyclo was more effective than RIF. When the growth of the tumor was inhibited by Cyclo, subsequent treatment with RIF did not lead to an additional retardation of tumor growth. Administration of RIF interfered with the beneficial effect of Cyclo when both agents were given concomitantly. RIF and Cyclo gave similar results to those obtained with RIF alone and these were inferior to those obtained with Cyclo alone.
Metabolic properties of isolated rat liver cell preparations enriched in epithelial cells other than hepatocytes
Authors: Ledda G. M. , Sells M. A. , Yokoyama S. , Lombardi B.
Published: February 2007

A selected fraction of non‐parenchymal cells was prepared from the liver of untreated rats, of rats 11‐13 days after ligation of the common bile duct, and of rats fed for 4‐5 weeks a choline devoid diet containing DL‐ethionine. The cell fraction isolated from these livers consisted of one type of mesenchymal cells (Kupffer cells), and of increasing proportions of γ‐glutamyltranspeptidase‐positive non‐parenchymal epithelial cells (bile ductule/oval cells). The activities of aminopyrine N‐demethylase and of aniline hydroxylase were determined in the three cell fractions, and were found to be less than 10% of the same enzyme activities of purified hepatocytes isolated from untreated rats. Primary cultures of untreated rat hepatocytes, and of the non‐parenchymal cell fraction prepared from the liver of untreated and treated rats, were exposed to aflatoxin B1. Less than 0.5% of the hepatocytes from untreated rats survived a 48 h exposure to a concentration of 10−6 m aflatoxin B1. On the other hand, 75% or more of the non‐parenchymal cells survived a 48 h exposure to a concentration of aflatoxin B1/cell two and a half times as great. It is concluded that non‐parenchymal epithelial cells of rat liver have low activities of aminopyrine N‐demethylase and of aniline hydroxylase in comparison to hepatocytes, and, in contrast to hepatocytes, are highly resistant to the cytotoxic action of aflatoxin B1. Preneoplastic and neoplastic hepatocytes are known to possess similar properties. Thus, the findings reported herein are consonant with the views that non‐parenchymal epithelial cells of rat liver may be alternate target cells, initiated by chemical carcinogens inducing hepatocellular carcinomas, and that the initiated cells may be progenitors of neoplastic hepatocytes.
Lectin‐resistant variants of mouse melanoma cells. II. In vitro characteristics
Authors: Tao Tien‐Wen , Jenkins Jennifer M. , Vosbeck Klaus , Matter Alex , Miller Marcia , Jockusch Brigitte M. , Shen Zhong‐Hou , Burger Max M.
Published: February 2007

Lectin‐resistant variants of B‐16 melanoma cells were selected with wheat‐germ agglutinin, ricin and concanavalin A. They exhibited altered metastasizing capacity and tumorigenicity in C57BL mice. Several in vitro properties were defined and compared including homotypic adhesiveness, microfilament organization, melanin release, activity of tyrosine hydroxylase, DNA content, and karyotypes. The possible relevance of these properties in vitro for the malignant behavior displayed in vivo is discussed. The usefulness of this approach of selecting surface variants to study the problem of metastasis is also discussed.
Comparison of fibrin clot retraction with other transformation parameters after hydridization of normal and established cell lines
Authors: Curatolo L. , Azzarone B. , Fally‐Crëpin C. , Morasca L. , MacIeira‐Coelho A.
Published: February 2007

The expression of transformation parameters (inhibition of cell division during cell crowding, anchorage dependence, loss of fibrin clot retractile activity and secretion of plasminogen activator) was studied in a hetero‐specific cellular hybrid, made between established L (TK−) cells and the normal human MRC‐5 cells. The hybrid nature of the cross was confirmed by the ability to incorporate [3H]‐thymidine, by growth in selective HAT medium, by the identification of human chromosomes and by the expression on the surface of 100% of hybrid cells of a human glycoprotein, which is recognized by the 4F2 monoclonal antibody. The hybrid cultures showed cell cycle inhibition which became less stringent with increasing population doublings and the loss of human chromosomes. Fibrin clot retraction and anchorage dependence were absent in spite of the presence of many human chromosomes. The two properties were present or lost simultaneously in the normal parent cells and in the transformed parent or hybrid cells respectively. The human type of plasminogen activator was secreted even with very little human genetic material left, and a complete dissociation between fibrin clot retraction and production of plasminogen activator was observed. The data strengthen the hypothesis that transformation is a multi‐step process that involves complex genetic control and where cells progressively express different phenotypes and escape growth control.
Lectins as probes for identification of tumor‐associated antigens on urothelial and colonic carcinoma cell lines
Authors: Paulie Staffan , Hansson Yngve , Lundblad Marie‐Louise , Perlmann Peter
Published: February 2007

In the search for tumor‐associated antigens, seven lec‐tins were used to investigate the cellular distribution of membrane‐associated glycoproteins on a panel of human cells derived from tumor or normal tissues. Surface labelled lysates of the different cells were precipitated with the lectins and the precipitates were separated on SDS‐PAGE. Comparison of the autoradiographic patterns revealed that a La‐reactive 115K glycopeptide (gp 115) was present on transitional‐cell carcinoma cells of the urinary bladder, on two spontaneously transformed urothelial cell lines and on a melanoma cell line. Gp 115 was absent from a non‐transformed urothelial cell line, a squamous bladder carcinoma line and five unrelated cell lines of miscellaneous tissue origin. When precipitation was performed with a rabbit antiserum raised against the La‐reactive components of a TCC cell line the same distribution of gp 115 was observed. From Helix pomatia hemagglutinin (HP) precipitates a 150K glycopolypeptide co‐migrating with a previously described HP‐reactive differentiation antigen associated with human T cells was present on one of the urothelial cell lines and on a colon carcinoma cell line. When different extracts depleted of ConA binding glycopeptides were compared, a group of three antigens (32K, 35K and 40K) were identified in the extracts of the colon carcinoma cell line, HT29. These antigens were shared by two other colon carcinoma cell lines but were absent from the unrelated cells of our panel. Furthermore, an extensively absorbed rabbit anti‐HT29 serum specifically precipitated one of these antigens (35K) from the three colon cell lines.
Quantitating the synergistic effect of smoking and alcohol consumption with the micronucleus test on human buccal mucosa cells
Authors: Stick Hans F. , Rosin Miriam P.
Published: February 2007

The micronucleus test was applied to exfoliated cells of the buccal mucosa of four population groups: (A) non‐smokers and non‐drinkers of alcoholic beverages, (B) non‐smokers but alcohol drinkers, (C) smokers but non‐drinkers, and (D) smokers and drinkers. An elevated frequency of micronucleated buccal mucosa cells was observed only in group D (smokers and alcohol drinkers). When group D was subdivided according to the number of cigarettes smoked, the frequency of micronucleated buccal cells and the average number of micronuclei per cell appeared to depend upon cigarette consumption. An approximately eight‐fold increase of micronucleated mucosa cells was seen among alcohol drinkers who smoked three or more packs of cigarettes per day, and an approximately 4.2‐fold elevation was observed when one to two packs were consumed. Neither smoking alone of up to and over 60 cigarettes per day nor ethanol drinking alone of up to 1.21 per day led to a detectable elevation of micronucleated buccal mucosa cells. Whether the strong synergistic effect between smoking and alcohol consumption, as seen by the frequency of micronucleated buccal mucosa cells, is related to their synergistic effect in the induction of oral cancers is an intriguing but open question.
Detection of H‐2Dd and H‐2Kd molecules in purified rauscher leukemia virus
Authors: Schaffar‐Deshayes L. , Choppin J. , Levy J. P.
Published: February 2007

Evidence is presented that an H‐2 antigenic activity is associated with Rauscher murine leukemia virions grown in vitro. Purified Rauscher MuLV grown in fibroblasts of BALB/c (H‐2d), C57BL6 (H‐2d) or (BALB/c × C57BL/6)F1 (H‐2d/b) were used to absorb the activity of anti‐Dd, anti‐Kd, anti‐Dd, or anti‐Db anti‐Kb antisera tested against H‐2‐related targets by cellular radioimmunoassay. The results show that Dd and Kd activities were associated with the virions grown in H‐2d or H‐2d/b fibroblasts. No H‐2b antigenic activity was detected in the virions grown in C57BL/6 or F1 fibroblasts. Immunoprecipitation of surface‐labelled spleen cells revealed that Rauscher MuLV grown in BALB/c or F1, fibroblasts inhibited the precipitation of the 48 000 dalton peaks characteristic of the Dd and Kd molecules whereas the precipitation of H‐2b molecules was not modified by Rauscher MuLV grown in the different cell lines. Class II molecules (la) were not detected in Rauscher virions. Comparison of the absorbing activities of intact and disrupted viruses suggests that the H‐2 activity was localized at the viral surface. Taken together, these results confirm the possible non‐random association of H‐2 molecules to type‐C viral particles whatever the nature of this association and its possible cellular or extracellular origin. However, the H‐2 antigens found in the virions being a non‐restricting element of anti‐viral cytolytic T lymphocytes in the same system, these results give no particular support to the “altered self” hypothesis.
Autocrine function of murine F‐MuLV induced myeloblastic cell lines
Authors: Heard J. M. , Fichelson S. , Choppin J. , Varet B.
Published: February 2007

Four in vitro permanent suspension cell lines have been established from tumoral organs of myelogenous leukemias developed in mice infected with two biologically cloned Friend helper viruses. Leukemic cells in culture were 100% typical myeloblasts exhibiting a strong myeloperoxidase positivity. A few cells were induced to granulocytic or macrophagic terminal differentiation by post‐endotoxin serum and by various chemical differentiation inducers such as DMSO, N‐butyrate and TPA. We investigated the conditions sustaining the clonal proliferation of these leukemic cells in semi‐solid cultures. Cloning efficiencies were increased by the vicinity of a large number of autologous cells and by the addition of autologous culture supernatant, indicating that the leukemic cells were able to stimulate their own in vitro growth. Cloning efficiencies were also increased by different sources of CSA, such as WEHI‐3B conditioned medium and post‐endotoxin serum. Moreover, the various cell lines stimulated each other through soluble factor(s) secreted in their culture supernatants. Proteins contained in these four culture supernatants were fractionated by successive ammonium sulfate precipitations and ion exchange chromatography. In the four cases the autostimulating activities were eluted in the same fractions as proteins stimulating the normal bone marrow cells colony formation (CSA). These data suggest that the myeloblastic leukemic cell autostimulating factor(s) might be related to the physiological CSA.
Collagenase activity in rabbit carcinoma: Cell source and cell interactions
Authors: Dabbous Mustafa Kh. , El‐Torky Mahmoud , Haney Lena , Brinkley Burchada , Sobhy Nahed
Published: February 2007

Fibroblast‐like cells (F‐cells) and epithelial‐like (E‐cells) derived from cultures of rabbit VX‐2 carcinoma released collagenase in both active and latent forms in serum‐free medium at a level higher than that of normal rabbit fibroblast cultures. The enhanced capacity of the F‐cells to release the enzyme, however, continued only for a few passages and then decreased significantly to a low level similar to that of the normal fibroblasts. The enzyme‐release by the E‐cells continued for a few more passages at a relatively moderate level, higher than that of normal fibroblasts. The release of collagenase in cultures of F‐cells was enhanced by the presence of E‐cells in mixed cultures as well as by medium conditioned by the E‐cells type. Addition of cytochalasin B at 2 μg/ml did not significantly effect the enzyme activity released in the cultures. Serum from tumor‐bearing rabbits appeared to stimulate the release of enzyme activity in cultures of either cell type.
Natural killer cell activity and spontaneous development of lymphoma. Effects of single and multiple injections of interferon into young and aged C57BL/6 mice
Authors: Bruley‐Rosset Martine , Rappaport Henry
Published: February 2007

The capacity of interferon (IFN) given once or repeatedly to augment natural killer (NK) cell activity in the spleen was tested in young and aged C57BL/6 mice. Multiple injections of 104 u IFN i.p. into 3‐month‐old or 12‐month‐old mice did not augment cytotoxicity mediated by NK cell activity; rather it reduced this activity in relation to the effect obtained with a single injection. When T and B cells or macrophages were removed in vitro, no restoration of NK‐cell activity, and therefore no suppressor cells, could be found in this system. In a long‐term experiment, B6 mice were chronically injected with 104 u of IFN or mock‐IFN from 5 months of age until death. No difference in the modification of NK‐cell activity was observed after IFN and mock‐IFN, regardless of the duration of treatment. However, the capacity of spleen cells to generate cytotoxic T cells after allogeneic stimulation in vitro or in vivo was increased in IFN‐treated mice. The median survival time was improved by 7 weeks through treatment with IFN compared to mock‐IFN, but was reduced by 9 weeks compared to the survival after treatment with saline. No significant difference in the incidence of spontaneous lymphoma resulted from IFN treatment, but the percentage of tumors observed in mice receiving mock‐IFN (68.1%) was higher than that in mice receiving saline (44.1%). These results indicate that, while a stimulating effect resulting in a delay in mortality and in tumor development can be attributed to IFN itself, the contaminating antigenic products are plausibly responsible for the deleterious effect of the total preparation.
Human normal CTL clones: Generation and properties
Authors: Zagury Daniel , Morgan Doris , Lenoir Gilbert , Fouchard Michèle , Feldman Michael
Published: February 2007

This study reports the production of clones of human killer T cells grown in the presence of TCGF4 following sensitization in MLC against (1) allogeneic cells, (2) autologous Bebv+ lymphocytes, or (3) autologous lymphoma cells. Sensitization against the tumor cells required the addition of macrophages. The expression of the cytotoxic activity of the cloned T lymphocytes required re‐stimulation with the specific stimulator cells. The cytotoxic activity seemed to be MHC‐restricted, since (1) cloned allosensitized CTL lysed their corresponding allogeneic targets, but did not lyse autologous Bebv+ cells or K562 cells; (2) cloned CTL sensitized against autologous Bebv+ cells lysed their autologous targets but not allogeneic Bebv+ targets or K562 cells; and (3) cloned CTL sensitized against autologous Burkitt lymphoma cells lysed their corresponding lymphoma targets or autologous Bebv+ targets but did not lyse allogeneic lymphoma cells or Bebv+ cells from the same allogeneic donors. The cloned CTL were homogeneous in expressing the OK T8 molecules and in being negative for T4, T10 or M1. At any given time, 25‐45% of the cloned cells manifested lytic activity. The ultrastructural properties and cell surface OK T markers were different from those of cloned human NK cells. Emphasis is focused on the differences between the structural, functional and culture characteristics of CTL clones produced by direct isolation of MLC responder cells forming conjugates with specific target cells and those of clones from transformed T‐cell lines or from T hybridomas.
The localization of prolactin binding sites in human breast tissue
Authors: Dhadly M. S. , Walker Rosemary A.
Published: February 2007

An immunohistochemical method involving the application of purified human prolactin and a specific antiserum to human prolactin, followed by the peroxidaseanti‐peroxidase immunoperoxidase technique, has been used to detect prolactin binding in benign and malignant human breast tissue. The use of fresh, frozen material has been found to be essential. Prolactin binding has been shown to be a consistent feature of benign breast tissue but a variation within samples has been noted which is irrespective of hyperplastic changes. Fifty six percent of breast carcinomas gave a positive reaction but heterogeneity of binding has been shown to be a significant feature. A relationship between the presence and extent of prolactin binding and good histological differentiation of the tumours has been noted. It is concluded that immunohistochemistry is a suitable method for the demonstration of prolactin binding sites in human breast tissue and can provide useful information with regard to tumour heterogeneity.
A study of glial fibrillary acidic protein (GFAP) in childhood brain tumours
Authors: Marsden H. B. , Kumar S. , Kahn J. , Anderton B. J.
Published: February 2007

A retrospective study of 366 primary brain tumours in childhood has been carried out. GFAP was detected in juvenile astrocytoma (76/121), adult astrocytoma (34/78), malignant glioma (0/8), other astrocytic tumours (2/4) and medulloblastoma (0/101). In eight medulloblastomas scanty positive cells were seen but were regarded as reactive rather than neoplastic. The presence of GFAP was only found to be of prognostic value in adult astrocytoma, where its occurrence was associated with a more favourable outcome.
Multiple genes in the H‐2 complex affect differently the number and growth rate of transplacentally induced lung tumours in mice
Authors: Oomen L. C. J. M. , Demant P. , Hart A. A. M. , Emmelot P.
Published: February 2007

Although several studies have demonstrated that the H‐2 haplotypes influence susceptibility to both spontaneous and carcinogen induced lung tumours in mice, little is known about the nature of their action. In this study, we analysed the effects of four haplotypes (a, h2, h4, b) with a C57BL/IOScSn background on the histological type of the tumours, their incidence, numbers and size. The tumours were studied in 8 and 16 week old progenies of mothers which were injected on the 15th day of pregnancy with N‐ethyl‐N‐nitrosourea. Even with the limited number of haplotypes tested, our data show that the effect of H‐2 genotype is both genetically and biologically complex. Lung tumours of the alveolar type were detected in appreciable numbers only in a and h2 mice, indicating that their incidence is controlled by gene(s) to the left of I‐E. On the other hand, tumours of the papillary type were present in all strains in approximately the same numbers, but their size differed between strains, being largest in a mice, intermediate in h2 and h4 mice, and smallest in b mice. Moreover, in contrast to a, h2 and h4 mice, in b mice the average tumour size did not increase in the time interval between the age of 8 and 16 weeks. Apparently, several MHC genetic factors are responsible for the control of growth and incidence of the transplacentally induced lung tumours. At least one factor maps to the left of I‐E, other(s) to the right of S. It is possible that these genes act through different mechanisms, since they affect the numbers of alveolar tumours, but with papillary tumours their main effect is on their size (growth intensity).
Metastatic clones selected from an RSV‐induced mouse sarcoma share a common marker chromosome
Authors: Di Renzo Maria Flavia , Doneda Luisa , Larizza Lidia , Comoglio Paolo M.
Published: February 2007

Previous work has shown that the metastatic potential of RSV‐transformed fibroblasts is correlated with the ability to form colonies in 0.6% (“hard”) agar. Metastatic subclones were selected by this property from the nonmetastasizing fibrosarcoma B77‐313 line. A marker chromosome was found at high frequency (90% of cells) in all the subclones studied. This marker was detectable in only 0.5% of the parental B77‐3T3 cells, demonstrating that metastatic clone precursors pre‐existed, as a small minority, in the parental line. The genotypic marker appeared to be steadily associated with the metastatic phenotype since, after prolonged in vitro propagation, the subclones retained both the marker chromosome and the high metastatic potential. Although the marker chromosome was constantly present, chromosomal numerical and structural aberrations were also found in 20% of the long‐term‐propagated subclone cells, supporting the suggestion that metastatic properties are associated with cytogenetic instability.
Control of endogenous cell regulators by the second‐stage tumor promoter phorbol‐12‐retinoate 13‐acetate
Authors: Simantov Rabi , Marks Friedrich , Furstenberger Gerhard , Sachs Leo
Published: February 2007

The phorbol esters phorbol 12‐retinoate 13‐acetate (RPA) and 12‐O‐tetradecanoyl phorbol 13‐acetate (TPA) were used to investigate the role of tumor promoters in the control of hormone response in normal and leukemic myeloid celts. RPA and TPA inhibited the binding of [20‐3H]phorbol 12,13‐dibutyrate to the leukemic cells in a competitive manner with 50% inhibition values of 5.2±l.3 and 1.1±0.6 nM, respectively. RPA, like TPA, enhanced (1) prostaglandin E,‐induced cyclic AMP synthesis, (2) the differentiation of leukemic cells induced by the normal myeloid differentiation‐inducing protein, and (3) the formation of normal myeloid cells colonies induced by the normal myeloid growth‐inducing protein. Both compounds can thus control endogenous cell regulators. Since RPA functions in the second stage of tumor promotion in mouse skin, it is suggested that the control of such endogenous regulators may involve biochemical pathways similar to those that are activated in the second stage of tumor promotion.
Interferon‐induced increase in neuraminidase‐releasable sialic acid and glycosphingolipid metabolism in mouse lymphoma and l1210 leukemic cell lines: Correlation with susceptibility to natural killer cell‐mediated lysis
Authors: Yogeeswaran G. , Grönberg A. , Welsh R. M. , Kiessling R.
Published: February 2007

Changes in sialoglyoconjugates and glycosphingolipid (GSL)5 metabolism were demonstrated in mouse EL4, P52 and YAC‐1 lymphoma and L1210 leukemia cell lines treated with β‐interferon (IFN). Expression of cell surface (neuraminidase‐releasable) sialic acid on IFN‐treated cells was markedly elevated (three‐ to six‐fold). The increase in neuraminidase‐releasable sialic acid is contributed by sialoglycoproteins and particularly by cell‐surface gangliosides in IFN‐treated cells. Incorporation of [3H]‐galactose into all GSL was elevated in IFN‐treated cells. Thin‐layer chromatographic analysis of GSL of IFN‐treated cells showed an increase in several GSL homologues with striking changes in ganglioside with chromatographic migration of GM2, GM1, and GD1a relative to control cells. IFN‐treated tumor‐cell lines became resistant to lysis by virus‐induced IFN‐activated natural killer (NK) cells, as shown previously, but addition of neuraminidase to IFN‐treated and untreated cells caused only a moderate increase in NK‐sensitivity. This suggests that IFN‐mediated protection of target cells from NK lysis was not due to a preferential masking of target structure by elevated levels of sialic acid. These membrane‐associated changes in GSL and sialic acid in IFN‐treated cells may be potentially significant, because a correlation between certain GSL expression, sialic acid phenotype and susceptibility of target cells to NK‐cell‐mediated lysis have been found in several other systems.
A new tumor promoter, dihydroteleocidin b, enhances cell growth and the production of murine leukemia virus by fibroblasts
Authors: Hoshino H. , Miwa M. , Fujiki H.
Published: February 2007

The effects of tumor promoters on the expression of murine leukemia virus (MuLV) were studied in tissue culture. Dihydroteleocidin B, an indole alkaloid, recently found to be a tumor promoter, enhanced not only the production of Moloney MuLV (M‐MuLV) by a mouse fibroblast cell line, C3H2K, persistently infected with M‐MuLV, but also growth of the C3H2K cells. The production of infectious M‐MuLV by M‐MuLV‐infected C3H2K cells that had been treated with dihydroteleocidin B for 1‐7 days was four or five times higher than that of control cells. C3H2K cells grew faster and became stationary at higher cell densities in the presence of dihydroteleocidin B than in its absence. The tumor‐promoting phorbol esters phorbol‐12, 13‐didecanoate and 12‐O‐tetradecanoylphorbol‐13‐acetate also enhanced the production of M‐MuLY, but their effects were not so strong as that of dihydroteleocidin B. These tumor promoters, however, did not induce production of endogenous MuLV in C3H2K or K‐BALB cells.
High‐density lipoprotein and extracellular matrix promotes growth and plating efficiency of normal human mammary epithelial cells in serum‐free medium
Authors: Biran S. , Horowitz A. T. , Fuks Z. , Vlodavsky I.
Published: February 2007

A routine procedure has been developed for the establishment in culture of normal primary and secondary human mammary epithelial cells. The high (80‐100%) rate of success resulted from the combined use of a serumfree medium supplemented with high‐density lipoprotein (HDL) and of cell plating on a naturally produced extracellular matrix (ECM). Plating on ECM greatly improved cell attachment, plating efficiency and initial outgrowth. HDL supported epithelial cell proliferation and prevented their detachment and degeneration while the omission of serum prevented the growth of stromal fibroblasts. Under these conditions we obtained from each specimen, and regardless of the patient's age, pure and actively dividing epithelial cell cultures forming a tightly packed and non‐overlapping cell monolayer covering the entire area of the culture dish. These epithelial cultures could be easily dissociated and subcultured at a split ratio of 1:10. The described procedure will promote studies on the role of hormones and growth factors in the proliferation and differentiation of human mammary epithelial cells and on the susceptibility of human breast epithelial cells to various transforming agents and anti‐cancer treatments.
Inhibition of experimental and spontaneous lung metastases of highly metastatic syrian hamster sarcoma cells by non‐activated bone marrow and peritoneal exudate cells
Authors: Deichman G. I. , Kashkina L. M. , Kluchareva T. E. , Vendrov E. L. , Matveeva V. A.
Published: February 2007

The possibility of inhibiting local tumor growth (experimental and spontaneous lung metastases) of the selected highly‐metastatic Syrian hamster sarcoma of STHE‐LM8 subline by means of non‐activated syngeneic and allogeneic spleen, bone marrow (BMC) and peritoneal exudate (PEC) cells was studied. Retroorbital inoculation of Syrian hamsters with native, or lethally irradiated allogeneic BMC and PEC, but not spleen cells, or hamster embryo cells effectively inhibited the development of experimental and spontaneous lung metastases induced by STHE‐LM8 cells in the animals. Spontaneous lung metastases were effectively inhibited in about 50 % of STHE‐LM8 tumor‐bearing animals (with or without tumor excision) inoculated with BMC five times at 5‐ to 7‐day intervals beginning from 1 ‐10 days after subcutaneous palpable tumor appearance. Experimental lung metastases were inhibited in 20‐80 % of animals inoculated with BMC or PEC once 5‐7 days before the tumor cells, simultaneously with them, or during the 5‐7 days following the inoculation of tumor cells, thus demonstrating that BMC metastasis‐inhibiting activity was expressed during 10‐14 days against single tumor cells, or small clusters of tumor cells, and was not effective at the stage of micro‐, or macrometastasis formation. BMC and PEC of normal allogeneic donors were significantly more active in metastasis inhibition than the same cells of tumor‐bearing animals. BMC of inbred normal Syrian hamsters of the ICV line were significantly less active, or did not inhibit experimental lung metastases either in syngeneic or in randombred allogeneic hamsters, thus apparently demonstrating an unknown genetic defect of their NR system.
Cellular immune response in the blood of cats is restricted to autochthonous feline sarcoma virus‐transformed cells
Authors: McCarty Janet M. , Grant Chris K.
Published: February 2007

The blood‐borne cytotoxic cellular immune response of cats to autochthonous fibroblasts transformed with feline sarcoma virus (FeSV) was examined. Peripheral blood lymphocytes (PBL) from immune animals were assayed for cytotoxic activity using a51Cr release microcytotoxicity assay. The time courses for appearance of cytotoxic cells were similar for all cats: effector lymphocytes appeared in the blood 7 days after immunization; peak activity occurred about day 16, and cytotoxic PBL were no longer detectable by 35 days. The specificity of cytotoxic lymphocytes was studied using autochthonous and allogeneic targets. PBL from each of five immunized cats killed autochthonous transformed fibroblast (ATF) targets, but the immune lymphocytes were not cytotoxic for non‐transformed autochthonous fibroblasts, for allogeneic fibroblasts transformed with FeSV, or for an allogeneic lymphoma cell line which produces feline leukemia virus (FeLV). Specific restriction of target‐cell killing to the ATF occurred at all effector:target‐cell ratios tested, and was maintained throughout prolonged assay incubation periods. The results suggest that for cytotoxicity to occur it is necessary for the immune lymphocytes to recognize a combination of virus‐associated antigens and “self” antigens on the ATF. The similarities between this restricted killing and that caused by cytotoxic T lymphocytes in other mammalian systems are discussed.
Cell‐mediated immune reactivity of sinclair melanoma‐bearing swine to 3 M KC1 extracts of swine and human melanoma
Authors: Hook R. R. , Hamby C. V. , Millikan L. E. , Berkelhammer J. , Stills H. F. , Oxenhandler R. W.
Published: February 2007

Leukocyte migration inhibition (LMI) assays were performed using 3 M KCI extracts to detect cell‐mediated immune reactions against tumor‐associated antigens (TAA) of swine melanoma. Positive LMI reactivity was 70% or greater in melanoma‐bearing swine compared to 10% reactivity or less in normal swine tested with extracts of either fresh or tissue‐cultured swine melanoma cells. Positive LMI reactivity was 10% or less in both melanoma and normal swine tested with extracts of normal fetal and adult swine tissues. Extracts of tissue‐cultured swine melanoma and human melanoma cells were equally capable of stimulating positive LMI reactivity in melanoma swine and human melanoma patients; normal swine and human donors demonstrated 10% or less positive LMI reactivity to these extracts. Positive LMI reactivity was not stimulated in swine melanoma or human melanoma donors by extracts of tissue‐cultured human breast tumor cells or fresh and tissue‐cultured mouse B16 melanoma cells. Evaluation of these results indicate that melanoma‐bearing swine develop cell‐mediated immune reactivity toward TAA on swine melanomas and, inasmuch as LMI assays were performed with allogeneic extracts, suggests the presence of common TAA on swine melanomas. Furthermore, these data suggest that swine and human melanoma cells may share some common TAA and that this common TAA is not expressed on mouse B16 melanoma cells.
Spontaneous in vitro malignant transformation in a xeroderma pigmentosum fibroblast line
Authors: Thielmann Heinz Walter , Fischer Elisabeth , Dzarlieva Rule T. , Komittowski Dimitri , Popanda Odilia , Edler Lutz
Published: February 2007

This paper deals with a spontaneous malignant transformation in one of our XP fibroblast lines. This cell line, designated XP29MA, was derived from a 14‐year‐old boy who did not show skin tumors or precancerous alterations either at the time of clinical examination or when the biopsy was taken. We have compared the following features in both the malignant and the benign cell line from which the malignant line developed: tumor formation in nude mice, repair capacity, cytogenetic status, light and electron microscopic characteristics. The benign cell line XP29MA had a doubling time of 4.3 d, did not form tumors in nude mice, showed a very low repair capacity (as determined by colony‐forming ability, unscheduled DNA synthesis and alkaline elution) but exhibited a normal cytogenetic and ultrastructural status. In contrast, the transformed cell line XP29MAmal grew three times faster, formed colonies in methyl cellulose, gave rise to fibrosarcomas in nude mice, showed a drastically higher repair capacity, and was characterized by an extreme genetic imbalance, resulting from numerical and structural chromosome alterations of Nos. 1, 3, 4, 8, 12, 16, 17, 18, 20 and 21. Ultrastructural examination revealed fusiform and polygonal cells, the latter exhibiting large indented nuclei, vesicular dilatations of the endoplasmatic re‐ticulum and numerous lysosomes. The higher repair capacity in XP29MAmal cells is tentatively explained in terms of reversion, enhancement of post‐replication repair and/or expression of SOS‐type functions.
Age at any birth and breast cancer risk
Authors: Trichopoulos Dimitrios , Hsieh Chung‐Cheng , Macmahon Brian , Lln Tong‐Ming , Lowe C. Ronald , Mirra Antonio P. , Ravnihar Bočena , Salber Eva J. , Valaoras Vasilios G. , Yuasa Shu
Published: February 2007

In an effort to assess the relative importance of age at first birth, age at subsequent births, and total parity to the occurrence of breast cancer, reproductive data from 4,225 women with breast cancer and 12,307 hospitalized women without breast cancer were analyzed by a multiple logistic regression model. Age at first birth was confirmed to be the most important reproductive risk indicator; it was associated with a 3.5 % increase of relative risk for every year of increase in age at first birth (the 95 % confidence interval of this estimate was 2.3 to 4.7 % increase per year). However, age at any birth after the first was also an independent and statistically significant risk indicator; it was associated with a 0.9% increase of relative risk for every year of increase in age at any (and every) birth (the 95 % confidence interval of this estimate was 0.4 to 1.5 % increase per year). There is evidence that the age of approximately 35 years represents for every birth a critical point; before this age any full‐term pregnancy confers some degree of protection; after this age any full‐term pregnancy appears to be associated with increase in breast cancer risk. The effect of parity is determined by the age of occurrence of the component pregnancies. While most pregnancies occur under the age of 35, the distribution varies from population to population, and this may account for the differences between populations in whether or not a protective effect is seen for births after the first, and if it is seen, its extent.
A semi‐automated procedure for aiding the diagnosis of cervical neoplasms based on the measurement of acid‐labile dna in exfoliated cells
Authors: Sincock A. M. , Middleton J.
Published: February 2007

Measurements of acid‐labile fractions of DNA in cells exfoliated from cervical neoplasms (invasive squamous‐cell carcinomas) using Feulgen techniques have shown elevated values in both abnormal and cytologically normal cell nuclei. These increased values occur early in the hydrolysis profiles before the Feulgen hydrolysis optimum for the cell nuclei of normal patients has been attained. They are of sufficient magnitude to enable a microcomputer programmed in BASIC to distinguish between normal and abnormal cells, even when the latter are of cytologically normal appearance. By semi‐automating the measurement procedure using a microcomputer interfaced with a Vickers M86 microdensitometer, the assessment of acid‐labile DNA in cell nuclei is proposed as a useful aid to the existing cytological diagnosis of cervical neoplasms.
The mechanism of interferon effect on cell transformation by murine sarcoma virus
Authors: Huleihel Mahmoud , Marvit Joshua , Aboud Mordechai
Published: February 2007

Mousee interferon (IFN) was found to inhibit murine sarcoirus (MSV)induced neoplastic transformation of normal rat kidney (NRK) cells. This effect was observed upon examining the formation of foci of morphologically altered cells and colonies of anchorage‐independent cells. IFN had no cytotoxic effect on MSV‐transformed NRK cells, nor on their focus or colony‐forming ability. It was therefore apparent that its inhibitory effect was directed against the viral role in cell transformation. In attempts to define the mechanism of this effect, we found that IFN delayed the initiation of the cytoplasmic viral DNA synthesis. However, the amount of this DNA eventually formed in IFN‐treated cells was the same as in the control cells. Furthermore, the transport of this DNA to the nucleus was slower in IFN‐treated cells, although all of it was finally transferred. However, while most of the viral DNA integrated into the genome of the control cells, very little integration occurred in IFN‐treated cells. The uninte‐grated viral DNA of these cells was slowly degraded. Therefore, if the cells recovered from the antiviral effect of IFN when intact viral DNA molecules still existed in their nucleus, they could resume viral DNA integration and cell transformation. IFN was found to block viral DNA supercoiling. Since supercoiled viral DNA is considered to be a precursor to integrated provirus, it seems that the inhibition of both integration and cell transformation is due to this impaired coiling.
Analysis of the growth characteristics of a primary BALB/c IgG plasmacytoma
Authors: Hentschel Roland , Kölsch Eckehart
Published: February 2007

Spontaneously arising and chemically or virally induced tumors usually cannot be analyzed in the early stages of tumorigenesis. Growth characteristics of these tumors thus are not available and it is unkown whether their expansion at any stage is influenced by the immune system. We have developed the following strategy to evaluate possible deviations from exponential growth in initial stages when a tumor is not yet manifest and in order to overcome the two main objections against most experiments in tumor immunology: use of possibly selected transplantable tumors and high initial cell doses. BALB/c mice received 0.5 ml of Pristane intraperitoneally three times within 16 weeks. This treatment induces plasmacy‐tomas in 58% of the animals within I year. Mice were bled twice a week beginning with the 5th week after the last injection and sera were stored. Guinea‐pig anti‐idiotypic antibodies were raised against the IgG myeloma protein of a plasmacytoma developing in mouse 6‐15 and a radioimmunoassay was set up. Sera of mouse 6‐15 were then tested in retrospect for appearance and increase of the myeloma idiotype Id 6‐15. We followed this idiotype thus for 19 weeks from a concentration of about 10 μg/ml up to 3 mg/ml serum. Plasmacytoma 6‐15 cell growth was calculated from the Id 6‐15 levels. In early phases wave‐like fluctuations were found, possibly due to varying ratios of secretor to total plasmacytoma 6‐15 cells. This phase was followed by an exponential increase in secretor cell number. At no time was there evidence for anti‐idiotypic auto‐antibodies against Id 6‐15. The data are discussed in connection with possibly early activation of cellular components of the immune system.
Homogeneously staining regions and tumorigenicity
Authors: Gilbert Fred , Balaban Gloria , Brangman Deborah , Herrmann Nira , Lister Ann
Published: February 2007

A homogeneously staining region (HSR), a chromosome abnormality associated with gene amplification, was found to increase in length coincident with an enhancement in tumorigenicity when cells from a human retinoblastoma cell line were serially passaged in athymic (nu/nu) mice.
Antilymphoma graft responses in the mouse brain: A study oft‐dependent functions
Authors: Puccetti P. , Giampietri A. , Campanile F. , Romani L. , Fioretti M. C.
Published: February 2007

The ability of mouse brain to provide T‐dependent anti‐lymphoma graft responses was studied in a model in which graded numbers of tumor cells were implanted intracerebrally into recipient hosts. By using survival criteria, it was possible to demonstrate the occurrence of both primary and secondary responses against tumor‐associated histocompatibility antigens in allogeneic models as well as tumor‐associated transplantation antigens in histocompatible recipients. The patterns of this in‐tracerebral graft resistance did not differ significantly from those of peripheral T‐dependent immune reactivity. The findings are discussed with regard to the concept of the brain as an immunologically privileged site.
Initiation of focal hyperplastic hepatic lesions by transplacental administration of ethylnitrosourea in rats of F1 generation, and no transmission of the effect to F2 and F3 generations
Authors: Ogawa Katsuhiro , Yokokawa Kinya , Tomoyori Takashi , Narasaki Masanobu
Published: February 2007

Administration of ethylnitrosourea (ENU) to pregnant rats in the late stage of gestation has been known to have a mainly neurocarcinogenic action on the progeny. However, when transplacental administration of ENU was combined in postnatal life with a brief dietary exposure to 2‐acetylaminofluorene (2‐AAF) and a two‐thirds partial hepatectomy, numerous focal hyperplastic lesions of γ‐glutamyltranspeptidase (GGT)‐positive hepatocytes emerged in the liver of the progeny. On the other hand, rats of F2 generation born of F1 parents and F3 rats born of F2 parents showed no increase in the incidence of hepatic lesions after treatment with the same dietary regimen. It was suggested that direct interaction between fetal liver cells and the carcinogen is important for occurrence of initiated hepatocytes and that the initiation effect on rat liver by ENU does not persist in the descendants of F2 and F3 generations.
Persistence of methylated purines in the dna of various rat fetal and maternal tissues and carcinogenesis in the offspring following a single transplacental dose of N‐methyl‐N‐nitrosourea
Authors: Likhachev A. J. , Alexandrov V. A. , Anisimov V. N. , Bespalov V. G. , Korsakov M. V. , Ovsyannikov A. I. , Popovic I. G. , Napalkov N. P. , Tomatis L.
Published: February 2007

Formation and loss of methylated purines in DNA of various fetal and maternal tissues were measured up to 7 days following intravenous administration of N‐[14C]methyl‐N‐nitrosourea to rats on the 21st day of gestation. Methylation products were detected in all tissues examined, the level in maternal liver being higher than in other tissues. The concentrations of 7‐methylguanine and 3‐methyladenine decreased faster in fetal than in corresponding maternal tissues, due to a higher rate of DNA synthesis in fetal tissues, as determined by incorporation of labelled thymidine. Removal of the promutagenic DNA lesion O6‐methylguanine was most efficient in maternal and fetal liver; but it was very poorly repaired in kidney and brain. The persistence of O6‐methylguanine relative to 7‐methylguanine was highest in the DNA of fetal brain. The principal targets for the transpacental carcinogenic effect of N‐methyl‐N‐nitrosourea under these experimental conditions were fetal neurogenic tissue and kidney; and malignant tumors developed at these sites in 31‐34% and 15‐16% of male and female descendants, respectively. These results support the concept that a complex interaction between DNA alkylation, repair and replication is the molecular basis of initiation of carcinogenesis by alkylating agents.
Neoplastic transformation of fetal lamb kidney cells by bovine leukemia virus
Authors: Rhim Johng S. , Kraus Matthias , Arnstein Paul
Published: February 2007

Neoplastic transformation of fetal lamb kidney (FLK) cells by bovine leukemia virus (BLV) is reported. Morphological transformation was observed in FLK cells within a few weeks of BLV inoculation. BLV‐transformed FLK cells had the following properties generally associated with viral transformation: (1) altered morphology; (2) increased growth rate; (3) colony formation in soft agar medium; (4) formation of large cell aggregates and growth in this aggregate form above an agar base; and (5) tumorigenicity in nude mice. The transformed cells contained BLV‐specific p24 and gp51 antigens and were virus producers. BLV was detected in transformed cells by syncytial assay. The transformed cells yielded high‐titered viral reverse transcriptase activity and viral particles. The transformed cells contained marker chromosomes (M1, M<2>, M<3>, M4 and M7) and a large submetacentric chromosome, but control cells did not. Thus, we demonstrated the neoplastic transformation of FLK cells by BLV.