bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural killer cell activity in reticulum‐cell sarcomas of SJL/J MICE. III. Characterization of the effector cells within RCS that mediate NK lysis
Authors: Fitzgerald Karen L. , McMaster John S. , Ponzio Nicholas M.
Published: February 2007

Various cell depletion techniques were employed to identify the cells responsible for the natural killer (NK) activity against YAC‐1 targets that is present in lymphoid tissues of SJL/J mice bearing transplantable reticulum‐cell sarcomas (RCS). The NK‐activating potential of irradiated RCS cells (X‐RCS) allowed a comparison of three NK‐cell activities in this model system: conventional, induced and RCS‐cell‐mediated cytotoxicity, represented by effector cells derived from lymphoid tissues of normal, X‐RCS‐injected and RCS‐bearing donors, respectively. Both the conventional and induced NK cells were resistant to pretreatment with anti‐la serum and C, whereas RCS‐mediated NK activity was significantly reduced by similar antiserum treatment. The cytotoxicity expressed by both conventional and induced NK cells was moderately radiosensitive, however, 5‐ to 10‐fold higher doses of irradiation were required to effect an equivalent reduction of RCS‐mediated NK activity. To further characterize the effector cells that mediated RCS‐associated NK activity, viable RCS tumor cells were injected into SJL F1 hybrids that either supported (SJL × C57EL/6 and SJL × A.TH) or did not support [SJL × B10.S(7R)] RCS growth. After pretreatment of RCS cell preparations taken from these F1 mice with alloantisera directed against the non‐SJL parental H‐2 haplotype, to remove F1 host cells (F1‐purified RCS), >75% of NK activity was recovered in the RCS‐injected SJL × C57BL/6 and SJL × A.TH F1 hybrids; however, <15% of NK activity was apparent in RCS‐injected SJL × B10.S(7R) F1 recipients. 89Sr treatment of SJL mice abrogated their ability to show increased (induced) NK activity following injection of X‐RCS. In contrast, viable, F1‐purified RCS cells demonstrated both growth and NK activity in 89Sr‐treated SJL mice that was comparable to that seen in normal controls. Treatment of effector cells with three different NK‐reactive antisera (αLy‐11.2, αNK‐1.2 and αasialo‐GM1) effectively depleted conventional and induced NK activities, but had a minimal effect on RCS‐cell‐mediated NK cytotoxicity. These data support the conclusion that RCS tumor cells of SJL/J origin possess NK cytotoxic function and that, by virtue of their pre‐B‐cell characteristics, they may represent a unique class of NK effectors.
Induction of target antigens and conversion to susceptible phenotype of NK‐cell‐resistant lymphoid cell line
Authors: Clark Edward A. , Sturge Jerrilyn C. , Falk Laurence A.
Published: February 2007

Two autologous Herpesvirus papio producer lymphoid cell lines and one autologous non‐producer line were compared for susceptibility to natural killer (NK) cell‐mediated lysis. The non‐producer cell line, 26CB‐1, was more resistant to NK cell killing compared to one viral producer counterpart 13CB‐1, but equally resistant when compared to another, 8CB‐1. Treatment with chemical agents that affect differentiation or activate the viral cycle, including n‐butyrate, luDR, 5‐azacytidine and tunicamycin, increased the susceptibility to killing of the non‐producer line but had less effect on the 13CB‐1 producer line. The increase in susceptibility was due to induction of new target antigens: activated 26CB‐1 cells were more effective at inhibiting NK‐cell‐mediated lysis and were bound by more NK cells than untreated control cells. The expression of NK target structures may be related to the differentiated state rather than to the viral production status of target cells.
Transformation of rat thyroid epithelial cells by kirsten murine sarcoma virus
Authors: Fusco Alfredo , Pinto Antonio , Ambesi‐Impiombato Francesco Saverio , Vecchio Giancarlo , Tsuchida Nobuo
Published: February 2007

Fischer rat thyroid epithelial cells (FRT) growing continuously in culture were infected with the Kirsten murine sarcoma virus KiMSV(KiMuLV) and found to produce this virus constitutively. Although the morphology of the FRT cells did not change appreciably, the cells became malignant after infection with KiMSV(KiMuLV) as shown by the growth of infected cells in semi‐solid media (uninfected FRT cells did not grow) and by the tumorigenicity of infected cells when injected into syngeneic animals (uninfected FRT cells or FRT cells infected with non‐transforming retro‐viruses were not tumorigenic). The induced tumors morphologically resembled moderately differentiated carcinomas. Two markers of thyroid epithelial differentiation were absent in the original FRT clone and remained unexpressed after transformation. Fully differentiated rat thyroid epithelial cells (FRT‐L cells) infected with another strain of the Kirsten murine sarcoma virus, the KiMSV(MolMuLV), were also transformed as demonstrated by the ability also of these cells to grow as carcinomas (after in vitro transformation) in syngeneic animals. Our results clearly demonstrate that the Kirsten murine sarcoma virus can transform in vitro cells of epithelial as well as of fibroblastic origin.
A prospective study of plasma prolactin levels and subsequent risk of breast cancer
Authors: Kwa H. G. , Cleton F. , Wang D. Y. , Bulbrook R. D. , Bulstrode J. C. , Hayward J. L. , Millis R. R. , Cuzick J.
Published: February 2007

Plasma prolactin was measured in 2,572 premenopausal, 628 menopausal, and 1,666 peri‐ and postmenopausal women who were apparently healthy. Breast cancer was subsequently diagnosed in 47 of these women at a median time of 5 years after blood collection (pre‐cancer cases). Prolactin levels in pre‐menopausal cases increased significantly with age whereas this was not found in matched controls. The perimenopausal cases were characterized by extreme variability in prolactin levels. In post‐menopausal women who developed breast cancer, the prolactin levels were significantly elevated, being at or above the 70th percentile for the controls. In this group the results are consistent with prolactin acting as a late‐stage tumour promoter.
Coffee and ovarian cancer
Authors: Trichopoulos Dimitrios , Papapostolou Michail , Polychronopoulou Antonia
Published: February 2007

Ninety‐two women with common epithelial tumors of the ovary and 105 comparison women admitted for various orthopedic conditions were interviewed regarding demographic, socio‐economic and biomedical characteristics, including their use of coffee and tobacco. There was no association between tobacco smoking and ovarian cancer. However a statistically significant trend association was noted between coffee drinking and ovarian cancer (p ∼ 0.03). The association could not be explained in terms of any other variable included in the present study. The relative risk for women drinking two or more cups of coffee per day was 2.2 with 95% confidence limits 1.0–4.8. Several descriptive epidemiologic data are compatible with a causal association between coffee and ovarian cancer.
Cyclosporin A permits the distinction between specific T and NK activity generated in A human MLC
Authors: Landegren Ulf , Ramstedt Urban , Axberg Inger , Örn Anders , Wigzell Hans
Published: February 2007

Human lymphocytes, activated in mixed lymphocyte culture (MLC), express cytolytic activity against a range of target cell types. Cyclosporin A (CyA) efficiently prevents the development of cytotoxic T cells directed against target cells expressing the phenotype of the stimulator cells whilst not preventing an increase in natural killing (NK) activity measured against tumor targets. The drug was further shown not to influence the short‐term induction of increased NK activity by interferon. Already established T killer cells are not sensitive to CyA. The drug thus seems to be selectively involved in the induction of immune responses requiring T‐cell proliferation.
Use of an agar culture technique for establishing lymphoid cell lines from Marek's disease lymphomas
Authors: Payne L. N. , Howes K. , Rennie M. , Bumstead Janene M. , Kidd A. W.
Published: February 2007

Lymphoblastoid cell lines derived from Marek's disease (MD) lymphomas have been established with difficulty by a number of workers. We have compared with conventional liquid culture methods the efficiency of a new technique for establishing lymphoid cell lines in which lymphoma cells were cultured initially in agar medium. Cells from 39/79 lymphomas gave rise to loose lymphoid colonies in the seeded agar after 7 days' incubation at 41°C. Two types of macrophage colony also developed. When lymphoid colonies in agar were transferred to liquid culture, 23/39 gave rise to permanent lymphoid cell lines, compared with 8/33 comparable cultures initiated in liquid medium. Twenty‐nine new cell lines have been developed from Rhode Island Red, line 6 and line 7 chickens. All carry T‐cell markers and the MD tumour‐associated surface antigen (MATSA) and showed variable but low responsiveness to lectin mitogens. The new cell lines, when first established, consisted mainly of small, lymphocytoid cells but, after varying times, these changed into typical lymphoblastoid lines and an increased expression of an embryonic antigen was associated with this change. The lymphocytoid line cells were more slowly growing and densitydependent than were the lymphoblastoid cells, and lymphocytoid lines grew better at 41°C and lymphoblastoid lines better at 37°C. MD virus could be rescued from some of the lines but others appeared to be true nonproducers.
The site of integration of the herpes simplex virus type 1 thymidine kinase gene in human cells transformed by an HSV‐1 DNA fragment
Authors: Kit Saul , Hazen Marion , Otsuka Haruki , Qavi Hamida , Trkula David , Dubbs Del Rose
Published: February 2007

To analyze the site of integration of the herpes simplex virus type 1 (HSV‐1) thymidine kinase (TK) gene in biochemically transformed human cells, TK‐HeLa‐(BU25) cells were transformed to the TK+ phenotype by a cloned, 2 kbp Pvull fragment of HSV‐1 DNA. The transformed cells [HeLa(BU25)/TF pAGO PP3] were fused with mouse LM(TK−) cells, and human‐mouse somatic cell hybrid clones (LH PP3 clones 1,2,3,5 and 6) were isolated in HATG‐ouabain selective medium. The HeLa(BU25)/TF pAGO PP3 cells and the LH PP3 hybrid clones expressed HSV‐1‐specific TK activity and a her‐pesvirus‐associated nuclear antigen, and contained herpesvirus nucleotide sequences. Molecular hybridization experiments were carried out to map the HSV‐1 and flanking cellular nucleotide sequences in the biochemically transformed cells. These experiments demonstrated that the HSV‐1 nucleotide sequences were integrated at a single site, and that the same cellular nucleotide sequences flanked the viral DNA in transformed HeLa(BU25)/TF pAGO PP3 and LH PP3 clone 5 cells. TK− revertant subclones isolated by growing the LH PP3 clone 5 cells in BrdUrd (and diphtheria toxin) failed to form colonies in HATG medium, but retained HSV‐1 nucleotide sequences. Isozyme analyses on 21 gene‐enzyme systems representing 21 human chromosomes revealed that all of the LH PP3 clonal lines expressed human hexosaminidase B, which has been assigned to chromosome 5, and all were sensitive to diphtheria toxin, which is also a marker for chromosome 5. Chromosome analyses showed that chromosome 5 was the only human chromosome present in mitoses of LH PP3 clone 5 cells and that human chromosome 5 was present in most of the mitoses of LH PP3 clone 1,2,3, and 6 cells. The latter clones also contained 1 or 2 additional human chromosomes in some of the cells. As expected from the molecular hybridization analyses, TK− revertants of LH PP3 clone 5 cells retained portions of chromosome 5 and expressed human hexosaminidase B. The results indicate that HSV‐1 nucleotide sequences were stably integrated in the biochemically transformed cells, most likely in human chromosome 5.
Relationship between fibrin clot retraction and tumorigenesis in C3H/10T1/2 cells
Authors: Azzarone B. , Brouty‐Boyé D. , MacIeira‐Coelho A.
Published: February 2007

Fibrin clot retraction (FCR) was studied in C3H/10T1/ 2 murine fibroblasts. These cells were able to induce FCR with high efficiency during resting phase as well as during active growth. C3H/10/T1/2 cells which became tumorigenic after X‐irradiation lacked FCR activity. Non‐tumorigenic revertant clones regained the capacity to induce FCR, while revertants which progressively back‐reverted to the neoplastic state showed intermediate FCR activity. These unstable revertants, when again fully tumorigenic, completely lost FCR activity.
Chromosome rearrangements involved in the origin of trisomy 15 in spontaneous leukemia of AKR mice
Authors: Herbst E. W. , Gropp A. , Tietgen C.
Published: February 2007

Trisomy 15, known to be the predominant chromosome abnormality in leukemic cells of the AKR strain, develops even in animals of the subline AKR/RblAld with two constitutive Robertsonian translocation chromosomes (6.15). Among 10 leukemic animals of this subline exhibiting chromosomal anomalies, 6 showed trisomy of the whole Robertsonian translocation chromosome with the expression of combined trisomy 6 and 15 as the most frequent abnormality. Besides this, rearrangements were observed in five animals, most of them resulting from centric fission of the Rb (6.15) translocation chromosome. Trisomy 15 with two Rb (6.15) and an extra acrocentric 15 was found in 44% of spleen cells in one animal, and a new Rb translocation of chromosomes II and 15 was seen in 50 % of spleen and thymus cells of another animal. In both cases trisomy 15 without simultaneous trisomy 6 resulted. Thus, the triplication of a whole Rb (6.15) is frequent in leukemic AKR/Rb (6.15)1 Aid, and ensuing double trisomy 6 + 15 is tolerated by the leukemic cell. But the development of trisomy 15 combined with centric fission of Rb (6.15) without simultaneous trisomy 6 is another principle realized in leukemogenesis.
Suppression of natural killer (NK) activity by splenic adherent cells of low NK‐reactive mice
Authors: Riccardi Carlo , Santoni Angela , Barlozzari Teresa , Cesarini Carla , Herberman Ronald B.
Published: February 2007

Adherent cells with the ability to inhibit NK activity were found in the spleens of young 8‐week‐old SJL/J mice. Such suppressor cells were also found in the spleens of other low‐NK‐reactive strains, but not in the spleen of age‐matched high‐NK‐reactive strains. These suppressor cells had the characteristics of macrophages, since they were plastic‐ and nylon‐adherent, phagocytosed latex and iron particles, and were resistant to treatment with anti‐Thy‐1.2 serum plus complement. Their inhibitory activity appeared to be due to their production and/or release of soluble suppressive factor(s). Their suppressor activity was similar to that of pyran copolymer‐activated macrophages, which were previously shown to be suppressive for cytotoxicity by NK cells. We suggest here that macrophages may be involved in the physiological regulation of NK activity and may contribute to the low NK activity in some strains of mice.
Specific cytotoxicity against autologous tumour and proliferative responses of human lymphocytes grown in interleukin 2
Authors: Vose Brent M. , Bonnard Guy D.
Published: February 2007

Peripheral blood lymphocytes of cancer patients were sensitized in vitro to autologous tumour cells in mixed lymphocyte‐tumour culture (MLTC). Blast cells were isolated on discontinuous Percoll gradients from MLTC which showed significant stimulation of [<3>H]‐thymidine incorporation. Cultured T cells (CTC) were derived from these blasts by growth in conditioned medium containing interteukin‐2 (IL‐2) and maintained for up to 51 days by repeated feeding with IL‐2 and in some cases by addition of irradiated allogeneic blood mononuclear cells as “fillers”. These cultures showed specific cytotoxic reactivity against autologous tumour and in only a few cases was natural killing (NK) of K562 cells apparent. Restimulation of CTC with tumour was measured in primed lymphocyte tests (PLT). Increased uptake of [<3>H]‐thymidine was found upon stimulation by autologous tumour and allogeneic tumour of the same site and histology but there was no response to non‐related tumours or to a panel of allogeneic lymphocytes. No sensitization to autologous HLA D/DR could be detected by restimulation or cytotoxicity against monocytes in the majority of cases. These data suggest that, by careful selection of sensitised blasts from MLTC, it is possible to obtain CTC with both helper (proliferative) and cytotoxic T cells and that such CTC have specific reactivity against tumour cells. These cellular reagents will be useful in defining the antigenicity of human neoplasms and possibly in therapy.
Establishment of B‐lymphoblastoid cell lines from Marek's disease virus‐induced tumors in turkeys
Authors: Nazerian K. , Elmubarak A. , Sharma J. M.
Published: February 2007

Four lymphoblastoid cell lines were established from tumors of turkeys inoculated with high doses of the GA strain of Marek's disease virus (MDV). Unlike other MD lymphoblastoid cell lines of chicken origin, these MDV transformed turkey lines appear to be B lymphocytes and produce immunoglobulin. Growth characteristics of these cell lines are slightly different; however, they all produce low levels of MDV‐specific antigen and carry the complete genome of the virus as determined by virus rescue in the chicken or in duck embryo fibroblast cultures. These cell lines are pathogenic for chickens and produce virus‐induced MD lesions. All four lines are free of the herpesvirus of turkeys, reticuloendotheliosis virus, and three lines are also free of avian leukosis virus. They all have typical normal turkey chromosomes and are positive for Marek's disease tumor‐associated surface antigen.
Production and characterization of marmoset lymphoblastoid interferon
Authors: Abb Jochen , Abb Hannelore , Deinhardt Friedrich
Published: February 2007

We describe the production of marmoset lymphoblastoid cell interferon (IFN). Optimal yields of IFN were obtained when EBV‐transformed lymphoblastoid cell lines (LCL) at a cell density of 1 × 106/ml were incubated with 100 HAU Sendai virus/ml for 24 h. Sendai‐virus‐induced marmoset lymphoblastoid cell IFN was acid‐stable and exerted antiviral activity on both homologous and heterologous human cells, thus allowing its classification as IFN α. Marmoset lymphoblastoid cell IFN did not inhibit the growth of herpesvirus‐transformed marmoset T‐ or B‐cell lines, but markedly enhanced marmoset NK‐cell activity against human myeloid leukemia target cells. The use of lymphoblastoid cell IFN in marmosets in vivo may contribute to an understanding of the pathogenic role of IFN in herpesvirus‐induced lymphoproliferative diseases.
The mechanism of genetic resistance to marek's disease in chickens
Authors: Powell P. C. , Mustill Brenda M. , Rennie M. , Lee Lucy F.
Published: February 2007

Genetic resistance to Marek's disease in RPL line‐6 chickens is expressed not only at the level of host immunological responses against virus and tumour antigens, but also at the level of target lymphoid cells for virus infection and transformation. The nature of the target cell involved was investigated. Spleen cells from susceptible line‐7 chickens adsorbed more Marek's disease virus and turkey herpesvirus in vitro than line‐6 spleen cells. In the case of Marek's disease virus this was reflected in the replicative ability of the virus in vivo. Transplantation of thymus fragments from 1‐day‐old line‐7 chickens into thymectomized line‐6 chickens conferred a high degree of susceptibility on the latter, but the transplantation of spleen or bursa fragments had no significant effect. The reverse procedure, i.e. grafting of line‐6 thymi into line‐7 chickens, did not diminish the susceptibility of the recipients. In each treatment group the observed titres of leukocyte‐associated viraemia correlated with the susceptibility of the group to Marek's disease. Histologically the grafted thymus fragments became depleted of lymphocytes immediately after transplantation. By 6 days there was substantial recovery, apparently as a result of repopulation of the thymic epithelium by host stem cells. This was confirmed by transplanting thymus fragments between individuals of opposite sexes. Karyotype analysis showed that the thymus contained lymphocytes of the sex of the recipient. However, karyotype analysis of lymphoma cells taken from recipient line‐6 chickens that had received thymus grafts from line‐7 birds of the opposite sex showed that, in the majority of cases, the lymphomas consisted of cells of donor origin. It is concluded that the susceptibility of line‐7 chickens is largely attributable to the greater susceptibility of their T‐lymphocytes to infection and transformation by Marek's disease virus, and that this susceptibility can be transferred to genetically resistant line‐6 birds by adoptive transfer of the cells in the form of thymus fragments.
Monoclonal antibodies to two mouse bladder carcinoma antigens
Authors: Hellström Ingegerd , Rollins Nicola , Settle Scott , Chapman Philip , Chapman Warren H. , Hellström Karl Erik
Published: February 2007

Carcinomas of the urinary bladder of mice were induced by 3‐methyl‐cholanthrene or FANFT [(4‐5‐nitro‐2‐furyl)‐2‐thioazolyl formamide]. On transplantation in vivo, tumor lines consisting of well‐differentiated transitional‐cell carcinomas were established. Some tumors were also explanted in vitro. A rat was immunized with a pool of carcinomas and normal bladder tissue and its spleen cells were hybridized with NS‐I mouse myeloma cells. Supernatants of hybrid cells (“hybridomas;”) were screened for antibody binding to antigens present in bladder carcinomas but not in normal syngeneic urinary bladder, with cell extracts as targets. Hybridomas that appeared to have the required specificity were cloned, tested further against transitional‐cell bladder carcinomas, an anaplasic bladder tumor, rhabdomyosarcomas, a mammary carcinoma, myelomas and lymphomas, and normal adult urinary bladder, kidney, lung, spleen, heart, brain, thymus, and whole embryo. Antibody formed by one hybridoma, 2H5, gave significant binding to membranes from five of seven transitional‐cell carcinomas but not to membranes from any other tissues. A second hybridoma, IE6, formed antibody to an antigen present in bladder carcinomas and normal liver and, in smaller amounts, in several other normal and neoplastic tissues. Fluorescence microscopy established that both antigens were present at the cell surface of transitional‐cell bladder carcinomas. Immunoprecipitation and SDS‐polyacrylamide gel electrophoresis were used to identify the target antigens from 125l‐labelled cell membrane proteins. The antibody formed by 2H5 was found to identify a protein with a molecular weight in the range of 140 kilodaltons, which was detected in transitional‐cell bladder carcinoma and, in small amounts, in normal bladder. The molecular nature of the antigen defined by hybridoma IE6 is not known.
Trophoblastic and mesenchymal structures in rat yolk sac carcinoma
Authors: Sobis H. , Van Hove L. , Vandeputte M.
Published: February 2007

The presence of trophoblastic and mesenchymal structures in primary as well as in transplanted rat yolk sac carcinomas (YSC) is described. These structures were only recorded in rat yolk sac carcinomas derived from displaced yolk sac but never in embryo‐derived yolk sac carcinomas. It is suggested that the endodermal carcinoma cells displaying either a parietal or a visceral yolk sac pattern as well as the mesenchymal and trophoblastic structures may have a common cell ancestor.
High‐frequency generation of new immunoresistant tumor variants during metastasis of a cloned murine tumor line (ESb)
Authors: Bosslet Klaus , Schirrmacher Volker
Published: February 2007

A metastatic variant of a chemically induced lymphoma (ESb) from a DBA/2 mouse was found to activate in syngeneic hosts specific anti‐tumor cytolytic T lymphocytes (CTL) which recognized on the tumor a distinct tumor‐associated antigen. Upon metastasis of a cloned ESB tumor line from an s.c. site to the spleen, the tumor cells which were originally sensitive to lysis by anti‐ESb CTL became specifically immunoresistant. The development of immunoresistant variants after tumor‐cell transplantation followed a defined kinetic and organ pattern: they were first detected in the spleen, then also in the liver and in the late stage of tumor progression they were the predominant tumor type in all involved organs. No immunoresistant tumor variants were generated in immunoincompetent animals such as nude (nu/nu) mice. Immunoresistant variants also developed when immunosensitive ESb clones were inoculated into animals specifically preimmunized against ESb. In fact, these variants were the only type of cells eventually growing out from such animals causing death from metastasis in spite of the specific immune status of the host. The change of tumor antigen expression described here differs from antibodyinduced antigenic modulation in that it is genetically transmitted and stable in tissue culture. The immunoresistant tumor variants which did not preexist in the starting, twice‐cloned cell population represent a new type of immune escape variant.
Regulation of rat alpha‐fetoprotein production by methionine during ethionine‐hepatocarcinogenesis
Authors: Miyazaki Mashiro , Watanabe Akiharu
Published: February 2007

The levels of serum alpha‐fetoprotein (AFP) in rats were determined during hepatocarcinogenesis with ethionine, and the effects of methionine administration on serum AFP elevation in these animals were studied with the aim of investigating regulatory mechanisms of AFP production during carcinogenesis. Elevation of serum AFP was observed 6 weeks following the start of feeding a diet containing 0.25% ethionine and again at the 22nd week of feeding, when a well‐differentiated hepatoma had already developed. These biphasic elevations of serum AFP concentrations in rats fed a 0.25% ethionine‐containing diet decreased abruptly and significantly following a change to the basal diet either supplemented with or without 0.7% methionine. The possibility that regulation of AFP production in these rats may correlate with methionine metabolisms is discussed on the basis of the experimental data obtained.
Cell locomotion, a contributing factor in spread of the v2 rabbit carcinoma
Authors: Haemmerli Gisela , Arnold Beatrice , Sträuli Peter
Published: February 2007

In histological sections of s.c. transplanted V2 rabbit carcinoma, single tumor cells and small tumor cell groups were found at some distance from the main tumor mass. This led to the question of whether locomotion could represent a contributing factor in the invasiveness of the V2 carcinoma. The behavior of V2 cells was therefore recorded under experimental conditions of increasing complexity: on glass, on the surface of a normal explanted rabbit mesentery, and on and within mesenteries of rabbits which had received intraperitoneal implants of V2 carcinoma. Time lapse cinematography showed the locomotory activity of V2 cells to be unaffected by the different substrates. In all instances the carcinoma cells migrated singly, on the two plane substrates also in small groups, under production of large leading lamellae. Intraperitoneally implanted V2 cells, in addition to their migration on the surface of the mesentery, penetrated into the interior with continuation of their characteristic translocative motility. Although cell locomotion could be established as a mechanism in the invasiveness of the V2 carcinoma, we do not consider it to be the only relevant factor. Tumor cell proliferation and destructive effects of proteinases appear to be other mechanisms contributing to the functional complex of local spread.
Farming and mortality from non‐Hodgkin's lymphoma: A case‐control study
Authors: Cantor Kenneth P.
Published: February 2007

A case‐control study of non‐Hodgkin's lymphoma (NHL) and its subtypes among males was conducted using computerized mortality listings from the State of Wisconsin for the years 1968‐1976. Age, year of death, race, county of usual residence, marital status, and usual occupation were abstracted for the 774 records of male deaths due to NHL and a matched series of deaths due to other causes. The frequency of farming occupation among NHL cases was compared to the frequency among controls, and odds ratios (OR) were calculated. Farming was more common among cases than among controls (OR=1.22). The association of NHL with farming occupation was greater among decedents under 65 years of age (ORequlas;1.7) than among those who were older. The younger decedents were at higher risk of reticulum‐cell sarcoma (ORequlas;2.7) than of other cell types. The strength of the association increased over the 9‐year study period. County levels of selected agricultural characteristics were used as surrogate measures of farming exposures in residence counties of farmers and were summarized by factor analysis. Major findings were of elevated risk among younger farmers for reticulum‐cell sarcoma in counties high in summary measures of general agricultural activity (ORequlas;3.2), of small grain acreage and acres treated with insecticides (ORequlas;6.6), and of wheat acreage (ORequlas;4.4). Given the limitations of the data, further investigation of non‐Hodgkin's lymphoma in farmers is warranted.
Prospective evaluation of the leukocyte adherence inhibition (lai) test in breast cancer using a panel of extracts from known and unknown primary tumors
Authors: Fritze D. , Fedra G. , Kaufmann M.
Published: February 2007

The antigen‐induced leukocyte adherence inhibition (LAI) test is an assay of cellular immune reactivity which was expected to offer a promising adjunct to currently available diagnostic and monitoring procedures in cancer patients. We have applied this assay to (1) 83 inpatients clinically suspected of having breast cancer, (2) 50 outpatients before mammography, and (3) 37 healthy women. In order to account for the known heterogenicity of breast cancer, we performed LAI assays with extracts from 15 primary tumors of known and 14 primary tumors of initially unknown histology. Thus, the problem of tumor specificity in the LAI assay was tackled in a doubleblind fashion. The results obtained clearly show that breast‐tissue‐specific rather than tumor‐specific responses were detected by LAI testing. The LAI assay failed to discriminate between high‐risk patients with and without cancer and between extracts from breast tumors with and without carcinoma. The results are discussed with regard to the many claims for the detection of specific tumor immunity in the literature.
A cell‐surface antigen which is present in the ganglioside fraction and shared by human melanomas
Authors: Yeh M.‐Y. , Hellström I. , Abe K. , Hakomori S. , Hellström K. E.
Published: February 2007

We have raised a hybridoma, 4.2, which forms an IgM antibody to an antigen expressed on cultivated cells from most human melanomas, more infrequently on cells from other human tumors, and very weakly on cultivated fibroblasts, T cells and B cells. The antigen can be detected in biopsy material of human melanoma and, in smaller amounts, in fresh samples of normal human lung and kidney. Preliminary biochemical characterization indicates that it is associated with the ganglioside fraction. We feel that the antigen (referred to as 4.2) has a sufficient degree of tumor specificity to be rated as a human melanoma‐associated antigen.
Modulation of protein phosphorylation in human colon adenocarcinoma cell membrane preparations by epidermal growth factor in vitro
Authors: Zenisek S. C. , Fernandez‐Pol J. A.
Published: February 2007

Incubation of membranes prepared from the human colon adenocarcinoma cell line LoVo in vitro with [γ‐32P]ATP demonstrated numerous components whose phosphorylation was stimulated several fold by epidermal growth factor (EGF). One major component of Mn 170 K, which was either undetectable or very weakly phosphorylated in the absence of EGF, was primarily affected by exposure to EGF. The phosphorylation of the 170 K Mr membrane component required the presence of Mn2+; Mg2+ was ineffective. Although the phosphorylation of many LoVo membrane components was significantly modified by cAMP or dibutyryl‐cAMP, none of these cyclic nucleotides appeared to be involved in the phosphorylation of the 170 K membrane component in the presence or absence of EGF. The phosphorylation system of the LoVo membranes efficiently utilized (γ‐32P)GTP in both the basal and EGF‐stimulated reactions. All the membrane components phosphorylated in the absence or presence of EGF, except a band comigrating with the tracking dye front, were digested by trypsin. The possible glycoprotein nature of the 170 K dalton phosphoprotein was indicated by the fact that the 170 K dalton band comigrated with a periodic acid‐Schiff base‐stained band. These findings suggest that one of the biochemical steps in the mechanism of action of EGF in LoVo cells is enhanced phosphorylation of several membrane proteins, especially that of a glycoprotein of Mr 170 K, by a membrane‐bound cyclic nucleotide independent protein kinase.
Interferon‐independent, lectin‐induced augmentation of murine natural killer cell activity
Authors: Brunda Michael J. , Varesio Luigi , Herberman Ronald B. , Holden Howard T.
Published: February 2007

The ability of lectins to augment natural killer (NK) cell activity was demonstrated using splenic effector cells from athymic nude mice. The addition of Helix pomatia agglutinin to the assay or pretreatment of the effector cells with lectin resulted in increased cytotoxicity against the human cell line K562, a relatively poor target for spontaneous mouse NK activity. When additional lectins were tested, NK activity was increased markedly by some lectins while others had no effect. The augmentation of cytotoxicity was dependent on the concentration of lectin added. Nylon‐wool‐nonadherent, nu/nu splenic effector cells mediated the lectin‐induced cytotoxicity, and antiasialo GMI plus complement abolished activity, indicating that the cells mediating the cytotoxicity were NK cells and not mature T cells, B cells or macrophages. When spleen cells from mice having different levels of NK activity were evaluated in this system, the magnitude of the lectin‐induced cytotoxicity obtained correlated with the level of spontaneous NK activity and no increased cytotoxicity was found using cell populations that had low spontaneous NK activity. By testing a panel of target cells, we found that certain human, mouse and rat cell lines, which had low to moderate susceptibility to spontaneous murine NK activity, were sensitive to lectin‐induced NK‐cell‐mediated cytotoxicity while others were completely resistant; resistance or susceptibility to cytotoxicity was not directly correlated with the ability of lectins to bind to the target cell. The lectin‐induced cytotoxicity was independent of interferon (IFN) since detectable levels of IFN were not produced in the cultures of lectins and effector cells, cytotoxicity was not increased when exogenous IFN was added to the assay, and inhibitors of RNA and protein synthesis, which block the action of IFN, had no effect on the cytotoxicity. These results indicate that NK cells can mediate lectin‐induced cytotoxicity and the implications of lectin interaction with NK cells are discussed.
Modulation of natural killer sensitivity of murine trophoblast cells by tumor promoter and interferon
Authors: Tanaka Kenichi , Chang Kenneth S. S.
Published: February 2007

The in vitro established lines of murine placental trophoblast cells showed little membrane expression of H‐2 antigens and a high degree of sensitivity to natural killer (NK)‐cell‐mediated cytotoxicity. This NK‐sensitivity was decreased either by short‐term treatment of these cells with murine interferon (IFN) or by culture for more than 4 days in the presence of a tumor promotor, 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA). This effect of TPA was reversible after removal of TPA from the culture medium. However, IFN treatment of trophoblast cells cultured previously in TPA medium resulted in restoration of NK‐sensitivity to the original level exhibited by cells untreated with IFN or TPA. The mechanism for this antagonistic effect is not clear. The decrease in NK‐sensitivity of IFN‐ or TPA‐treated trohphoblast cells was not due to the loss of NK‐recognition membrane structures, or to induction of prostaglandin which elevates cyclic‐AMP levels. Inhibition of protein synthesis by cycloheximide restored the NK‐sensitivity of TPA‐treated trophoblast cells, indicating the possible contribution of de novo synthesized protein(s) which could confer NK‐resistance. The TPA‐treated trophoblast cells became more tumorigenic, producing larger tumors and a higher mortality than the untreated controls when inoculated into mice. The possible roles of NK cells in trophoblastic diseases and feto‐maternal relationships are discussed.
Cross‐reactions between tumor cells and allogeneic normal tissues. inhibition of a syngeneic lymphoma outgrowth in h‐2 and non‐h‐2 alloimmune balb/c mice
Authors: Parmiani Giorgio , Luisa Sensi M. , Carbone Giusi , Colombo Mario , Pierotti Marco , Ballinari Dario , Hilgers Jo , Hilkens John
Published: February 2007

To test whether alloimmunization with H‐2 or/and non‐H‐2 different normal tissues may increase the immunity to syngeneic tumors, groups of BALB/c (H‐2d) mice were immunized with a series of allogeneic lymphoid cells and then challenged i.p. with syngeneic lymphoma cells. The outgrowth of otherwise lethal doses of the Moloney virus‐induced lymphoma YC8 and of its clones was inhibited in BALB/c mice immune to DBA/2 (H‐2d), C3Hf (H‐2k), C3H.SW (H‐2b), C3H.OH (H‐2o2) and to B10 background tissues but not in mice immunized to A/He, BALB.K (H‐2k) or BALB.B (H‐2b) normal tissues. Anti‐YC8 effect was also induced by immunizing BALB/c recipients with a pool of five different allogeneic cell lines which included C3Hf, C57BL/6J (H‐2b), N:NIH (H‐2q), B10.M (H‐2f), and DBA/2 lymphoid cells. No growth inhibition of other BALB/c lymphomas induced by Moloney virus (LSTRA), X‐rays (RL♂I) or urethane (UR‐I) was evident in alloimmune mice. In vivo transfer of growth inhibition of YC8 was obtained with BALB/c anti‐B10.D2 peritoneal exudate cells in a Winn assay. The ability of these alloimmune lymphoid cells to delay significantly the survival time of BALB/c mice injected with the mixture of immune cell and YC8 cells was abrogated by anti‐Thy 1.2 plus C' treatment. In addition, nu/nu BALB/c mice were unable to develop resistance to YC8 outgrowth after alloimmunization. The results of this study show that: (1) syngeneic growth of a lymphoma can be prevented by alloimmunization with normal cells; (2) this cross‐reaction involved non‐H‐2 antigens; (3) the phenomenon appeared to be mediated by T cells.
Induction of γ‐glutamyltranspeptidase‐positive altered hepatocytic lesions by combination of transplacental‐initiation and postnatal‐selection
Authors: Ogawa Katsuhiro , Yokokawa Kinya , Tomoyori Takashi , Onoé Tamenori
Published: February 2007

The purpose of this study was to induce in postnatal life the selective growth of altered hepatocytic populations which had been induced in utero by various chemicals. Pregnant rats of a Wistar strain were given a single dose of various chemical carcinogens on the 18th gestational day. From two months postpartum, both the mothers and offspring were given a diet containing 2‐acetylaminofluorene (2‐AAF) at a concentration of 0.02% for two weeks. Then, at the end of the first week after the 2‐AAF feeding, a two‐third partial hepatectomy was performed. All the animals were killed one week after the partial hepatectomy and were examined for the incidence of γ‐glutamyltranspeptidase (GGT)‐positive altered hepatocytic foci in the liver. The transplacental administration of not only a hepatic carcinogen, diethylnitrosamine (DEN) but also 7,12‐dimethylbenzanthracene (DMBA), which does not usually produce hepatocellular carcinomas in adult rats, induced GGT‐positive altered hepatocytes in the liver of the offspring. These hepatocytes grew into grossly visible hyperplastic nodules within a week after the two‐third partial hepatectomy. The possible applicability of the transplacental initiation‐postnatal selection model for the short‐term assay of transplacental carcinogenicity is discussed.
Anti‐tumor immunity in b‐lymphocyte‐deprived mice. iii. immunity to primary moloney sarcoma virus‐induced tumors
Authors: Gordon Julius , Holden Howard T. , Segal Shraga , Feldman Michael
Published: February 2007

Tumor induction and immunity to tumors were studied following the injection of Moloney sarcoma virus (MSV) into mice whose B‐lymphocyte functions had been suppressed by the chronic administration of anti‐IgM antibodies. Two preparations of MSV were used; one which gives rise to tumors which uniformly regress in normal adult mice, and another which elicits progressively growing tumors in the majority of recipients. The tumor incidence, mean tumor size, and tempo of regression were not modified by treatment with anti‐IgM. However, whereas tumors induced by the regressor virus were all rejected in 19 NRG‐treated and 29 untreated recipients, continued growth was obtained in 2 of 23 B‐lymphocytedeprived mice. Furthermore, in 9 additional mice from this group, apparent rejection was followed by tumor recurrence at the site of the initial tumor. Continued growth was accompanied by widespread metastasis. These tumors were freely transplantable to normal syngeneic recipients. Metastasis and transplantability were also detected in 7 of 24 anti‐IgM‐treated mice given progressor virus, but were not seen in the control animals. Recurrence and metastasis was obtained despite the presence of high levels of specific cytotoxic T lymphocytes in the spleen. It is concluded that B lymphocytes or their products play an essential role in host protection against MSV‐induced tumors.
Activation of an endogenous mouse type c virus by uv‐irradiated murine cytomegalovirus
Authors: Sergiescu Dina
Published: February 2007

Infection of Kirsten sarcoma virus‐transformed non‐producer BALB‐3T3 mouse cells with UV‐irradiated mouse cytomegalovirus (MCMV) resulted in activation of a xenotropic type C virus detected by infectious center formation in permissive rat or mink cells. The levels of type C virus activated by MCMV were related to the UV dose applied. Unter optimal conditions the frequencies of activation varied from 3.0 to 8.0 × 10−4. The capacity of MCMV to activate type C virus was abolished by heat inactivation and by neutralization with specific antiserum against MCMV. Virus induction decreased under conditions of cell exposure to hydroxyurea or actinomycin D, inhibitors of DNA and RNA synthesis, respectively, with actinomycin D having a greater inhibitory effect. This suggests that both DNA and RNA synthesis are required for UV‐MCMV induction of murine xenotropic virus.
Tumor enhancing T lymphocytes in mice: Further studies on characteristics and mechanism of activity
Authors: Small Myra
Published: February 2007

In order to test the possibility that tumor‐enhancing T lymphocytes can suppress other lymphoid cells, such as those with anti‐tumor activity, their effect was tested in an allogeneic response of cell‐mediated lysis. Normal thy‐mocytes and spleen cells from mice with advanced tumors, two populations which enhance the growth of solid tumors, both suppressed the generation of CML. Since these results suggest that the mechanism of enhancement by T cells may resemble suppression in other immune responses, we looked for Fc receptors on the sensitized cells involved in tumor enhancement Cells expressing Fc receptors appeared to be necessary for enhancement of tumor growth to occur.
Effect of mouse interferon on cell transformation and virus production in rat cells exogenously infected with moloney murine sarcoma and leukemia viruses
Authors: Huleihel Mahmoud , Aboud Mordechai
Published: February 2007

Foci of transformed cells, produced by MSV(124), appeared to result only from the primary infection, since this virus stock yielded a virus‐nonproducing infection. On the other hand, the majority of foci scored in MSV/MLV‐infected cultures, were generated by multiple secondary infections with the progenies of the primary infection. Mouse interferon (IF) was highly inhibitory for cell transformation by both virus stocks. However, this inhibition was apparent in MSV(124) infected cultures only if IF was added at least 12 h before infection, whereas in MSV/MLV‐infected cultures IF was highly effective even if added 24 h after infection. The inhibition of focus formation by MSV(124) was irreversible after removal of IF, suggesting that IF inhibited an early step before provirus integration into the host genome. By contrast, in MSV/MLV‐infected cultures focus formation was almost completely restored after recovery from the IF effect Nevertheless, examination of virus production after IF removal proved that in MSV/MLV infection, too IF exerted and inhibitory effect before provirus integration.
Cell‐surface antigens of a clonal human embryonal carcinoma cell line: Morphological and antigenic differentiation in culture
Authors: Andrews Peter W. , Goodfellow Peter N. , Shevinsky Lynne H. , Bronson David L. , Knowles Barbara B.
Published: February 2007

A cloned human embryonal carcinoma (EC) cell line has been derived from a testicular teratocarcinoma, and reproducibly forms EC tumors when injected into athymc (nu/nu) mice. These human EC cells are characterized by a newly described stage‐specific embryonic antigen, SSEA‐3. Unlike murine EC cells, they express major histocompatibility antigens (HLA‐A, B, C and β2‐microglobulin) but do not express the embryonic antigen SSEA‐I. We also report that these cells appear to be capable of differentiation and that this can be induced by initiating cultures at low cell density. Differentiation is marked by the appearance of morphologically distinct cells and by the induction of SSEA‐I, whereas the expression of other antigens, including SSEA‐3, is initially diminished. This well‐characterized system of human EC cells provides a model for the future investigation of other human teratocarcinoma cell lines and for the analysis of cellular differentiation during early human development.
In vitro transformation by avian erythroblastosis virus recruits cells of erythroid lineage with varying degree of differentiation
Authors: Therwath Ahmedunny , Scherrer Klaus
Published: February 2007

We have previously shown that AEV infection of leukosis‐free chickens provokes an erythroleukemia in the infected birds, and that the target cell for virus transformation is most likely an early pro‐erythroblast comparable to the BFU‐E. The virus infection correlates with a block in differentiation which was studied at a specific cellular gene level, namely that of the globin genes. In live birds, the viral transformation has been found to affect the transcriptional activity of two out of three adult globin genes and the phenotypic expression of the third. Indeed, the αA gene that is transcribed is silent as well, since its transcription product is fully eliminated in the nucleus following an “abortive processing”. Chick bone marrow cells can also be transformed in vitro by AEV in which case the virus recruits, as targets, cells of the erythroid lineage belonging to a wider spectrum and hence in varying degrees of differentiation. In contrast to the results obtained with in vivo transformed cells, molecular hybridization with globin cDNA probes showed that in the erythroblasts transformed in vitro under tissue culture conditions all the three adult globin genes are transcriptionally active. In fact, low but detectable amounts of globin mRNA sequences are present in both the nuclear and cytoplasmic compartment of the cell prior to exposure to any chemical inducers of red cell differentiation. Judging from our present results, we may propose that AEV transformation in vitro does not shut off but only modulates the already functioning erythroid cell differentiation program.