bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation of a series of novel variants of murine mammary tumor viruses with broadened host ranges
Authors: Howard David K. , Schlom Jeffrey
Published: February 2007

We have previously isolated mouse mammary tumor virus (MMTV) host range variants by serial virus passage in feline cells. These variants productively infect cells of a broad range of species but replicate most efficiently in feline cells. We report here the isolation of a series of novel MMTV host range variants that have the ability to replicate with high efficiency in murine, rat, canine and human cells, respectively; these variants were isolated by serial virus passage in cells of each respective species. These new variants, furthermore, all retained their ability to efficiently replicate in feline cells, and each exhibited unique host range properties. The novel MMTV variants obtained from murine, rat, feline, canine, and human cells showed no overt evidence of recombination with endogenous type‐C viruses in that they retained their antigenic reactivities in group‐specific radioimmunoassays for MMTV polypeptides, and were unreactive for type‐C virus proteins when tested by radioimmunoassays and DNA polymerase assays. These novel MMTV host range variants now broaden the spectrum of studies that can be undertaken involving MMTV replication and the initiation and promotion of virus‐mediated mammary cell transformation.
Potential diagnostic and prognostic significance of the transformation‐enhancing factor(s) in the plasma cryoprecipitate of tumor patients
Authors: Mignatti Paolo , Ascari Edoardo , Barlati Sergio
Published: February 2007

A biological activity which enhances cell transformation (TEF) in Rous sarcoma virus temperature‐sensitive mutant‐infected cultures has been evidenced in the plasma cryoprecipitate from patients affected with different types of neoplastic disease. In the present paper we report data on the analysis of TEF activity in the plasma cryoprecipitates from leukemic and tumor patients tested either before or during specific antineoplastic treatments. The screening of 57 cases of different neoplastic diseases and of 57 controls, healthy subjects or patients affected with other non‐neoplastic diseases indicates that TEF activity is generally related to the presence of neoplasia. Furthermore, a follow‐up of patients from the onset of the disease through its evolution during therapy suggests that variations of TEF activity in the plasma cryoprecipitate correlate well with the clinical and pathological conditions, thus indicating the TEF as a potential marker for monitoring cancer patients.
Circulating immune complexes in patients with bone tumours
Authors: Eiras Amada Segal , Robins R. A. , Baldwin R. W. , Byers V. S.
Published: February 2007

Sera from 62 patients with osteogenic sarcoma and 12 with malignant giant‐cell tumour were tested for the presence of immune complexes by the 125I‐Clq binding assay. Elevated serum Clq binding activity was found in 67.7% of the osteogenic sarcoma patients and in 75% of the giant‐cell tumour patients. These results were compared with those obtained with five sera from patients with benign bone tumours and 20 sera from normal young donors. In the last two groups, the incidence of elevated Clq‐binding activity was 0% and 5%, respectively. In some patients with giant‐cell tumours, preand post‐operative serum samples were studied, showing a decrease in test values after tumour resection. Preliminary sequential studies of individual patients indicate that the 125I‐Clq binding assay may be useful for monitoring patients with bone tumours.
Kaposi's sarcoma and its relationship to cytomegalovirus (CMV) III. CMV DNA and CMV early antigens in Kaposi's sarcoma
Authors: Giraldo G. , Beth E. , Huang E.‐S.
Published: February 2007

DNA‐DNA reassociation kinetics, anti‐complement immunofluorescence (ACIF) and ACIF‐blocking tests were used to search for cytomegalovirus (CMV) gene products in Kaposi's sarcoma (KS) biopsies and early cell cultures deriving from them. Three of eight tumor biopsies were positive for CMV DNA; two of them at 0.35 genome/cell and one at one copy of 25% genome/cell. CMV‐related antigens, mainly localized in the nucleus, were found in cryostat sections of seven of 31 tumor biopsies and four of 12 KS cell lines at early passage level. It appears that the antigen is present in a high number of tumor cells, like the Epstein‐Barr virus nuclear antigen (EBNA) in EBV‐transformed cells. Inevitably, the increasing data concerning the oncogenic potential of CMV lead on to consideration of the increasing evidence of its association with Kaposi's sarcoma, a multiple hemorrhagic sarcoma with an epidemiologic distribution in Africa similar to that of Burkitt's lymphoma.
Chromosome abnormalities, clinical and morphological manifestations in metamorphosis of chronic myeloid leukemia
Authors: Oläh Éva , Kiss Attila , Jakq János
Published: February 2007

Seventeen cases of chronic myeloid leukemia (CML) in metamorphosis have been investigated by cytogenetic methods. Six patients were studied in slow transformation and others in the terminal blastic phase of the disease. Of these, 3 cases were myeloid, 3 myelomonocytic, I megakaryoblastic, I promyelocytic and 4 lymphoid in their morphological and cytochemical appearance. Some correlation could be observed between the clinical, morphological, cytochemical and cytogenetic findings of the different subgroups. The results demonstrate the importance of chromosome investigations in the early diagnosis of metamorphosis and in distinguishing the different subgroups of the terminal stage of CML.
Effect of the intermittent administration of N‐nitrosopyrrolidine (NPYR) on the tumor incidence in Sprague‐Dawley rats
Authors: Habs M. , Habs H. , Schmähl D.
Published: February 2007

N‐Nitrosopyrrolidine (NPYR) was administered orally to 320 Sprague‐Dawley rats. An additional group of 80 rats served as an untreated control. There were four experimental groups in which the effects of different periods of dosing and varied intervals without treatment were compared. The total dose for all the groups was constant and was 792 mg/kg body weight. The schedules of carcinogen application had a significant effect on the observed cancer risk. The different tumor indicences in the individual groups could not be attributed to differences in the survival pattern, but were related to the changes in the different treatment schedules.
Cytolytic activity against tumor cells by macrophage cell lines and augmentation by macrophage stimulants
Authors: Taniyama Tadayoshi , Holden Howard T.
Published: February 2007

Previous studies have shown that macrophage cell lines retained the ability to phagocytize, to secrete lysosomal enzymes, and to function as effector cells in antibody‐dependent cellular cytotoxicity. In this paper, the cytolytic activity of murine macrophage cell lines against tumor target cells was assessed using an 18‐h 51Cr release assay. Of the macrophage cell lines tested, RAW 264, PU5‐1.8 and IC‐21 had intermediate to high levels of spontaneous cytolytic activity, P388D1 and J774 had low to intermediate levels, while WEHI‐3 showed little or no cytolytic activity against RBL‐5, MBL‐2 and TU‐5 target cells. Tumor‐cell killing by macrophage cell lines could be augmented by the addition of macrophage stimulants, such as bacterial lipopolysaccharide and poly I:C, indicating that the activation of macrophages by these stimulants does not require the participation of other cell types. Treatment with interferon also augmented the tumor‐cell killing by macrophage cell lines. Although the mechanism by which these cell lines exert their spontaneous or boosted cytotoxic activity is not clear, it does not appear to be due to depletion of nutrients since cell lines with high metabolic and proliferative activities, such as WEHI‐3 and RBL‐5, showed little or no cytotoxicity and supernatants from the macrophage cell lines did not exert any cytotoxic effects in their assay. Thus, it appears that the different macrophage cell lines represent different levels of activation and/or differentiation and may be useful for studying the development of these processes as well as providing a useful tool for analyzing the mechanisms of macrophage‐mediated cytolysis.
FV‐2r‐mediated resistance of mouse bone‐marrow cells to friend spleen focus‐forming virus infection
Authors: Yoosook Chalobon , Steevesz Richard , Lilly Frank
Published: February 2007

A target cell assay based on the formation of infectious centers (IC) was used to characterize the Fv‐2resistance gene of mice. Dose‐response curves were obtained for the number of IC generated from incubated mixtures of bone‐marrow cells and Friend virus (FV). The hemopoietic stimulus of bleeding increased the frequency of potential 〈target〉 cells capable of forming 1C in DBA/2 but not in D2.Fv‐2r mice; however, even without the bleeding stimulus D2.Fv‐2r mice contained fewer target cells in their bone marrow than DBA/2 mice. During the first 48 h postinfection a massive dose of FV overcame the inhibitory effect of the FV‐2r gene as measured by the release of FV from the spleen. However, the concentration of 1C recoverable from the spleens of these infected mice was still much lower in the D2.Fv‐2r strain. When irradiated F1 hybrid hosts were used as recipients for the proliferation of infected donor cells, splenic 1C were not generated as efficiently from infected bone‐marrow cells of D2.Fv‐2r origin as from those of DBA/2 origin. However, the amounts of SFFV recoverable were approximately the same. Similarly, after in vitro infection there was no great difference between the amounts of SFFV released from bonemarrow cells of DBA/2 and D2.Fv‐2r mice. We conclude that the primary effect of the Fv‐2r gene may be to inhibit the formation and proliferation of 1C in vivo, and that SFFV replication could be inhibited secondarily.
Metastasis: Reticuloendothelial system and organ retention of disseminated malignant cells
Authors: Glaves Dorothy
Published: February 2007

The lung retention patterns of B16 melanoma cells were determined after intravenous injection of [125l]dUrd‐labelled tumor cells into B16 melanomabearing mice. Experiments were performed with mice undergoing acute or chronic reactions to bacterial endotoxin or zymosan, both of which were shown to modify the activity of the reticuloendothelial system as assessed by carbon clearance assays. On the one hand, the release of arrested melanoma cells from the lungs was retarded in mice with both endotoxin‐ and zymosaninduced acute inflammation. There was a parallel increase in the numbers of pulmonary tumor nodules which developed after injection of non‐radiolabelled melanoma cells into similarly treated groups of mice. On the other hand, fewer tumor cells were retained in the lungs of mice undergoing chronic responses to endotoxin, and fewer pulmonary tumor nodules subsequently arose after injection of unlabelled cells. However, in mice pre‐treated with zymosan, retention of melanoma cells was not different from that in controls and greatly increased numbers of pulmonary nodules grew in zymosan pre‐treated mice receiving nonradiolabelled cells. These experiments were discussed in terms of the contribution of the reticuloendothelial system to the release of arrested cancer cells from the pulmonary vasculature.
Establishment of a cell line (NPC/HK1) from a differentiated squamous carcinoma of the nasopharynx
Authors: Huang D. P. , Ho J. H. C. , Poon Y. F. , Chew E. C. , Saw D. , Lui M. , Li C. L. , Mak L. S. , Lai S. H. , Lau W. H.
Published: February 2007

A long‐term cell culture epithelioid cell line was established from a recurrent squamous carcinoma of the nasopharynx of a Chinese male 17 1/2 years after radiation therapy. The cell line, designated NPC/HKI, has been passaged 72 times over a period of 1 year. The cells have been shown by light and electron microscopies to be of the squamous epithelial type. When they were transplanted subcutaneously into the back of athymic nude BALB/c (nu/nu) mice, tumors developed at the sites of inoculation, which on histological examination were shown to be well‐differentiated squamous carcinomas, similar in morphology to the recurrent human tumor from which they were derived. Karyotypic analysis of cells from the cell line demonstrates an aneuploid human type with a modal chromosome number of 74 with both numerical and structural aberrations. Viral particles or Epstein‐Barr viral nuclear antigen (EBNA) has not been demonstrated in the cells from the primary culture or several of the subcultures tested. The presence of EBNA in touch smears prepared from the biopsy tissue was inconclusive. Infection of the subcultured cells with EBV from P3HR1 and B95‐8 cells was unsuccessful.
Multiple cases of Burkitt's lymphoma and other neoplasms in families in the north mara district of Tanzania
Authors: Brubaker G. , Levin A. G. , Steel C. M. , Creasey G. , Cameron H. M. , Linsell C. A. , Smith P. G.
Published: February 2007

In an area of Tanzania in which Burkitt's lymphoma (BL) is endemic, five families are described in which multiple cases of BL were found or BL occurred with other neoplasms. The patients include two brothers and one half‐brother with BL, two brothers with BL, a woman with nasopharyngeal carcinoma (NPC) whose daughter had BL, a boy with BL whose sister developed chronic myelogenous leukaemia (CML), and a man with CML whose son developed BL. The two full‐sib pairs with BL is significantly more than would be expected to have arisen by chance and the association of BL with NPC and CML among close relatives is remarkable in view of the rarity of the last two neoplasms in the study area. It is suggested that genetic factors may be important in determining susceptibility to the three malignancies in this population, but the possibility that the clustering of cases within families may be due to local environmental factors cannot be excluded.
Membrane‐associated antigens on tumor cells from transitional‐cell carcinoma of the human urinary bladder. I. Immunological characterization by xenogeneic antisera
Authors: Schneider Michael U. , Troye Marita , Paulie Staffan , Perlmann Peter
Published: February 2007

An antiserum was raised in rabbits by immunization with a human tumor cell line, T‐24, derived from transitional cell carcinoma (TCC) of the urinary bladder. The specificity of the IgG fraction was assessed by antibody‐dependent cellular cytotoxicity (ADCC), using purified blood lymphocytes from healthy human donors as effector cells and seven human cell lines as target cells (T‐24 and two additional TCC‐lines, two normal urothelial lines, one colon carcinoma and one malignant melanoma). The IgG induced strong lysis of all seven target cell types. However, lysis of the five urothelial lines was significantly stronger than that of the control tumors. Conversely, antisera to either of the control tumors induced a significantly stronger lysis of the homologous tumors than of the urothelial cells. All antisera contained antibodies to fetal bovine serum but removal of these by absorption did not change the specificity of the ADCC reactions. When the anti T‐24 serum was exhaustively absorbed with glutaraldehyde‐fixed spleen homogenate, the cytotoxicity to the control tumor targets was abolished. Although absorption reduced the antibody titer of the IgG preparation, ADCC to the TCC targets remained at a high level. There was no difference in the degree of lysis of the three TCC targets. Lysis of the two target lines from normal urothelium was slightly lower than that of the tumor cells. The results indicate that the anti‐TCC serum contained antibodies to one or several antigens shared by five urothelial cell lines but not by the control tumors. Whether or not it also contained antibodies to TCC‐associated antigens remains to be established. The molecular basis for these findings will be given in the accompanying paper.
Plasma membrane‐associated antigens on tumor cells derived from transitional‐cell carcinoma of the human urinary bladder. II. Identification at the molecular level of plasma membrane‐associated antigens
Authors: Schneider Michael U. , Paulie Staffan , Troye Marita , Perlmann Peter
Published: February 2007

The surface proteins of seven human cell lines (three bladder carcinomas (TCC), two normal urothelial lines, one colon carcinoma, and one malignant melanoma) were labelled with 125I by the glucose oxidase‐lactoperoxidase technique. Plasma membranes of the cells were isolated and analysed by sodium dodecyl sulphate electrophoresis (SDS‐PAGE). When analysed under reducing conditions by staining with protein stain, ˜45 distinct membrane polypeptides were detected in all membrane preparations. Although the banding patterns for all cell lines were very similar, a 23 K and a 110 K band were only seen in the five unrothelial lines. When the same gels were analysed by autoradiography, between 13 and 17 bands were detected for each of the cell lines. However, in this case, analysis revealed individual and stable banding profiles for each. One 180 K band and one 100 K band were only seen in the auto‐radiographs of the two normal lines but not in those of the tumor membranes. Analysis under non‐reducing conditions gave similar results. The antigenicity of these surface components was analysed by incubating detergent extracts of surface‐iodinated cells with IgG from a rabbit anti‐TCC serum, absorbed with fetal bovine serum and bound to protein A (from Staphylococcus aureus) on a matrix of Sepharose 4B. Analysis of the eluates by autoradiography after SDS‐PAGE under reducing conditions showed that many of the labelled polypeptides were antigenic and shared by all seven cell lines. Analysis of eluates from IgG preparations, exhaustively absorbed with human spleen, revealed the presence of at least one antigenic 110 K polypeptide confined to the membrane of the urothelial cells. Preparation of a rabbit antiserum to this 110 K component, isolated from one of the TCC‐lines and tested by ADCC, indicated that this polypeptide constitutes an important surface antigen, present on urothelial cells of both TCC‐and normal origin but absent from the colon carcinoma and malignant melanoma used for control.
Long‐term experience with burkitt's lymphoma in uganda
Authors: Olweny Charles L. M. , Katongole‐Mbidde Edward , Otim David , Lwanga Stephen K. , Magrath Ian T. , Ziegler John L.
Published: February 2007

The cumulative results and long‐term follow‐up of all patients with Burkitt's lymphoma treated at the Uganda cancer Institute Kampala are reported. The annual admission rate is 29. The tumor patients commonly present with jaw swelling (72%), abdominal swelling (56%) and central nervous system involvement (30%). Complete response rate is achieved in a high proportion of patients (81 %). About 50% of these relapse, equal numbers relapsing before and after 3 months. The most important factor influencing remission duration and survival is disease stage. Other important factors are treatment protocols and, to a lesser extent, the type of relapse. Central nervous system relapse does not necessarily augur poor prognosis as second remissions and long‐term survival can be achieved with appropriate therapy. Presently 25% of all treated patients have survived free of disease well beyond 5 years.
NATURAL CELLULAR REACTIVITIES MEDIATED BY SPLENOCYTES FROM MICE BEARING THREE TYPES OF PRIMARY TUMOR
Authors: Ehrlich Rachel , Efrati Margalit , Bar‐Eyal Aviva , Wollberg Miriam , Schiby Ginette , Ran Maya , Wrrz Issac P.
Published: February 2007

The ability of splenocytes from mice bearing three types of primary tumor to lyse YAC‐l target cells (NK activity) and to inhibit [125l]dUrd incorporation ([125l]dUrd l‐l = cytostasis) into B16‐F10 target cells was compared to the ability of normal splenocytes to perform such activities. The tumor systems used were urethane‐induced lung adenomas in BALB/c mice, di‐methylbenzanthracene (DMBA)‐induced tumors in hormonally‐stimulated BALB/c mice and mammary tumors in force‐bred C3HeB mice. The two types of natural cellular reactivity in lung adenoma‐bearing mice were unaffected. The NK activity of mice bearing DMBA and forced‐breeding‐induced tumors was suppressed. The cytostatic ability of splenocytes from mice bearing DMBA‐induced tumors was significantly elevated. The spleens of mice bearing primary DMBA‐induced tumors contained cells able to suppress NK activity or to compete against target cells for NK cells.
Plasminogen activator synthesis accompanying chemical carcinogen‐induced in vitro transformation of syrian hamster and guinea‐pig fetal cells
Authors: Slsskin Enid E. , Weinstein I. Bernard , Evans Charles H. , Dipaolo Joseph A.
Published: February 2007

The production of the extracellular protease, plas‐minogen activator, in relationship to growth in semi‐solid medium and tumorigenicity has been studied in Syrian hamster embryo and strain 2 guinea‐pig embryo cell culture models of chemical carcinogenesis. Whereas normal hamster and guinea‐pig embryo cells had negligible levels of plasminogen activator, neoplastically transformed cells derived from cultures exposed to chemical carcinogens had high levels of plasminogen activator and grew as progressively enlarging colonies in soft agar. The development of plasminogen activator secretion in relation to neoplastic transformation was further studied in the guinea‐pig cells where the latent period between carcinogen exposure and neoplastic transformation ranged from 4 months to more than one year. The production of plasminogen activator in this system also exhibited a long latent period, and acquisition of extracellular plasminogen activator correlated temporally with growth in agar and tumorigenicity. Plasminogen activator and growth in semi‐solid agar in concert are useful markers for identification of neoplastic cells transformed in culture following exposure to a chemical carcinogen.
Induction of the EBV cycle in B‐lymphocyte‐derived lines is accompanied by increased natural killer (NK) sensitivity and the expression of EBV‐related antigen(s) detected by the ADCC reaction
Authors: Patarroyo Manuel , Blazar Beverly , Pearson Gary , Klein Eva , Klein George
Published: February 2007

Human B‐lymphocyte‐derived lines were forced to enter the EBV‐cycle by superinfection with the P3HR‐l substrain of EBV or sodium butyrate treatment. The induced cells were used as targets for natural killing (NK) and EBV‐specific, antibody‐dependent cellular cytotoxicity (ADCC). Two Burkitt lymphoma lines, Raji and Daudi, and one normal adult derived lymphoblastoid cell line, NAD‐7, were comparable in their ADCC‐sensitivity after induction, but only the Burkitt lymphoma‐derived lines showed a major increase in NK‐sensitivity. The superinfection‐induced membrane change, responsible for both NK and ADCC sensitivity, is an early function of the viral cycle, correlated with the appearance of early antigens (EA). Indirect evidence indicates that the NK and ADCC target sites are different but this problem requires further investigation. Sodium butyrate induced an increased NK sensitivity and EBV‐related ADCC sensitivity in the Burkitt lymphoma‐derived P3HR‐l line. Lymphocyte effectors from different donors showed great differences in their NK and ADCC activity. Optimal ADCC could be demonstrated with effectors that were intermediate in their NK‐activity.
Evidence of separate pathways for viral and chemical carcinogenesis in c3h/stwi mouse mammary glands
Authors: Smith Gilbert H. , Arthur Larry A. , Medina Daniel
Published: February 2007

Mammary tumors in mice may arise as the result of exogenous infection with the mouse mammary tumor virus [MMTV(S)], usually via the milk; by the action of endogenous MMTV genes which are transmitted genetically and are sometimes expressed as infectious virus [MMTV(L)]; or by the action of chemical carcinogens. We have examined the etiological relationship between chemical and virus in the induction of mammary cancer in C3H/StWi mice. Mammary tumors were induced with 7.12‐dimethylbenz(a)anthracene (DMBA) in virgin C3H/StWi mice infected with exogenous mouse mammary tumor virus (C3H/StMTV) and in uninfected C3H/StWi females. The percent tumor risk in females whose glands were infected with exogenous mouse mammary tumor virus [MMTV(S)] was not different from that of MMTV(S)‐negative, C3H/StWi mice following treatment with DMBA. This result suggested that there was no synergistic effect between the two carcinogens, exogenous MMTV and Dmba. All the tumors arising in DMBA‐treated C3H/StMTV virgins were positive for MMTV env gene product, gp52 and MMTV gag gene product, p27 by radioimmune competition assay. MMTV(S)‐induced hyperplastic alveolar nodules (HAN) were observed in 62 % of the untreated C3H/StMTV glands at 8 months of age. Therefore, MMTV(S) was present and active in the mammary gland during the experimental period but had no enhancing influence on the sensitivity of the gland to carcinogenesis by DMBA. Tumors appearing in DMBA‐treated C3H/StWi virgin females were also tested for MMTV gp52 and p27 antigens to determine the presence of endogenous MMTV gene activity. Only occasional C3H/StWi tumors were positive and in most of these, p27, but not gp52 was detected, suggesting non‐coordinate expression of these endogenous MMTV gene products. Both alveolar (HAN) and ductal hyperplasia (DH) were found in DMBA‐treated C3H/StMTV glands, whereas only DH were found in DMBA‐treated C3H/StWi mice. Nevertheless, the DMBA‐induced C3H/StMTV tumor histopathology was remarkably indistinguishable from that in tumors produced by DMBA in C3H/StWi mice, implying that in both groups, tumors arose primarily from the chemically‐induced mammary dysplasias. These data taken together appear to support the conclusion that DMBA and Mmtv follow separate pathways to the induction of cancer in the mouse mammary gland.
Regulation of natural killer activity in vivo. II. The effect of alcohol consumption on human peripheral blood natural killer activity
Authors: Saxena Queen B. , Mezey Esteban , Adler William H.
Published: February 2007

Natural killer (NK) activity of human peripheral blood lymphocytes (HPBL) was studied in 32 alcoholics and 15 control subjects in a 4‐h chromium release assay using K562 tumor target cells. The natural killer activity of human peripheral blood lymphocytes in alcoholics was significantly higher than the level found in the control group. NK activity of PBL from alcoholics was still higher than that of similarly treated PBL from control subjects after carbonyl iron and magnet treatment, or after passage through a nylon wool column or after removal of cells rosetting with sheep erythrocytes. Changes in T cell, B cell or macrophage populations, therefore, are not the mechanism for increased NK activity in alcoholics.
Transformed and neoplastic phenotype: Reversibility during culture by cell density and cell shape
Authors: Brouty‐boye Danièle , Tucker Robert W. , Folkman Tudah
Published: February 2007

The ability of parental and transformed mouse C3H (10T1/2) cells to grow when held at a graded series of cell shapes (flat to round) was studied using substrata of decreasing adhesivity. The parental cells showed a decrease in growth when they reached the most rounded configurations. In contrast, transformed cells proliferated at the same rate regardless of cell shape. In addition, when transformed cells were serially passaged at low density on highly adhesive plastic, which maintained cells in a flat configuration, a reversion from the transformed phenotype to a non‐transformed phenotype occurred with the concomitant return of growth control by cell shape. However, when transformed cells were passaged at low density on a substratum which prevented cell spreading, the reversion to the parental phenotype did not occur and the cells escaped the growth control of cell shape and remained tumorigenic. Thus, in this cell system it appears that a change in cell configuration can dictate whether or not the transformed and neoplastic phenotype will be expressed.
Chromosome analyses of lymphoid cell lines derived from patients with chronic lymphocytic leukemia
Authors: Najfeld V. , Fialkow P. J. , Karande A. , Nilsson K. , Klein G. , Penfold G.
Published: February 2007

To study chromosome complements of chronic lymphocytic leukemia cells, six Epstein‐Barr virus‐transformed lymphoid lines were established from two patients with this disease who were heterozygous for the X‐chromosome‐linked enzyme glucose‐6‐phosphate de‐hydrogenase (G6PD). Immunoglobulin and G6PD were used as markers of the leukemic versus normal cell origin of the cell lines. The two lines, derived from putative normal cells, had no chromosomal changes. In contrast, chomosome abnormalities were found in each of the four cell lines of presumed leukemic cell origin. Although the chromosome aberrations are not as specific as the Philadelphia chromosome, there appears to be non‐random involvement in chronic lymphocytic leukemia of some chomosomes, such as the No. 12.
Cytotoxicity to tumor cells of monocytes from normal individuals and cancer patients
Authors: Gerrard Theresa L. , Terz Jose J. , Kaplan Alan M.
Published: February 2007

This study was aimed at characterizing the parameters which regulate human monocyte‐mediated cytotoxicity to tumor cells as well as characterizing the target cell specificity, kinetics, etc., of the cytotoxic mechanism. Normal human peripheral blood monocytes were cytotoxic to tumor cells in an in vitro assay, measuring release of [3H]thymidine from human target cells. Monocyte cytolysis was observed with several adherent tumor lines including T24, a bladder cancer line; LR, a melanoma line; and an SV40‐transformed W138 fibroblast line, with maximal cytolysis observed at 72 h. Lymphokines were not required to induce and only infrequently enhanced monocyte cytotoxicity. Prolonged exposure of monocytes to lymphokines or in vitro culturing of monocytes prior to lymphokine exposure did not alter the monocytes' response to lymphokine signals with respect to cytotoxicity. Lymphokines induced monocytes to exhibit enhanced spreading, suggesting that monocytes were susceptible to lymphokine signals but that the development of cytolytic function was independent of lymphokines. In contrast to the cytolysis of adherent tumor cells, monocytes were less effective in killing the non‐adherent lymphoid target cells K562, Raji, and CEM. Monocytes were selectively cytotoxic to tumor cells and generally did not kill normal human fibroblast cell lines or PHA‐stimulated lymphocytes. Monocytes from cancer patients exhibited normal cytotoxicity to several human tumor lines. Plasmas from some cancer patients were inhibitory to cytotoxicity mediated by both autologous monocytes and normal monocytes.
Non‐random duplication of chromosome 15 in murine T‐cell leukemias: Further studies on translocation heterozygotes
Authors: Wiener F. , Spira J. , Babonits M. , Haran‐Ghera N. , Klein G.
Published: February 2007

Four combinations of translocation heterozygotes with cytogenetically distinct chromosomes 15 were used to investigate whether the T‐cell leukemia‐associated duplication of chromosome 15 is a non‐random or a random event. In leukemias of AKR X CBAT6T6 F1 (Group I) and C57BL X CBAT6T6 F1 (Group IV) crosses the duplication was non‐random, affecting the AKR‐derived chromosome 15 (Group I) and CBAT6T6‐derived T (14;15) 6 chromosome (Group IV), respectively. In contrast, in leukemias induced in CBA X CBA T6T6 F1 combinations (Group III) ‐ where both chromosomes 15 (normal and translocated) were CBA‐derived ‐ the duplication was random. Similarly, in the Rb6;15 X CBAT6T6 F1 cross (group II) the duplication of chromosome 15 appeared to be random. The results supported the hypothesis that the genetic content of chromosome 15 rather than its translocated state is decisive for the preferential duplication of this chromosome in T‐cell leukemogenesis. However, the genetic background of the strain from which chromosome 15 is derived may also influence the duplication pattern of individual tumors.
Inhibition of murine tumor growth and prostaglandin synthesis by indomethacin
Authors: Fulton Amy M. , Levy Julia G.
Published: February 2007

Inhibition of the growth of a transplantable methylcholanthrene‐induced tumor was achieved in mice by administering indomethacin or aspirin in the drinking water, these drugs having in common the ability to inhibit prostaglandin synthesis. Indomethacin was able to reduce the levels of prostaglandin E (PGE) in the tumor tissue. When tumors from these animals were cultured in vitro, the culture supernatant fluid from drug‐treated animals showed lower levels of PGE released into the media, but after several days in culture, tumor cells from indomethacin‐treated animals fully recovered their ability to produce PGE. The relative size of tumors in untreated animals was directly related to the amount of PGE activity present in these tumors.
Expression of metastatic potential of tumor cells in young nude mice is correlated with low levels of natural killer cell‐mediated cytotoxicity
Authors: Hanna Nabil
Published: February 2007

Of 6‐ and 3‐week‐old nude mice given intravenous injections of murine tumor cells with well‐defined metastatic properties, only the 3‐week‐old mice developed lung tumor colonies in significant numbers. The quantitative differences in metastatic potential among tumor cell lines injected into syngeneic recipients were also maintained following intravenous injection into young nude mice. Successful metastasis in 3‐week‐old nude mice is correlated with the low levels of natural killer cell activity detected in these young recipients. Boosting of the natural killer cell activity of 3‐week‐old nude mice by the administration of bacterial adjuvants and interferon inducers significantly inhibited metastasis formation. The differences in metastasis development could not be attributed to differences in the initial arrest of tumor cells in the pulmonary vascular bed, but rather to a better survival of the arrested cells in the lungs of 3‐week‐old nude mice as compared with 6‐week‐old counterparts. We conclude that low levels of NK cell activity are associated with increased incidence of experimental metastasis.
Association of hepatitis b virus infection with hepatocellular carcinoma in american patients
Authors: Yarrish Robert L. , Werner Barbara G. , Blumberg Baruch S.
Published: February 2007

Thirty‐four patients from the Philadelphia area with hepatocellular carcinoma (HCC) were matched with colon cancer patients, lung cancer patients and blood donors according to age and sex. Sera from the four groups were tested to determine the prevalence of hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti‐HBs), and antibody to hepatitis B core antigen (anti‐HBc). Five of the HCC patients (14.7%) and none of the controls were positive for HBsAg. At least one of the three serologic markers of hepatitis B virus (HBV) infection was found in 51.5 % of the HCC patients, 5.3 % of the colon cancer patients, 11.1% of the lung cancer patients, and 10.7% of the blood donors. Twelve of the seventeen seropositive HCC patients (70.6%) were positive for anti‐HBc alone, while all of the seropositive lung cancer patients and donors were positive for anti‐HBs alone. Sera positive for any HBV marker were also tested for e antigen (HBeAg) and its antibody (anti‐HBe). Four of the HCC patients (23.5 % of the seroposi‐tives) had anti‐HBe, while none of the sera tested had HBeAg. A history of alcoholism did not appear to influence HBV seropositivity in the HCC patients. This study supports the hypothesis that HBV infection is closely associated with HCC even in areas where both conditions are uncommon. The wide disparity between seropositivity for HBsAg and anti‐hbc in the HCC patients is an unusual feature, for which an age effect may be the best explanation.
Prognosis of stage I melanoma of the skin. Who collaborating centres for evaluation of methods of diagnosis and treatment of melanoma
Authors: Cascinelii N. , Morabito A. , Bufalino R. , Esch E. P. Vander , Preda F. , Vaglini M. , Rovini D. , Orefice S.
Published: February 2007

Prognosis of stage I melanoma of the skin was evaluated in 747 previously untreated patients observed by the WHO Collaborating Centres for Evaluation of Methods of Diagnosis and Treatment of Melanoma from September 1967 to September 1975. The mean follow‐up period of these patients was 8.9 years. Sex, maximum diameter of melanoma, elevation on skin surface, histologic type, levels of invasion and maximum tumor thickness were found to be significantly related to survival when considered one by one. However, multifactorial analysis showed that sex and maximum thickness only had a significant impact on survival of stage I melanoma patients.

The effect of sex was not evident in patients with maximum tumor thickness not exceeding 2 mm (81 % 5‐year survival for males and 87% for females and a p value >0.05), while females did significantly better (p <10−4) when maximum thickness of primary was over 2 mm.
A case‐control study of diet and colo‐rectal cancer
Authors: Jain M. , Cook G. M. , Davis F. G. , Grace M. G. , Howe G. R. , Miller A. B.
Published: February 2007

A case‐control study of cancer of the colon and rectum has been conducted in Calgary, Alberta and Toronto, Ontario, Canada. A total of 348 cases of cancer of the colon and 194 cases of cancer of the rectum were individually matched by age, sex and neighbourhood of residence to 542 population controls and frequency matched to 535 hospital controls who had undergone an abdominal operation. Each subject received a personal medical history questionnaire and a quantitative diet history questionnaire. Data on a number of potential non‐nutrient risk factors for bowel cancer and on the consumption of 9 nutrients in the 2‐month period up to 6 months before interview were analysed. The dietary data thus refer to recent diet consumed in a period antedating the diagnosis of, and in most cases symptoms from, large‐bowel cancer in the cases, and a corresponding time period in the controls. The major findings were an elevated risk for those with a history of bowel polyps, and for those with an elevated intake of calories, total fat, total protein, saturated fat, oleic acid and cholesterol. No association was seen with an elevated intake of crude fibre, Vitamin C and linoleic acid. The nutrients for which an increased risk was demonstrated were highly correlated, though multivariate analysis using logistic regression indicated highest risk for saturated fat, with evidence of a dose‐response relationship. The findings in both cancer sites, both sexes and with both sets of controls were quantitatively very similar. The population‐attributable risk for colon and rectal cancer combined was estimated from the neighbourhood controls to be 41% for males and 44% for females for saturated fat intake and 9.8% and 6.4% respectively for any history of polyps.
Comparison of steroid receptor levels in renal‐cell carcinoma and autologous normal kidney
Authors: Hemstreet George P. , Wittliff James L. , Sarrif Awni M. , Hall Miles L. , McRae Lillian J. , Durant John R.
Published: February 2007

Since a number of renal‐cell carcinomas regress with hormonal manipulation, we have identified and measured the levels of estrogen, progestin and glucocorticoid receptors in 47 autologous pairs of normal and neoplastic kidney tissues. High‐affinity receptors for these hormones were detected in kidney tissues of both sexes by means of a dextran‐coated charcoal assay. Glucocorticoid receptors were demonstrated in renal cancer tissues for the first time, and were higher in the tumor (mean 31.3 ± sem 5.6) than in the normal tissue (mean 18.5 ± sem 3.1 fmol/mg cytosol protein). There was a significant difference in the quantities of progestin receptors (expressed as fmol/mg cytosol protein) in normal (mean 18.4 ± sem 3.3) versus neoplastic (mean 10.4 ± sem 4.0) kidney specimens (p < 0.007). There was a significant difference between the binding affinity of the progestin receptor in the male tumors (Kd = 2.2 ± sem 0.9 nM, n = 10) and that of the females, (Kd = 9.3 ± sem 6.5 nM) (p < 0.04). When an affinity of < 9.9 × I0−9M and > 10 fmol/mg cytosol protein were used as criteria for classifying a tissue as positive for progestin receptors, only 17% of tumors contained these receptors while 45% of normal tissues exhibited them. According to these criteria, no differences were observed in the frequency of occurrence of either estrogen receptors or glucocorticoid receptors in tumor versus normal kidney. Data from this study suggest that the use of endocrine therapy should be re‐examined in the treatment of renal‐cell carcinoma.
Effect of lentinan on the production of migration inhibitory factor induced by syngeneic tumor in mice
Authors: Zákány József , Chihara Goro , Fachet József
Published: February 2007

Attempts were made to reveal the mechanism of the inhibitory effect of lentinan on methylcholanthrene‐in‐duced transplantable fibrosarcoma (A/Ph.MC.SI) isografts. Since the involvement of a delayed‐type hypersensitivity response can be supposed to operate against this syngeneic tumor, the enlargement of regional lymph nodes, the DNA synthesis activity and the migration inhibitory factor producing capacity of the regional lymph‐node cells were studied in the control and lentinan‐treated, tumor‐bearing mice at different times after tumor implantation. The only parameter affected until the first sign of tumor inhibition on the 8th day was the MIF‐producing capacity. Regional lymph‐node cells in the lentinan‐treated mice showed a peak response at this time while practically no MIF was produced by cells of non‐treated mice. The early phase of the developing anti‐tumor reaction (enlargement of and proliferation in the lymph nodes) was initiated in all recipients but only some of them could reject the tumor in the non‐treated group in contrast to lentinan‐treated animals that rejected the tumors in all cases. It can be supposed that a tumor‐induced immunosuppression emerges in the tumor‐bearers and can be overcome by lentinan treatment, most likely through enhancement of the MIF production. For measurement of MIF activity a continuously dividing in vitro macrophage‐like cell line was established and employed in the microwound migration assay.
In vitro NK‐activity and in vivo resistance to leukemia: Studies of beige, beige/nude and wild‐type hosts on C57BL background
Authors: Kärre Klas , Klein Gunnar O. , Kiessling Rolf , Klein George , Roder John C.
Published: February 2007

The bg mutation in C57BL mice causes a partial impairment of NK activity, and has therefore been proposed as a model to evaluate the in vivo function of NK cells. In thepresent report, we studied natural resistance against the ascitic lines of one chemically and two virally induced syngeneic leukemias in C57BL bg/bg mice and their phenotypically normal heterozygous +/ bg littermates. S.c. threshold inocula of all three leukemia lines grew faster and caused death earlier in bg/bg than in +/bg mice, and two of the lines were rejected completely at a significantly higher frequency in +/bg control animals. The +/bg mice also eliminated [125]‐IdUrd‐labelled leukemia cells at a faster rate than bg/bg mice, as measured by pulmonary, hepatic and splenic radioactivity retained 18‐30 h after i.v. injection Direct splenic killing of 51Cr‐labelled leukemia cells was also studied in vitro, and was found to be severely depressed in bg/bg compared to +/bg. This natural killer activity was independent of adherent cells and showed a rapid, but transient, increase after inoculation of the tumor cell doses used in the transplantation tests. It was also possible to study the bg mutation in T‐cell‐free mice, by combining it with the nu mutation on a C57BL background. The NK activity of such beige‐nude mice was found to be partially impaired compared to nude (non‐beige) or wild‐type animals, but higher than that of beige (non‐nude) mice. Our results suggest that NK cells may be responsible for elimination of small numbers of tumor cells in the intact syngeneic host. The further use of beige and beige‐nude mice in studies of transplanted and primary tumors is discussed.
THE EFFECT OF DIET ON AUTOGENOUS IMMUNITY TO MOUSE MAMMARY TUMOR VIRUS IN C3H/Bi MICE
Authors: Day Noorbibi K. , Fernandes Gabriel , Witkin Steven S. , Thomas Edward S. , Sarkar Nurul H. , Good Robert A.
Published: February 2007

Antibody levels to mouse mammary tumor virus (MuMTV) in sera of C3H/BI, C57BL/6 and AKR mice were assayed by an enzyme‐linked immunosorbent assay (ELISA). It was found that antibody levels to MuMTV were highest in sera of C3H/Bi females which have a high incidence of breast cancer and low in male C3H/Bi and female C3H/Bi foster‐nursed on C57BL/‐6 females. Sera of C57BL/6 and AKR mice showed very low or undetectable levels of antibody to MuMTV. Reduction of caloric intake sufficient to inhibit mammary tumor formation strikingly inhibited formation of antibody against MuMTV. The lowest levels of antibody were observed in sera of mice fed 10 cal/day of a defined diet. Significantly higher levels developed in the sera of mice fed 16 cal/day of the same defined diet. The highest antibody levels against MuMTV, however, were seen in sera of mice fed lab chow ad libitum but no correlation was evident between levels of antibody and tumor size. These studies indicate that dietary caloric restriction has a profound influence on the development of both mammary adenocarcinoma and antibody responses to MuMTV.
Inhibition of endogenous murine retrovirus expression by L‐β‐3, 4‐dihydroxyphenylalanine (l‐dopa) methyl ester
Authors: Suk William A. , Ceccorulli Lisa M. , Long Cedric W.
Published: February 2007

Induction of endogenous xenotropic type‐C virus from Kirsten sarcoma‐virus‐transformed BALB/c (K‐BALB) mouse cells was inhibited by short‐term exposure to L‐β‐3, 4‐dihydroxyphenylalanine (L‐dopa) methylester. Partially synchronized cells cultured for 1–4 h with 0.8–1.6 mM L‐dopa methyl ester and subsequently induced with 5‐iododeoxyuridine (IdUrd), cycloheximide and histidinol showed inhibition of virus activation. Incorporation of thymidine, uridine and leucine was measured at the end of the drug treatment and during the subsequent induction period. L‐dopa methyl ester had a pronounced effect on DNA synthesis, reducing it by more than 85% during a 4‐h incubation period, whereas RNA and protein synthesis remained largely unaffected. Removal of the drug and replacement with fresh medium did not reverse DNA synthesis or virus activation during the subsequent induction interval. L‐dopa methyl ester was also shown to potentially function as an analogue of tyrosine in this cell system. These results suggest that inhibition of virus induction may be caused by inhibiting the normal progressing of cells through the S phase of the cell cycle.
Lymphotoxin: An anticarcinogenic lymphokine as measured by inhibition of chemical carcinogen or ultraviolet‐irradiation‐induced transformation of syrian hamster cells
Authors: Evans Charles H. , Dipaolo Joseph A.
Published: February 2007

Syrian‐hamster‐derived lymphotoxin inhibits benzo(a)pyrene and ultraviolet carcinogen‐induced in vitro morphologic transformation of diploid secondary passage hamster embryo cells. When lymphotoxin is added up to 4 days post carcinogen, the reduction in the frequency of morphologic transformation 6 days after carcinogen treatment varies directly with lymphotoxin concentration. The frequency of transformation does not change following re‐feeding with lymphotoxin‐free medium and incubation for 6 additional days. Furthermore, transformation by ultraviolet is prevented when cells are pulsed with lymphotoxin for as few as 6 hours after irradiation. Thus, lymphotoxin has the potential to irreversibly inhibit the first recognizable morphologic step of carcinogenesis.