bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural anti‐tumor serum reactivity in balb/c mice. I. Characterization and interference with tumor growth
Authors: Ménard Sylvie , Colnaghi Maria I. , Porta Giuseppe Della
Published: February 2007

A natural cytotoxic reactivity directed against syngeneic or allogeneic tumor cells was demonstrated in serum of BALB/c mice by an in vitro cytotoxicity test using rabbit serum as the source of complement. The reactivity, studied on syngeneic fibrosarcoma cells, was found to be minimal in mice less than 10 weeks old and to increase progressively with age. T‐deprivation determined an increase of reactivity in young mice to levels reached spontaneously only by the serum of 40‐week‐old mice. The BALB/c serum also revealed natural anti‐thymus antibodies. Non‐identity between anti‐tumor and anti‐thymus antibodies was demonstrated by direct cytotoxicity and absorption tests. An inoculum of syngeneic fibrosarcoma cells increased the level of anti‐tumor serum reactivity in both normal and T‐deprived young mice. The natural anti‐tumor cytotoxicity revealed in vitro seemed to exert a specific in vivo protection as suggested by the indirect correlation found between the level of the natural anti‐tumor reactivity and the growth of a transplanted fibrosarcoma.
Natural anti‐tumor serum reactivity in balb/c mice. II. Control by regulator t‐cells
Authors: Colnaghi Maria I. , Ménard Sylvie , Porta Giuseppe Della
Published: February 2007

By a complement‐dependent cytotoxicity test, 37 sera from 1‐ to 18‐month‐old BALB/c mice were tested for natural anti‐tumor and anti‐thymus immune reactivity. The level of anti‐tumor and anti‐thymus antibodies increased with age, and a high individual variability, particularly evident in the older animals, was found. The appearance of the spontaneous antibodies was correlated to the T‐cell status of mice. Animals with the higher spleen T‐cell content were those with the higher anti‐thymus and the lower anti‐tumor natural antibody level, and vice verso. In T‐deprived mice the anti‐tumor response increased, whereas the anti‐thymus response was not influenced. An inoculum of T cells from young to older syngeneic mice yielded a decrease of the anti‐tumor response and an increase of the anti‐thymus response. Homeostatic immunologic mechanisms, in which the cellular and the humoral system alternate in the tumor cell control, are suggested.
Cancer in the africans and arabs of zanzibar
Authors: Chopra Saif A. , Chopra Fatima S.
Published: February 2007

Among 392 cancers histologically diagnosed in Zanzibar during 1957–62 and 1964–67, a definite pattern seems to emerge. Skin and cervix cancers were the most common types in both Africans and Arabs. Skin cancer was predominantly of the squamous cell type. The Zanzibar Arabs thus appear to be protected against basal cell carcinoma which in the Arab desert community has been diagnosed with about the same frequency as squamous‐cell carcinoma. In the same manner, the Zanzibar Arab immigrants seem to have a reduced risk for stomach and oesophageal cancers, which are common in other Arab countries. This is probably because Arabs in Zanzibar have adopted the dietary habits and other customs of the Zanzibar Africans in whom cancer of the alimentary tract seems to be uncommon. On the other hand, unlike Zanzibar Africans, the Arabs have an increased risk for Hodgkin's disease similar to that of the Middle East Arab population.
Heterogeneity of epstein‐barr virus originating from P3HR‐1 cells. I. Studies on ebna induction
Authors: Fresen Karl‐Otto , Merkt Barbara , Bornkamm Georg W. , Hausen Harald Zur
Published: February 2007

Infection of EBV‐negative human B‐lymphoma cells of the lines BJAB and Ramos with EBV from P3HR‐1 or B 95‐8 cells resulted in gradual conversion of these cells to EBNA synthesis. Whereas B 95‐8 virus‐infected cells exhibited a uniform brilliant EBNA fluorescence, two distinct fluorescence patterns were observed in P3HR‐1 virus‐converted BJAB and Ramos cells, a faint granular and a brilliant fluorescence, with predominance of the faint granular pattern. Cloning of P3HR‐1 virus‐converted BJAB cells resulted in 20 clones, 11 of them showing the heterogenous parental pattern, six revealing exclusively faint granular EBNA staining, and three with brilliantly stained nuclei, containing also a varying percentage of EBNA‐negative cells. Further subcloning of one of the latter clones resulted in 26 subclones with brilliant EBNA expression, always segregating a significant percentage of EBNA‐negative cells and one entirely EBNA‐negative subclone. Reassociation kinetics did not reveal striking differences in the genome content of clones showing exclusively the faint granular or the brilliant type of EBNA expression. The EBNA‐negative clone did not contain detectable amounts of EBV‐DNA. Upon superinfection of the converted clones by the parental P3HR‐1 virus, a significant increase in EA induction was noted when compared to non‐converted BJAB and Ramos cells. This accounted in particular for cells with faint granular EBNA expression. These data support previous interpretations (Fresen and zur Hausen, 1976), suggesting the existence of at least two populations of EBV molecules within P3HR‐1 cells. The reason for the apparently labile association of P3HR‐1 EBV genomes inducing the brilliant EBNA fluorescence in BJAB cells still remains obscure. The possible existence of a “helper” effect, exerted by the faint granular EBNA‐inducing virus in stabilizing the persistence of the former, is discussed.
Tumour‐specific antibodies reactive with cell‐surface antigens in children with wilms' tumour
Authors: Kumar Shant , Waghe Madhav , Taylor Geoffrey
Published: February 2007

Tumour‐specific antibodies directed against membrane antigens were demonstrated by immuno‐fluorescence in three of 45 patients with Wilms' tumour. Antibody capable of collaborating with K cells to kill Wilms' tumour was present in two additional patients. No patient exhibited both membrane immunofluorescence and K‐cell collaborating antibody. Of 27 patients with non‐renal solid tumours and 52 age‐matched controls, none possessed tumour‐specific antibody.
Studies on epstein‐barr virus‐related antigens. II. Biochemical properties of soluble antigen in raji burkitt lymphoma cells
Authors: Matsuo T. , Osato T. , Nishi S. , Hirai H.
Published: February 2007

Biochemical properties of Epstein‐Barr virus (EBV)‐related soluble antigen in non‐producer Raji Burkitt lymphoblastoid cells, assayed by the indirect single radial immunodiffusion (ISRD) test, were investigated. The soluble ISRD antigen retained activity even after exposure to a temperature of 80°C. The antigen was precipitated in 40% saturated ammonium sulfate and ISRD activity was recovered from the precipitate when reconstituted into a solution. Isoelectric focusing and crossed immuno‐electrophoretic analyses revealed that the isoelectric point of the ISRD antigen is pH 4.8 with an electrophoretic mobility similar to that of serum α‐globulin. With Sephadex G‐200 or Sepharose 6B gel filtration, ISRD activity was obtained as a single peak which corresponded to the activity absorbing anti‐complement immunofluorescence. The molecular weight of the present EBV‐related soluble antigen was estimated to be 220,000–240,000 daltons.
Metabolism of the carcinogenic hydrocarbon benzo(a)pyrene in human fibroblast and epithelial cells. II. Differences in metabolism to water‐soluble products and aryl hydrocarbon hydroxylase activity
Authors: Yamasaki Hiroshi , Huberman Eliezer , Sachs Leo
Published: February 2007

Aryl hydrocarbon (benzo(a)pyrene) hydroxylase (AHH) activity and metabolism of benzo(a)pyrene to water‐soluble products were measured in cultures of body fibroblasts and kidney epithelial cells from different human embryos. AHH activity at 24 h after treatment with or without benz(a)anthracene was determined in cultures from 23 embryos, and 3 days' accumulated metabolism of benzo(a)pyrene to water soluble products was measured in cultures from 18 embryos. The body fibroblasts from the different embryos could be divided into three groups according to the amount of water‐soluble products, but not according to the AHH activity. These three groups were not found by either assay in the cultures of kidney epithelial cells. In both fibroblast and epithelial cells, high metabolism to water‐soluble products was not necessarily associated with high AHH activity. The results extend our previous finding (Huberman and Sachs, 1973) of three presumably genetic groups for BP metabolism to water‐soluble products in human fibroblast but not in epithelial cells and indicate that this grouping was not found in these cells by measuring AHH activity.
Genetic transmission of mammary tumour virus by gr mice
Authors: Van Nie Robertha , Verstraeten A. A. , De Moes J.
Published: February 2007

By immunodiffusion assay (ID‐test) milk samples of mice of several strains and of F1‐hybrids of the GR strain were tested for the presence of mammary tumour virus (MTV) antigens. The results clearly demonstrated that the presence of viral antigens in the milk of the first lactation period is restricted to mice harbouring endogenous MTV‐GR. Viral antigens were detectable in about 50% of the milk samples collected during the first (occasionally the second) lactation periods of mice of the segregating backcross I (Bc I) populations: DBAf × (DBAf × GR), AKR × (AKR × GR), BALB/c × (BALB/c × GR) and C57BL × (C57BL × GR), indicating that one dominant gene is responsible for the presence of viral antigens in the milk of GR mice. The proposed gene symbol is Mtv‐2. Milk samples from female mice of three different Bc II populations were tested for the occurrence of viral antigens. In the first Bc II: [BALB/c × (BALB/c × GR)] × BALB/c 33 out of 51 mice, descending from ID‐positive mothers, had ID‐positive milk and only one out of 71 mice, which were the progeny of ID‐negative Bc I mothers, was ID‐positive. These results may be influenced by the MTV transmitted extrachromosomally via the milk of the mother. The two other Bc II populations were derived from Bc I fathers, either [BALB/c × (BALB/c × GR)] or [(BALB/c × GR) × BALB/c] f and BALB/c females. The results obtained with these Bc II populations suggested that 6 Bc I fathers were heterozygous for Mtv‐2. Since the segregation ratio (60:29) in the Bc II population (progeny of these 6 Bc I ♂♂) deviates significantly from the expected 1:1 ratio, one may assume extrachromosomal transmission of MTV via the seminal fluid of the father to the progeny. A close correlation was found between the presence of MTV antigens in the milk and the occurrence of both early mammary tumours after hormone treatment and spontaneous mammary tumours before the age of 13 months. These results suggest that the early appearance of mammary tumours in the GR strain and the early expression of MTV antigens in the milk appear to be controlled by the same genetic factors.
Viruses and renal carcinoma of rana pipiens. XV. The presence of virus‐associated membrane antigen(s) on lucké tumor cells
Authors: Naegele R. F. , Granoff A.
Published: February 2007

Virus‐specific antigens were detected in Lucké turnor cells by indirect immunofluorescence using antiserum prepared against Lucké herpesvirus. Intracellular fluorescence, both cytoplasmic and nuclear, was observed only in acetone:methanol‐fixed tumor cells that contained herpesvirus detected by electron microscopy. The number of positive cells correlated well with the number of cells containing virus. In contrast, both virus‐containing and virus‐free cells exhibited membrane fluorescence when viable unfixed tumor cells were tested. A striking reduction in the number of membrane fluorescent cells was observed with an increase in the length of time that tumor cells were in primary culture. No reaction was observed with a variety of normal R. pipiens cells. Absorption of the antiserum with normal frog kidney tissue had no effect on the number of positive cells whereas absorption with virus‐free tumor reduced the reaction; absorption with virus‐containing tumor eliminated it. These findings provide the first demonstration that the Lucké herpesvirus genome resident in virus‐free tumor cells expresses a virus‐associated membrane antigen(s).
Epstein‐barr virus antibodies in tonsillar carcinoma patients
Authors: Vonka V. , Šibl O. , Suchánková A. , Simonová I. , Závadová H.
Published: February 2007

Sera from 18 tonsillar carcinoma patients and from 18 matched control subjects were examined for the presence of antibodies to viral capsid antigen (VCA), early antigen (EA) and nuclear antigen (EBNA) of EB virus. Antibodies to all three antigens were found more frequently and in significantly higher titres in the tonsillar carcinoma patients than in control subjects.
Effect of human leukocyte interferon on the growth of human osteosarcoma cells in tissue culture
Authors: Strander Hans , Einhorn Stefan
Published: February 2007

Nine osteosarcoma cell lines, originally developed from six osteosarcoma tumours in five patients, and two cell lines of non‐tumour origin (glia and fibro‐blast) were grown in vitro in the presence of human leukocyte interferon (L‐IF). L‐IF exerted a dose‐dependent inhibition of growth in all these lines. The inhibitory activity displayed characteristics typical of interferons. Inhibition of cell growth occurred at a much lower L‐IF concentration for the osteosarcoma than for the non‐tumour‐derived lines. Inhibition of tumour cell growth was observed at concentrations obtained in the serum of osteosarcoma patients treated with interferon.
Chromosome 14 translocation in african and north american burkitt's lymphoma
Authors: Kaiser‐Mccaw Barbara , Epstein Alan L. , Kaplan Henry S. , Hecht Frederick
Published: February 2007

Two established North American Burkitt lymphoma cell lines were studied by chromosomal banding techniques. The SU‐AmB‐1 line previously shown to be negative for the Epstein‐Barr virus (EBV) was found to have, among other changes, a translocation from the long arm (q) of chromosome 8 onto 14q. The SU‐AmB‐2 line, which contains the EBV genome, also displayed the same 8/14 translocation. These results were compared with data from three EBV‐positive tumor cell lines derived from patients with African Burkitt's lymphoma. Our findings indicate that a translocation from 8q onto 14q occurs in both African and North American Burkitt lymphomas, and that this abnormality apparently is not related directly to EBV. This chromosome translocation therefore may be an important event in the development of human lymphocytic malignancy, analogous to the occurrence of the Philadelphia chromosome rearrangement in chronic myelogenous leukemia.
Relationship of human natural lymphocyte‐mediated cytotoxicity to cytotoxicity of breast‐cancer‐derived target cells
Authors: Cannon Grace B. , Djeu Julie , Bonnard Guy D. , West William H. , Herberman Ronald B.
Published: February 2007

Mononuclear cells from 115 individuals were tested in a 4‐h chromium release assay against two breast‐cancer‐derived cell lines, G11 and MCF‐7, and a myeloid line, K‐562, shown previously to be sensitive to natural cytotoxicity. These data were analyzed in a manner designed to detect hyperreactivity against the breast cell lines relative to the level of reactivity against K‐562. A high proportion of breast cancer patients were found to be relatively hyperreactive against G11 (12/18 or 67%) and against MCF‐7 (10/18 or 56%). Fibroadenoma patients were very similar to the normal females, with 0/11 hyperreactive to G11 and 1/11 (9%) to MCF‐7. However, several normal males (7/17 or 41%) were hyperreactive to G11 but not to MCF‐7 (2/17 or 12%). Colon cancer and lung cancer patients were also more hyperreactive to G11, 4/8 or 50% and 4/6 or 67%, respectively, than they were to MCF‐7, 1/8 or 13% and 1/6 or 17%, respectively. Only fibrocystic patients resembled the breast cancer patients, with some but not as many individuals being hyperreactive to G11 (3/8 or 38%) and to MCF‐7 (2/8 or 25%). With another group of individuals reproducibility of the method was demonstrated, with only 1/14 or 7% of normal females and 12/17 or 70% of breast cancer patients being hyperreactive to G11. Thus, natural cytotoxicity toward K‐562 can be related to breast cancer‐associated cytotoxicity toward MCF‐7 in a way that distinguishes a majority of brest cancer patients specifically from other groups of individuals.
Radioimmunoassay for the major structural protein of mason‐pfizer monkey virus: Attempts to detect the presence of antigen or antibody in humans
Authors: Charman Howard P. , Rahman Rukhsana , White Martin H. , Kim Nancy , Gilden Raymond V.
Published: February 2007

The 25,000 dalton protein of Mason‐Pfizer monkey virus (MPMV) was isolated by gel filtration chromatography. In agreement with results from other laboratories, antisera to type‐C and the non‐type‐C bovine leukemia and equine infectious anemia viruses did not precipitate 125I‐labelled MPMV p25. In addition, these viruses did not cross‐react in a competition radioimmunoassay for MPMV p25. Twenty‐one human tissues (15 breast carcinomas, 2 normal breasts, 3 acute myelogenous leukemias and 1 sarcoma) were fractionated by detergent solubilization, ammonium sulfate precipitation, and DE‐52 anion exchange chromatography. These methods were shown to be highly effective for purification of MPMV p25. Under assay conditions which minimized incubation damage to the 125I‐MPMV p25, all tissues failed to react in the competition radioimmunoassay (RIAT). Two hundred and two human sera or plasma specimens, including those from patients with breast cancer and 33 age‐matched controls, from 50 patients with hematologic malignancies, from 12 patients with amyotrophic lateral sclerosis, and from 14 patients with systemic lupus erythematosis, were examined for antibodies to MPMV p25. With the exception of two multiple myeloma plasmas which produced artifactual false positive reactions based on hypergammaglobulinemia, a known complication of salt precipitation radioimmunoassays, the remainder of the specimens were negative for evidence of MPMV p25 antibodies.
“sternberg‐reed” giant cells of hodgkin's disease: Cultivation in vitro, heterotransplantation, and characterization as neoplastic macrophages
Authors: Kaplan Henry S. , Gartner Suzanne
Published: February 2007

Cells from the involved spleens of 25 patients with Hodgkin's disease have been grown in long‐term culture and compared with normal spleen macro‐phage cultures from control cases. The Hodgkin's spleen cell culture contained mono‐, bi‐, and multinucleate giant cells, many closely resembling Sternberg‐Reed cells, which were adherent, phagocytically active and neoplastic by the dual criteria of aneuploidy and heterotransplantability. Lysozyme secretion was consistently observed in all Hodgkin's cultures tested. The giant cells possessed both Fc and complement (C3b) receptors, and lacked lymphocyte markers such as C3d receptors, surface IgM, and the capacity to form E‐rosettes. Binucleate and multinucleate cells, as well as mononuclears, were capable of active DNA synthesis, and binuclear mitotic figures were observed. It is concluded that these cells are the in vitro descendants of the Sternberg‐Reed and Hodgkin neoplastic cell population, and that they are derived from macrophages or closely related cells of the mononuclear phagocyte system.
Origin of embryo‐derived yolk sac carcinomas
Authors: Damjanov Ivan , Škreb Nikola , Sell Stewart
Published: February 2007

The origin of yolk sac carcinoma obtained from rat embryos transplanted to extrauterine sites was traced to the extraembryonic portion of 9‐day egg‐cylinders. Under appropriate conditions cells of the extraembryonic portion of the egg cylinder differentiate into cells of parietal yolk sac epithelium, continue to proliferate and form retransplantable malignant tumors. Serum concentrations of alphafetoprotein were elevated in rats bearing yolk sac carcinomas and in some animals bearing teratomas admixed with yolk sac carcinoma. Possible factors that regulate the survival and proliferation of yolk sac epithelium in extrauterine sites are briefly discussed.
Induction by cigarette smoke of aryl hydrocarbon hydroxylase activity in the rat kidney and lung1
Authors: Van Cantfort Jacques , Gielen Jacques
Published: February 2007

In both the rat kidney and lung, inhalation of cigarette smoke diluted with air (1/15) for a limited period of time (15 min) specifically induces aryl hydrocarbon hydroxylase (AHH)<2> in less than 4 h. Up to four successive inhalations administered at 2‐h intervals additively induce both lung and kidney hydroxylase activities. The maximal effect corresponds to about 10 times the control value. Compared to the kidney enzyme, the lung AHH activity is about three or four times more sensitive to small concentrations of cigarette smoke. The biological half‐life of the lung AHH activity is longer than 24 h, while it is only 3–4 h in the kidney. In both tissues, the induced enzyme presents the same in vitro thermolability and sensitivity to various inhibitors. For the establishment of the AHH induction, protein synthesis is continuously required, while RNA synthesis is only necessary during the first 2 h following the smoke treatment.
Depressed in vitro peripheral blood lymphocyte response to mitogens in cancer patients: The role of suppressor cells
Authors: Zembala Marek , Mytar Bozena , Popiela Tadeusz , Asherson Geoffrey L.
Published: February 2007

The reactivity of peripheral blood lymphocytes from patients with advanced malignancy was assessed by mitogen‐induced stimulation of protein synthesis as measured by 3H‐leucine incorporation. It was confirmed that the lymphocyte response of patients was depressed. Furthermore, the lymphocytes of 15 out of 27 cancer patients, selected because of their low responses, inhibited the reactivity of normal lymphocytes in co‐cultures. The lymphocytes from one patient with Hodgkin's disease were also inhibitory. In contrast, lymphocytes from healthy subjects, patients with chronic lymphocytic leukaemia, lymphosarcoma or multiple myeloma caused no suppression. Experiments with purified cell populations from patients with carcinoma indicated that purified T cells responded to mitogens while unseparated lymphocytes failed to respond and that the inhibitory activity was due to adherent cells, presumably monocytes. There was no evidence for B‐cell‐mediated suppression. However, in two cases inhibition was caused by isolated T cells of the patients and not by adherent cells. These experiments suggested that one mechanism for the depression of cell‐mediated immunity seen in patients with advanced cancer may be the nonspecific suppression of certain T‐cell functions by circulating monocytes.
Fibrinolysis associated with human neoplasia: Production of plasminogen activator by human tumours
Authors: Nagy Biserka , Ban Jasna , Brdar Branko
Published: February 2007

The plasminogen‐dependent fibrinolytic activity of several human tumours has been studied. The following neoplastic tissues, which were obtained from cancer patients by either surgery or biopsies, were examined: cervical, mammary, prostatic, ovarian, lung carcinomas, melanoma, basalioma. Fibrinolysis was measured in lysates either of tumour tissue specimens or of respective cell cultures. This measurement was based on release of radioactivity from 125I‐fibrin‐coated Petri dishes. All examined tumours showed elevated levels of plasminogen‐dependent fibrinolytic activity. However, normal control tissues had little or no activity. These results indicate that the fibrinolysis might be useful in differentiating between malignant and normal tissues.
Characterization of EBV‐genome negative “null” and “T” cell lines derived from children with acute lymphoblastic leukemia and leukemic transformed non‐Hodgkin lymphoma
Authors: Schneider Ulrich , Schwenk Hans‐Ulrich , Bornkamm Georg
Published: February 2007

Sixty‐two explants from peripheral blood, bone marrow and cerebral fluid of children with acute lymphoblastic leukemia (ALL) and leukemic transformed non‐Hodgkin lymphoma (NHL) were cultivated for at least 8 weeks. Although lymphatic cells persisted up to 16 weeks in tissue culture, no proliferation was observed in 54 cultures. From the remaining cultures, eight permanently growing cell lines were obtained. Five of these were EBNA (Epstein‐Barr virus‐specific nuclear antigen)‐positive. Three, however, were EBNA‐negative and lacked Epstein‐Barr virus genomes. Two cell lines (KM‐3 and SH‐2) expressed neither B nor T cell characteristics. One line (JM) expressed T cell characteristics and complement receptors. The growing lymphatic cells represented leukemic cells, since the pattern of cytochemical staining and that of membrane receptors of lymphoblasts from the same donor prior to cultivation were identical. All leukemic cell lines were derived from patients in relapse. In contrast, no proliferation of leukemic cells occurred in explants from patients revealing the first manifestation of the disease. These results suggest enhanced growth potential of lymphoblasts resisting antileukemic therapy.
Neutralizing EBV‐specific IgA in throat washings of nasopharyngeal carcinoma (NPC) patients
Authors: Desgranges C. , De‐Thé G. , Ho J. H. C. , Ellouz R.
Published: February 2007

Throat washings from 26 nasopharyngeal carcinoma (NPC) patients from Hong Kong and Tunisia were studied for the presence of transforming EBV. Only six (23%) were found positive which led to the hypothesis of a neutralizing factor in such salivas. The search for EBV‐specific antibodies showed that NPC saliva contained neutralizing VCA and EA IgA (54 and 27% respectively) and VCA and EA IgG (73 and 54% respectively). Both transforming and non‐transforming throat washings contained virus particles as visualized by electron microscopy, but in non‐transforming salivas (containing IgA and IgG) the particles were found to be clumped. Comparative study of throat washings from patients with Burkitt's lymphoma (BL), infectious mononucleosis (IM), immunodeficiencies, other cancers, and healthy subjects showed that IgA were restricted to NPC cases.
Detection of SV40 T antigen with labelled antibodies: Radioimmunoassay and autoradiography
Authors: Flügel R. M. , Crefeld T. , Munk K.
Published: February 2007

SV40 T antigen, partially purified from SV80, a human cell line, has been used to develop a sensitive solid phase radioimmunoassay. In this assay SV40 T antigen was immobilized on microtiter plates, reacted with hamster anti‐SV40 T antibody and subsequently with 14C‐labelled anti‐hamster IgG. The test detected approximately 20 ng of partially purified SV40 T antigen and is rapid and more convenient than the complement fixing reaction. An immunoautoradiographic method which permits the determination of the cellular localization of SV40 T antigen and which is possibly more sensitive than the indirect immunofluorescence method is also described.
An analysis of the factors allowing promotion (rather than inhibition) of tumour growth by corynebacterium parvum
Authors: Bomford R.
Published: February 2007

The following factors were found to determine whether C. parvum (CP) treatment promoted rather than inhibited the growth of methylcholanthrene‐induced fibrosarcoma cells injected into CBA mice. (1) The dose of tumour cells. Promotion occurred only with low doses, around the TD50. (2) The route of injection of CP. Greater promotion was caused by intravenous (IV) than by subcutaneous (SC) administration. Addition of irradiated tumour cells to SC CP resulted in tumour inhibition. (3) The dose of CP. Promotion increased with increasing dose of either SC or IV CP. (4) The time of CP injection relative to tumour challenge. Promotion only occurred when CP was given before tumour cells, except when using IV CP and very few tumour cells. With increasing doses of tumour cells, first post‐treatment with IV CP and then pre‐treatment became inhibitory. The effect of CP on established immunity to tumour cells was also studied. Mice were immunized by tumour amputation. The resistance to tumour challenge thus generated could be abrogated by CP given before challenge, most effectively by a high dose IV. The data are interpreted according to the following hypothesis. (1) CP suppresses the expression of cell‐mediated immunity to tumour antigens. (2) This is caused by trapping of anti‐tumour effector cells at the site of CP deposition. (3) Promotion can only occur when CP is given before effector cells have reached the tumour site.
Primary tumor immunity in nude mice
Authors: Prehn Liisa M. , Outzen Henry C.
Published: February 2007

Tumor implants grew better in radiated or in newborn nu/nu mice than in adult nu/nu controls when, and only when, the tumors were demonstrably immunogenic in normal mice. This result suggests primary immunity. No evidence of immunological memory was found by immunization‐challenge type experiments in the nude mice.
Carcinogenicity of DDT (dichlorodiphenyl trichloroethane) in pure inbred Swiss mice
Authors: Kashyap S. K. , Nigam S. K. , Karnik A. B. , Gupta R. C. , Chatterjee S. K.
Published: February 2007

Inbred Swiss mice were treated with technical DDT (1) orally with the diet or by intubation; (2) subcutaneously and (3) by skin painting. The total duration of the experiment was 80 weeks. There was no difference in body growth and mortality between the experimental and control groups. Toxic manifestations of DDT were observed in treated mice in the form of tremor, convulsions and corneal opacity usually after 40 weeks. Oral and subcutaneous DDT treatment resulted in a significant increase in the incidence of tumours mainly of lymphoid tissues, lung and liver. The highest tumour incidence was recorded in the group of mice receiving DDT by subcutaneous injections. Males and females were equally susceptible. No evidence of carcinogenicity was observed in the painted group.
Transformation of normal hamster cells by benzo(a)pyrene diol‐epoxide
Authors: Mager Rivka , Huberman Eliezer , Yang Shen K. , Gelboin Harry V. , Sachs Leo
Published: February 2007

The frequency of cell transformation was determined after treatment of normal hamster embryo cells with benzo(a)pyrene (BP) and six of its metabolites. These metabolites included the trans 4,5‐, 7,8‐ and 9,10‐dihydrodiols; the 4,5‐epoxide; and two stereoisomers of the non‐K‐region diol epoxides r‐7, t‐8‐dihydroxy t‐9, 10‐oxy‐7,8,9,10‐tetrahydro‐benzo(a)pyrene (diol‐epoxide I) and r‐7, t‐8, dihydroxy c‐9, 10‐oxy‐7,8,9,10‐tetrahydrobenzo(a) pyrene (diol‐epoxide II). The trans 7,8‐dihydrodiol was more active than the other two dihydrodiols tested and was also more active than the parent hydrocarbon BP. Of the three epoxides tested, the diol‐epoxide I was more active than the 4,5‐epoxide and diol‐epoxide II. The results suggest that diol‐epoxide I is a major cell‐transforming metabolite of BP.
Biological characterization of a tumour‐growth‐promoting factor from ascitic fluid of tumour‐bearing mice
Authors: Henriksen Ole , Law Lloyd W.
Published: February 2007

Tumour‐growth‐promoting activity has been observed in ascitic fluids of mice with progressively growing SV40‐ and chemically induced tumours. Administration of ascitic fluid to animals together with a normally non‐tumorigenic dose of SV40‐transformed tissue culture cells (TU‐5) will cause these cells to grow progressively and eventually kill the animals. Also, the mKSA‐specific, immunologically non‐responsive state (the eclipse phase) of mice bearing large mKSA tumours can be maintained by administration of ascitic fluid or serum from tumour‐bearing animals after the tumours have been surgically removed. Normally, complete immunity to a secondary tumour cell challenge is re‐established approximately 10 days after removal of the primary tumour, but daily injections of ascitic fluid or serum will maintain eclipse so that a secondary challenge of tumour cells will grow progressively. The active component apparently acts non‐specifically, since ascitic fluid from an unrelated tumour also is able to maintain the mKSA‐specific eclipse phase. The ascitic fluid has no apparent immunosuppressive activity in vivo.
Binding of soluble form of fibroblast surface protein, fibronectin, to collagen
Authors: Engvall Eva , Ruoslahti Erkki
Published: February 2007

Fibronectin, a plasma protein immunologically identical with a major surface protein of normal fibroblasts, was found to bind to collagen and gelatin. A solid phase enzyme immunoassay was used for the binding tests. Collagen, gelatin or various control proteins were adsorbed to a plastic surface. Binding of fibronectin was detected using purified fibronectin antibodies conjugated to alkaline phosphatase. Circulating fibronectin and fibronectin obtained from fibroblast cultures both showed specific binding to collagen and gelatin. Preparative affinity chromatography of plasma on gelatin coupled to Sepharose gave electrophoretically and immunologically pure fibronectin in high yields. Malignantly transformed fibroblasts lack surface fibronectin. Our findings suggest the possibility that this results in a lack of anchorage to the surrounding intercellular matrix, which could contribute to the malignant growth behavior.
Epstein‐Barr herpesvirus infection: Inhibition by immunologically induced mediators with interferon‐like properties
Authors: Lai P. K. , Alpers P. , MacKay‐Scollay E. M.
Published: February 2007

When sensitized leukocytes were re‐exposed to EBV antigen or to tuberculin‐purified protein derivatives, they produced lymphokines, including the migration inhibition factor, which inhibited the migration of guinea‐pig peritoneal exudate cells, and other lymphokines with the characteristics of interferon, which inhibited EBV‐induced transformation and EBV superinfection of target cells. Unsensitized leucocytes from sero‐negative adults and from neonates did not produce lymphokines when challenged with the antigens. This indicates that cell‐mediated immunity and its associated soluble mediators may be involved in the control of EBV infection and that the interferon release assay is a useful in vitro correlate for the study of cellular immunity to EBV.
Nucleic acid content and cell cycle distribution of five human bladder cell lines analysed by flow cytofluorometry
Authors: Traganos F. , Darzynkiewicz Z. , Sharpless T. , Melamed M. R.
Published: February 2007

Five human bladder cell lines, four derived from tumor tissue and the fifth originating from presumed benign transitional epithelium, were examined by flow cytofluorometry to estimate the DNA and RNA content per cell during exponential and stationary phases of growth. A new staining technique was employed using acridine orange to differentially stain DNA and RNA in unfixed cells made permeable to the dye and other reagents by treatment with detergent at low pH. Stemline chromosome numbers for each cell line correlated well with relative DNA content of the G1 population as measured by this technique. In addition, the simultaneous measurements of DNA and RNA per cell yielded cell cycle distributions for each cell line. The ratio of stainable RNA/DNA was lower for all cell lines derived from bladder tumors as compared to the presumed normal cell line, indicating high nuclear/cytoplasmic ratios for the former.
Synthesis of type‐C virus particles from murine cultured cells induced by iododeoxyuridine. VI. Biosynthesis of reverse transcriptase
Authors: Reitz M. S. , Wu A. M. , Gallo R. C.
Published: February 2007

Treatment with 5‐iodo‐2'‐deoxyuridine (IdUrd) of BALB/3T3 cells non‐productively transformed with Kirsten murine sarcoma virus (K‐BALB) results in the induction of extracellular type‐C virus production with a concomitant appearance of intracellular reverse transcriptase. Production of BALB virus‐2 (v‐2) and its Kirsten sarcoma virus pseudo‐type, occurring 2‐3 days after IdUrd treatment, is inhibited and stimulated by interferon and dexamethasone, respectively, By contrast, and as previously reported, neither compound affects synthesis of N‐tropic virus (BALB virus‐1) which is produced later (5‐7 days) after IdUrd treatment. The stimulatory and inhibitory activities of these compounds are partially antagonistic since: (1) the simultaneous presence of both dexamethasone and interferon results in a virus production level between those observed with either compound alone; and (2) increasing the dexamethasone concentration at a fixed interferon concentration increases virus production. However, the effects of these two compounds on the appearance of an intracellular viral protein (reverse transcriptase) after IdUrd treatment were unexpected. The post‐induction appearance of intracellular reverse transcriptase is inhibited by interferon but is not affected by dexamethasone. This suggests that dexamethasone stimulates a step after protein synthesis, and that interferon inhibits an earlier step (translational or pre‐translational) or that it enhances degradation of viral proteins. When interferon and dexamethasone are both present, no inhibition of the appearance of reverse transcriptase is observed. Thus, dexamethasone has a second effect on virus production, namely to prevent the inhibition by interferon of the appearance of intracellular reverse transcriptase. Since dexamethasone completely overcomes the inhibitory effect of interferon on intracellular reverse transcriptase levels, but only partially reverses the inhibition by interferon of virus production, interferon (in the presence of dexamethasone) must also inhibit a post‐translational step in virus production. This step may or may not be the same as the late dexamethasone‐sensitive step. Thus, both dexamethasone and interferon appear to have both translational (or pre‐translational) and post‐translational effects on the production of xenotropic (v‐2) mouse type‐C virus. This suggests that BALB/c mouse cells restrict the production of xenotropic endogenous virus at two distinct sites.
Separation of the moloney leukemia virus‐determined cell surface antigen (MCSA) from known virion proteins associated with the cell membrane
Authors: Siegert Wolfgang , Fenyö Eva Maria , Klein George
Published: February 2007

Cell membranes of Moloney lymphoma cells (YAC, of strain A origin) were solubilized by NP40. The antigenicity of the solubilized protein fraction was assayed by inhibition of the corresponding cytotoxic reaction against YAC target cells. The Moloney leukemia virus (MLV)‐determined cell surface antigen (MCSA) was detected with mouse antisera, produced by the repeated inoculation of heavily irradiated YAC cells into syngeneic mice. Virion proteins gp71, p30, p15, p12 and p10 were identified with goat or rabbit antisera against purified Rauscher and Friend leukemia virus proteins. MCSA was found to bind to Con‐A—Sepharose and was eluted by mannoside together with H‐2a and gp71. In contrast, p30, p12, p10 and part of p15 and p15(E), were not retained on the column and could be separated from MCSA. Passage of the glycoprotein fraction through Sephadex G‐200 led to the separation of MCSA activity from gp71 and H‐2a. MCSA eluted between the immunoglobulin (IgG) and the bovine serum albumin (BSA) size markers. MCSA could be also separated from the known viral proteins and from H‐2 by velocity centrifugation in sucrose gradients. It sedimented with approximately 6.6 S ahead of gp71 (4.4 S) and H‐2 (3.2 S). It is suggested that MCSA may be a glycoprotein with an approximate molecular weight of 110,000 and distinct from the known viral proteins gp71, p30, p15, p15(E), p12, p10 and from H‐2.
Tumor necrosis and cell detachment
Authors: Weiss Leonard
Published: February 2007

Cell detachment from and around Walker 256 tumors grown in rats is quantitated by a standardized in vitro shaking procedure. The volume of cells detached from cancers of similar size is virtually the same in tumors growing in the liver, the spleen, in intramuscular and in subcutaneous sites. In cystic tumors, greater volumes are detached from the innermost regions of the walls adjacent to necrotic material than from the outermost parts. More liver perenchymal cells are shaken free of liver adjacent to a tumor interface than from regions 0.5 and 1.0 cm distant from it. Detachment of tumor and liver cells is also enhanced by prior incubation of tissue samples with necrotic extracts. It is suggested that the necrotic regions of tumors, and products derived from them, facilitate the detachment of tumor cells and cells composing the normal tissues surrounding them, thereby potentially promoting metastasis and invasion.
Natural cytotoxicity to human leukemia mediated by mouse non‐t cells
Authors: Haller Otto , Kiessling Rolf , Örn Anders , Kärre Klas , Nilsson Kenneth , Wigzell Hans
Published: February 2007

Natural killer (NK) cells cytotoxic for certain syngeneic or allogeneic tumor cells have been described in various species, including mouse, rat and man, as a new type of effector cell. In this paper, we show that mouse NK cells also function in a xenogeneic system. Established human hematopoietic cell lines were used as targets for normal mouse spleen effector cells in a short‐term 51Cr release assay. Nine malignant lymphoma, two myeloma and four leukemia lines as well as six lympho‐blastoid cell lines of presumed non‐neoplastic origin were tested. Specific and reliable killing was obtained with the T leukemias MOLT‐4, JM, CCRF‐H‐SB‐2 and the myeloid leukemia K 562. Most other lines were sensitive to some degree but their susceptibility and the specificity of the reactions were of doubtful significance. The heterologous cytotoxic reactivity was shown to be caused by the same kind of murine effector cells that mediate NK activity against certain mouse lymphomas by the following criteria: (1) the differences in killing capacity found between spleen cell preparations from genetically “high” or “low” NK‐reactive inbred mouse strains did apply in this heterologous system; (2) cytotoxicity was related in a typical manner to the age of the effector cell donor; (3) spleen cells from T‐deficient nude mice were highly cytotoxic; (4) removal of T cells, B cells and phagocytic cells using standard fractionation procedures did not abrogate the lytic ability of the remaining spleen cell population. Specificity of lysis was assessed using unlabelled cells as competing targets together with labelled target cells. When competitor cells were identical to the target cells, good competition was achieved. Mouse or human cell lines insensitive to lysis by mouse NK cells had no competitive capacity for target cells of either species. Using NK sensitive lines, competition between mouse and human cells was found to be unidirectional with the most sensitive tumors being the best inhibitors. Thus, unlabelled mouse T lymphoma YAC‐1 cells were efficient competitors for lysis of human T leukemia lines. Conversely, susceptible human cells used as competitors did not significantly inhibit killing of YAC‐1 targets. The implications of these findings are discussed.
Establishment of simian sarcoma virus, type 1 (SSV‐1)‐transformed non‐producer marmoset cell lines
Authors: Bergholz Carolyn M. , Wolfe Lauren G. , Deinhardt Friedrich
Published: February 2007

Simian sarcoma virus, type 1 (SSV‐1)‐transformed non‐producer cell lines were established by infection of normal marmoset fibroblast cells (HF) with limiting dilutions of SSV‐1. Four focus‐derived cell lines were identified as non‐producers by assay of culture fluids for focus‐forming activity and by the mixed culture cytopathogenicity test with XC cells. Further studies failed to detect production of type‐C virus by 3H‐uridine labelling, reverse transcriptase assay or electron microscopy. The non‐producer cell lines, designated HF/SSV‐NPI, IV, V, and VI, appeared morphologically transformed and cloned in soft agar with the same efficiency as HF/SSV‐1 virus‐producing transformed cells. Expression of either cytoplasmic or cell surface virus‐related antingens was not detected by immunofluorescence or serum cytotoxicity tests. The presence of sarcoma genome in the transformed non‐producer cell lines was demonstrated by rescue of focus‐forming activity following superinfection with non‐transforming helper virus or by cocultivation with helper‐virus‐producing cell lines. The SSV‐1‐transformed non‐producer primate cells provide a useful tool for future studies.
The effect of azathioprine on host cell infiltration and growth of a murine fibrosarcoma
Authors: Evans R.
Published: February 2007

Azathioprine (AZ) was injected into C57 Black mice before or after IM implantation of the syngeneic fibrosarcoma FS6, and observations were made on tumour growth and on the cellular composition of the fibrosarcomas. When multiple injections were given to the tumour‐bearing host the tumours regressed. The percentage of tumour‐associated macrophages remained essentially stable as regression occurred whereas the percentage of θ‐antigen‐positive cells increased. In the case of single IP injections of AZ, changes in the cellular composition of tumours were seen only when AZ was given 1‐72 h before implantation but not when it was given after implantation. Compared with controls there was a 2‐ to 3‐week delay in the appearance of large numbers of tumour‐associated macrophages. The percentage of θ‐antigen‐positive cells within the tumours mass was elevated 7 days post AZ treatment but the level declined to control values between days 10 and 13. The significance of the results is discussed in relation to the dependency of the macrophage content of this tumour upon the development of an immune response towards the tumour.
Inhibition of the growth of lymphoid tumours in syngeneic athymic (nude) mice
Authors: Warner Noel L. , Woodruff Michael F. A. , Burton Robert C.
Published: February 2007

A comparison of the growth of a number of BALB/c tumours in BALB/c, BALB/c.nu/+ (heterozygous nude) and BALB/c.nu (homozygous) nude mice has shown that a majority of BALB/c lymphoid tumours grow at a significantly reduced rate in BALB/c.nu mice. The three non‐lymphoid BALB/c tumours (carcinomas and sarcomas) tested and a minority of lymphoid tumours, however, grew as well, or better, in the BALB/c.nu mice. Furthermore a correlation, without exception to date, has emerged from a comparison between the susceptibility of a tumour cell line to in vitro lysis by spleen cells from syngeneic nude mice and its growth in vivo in syngeneic nude mice. Only those lymphoid tumour cell lines lysed in vitro show the reduced growth rate in syngeneic nude as compared to syngeneic normal mice. Tumour cell lines, both lymphoid and non‐lymphoid, which are resistant to in vitro lysis do not show the reduced in vivo growth rate in syngeneic nude mice. Both the in vivo and in vitro effect can be partially abolished by irradiating the nude mice prior to use, suggesting that a radiation‐sensitive non‐T‐cell surveillance of lymphoid tumours is operating in nude mice. While the identity of the antigens is still unknown, the specificity of the phenomena suggest that C‐type RNA oncogenic viral determined antigens are involved.
Establishment of a human medulloblastoma cell line
Authors: McAllister R. M. , Isaacs H. , Rongey R. , Peer M. , Au W. , Soukup S. W. , Gardner M. B.
Published: February 2007

A cell line consisting of polygonal and fusiform cells was derived from a cerebellar medulloblastoma. Cells grew to high population density in liquid medium and formed colonies in agar medium. No neural or glial elements could be demonstrated in the cultured cells by electron microscopy nor were virus particles detected. The cells formed tumors in nude mice and in antithymocytic serum (ATS)‐treated hamsters. The tumors had a microscopic appearance similar to that of the medulloblastoma from which the cell line was derived. The cell line and lines derived from the transplant tumors in two hosts had four common “marker” chromosomes as well as non‐specific cytogenetic changes.