bluuebunny/crossref_metadata_2025 huggingface dataset:
Specificity of cell‐mediated cytotoxicity against human melanoma lines: Evidence for “non‐specific” killing by activated T‐cells
Authors: Hersey P. , Edwards A. , Edwards J. , Adams E. , Milton G. W. , Nelson D. S.
Published: February 2007

The specificity of cell‐mediated cytotoxicity against melanoma cells in vitro has been analyzed in a large number of studies with cells both from normal and melanoma subjects. As in a number of other, recent, similar human studies, no evidence for tumour specificity was found. Effector cells in peripheral blood responsible for the cytotoxic reaction were examined by cell separation methods based on red cell rosette formation and separation through Hypaque‐Ficoll mixtures. The evidence suggests that nonspecificity results from killing by cells separating largely in the non‐sheep red blood cell rosetting fraction and which have cytotoxic specificity directed broadly to cells with abnormal membranes. Further analysis revealed that the cells were non‐phagocytic and did not bear receptors for complement. They appear to be activated into cell division and to bear surface receptors for the Fc portion ofIgG. Additional evidence is presented suggesting that the cells mainly responsible are activated thymus‐dependent cells present in the circulation of both tumour‐bearing and normal subjects.
Early alterations in plasma esterases with associated pathology following oral administration of diethylnitrosamine and butylated hydroxytoluene singly or in combination
Authors: Tyndall R. L. , Colyer S. , Clapp N.
Published: February 2007

Plasma esterase changes are apparent in BALB/c mice within 3 weeks after feeding them laboratory chow with 0.75% of the antioxidant BHT added. Other esterase changes, different from those in BHT‐treated animals, are also apparent in plasma of mice during exposure to the carcinogen DENA. Interference with these DENA esterase alterations is apparent in plasma of mice treated concomitantly with both DENA and BHT. Esterase changes resulting from either the carcinogen or antioxidant exposure precede the overt histologically detected changes induced by these compounds. The early esterase changes and subsequent tumorigenesis resulting from DENA exposure are more severe in female mice. Some of the esterases altered by DENA or BHT exposure are testosteronerelated.
A fetuin‐like antigen from human nephroblastoma
Authors: Wise K. S. , Allerton S. E. , Trump G. , Powars D. , Beierle J. W.
Published: February 2007

An antigen was detected in pooled human nephroblastomas using antiserum prepared in rabbits against an ethylenediaminetetra acetic acid (EDTA) extract of the tumors. This antigen was not found in normal human plasma or kidney extracts, and was not related to the ABO or Forssman blood groups. The antigen was detected in extracts of cultured nephroblastoma cells, but was not present in extracts of normal human fetal kidney cell cultures. The antigen is believed to be present at the cell surface, as cell viability was not significantly lowered during the extraction procedure. A reaction of complete identity was demonstrated by Ouchterlony double diffusion experiments with this antigen and purified bovine fetuin. The antigen was not found in extracts of human fetal spleen, thymus or kidney, nor in human fetal serum. Furthermore, the antigen does not possess determinants in common with the human alpha‐fetoprotein of hepatomas, nor was it detected in human renal clear cell carcinoma. Initial characterization of the antigen showed it to be nondialysable, not sedimentable at 100,000 × g for 2 h, stable to repeated freeze‐thawing and to incubation at 56° C for 1 h, and water soluble over a wide ph range. The antigen was susceptible to digestion with pronase and trypsin and possibly hyaluronidase, but not to ribonuclease or neuraminidase. The protein portion is therefore of major importance to the structural integrity of this antigen. The relationship between this antigen and other abnormal materials reported previously in nephroblastoma patients is being studied.
Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. II. Characterization of effector cells
Authors: Herberman Ronald B. , Nunn Myrthel E. , Holden Howard T. , Lavrin David H.
Published: February 2007

Studies were performed to characterize the effector cells responsible for natural cytotoxicity of mouse lymphoid cells against a variety of syngeneic and allogeneic tumor lines. Since spleen cells from normal nude mice were found to be highly cytotoxic, they were used for most of these experiments. Only a small proportion of the reactivity was affected by treatment with anti‐θ serum plus complement. Macrophages did not appear to be responsible for the reactivity, since treatment with carbonyl iron/magnet or carrageenan did not affect the levels of cytotoxicity. The effector cells were non‐adherent, since passage over nylon columns resulted in a considerable increase in activity. The active cells did not have receptors for immunoglobulin or complement, since removal of cells with these receptors by columns or monolayers containing sheep erythrocyteantibody (EA) complexes or EA‐complement complexes did not remove activity. Antibody‐dependent cell‐mediated cytotoxicity appeared to be ruled out as the mechanism for natural cytotoxicity, since aggregated gamma globulin and a potent anti‐immunoglobulin reagent did not inhibit reactivity, and since no role for humoral factors could be demonstrated. The natural effector cell was found to be quite labile at 37° C, losing much of its activity after 4 h. Since no surface markers could be detected on the effector cells, and the mechanism for cytotoxicity appeared distinct from others previously described, it is proposed that the natural cytotoxicity against mouse tumor cells is mediated by a unique subpopulation of lymphoid cells, which are tentatively designated N‐cells.
Comparison of intracytoplasmic A particles and intracisternal A particles
Authors: Wivel Nelson A. , Smith Gilbert H. , Ozer Harvey L.
Published: February 2007

Intracytoplasmic A particles and intracisternal A particles are associated with mouse tumors of various types, and both can coexist in the cytoplasm of the same cell. The designation of both as A particles is based on the recognition that they share morphological similarities. A comparison of purified isolates of these two particles reveals that the structural protein profiles are different, but that there is some antigenic crossreaction as demonstrated by immunodiffusion and complement fixation. This result does not appear to involve the major structural protein of intracisternal A particles, but may reflect the presence of common antigenic determinants located on minor proteins.
Restoration of specific immunity against SV40 tumor‐specific transplantation antigen to lymphoid cells from tumor‐bearing mice
Authors: Blasecki John W. , Tevethia Satvir S.
Published: February 2007

Specific cell‐mediated immunity to SV40 tumor‐specific transplantation antigen (TSTA) in BALB/c mice undergoing progressive tumorigenesis by syngeneic SV40‐transformed cells (VLM) was investigated in vivo using a tumor‐cell neutralization test. Specific cellular reactivity to SV40 TSTA was not detected in BALB/c mice bearing large tumors (10‐15 mm mean diameter) but was demonstrable after tumor excision. Specific cytotoxic reactivity against syngeneic SV40‐transformed cells in vivo could be restored to lymphoid cells from VLM tumor‐bearing mice either by culturing the lymphoid cells in vitro or by treating them with papain or trypsin. Enzyme‐treated lymphoid cells from MCA tumor‐bearing BALB/c mice had no cytotoxic reactivity against VLM cells. These studies suggest that tumor‐bearing hosts possess lymphocytes which are sensitized to the TSTA of the tumor but that the reactivity of these lymphocytes is blocked.
Spleen‐cell reactivity against transplanted neurogenic rat tumors induced by ethylnitrosourea: Uncovering of tumor specificity after removal of complement‐receptor‐bearing lymphocytes
Authors: Cornain Santoso , Carnaud Claude , Silverman David , Klein Eva , Rajewsky Manfred F.
Published: February 2007

Spleen cells from BDIX‐rats bearing either GVIAI‐tumor (a syngeneic mixed glioma) or NVI Ac‐tumor (a cloned syngeneic neurinoma of the peripheral nervous system) were cytotoxic to both tumor cells in vitro. However, the tumors displayed individually distinct antigenic specificities by in vivo rejection tests. Their in vitro cross‐reactivity disappeared when a particular subpopulation of the spleen cells was used. The procedure of lymphocyte purification included three consecutive steps: treatment with carbonyl iron and magnetism, passage through a nylon wool column, and finally removal of complement receptor‐bearing cells present in the colum‐excluded population. Cross‐reactivity between the syngeneic tumors persisted after the first two steps of lymphocyte purification. In contrast, specific cytotoxic reactions were observed against each individual tumor subsequent to the removal of the remaining C3 receptorpositive but surface Ig‐negative cells. While killer cells were present in normal spleen‐cell populations, these were almost completely eliminated by passage through the nylon wool column.
Carcinogenicity of methylated nitrosopiperidines
Authors: Lijinsky William , Taylor H. Wayne
Published: February 2007

The carcinogenicity of nitrosopiperidine and five methylated derivatives was compared by feeding them to rats at equimolar concentrations in drinking water, at the rate of 20 ml per day, 5 days a week. The maximum treatment time was 50 weeks. Nitrosopiperidine, 2‐methyl‐, 3‐methyl‐ and 4‐methyl‐nitrosopiperidine induced tumors of the nasal turbinates or upper gastrointestinal tract in almost 100% of the animals. There was a significantly longer time to death from these tumors in the group treated with 2‐methylnitrosopiperidine and a number of hepatocellular carcinomas appeared in this longer lived group. Very few tumors of these sites were seen in rats treated with 2,6‐dimethyl‐ or 2,2,6,6‐tetramethyl‐nitrosopiperidine. It was concluded that blockage by methyl groups of one or more carbon atoms alpha to the nitroso function in nitrosopiperidine significantly reduces carcinogenic activity of the molecule.
Nuclear proteins of rat liver and of an aminoazo‐dye‐induced hepatoma
Authors: Fujitani Hideo , Holoubek Viktor
Published: February 2007

Nuclear proteins of rat liver and rat ascites hepatoma were fractionated by extraction in solutions of different salt concentration and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The difference between the electrophorograms of the different fractions of nuclear proteins isolated from liver and from hepatoma was found in the bands which have the same electrophoretic mobility as the main proteins of informofers and are extracted from nuclei at salt concentrations which extract informofers. These changes in the electrophoretic patterns of proteins with the solubility and mobility of the proteins of informofers could be related to the defective processing of heterogeneous nuclear RNA in the hepatoma. In addition the identity of electrophorograms of nuclear proteins isolated from liver and from hepatoma and the identity of most bands in the electrophorrgrams of nuclear proteins which are soluble in 0.35 M NaCl and chromosomal proteins which are not soluble at this salt concentration support the notion that these nonhistone nuclear proteins which can be identified as the major bands in electrophorograms of chromosomal proteins are not the specific regulators of gene expression.
Evidence for two factors in sera of tumor‐immunized mice which induce specific lymphoid cell‐dependent cytotoxicity: IgG2 and a rapidly appearing factor not associated with IgG or IgM
Authors: Pollack Sylvia B. , Nelson Karen
Published: February 2007

As previously shown, sera from tumor‐bearing mice can induce specific antiserum‐dependent lymphoid cell‐mediated cytotoxicity (ADC) to syngeneic tumor cells in vitro. The ADC activity in such sera is now shown to be removed by adsorption of the sera to Sepharose‐linked rabbit anti‐mouse immunoglobulin or to goat anti‐mouse IgG2. Immunoglobulins recovered by elution from the affinity columns mediated ADC to the specific tumor cells. In addition, the eluted immunoglobulin passively “armed” normal lymph‐node cells in vivo so they were specifically cytotoxic when tested in vitro. Sera taken 48 h after inoculation of tumor or syngeneic tumor cells (before the appearance of palpable tumor) were also shown previously to induce lymphoid cell‐mediated cytotoxicity in vitro. This cytotoxic activity was not removed by adsorption of the sera to either anti‐IgG or anti‐IgM‐linked Sepharose. Thus both IgG and an early‐appearing serum component which is apparently neither IgG nor IgM can induce specific cell‐mediated cytotoxicity by non‐immune lymphoid cells in vitro.
A case/control study of the association between primary liver cancer and hepatitis b infection in senegal
Authors: Prince Alfred M. , Szmuness Wolf , Michon Jacqueline , Demaille Jacques , Diebolt Georgette , Linhard Jacques , Quenum Cyprien , Sankale Marc
Published: February 2007

A case/control study has been carried out to determine by radioimmunoassay and passive hemagglutination techniques the prevalance of hepatitis B surface antigen (HBsAg) and antibody (anti‐HBs) in patients with primary liver cancer (PLC) and age/sex‐matched hospital controls with cancers of other sites (OCC) and similarly matched controls without cancer (NCC). HBsAg was found in 61.2% of 165 cases of PLC as compared to 11.7% of 154 OCC and 11.3% of 328 NCC. The frequency of HBsAg in PLC patients was significantly higher (72.2%) in those with detectable alpha fetoprotein as compared to those without (40.3%). There was no difference in the frequency of HBsAg in PLC patients with and without accompanying cirrhosis. No significant difference in potential hepatitis exposure history was found in the three study groups.
Tumour metastasis in mice with reduced immune reactivity. III. Studies with three weakly antigenic tumours in thymectomized and/or sub‐lethally irradiated mice
Authors: Suurküla Mart , Boeryd Bernt
Published: February 2007

A previous observation that increased spontaneous metastasis formation from the highly antigenic MCA‐induced sarcoma MCG101 occurred in immunosuppressed C57BL/6J mice prompted the present study to establish whether or not tumours capable of inducing only weak transplantation resistance would behave similarly. One MCA‐induced sarcoma, MCG12, one epidermoid carcinoma, EpCal in CBA mice and a spontaneous mammary carcinoma, MaCal in C3H mice, were transplanted into adult thymectomized and/or sub‐lethally irradiated mice at different intervals after irradiation. The effects of the treatments on the immunoreactivity were monitored in separate groups by determining the primary and secondary responses to SRBC and the survival of first set allogeneic skin grafts. The treatments resulted in a significantly increased incidence of mainly the lymph‐node metastases with MCG12 and of only the lung metastases with EpCal. No increase in metastases was noted with MaCal. Thymectomy potentiated the increase in metastases from MCG12 in irradiated mice but unexpectedly so only for a limited time after irradiation. Local growth of MCG12 and MaCal at the transplantation site was more rapid in females than in males. The changes in tumour growth and spread induced by the treatments varied with tumour‐host system, sex and time of transplantation after irradiation and did not conform well with any of the tested parameters of immunoreactivity. There was no close parallel between the effects of the treatments on growth and spread of the tumours.
Cellular immunity to transitional cell carcinoma of the urinary bladder. III. Effects of hydrostatic pressure therapy
Authors: O'Toole Carol , Helmstein K. , Perlmann P. , Moberger G.
Published: February 2007

The effects of hydrostatic pressure therapy on in vitro cellular cytotoxicity responses have been studied in 19 patients with transitional cell carcinoma of the bladder (TCC). Cytotoxicity was quantitated against allogeneic targets in a microplate assay or by 51chromium isotope release. Two types of reactivity were detected, the most common being a differential cytotoxicity for targets derived from TCC, in either short‐term or long‐term tissue culture. This reaction is operationally termed “tumor‐specific”. Less frequently, a general cytotoxicity for targets of diverse histogenic origins was observed. For the present, this is termed “non‐specific”. Nine patients were tested before pressure therapy and of these only two gave a specific reaction and one a non‐specific reaction, while six were non‐reactive. Eighteen patients were tested at varying intervals after treatment and of these 11 gave a specific reaction and one a non‐specific effect, while six were non‐reactive. Three individuals who were non‐reactive prior to therapy had a specific reaction post therapy. Two who reacted specifically before therapy became non‐reactive after therapy. Two cases remained non‐reactive throughout and the single case which gave a non‐specific effect before therapy became non‐reactive post therapy. The results of serial in vitro testing for cytotoxicity are presented with individual case histories, tumor staging and grading and the clinical outcome of hydrostatic pressure therapy.
Immunotherapy and vaccination against cancer with non‐living BCG and cord factor (trehalose‐6,6′‐dimycolate)
Authors: Bekierkunst A.
Published: February 2007

A vaccine containing non‐living BCG and living tumour cells prevented the growth of 106 tumour cells introduced distally into the skin of guinea‐pigs at the time of vaccination. A similar effect was achieved when living tumour cells of the vaccine were replaced by tumour cells pretreated with mitomycin C. The efficacy of the vaccine was significantly increased when cord factor was added to the vaccination mixture. The percentage of cures was about 88% (17 cases) in experiments in which the vaccine contained living tumour cells, 100% (10 cases) when mitomycin C‐treated cells were used. The significance and implications of the above findings are discussed.
Ultrastructural alterations and modifications of nuclear RNA of rat liver by the combined action of thioacetamide and aflatoxin
Authors: Reynier M. O. , Lafarge‐Frayssinet C. , Frayssinet C.
Published: February 2007

When aflatoxin is administered to thioacetamide‐treated rats, the synthesis of nuclear RNA not only stops but the RNA that had accumulated in the nuclei by thioacetamide action disappears, probably by degradation “in situ” as none appears in the cytoplasm. Morphologically, the lesions provoked by aflatoxin add to those caused by thioacetamide. In the gigantic nucleoli that develop upon exposure to thioacetamide, aflatoxin provokes atypical segregations that result in the formation of larger and larger spaces in the nucleoli.
A study of the oncogenicity of adenovirus type 2 transformed rat embbyo cells
Authors: Harwood Lesley M. J. , Gallimore P. H.
Published: February 2007

Rat embryo cells were transformed by adenovirus type 2 at different multiplicities of infection. The oncogenic potential of the resulting transformed lines varied considerably but a relationship was found to exist between transforming virus dose and oncogenicity of the resulting transformed lines. Possible reasons for the considerable variation in oncogenicity of the transformed lines are discussed, giving particular consideration to cellular antigenicity and recent molecular biology studies of adenovirus type 2 transformed cell lines.
Transformation of mouse cells after infection with ultraviolet irradiation‐inactivated herpes simplex virus type 2
Authors: Boyd Ann Lewis , Orme Thomas W.
Published: February 2007

A transformed mouse cell line (H238) was obtained following the infection of 238 mouse cells with ultraviolet (UV) irradiation‐inactivated herpes simplex virus type 2 (HSV‐2). The transformed cells produced tumors with a 100% incidence within 8 weeks in 6‐week‐old syngeneic BALB/c mice at an inoculum of 1 × 106. Indirect immunofluorescence (IF) tests revealed the presence of HSV antigens in the transformed cells. Antibodies to HSV‐2 were found in the sera of tumor‐bearing animals by neutralization and IF techniques. Neither HSV‐2 infectious virus nor viral antigens could be detected by the transfer of transformed‐cell DNA into permissive cells.
Antibody‐dependent cell‐mediated cytotoxicity for human monolayer target cells bearing blood group and transplantation antigens and for melanoma cells
Authors: Kodera Yoshihisa , Bean Michael A.
Published: February 2007

A sensitive assay for antibody‐dependent cell‐mediated cytotoxicity (ADCMC) was developed utilizing serum from a patient with gestational choriocarcinoma and the 3H‐proline microcytotoxicity test for detection of destruction of monolayer target cells. Conditions for optimal expression of ADCMC were investigated using serum from this patient and skin fibroblasts from her husband and daughter as target cells with semi‐purified blood leukocytes from normal donors as effector cells. Factors critical for optimal expression of ADCMC in this assay are the selection of effector cell donors possessing high levels of activity in the presence of serum with known lymphocyte‐dependent antibody (LDA), the effector cell preparative technique, and incubation for up to 40 h. Tris‐NH4Cl lysis of red blood cells was found significantly to reduce effector cell activity. Under optimal conditions, the LDA titer of this patient's serum was >10−4. The sensitivity of the assay was confirmed by the detection of LDA activity of an anti‐blood‐group antibody at dilutions not demonstrating hemagglutination, and by the induction of ADCMC for blood group A antigen‐bearing target cells by normal sera of B and O blood groups. In a preliminary study of sera from 16 melanoma patients on the corresponding autologous tumor target cells, four had significant LDA. Further studies are under way to determine specificity, incidence, and relationship of LDA‐positive autologous sera to course of disease.
Leukocyte adherence inhibition and specific immunoreactivity in malignant melanoma
Authors: Halliday W. J. , Maluish Annette E. , Little J. H. , Davis N. C.
Published: February 2007

The leukocyte adherence inhibition (LAI) test has been used to assess specific anti‐tumour immunoreactivity in 80 patients with malignant melanoma, 21 of whom had apparently been successfully treated by surgey, and 44 control subjects. Reaction with melanoma extracts in vitro enabled the activity of blood leukocytes to be detected by inhibition of their adherence to glass, while serum was tested for factors which modified this inhibition. Of the patients with tumours (ranging from primary melanoma in situ to advanced disseminated disease), 22/24 had active leukocytes and 50/58 had serum blocking factor; two of the sera, from patients with regressing tumours, were unblocking. After surgery with no clinical recurrence, leukocytes continued to be active except when tested several years after operation. Blocking factor rapidly disappeared in 16/20 patients tested, and in several patients examined serially the serum became unblocking. In three cases, persistence of serum blocking was followed by clinical diagnosis of metastases. Leukocyte activity was never detected in control subjects (0/10), many of whom had other kinds of tumours or skin lesions. Blocking activity in serum was found in only 3/38 controls with no history of melanoma (1 had a fibrosing cellular blue naevus and 2 had liver disease). Thus the LAI test correlated well with clinical and pathological findings, and shows great promise for the reliable, rapid and specific immunodiagnosis of malignant melanoma.
Retention of tritium during the binding of tritiated benzo(a)pyrene to DNA
Authors: Osborne M. R. , Thompson M. H. , King H. W. S. , Brookes P.
Published: February 2007

Chemical conversion of generally tritiated benzo (a) pyrene to 6 and 1,6‐substituted derivatives resulted in 30% and 48% loss of tritium respectively. Metabolism of [3H], [14C]‐benzo (a) pyrene by rat liver microsomes yielded 3‐hydroxybenzo (a) pyrene with 30% loss of tritium, a mixture of quinones with 50% loss of tritium and three dihydrodiol metabolites which had retained all the tritium of the parent hydrocarbon. DNA isolated from mouse embryo cells which had been exposed to [3H], [14C]‐benzo (a)pyrene, and DNA with this hydrocarbon bound following in vitro rat liver microsomal incubation were degraded enzymically and the hydrocarbon‐deoxyribonucleoside products isolated. The tritium contents of the products obtained from both DNA samples were very close to those of the original double labelled benzo (a)pyrene. These results are inconsistent with a phenol or quinone intermediate being responsible for the reaction with DNA, but fully consistent with a diol epoxide intermediate as proposed by Sims et al. (1974).
Rejection of tumor cells in vitro: A T‐cell‐mediated reaction
Authors: Berczi I. , Sehon A. H.
Published: February 2007

Cytotoxic lymphoblasts (LBC) were produced by the co‐cultivation of guinea‐pig lymphoid cells from the thymus, lymph nodes, spleen, bone marrow and blood with syngeneic methylcholanthrene‐induced sarcoma (MC‐D) cells. The cytotoxic reaction was inhibited by pretreatment of the lymphoid cell populations with a rabbit antiserum specific for guinea‐pig thymus‐derived (T) lymphocytes. Supernatants of LBC inhibited the migration of peritoneal exudate cells, but did not contain lymphotoxin or a skin reactive factor. It is concluded that the cytotoxic cells are of T‐cell origin.
Isozyme pattern of fructose diphosphate aldolase during hepatocarcinogenesis induced by 2‐acetylaminofluorene in rat liver
Authors: Silber Danuta , Checinska Ewa , Rabczynski Jerzy , Kochman Marian
Published: February 2007

The biosynthesis of aldolase A and B subunits has been studied in rat liver during the administration of carcinogen AAF

The abbreviations used in this paper are: FDP — fructose‐1,6‐diphosphate; F‐1‐P — fructose‐1‐phosphate; AAF — 2‐acetylaminofluorenea

. Transition from a predominance of aldolase B to A was observed during carcinogenesis in rat liver. Changes in isozymic pattern and FDP to F‐1‐P cleavage activity ratio were observed before histological alterations typical of hepatoma could be detected. Our data support the hypothesis of dedifferentiation during hepatocarcinogenesis which in an early stage results in switching on of the gene for aldolase A with simultaneous continuation of biosynthesis of aldolase B within single cells.
Colcemid‐induced polyploidy and aneuploidy in normal and tumour cells in vitro
Authors: Stavrovskaya A. A. , Kopnin B. P.
Published: February 2007

The frequency of colcemid‐induced genome mutations (aneuploidy and polyploidy) in normal and SV40‐transformed cultures of Djungarian hamster embryonic cells was studied. Genome mutations were easily induced by the drug in transformed but not in normal cultures. Elevation of colcemid concentration and prolongation of the incubation period did not substantially increase the frequency of genome mutations in normal cells. An attempt was made to study the causes of the differences in sensitivity to colcemid‐mutagenicity of normal and transformed cells. Transformed cells did not include more 3H‐colchicine than normal cells, and binding of the drug to cell homogenates was similar in both kinds of cultures. According to these data the higher sensitivity of transformed cells to colcemid is not connected either with increased permeability of the cell to the drug or with changes in its binding to tubulin.
Interactions between endogenous baboon type‐C virus and oncogenic viruses. I. Syncytium induction and development of infectivity assay
Authors: Ahmed Mumtaz , Korol Wlo , Larson David L. , Harewood Ken R. , Mayyasi Sami A.
Published: February 2007

Cells releasing the endogenous baboon virus (BV) can interact with human KC cells containing the Rous sarcoma virus (RSV) genome, resulting in cell fusion and syncytium formation. This interaction has been utilized in the development of a sensitive infectivity assay for BV. The titration pattern is of a one‐hit type, demonstrating a linear relationship between virus concentration and number of syncytial plaques obtained in the KC co‐cultivation assay. Endpoint titration comparisons indicate that the KC test is as sensitive as the immunofluorescence or the RNA‐directed DNA‐polymerase assays. Attempts to develop an XC test for BV failed, indicating that while BV can interact with the RSVgenome it will do so in the human KC cells and not in the rat XC cells. Syncytia are also induced when KC cells are directly exposed to cell‐free BV; however, a linear dose relationship is not obtained. When syncytium‐positive KC cultures are passaged, the syncytia disappear and a chronic BV infection is established. These KC‐BV cells then lose the ability to interact with either the endogenous cat RD‐114 virus or the Mason‐Pfizer virus which are known to form syncytia with KC cells.
Isolation of tumor‐specific antibodies from effusions of ovarian carcinomas
Authors: Dorsett Brent H. , Ioachim Harry L. , Stolbach Leo , Walker John , Barber Hugh R. K.
Published: February 2007

Peritoneal effusions of patients with ovarian cancer contain sizable amounts of free and complexed immunoglobulins. By means of salt precipitation procedures, antibodies were recovered that after purification and concentration displayed a high degree of specificity against ovarian carcinoma cells. In indirect immunofluorescence, immunoglobulins recovered from seven different peritoneal effusions showed bright cytoplasmic staining with tissue cultures and fresh suspensions of ovarian carcinoma cells but not of normal ovaries or non‐ovarian tumors. Immunoglobulins isolated from fluids of benign ovarian cysts or from effusions of non‐ovarian tumors were negative in immunofluorescence tests. Autologous antibodies recovered from peritoneal effusions will be hopefully utilized in sensitive radioimmunoassay tests that are greatly needed for the early detection of ovarian cancer, the leading cause of death from gynecologic neoplasia.
Lymphocyte stimulation by autologous tumor cells in the presence of serum from the same patient or from healthy donors
Authors: Vánky F. , Klein E. , Stjernswärd J. , Trempe G.
Published: February 2007

Lymphocyte blastogenesis induced by autologous tumor biopsy cells, by allogeneic lymphocytes and by PHA, was performed in the presence of autologous or allogeneic serum collected from normal blood donors. In 13 of the 15 cases lymphocyte stimulation by autologous tumor cells was inhibited in the presence of autologous serum. In contrast, autologous serum somewhat enhanced the blastogenic effect of PHA and allogeneic lymphocytes.
Immune enhancement of the tumorigenicity of hamster brain tumor cells persistently infected with measles virus
Authors: Evermann James F. , Burnstein Theodore
Published: February 2007

Studies were conducted on the tumorigenicity of a hamster brain tumor (HBT) cell line persistently infected with measles virus (MV). This cell population, termed HBT‐M, exhibited decreased tumorigenicity in weanling hamsters when implanted intracutaneously. The lowered tumorigenicity of the HBT‐M cells could be counteracted by concurrent hydrocortisone treatment restoring the tumor‐producing capacity to levels comparable to those of the highly tumorigenic HBT cells. It was also determined that prior immunization of hamsters with MV resulted in enhancement of tumor formation from usually subtumorigenic doses of HBT‐M cells. This increase in tumorigenicity appeared to correlate with high titers of MV antibody. Treatment of hamsters with cyclophosphamide resulted in a reduction of MV antibody titers and effected a decrease of HBT‐M cell tumorigenicity to control levels. Preliminary studies with passive immunizations indicated that the enhancing factor could be transferred in the sera from hamsters hyperimmunized with MV. These data suggested that MV antibody may potentiate the development of neoplasia of cells persistently infected with MV in a manner similar to the enhancement of tumor growth by blocking antibody.
Secondary specific immune response in vitro to MSV tumor cells
Authors: Senik A. , Hebrero F. Pozzo , Levy J. P.
Published: February 2007

The interactions which occur between antigenic tumor cells and normal or immune lymphoid cells in a 3‐day in vitro culture, have been studied with a murine sarcoma virus (MSV)‐induced tumor. The 3H‐thymidine incorporation of lymphoma cells growing in suspension, and the radioactive‐chromium release of freshly sampled lymphoma cells regularly added to the culture, have been compared to determine the part played by immune lymphoid cells in cytolysis and cytostasis of the tumor‐cell population. The cytolytic activity increases in the culture from day 0 to day 3. It is due, predominantly, to T‐cells, and remains specific to antigens shared by MSV tumors and related lymphomas. This activity would be difficult to detect unless freshly sampled ascitic cells were used as targets, since the lymphoma cells spontaneously lose a part of their sensitivity to immune cytolysis during in vitro culture. The method used in the present experiments is a secondary chromium release test (SCRT), which measures the in vitro secondary stimulation of cytotoxic T‐lymphocytes (CTL) by tumor cells. In the absence of stimulatory cells, the CTL activity would have rapidly fallen in vitro. The cytostatic activity also increases during the 3 days in vitro, in parallel to the cytolytic activity: it is due to non‐T‐cells and remains mainly non‐specific. The significance of these data for the interpretation of in vitro demonstrated cell‐mediated anti‐tumor immune reactions is briefly discussed, as well as their relevance in the in vivo role of immune CTL.
Selective and non‐selective lymphocytotoxicity in human melanoma: Observation on the effect of long‐term culture and fetal bovine serum on target‐cell sensitivity to lymphocytes
Authors: Mukherji Bijay , Vassos Douglas , Flowers Arlene , Binder Sheldon C. , Nathanson Larry
Published: February 2007

In vitro cell mediated cytotoxicity (CMC) assays have been conducted in a human melanoma system with a 3H‐proline retention technique. Melanoma target cells from long‐term cultures (“cell lines”) are found to exhibit increased susceptibility for lymphocyte cytotoxicity in comparison to the same target cells from short‐term culture. The higher sensitivity of the “cell line” derived target cells is seen with lymphocytes, irrespective of diagnosis of the donor. In parallel experiments with the target cells grown in medium supplemented with fetal calf serum (FCS) and AB+ human serum (from a normal male donor), the melanoma target cells grown with FCS do not show any enhanced cytotoxicity, suggesting no causal relationship of such enhanced sensitivity of “cell line” ‐derived target cells to “heterologous melanoma antigens” that might have been acquired by the target cells following the use of FCS in tissue culture. In controlled assays of in vitro CMC, lymphocytes from melanoma patients (14/44) exhibited selective cytotoxicity (destruction of only one target‐cell type) against the melanoma target cells, whereas only 3/97 control lymphocytes (other malignancies and normal donors) showed such melanoma‐selective cytotoxicity. This difference is statistically significant at p<0.001. Non‐selective cytotoxicity (destruction of two or more unrelated target cell types) was seen with lymphocytes from 9/44 melanoma patients, 13/51 patients with other malignancies and 8/46 normal donors. No correlation of selective cytotoxicity could be established with donors' age, sex, stage of disease, therapy or history of blood transfusion. Such a correlation may emerge as our series becomes larger. Despite the lack of any correlation between selective cytotoxicity and disease status, our study reaffirms the existence of selective cytotoxicity by melanoma patients' lymphocytes against melanoma target cells.
Studies on the role of macrophages in regulation of growth and metastasis of murine chemically induced fibrosarcomas
Authors: Wood Gary W. , Gillespie G. Yancey
Published: February 2007

Murine solid tumors were shown to contain 9‐54% medium to large non‐malignant cells bearing receptors for immunoglobulin Fc. These cells rapidly adhered to plastic surfaces, were trypsin‐resistant, were capable of phagocytosis of latex particles and were sensitive to the lytic effects of anti‐macrophage serum and complement. Purified Fc‐receptor‐positive cells failed to produce tumors, which strongly suggested that they were macrophages. When tumor‐cell suspensions, depleted of macrophages by adherence to plastic surfaces, were injected subcutaneously into normal syngeneic mice, the tumors displayed an increased potential for metastasis. By contrast, control animals which received tumor‐cell suspensions containing their normal complement of macrophages invariably developed progressive localized tumors. The survival times of mice injected with macrophage‐depleted tumor‐cell suspensions were significantly shorter (p<0.05) than those for animals inoculated with intact tumor‐cell suspensions. These studies confirm the existence of a substantial number of macrophages within progressing syngeneic murine solid tumors and strongly suggest a regulatory role for the macrophages in the growth and metastasis of the tumor.
In vitro detection of cellular immunity to melanoma antigens in man by the monocyte spreading inhibition test
Authors: Mažuran Renata , Mujagic H. , Malenica B. , Silobrčic V.
Published: February 2007

In vitro inhibition of monocyte spreading (a correlate of cellular immunity) was used to detect cell‐mediated immune reactions of melanoma patients to specific melanoma antigens. Two soluble preparations of human melanoma antigens (MA‐1 and MA‐2) and one of a breast carcinoma (BCA) were prepared. The preparations were incubated in vitro with mononuclear cells isolated from the blood of 24 patients with melanoma, six patients with malignancies other than melanoma and 14 healthy donors. Spreading of monocytes from healthy donors was not inhibited by either MA‐1 and MA‐2 or BCA. MA‐1 and MA‐2 significantly inhibited the spreading of monocytes from patients with melanoma, while monocytes from patients with other malignancies were not affected. Spreading of monocytes from patients with melanoma was inhibited by the preparation of BCA. We conclude that inhibition of monocyte spreading can detect, in vitro, a cellular immune reaction to specific melanoma antigens in patients with melanoma.
EBV‐determined nuclear antigen (EBNA)‐positive cells in the peripheral blood of infectious mononucleosis patients
Authors: Klein George , Svedmyr Erick , Jondal Mikael , Persson Per Olof
Published: February 2007

After removal of SRBC rosette‐forming T‐cells from the peripheral blood, the residual, largely B‐lymphocyte fractin of five infectious mononucleosis patients was found no contain 0.5‐2% blast cells, positive for the EBV‐determined nuclear antigen (EBNA). There was a rough parallelism between the presence of large lymphoblasts in the hematological smear, EBNA‐positive large blasts in the B‐cell fraction and the ability of the T‐cell fraction to expert an EBV‐specific lymphocytotoxicity on established cell lines in vitro. EBNA‐positive B‐cells and EBV‐specific killer T‐cells disappeared after the acute phase of the disease.
Characteristic chromosomal abnormalities in biopsies and lymphoid‐cell lines from patients with burkitt and non‐burkitt lymphomas
Authors: Zech L. , Haglund U. , Nilsson K. , Klein G.
Published: February 2007

The karyotypes of cells from 10 Burkitt lymphoma (BL) biopsies, eight cell lines established from BL and nine cell lines from non‐BL sources were studied by chromosome banding techniques. With the exception of the BL‐derived cell lines BJAB, GC‐BJAB, Maku and U‐8691 all biopsies and lines of Burkitt origin contained an extra band at the distal region of the long arm of one chromosome 14. An extra band on chromosome 14 was also found in cells of one non‐BL biopsy, in cells from a lymphosarcoma‐derived cell line and in a longestablished cell line derived from the pleural exudate of a patient with Hodgkin's disease. A distal region at the long arm of one chromosome 8 was missing in all metaphase figures of good technical quality in the same material. The size, morphology and stainability of missing region corresponded fairly well to the extra region at chromosome 14. We therefore suggest that the chromosome 14 marker represents a translocation between chromosomes 8 and 14,t (8q‐; 14q+). The translocation was present neither in lymphocytes of peripheral blood of five Burkitt patients nor in five lymphoblastoid cell lines of non‐BL origin. Trisomy 7 was found in two of the 10 BL biopsies, in two BL‐derived cell lines, in one non‐BL biopsy, in two lymphosarcoma‐derived cell lines and in one cell line derived from a patient with Hodgkin's disease.
Comparative studies of Epstein‐barr virus strains from Ghana and the United States
Authors: Gerber Paul , Nkrumah Francis K. , Pritchett Randall , Kieff Elliott
Published: February 2007

A high incidence of oropharyngeal excretion of Epstein‐Barr virus (EBV) has been observed in African children with Burkitts lymphoma (BL) (48%) and matched controls (45%). This compares with an incidence of 77% in American patients with infectious mononucleosis (IM) and 13% in age‐matched controls. Cross‐neutralization tests between EBV strains derived from BL and IM patients and their sera failed to detect differences in the major neutralizing antigenic components. Cord‐blood lymphocytes transformed by American EBV expressed only early viral functions (EBV nuclear and soluble complement‐fixing antigens) and produced no detectable transforming activity. By contrast, cord‐blood lymphocytes transformed by African EBV strains contained 0.2‐0.3% of cells with EBV capsid and early antigen and produced EBV with transforming activity. These cells contained twice as many copies of EBV homologous DNA as the cells tranformed by American EBV strains.
Macrophage activation and anti‐tumor activity of biologic and synthetic agents
Authors: Morahan Page S. , Kaplan Alan M.
Published: February 2007

Systemic administration of the synthetic immunopotentiator pyran, was as effective as the use of the biologic immunopotentiator BCG in activating macrophages and in inhibiting the Lewis lung carcinoma and MCA 2182 sarcoma. Several other synthetic polyanions also activated macrophages and exhibited some anti‐tumor activity, but none were as effectives as pyran. Cell‐wall fractions such as the Ribi vaccine and MER were considerably less effective than BCG. The anti‐tumor activity of pyran against the virtually non‐immunogenic Lewis lung carcinoma involved non‐specifically activated macrophages, and both anti‐tumor activity and macrophage activating ability persisted over a 100‐fold range of drug from 0.5 mg/kg to 50 mg/kg. The ability of activated macrophages to destroy tumor cells was abrogated by treatment with trypan blue, an inhibitor of macrophage lysosomal enzymes. In addition, preincubation of tumor cells with activated peritoneal cells at effector‐cell:target‐cell ratios of 20:1 and 5:1 markedly decreased tumor incidence and mortality. Glycogen‐stimulated or unstimulated peritoneal cells were completely inactive in inhibiting tumor growth in vivo or exhibiting cytotoxicity in vitro, demonstrating the requirement for activated macrophages selective for tumor‐cell destruction.
Tumor‐bound immunoglobulins. I. Further analysis of the characteristics of binding of immunoglobulins to In vivo‐grown tumor cells
Authors: Dorva G. , Klein E. , Witz I. P. , Wigzell H.
Published: February 2007

Immunoglobulin (Ig) “coating” on different in vivo growing mouse tumors was investigated using several approaches. Radioiodine‐labelled purified protein A from Staphylococcus aureus, a specific ragent for Fc of IgG, and/or iodinated pruified antibodies against mouse immunoglobulins, were fixed by various in vivo‐grown mouse tumor cells, but not by the corresponding in vitro‐cultivated tumor cells. Removal of host macrophages from the in vivo tumor‐cell preparations did not affect the fixation of anti‐mouse Ig reagents by the tumor cells. After an initial lag period in vivo, the intensity of the Ig coating of tumor cells increased with time after tumor inoculation. Conversely, the detectable coating decreased rapidly as a function of time after ascites tumor cells were explanted in vitro at 37°C. Iodoacetamide did partially block this 37°C in vitro‐induced “uncoating process”. Surfacebound Ig could also be released from in vivo‐coated tumor cells treated at low pH in vitro. Analysis of the behavior of tumor‐bound Ig indicated a composite pattern. At the membrane level, uncoating was best shown with in vitro incubation favorable to cellular metabolism; however IgG was detected equally well in the supernatants of the cells, whether they were incubated at 37° C or at 4° C, and so for has failed to display antibody activity towards uncoated tumor cells. This was in contrast to the case of IgG released from ascites tumor cells cultured at low pH in vitro: such eluted Ig, when neutralized, could rebind to the “same” uncoated tumor cells. Under favorable metabolic conditions, the fate of tumor‐bound Ig might be one of internalization and/or of degradation.
Inhibition of cell‐mediated cytotoxicity to chemically induced rat tumours by soluble tumour and embryo cell extracts
Authors: Zöller M. , Price M. R. , Baldwin R. W.
Published: February 2007

When lymph‐node and spleen cells from rats bearing or immunized against aminoazo dyeinduced rat hepatomas or 3‐methylcholanthreneinduced rat sarcomas were pretreated with 3 m KCl extracts of these tumours, their cytotoxicity for cultured cells from the corresponding tumour was specifically inhibited. In cross‐test combinations of target tumour and tumour‐bearer effector‐cell donor, tumour extracts only inhibited cytotoxic responses when they were derived from the tumour homologous to the target‐cell and not when the extract was from the tumour borne by the effector‐cell donor. One component of the tumour‐bearer cytotoxic response was shown to be directed against tumour‐associated embryonic antigens since soluble extracts of embryos or tumour extracts containing embryonic antigens inhibited tumour‐bearer cell‐mediate cytotoxicity in both specific and cross‐test combinations of target tumour and effector cells. These findings are discussed in relation to tumour antigen expression and the immune responses that these tumour‐associated antigens may evoke in tumour‐bearing rats.
Detection of private and common tumor‐associated antigens in murine sarcomas induced by different chemical carcinogens
Authors: Fritze D. , Kern D. H. , Humme J. A. , Drogemuller C. R. , Pilch Y. H.
Published: February 2007

Two fibrosarcomas of similar histological type, induced in C3Hf mice by either methylcholanthrene or 3,4‐benz(a)pyrene, were shown to have individually unique tumor‐rejection antigens in classical transplantation‐type experiments. By contrast, sera of autochthonous mice, which resisted only transplants of the immunizing sarcoma, were found to contain complement‐dependent cytotoxic antibodies, specific for both sarcomas, in vitro. The existence of individually unique as well as common tumor‐associated antigens in chemically‐induced murine sarcomas is suggested. The private. “tumor transplantation‐type” antigens elicited tumor rejection responses in vivo. The common tumor‐associated antigens, although immunogenic in autochthnous hosts, inducing the production of tumor‐specific antibodies, failed to induce transplantation crossresistance in vivo. This study supports the contention that, in carcinogen‐induced murine tumors, and perhaps in human neoplasms as well, the evaluation of humoral (and cell‐mediated) immune responses in vitro may not reflect tumor rejection‐type immune responses in vivo.