bluuebunny/crossref_metadata_2025 huggingface dataset:
Transplantation immunity to individually unique antigens of chemically induced bladder tumors in mice
Authors: Wahl D. V. , Chapman W. H. , Hellström I. , Hellström K. E.
Published: February 2007

We have previously shown that lymphocyte‐mediated immunity to common bladder tumor antigens can be demonstrated in vitro. In this study we used two carcinomas and two sarcomas of the urinary bladder of BALB/c mice to immunize syngeneic animals against tumor‐specific transplantation antigens (TSTA) in order to determine whether common and/or individually unique antigens could be detected by resistance of the mice to challenge with tumor cells. Strong transplantation resistance was induced against each individual tumor line by immunizing with the respective line. No evidence could be obtained for the presence of TSTA common to the two carcinomas or to the two sarcomas (or to all four tumors).
Cell‐surface antigens of murine sarcoma‐virus‐transformed non‐producer cells: Further evidence for lack of transplantation immunity
Authors: Greenberger Joel S. , Stephenson John R. , Aoki Tadao , Aaronson Stuart A.
Published: February 2007

Previous studies have indicated that cells transformed by murine sarcoma virus (MSV) in the absence of virus production lack detectable transplantation antigens. Recent findings that antibodies to a surface antigen associated with MSV‐transformed cells can be elicited by hyperimmunization, led to the present studies. Attempts were made to detect transplantation immunity to MSV‐transformed cells in animals producing this antibody. Mice, hyperimmunized with an MSV‐transformed non‐producer clone of BALB/3T3, failed to demonstrate a higher resistance than BALB/3T3 hyperimmunized mice to tumor induction by either the homologous non‐producer cell or MSV itself. Under these conditions, both MSV non‐producer cell hyperimmunized tumor‐bearing and non‐tumor‐bearing mice showed antibodies to the MSV‐associated cell surface antigen. Thus, even in mice possessing this antibody, there is no transplantation immunity to MSV non‐producer cells.
The growth and metastasis of an allografted lymphoma in normal, deprived and reconstituted mice
Authors: Weston B. J. , Carter R. L. , Easty G. C. , Connell D. I. , Davies A. J. S.
Published: February 2007

The growth of the EL4 lymphoma has been studied in thymus‐deprived, reconstituted and normal CBA/Lac mice. In normal mice the lymphoma grew slowly and progressively after intradermal injection, killing the host between 39 and 64 days later, depending upon the number of cells injected: no metastases were seen. In deprived mice the tumour grew more rapidly and killed all mice between 17 and 20 days: 50% had distant metastases. Reconstituted mice resembled normal mice. Intravenous injection of lymphoma cells was also followed by early death, within 16 days, of deprived mice: all had widespread tumour growth in the viscera. Normal and reconstituted mice survived considerably longer, some being free of tumour at over 200 days after injection; death was associated with localized tumour growth in soft tissues. Studies of the clearance of 125IUDR‐labelled tumour cells and an examination of early histological changes showed that this difference in the distribution of tumour growth was not due to differences in rate of clearance of cells from the blood or lungs. It appeared likely that the differences between thymus‐deprived and reconstituted mice were due to the survival of rather small numbers of tumour cells in a variety of tissues.
Cytogenetic studies in permissive and abortive infections by adenovirus type 12
Authors: McDouoall J. K. , Vause K. E. , Gallimore P. H. , Dunn A. R.
Published: February 2007

Chromosome re‐arrangements have been found in human cells infected in vitro with adenovirus type 12. Dicentric and ring chromosomes and chromatid re‐arrangements were induced in cells infected during transition from GI to S phase. In non‐permissive hybrid cells the development of monoclonal stem lines, associated with the persistence of the viral genome, has been demonstrated. Persistence of the virus in these cells results in continued induction of the uncoiler region of human chromosome E17. The association of viral nucleic acid with host‐cell chromosomes has been confirmed by the in situ hybridization method.
Specific and non‐specific immunologic reactivity of regional lymph‐node lymphocytes in human malignancy
Authors: Ambus U. , Mavligit G. M. , Gutterman J. U. , McBride C. M. , Hersh E. M.
Published: February 2007

The in vitro blastogenic responses of lymphocytes from peripheral blood leukocytes (PBL) and lymph‐node leukocytes (LNL) of cancer patients were examined simultaneously in paired studies. The lymph nodes were obtained at the time of surgical tumor extirpation from the area draining or adjacent to the tumor, but were determined to be tumor‐free. There was an inverse relationship between the responses of PBL and LNL to tumor cells (TC). In those subjects where the PBL responses to TC were positive (stimulation index >3), the responses of LNL were usually negative and significantly lower. In those subjects where the LNL responses to TC were positive, the PBL responses were usually negative and significantly lower. A positive response by LNL to TC correlated with a significantly higher mixed lymphocyte culture response among LNL than among PBL. There was no correlation of these responses to TC with the PBL or LNL responses to phytohemagglutinin. There was a trend for the PBL response to TC to be higher than that of the LNL in patients with gastrointestinal cancer and melanoma and lower than that of LNL in patients with breast and squamous cell carcinoma. Stage of disease and age also influenced these results.
Detection of cytotoxic T lymphocytes in the EL4 mouse leukemia system: Increased activity of immune spleen and peritoneal cells following preincubation and cell fractionation procedures
Authors: Vasudevan D. M. , Brunner K. Theodor , Cerottini Jean‐Charles
Published: February 2007

The cytotoxic activity of spleen and peritoneal cells from C57Bl/6 mice immunized with irradiated syngeneic EL4 leukemia cells was tested in vitro on 51Cr labelled target cells following various fractionation and purification procedures. At the peak of the response, immune spleen cells showed very low cytotoxic activities. Fractionation on a simple BSA density gradient yielded a low‐density (less than 1.08 g/cm3) spleen‐cell population with a five‐ to 10‐fold increased cytotoxic activity. A similar increase was observed after preincubation of immune spleen cells for 24 h at 37° C, confirming results of Ortiz de Landazuri and Herberman (1972). A successive application of preincubation followed by BSA gradient separation resulted in a cumulative 30‐ to 100‐fold increase in cytotoxicity. Removal of high‐density small lymphocytes before preincubation led to populations with considerably decreased activity, suggesting the formation of low‐density cytotoxic lymphocytes from high‐density precursors during preincubation. Immune peritoneal cells showed a three‐ to five‐fold increase in cytotoxicity after (1) removal of phagocytic cells, (2) 24 h preincubation followed by removal of adherent cells, and (3) removal of phagocytic cells followed by preincubation. This indicated that adherent cells were not involved in but appeared to inhibit the cytotoxic activity of immune peritoneal cells. Treatment of preincubated or gradient‐separated immune spleen and peritoneal cells with anti‐θ serum and complement and passage through Sephadex lg‐anti‐Ig columns demonstrated the T‐cell nature of the cytotoxic effector cells. In vitro studies also showed an enhanced protective effect of pretreated immune spleen cells when compared to the original population.
Influence of interferon on virus‐particle synthesis in oncornavirus‐carrier lines. II. Evidence for A direct effect on particle release
Authors: Billiau A. , Edy V. G. , Sobis H. , De Somer P.
Published: February 2007

Interferon treatment of murine C‐type oncornavirus carrier lines results in a drastic inhibition of extracellular virus formation. When such cells are subcultured in the presence of interferon, synthesis of extracellular C‐type virus remains depressed until the interferon treatement is discontinued. Cell‐associated virus as seen in the electron microscope or as detected by uridine incorporation is not proportionally inhibited. Several possibilities to explain this discrepancy are tested. The most likely hypothesis is that interferon treatment primarily inhibits virus release.
Lactose synthetase induction by hormones in normal and tumorous GR mouse mammary tissue
Authors: Schulein M. , Daehnfeldt J. L. , Briand P.
Published: February 2007

To analyse the effect of hormones on protein synthesis in hormone‐induced GR mouse mammary tumors, a comparative study was made of the A and B protein contents of the hormone‐inducible enzyme lactose synthetase (EC 2.4.1.22). The A protein could be induced by estrone and progesterone separately and in combination in mammary glands of ovariectomized mice. Increased amounts were demonstrated during pregnancy, when peak levels were recorded in the lactating gland. A three‐fold increase was found in primary tumors as well as in transplanted hormone‐dependent and independent tumors, as compared to the level in normal mammary tissue. However, no significant difference could be demonstrated between A protein activity in the two types of tumors, and no further increase was observed in animals with independent tumors following hormonal treatment. The B protein could be demonstrated in normal mammary tissue of intact as well as ovariectomized animals. There was a decrease in pregnant animals, while peak values were recorded in lactating animals. A rise in B protein could be induced by estrone in normal mammary tissue. Progesterone blocked the induction. However, no significant level of B protein could be demonstrated in primary tumors or in transplanted hormone‐dependent and ‐independent tumors. Nor was any increase noted in animals with independent tumors after hormone treatment. We conclude that hormonal induction of B protein is repressed in GR mammary tumors. The A protein also is no longer hormone‐inducible, but the level is high compared to that of normal unstimulated mammary gland.
Cell‐mediated anti‐tumor immunity in oncorna virus‐induced tumors: Specific cytostasis of tumor cells by spleen and lymph‐node cells
Authors: Senik A. , De Gioroi L. , Levy J. P.
Published: February 2007

The cytostatic effect of lymphoid cell (LC) suspensions from MSV‐induced tumorbearing mice has been tested in the “cytostasis assay” (CA) according to Chia and Festenstein (1973). The target cells (TC) were syngeneic lymphoma cells in suspension. Specific cytostasis was observed mainly at low LC/TC ratios while non‐specific effects could be detected when ratios higher than 25/1 were used. The serum of MSV‐tumor‐bearing mice can either inhibit or stimulate immune cytostasis. Non‐immune lymphoid cells can be armed by this kind of stimulating serum which suggests that an indirect mechanism, possibly antibody‐dependent, is involved in this cell‐mediated immune reaction. The kinetics of the immune response in CA have been studied by comparison with the kinetics of the immune response which can be detected in the chromium release test (CRT) with the same target cells. The cytostasis response in CA persists long after tumor rejection while the CRT activity decreases rapidly, confirming that CA and CRT would probably detect two different effects of the immune lymphoid cells on the same target cells. These results are briefly dicussed.
Immunopathologic changes in patients with cutaneous malignant melanoma following intratumoral inoculation of BCG: Correlation with cell‐mediated immunity
Authors: Lieberman Ronald , Epstein William , Fudenberg H. H.
Published: February 2007

Six patients with cutaneous melanoma were treated with intratumoral Bacillus Calmette‐Guérin (BCG). Four showed good responses with regression of injected and, frequently, of uninjected lesions, whereas two developed dissemination and died. Three of four responders remain in complete remission. Two straìns of BCG were used; there was no detectable difference in therapeutic efficacy. Three of four responders showed a significant increase in lymphocyte stimulation (LS) to melanoma antigens, and all responders showed a marked increase in phytohemagglutinin (PHA). Non‐responders showed no increase to either stimulant. All responders were negative for leukocyte migration inhibition (LMI) to melanoma antigens before BCG, but two of four responders converted to positive after BCG therapy. Of the non‐responders, one was positive and one was negative before therapy; there was no change following BCG. There was a marked increase in active rosette‐forming cells (RFCS) in all responders and in only one of two non‐responders. Preliminary studies suggest that BCG also affects the level of circulating inhibitors which abrogate the activity of immune lymphocytes to melanoma antigens. A definite sequence occurs following intratumoral BCG: (1) disruption of melanogenesis with release of pigment from tumor cells (3‐6 h); (2) inflammatory response of polymorphonuclear leukocytes (PMNS) and mononuclear cells which remain at the tumor periphery (6‐24h); (3) tumor‐cell death (24h); and (4) granulomas replacing tumor (2 weeks). The response to BCG resembles the immunologic and histopathologic changes observed in halo nevi. These studies suggest that BCG activates both tumor‐specific and non‐specific immune responses. Thus, in vitro parameters of cell‐mediated immunity (CMI) are affected by BCG and some, particularly LS, LMI and the active rosette test, seem to correlate with clinical response.
A microassay for humoral cytotoxicity demonstrating sublethal effects of antibody
Authors: Cleveland P. H. , McKhann C. F. , Johnson K. , Nelson S.
Published: February 2007

A sensitive and objective microassay has been developed for detection of antibodies against tumor‐associated antigens of murine sarcoma cells, by measuring the ability of cells to incorporate 3H‐thymidine after exposure to immune serum and complement. The cytotoxic effect detected by this method reflects cytostasis as well as cell death. This study also demonstrated that incubation periods longer than 4 h are required for the maximum cytotoxic effects of immune sera on sarcoma cells to become manifest.
Cytotoxity of non‐T versus T‐lymphocytes from melanoma patients and healthy donors on short‐ and long‐term cultured melanoma cells
Authors: De Vries Jan E. , Cornain Santoso , Rümke Philip
Published: February 2007

Lymphocytes from 25 healthy donors were separated into T‐ and non‐T‐fractions by means of E and EAC rosette‐formation. The unfractionated lymphocyte population was tested simultaneously with E and non‐EAC rosette‐forming cells (T‐cells) and EAC and non‐E rosette‐forming cells (non‐T cells) on melanoma cells from cell lines and short‐term cultures. More frequent and stronger cytotoxic effects were seen on melanoma target cells from cell lines than from short‐term cultures. The cytotoxic effects of the unfractionated lymphocyte populations were always recovered in the non‐T‐cell populations. Occasionally also T‐cell cytotoxicity was seen on melanoma cells from cell lutes. Compared to the T‐cell effects, the non‐T cells always showed stronger cytotoxic effects. Lymphocytes from selected melanoma patients (patients with known cytotoxic lymphocytes) were also tested tegether with lymphocytes from healthy donors. The cytotoxic effects scored with the unfractionated melanoma patients' lymphocytes, which in general were stronger than the effects seen with the corresponding lymphocyte populations from healthy donors, again appeared to be located mainly in the non‐T‐cell populations.
Cellular immune response to virus‐specific antigen in hamsters bearing isografts of cytomegalovirus‐transformed cells
Authors: Murasko Donna M. , Lausch Robert N.
Published: February 2007

The immune response of hamsters to syngeneic transplants of hamster embryo fibroblasts (HEF) transformed by cytomegalovirus (CMV) was investigated. Using the microcytotoxicity assay it was found that spleen cells from tumor‐bearing hosts consistently killed both homologous tumor cells and CMV‐infected human embryonic lung (HEL) cells. No significant cytotoxicity was observed when uninfected HEL, normal HEF, or HEF transformed by herpes simplex virus type 1 (HSV‐1) or PARA‐(defective SV40)‐adenovirus 7 (PARA‐7) served as the target cells. Spleen cells from animals bearing isografts of HSV‐1‐ and PARA‐7‐transformed cells were cytotoxic for their respective tumor cells but not for CMV‐transformed cells. Further studies showed that spleen cells from CMV or CMV‐infected HEL immunized hamsters were specifically cytotoxic for CMV‐transformed hamster cells. No antibody cytotoxic for CMV‐transformed cells was detected in the sera of CMV or CMV‐infected HEL‐immunized hosts, or in sera from tumor‐bearing animals. The results corroborate previous serological data that hamster cells transformed by CMV express virus‐related membrane antigen (s), and demonstrate that such antigen (s) can induce a cell‐mediated immune response in the tumor‐bearing host.
Effect of the Fv‐1 gene on leukemia virus in mouse cell heterokaryons
Authors: Tennant Raymond W. , Myer Fred E. , McGrath Lorraine
Published: February 2007

The effect of the Fv‐1 mouse gene restriction of N‐ and B‐tropic mouse leukemia viruses was examined by determining the fate of the viruses in heterokaryons of permissive and non‐permissive cells. Virus expression in cultures of fused cells was analyzed by simultaneous autoradiography and fluorescent antibody assay, which permitted the detection of virus‐induced proteins specifically in heterokaryons or cells of either parental type. Heterokaryons were found to dominantly restrict both N‐ and B‐tropic virus, but not NB‐tropic virus which infects either cell type with equal efficiency. Fusion of permissive cells with non‐permissive cells at increasing intervals after infection showed that the restriction affects some virus function within at least 12 h of infection. These results indicate that the Fv‐1 gene locus, or gene product, affects some post‐penetration events required for virus protein synthesis.
Flow microfluorometry analysis of DNA content in chinese hamster cells following infection with simian virus 40
Authors: Horan P. K. , Jett J. H. , Romero A. , Lehman J. M.
Published: February 2007

Infection of secondary Chinese hamster cells with SV40 virus induces a population of cells into consecutive S periods. These changes in DNA content were examined at various times post infection by means of flow microfluorometry (FMF) which enabled a kinetic analysis to be made. At 12 h post infection, a population of 6C cells was observed which was induced from late S or G2 cells. By 24 h post infection, cells at 8C, 10C, 12C, 16C, and intermediate DNA contents were detected. The induction of this population of cells occurred within the first 24 h post infection. At later time intervals, there was a decrease in total number of cells with DNA contents of 8C or 16C.
Immunochemical identification of beta1‐globulin of the pregnancy zone” in serum of patients with trophoblastic tumors
Authors: Tatarinov Yu. S. , Mesnyankina N. V. , Nikoulina D. M. , Novikova L. A. , Toloknov B. O. , Falaleeva D. M.
Published: February 2007

Sera from 181 patients, 37 of which suffered from trophoblastic tumors (hydatidiform mole, destructive hydatidiform mole, and chorioepithelioma of the uterus), 100 patients—with other forms of tumors and 44 patients with various gynecological diseases, were studied with the use of an immunological test for the detection of beta1‐globulin of “pregnancy zone”. In the control group there were 106 serum samples of women at different stages of pregnancy and 257 samples of normal adults (165 women and 92 men). Thus, 544 serum samples from patients and from normal adults were studied. The immunochemical test for the beta1‐globulin was positive in patients with trophoblastic tumors before surgical removal or before chemotherapy. After surgery and/or complete course of chemotherapy, the test for beta1‐globulin became, as a rule, negative. This globulin is detected also in normal pregnancy serum. It is supposed that the beta1‐globulin of “pregnancy zone” is synthetized in the placenta and is released in the circulation of women during normal pregnancy; also it is produced by cells of trophoblastic tumors. The diagnostic and prognostic significance of the immunochemical test for the “pregnancy zone” beta1‐globulin in trophoblastic tumors is discussed.
Effect of anti‐embryo immunization on methylcholanthrene‐induced sarcoma growth in BALB/c mice
Authors: Parmiani G. , Lembo R.
Published: February 2007

The effect of immunization with embryonic tissues on challenge with two methylcholanthrene‐induced fibrosarcomas (MCA‐I and II) has been studied in BALB/c mice. No anti‐tumor protection was elicited by multiple intrastrain pregnancies and by immunizing with either X‐irradiated or mitomycin‐C‐blocked cells of syngeneic or allogeneic embryos obtained from primiparous females. Enhancement was found in anti‐embryo immunized males, but not females, and in multiparous females upon transplantation of MCA‐I sarcoma cells. Immunization with syngeneic embryonic cells in complete Freund's adjuvant, with embryomas or with syngeneic embryos kept in cell‐impermeable diffusion chambers, resulted in an enhancement of MCA‐II cells while allogeneic embryonal immunization was ineffective. The immunologic nature of the phenomenon was supported by experiments in which immunosuppression prevented the development of the enhancing response in mice injected with embryonic tissues. In neutralization experiments neither lymphocytes nor serum from anti‐embryo‐immune or multiparous mice caused any stimulatory or inhibitory effect on the admixed tumor cells.
Report of the scientific meeting on some developments in the methodology of controlled clinical trials in cancer
Authors: Armitage P. , Block J. B. , Saracci R.
Published: February 2007

This paper summarizes discussions which took place recently between statisticians and medical practitioners about methodological developments in clinical trials in cancer. Some recent mathematical theories for the analysis of censored survival data enable comparisons to be made between the effects of different treatments without rigid assumptions about the shape of the survival curve, and taking into account various disturbing variables. The use of computers for data processing is increasingly important, and great benefits can be derived from the use of general computer programs. Many clinical studies of new agents are of limited value because of the inadequacy or absence of controls. The value of randomization is well known, but some attention is being given to the possibility that randomization might be dispensed with in certain circumstances. Another possibility is the use of special methods of allocation which tend to place the majority of patients on the better treatment. These various suggestions for new approaches to the design of trials are especially important in view of the large number of possible questions to be investigated by trials and the limited resources available.
Demonstration of epstein‐barr virus‐associated nuclear antigen in nasopharyngeal carcinoma cells from fresh biopsies
Authors: Huang D. P. , Ho J. H. C. , Henle W. , Henle G.
Published: February 2007

Fresh nasopharyngeal carcinoma (NPC) biopsies were treated in several ways to yield satisfactory cell preparations for detection of Epstein‐Barr virus (EBV)‐associated nuclear antigen (EBNA) by anti‐complement immunofluorescence tests. If the cells were well dispersed (trypsinization or extensive mechanical dispersal) few or none of them were EBNA‐positive. In contrast, if the biopsy preparations contained small to moderately sized tissue fragments (touch preparations or limited mechanical dispersal), nuclear staining was detected in nearly every cell at the margin of the fragments or in cell sheets protruding from them. The stained cells corresponded to the carcinoma cells when compared to histologically stained replicate cell preparations. Nuclear staining was obtaining with anti‐EBNA positive sera [healthy donors, NPC patients, convalescents from infectious mononucleosis (IM)], shown to be free of antibodies to other nuclear antigens, but not with anti‐EBNA negative sera (healthy donors or patients in the early acute phase of IM). These results confirm and extend previous reports that the carcinoma cells harbor EBV genomes. The implications of these findings are discussed.
Cell surface antigen induced by avian tumor viruses in hamster cells transformed by a temperature‐sensitive mutant of rous sarcoma virus
Authors: Aupoix Michèle C. , Biquard Jean‐Michel , Cachard Annie
Published: February 2007

Hamster cells (BHK21/13) transformed at the permissive temperature by a temperature‐sensitive mutant (FU 19) of the Schmidt‐Ruppin strain of Rous sarcoma virus exhibited a temperature‐dependent expression of virus‐induced surface antigen (VISA) as assayed by mixed haemadsorption test. This temperature‐dependence of VISA was not observed in cells transformed by the wild‐type virus (SR4), although the number of positive cells was reduced at the restrictive temperature (41° C) when compared to cells incubated at the permissive temperature (37° C). The relations between cell transformation and expression of VISA are discussed.
Effect of ethidium bromide and fractionated X‐irradiation on rauscher leukemia development
Authors: Okunewick James P. , Brozovich Barbara J. , Kuhnert Paul M.
Published: February 2007

Studies were carried out to evaluate further the in vivo effectiveness of reversetranscriptase inhibitors in the therapy of Rauscher viral leukemia. Ethidium bromide, given in multiple doses, was found to be without significant effect on the survival of mice which already had established Rauscher disease as the result of injection with virus 2 weeks earlier. However, the initiation of ethidium bromide treatment immediately after virus did result in the beneficial effect of an increase in the mean survival time of the infected animals. On the other hand, at the virus titers used, 4‐N‐benzyl‐4‐N‐demthylrifampicin showed no significant therapeutic action in either case, even though other studies had suggested that it might be effective for this purpose. A total of 1,000 R of fractionated X‐irradiation given to animals with established leukemia also resulted in increased mean survival times, but the combination of irradiation and ethidium bromide treatment of similar mice resulted in only a marginal improvement over irradiation alone. It is suggested that these reverse‐transcriptase inhibitors, though active against the free virus, may not be effective against the already transformed tumor cell.
Specific tumor‐induced suppression of lymphocyte activity in the antibody‐dependent tumoricidal reaction
Authors: Stolfi R. L. , Stolfi L. M. , Fugmann R. A. , Martin D. S.
Published: February 2007

Although lymphocytes from normal, unsensitized CD8F1 mice demonstrated an antibody‐dependent cytotoxic reaction against syngeneic breast tumor cells in vitro, lymphocytes from mice carrying breast tumors exceeding 1 g in weight invariably failed to demonstrate cytotoxicity against cells from the lymphocyte donor's tumor in the antibody‐dependent reaction. Further, the tumor‐induced suppression of this antibody‐dependent lymphocyte reactivity was found to be tumor‐antigen‐specific, in that lymphocytes from an animal bearing a large tumor nevertheless were capable of participating in an antibody‐dependent cytotoxic reaction against syngeneic breast tumor cells that were antigenically distinct from those of the lymphocyte donor. The specificity of suppression of antibody‐dependent lymphocyte reactivity observed here indicates that only a small sub‐group of those lymphocytes with potential for antibody‐dependent cytocidal reactions actually participates in the reaction against any one particular antigen. This suggests a previously unrecognized antigen specificity at the level of the effector cell in the antibody‐dependent cytotoxic reaction.
Functional and biochemical parameters of activation related to macrophage cytostatiic effects on tumor cells
Authors: Keller R. , Keist Ruth , Ivatt R. J.
Published: February 2007

The cytostatic action of non‐immune, activated peritoneal rat macrophages (AM) on tumor targets largely depends upon the duration of their culture in vitro. AM show full cytostatic activity for the first 12‐24 h of culture followed by gradual loss. This distinctive pattern of cytostatic activity displayed by AM was compared with the course of a variety of functional, metabolic and biochemical parameters. DNase, RNase, esterase, acid phosphatase, glucose oxidation and cellular adherence remained unchanged or decreased whereas prolonged culture led to an increase in activity of other lysosomal enzymes. Pinocytosis and phagocytosis were most marked in macrophages between 12‐60 h whereas elevation in macrophage protein synthesis was high only after 4 to 12 h of culture, followed by a gradual decline. Thus the capacity of macrophages to stop proliferation of tumor targets closely parallels the level of protein synthesis, whereas other parameters of macrophage function such as lysosomal enzymes, glucose oxidation, cellular adherence, pinocytosis and phagocytosis, manifested a clearly different timecourse.
The mechanism of the autonomy of division of ascitic tumor cells
Authors: Malenkov A. G. , Artamonova V. A. , Kakushkina M. L. , Slivinsky G. G. , Voejkov V. L.
Published: February 2007

A bovine serum gradient was used to separate ascites tumor cells into fractions according to size and position in the cell cycle. Cells from different fractions were treated with RNase or tween 80, and the influence of this treatment on protein synthesis, membrane permeability and dry mass of the cells was studied. The results suggest that the treatment triggered events in G1 cells which may resemble processes needed for the initiation of normal cell growth.
The effects of cyclophosphamide on in vitro correlates of tumor immunity
Authors: Steele G. , Sjögren H. O. , Ankerst J.
Published: February 2007

The effects of cyclophosphamide (CY) on tumor immunity against isografts of rat sarcomas induced by polyoma virus were studied using in vitro techniques. Groups of sarcoma‐bearing animals received CY (250 mg/kg intraperitoneally 11 days after isografting) CY (150 mg/kg IP 8 days after isografting), or IP injections of 0.9% NaCl. In control rats tumor growth was progressive. All CY‐treated animals showed transient tumor regression of at least 50% of their pretreatment tumor volume. Despite a drastic depression in numbers of blood leukocytes as well as lymph‐node cells following CY treatment, animals treated with 150 mg/kg CY were shown to have blood lymphocyte and lymph‐node cell cytotoxicity in vitro against plated sarcoma target cells comparable to untreated sarcoma‐bearing animals. Sera obtained from sarcoma‐bearing rats prior to CY treatment specifically blocked lymphocyte cytotoxicity against sarcoma target cells. After CY treatment serum blocking activity could not be demonstrated during the period of tumor regression, but reappeared in parallel with tumor regrowth. Antibodies cytotoxic to sarcoma target cells when homologous complement was added could not be demonstrated in sera obtained from animals before CY treatment, but were present after treatment during tumor remission. Following CY treatment, sera obtained from treated animals, when mixed with blocking sera from control animals, could counteract or unblock the blocking activity of tumor‐bearer sera. Unblocking capacity was present only in sera obtained during CY‐induced tumor remission. Serum IgG concentration was significantly and temporarily decreased after CY treatment.
Chromosome analysis and agglutination by concanavalin A of primary simian‐virus‐40‐induced tumors
Authors: Lehman John M. , Bloustein Paul
Published: February 2007

Tumors induced by SV40 virus in newborn and adult Syrian hamsters were analyzed for their growth properties in vitro, transplantation, agglutination with concanavalin A and chromosome constitution. Following transfer to culture flasks tumor cells grew for 2‐3 weeks, then went through a “degenerative phase”. Eventually lines were established which became adapted to in vitro culture conditions. Agglutination properties of these tumor cells were similar to those of cells transformed in vitro with SV40 virus. Of five subcutaneous and six intratesticular tumors that were analyzed for their chromosome constitution, all had a hypotetraploid chromosome number distribution. The results of the chromosome studies suggest a similar pattern in the evolution of malignant properties of cells transformed in vitro and in vivo following infection with SV40 virus.
Inhibition by streptovaricins of rauscher leukemia virus splenomegaly
Authors: Borden Ernest C. , Carter William A. , Sensenbrenner Lyle L. , Owens Albert H. , Lichtenstein Judith , Gray Gary D. , Neil Gary L. , Nichol F. Richard , Li L. H.
Published: February 2007

Streptovaricins (Sv), ansa macrolide antibiotics, inhibited Rauscher leukemia virus (RLV) splenomegaly by 25‐50%. All streptovaricins tested were effective when administered orally either by diet ad lib or by intubation from infection to time of killing. When delivered by intubation, Sv wus measurable in plasma. For up to 6h. SvC, at 300 mglkglday, reduced mean splecln weight of infected mice, from 478±51 (SE) mg to 300555 (SE) mg. Rijampicin, at 250 mglkglday, had no similar activity. Decrease in caloric intake and in body‐weight gain also resulted in an inhibition of RL V splenomegaly; although Sv‐treated mice gained weight, the increase was usually slightly less than controls. However, mice treated with a Sv diet for a week prior to infection, after an initial period of weight loss, gained at a rate equivalent to a controlgroup, and when killed had a marked reduction in splenomegaly. The selectivity of streptovaricins and specificity for viral events was suggested by several observations: (I) Splenomegaly and mortality, induced by L1210 or a non‐injective transplantable tumor of RL V oriAjin, was not inhibited. (2) No inhibition of normal hematopoietic spleen colonies was observed. (3) Host immune responses, including cellular and humoral immunity and interjeron production and action, were not inhibited. Thus, although the effect of slightly decreased weight and intake could not be unequivocally established, the findings were most compatible with a selective inhibition of RL V splenomegaly by Sv.
Leukocyte adherence inhibition as measured by a radioisotopic technique for detection of cell‐mediated tumor immunity
Authors: Pierce G. E. , Devald B. L.
Published: February 2007

It has been previously reported that cell‐mediated tumor immunity may be detected by leukocyte adherence inhibition (LAI) as determined by a visual counting technique in the presence of soluble tumor antigen. In the present experiments leukocyte adherence was measured by a radioisotopic technique. Peripheral blood mononuclear cells from Wistar/Fu rats and lymph‐node cells (LNC) from C3H/J mice were labelled with Technetium 99m (99mTc) and incubated with medium alone and with medium containing tumor antigens (high dilutions of dialyzed tumor homogenates) in the wells of plastic tissue‐culture plates. After incubation, fluid and non‐adherent cells were removed. The ratio of residual radioactivity in wells with antigen to that in wells without antigen was determined. Adherence of blood mononuclear cells from rats bearing syngeneic transplants of a polyoma‐virus‐induced tumor was inhibited by dialyzed homogenates of this tumor. Adherence of blood mononuclear cells from normal rats was not inhibited. Adherence of LNC from mice bearing syngeneic transplants of a 3‐methylcholanthrene (3‐MCA)‐induced fibrosarcoma was inhibited by dialyzed homogenates of this tumor. Adherence of LNC from normal mice or from mice bearing a different 3‐MCA‐induced tumor was not inhibited. These results support the use of LAI as a simple test for cell‐mediated tumor immunity. Measuring relative leukocyte adherence with the radioisotope 99mTc eliminates possible bias in counting and permits multiple replicate determinations with a small number of leukocytes.
Cytotoxic effect of lymphocytes from pregnant mice on cultivated tumor cells. I. Specificity, nature of effector cells and blocking by serum
Authors: Hellström Ingegerd , Hellström Karl Erik
Published: February 2007

Lymph‐node and spleen cells from pregnant BALB/c mice were found to be cytotoxic (by a microcytotoxicity assay) to cultivated syngeneic tumor cells. Target cells included a series of in vitro transformants derived from BALB/c 3T3 cells (3T3‐MSV, 3T3‐SV40 and 3T12), as well as two lines of tumors induced in vivo. Skin fibroblasts and nontransformed 3T3 cells were not similarily affected. The cytotoxic lymphocyte effect was decreased by treatment with anti θ serum and complement but was not removed by passage through a column removing cells with immunoglobulin at their surface. It could be blocked by serum taken from pregnant mice and from mice carrying methyl‐cholanthrene‐induced sarcomas. These sarcomas could be different from the ones used as targets in vitro, but the blocking effect was higher when serum was tested from mice carrying the respective tumor studied. The blocking activity of serum from pregnant mice was removed by absorption with neoplastic cells, taken either from culture or directly from mice, and with fresh embryonic cells, but not to the same extent by absorption with explanted fibroblasts, 3T3 cells, or adult kidney cells. Absorption was most effective when the same line of cells was used as targets. Both the cytotoxic lymphocyte effect and the blocking serum activity were seen already during the first pregnancy and lasted for at least 1 month subsequent to delivery. Serum from pregnant mice could „arm”︁ control lymph‐node cells and produce a lymphocyte‐dependent cytotoxic effect on neoplastic, but not on control, target cells.
Pilot experiments with eb virus in owl monkeys (aotus trivirgatus). III. Serological and biochemical findings in an animal with reticuloproliferative disease
Authors: Epstein M. A. , Zur Hausen H. , Ball G. , Rabin H.
Published: February 2007

Nucleic acid hybridization with EB virus complementary RNA has demonstrated unequivocally that EB virus DNA is present in the cells of a continuous lymphoblastoid line established in culture from a pathological lymph node of an owl monkey with reticuloproliferative disease after inoculation with EB virus. There were 48 to 49 EB virus genome equivalents per cell. In addition, serological studies showed that the diseased owl monkey developed specific antibodies to EB virus capsid antigens. The antibodies were first detected by indirect immunofluorescence in serum sampled 13 weeks after inoculation, and were not found in sera from other animals without the disease. None of the monkeys developed heterophile antibodies. The significance of the biochemical and serological findings is discussed in relation to the nature of the reticuloproliferative disease and the possibility of tumour‐induction by EB virus.
Cytotoxic effect of lymphocytes from pregnant mice on cultivated tumor cells. II. Blocking and unblocking of cytotoxicity
Authors: Hellström Ingegerd , Hellström Karl Erik
Published: February 2007

Sera from BALB/c mice transplanted with either of two syngeneic, methylchol‐anthrene‐induced sarcomas (1315 and 1321) were found to block (i.e. abrogate) the cytotoxic effect of lymph‐node cells (LNC) from multiparous mice on cultivated tumor cells. The blocking activity was seen even at high serum dilutions (up to 1:320). It was found to persist in mice whose tumors had been removed 8–11 days previously. These mice had transplantation resistance against individually unique antigens of the respective sarcoma to which they had been immunized, but not against any common, putatively embryonic ones. In keeping with this finding, their sera did not block LNC‐mediated cytotoxicity to the unique transplantation antigens, when tested 8–11 days after removal of the immunizing tumor. Sera from rabbits immunized with BALB/c embryonic tissues and subsequently absorbed with normal adult BALB/c cells, were found to cancel („unblock”︁) the blocking activity of serum from multiparous mice. The specificity of this unblocking effect and its potential usefulness as a tool to study immune reactions to embryonic tumor antigens need to be established.
Occurrence of nervous‐tissue tumors in cattle, horses, cats and dogs
Authors: Hayes Howard M. , Priester William A. , Pendergrass Thomas W.
Published: February 2007

From 11 North American veterinary university hospitals and clinics, 248 animals with a confirmed diagnosis of nervous‐tissue tumor were identified; 7 tumors were found in cattle, 28 in horses, 14 in cats, 199 in dogs, and none in other species. Tumors were divided for analysis into three categories—glial, meningeal, and peripheral nerve. In cattle and horses, all tumors involved peripheral nerves, the risk of which, in horses, reached a plateau at 4–6 years of age and remained constant thereafter. In cats, the tumors were equally distributed among the three tumor categories whereas, in dogs, twice as many glial tumors as meningeal and peripheral nerve tumors were found. The risk for glial tumors in dogs reached a peak at 10–14 years of age, for meningeal at 7–9 years, and for peripheral nerve at 2–3 and 7–9 years. Three canine breeds—English bulldog, boxer, and Boston terrier— had an excessive risk of glial tumors. Except for an excess of skin tumors in dogs with peripheral nerve tumors, there was no unusual occurrence with second primary neoplasms for any species. There was no detectable predisposition by sex for any of the categories of nervous‐tissue tumors among any of the four species. The role of genetic abnormalities associated with nervous‐tissue tumors and other etiologic factors (e.g., chronic hypoxia) may be clarified by further studies involving canine breeds of „bulldog”︁ ancestry.
Infectious dna recovered from avian tumor‐virus‐producing cells
Authors: Vigier P. , Montagnier L.
Published: February 2007

A single treatment of chick embryo fibroblasts with DNA recovered from chick embryo fibroblasts productively infected and transformed with four different strains of RSV, or productively infected with two different strains of RAV, resulted in virus production and cell transformation (in the case of RSV) two or three passages after treatment (8–25 days). The virus recovered from cultures was phenotypically identical to that produced by the donor cells. No virus production nor cell transformation resulted from treatment of control cultures with DNA digested with DNAse. Infectious RSV‐DNA was recovered from purified donor cell nuclei and was associated with the precipitable fraction of DNA prepared according to the method of Hirt (1967). It also sedimented with cellular DNA in density gradients, and with high molecular weight DNA (2–4 × 107 daltons) in sucrose gradients, which suggests that it is associated and may be integrated with chromosomal DNA. In some experiments, DNA fractions of lower molecular weight (down to 6 × 106 daltons) were also infectious. DNA from virus‐producing RSV‐transformed cells also gave rise to virus and Rous cells in cultures of fibroblasts from gs‐ embryos. However, the amount of DNA required for successful infection varied widely between experiments, and no reproducible dose‐effect relationship was observed. The frequency of DNA‐treated cells which produced virus remained low, even when the assay cultures were pretreated with 5‐bromodeoxyuridine.
Effect of testosterone and estradiol‐17β on synthesis of dna, rna and protein in human breast in organ culture
Authors: Finkelstein Michael , Geier Avraham , Horn Hadassa , Levij I. S. , Ever‐Hadani Pnina
Published: February 2007

Effects of testosterone (T) and estradiol‐17β (E2) on the synthesis of DNA, RNA and protein were studied in explants of the following types of malignant and non‐malignant human female breast grown in organ culture: cystic mastitis (7 cases), fibroadenoma (8), carcinoma (17) and uninvolved tissue from cancer‐bearing breast (8). In cultures of cystic mastitis T uniformly inhibited the incorporation of thymidine‐3H into DNA, uridine‐3H into RNA and L‐amino acids‐14C (AA‐14C) into protein. E2 inhibited the incorporation of thymidine‐3H, but had a variable effect on the incorporation of uridine‐3H and AA‐14C. Cultures of fibroadenoma, with no steroid added, were highly proliferative especially at the outer surface, but the incorporation of thymidine‐3H, uridine‐3H and AA‐14C was much lower than in cystic mastitis. Whereas in fibroadenoma T uniformly inhibited the synthesis of DNA, RNA and protein, the effect of E2 was variable: in most cases it inhibited the synthesis of DNA, but in one it stimulated it appreciably; in the majority of cases E2 stimulated RNA and protein synthesis. In cultures of cancerous tissue T depressed, in most cases, the incorporation of thymidine‐3H, uridine‐3H and AA‐14C, but it stimulated it in 4 out of 17. E2 inhibited the synthesis of DNA, RNA and protein in 6 cases (2 of them were inhibited by T), stimulated them in 9 (one stimulated by T) and had no clear effect in 2. The effect of the steroids on the explants of uninvolved tissue was variable and did not always parallel their effect on the cancerous tissue from the respective patients.
Antigens associated with chemically induced intestinal carcinomas of rats
Authors: Martin F. , Martin M. S. , Bordes M. , Knobel S.
Published: February 2007

Rabbits were immunized with extracts of primary or grafted intestinal adenocarcinomas induced by carcinogenic drugs in inbred rats. After absorption with normal tissue extracts, the antisera were able to recognize three tumor‐associated antigens. Two of them were glycoproteins, present in cancer cells but also, in trace amounts, in mucous cells of the normal digestive tract. The third antigen is not detectable in the normal digestive system, but present in normal spleen; on immunofluorescence, it is not located in the cancer cells, but in polymorphonuclear cells infiltrating the tumor. None of the three antigens cross‐reacts with human carcinoembryonic antigen, or human or rat alphafetoprotein. On the other hand, one of the glycoprotein antigens is immunologically related to the human blood group A substance.
Defects in cell‐mediated immunity during growth of a syngeneic simian virus‐induced tumor
Authors: Howell Stephen B. , Dean Jack H. , Law Lloyd W.
Published: February 2007

Four assays of tumor‐specific cell‐mediated immunity were compared during growth of a syngeneic Simian‐virus‐40‐induced tumor, mKSA. Major differences were found in immunity detected by the tumor neutralization test (the Winn test), direct tumor challenge, the microcytotoxicity assay and the 51chromium‐release lymphocytotoxicity assay. Progressive growth of the neoplasm followed by loss of immunity (the eclipse phenomenon) was documented with the Winn test. It was established that this eclipse phenomenon represented a lesion in the T‐cell system of tumor‐bearing hosts. This lesion was found to be specific and unrelated to anatomic tumor location. The ability to produce graft‐versus‐host reactions, and the ability to respond to mitogens, were found to be generally intact in tumor‐bearing animals. Cells capable of recognizing mKSA tumor antigens and reconstituting an immune response following surgical removal of tumor or upon transfer to normal mice were found in the spleens of mice bearing advanced tumors. No suppressor cells that might account for the eclipse phenomenon could be demonstrated. Tumor‐bearer serum did not block neutralizing activity of immune spleen cells in the Winn test, and immune cells were capable of neutralizing tumor even in tumor‐bearing hosts. The possibility that the lesion is intrinsic to T‐cell precursors of effector cells is discussed.