bluuebunny/crossref_metadata_2025 huggingface dataset:
The requirement for monocytes in spontaneous cytotoxicity by lymphocytes from healthy donors and melanoma patients
Authors: de Vries Jan E. , Mendelsohn John , Bont Willy S.
Published: February 2007

Lymphocytes from 12 healthy donors were depleted of monocytes by velocity sedimentation at unit gravity (average monocyte contamination 0.2%) and tested for spontaneous cytotoxicity (SC) against tumor target cells in 24 h microcytotoxicity assays. Sixty percent of all lymphocytes were recovered in this monocyte‐de‐pleted lymphocyte fraction (LF). In contrast, with the corresponding unfractionated lymphocytes (UL) the LF cells were not spontaneously cytotoxic on T24 bladder carcinoma, NKI‐1, NKI‐7, NKI‐8, NKI‐1O melanoma, and MC‐1 mammary carcinoma cell line cells and target cells derived from two short‐term melanoma cultures (Me 215 and Me 223). SC of the LF could be restored by reconstitution with autologous monocytes, which were obtained >80% pure in the same velocity sedimentation procedure. Addition of 4–8% monocytes was sufficient to restore the SC of the LF to the level achieved with the corresponding UL, whereas maximal induction of SC was observed after addition of 8–16% monocytes. Higher numbers of monocytes had suboptimal effects. SC of the LF could also be restored by monocyte culture supernatants. The spontaneous cytotoxic effector cells were characterized as non‐E rosette‐forming, membrane slg‐negative Fc‐receptor‐bearing lymphocytes, a proportion of which probably also bear C3‐receptors. Since the LF was not spontaneously cytotoxic, in spite of the presence of Fc‐receptor bearing lymphocytes, it is concluded that monocyte help, mediated via soluble factors, is required. Evidence is presented that the lack of SC by the LF might be attributable to the failure of these cells to make appropriate contact with the target cells. LF/target cell contact followed by target cell kill occurred after addition of monocytes. Effector/target cell contacts, artificially established by agglutinins, did not result in target cell kill. Thus the effector/target cell contacts observed in the presence of monocytes suggest recognition of particular membrane determinants involved in SC.

An identical requirement for monocytes was observed with LF cells from 5 stage I and 5 stage II melanoma patients tested for SC against both melanoma and non‐melanoma target cells. This indicates that either the cytotoxicity against melanoma cells with lymphocytes from melanoma patients is of the same nature as the SC of lymphocytes from healthy donors, or that specific melanoma‐associated cellular cytotoxicity also requires monocyte help.
Distribution of tumor‐associated antigen cea and cross‐reacting NCA in fetal organs
Authors: Gadler H. , Bremme K. , Wahren B.
Published: February 2007

The organ distribution of the tumor‐associated car‐cinoembryonic antigen (CEA), and that of the normal tissue component NCA (non‐specific cross‐reacting antigen) have been investigated in the fetus. Organ extracts from five fetuses between 14 and 21 weeks of age were analysed by radioimmunoassay using specific antisera. CEA was detected in large amounts (800‐1,650 ng/g) in fetal colon and in barely detectable amounts in lung and placental tissue. This differed from NCA, which could be detected in almost all organ extracts analysed. The highest concentration of NCA was measured in fetal colon and the content increased with the gestational age of the fetus. High amounts of NCA were also found in the liver, spleen and placenta! tissue. The gel elution profiles of CEA and NCA from an amniotic fluid pool and a pool of colonic extracts were also determined. CEA eluted similarly to the marker 125I‐CEA purified from liver metastasis of colonic carcinoma. The NCA‐reactive material was found in three distinct peaks.
Separation of the tumor‐associated transplantation antigen (TATA) from the alien H‐2k antigens expressed on a methylcholanthrene‐induced tumor
Authors: Rogers Michael J. , Law Lloyd W. , Pierotti Macro , Parmiant Giorgio
Published: February 2007

The tumor‐associated transplantation antigen (TATA), alien H‐2k antigens and normal H‐2d antigens expressed on a methylcholanthrene‐induced tumor were monitored during gel filtration and lectin affinity chromatography of detergent‐solubilized tumor‐cell membranes. TATA was resolved from both the normal and alien H‐2 antigens by these techniques. The relationship between histocompatibility antigens and TATA is discussed.
Suppression of friend leukemia virus by bacillus calmette‐guérin and a streptococcal preparation, OK‐432
Authors: Tsuruo Takashi , Iida Harumi , Tsukagoshi Shigeru , Sakurai Yoshio
Published: February 2007

OK‐432, a streptococcal preparation, and BCG effectively inhibited splenomegaly in Friend leukemia virus (FLV)‐infected mice. Divided drug dosage resulted in stronger inhibition than single administration. When the second dose was fixed at the 3rd pre‐infection day, the best timing for the first dose was approximately 30 days before infection. The optimal dosages were 100–600 KE/kg for OK‐432 and 25–100 mg/kg for BCG. Transfer of peritoneal exudate cells (PEC) from immunomodulator‐treated mice, but not PEC from untreated mice, conferred resistance against FLV which was highest when PEC were transferred I day before FLV infection. The transfer of PEC on the day of or one day after infection had no protective effect. Inactivation also occurred when FLV was incubated in the presence of PEC from immunomodulator‐treated mice, however, no significant effect was observed for PEC from untreated mice.
Resistant hepatocytes as early changes in liver induced by polycyclic aromatic hydrocarbons
Authors: Tsuda Hiroyuki , Farber Emmanuel
Published: February 2007

Induction of putative preneoplastic hepatocytes which are resistant to cytotoxic effect of 2‐acetylamino‐fluorene (2‐AAF) by five carcinogenic polycyclic aromatic hydrocarbons (PAH) was tested using γ‐glutamyl transpeptidase (γ‐GT) as a histochemical marker enzyme. Bgenzo (a) pyrene [B(a)P], 7,12‐dimethylbenz(a) anthracene (7,12‐DMBA), 3‐methylcholanthrene (3‐MC), dibenz (a, h)‐anthracene [DB(a, h)A] and benzo (a) anthracene [B(a)A] were given 12 h after partial hepatectomy (PH) followed by 2‐AAF and carbon tetrachloride (CCI4) feeding, a procedure developed by this laboratory. All of the five PAHs induced a significantly increased number of γ‐GT positive foci when compared with sham‐hepatectomized (SH) or vehicle control groups. The numbers of γ‐GT‐positive foci induced by B(a)P, 7,12‐DMBA, 3‐MC and DB (a, h)A were significantly different from all of the parent compounds, anthracene, naphthalene, pyrene and phenanthrene. B(a)A did not induce significantly increased number of foci only when compared to anthracene. Possible usefulness of this system for in vivo short‐term assay is discussed.
Bovine leukemia virus‐specific antibodies in french cattle. III. Prevalence of the BLV‐gp 51 radioimmunoassay for the detection of BLV‐infected animals
Authors: Levy D. , Deshayes L. , Parodi A. L. , Levy J. P.
Published: February 2007

The control of the spread of BLV infection among cattle requires very sensitive methods of detection. The BLV‐gp5I radioimmunossay presents great advantages over the other serological methods, including the BLV‐p24 radioimmunoassay. This is clear from studies of normal animals from the high‐leukemia‐incidence region which show that anti‐gp5I antibodies reach higher titers than anti‐p24 or may even exist alone. Moreover, a sequential survey reveals that the anti‐gp antibodies appear earlier. On the other hand, it was not possible to detect a viral antigen expression in the tissues of the infected animals.
Cytotoxic effector cells with the characteristics of natural killer cells in the lungs of mice
Authors: Puccetti Paolo , Santoni Angela , Riccardi Carlo , Herberman Ronald B.
Published: February 2007

Cells with in vitro cytotoxicity against tumor targets in a short‐term 51Cr release assay have been recovered from the lungs of mice that were either untreated or injected with biological or synthetic agents 1–3 days earlier. The cytotoxic effector cells were non‐adherent, non‐phagocytic and shared many characteristics with splenic natural killer (NK) cells. This finding is discussed with particular regard to our previous observations on the rapid in vivo elimination from the lungs of intravenously injected, radiolabelled tumor cells.
Characterization of lymphocyte subsets in spontaneous mouse mammary tumors and host lymphoid organs
Authors: Santer V. , Mastromarino J. H. , Lala P. K.
Published: February 2007

The subsets of small lymphocytes (surface lgm‐positive or B, Thy‐I‐positive or T and «double‐negative» or null) appearing within spontaneous mammary tumors of C3H retired breeder female mice and in various lymphoid organs of the host at different stages of tumor development were characterized directly using a radioautographic method. Tumor‐bearing mice showed early transient splenomegaly and progressive atrophy of the thymus. The proportion of T small lymphocytes increased with tumor age within the tumor and in the spleen, blood and thymus; then, except in the spleen, these proportions declined again by 8 weeks of tumor growth. The incidence of B small lymphocytes showed no change in the tumor or thymus; there was an increase in the blood after 3 weeks, and a small decrease in the spleen after 7 weeks. At all the sites examined, the proportion of null small lymphocytes declined from an initial high level observed in the elderly tumor‐free control mice, and then recovered to control levels after 7 weeks. The absolute numbers of T and null cells in the spleen changed in parallel to their proportions, while splenic B‐cell numbers increased at 1–3 weeks. In the thymus the absolute numbers of all subsets decreased, with a late recovery of null cell numbers. Age‐matched control mice showed higher proportions of null cells in the spleen, blood and thymus, and lower proportions of T cells in the blood and spleen, than did young normal mice. This spontaneous tumor appears to be characterized by an increase in T cells, rather than in null cells, as observed for rapidly growing transplanted tumors. The null cell rise in the present case takes place before the clinical appearance of tumors. In both cases, however, tumor‐infiltrating B cells exhibited low levels of surface Ig, possibly related to a low level of maturation. The functional significance of these findings remains to be determined.
Tumour‐related changes in natural killer cell activity in melanoma patients. Influence of stage of disease, tumour thickness and age of patients
Authors: Hersey P. , Edwards Anne , McCarthy W. H.
Published: February 2007

The influence of tumour growth on the natural killer (NK) activity of melanoma patients was examined by analysis of NK activity in 51 Cr release assays before and at intervals after surgical removal of localized melanoma. In patients with Stage I and II melanoma, removal of the tumour was associated with changes in the level of NK activity which were not detected in patients who had surgery for skin graft after previous removal of the primary melanoma. The changes in NK activity after removal of melanoma were however different in patients with Stage I compared to Stage II melanoma. In the former, NK activity which appeared specifically directed toward melanoma cells was maximal 2–4 weeks after removal of the tumour and then decreased to normal levels. The NK activity after surgery was directly related to the thickness of the tumour. In patients with Stage II melanoma, NK activity did not increase but fell to low levels after removal of the tumour. The level of NK activity in these patients was not related to the thickness of their primary melanoma. In patients with Stage I and II melanoma the NK activity against melanoma cells showed a significant increase with age. The reason for the different sequence of changes in NK activity after removal of melanoma in the two patient groups is unknown. It is suggested however that the differences observed in patients with Stage II melanoma may reflect differences in the tumour or host response which contributed to the spread of the tumour to regional lymph nodes in these patients.
Induction of morphological and functional differentiation of human promyelocytic leukemia cells (HL‐60) by compounds which induce differentiation of murine leukemia cells
Authors: Collins S. J. , Bodner A. , Ting R. , Gallo R. C.
Published: February 2007

Various compounds active in promoting in vitro differentiation of certain murine leukemia cell lines (Friend erythroleukemia cells and mouse myeloid leukemia cells) were tested for their capacity to induce differentiation of HL‐60 cells, a human promyelocytic leukemia cell line capable of terminally differentiating in vitro to functionally mature granulocytes. Polar planar compounds including hexamethylene bisacetamide (HMBA), certain purines (particularly hypoxanthine), and actinomycin‐D induced morphological and functional (as assessed by the capacity to reduce NBT dye) differentiation of HL‐60. In contrast, hemin, ouabain, prostaglandin E1, X‐irradiation, dexamethasone and some other anti‐leukemic chemotherapeutic agents induced little if any significant differentiation of HL‐60 cells. These results, together with previous observations with murine leukemia cells, suggest that the human HL‐60 cells share common cellular target sites for the inducing action of polar planar compounds, hypoxanthine and actinomycin‐D with some murine leukemic cells. In contrast, hemin, ouabain and prostaglandin E, may be specific for mouse erythroleukemia cells, while X‐irradiation and chemotherapeutic agents induce differentiation of both types (erythroid and myeloid) of mouse leukemic cells, but have little effect on HL‐60 cells.
Evaluation of the humoral response of glioma patients to a possible common tumor‐associated antigen(S)
Authors: Martin‐Achard Alec , Diserens Annie‐Claire , de Tribolet Nicolas , Carrel Stefan
Published: February 2007

Cytotoxic antibodies against glioblastoma‐associated antigen(s) have been sought for in glioma patient sera. Complement‐dependent cytotoxicity (CDC) and antibody‐dependent cell‐mediated cytotoxicity (ADCC) assays were used to test sera from 80 patients using 51Cr labelled target cells derived from eight different glioblastoma lines. As more positive sera were detected with ADCC than with CDC, ADCC assay was used for the remainder of the study. Cytotoxic antibodies were detected in the sera from 8 of 80 glioma patients (10%) by CDC and in 20 of 143 (14%) by ADCC. Fourteen per cent of 27 meningioma patients and 16% of 25 normal donors used as controls were found to react in ADCC against the same glioblastoma cell lines. The positive serum samples showed extensive cross‐reactions with the different glioblastoma cells, but the pattern of reactivity was different for each serum tested. The antibodies detected did not seem to be directed against tumor‐associated antigen(s), since the positive sera were found to have a similar ADCC reactivity against unrelated tumor cells and normal fibroblasts. Moreover, their antiglioma reactivity was absorbed by cells of unrelated tumors and by normal platelets. These results do not support previous reports of specific humoral responses in glioma patients against common tumor‐associated antigen(s).
The generation of tumor heterogeneity in vivo
Authors: Chow D. A. , Greenberg A. H.
Published: February 2007

In order to determine whether host factors may contribute to the generation of tumor heterogeneity, the phenotypic stability of cells from a cloned tumor was examined during proliferation in tissue culture and in the syngeneic host. Growth of this cloned tumor was initiated both in vivo and in vitro, and the tumor populations were sampled at different time intervals by subcloning. The susceptibility of these tumor subclones to the cytotoxic action of natural antibodies and complement was used as a marker of their membrane phenotype. The extent of phenotypic variation of the clones in one sample was considered to be a measure of tumor heterogeneity. Following these procedures, we observed that a clone of the L5178Y murine lymphoma maintained its homogeneity during 5 months of in vitro culture. In contrast, a single passage of the same tumor clone for 31/2 weeks or 3 months in the syngeneic host resulted in the generation of a population of cells exhibiting a significant increase in heterogeneity. This relative instability of tumor phenotype in vivo suggests that the host milieu may allow the generation of tumor heterogeneity. Genetic or epigenetic mechanism(s) may be involved although the high frequency of new phenotypes argues against a role for somatic mutation.
Metabolism of benzo[a]pyrene by cultured tracheobronchial tissues from mice, rats, hamsters, bovines and humans
Authors: Autrup Herman , Wefald Franklin C. , Jeffrey Alan M. , Tate Hussein , Schwartz Rochelle D. , Trump Benjamin F. , Harris Curtis C.
Published: February 2007

The metabolism of benzo[a]pyrene (BP)4by cultured tracheobronchial tissues from different species ‐ human, bovine, hamster, rat and mouse ‐ has been investigated. The total metabolism, as measured by both organic solvent‐extractable and water‐soluble metabolites of BP, was substantial in the respiratory tract from humans and from animal species susceptible to the carcinogenic action of BP. The ratio of organic‐extractable metabolites to water‐soluble metabolites was greater than one in hamster, human and C57BI/6N mouse, but less than one in rat, bovine and DBA/2N mouse, suggesting that determination of both activation and deactivation pathways are important in assessing carcinogenic risk of a chemical. Sulphate esters and glutathione conjugates were the major water‐soluble metabolites in all animal species; tetrols and diols were the major organic extractable metabolites. The level of trans‐7,8‐dihydro‐7,8‐dihydroxybenzo[a]pyrene, the proximate carcinogenic form of BP, was three times higher in C57BI/6N than in DBA/2N mouse trachea. Trans‐9,10‐dihydro‐9,10‐dihydroxybenzo[a]pyrene was the major metabolite formed by cultured hamster trachea. The binding levels of BP to cellular DNA were quite similar in all tissues, although slightly higher binding was observed in hamster trachea. Wide inter‐individual variation in the binding of BP to DNA was seen in tissues from outbred species. The major BP‐DNA adducts in all animal species were formed by interaction of benzo[a]pyrene diol‐epoxide with the 2‐amino group of deoxyguanosine. Both stereoisomeric forms of (±)‐(7β,8α)‐dihydroxy‐(9α, 10α)‐epoxy‐7,8,9,10‐tetrahydro‐benzo[a]pyrene (BPDE I) reacted with deoxyguanosine, the (7R)‐form being the most reactive. No difference in the relative distribution of the various adducts was seen between the species except in the CD rat, where BPDE‐deoxyadenosine adducts accounted for 20% of the total modification. In cultured hamster trachea the persistence of the different adducts was similar. In conclusion, the metabolism of BP is qualitatively similar in tracheobronchial tissues from both humans and animal species in which BP has been experimentally shown to be carcinogenic.
Cancer cell traffic from the lungs to the liver: An example of metastatic inefficiency
Authors: Weiss Leonard
Published: February 2007

It is probable that metastasis is an inefficient process in terms of cancer cells. One cause of this inefficiency may be that cancer cells temporarily arrested in one organ are «processed» by it, so that they die before or shortly after arrival in another organ. In the present experiments, the lung‐to‐liver traffic of [125I]dUrd‐labelled W‐256 cancer cells is examined over the course of 27 h in tumor‐bearing and non‐tumor‐bearing rats, following injection into, and sampling from, various points in the cardiovascular system. Following tail‐vein injections, W‐256 are temporarily arrested in the lungs and slowly released; some of the released cells are then temporarily arrested in the liver. Two percent of the cells detected in the lungs are non‐viable compared with approximately half of those in the liver; these measurements of viability correlate with a higher (10:I) incidence of lung transplants over liver transplants, and with the observation that extrapulmonary metastases are uncommon with this tumor. Direct injections of cancer cells into the liver indicate that the reduced viability of cancer cells at this site is not due to an inherently hostile hepatic environment. Injections into and sampling from, other sites indicate that only small proportions of cells were killed on their way to the lungs, during their arrest in the pulmonary capillaries and arterioles, or between the left ventricle, aorta, hepatic artery and liver. Pretreatment of W‐256 cells with neuraminidase, which is expected to make them more deformable, did not affect the viability of cells in the liver, thereby arguing against «processing» occurring during transit in the pulmonary circulation distal to the initial arrest sites. By a process of elimination it is concluded that a significant amount of trauma resulting in cancer cell death occurs during the events culminating in their release from temporary arrest sites at the pulmonary vascular endothelium. As the lungs are commonly the first organ encountered by circulating tumor cells, it is suggested that the low viability of cells released from the lungs contributes to metatastic inefficiency.
Natural killer cell activity associated with reticulum cell neoplasms
Authors: Chang Kenneth S. S. , Log T.
Published: February 2007

A marked increase in natural killer (NK) activity is observed with lymphoid cells prepared from SJL/J mouse spleen and lymph nodes, in which a transplantable reticulum‐cell neoplasm (RCN) is growing. The killer cells are non‐adherent, non‐phagocytic, relatively resistant to X‐ray, and scarcely or only partially inactivated by treatment with anti‐Thy 1.2 serum and complement. The killer activity is directed against a wide variety of tumor target cells, not requiring homology in histocompatibility, but is selective and not indiscriminate. Kinetics of in vivo development on NK activity, competitive inhibition of in vitro cytotoxicity by target cells and their membrane extracts are described. The NK activity appears to increase in parallel with the infiltration and growth of RCN in these organs. No such augmented NK activity was observed with other types of tumors that grew in these organs of SJL/J mice. (C57BL/6 × SJL/J)F1 mice pretreated with silica to abrogate Hh restriction and subsequently injected with RCN of SJL/J (H‐2s) origin supported the growth of transplanted RCN. The high NK activity associated with this RCN was markedly reduced by in vitro treatment with anti‐H‐2b serum plus complement, indicating the host origin of NK cells. However, the close association of RCN growth with elevated NK activity may indicate a special function of RCN in promoting NK activity by an unknown mechanism(s) of cellular interactions.
Differential inhibition of epstein‐barr virus induction by the amino acid analogue, L‐canavanine
Authors: Yamamoto Naoki , Mueller‐Lantzsch Nikolaus , Hausen Harald Zur
Published: February 2007

The effect of an amino acid analogue, L‐canavanine, on the synthesis of Epstein‐Barr virus (EBV) antigens was investigated in lymphoblastoid cells. The analysis revealed that after infection of BJAB and NC‐37 cells with P3HR‐I EBV synthesis of early antigen (EA) was not affected by canavanine in concentrations up to 8.4 mM. The synthesis of EBV‐determined nuclear antigen (EBNA) and of viral capsid antigen (VCA) was significantly inhibited at concentrations higher than 2.8 mM. Spontaneous induction of EA in P3HR‐I cells was not affected by canavanine. On the other hand, EA induction by the tumor promoter TPA, by iododeoxyuridine (IdUrd), by antiserum to human IgM and by n‐butyric acid was clearly inhibited by this treatment. Application of 0.3 mM canavanine resulted in more than 95% inhibition of EA induction by TPA. Under these conditions cell growth and incorporation of radiolabelled amino acids into an acid‐insoluble fraction was significantly impaired. Differential treatment of the cells with canavanine established that EA induction was completely suppressed when the cells were treated concomitantly with canavanine and TPA. Subsequent treatment with canavanine after prior exposure to TPA resulted in some viral antigen induction depending on the time period of TPA exposure. Pretreatment of the cells overnight with canavanine followed by washing and addition of the tumor promoter did not suppress EA induction by TPA. These data support the concept that EA induction by superinfection follows a different pathway from antigen induction by chemical inducers.
Humoral immune response in glioma patients: A solubilized glioma‐associated membrane antigen as a tool for detecting circulating antibodies
Authors: Birkmayer Georg D. , Stass H.‐P.
Published: February 2007

Plasma membranes from normal and neoplastic human brain tissue were isolated and compared morphologically, biochemically and immunologically. Their ultrastructure was identical, electrophoresis on polyacrylamide gel revealed at least 24 protein components, four of which were absent from membranes of normal tissue, whereas one was missing in the tumor pattern. The tumor‐associated components could be solubilized by the non‐ionic detergent Triton‐X100 and were used as an antigen source for the immunological characterization of glioma membranes. By means of a rabbit antiserum immunologically identical components could be detected in the Triton extract of the membranes from all the 20 human gliomas tested so far, but not in normal or fetal brain, nor in liver, kidney or spleen tissue. These data indicate that the solubilized membrane components contain common glioma‐associated membrane antigens which might be used in the detection of circulating antibodies in the sera of glioma patients. Of the 24 samples of sera tested so far, 19 (79%) contained precipitating antibodies against these membrane components as revealed by countercurrent electrophoresis.
Differential expression of trophoblast‐specific membrane antigens by normal and abnormal human placentae and by neoplasms of trophoblastic and non‐trophoblastic origin
Authors: Loke Y. W. , Whyte A. , Davies S. P.
Published: February 2007

Using a specific antiserum to human syncytial trophoblast plasma membrane (TrPM), we have investigated the expression of these antigens on a variety of trophoblastic and non‐trophoblastic tissues by a standard peroxidase/anti‐peroxidase staining method. Normal placenta (first‐trimester as well as full‐term), placenta from tubal pregnancy and placenta accreta were all found to express TrPM antigens. However, malignant change in trophoblast neoplasms appeared to be accompanied by a loss of these antigens, with 7 out of 10 specimens of hydatidiform mole staining positively while 3 specimens of invasive mole and 7 specimens of choriocarcinoma were all negative. In contrast, a number of malignant tumours of non‐trophoblastic origin such as carcinomas of the colon, cervix, bladder and hepatomas were found to express TrPM antigens. The possible significance of the reversal to a trophoblast phenotype by malignant neoplasms of non‐trophoblastic origin is discussed.
Humoral immune responses to human lymphoma cell heterotransplants in the central nervous system of athymic, nude mice
Authors: Adelman Daniel C. , Miller Richard A. , Kaplan Henry S.
Published: February 2007

Human malignant lymphoma cells may be readily heterotransplanted into the brains of athymic nude mice. We have examined humoral immune responses to these lymphoma cells and have found a primary cytotoxic IgM and a late cytotoxic IgG response. Nude mice with tumors growing intracerebrally were injected intravenously with fractionated IgM or IgG anti‐lymphoma cell antibody obtained from heterozygous immunocompetent animals. Frozen brain sections from these mice stained with fluoresceinated antibodies to mouse IgG and IgM revealed the presence of IgG but no IgM. Thus, IgM could not cross the blood‐brain barrier to react with the heterotransplanted lymphoma cells. It is proposed that xenogeneic tumor cells grow readily within the brains of nude mice because these cells are protected from a primary host cytotoxic IgM response by the blood‐brain barrier. The blood‐brain barrier renders the brain an immune sanctuary within which the impaired cell‐mediated immune responses of nude mice are further compromised by the exclusion of a major component of the humoral immune response.
In vivo natural reactivity of mice against tumor cells
Authors: Riccardi C. , Santoni A. , Barlozzari T. , Puccetti P. , Herberman R. B.
Published: February 2007

A rapid in vivo clearance of tumor cells was found in normal mice following intravenous inoculation of [125l]dUrd‐labelled YAC‐1 and RBL‐5 cultured cell lines derived from lymphomas. The ability of mice to eliminate tumor cells from spleen, liver and lungs during the first 4 h, as evaluated by the recovery of radioactivity in these organs, was found to correlate with the level of natural killer (NK) cell reactivity in their spleen and lungs, as measured simultaneously in vitro in a shortterm 51Cr release assay (CRA). Lower recovery of radioactivity was found in mouse strains with high spontaneous levels of NK activity. The degree of clearance was also found to be age‐dependent and older mice of several strains, whose NK activity had declined to low levels, were less effective in eliminating tumor cells. In vivo treatment with interferon and interferon inducers (poly I:C, pyran copolymer, Corynebacterium parvum, murine sarcoma virus) increased the levels of NK activity in the spleen and lungs and also augmented the in vivo clearance of tumor cells from the lungs and liver. Immunopharmacological treatments with antimacrophage agents (silica, iota‐carrageenan, Seakem‐carrageenan), antineoplastic drugs (dexamethasone, cyclophosphamide, 5‐(3,‐3′dimethyl‐I‐triazeno)‐imidazole‐4‐carboxamide, 4‐amino‐L‐D‐arabinofuranosyl‐2‐(IH)‐pyrimidone, adriamycin) or irradiation (850 R γ‐ray) had comparable effects on both in vitro cytolytic activity and in vivo clearance of tumor cells. When the susceptibility to in vitro and in vivocytotoxicity by several other tumors was examined, the lines with detectable sensitivity to lysis by NK cells were found to be cleared in vivo to a greater degree in a high NK strain (CBA) than in a low NK strain (SJL). In contrast, NK‐resistant lines were cleared at approximately the same rate in both strains. However, the actual levels of in vivo clearance and the degree of difference between the strains for the various NK‐sensitive lines did not correlate well with their relative sensitivities to lysis in vitro. In the various situations in which the in vivo recovery of a particular NK‐sensitive line was studied relative to the levels of NK reactivity in the recipients, the best correlations were seen with clearance from the lungs. In several instances, clearance from the spleen did not correlate well with splenic NK activity. These data indicate that rapid in vivo clearance of radiolabelled NK‐sensitive tumor cell lines is appreciably influenced by levels of NK reactivity, but that other factors are probably also involved.
Effector and enhancing lymphoid cells in plasmacytoma‐bearing mice. I. Methodological studies on the winn assay
Authors: Wang K. C. , Berczi I. , Sehon A. H.
Published: February 2007

Some parameters of the Winn assay for the detection of tumor‐suppressing (“effector”) and tumor‐enhancing lymphoid cells were studied in BALB/c mice. Spleen cells of mice that were preimmunized with mitomycin‐C‐treated MOPC‐104E plasmacytoma cells were inhibitory in this test system for both the MOPC‐104E and the HOPC‐1 plasmacytomas, thus indicating cross‐reactivity. Spleen cells taken from mice 6 days after the surgical removal of 15‐day‐old MOPC‐104E tumors inhibited the growth of lethal doses of MOPC‐104E cells in normal recipients, but no inhibition was observed 2 days after the removal of 18‐day‐old tumors. Spleen cells from mice bearing MOPC‐104E for 13 days enhanced tumor growth. This enhancement was not influenced significantly by the wide dose range (from 105 to 3 × 107) of MOPC‐104E cells used to initiate tumors in the lymphoid cell donors, although a tendency for stronger enhancing potential occurred after low tumor doses. When spleen cells from donors bearing MOPC‐104E for 10 days were injected at the constant tumor‐lymphocyte ratio of 1:30 with increasing numbers of tumor cells (from 5 × 105 to 2 × 106), tumor inhibition occurred at the lowest dose only, while no significant effect was observed at higher tumor cell doses. When a constant dose (5 × 105) of tumor cells was injected with spleen cells from 10‐day tumor‐bearers at tumor/lymphocyte ratios of 1:10, 1:40 and 1:160, a significant tumor inhibition occurred only at the ratio of 1:40. The relevance of the Winn test to the study of immune mechanisms in tumor‐bearing hosts is discussed.
Effector and enhancing lymphoid cells in plasmacytoma‐bearing mice. II. Dynamic changes during tumor progression
Authors: Wang K. C. , Berczi I. , Hoffmann E. G. , Sehon A. H.
Published: February 2007

The Winn assay was used for the study of effector (tumor‐inhibiting) and enhancing (tumor‐promoting) lymphoid cells in BALB/c mice bearing MOPC‐104E plasmacytomas. Kinetic studies with thymus, lymphnode, spleen and bone‐marrow cells revealed that spleen, lymph node and to a lesser extent bone‐marrow cells from 7‐ and 10‐day tumor‐bearers inhibited MOPC‐104E growth, while at day 13 all three cell populations enhanced tumor growth. However, at day 16 strong tumor inhibition was observed again by spleen cells and to a lesser extent by lymph‐node cells and thymocytes. Peritoneal cells from normal and tumor‐bearing (7 and 10 days) animals enhanced tumor growth significantly. Separation of spleen cells on nylon wool columns showed that at 10 days the effector cells were T lymphocytes, but at a later stage (35 days) a different effector mechanism was present in the spleen. Treatment of MOPC‐104E recipients with carrageenan or silica had little influence on tumor growth, but marked tumor inhibition occurred after lethal irradiation and bone‐marrow reconstitution. This latter observation, together with the finding that bone‐marrow, lymph node and peritoneal cells from normal donors enhanced tumor growth inseveral experiments, suggests that this plasmacytoma, like hormone‐dependent tumors, requires lymphocyte‐derived growth factors.
Spontaneous immune response of bovine leukemia‐virusinfected cattle against five different viral proteins
Authors: Deshayes Laurence , Levy Daniel , Parodi André L. , Levy Jean‐Paul
Published: February 2007

The sera from cattle exposed to bovine leukemia virus (BLV) have been studied by the radioimmunoprecipitation assay (RIPA) of disrupted virus proteins. All sera of animals with the adult form of lymphosarcoma precipitated four different viral proteins: gp51, gp35, p24 and p12. In contrast, the sera of five animals with the juvenile or thymic forms of bovine lymphosarcoma were completely devoid of precipitating activity against BLV proteins, confirming the absence of relationship between these rare malignant diseases and BLV infection. The sera of non‐leukemic cattle from areas of high risk of exposure to BLV were either negative or positive to a lower degree than the sera of lymphosarcomatous cows. When positive they precipitated gp51, p24 and p12. Only one serum precipitated gp35. The difference was probably quantitative, the sera of leukemic animals having higher levels of precipitating activity against all the viral proteins. The anti‐gp51 reactivity was in most cases the strongest, whatever the origin of the serum. In the rare sera which were positive in the classical antigp51 radioimmunoassay (RIA) but negative in the antip24 RIA, an anti‐p24 activity was, however, detected by the RIPA. These results suggest that BLV‐infected cows regularly produce antibodies reacting with four different viral proteins including minor viral components. In three cases with no other special features a low level of activity was detected against a fifth component: p15. There was no apparent correlation, however, between the antibody response and an hypothetical protection against BLV‐induced disease.
Human cell line (COLO 357) of metastatic pancreatic adenocarcinoma
Authors: Morgan R. T. , Woods L. K. , Moore G. E. , Quinn L. A. , McGavran L. , Gordon S. G.
Published: February 2007

A continuous human cell line, COLO 357, with exceptional characteristics was derived from a metastasis of a pancreatic adenocarcinoma. COLO 357 grew as an adhering monolayer with a cell doubling time of 21 h and grew with 10% clonal efficiency in soft agar. COLO 357 cells had numerous lamellar inclusions. The cells elaborated the pancreatic enzymes trypsin, elastase and chymotrypsin. COLO 357 also secreted appreciable amounts of carcinoembryonic antigen and human chorionic gonadotropin. COLO 357 had a chromosome mode of 53 with 20 identifiable Giemsa‐banded marker chromosomes. Nine nucleolar organizing regions were found by silver‐stained metaphase preparations. COLO 357 has been “fingerprinted” for seven allelic isozymes. This cell line has been maintained in active culture for over 2 years, is preserved in a cell bank, and is available to other investigators.
Distribution and characterization of alpha hCG in the serum and tumor cytosol of patients with breast cancer
Authors: Shindelman Jeffrey E. , Ortmeyer Ann E. , Wada H. Garrett , Stockdale Frank , Sussman Howard H.
Published: February 2007

Serum and tumor tissue from breast cancer patients were evaluated for the presence of alpha subunit of hCG, by means of the specific radioimmunoassay. Elevated serum levels occurred in 0/50 (0%) of normal female controls, 1/17 (6%) of patients with benign breast disease, 3/53 (6%) of patients with primary breast cancer, and 12/84 (14%) of patients with metastatic breast cancer. Cytosols from 10/56 (18%) primary tumors and 10/37 (28%) metastatic tumors were found to contain the alpha subunit. Comparison of serum and tumor cytosol levels in nine patients with metastatic disease showed a correspondence between elevated cytosol levels and elevated serum levels. No similar correspondence in 25 patients with primary disease was observed. Alpha subunit was isolated from one tumor cytosol and was characterized with respect to its immunochemical cross‐reactivity and molecular weight as compared with native alpha subunit from hCG. For both parameters, the native and ectopic alpha subunit were found to be identical.
Multiple antigenic specificities within primary 3‐methylcholanthrene‐induced rat sarcomas and metastases
Authors: Pimm M. V. , Embleton M. J. , Baldwin R. W.
Published: February 2007

Sarcomas were induced in WAB/Not rats by subcutaneous injection of 10, 5 or 1 mg 3‐methylcholanthrene (MCA) but not by 0.1 mg. Although tumours appeared earlier in rats given 10 mg MCA, compared with 1 mg, the majority of transplant lines from primary tumours were immunogenic and there was no correlation between the inducing dose of carcinogen and the growth characteristics or immunogenicities of the transplant lines. Most importantly sublines established from opposite poles of primary sarcomas were antigenically distinct in a substantial portion of cases, indicating that the primary tumours consisted of antigenically heterogeneous populations of cells. Furthermore, with one rat, renal and pulmonary metastases were antigenically distinct from a peritoneal secondary and the primary growth. These findings indicate that primary carcinogen‐induced tumours may be polyclonal in origin and this has implications for both the understanding of the carcinogenic process, and for the immunotherapy of malignant disease.
Inhibition of effector cell functions in natural killer cell activity (NK) and antibody‐dependent cellular cytotoxicity (ADCC) in mice by normal and cancer sera
Authors: Nair P. N. M. , Fernandes G. , Onoé K. , Day N. K. , Good R. A.
Published: February 2007

Effector cells mediating natural killer (NK) cell activity and antibody‐dependent cellular cytotoxicity (ADCC) have been receiving considerable interest recently as they may represent an additional cellular defense mechanism against maglinancy. Spleen cells from normal young C3H (MTV+) female mice were found to have relatively high natural killer (NK) activities toward RL 1 and YAC‐1 tumor cell lines and high antibody‐dependent cell‐mediated cytotoxicity (ADCC) activities toward chicken RBC and SB tumor targets. Serum inhibition of NK and ADCC activities was either not demonstrable or only seen at low levels in the young mice. Following injection of a transplantable mammary adenocarcinoma that grew progressively in these mice, both NK and ADCC activities decreased and serummediated inhibition of both NK and ADCC increased as the tumors grew. NK and ADCC activities declined with age in C3H (MTV+) mice, and the serum inhibition of NK and ADCC activities of young mice increased with age. Aging mice, however, which had developed spontaneous mammary adenocarcinoma, although having increased levels of inhibitor against both NK and ADCC activities and decreased NK and ADCC activities of their spleen cells as compared to young normal mice, did not have different levels from those of aging mice which had not developed the mammary tumor. Correlation was poor between the amount of serum inhibitor(s) on NK and ADCC activities. NK versus RL 1 and ADCC for chicken RBC were not correlated, but NK versus YAC‐1 and ADCC for the tumor cell line SB appeared to be correlated. Decreasing NK and ADCC and increasing serum inhibitory activity toward these functions appeared to correlate with tumor progression. Sera from transplantable tumor‐bearing young C3H mice contained increased amounts of circulating immune complexes, but the amount of circulating immune complexes was only weakly correlated with the serum inhibition of NK activity of spleen cells from young animals by sera from tumor‐bearing young mice. These findings indicate that a serum blocking factor(s) that can inhibit natural cell‐mediated cytotoxicity or antibody‐mediated cytotoxicity in vitro must be considered in analyzing host resistance to tumor growth.
Liver and kidney tumors induced by N‐nitroso‐dimethylamine in Xenopus borealis (Parker)
Authors: Khudoley V. V. , Picard J. J.
Published: February 2007

N‐nitroso‐dimethylamine dissolved in aquarium water at a concentration of 400 ppm (1/4 of the LD 50/30d) induced malignant tumors in 39 (54.2%) out of 72 young adult animals of the amphibian species Xenopus borealis. The first tumor was detected at 11 weeks, and the average latency was 35.1 weeks. Tumors were located in the liver (32 cholangiocarcinomas and 13 hepatocellular cancers) and the kidney (9 adenocarcinomas and 2 anaplastic cancers). Thirteen animals bore two or more types of tumors. These results demonstrate that a high percentage of tumors can be induced in amphibians by chemical carcinogens if appropriate methods are used.
Augmentation of tumoricidal activity of human monocytes and macrophages by lymphokines
Authors: Mantovani Alberto , Dean Jack H. , Jerrells Thomas R. , Herberman Ronald B.
Published: February 2007

Monocytes were separated from peripheral blood mononuclear cells of normal human donors by adherence on plastic conditioned by cell lines (microexudatecoated plastic) and harvested by exposure to ethylene diamine tetra‐acetic acid. Cytolytic activity was tested by incubating effector cells for 48 h with the murine SV40‐transformed TU5 kidney line or the human lung cancer‐derived CaLu line prelabelled with tritiated thymidine. Lymphokine‐containing supernatants were obtained from in vitro cultures of lymphoid cells with phytohemagglutinin (PHA)1, purified protein derivative (PPD), or with Corynebacterium parvum strains CN6134 or CN5888. The monocytes had significant levels of spontaneous cytotoxicity and exposure to lymphokine supernatants markedly enhanced their tumoricidal activity. Augmentation of monocyte‐mediated cytotoxicity required a minimal exposure to lymphokine supernatants for 4 h and was maximal after 24 h of preincubation. Treatment of the effector cells with anti‐human T‐cell serum and complement did not affect either their spontaneous or their lymphokine‐stimulated cytotoxicity, whereas silica impaired both reactivities. Supernatants of cultures with PHA, PPD and C. parvum CN6134 had significant levels of interferon (IF). Since partially purified human fibroblast or leukocyte IF was able to stimulate monocyte‐mediated cytotoxicity, the IF in these supernatants could play some role in the stimulation of the monocytes. However, C. parvum CN5888 supernatants, which had little IF, enhanced monocyte cytotoxicity as effectively as the C. parvum CN6134 supernatants, strongly suggesting that lymphocyte mediators other than IF can augment the tumoricidal activity of these effector cells. Mature macrophages obtained by in vitro cultivation of monocytes for 4–7 days retained natural cytolytic activity and showed enhanced cytotoxicity in the presence of lymphokines. However, more prolonged in vitro cultivation (> 10 days) resulted in cultures of epithelioid and multinucleated cells which had little natural cytotoxicity and were not responsive to lymphokines.
Antibodies reactive with the mouse mammary tumor virus in sera of breast cancer patients
Authors: Witkin Steven S. , Sarkar Nurul H. , Kinne David W. , Good Robert A. , Day Noorbibi K.
Published: February 2007

IgG binding to purified mouse mammary tumor virus (MuMTV) was quantitated by an enzyme‐linked immunoassay (ELISA) using sera from patients with breast cancer or benign breast disease, or from healthy agematched controls. Significantly greater binding (p<0.01) was found in breast‐cancer‐derived sera than in the other categories. In addition to IgG reactivity, three breast cancer sera also possessed IgA and IgM reactive with MuMTV by the ELISA assay. Only IgG was reactive in the majority of sera while two sera possessed MuMTV binding activity only in the IgM fraction. Both IgG binding and virolysis of MuMTV were greatly reduced by preincubation of sera with MuMTV. The specificity for MuMTV was further explored with IgG of serum from one breast cancer patient. Human antibody reactive with MuMTV was progressively diminished by preincubating the human serum with increasing concentrations of MuMTV but not by incubation with the type‐C AKR murine leukemia virus. Preincubation of MuMTV with a breast cancer serum partially blocked the reactivity of gp52 antiserum with the virus. The results suggest that an antigen related to an MuMTV envelope component is expressed in breast cancer.