bluuebunny/crossref_metadata_2025 huggingface dataset:
Carcinogenic potential of hycanthone in mice and hamsters
Authors: Bulay Orhan , Urman Huseyin , Patil Kashinath , Clayson David B. , Shubik Philippe
Published: February 2007

Hycanthone was administered to Schistosomo monsoni‐infected and non‐infected Syrian golden hamsters and Swiss mice by intraperitoneal and intramuscular injection of amounts up to the maximum tolerated dose. No tumors attributable to treatment were observed in hamsters. In infected mice, the overall incidence of hepatomas and hepatocellular carcinomas increased from 3.4% in untreated mice to 10.6% in those treated with hycanthone. Non‐infected control mice developed 0.8% of these tumors compared to 10.2% in mice treated with hycanthone. Despite the use of high dose levels of hycanthone, statistical significance was attained only with non‐infected female mice injected intraperitoneally and intramuscularly with hycanthone and then only at confidence levels of 92 and 95% respectively.
Cancer progression and monocyte inflammatory dysfunction: Relationship to tumour excision and metastasis
Authors: Normann S. J. , Schardt M. , Sorkin E.
Published: February 2007

In a longitudinal study performed before and after surgical resection of a chemically‐induced, transplanted rat tumour we found that a monocytosis‐and tumour‐Induced anti‐inflammatory effect directed against macrophages was promptly corrected by tumour excision but recurred with metastasis. These observations indicate that the monocyte abnormalities are acquired and related to cancer progression. The anti‐inflammatory effect required relatively large primary or metastatic tumour burdens. Our findings support the clinical impression that monocyte abnormalities are associated with a poor prognosis.
Effect of Corynebacterium parvum on hemopoietic stem‐cell kinetics
Authors: Eliopoulos George , Andre Simonne , Anagnou Nick P. , Matsis Constantin , Halpern Bernard
Published: February 2007

The intravenous administration of 548 μg of killed Corynebocterium parvum(C. parvum)Into C57BL mice leads to a significant decrease in the number of bone‐marrow colony‐forming‐units in spleen (CFUs) as early as 12 h after the injection of the bacterium. This decrease persisted in varying degrees for 3 weeks. After an initial fall at 24 h, the splenic CFUs exhibited a rapid expansion and reached values 10 times higher than the control range on the ninth day. A significant rise in the number of circulating CFUs, reaching a first peak at 2 h and a second one on the fifth day, was also observed. The pro‐liferative status of femoral CFUs was increased at 48 and 72 h, while that of splenic CFUs presented a significant increase only 48 h after the injection of C. parvum. The sequence of events which were observed in these experiments Indicates that an accelerated migration of hemopoietic stem cells from bone marrow to spleen via the blood circulation has to take place.
Cytolytic and cytostatic anti‐tumor activities of macrophages from mice injected with murine sarcoma virus
Authors: Puccetti Paolo , Holden Howard T.
Published: February 2007

We have characterized the cytolytic activity of adherent cells isolated from enzymatically disaggregated tumors or from the peritoneum of mice injected with murine sarcoma virus (MSV) using an 18‐h51 Cr release assay and compared it with the cytostatic activity present in the same effector population. Cytolytic activity of peritoneal exudate cells peaked 14 days after inoculation of MSV. Injection of thioglycolate increased ten‐fold the number of cells recovered from each animal and these cells exhibited the same level of cytotoxicity as did those obtained from uninduced animals. Fourteen days after MSV inoculation, cytolytic activity was also detected in the adherent cells isolated from the tumor and these cells had higher levels of reactivity than the peritoneal cells. Several lines of evidence indicated that the cytolytic effector cells were macrophages: the effector cells were adherent and phagocytic; were inactivated by silica and carrageenan, and removed by the carbonyl iron/magnet technique; and were not affected by treatment with anti‐Thy 1.2 plus complement. Furthermore, the effector cells were heterogeneous since, when they were separated by 1 g velocity sedimentation, there were several peaks of activity corresponding to macrophages with different sizes. Cytotoxicity was not specific since several antigenically unrelated target cells could be lysed. Cytostasis was measured by performing cell counts on the target cells as well as by the usual growth inhibition assay in which incorporation of [3H]thymidine is used as the indicator of proliferation. At low A:T ratios (10:1 to 1.25:1) there appeared to be no cytolytic activity since there was no significant decrease In the number of target cells at any time during the incubation. However, there was marked inhibition of growth as measured both by cell counts and by [3H]thymidine incorporation. The lytic effects were only detected at A:T ratios approximately ten times higher than those required for the inhibition of proliferation. Therefore, macrophages that can exert cytolytic and cytostatic anti‐tumor activity are present within MSV tumors which subsequently regress. This suggests a role for the macrophages in the anti‐tumor immune response that may be complementary to the well‐established specific cytolytic activity of immune T lymphocytes.
K562—A human erythroleukemic cell line
Authors: Andersson Leif C. , Nilsson Kenneth , Gahmberg Carl G.
Published: February 2007

We have studied the surface membrane properties of the human leukemic cell line K562 which previously has been reported to represent an early stage of granulocyte maturation. The surface glycoprotein pattern of the K562 cells obtained after galactose oxidase‐NaB[3H]4 labelling and slab gel electrophoresis shows striking similarities with that of normal erythrocytes but is completely different from the patterns of normal and malignant cells of various stages of the myeloblast to granulocyte differentiation. Moreover, the K562 cell expressed the major red cell sialoglycoprotein, glycophorin, on its surface as shown by immuno‐fluorescence and by immuneprecipitation from labelled membrane preparations. As glycophorin is exclusively found on erythroid cells in human bone marrow we conclude that the K562 is a human erythroleukemic line.
Immunoglobulin‐producing cells in the “transitional” mucosa adjacent to adenocarcinomas of the human large bowel
Authors: Rognum T. O. , Brandtzaeg P. , Baklien K. , Hognestad J.
Published: February 2007

Quantification of IgA‐, IgM‐and IgG‐producing immunocytes was performed in a defined mucosal tissue unit adjacent to 16 adenocarcinomas of the large bowel, and compared with data for control units from 15 histologically normal specimens. The thickness of the “transitional” mucosa adjacent to the tumours was markedly increased. Thus, the average cancer‐associated unit showed a 2.6‐fold increase in height and its number of immunoglobulin‐producing cells was raised 2.8 times. The numerical increase for IgA cells was 2.1, for IgM cells 5.1, and for IgG cells 13.0; the percentage proportions of these cell classes were changed from 91:6:3.6 to 71:12:17. Only very rare IgD‐and IgE‐producing cells were seen. The immunocyte density in 6‐μm‐thick sections (cell number/mm2 of lamina propria) was 823, 136 and 201 for the IgA, IgM and IgG class, respectively, compared to the normal figures of 1,186, 73 and 49. The density of IgG and IgM cells was thus significantly increased and that of IgA cells decreased in the lamina propria of the “transitional” mucosa. The intra‐individual scatter of all variables, including mucosal height, was large in the “transitional” mucosa, but the variables became normalized approximately 1 cm from the tumour. The excessive rise in the local production of IgG, with no concomitant increase in the density of IgA cells, indicates that there are local stimulatory factors bypassing the secretory IgA immune system. Further studies are needed to show if this local immune response reflects production of tumour‐specific antibodies or is merely due to increased penetrability for antigens from the gut lumen passing through the tumour lesion.
A rapid in vitro assay for carcinogenicity of chemical substances in mammalian cells utilizing an attachment‐independence endpoint
Authors: Traul K. A. , Kachevsky V. , Wolff J. S. , Hink R. , Nanna U.
Published: February 2007

Rauscher leukemia virus (RLV)‐infected rat embryo cells have been shown to be sensitive to neoplastic transformation by a variety of chemical carcinogens. The mass assay technique normally used requires 6 to 15 weeks before morphologically altered foci of cells are observed. While growth in soft agar is considered to be one of the best in vitromeans for confirming neoplastic transformation, this assay requires 4 additional weeks beyond focus formation. We have devised a rapid new assay for determining carcinogenicity of chemicals. The method takes advantage of the range of chemical sensitivity of RLV‐infected rat embryo cells, but provides, in 10 days, for a readout based on the ability of transformed cells to survive under conditions which select for attachment independence. The target cells, 2FR450, were treated for 72 h with chemical and then plated into Petri dishes containing a solid bottom layer of agar/medium. Viable cell counts were made 3 and 6 days later and compared to parallel data from solvent‐treated control cells. 2FR450 cells treated with any of 10 chemical carcinogens, including such diverse compounds as benzo(a)pyrene, 3‐methylcholanthrene, 2‐acetylaminofluorene, NiSO4and urethane, showed an average increase of 225% in survival over controls. Phenanthrene, a non‐carcinogen, induced no increase in survival of 2FR450 cells. This assay appears to permit detection of carcinogens of various chemical types with a simple test readout within 10 days.
A quantitative determination of the covalent binding of a series of polycylic hydrocarbons to dna in mouse skin
Authors: Pcchillips David H. , Grover Philip L. , Sims Peter
Published: February 2007

The extents of reaction of seven 3H‐labelled polycyclic hydrocarbons with DNA in mouse skin following their topical application have been studied. DNA isolated from the treated areas was hydrolysed enzymically to deoxyribonucleosides and the products chromatographed on Sephadex LH20 columns. The levels of binding of hydrocarbon to DNA were determined from the amounts of radioactivity eluted from Sephadex LH20 columns in those fractions containing hydrocarbon‐DNA adducts. Tritium incorporation into normal deoxyribonucleosides was examined by rechromatography of material on AG50W‐X4 columns and in some instances was found to account for a substantial proportion of the total radioactivity associated with DNA samples. Following treatment of mice with 1 (imol hydrocarbon/mouse, 7, 12‐dimethylbenz(a)anthracene, the most potent carcinogen studied, became bound to DNA to the greatest extent (43 pmol/mg DNA), Benzo(a)pyrene and 3‐methylcholanthrene, the next most active compounds, became bound to DNA to similar extents (27 pmol/mg DNA and 25 pmol/mg DNA), as did 7‐methylbenz(a)anthracene (25 pmol/mg DNA) although it is a less active compound. Dibenz‐(a,h) anthracene, another moderately active hydrocarbon, became bound to DNA to the extent of 15 pmol/mg DNA, and the very weakly active compounds, benz(a)anthracene (2 pmol/mg DNA) and dibenz(a,c) anthracene (10 pmol/mg DNA) became bound to DNA to the lowest extents. Dibenz(a,h))anthracene differed from the other hydrocarbons in showing a maximum level of binding 72 h after treatment, compared with 19–24 h for the other compounds.
Serological identification of neoantigens on mouse fibroblasts which have undergone “spontaneous” malignant alteration in vitro
Authors: Willumsen Berthe Marie , Ulrich Kay , Kieler Jørgen
Published: February 2007

ST‐L1 is a cell line established from lung explants from a normal ST/a mouse. The ST‐L1 cells have undergone spontaneous malignant alteration in vitro. The cells were rejected after inoculation into syngeneic immunocompetent hosts, and a syngeneic humoral immuneresponse against the ST‐L1 cells has been detected. The specificity of this humoral response was investigated. The syngeneic response to ST‐L1 was characterized by indirect immunofluorescence tests and by immunoprecipitation of radiolabelled cells and of a C‐type virus produced by the cell lines. The specific anti‐ST‐L1 reactivities were found to be directed against the envelope glycoprotein of an endogenous C‐type virus expressed by the antigenic cell line.
Tumor metastases and cell‐mediated immunity in a model system in DBA/2 mice. I. Tumor invasiveness in vitro and metastasis formation in vivo
Authors: Schirrmacher V. , Shantz G. , Cauer K. , Komitowski D. , Zimmermannn H.‐P. , Lohmann‐Matthes M.‐L.
Published: February 2007

A syngeneic model system for the study of tumor metastases and cell‐mediated immunity is described. The system consists of two related, chemically induced murine lymphomas, the non‐metastasizing parental line Eb and its metastasizing variant ESb. An unrelated, chemically induced tumor (MDAY) is included for specificity controls. Serological typing revealed that both Eb and ESb were of T lymphoid origin and expressed the H‐2K and H‐2D molecules of the host strain DBA/2. By various electron microscope techniques, morphological differences were observed between the two cell lines. In comparison to Eb cells, ESb tumor cells had a more polymorphic nucleus with many in vagi‐nations of the nuclear envelope and a more prominent expression of microvilli on the cell surface. An in vitro organ culture test for tumor invasiveness, presented here for the first time in a syngeneic murine system, revealed that ESb but not Eb tumor cells had the ability to attach to and invade normal tissue. Accordingly, ESb tumor cells showed higher malignancy in vivo. This was apparent from their higher tumorigenicity and their ability to disseminate and metastasize and to kill recipient mice more quickly. Upon histological examination of the local primary tumors a striking difference was noticed with regard to the degree of infiltration by host‐derived mononuclear cells, mostly histiocytes. The non‐metastasizing tumor Eb was heavily infiltrated while tumor ESb contained only a few of these cells. The differences between the tumor lines ESb and Eb are considered in the light of their possible relevance for metastases in general. The etiology of the two tumors is discussed in particular with respect to their relatedness.
Tumor metastases and cell‐mediated immunity in a model system in DBA/2 mice.: Iv. Antigenic differences between a metastasizing variant and the parental tumor line revealed by cytotoxic T lymphocytes
Authors: Schirrmacher V. , Bosslet K. , Shantz G. , Clauer K. , Hijbsch D.
Published: February 2007

The syngeneic cytotoxic T‐cell response against a metastasizing murine lymphoma variant was investigated and compared with the response against the non‐metastasizing parental tumor line Eb. Anti‐tumor cytotoxicity was not detectable in a 4‐h 51Cr release assay in spleens taken directly from tumor‐bearing animals (primary CMC). After restimulation in vitro (secondary CMC) however, high anti‐tumor cytotoxic activity was detected. This activity was mediated by immune T lymphocytes as shown by its sensitivity to treatment with anti‐Thy 1.2 serum and complement. Ten cells of the metastasizing tumor ESb, inoculated subcutaneously, were sufficient to raise a local tumor and metastases and to induce cytotoxic T memory cells in the spleens. In contrast, about 104 cells were required to raise a local tumor and to induce splenic cytotoxic T memory cells, when the parental tumor Eb was tested. The specificity studies of the anti‐tumor cytotoxic activity demonstrated that cytotoxic T cells could distinguish unrelated, chemically induced syngeneic tumors and also recognize antigenic differences between the parental tumor Eb and its variant ESb. Eb and ESb tumor cells were recognized as carrying distinct antigens at the responder cell level, the stimulator cell level and the target cell level. The in vivo significance of these findings is discussed.
Circulating immune complexes and prognosis in human malignant lymphoma, a prospective study
Authors: Heier Hans Erik , Landaas Tone Ø. , Marton Per F.
Published: February 2007

Sera from 53 patients with Hodgkin's disease (HD) and 56 patients with non‐Hodgkin malignant lymphoma (NH) were investigated, prior to treatment, for the presence of circulating immune complexes (CIC) by the 125l‐C1q‐binding radio‐assay. The patients were then followed for 14–31 months. No significant association was found between the presence of CIC and achievement of complete remission in any of the groups. In none of the groups could a difference be found between the survival rates of patients with and without CIC in their sera prior to treatment. About half of the patients were retested for the presence of CIC after completion of initial therapy. No significant association was found between the presence of post‐treatment CIC and lack of complete remission in any of the patient groups. In the HD group, both pre‐and post‐treatment CIC appeared to be most frequent among patients over 50 years. No such association was found in the NH group.
Cell surface glycoprotein analysis: A diagnostic tool in human leukemias
Authors: Andersson Leif C. , Gahmberg Carl G. , Shmes Martti A. , Teerenhovi Lasse , Vuopio Pekka
Published: February 2007

We have radiolabelled surface glycoproteins of different types of leukemic cell. The labelled proteins were separated by polyacrylamide slab gel electrophoresis and visualized by fluorography. Surface glycoprotein patterns discriminatory for acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL). acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) were found. We conclude that the analysis of the surface glycoprotein profile provides a useful method for the classification of leukemic cells according to cell type and stage of differentiation.
Burkitt's lymphoma in Ghana: Urban‐rural distribution, time—space clustering and seasonality
Authors: Biggar Robert J. , Nkrumah Francis K.
Published: February 2007

Epidemiological data are summarized from 236 cases of Burkitt's lymphoma (>90% cytologically or histologically confirmed) seen from 1970 through 1975 at Korle Bu Hospital, Accra, Ghana. The rate of referral from rural areas was greater than that from urban areas, despite a probable bias toward referral from urban areas. The distribution of cases in Ghana appeared to be non‐random but we attribute this to variable access to medical care and physician interest. Rainfall did not appear to be an important factor. Seasonal variation and time—space clustering were not observed. The incidence here seems lower than that reported in East Africa. We found no evidence of an environmental influence with a short incubation period, as has been postulated for this disease in East Africa. The higher risk among rural patients is consistent with severe malaria being a factor in the etiology of Burkitt's lymphoma.
The metabolic activation of benzo(a)pyrene and 9‐hydroxybenzo (a) pyrene by liver microsomal fractions
Authors: Lubet Ronald A. , Capdevila Jorge , Prouoh Russell A.
Published: February 2007

A rat liver microsome‐mediated bacterial mutagenicity test showed 9‐hydroxybenzo (a) pyrene to be significantly more effective as a pre‐mutagen than benzo (a) pyrene. Experiments measuring the ability of these compounds to be metabolically activated to moieties that alky late exogenous DNA demonstrated that 9‐hydroxybenzo (a) pyrene was almost six times more effective than benzo (a) pyrene itself. Addition of trichloropropene‐2,3‐oxide to the reaction mixture enhanced the mutagenicity and DNA alkylation by benzo (a) pyrene but had little or no effect on the 9‐hydroxybenzo (a) pyrenemediated mutagenicity and alkylation. On the other hand, 7,8‐benzoflavone inhibited the microsome‐mediated mutagenicity and DNA alkylating activity of both hydrocarbons.
Inverse correlation between cell‐surface adhesiveness and malignancy in mouse fibroblastoid cell lines
Authors: Bubeník Jan , Perlmann Peter , Fenyö Eva Maria , Jandlová Táň , Šuhajová Eva , Malkovský Miroslav
Published: February 2007

The correlation between tumorigenicity and cell‐surface adhesiveness was investigated in eight mouse fibroblastoid cell lines. Four of the lines (Mc 11‐Mc 15) were derived from mouse MC‐induced fibrosarcomas, two were derivatives of L cells (A9, A9HT), and two (clone 3 and clone 7 H7F4) were obtained by fusion of A9HT cells with normal diploid mouse lymphocytes. Quantitative comparison of cellular adhesive properties by the Latex particle adherence assay indicated that higher malignancy of some lines (Mc 11, 13, 14, A9HT cl 7 H7F4) was regularly associated with lower cell‐surface adhesiveness and, conversely, lower malignancy of the other lines (Mc 15, A9, cl 3) with high cell‐surface adhesiveness. The differences in adhesiveness of cell lines of high and low malignancy were determined by cell subsets not attaching any Latex particles (24.6–61.9% of cells in highly and 4.6–12.0% in slightly tumorigenic lines) and cell subsets attaching more than 25 Latex particles per cell (14.6–17.2% In highly and 46.1–71.4% in less tumorigenic lines).
Discrepant effects of interferon on murine syngeneic ascites tumors and their solid metastastzing counterparts
Authors: Ryd W. , Hagmar B. , Lundgren E. , Strannegård Ö.
Published: February 2007

The effects of interferon on mice with syngeneic tumors growing either intraperitoneally or as solid tumors were analyzed. The same dose that depressed the growth of ascites tumors, enhanced growth and in one case metastasizability of the corresponding solid tumors. The possibility that this was due to some host reaction is discussed. It seems important to develop animal models for analyzing interferon effects before treatment is initiated in human tumor disease.
Oesophageal cancer and alcohol consumption; importance of type of beverage
Authors: Tuyns A. J. , Péquignot G. , Abbatucci J. S.
Published: February 2007

The role of alcohol consumption in oesophageal cancer in Normandy has been studied by a retrospective study of 312 male cases and 869 controls. The linear relationship between the logarithm of risk and overall daily alcohol consumption was confirmed after adjustment for tobacco. The role of each specific alcoholic beverage was further investigated by computing relative risks for individuals consuming a given beverage and for those drinking other beverages only, within each overall alcohol consumption category. It is concluded: (1) that there is a linear relationship between the logarithm of risk of oesophageal cancer and overall daily ethanol consumption, whatever the beverage; (2) that the effect is more marked for strong beverages (digestives) than for lighter beverages; (3) that there is an additional risk related to apple brandy and cider.
Ultrastructural and immunocytochemical localization of immunoglobulin synthesis in tumor cells in Hodgkin's disease
Authors: Reynès M. , Paczynski V. , Galtier M. , Diebold J.
Published: February 2007

An immunocytochemical and uitrastructural study using the Fab fragment of an anti‐human Ig antibody labelled with peroxidase was carried out on affected lymph nodes from five Hodgkin's disease patients. The tumor cells (Reed‐Sternberg cells and Hodgkin cells) showed an exclusively hyaloplasmic granular staining. By comparing these grains with ribosome staining of the endoplasmic reticulum of plasma cells it could be suggested that they are free risobomes. This ribosomal Ig synthesis is a major argument for the B lymphocyte nature of Reed‐Sternberg and Hodgkin cells. The total absence of vacuole staining allows us to conclude that these cells are not histiocytic or macrophage derivatives.
Some environmental and bodily characteristics of melanoma patients. A case‐control study
Authors: Klepp Olbjørn , Magnus Knut
Published: February 2007

A case‐control study Including 78 patients with malignant melanoma of the skin and 131 controls with the diagnoses of malignant lymphoma, testicular cancer or bone and soft‐tissue sarcoma, was performed at the Norwegian Radium Hospital 1974–1975. The questionnaire contained questions for evaluating the comparability between cases and controls, and questions bearing on the relation between sun exposure and malignant melanoma. No essential difference between cases and controls was found as regards hair and eye colour, time spent outdoors during leisure, and degree of solar exposure. The melanoma patients liked sunbathing less than controls, worked more outdoors, more often went to Southern Europe for sunbathing and more often used sun lotions. These differences, however, were not clearly statistically significant. Highly significant differences were demonstrated as regards the tolerance of sun exposure and propensity to freckling. The melanoma patients tolerated sun exposure less well and freckled more easily than the controls. Although attempts were made to eliminate bias, there are still limitations and loop‐holes in the study, and the relative risks demonstrated are not large enough to be of great immediate practical or scientific value. It seems justified, however, to advise persons with a low sun exposure tolerance to be cautious in following the sun‐tandemanding fashions. The study may also provide certain clues for the planning of future epidemiological and clinical studies regarding the etiology of malignant melanoma.
Immunosurveillance in pre‐malignant occupational bladder disease
Authors: Taylor G. , Kumar S. , Brenchley P. , Wilson P. , Costello B. , Shaw G. H.
Published: February 2007

A population of workers exposed to bladder carcinogens has been studied by comparing their immunoreactivity against bladder cancer cells and against a control cancer cell with that found in normal individuals and in patients with bladder cancer. Data are presented which indicate equivalent increases in specific reactivity against bladder cancer cells in clinically normal carcinogen‐exposed workers and in patients with bladder cancer. Increases in reactivity are related to degree of exposure and also to early malignant changes in the urothelium. This indicates that immune recognition of tumour antigens does occur before development of overt malignancy.
Establishment and characterization of a human null‐cell lymphoblastic lymphoma cell line (K‐LL‐3)
Authors: Smith Stephen D. , Rosen David
Published: February 2007

A new cell line (K‐LL‐3) with exceptional characteristics was derived from a bone‐marrow aspirate from a patient with poorly differentiated lymphoblastic lymphoma. The cell line was established and the cells maintained on agar feeders for over 1 year. The morphology and cytochemical staining of the primary tumor and the cell line were remarkably similar. The growth characteristics, chromosome pattern, cell‐surface receptors and Epstein‐Barr virus studies clearly differentiated this cell line from non‐malignant lymphoblastoid cell lines. The assay technique used was able to correlate in vitro colony growth with the patient's clinical course. The cells grew on the agar as colonies rather than as a single‐cell suspension, and individual colonies could be aspirated and successfully passaged. The K‐LL‐3 cells lacked cell‐surface markers (cytoplasmic and surface immunoglobulins, Fc receptors, C3 receptors, SRBC) except HL‐A and thus were classified as null cells. These cells were EBNA (Epstein‐Barr virus‐specific nuclear antigen) negative and had a pseudodiploid 46XY karyotype.
Murine natural anti‐tumor antibodies. I. Rapid in vivo binding of natural antibody by tumor cells in syngeneic mice
Authors: Wolosin L. B. , Greenberg A. H.
Published: February 2007

A competitive radioimmunoassay (RIA) for the detection of cell‐bound antibody was used to study the in vivo acquisition of immunoglobulin (Ig) by tumor cells. Several tumor lines acquired Ig rapidly between 3 and 18 h after intraperitoneal implantation into normal syngeneic mice and this Ig was recovered by elution with basic or acid buffers. The Ig eluted from the L5178Y lymphoma showed higher binding to the L5178Y than to thymocytes, bone‐marrow cells, 1509a sarcoma and P‐815‐X2 mastocytoma. In addition, binding of the eluates to the L5178Y was specifically inhibited by L5178Y cells or by solubilized membrane antigens of the L5178Y. The in vivo acquisition of Ig by the L5178Y could also be blocked by the IV and IP injections of tumor antigen although both L5178Y and 1509a solubilized membrane antigens were effective. Some of the Ig acquired by the tumor cells was found to be complement‐fixing antibody since normal rabbit complement lysed 80% of L5178Y cells obtained from the peritoneal cavity of syngeneic mice 18 h after implantation, but did not lyse in vitro L5178Y cells. The in vivo binding of the complement‐fixing antibodies was also inhibited by tumor antigens in the same way as the acquisition of Ig detected by RIA. It was shown that the acquisition of Ig during the first 18 h of IP growth was a T‐independent phenomenon because tumor cells acquire as much Ig in AT × BM mice as in sham‐thymectomized controls. In a study with 11 different clones derived from the L5178Y lymphoma, a high correlation (r = 0.75, p<0.005) was found between the amount of Ig acquired after in vivo implantation and the amount of Ig bound to the cells after in vitro incubation with normal syngeneic serum. It is suggested that the rapid in vivo acquisition of Ig was due to the in vivo binding of natural antibodies to tumor cells.
Treatment of micrometastases from lewis lung carcinoma with abrin and cyclophosphamide, given singly and in combination
Authors: Gundersen Stein , Fodstad Öystein
Published: February 2007

The effect of the plant toxin abrin and of cyclophosphamide given as adjuvant chemotherapy after irradiation of the primary tumor was studied in mice bearing intramuscularly growing Lewis lung carcinoma. The chemotherapy was given immediately after irradiation performed 9 days after inoculation of 105 tumor cells. The drugs were given in bolus injections either as single agents or concurrently. The therapeutic effect was assessed by recording the appearance of lung metastases on day 21 or the number of long‐term survivors, i.e. animals alive at day 60. In the control group 21±3.4 (SD) macroscopic lung colonies was recorded on day 21. Mean survival time was 25.5 days with none of the mice alive at day 60. The optimal abrin dose (612.5 ng/kg IV) reduced the number of lung metastases to 2.3±0.8 and yielded 37% long‐term survivors (11/30). The optimal dose of cyclophosphamide (150 mg kg IP) reduced the number of lung colonies to <1 and yielded 61% survivors (14/23). Small to moderate doses of abrin significantly potentiated the therapeutic effect of cyclophosphamide without increasing the toxicity. The best results (18/20 or 90% long‐term survivors) were obtained when the optimal dose of cyclophosphamide, 150 mg/kg, was combined with 350 ng/kg of abrin. The results obtained in this highly resistant tumor suggest that combinations of the two drugs may be useful also in other tumor types.
Reproducibility and relation to specific and non‐specific anti‐tumor resistance of the tumor “sneaking through” phenomenon
Authors: Deichman G. I. , Kluchareva T. E. , Kashkina L. M. , Matveeva V. A.
Published: February 2007

The reproducibility and immunological specificity of the tumor “sneaking through” phenomenon and enhancement of tumor growth were studied in syngeneic and random‐bred Syrian hamsters by means of a quantitative modification of the transplantation test. After primary challenge the phenomenon was neither observed in normal animals nor in animals effectively immunized against tumor. However, it was regularly observed in some “immune” animals after secondary challenge. In primary challenge of animals “sneaking through” phenomenon was most often observed in animals pretreated with large doses of heat‐inactivated tumor cells. This characteristic could not be transferred with serum of pretreated animals. In contrast to specific tumor immunity, the “sneaking through” phenomenon appeared to be immunologically non‐specific. This was observed in cross‐transplantation tests with tumor cells bearing different TSTAs. Thus, TSTA is not an inducer and apparently not a target for a response leading to enhancement of tumor growth in pretreated hamsters. Experiments demonstrating enhanced tumor growth in pretreated animals at the same time demonstrate two other possibly more essential findings: (1) normal animals are naturally resistant to transplantation of 1 to about 1 × 103 (or more) tumor cells; and (2) this resistance can be totally abrogated by the pretreatment of normal animals with tumor cell preparations. The preliminary data demonstrate that abrogation of natural anti‐tumor resistance in adult hamsters subsequently inoculated with SV40 leads to rapid development of primary tumors in such animals. The development of specific anti‐tumor immune response in animals treated with inactivated tumor cell preparations was also studied. Significant non‐specific inhibition of primary and secondary anti‐tumor immune response in Syrian hamsters treated with inactivated syngeneic tumor cells was observed. The data obtained are considered to demonstrate two anti‐tumor defense systems in the animal, i. e., nonspecific natural resistance and specific anti‐tumor immunity. The first seems to be responsible for elimination of low numbers of tumor cells in the normal organism and also to be essential for effective induction and functioning of the specific anti‐tumor immunity.
Long‐term T‐cell‐mediated immunity to Epstein‐Barr virus in man. II. Components necessary for regression in virus‐infected leukocyte cultures
Authors: Rickinson A. B. , Moss D. J. , Pope J. H.
Published: February 2007

Regression of EB‐virus‐induced transformation occurs exclusively in cultures of leukocytes from seropositive donors. Studies have shown that the strength of regression could be assayed in terms of the proportion of T cells which must be added to the autologous EB virus‐infected T‐cell‐depleted population in order to establish regression in the culture. The in vitro regression phenomenon was strongly T‐cell‐dependent but did not require the presence of either monocytes or, as a potential antigenic stimulus, the residual viral envelope material on the surface of virus‐infected B cells. The T‐cell‐depleted population from seropositive donors sometimes transformed (7/60 cultures) without the experimental addition of virus. Regression appeared to be independent of cytotoxic mechanisms involving anti‐viral antibodies and not to be mediated by soluble factors released into culture medium.
CEA and non‐specific cross‐reacting antigen (NCA) in medullary carcinomas of the thyroid
Authors: Burtin P. , Calmettes C. , Fondaneche M. C.
Published: February 2007

An immunohistological study of five cases of medullary carcinoma of the thyroid was undertaken with monospecific antisera against CEA and NCA. CEA was present in different areas of the tumors: cell cytoplasm, cell membrane at its apical pole when the tumor had a pseudoglandular organization, deposits in the lumen of pseudoglands, and peri‐and extra‐cellular deposits. From these extra‐cellular deposits, CEA could easily reach the circulation, thus causing rising serum levels up to high values. NCA was found in the same tumors and in the same localizations.
Intracranial heterotransplantation of human hematopoietic cells in nude mice
Authors: Schaadt Michael , Kirchner Hartmut , Fonatsch Christa , Diehl Volker
Published: February 2007

A panel of established cell lines and many primary cell specimens from lymphomas and leukemias as well as from normal lymphatic tissues were tested for tumorigenicity by intracranial hetero‐transplantation in nude mice. Not only lymphoma and leukemia cell lines, but also lymphoblastoid cell lines, lacking markers of malignancy, were tumorigenic in the brains of nude mice. These findings indicate that tumorigenicity following intracranial heterotransplantation in nude mice cannot be used as proof for the malignant nature of established cell lines. Heterotransplantation of primary cell specimens yielded only a few tumor takes. When primary cells were infected with exogenous Epstein‐Barr virus prior to the transplantation procedure, tumorigenicity could be significantly increased. Cytogenetic evaluation of tumors growing after intracranial transplantation of human hematopoietic cells showed, in some cases, a selection of cytogenetically aberrant cell clones.
Relationship between the Epstein‐Barr virus genome and nasopharyngeal carcinoma in Caucasian patients
Authors: Andersson‐Anvret Maria , Forsby Nils , Klein George , Henle Werner , Biörklund Anders
Published: February 2007

In order to explore whether undifferentiated nasopharyngeal carcinoma (NPC) shows a regular association with Epstein‐Barr virus (EBV), regardless of the geographical and ethnic origin of the patient, a correlated histopathological and nucleic acid hybridization study was performed on biopsies from Caucasian patients with nasopharyngeal carcinomas and from various controls. Among 12 undifferentiated NPCs, 11 were positive for EBV‐DNA, with multiple copies of the viral genome per cell. Serological tests showed elevated anti‐VCA and anti‐EA (DA) titers. Six NPCs with various degrees of squamous differentiation, four malignant lymphomas of the nasopharynx and seven carcinomas located outside the nasopharynx were EBV‐DNA negative. These findings further stress the uniqueness and regularity of the association between EBV‐DNA and undifferentiated NPC. Clearly, the association extends over geographical barriers and holds true not only in the previously studied, moderate‐incidence African ethnic group, but also in the low‐incidence Western patients.
HLA antigens in familial Hodgkin's disease
Authors: Greene Mark H. , McKeen Elisabeth A. , Li Frederick P. , Blattner William A. , Fraumeni Joseph F.
Published: February 2007

In a study of 13 families prone to Hodgkin's disease, the probands showed significant excesses of the HLA antigens Bw35 (7 cases) and Bw37 (3 cases). Although based on a small number of patients, the results suggest that immunogenetic mechanisms account at least partly for the familial predisposition to Hodgkin's disease.
Macrophage‐dependent, NK‐cell‐independent “natural” surveillance of tumours in syngeneic mice
Authors: Chow D. A. , Greene M. I. , Greenberg A. H.
Published: February 2007

The present study, which was designed to further characterize the “natural” T‐independent rejection of syngeneic tumours (Greenberg and Greene, 1976), has revealed the following points: (1) no detectable DBA/2 NK cell activity was demonstrated against the syngeneic tumour lines studied, and these tumours were insensitive to NK cells from high‐activity strains; (2) in addition the tumour frequencies in old and young mice receiving small tumour inocula were identical, in contrast with the reported decline in NK cell activity with age, suggesting that the surveillance of small inocula of these tumours was NK‐cell‐independent; (3) injection of silica intraperitoneally enhanced the frequency of tumours in normal and immunodeficient AT × BM mice, suggesting that the rejection mechanism was macrophage‐dependent; (4) the effects of silica injection were maximal if administered 3 days prior to tumour injection, indicating that the period of time in which the rejection mechanism must act was very limited; (5) silica markedly decreased the survival of AKR mice dying of spontaneous tumours, providing evidence that the effect of this agent was not limited to model systems but would influence the appearance of spontaneous tumours; (6) reticuloendothelial stimulants such as Mycobacterium butyricum and proteose peptone decreased the tumour frequency of small tumour inocula, indicating that the effector mechanism can be stimulated; and (7) soluble tumour antigen enhanced the tumour frequency in normal and immunodeficient mice, suggesting that the specific receptor molecule of the surveillance mechanism was not thymus‐dependent.
Effect of interferon on chronic infection of human cells by xenotropic type‐C viruses
Authors: Périès J. , Canivet M. , Rhodes‐Feuillette A. , Todaro G. J.
Published: February 2007

Different preparations of human interferon inhibit virus production in human cells chronically infected by a variety of type‐C xenotropic viruses. Some of these viruses have been incriminated in the development of leukemia in primates. The characteristics of blocking of viral multiplication are similar to those described for the effect of mouse interferon on ecotropic viruses. The amount of free virus in culture supernatants is strongly decreased while intracellular protein p30 stays unchanged or is slightly increased. On the other hand, the inhibitory effect is reversible. The withdrawal of interferon results in a rapid increase in virus production as detectable in supernatant fluids. In the light of these results it is suggested that human interferon might be useful in the treatment of some blood malignancies suspected of being related to infection with xenotropic type‐C viruses.
The effect of long‐term food restriction on tumours in rodents
Authors: Tucker Mary J.
Published: February 2007

The effect of restricting food intake by approximately 20% was studied in rats and mice. Both species were fed a similar “natural” diet composed chiefly of cereals and bone meal. The duration of the rat study was 24 months, but mice were studied for their whole lifespan of 36 months. In the mice, restriction increased longevity, and in both species the incidence of tumours was reduced and the onset delayed. The effect upon the different types of tumour varied; some types appeared to be unaffected by restriction, but the most common types in each species, liver tumours in mice, pituitary, mammary and skin tumours in rats, were significantly reduced.
Epstein‐Barr virus‐induced membrane antigens: Immunochemical characterization of triton X‐100 solubilized viral membrane antigens from EBV‐superinfected raji cells
Authors: Qualtiere Louis F. , Pearson Gary R.
Published: February 2007

In an attempt to qualitatively identify the membrane antigen (MA) complex induced by Epstein‐Barr virus (EBV) infection of lymphoblastoid cells, superinfected Raji cells were surface labelled with 125I by the lactoperoxidase method and solubilized with Triton X‐100, then the 125(‐labelled membrane proteins were precipitated by sera containing high antibody titers to MA. Analysis of these immune precipitates on sodium dodecyl sulfate polyacrylamide gel electrophoresis identified four major EBV‐specific membrane proteins with molecular weights (mol. wt) of 280,000, 250,000, 170,000 and 90,000. Sera from patients with Burkitt's lymphoma (BL), nasopharyngeal carcinoma (NPC) and infectious mononucleosis (IM) and from EBV‐infected disease‐free individuals showed differential patterns of reactivity to these antigens with some sera only recognizing three or less of the antigens. The results from investigations with these sera also indicated that these major proteins were not related to EBV‐induced viral capsid antigens (VCA) or the virus‐associated early antigen (EA) complexes as defined by immunofluorescence. Metabolic labelling of EBV‐infected Raji cells with [14C]glucosamine, followed by Triton X‐100 solubilization and radioimmune precipitation, identified the 280,000, 250,000 and 90,000 components as glycoproteins. The lactoperoxidase‐labelled 170,000 molecular weight component was not significantly glycosylated and, therefore, could not be categorized as a glycoprotein on the basis of this study. In addition, a glycoprotein with a mol. wt of 130,000 was identified by this approach which also appeared to be specified by EBV. The results from these investigations, therefore, indicated that the EBV‐induced MA complex was composed of four major glycoproteins and one non‐glycosylated high mol. wt protein.
Tumour antigens and alloantigens. I. Relation of a rat tumour‐specific antigen with normal alloantigens of the host strain
Authors: Bowen J. Gareth , Baldwin R. W.
Published: February 2007

It has been shown that tumour‐specific antigen from a chemically‐induced rat hepatoma is capable of binding to immunoadsorbent columns made from the Ig fractions of antisera raised in allogeneic animals against a variety of normal tissues. This reactivity is observed with antisera directed against normal syngeneic liver, spleen and lymph‐node cells but it is not detected in normal sera, F, hybrid sera or an antiserum directed against syngeneic erythrocytes. This phenomenon is specific since soluble extracts of normal syngeneic liver, but not of normal altogeneic liver, are capable of inhibiting the binding of hepatoma‐specific antigen to an immunoadsorbent column of Ig from an allogeneic anti‐normal‐liver antiserum. Syngeneic and allogeneic rats were immunized with immune complexes made from xenogeneic sera, alloantisera or syngeneic immune serum and soluble extracts of normal tissue and affinity‐chromatography‐purified hepatoma‐specific antigen. The resulting sera were examined by means of the membrane immunofluorescence test for reactivity against a panel of syngeneic and allogeneic cells. Xeno‐antisera directed against normal syngeneic tissue precipitated with purified hepatoma antigen and this material generated tumour‐specific antibody following immunization into syngeneic rats. The phenomenon of cross‐reactivity of one chemically‐induced rat hepatoma‐specific antigen with normal syngeneic alloantigens is not a unique phenomenon as preliminary results indicate that two other immunologically distinct hepatomas show similar characteristics.
Tumour antigens and alloantigens. II. Lack of association of rat hepatoma‐D23‐specific antigen with β2 microglobulin
Authors: Bowen J. Gareth , Baldwin R. W.
Published: February 2007

It has previously been shown that the tumourspecific antigen of the chemically‐induced rat hepatoma D23 has determinants recognised by alloantisera raised against normal syngeneic liver and spleen. However, no reactions were observed with alloantisera raised against syngeneic erythrocytes suggesting that the alloantigenic determinant responsible for this cross‐reactivity is not a major serologically‐defined histocompatibility antigen. This concept has been further examined using a defined turkey anti‐rat β2 microglobulin antiserum. This antiserum failed to block the binding of syngeneic antihepatoma D23 sera to hepatoma D23 target cells as assessed using membrane immunofluorescence and complement‐dependant 51Cr release tests. Furthermore, immune precipitates formed from soluble tumour extracts containing hepatoma D23 specific antigen with turkey anti‐rat β2 microglobulin failed to generate a tumour‐specific antibody response in syngeneic rats although a cross‐reactive antiserum was produced following immunization of allogeneic rats with the immune precipitate.