bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor neutralization by immune in vitro‐sensitized splenocytes depends on an interaction with bone‐marrow‐derived cells
Authors: Scuderi Philip , Rosse Cornelius 
Published: February 2007

AbstractIn a Winn assay, the inhibition of methylcholanthrene‐induced sarcoma growth by tumor‐immune, secondarily in vitro‐sensitized splenocytes was augmented by normal unsensitized bone‐marrow cells. Bone‐marrow cells augmented the effect of a fixed number of sensitized splenocytes in a dose‐dependent manner, yet had no tumor‐neutralizing capacity by themselves. The marrow's capacity to enhance tumor neutralization was not shared by normal splenocytes, thymocytes or lymph‐node cells. When two non‐cross‐reacting tumors were used, marrow cells were capable of augmenting tumor neutralization only if admixed with sensitized splenocytes and the sensitizing neoplasm. Equal numbers of bone‐marrow cells administered intravenously to recipients of an admixture of sensitized splenocytes and tumor were unable to augment neutralization, suggesting a direct interaction between sensitized lymphocytes and normal bone‐marrow cells in the inhibition of tumor growth.
In vitro effects on tumor cells of macrophages isolated from an early‐passage chemically‐induced murine sarcoma and from its spontaneous metastases
Authors: Mantovani Alberto 
Published: February 2007

AbstractMacrophages were isolated by adherence from an early‐passage chemically‐induced tumor in C57BL/6 mice and from its spontaneous lung metastases. Cytolytic activity was measured as release of [3H]‐thymidine from prelabelled tumor cells and cytostasis in a post‐labelling assay. Normal, unstimulated peritoneal mac‐rophages exhibited low but significant non‐specific cytotoxic activity at attacker to target (A:T) ratios ≧ 20:1, whereas stimulation of tumor‐cell proliferative capacity was consistently observed at A:T ratios ≦ 2:1. Macrophages from the peritoneal cavity of tumor‐bearing mice, from the primary tumor or from pooled secondaries had baseline cytotoxic or growth‐enhancing (depending on the A:T ratio) potential similar to that of control peritoneal macrophages. In vitro exposure to endotoxin, lymphokine supernatants or partially purified fibroblast interferon augmented the tumoricidal activity of normal and tumor‐associated macrophages; tumor‐associated macrophages showed no evidence of enhanced responsiveness to these activating stimuli. Tumor cells from the primary neoplasm and its spontaneous metastases were equally susceptible to macrophage tumoricidal activity. It is inferred from in vitro data that the relatively low numbers of non‐activated macrophages present within poorly immunogenic metastasizing tumors may have no direct effect or actually stimulate tumor‐cell proliferative capacity at the primary tumor site; conversely, disseminating tumor cells might encounter sufficient numbers of mononuclear phagocytes in the circulation and in lungs to permit the expression of macrophage cytotoxicity, at least during the early steps of metastasis formation.
Kinetics of inflammation and sarcoma cell development in primary moloney sarcoma‐virus‐induced tumors
Authors: Becker Susanne , Haskill Stephen 
Published: February 2007

AbstractThe kinetics of ‘sarcoma’ cell appearance and inflammatory cell infiltration into primary Moloney sarcoma virus (MSV)‐induced tumors has been studied in normal and partially immunosuppressed anti‐lymphocyte‐globulin (ALG)‐treated A/WySn mice. The ALG treatment facilitated an earlier appearance of gp70‐positive ‘sarcoma’ cells accompanied by an intense inflammatory response. Time course pulse‐labelling studies showed that a decreasing proportion of gp70‐positive ‘sarcoma’ cells were incorporating [3H]‐thymidine in vivo in both normal and immunosuppressed mice as the lesion progressed to maximum size. ALG‐treated mice inoculated with MSV were given a single injection of [3H]‐thymidine immediately prior to extensive appearance of gp70‐positive ‘sarcoma’ cells (day 6) and were studied for the presence of labelled gp70‐positive cells 2 h, 2 days and 6 days post labelling. The data indicate that few cells divided during the time in which an 8‐ to 10‐fold increase in virus‐positive ‘sarcoma’ cell number occurred. These experiments provide evidence that recruitment rather than proliferation of virus‐positive cells occurred. The results also suggest that, within the tumor, defense mechanisms develop which restrict sarcomacell proliferation also in ALG‐treated mice. The composition of inflammatory cells during the course of tumor progression and regression in the uncompromised mice revealed that the proportion of lymphocytes was highest early and late during tumor development, dropping to a minimum at the peak size of the tumor. Macrophages and granulocytes constituted 70–80% of the total cells recovered at peak tumor size and the onset of regression. In the ALG‐treated mice, the proportions of macrophages, granulocytes, and infrequent lymphocytes remained constant throughout the duration of the tumor progression. A decrease in total cells, including a decrease in gp70‐positive cells, was noticed before a change in the proportion of infiltrating lymphocytes occurred due to recovery of the immune system. The composition of the inflammatory cells at onset of regression suggests that macrophages and granulocytes are of major importance in the defense against MSV infection.
Systemic and in situ natural killer and suppressor cell activities in mice bearing progressively growing murine sarcoma‐virus‐induced tumors
Authors: Gerson J. M. , Varesio L. , Herberman R. B. 
Published: February 2007

AbstractThe activity of systemic and in situ natural killer (NK) cells was measured in 3‐ to 5‐week‐old CBA mice with progressively growing murine sarcoma virus (MSV)‐induced tumors. Splenic NK activity was depressed in tumor‐bearing mice. NK activity was quite low or not detectable in unfractionated cell suspensions from the tumors 10–12 days after inoculation of virus, but activity was observed upon depletion of phagocytic and/or adherent cells. To determine whether this in situ inhibition of NK activity was correlated with the presence of previously described suppressor cells, subpopulations of cells from the tumors were tested for their ability to suppress various responses of normal spleen cells: NK activity, lymphoproliferative responses to concanavalin A, and proliferation‐independent production of macrophage inhibition factor. A similar pattern of suppressor activity was seen in all of the assays, indicating the presence of pleiotropic suppressor cells in progressively growing MSV‐induced tumors.
Extravascular natural cytotoxicity in man: Anti‐K562 activity of lymph‐node and tumour‐infiltrating lymphocytes
Authors: Moore M. , Vose B. M. 
Published: February 2007

AbstractA major distinction is reported between the cytolytic activity of peripheral blood lymphocytes (PBL) and that of lymph‐node and tumour‐infiltrating lymphocytes (TIL) against targets of the NK‐sensitive K562 cell line in short‐term 51Cr release assays. In the PBL of normal donors and lung cancer patients in whom disease was advanced anti‐K562 reactivity, though variable, was consistently detectable and this activity could be augmented to a similar extent in patients and controls by treatment of effectors with exogenous interferon (IF). By contrast anti‐K562 activity in lymph‐node cells (LNC) and TIL was virtually absent and significant levels could not be induced by exposure to IF. This activity was not attributable to coexistent suppressor cells for NK function since admixture of LNC and TIL with normal PBL failed to modulate K562 killing by the latter. The results imply that K562‐reactive NK cells and their precursors may frequently be present at sub‐threshold levels in the lymph nodes of tumour‐bearing patients and a similar explanation could account for the inactivity of TIL. However, in the latter situation, actively‐induced NK dysfunction in situ incapable of regeneration by IF, and attributable to as yet undefined tumour‐associated factors, may also be involved.
Tumor biopsy cells participating in systems in which cytotoxicity of lymphocytes is generated. Autologous and allogeneic studies
Authors: Vánky F. , Argov S. , Klein E. 
Published: February 2007

AbstractFreshly separated tumor cells from sarcomas and carcinomas were used in various roles in lymphocyte‐target cell interaction assays. They were poorer allogeneic stimulators than lymphocytes. They were however good allotargets for the cytotoxicity generated in mixed lymphocyte cultures. They were also killed as third party targets by lymphocytes activated in MLC. In a proportion of experiments, lymphocytes activated in MLC killed autologous tumor cells. Autotumor killer effect was generated in the majority of mixed cultures containing lymphocytes and tumor biopsy cells from the same individual. Generation of cytotoxicity against K562 was a good measure of lymphocyte activation and could be used as a sensitive indicator for the occurrence of the recognition step in the mixed cultures. We propose that for the search of lymphocytes with specific receptors, activation is a more reliable parameter than specific cytotoxicity since the latter function is also influenced by the sensitivity of the target. The results confirmed that patients with carcinomas and sarcomas possess autotumor‐reactive lymphocytes. These can be activated for cytotoxicity by in vitro confrontation with the tumor cells and occasionally through stimulation which is unrelated to the tumor cells.
Lymphocyte‐dependent antibodies to antigen 3.1, a cell‐surface antigen expressed by a subgroup of human melanomas
Authors: Hellström Ingegerd , Hellström Karl Erik , Yeh Ming‐Yang 
Published: February 2007

AbstractPrevious work from our laboratory has led to the isolation of a monoclonal IgG2a mouse antibody, 3.2, which is specific for an antigen, 3.1, that is strongest expressed by a group of human melanomas. We have now demonstrated that this antibody can mediate antibody‐dependent cellular cytotoxicity (ADCC) to human melanoma cells expressing antigen 3.1, and that lymphocytes from human peripheral blood can be used as the source of K cells. A monoclonal IgG1 antibody, 3.1, to the same determinant of antigen 3.1 gave only weak and inconsistent ADCC.
Spontaneous cytogenetic abnormalities in lymphocytes from thirteen patients with ataxia telangiectasia
Authors: Taylor A. M. R. , Oxford J. M. , Metcalfe J. A. 
Published: February 2007

AbstractAtaxia telangiectasia (AT) is a human autosomal recessive disorder in which patients show a marked predisposition to malignant disease and cytogenetic abnormalities. We report here the levels of spontaneously occurring chromosome aberrations and particularly the presence of cytogenetically marked clones of cells in peripheral lymphocytes of 13 patients. There is a variation between the patients with respect to frequency of different aberration types, and clones are present in 5/13 patients. Several of these patients appear to have more than a single clone, possible clones or subclones. There is no evidence for any malignant disease in any of these patients. A description is given from one of these patients, of the most complex clone so far reported in an AT patient without malignant disease. The development of such a complex clone might be important as a step in malignant change. Similarities between this clone and one reported in an AT patient with T‐cell chronic lymphocytic leukaemia are discussed.
Demonstration of the transferrin receptor in human breast cancer tissue. Potential marker for identifying dividing cells
Authors: Shindelman Jeffrey E. , Ortmeyer Ann E. , Sussman Howard H. 
Published: February 2007

AbstractA transferrin receptor was demonstrated in tumor tissue from 10 patients with breast carcinoma and one patient with breast sarcoma. Binding studies were conducted by measuring the amount of 125I‐transferrin binding to microsomal preparations of the tumor tissue. Elevated levels of specific transferrin binding were found in the tumors with a range of 11–35% of bound transferrin, whereas microsomes prepared from non‐neoplastic breast tissue samples bound only 2.3% and 2.4% of the transferrin. Scatchard analysis of binding studies conducted with tissues from a breast cancer and from a breast sarcoma indicate that the receptor has a Ka = 9.0 × 108M. The binding site is specific for transferrin, as studies show that non‐radioactive transferrin displaced labelled transferrin, while human IgG and human albumin did not. The receptor‐transferrin complex was precipitated from a detergent extract of the breast sarcoma with antiserum to human transferrin. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of the immunoprecipitate gave a polypeptide of Mr 90,000 daltons, which is of similar molecular weight found for the putative transferrin receptor in all of a series of human cultured cell lines previously examined.
Carcinomas induced by cell lines cultivated from normal mouse placentas
Authors: Log T. , Chang K. S. S. , Hsu C. 
Published: February 2007

AbstractCell lines have been established from placentas of various strains of mice by in vitro cultivation. The established lines appear to be trophoblast cells as judged from their production of gonadotropin‐like substance and steroid hormones. The cell lines lack detectable H‐2 antigen, Fc receptor sites, Thy I antigen and surface immunoglobulin determinants. In addition, the cells are resistant to murine type‐C RNA tumor virus infection. The resistance is due to a block of viral replication after the stages of viral adsorption and penetration. The cell lines induced carcinomas after injection into adult mice of original host strains. Usually at least 2 × 106 cells are required to induce tumors by i.p. or s.c. injection. Transplantation of the tumor cells to various strains of mice revealed that some strains accepted and some strains rejected the transplant. Genetic crossings between susceptible and resistant mouse strains indicate that susceptibility to transplantation of tumor is determined by a single pair of dominant autosomal genes.
Genetic resistance to herpesvirus‐induced lymphoma at the level of the target cell determined by the thymic microenvironment
Authors: Gallatin W. Michael , Longenecker B. Michael 
Published: February 2007

AbstractThe mechanisms responsible for non‐major‐histocompatibility‐complex (MHC)‐associated genetic resistance to Marek's disease (MD) were studied in resistant line 6 and susceptible line 7 chickens. Adoptive transfer of specific‐pathogen‐free (SPF) adult spleen cells from the susceptible line into irradiated 8‐day‐old resistant recipients significantly increased MD mortality following contact exposure to Marek's disease virus (MDV). No protective effect was observed following transfer of spleen cells from line 6 donors into susceptible line 7 recipients. Lymphocytes from the susceptible line 7 were shown by earlier experiments to have a higher capacity to adsorb the herpesvirus of turkeys (HVT). Fragments of thymic stroma from line 6 and line 7 were grafted onto the chorioallantoic membrane (CAM) of line 6 embryos. Following revascularization and repopulation of the grafts with lymphocytes of resistant host origin, the virus adsorption capacity of the non‐lymphoid stromal and lymphoid portions of the grafts was assayed in vitro by focus inhibition. While no difference in adsorption was observed between the line 6 and line 7 donor origin stromal cells, significantly more virus was adsorbed by the repopulating line 6 lymphoid cells harvested from the susceptible line 7 grafts than by line 6 lymphocytes from syngeneic line 6 grafts. The genotype of the thymic microenvironment was, therefore, found to be a determining factor in the expression of the high virus‐binding phenotype. Virus neutralizing monoclonal antibodies against HVT were prepared and used in the new in vitro antibody‐directed rosetting assay (ADRA) to determine the frequency of virus‐binding cells in the lymphoid organs of these two lines. Virus‐binding leukocytes were more frequent in the line 7 susceptible birds. In a time‐course study, following reconstitution of irradiated, third‐party, histocompatible recipients with SPF line 7 spleen cells, a sharp increase in MDV‐infectious centres was observed in peripheral blood at day 17 post exposure. A decrease in infectious centres was observed, however, at the same time point in recipients of line 6 spleen cells. The explanation for the difference in MD mortality seen in line 6 and line 7 is, thus, complex and may reflect separate resistance mechanisms which operate at more than one level. First, resistance is manifested at the level of a direct interaction between MDV and its target T lymphocyte with the thymic microenvironment playing a key role in the event. Second, and later during the course of infection, genetic variation in the capacity for immune surveillance against MDV‐infected and/or transformed cells may come into play. Whether these two properties segregate independently or not has yet to be determined.
Clonal variation and functional correlation of organ‐specific metastasis and an organ‐specific metastasis‐associated antigen
Authors: Shearman P. J. , Longenecker B. M. 
Published: February 2007

AbstractMonoclonal antibodies were used to probe the cell surface of organ‐selected metastatic variant cells. Previously we defined a liver metastasis‐associated antigen (LMAA) by means of the reaction of a monoclonal antibody with a liver metastasis selected tumour variant cell line, MDCC‐AL2. The monoclonal anti‐LMAA antibodies specifically inhibit liver metastasis of AL2. There is a correlated, clonal variation in LMAA expression and liver metastasis in both the AL2 cell line and an overy‐selected metastatic variant MDCC‐AL3. The variation in liver metastatic ability is thought to represent clonal progression of the tumour cell lines. The LMAA probably represents only one of the ways in which a tumour cell may give rise to a liver metastasis. Two hypotheses are discussed utilizing the LMAA in a functional role in the specific trapping of metastatic tumour cells in the liver or the successful colonization of the liver by metastatic tumour cells.
Inter‐individual differences in oxidative benzo(a)pyrene metabolism by normal and tumorous surgical lung specimens from 105 lung cancer patients
Authors: Sabadie N. , Richter‐Reichhelm H. B. , Saracci R. , Mohr U. , Bartsch H. 
Published: February 2007

AbstractOxidative benzo(a)pyrene (BP) metabolism was studied in 12,000 g(S12) supernatant fractions of surgical lung specimens obtained from lung cancer patients undergoing surgical resection. Arylhydrocarbon (BP)hydroxylase (AHH) activity was determined in both normal and tumorous lung tissue specimens from the same patient. A more than 20‐fold inter‐individual variation in AHH activity was found in both the normal and the tumorous lung tissue samples investigated. The apparent KM of the pulmonary enzyme (1–2.5 × 10−4 M) was identical in tumorous and normal tissue. High‐performance liquid chromatography (HPLC) of ethyl acetate‐extractable BP metabolites from the normal lung tissue of six patients identified phenols, dihydrodiols and quinones of BP. The mean yields of these metabolites were very similar to those obtained in assays in the presence of lung S12 from BDVI rats, except that more trans−9, 10‐dihydro‐9, 10‐dihydroxy‐BP (BP‐9, 10‐diol) was formed in the presence of human lung S12. The formation of 3‐hydroxy‐BP (3‐HO‐BP) and BP‐9, 10‐diol in human lung specimens, however showed variations up to 7‐ and 13‐fold, respectively. In normal lung specimens, the total amounts of 3‐HO‐BP and 9‐HO‐BP formed correlated positively with the total amounts of trans‐7, 8‐dihydro‐7, 8‐dihydroxy‐BP (BP‐7, 8‐diol), BP‐9, 10‐diol and trans‐4, 5‐dihydro‐4, 5‐dihydroxy‐BP (BP‐4, 5‐diol) formed (r = 0.83; p < 0.05). A positive correlation was also found between the AHH activity in normal and tumorous tissue from all cancer patients (r = 0.24; p < 0.05). The ratio (R) of AHH activity in tumorous tissue to that in normal tissue from the same lung cancer patient was < 1 in 73 patients, 1 in 2 patients, and > 1 in 11. In 7 of 10 subjects who underwent surgical resection for suspected lung tumours, but in whom histological analysis revealed no malignant tissue, R was > 1 for the AHH activity in the inflammatory tissue to that in normal tissue. The observation of consistently lower AHH activity in malignant lung tissue parallels findings in hyperplastic liver nodules induced in rats by hepatocarcinogens. The frequency distribution of pulmonary AHH activity in normal and tumorous tissue from 105 lung cancer patients, with all types of tumours, was compatible with a unimodal distribution of the enzyme activity. In a subset of 43 patients with squamous‐cell carcinoma, the same distribution was seen; in those patients, AHH activity in tumorous tissue correlated negatively (r = −0.18; p > 0.10) with the number of cigarettes smoked per day prior to surgery. No differences were observed between the mean values for AHH activity in cases of squamous‐cell carcinoma and those of adenocarcinoma. No relationship was found between AHH activity in normal or tumour tissue and the age of patients. Whether differences in pulmonary AHH activity represent a host risk factor in persons who smoke remains to be investigated.
Special report animal species in which n‐nitroso compounds induce cancer
Authors: Bogovski P. , Bogovski S. 
Published: February 2007

AbstractIn reviews on the carcinogenicity of N‐nitroso compounds (NC) the number of animal species in which these compounds induce cancer is understated. In recent years additional species have‐been used in experiments. Tumours have been induced by NC in 39 species which belong to 36 genera, 25 families, 17 orders and five classes of animals. The names of these taxa are presented in Latin and the common names of species are given in English, French and German. The carcinogenic action of eight NC in various species is tabulated.
Cell‐mediated suppression of tumor immunity has a non‐specific component. I. Evidence from transplantation tests
Authors: Hellström Karl Erik , Hellström Ingegerd 
Published: February 2007

AbstractWe have first demonstrated that the growth of a transplanted, 3‐methyl‐cholanthrene‐induced BALB/c sarcoma, MCA‐1425, in specifically immune syngeneic mice, was facilitated when the MCA‐1425 tumor cells were injected together with either a mixture of irradiated MCA‐1425 cells and thymus cells from mice immune to MCA‐1425 or a mixture of irradiated cells from an antigenically different BALB/c sarcoma, MCA‐1460, and thymus cells from mice immune to MCA‐1460. We then performed Winn assays to study the induction of an immune response that could prevent the outgrowth of MCA‐1425 cells in irradiated syngeneic recipients. Tumor immunity was found to be suppressed, if the mice immunized by a subcutaneous transplant of MCA‐1425 cells and used as lymphocyte donors, were injected intraperitoneally with cells from either a different sarcoma, MCA‐1460, or from 12‐day BALB/c embryos. We tentatively attribute our findings to antigen‐non‐specific suppressor effector cells and postulate that an antigen‐specific event is often involved in their induction.