bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibronectin from human germ‐cell tumors resembles amniotic fluid fibronectin
Authors: Ruoslahti Erkki , Jalanko Hannu , Comings David E. , Neville A. Munro , Raghavan Derek
Published: February 2007

Three human germ‐cell tumors established as xeno‐grafts in immunosuppressed mice were shown to produce fibronectin. Immunoperoxidase tissue staining with a specific antiserum revealed human fibronectin in some tumor cells. The cyst fluid which accumulated in the tumors contained human fibronectin as shown by a species‐specific radioimmunoassay. Human fibronectin was isolated from two of the tumor fluids and compared to previously characterized fibronectins. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis and gel electrofocusing showed that the germ‐cell fibronectins resembled amniotic fluid fibronectin with regard to subunit molecular weight and isoelectric point. The distinct features of the amniotic fluid and germ‐cell tumor fibronectin suggest that such fibronectins may provide new oncodevelopmental markers.
Monoclonal anticolon carcinoma antibodies in complement‐dependent cytotoxicity
Authors: Herlyn D. M. , Koprowski H.
Published: February 2007

Hybridoma‐derived monoclonal anticolon carcinoma (ACC) antibodies mediated specific complement‐dependent cytotoxicity (CDC) against human colon carcinoma cells either grown in culture or obtained directly from patients. These ACC antibodies did not lyse normal colonic mucosa or other normal and malignant human cells. Absorption of these antibodies to cells of established colon carcinoma cell lines totally eliminated their specific lytic capacity. ACC antibodies were able to bind in vivo to colon carcinoma cells grown in nude mice but did not bind to lung or kidney cells from tumor‐bearing animals. These monoclonal antibodies did not, however, inhibit the growth of colon carcinoma tumor cells in nude mice.
Mouse fibroblasts transformed by rous sarcoma virus express a virus‐specific non‐virion transplantation antigen
Authors: Prat Maria , Tarone Guido , Comoglio Paolo M.
Published: February 2007

Rous sarcoma virus (RSV)‐transformed fibroblasts from different animal species a serologically detectable virus‐induced non‐virion cell surface antigen (VCSA), whose expression is controlled by the transforming viral srcgene and by a cellular gene. Now, by in vivo immunization, we have found that RSV‐transformed fibroblasts from different mouse strains share a virus‐specific transplantation antigen. In fact, only animals immunized with irradiated syngeneic or allogeneic fibroblasts transformed by RSV, but not animals immunized with cells transformed by different oncogenic agents, rejected a lethal dose of syngeneic RSV‐induced tumor cells. Immunoprecipitation tests with monospecific antisera showed that the expression of this antigen did not correlate with the presence of intracellular viral proteins other than the src gene product pp60src. However, hyperimmunization of mice with hamster or quail fibroblasts transformed by RSV, that express a high level of pp60src, did not induce transplantation resistance. It is concluded that the expression of both the serologically‐defined VCSA and the transplantation antigen is the result of the interaction of pp60src with host cell gene product(s) rather than the simple exposure of pp60src at the outer cell surface.
A genetic approach to the role of energy metabolism in the growth of tumor cells: Tumorigenicity of fibroblast mutants deficient either in glycolysis or in respiration
Authors: Franchi A. , Silvestre P. , Pouysségur J.
Published: February 2007

To analyze the role of the cell energy metabolism in the expression of the malignant phenotype, we isolated fibroblast mutants with specific defects either in aerobic glycolysis or in respiration. From the anchorage‐independent and tumorigenic subclone (023) of Chinese hamster lung fibroblasts, we selected two mutants. The first, DS7, is deficient in aerobic glycolysis and glucose transport as a consequence of a block in phosphoglucose isomerase activity. DS7 is strictly dependent upon respiration for cell viability. The second mutant, GSK3, is unable to oxidize glucose as a result of a defect in oxidative metabolism, therefore its energy for growth relies exclusively on aerobic glycolysis. When injected into nude mice, these two mutant cells have kept the capacity to form tumors. For both mutants we observed an increase in the latency of tumor formation and a decreased tumorigenicity only for the respiration defective cells. The tumoral cells analyzed after passaging in vivo have retained the respective phenotypes, glycolysis‐ and respiration‐, of the injected cells. Finally, from the anchorage‐dependent and non‐tumorigenic Fisher rat fibroblast cell line, FR 3T3, we isolated mutants with a 6‐fold derepressed aerobic glycolysis and high glucose transport rate. In spite of this transformed character, these mutants (GSR 16/24) have kept the normal growth characteristics of the parent FR 3T3 (anchorage dependency and non‐tumorigenicity). These results indicate that only one of the two energy metabolisms of the mammalian cell ‐ respiration or aerobic glycolysis ‐ is enough for the expression of the malignant phenotype. Therefore, the high aerobic glycolysis of tumoral cells should be regarded as a non‐essential character of tumoral growth.
Effect of bacillus calmette‐guéarin cell wall skeleton on the induction of the cytotoxic and suppressor T cells against syngeneic tumor in the mouse
Authors: Koyama Shohei , Fujimoto Shigeyoshi , Tada Tomio , Sakita Takao
Published: February 2007

The effect of Bacillus Calmette‐Guérin cell wall skeleton (BCG‐CWS), which is one of the well‐established immunopotentiators, on the induction of either cytotoxic or suppressor T cells against syngeneic tumor S1509a was investigated by an in vitro assay system. BCG‐CWS showed an apparent augmenting activity in the induction of cytotoxic T cells against a syngeneic tumor when it was administered subcutaneously into mice with mitomycin C (MMC)‐treated tumor cells in a form of oil‐in‐water emulsion. In addition, cytotoxic T cell activity was dominantly generated in regional lymph nodes. Furthermore, the immunized animals developed stronger resistance against the second inoculum of the same viable tumor cells. However, BCG‐CWS had no effect on the induction of suppressor T cells in tumor‐bearing host (TBH), and could not induce cytotoxic T cells against the homologous tumor in TBH in which suppressor T cells had been readily activated. The growth of tumor was neither suppressed nor enhanced, even if an oil‐attached BCG‐CWS was administered in TBH.
Antagonistic action of retinoic acid and teleocidin on the proliferation and epidermal growth factor binding of rat hepatoma cells
Authors: Kaneko Yoshiyasu
Published: February 2007

Rat hepatoma cells were cultured in a medium with suboptimal concentration of fetal calf serum. In this low serum culture, retinoic acid inhibited the cell proliferation and enhanced the number of receptors for epidermal growth factor (EGF). On the contrary, teleocidin, a possible naturally occurring tumor promoter from Streptomyces, was a weak mitogen and inhibited EGF binding. A concurrent treatment of AH66 cells with these two compounds showed that they acted antagonistically. Retinoic acid inhibited the mitogenic action of teleocidin, while teleocidin suppressed the retinoic‐acid enhancement of the number of EGF receptors. Retinoic acid could not prevent the alterations of the cell surface properties induced by a prolonged treatment with teleocidin. Furthermore, these two compounds appeared to be involved in the regulation of glycoprotein synthesis and the stimulation of cellular glycoprotein synthesis by retinoic acid was abolished by teleocidin. The present data suggest that retinoic acid selectively antagonizes the mitogenic action of teleocidin, and also indicate that the hepatoma cell cultures appear to provide a useful system for exploring the mechanisms of action of both retinoic acid and teleocidin.
Suppressor cell activity in melanoma patients. II. Concanavalin A‐induced suppressor cells in relation to tumor growth and suppressor T‐cell subsets
Authors: Werkmeister J. , Phillips Georgina , McCarthy W. , Hersey P.
Published: February 2007

The relative proportions of T, B and Tγ suppressor cells were determined sequentially in peripheral blood of melanoma patients before and after surgery. Concanavalin A (Con A)‐induced suppression against lymphocyte mitogenesis of melanoma patients and age‐matched controls was measured concurrently. The mean percentage of Tγ cells was significantly higher (p < 0.001) in melanoma patients before surgery (21.8 ± 5.4) compared to a group of age‐matched controls (14.9 ± 5.4). There was a tendency for the proportion of Tγ cells in patients to decrease after surgery, although the relative levels of Tγ were still significantly elevated (p < 0.05) 6–8 weeks after surgery when compared to normal controls. The mean percentage of T and B cells in melanoma patients before and after surgery was comparable to that observed in normal controls. The degree of Con‐A‐induced suppression in patients increased significantly after surgery particularly at 6–8 weeks (p < 0.02). No difference in Con‐A‐induced suppressor cell activity was observed between melanoma patients and controls before or after surgery. An inverse relationship was found between the amount of Con‐A‐induced suppression and percentage of Tγ cells in melanoma patients before surgery. Similar associations were not apparent in patients after surgery or in normal control populations. The inverse correlation of Con‐A‐induced suppression with Tγ cell numbers suggests that the former may measure potential suppressor cell activity whereas the Tγ cells may indicate active suppressor cells. The significance of these findings for the monitoring of suppressor cell activity in vivo and their role in suppression of immune responses in melanoma patients is discussed.
Influence of serum thymic factor (FTS) on radiation‐induced leukaemogenesis in thymectomized akr mice
Authors: Legrand E. , Daculsi R. , Bach J. F. , Duplan J. F.
Published: February 2007

The influence of serum thymic factor (FTS) on extrathymic leukaemogenesis induced in thymectomized AKR mice by fractionated sub‐lethal irradiation was studied. Thirty‐day‐old thymectomized mice were submitted to four doses at weekly intervals (1.75 Gy) and thereafter treated with FTS (I ng) for 9 days. Two groups were restored with either bone marrow or spleen cells prior to FTS treatment. In another group, mice were treated with FTS (12 ng) for I month after thymectomy and prior to irradiation. Results indicated that primarily irradiation and FTS, and, to a lesser extent, restoration and age of the mice at the time of their first radiation exposure influenced leukaemogenesis. Irradiation increased the spontaneous low incidence of extrathymic leukaemia (5 %) up to 50 %. Although nothing is yet known about the expression of endogenous retroviruses in thymectomized AKR mice, the possible expression of leukaemogenic recombinants, either identical to or different from mink‐cell‐focus‐inducing viruses (MCF), might explain this enhancing effect of radiation on leukaemogenesis. Mice developed two types of leukaemias: “null” leukaemias whose cells bore no detectable antigen or surface immunoglobulin, and B leukaemias. Among the null leukaemias, two kinds could be distinguished: “early” ones which were observed before 450 days, and in which BM and spleen were similarly involved, and “late” ones which displayed the same characteristics as B leukaemias, i.e. delayed appearance (after 450 days) and splenic origin. Although FTS did not modify the overall frequency of leukaemias, it increased significantly the incidence of the “early” null ones. It had no effect on the frequency or the latency of late null and B leukaemias. Any population of negative T cells sensitive to FTS could be an acceptable candidate for “early” null leukaemogenesis. The origin of “late” null leukaemias remains an open question.
Non‐specific cytotoxic cells generated in vitro in response to a weakly immunogenic murine adenocarcinoma. In vivo correlations
Authors: Pope Barbara L. , Justice Robert L. , Sarma Chander , Martin W. John
Published: February 2007

Tumor 85 adenocarcinoma cells, which are very weakly immunogenic for C3H/HeN (C3H) mice, provide a model tumor system for studying the parameters of induction of a cell‐mediated immune response which does not appear to be a traditional cytotoxic T‐cell or NK‐cell response. Mice pre‐immunized with irradiated tumor 85 cells are protected about 50% of the time from a challenge of viable tumor 85 cells although it is never possible to protect 100% of the immunized mice. Optimal protection is observed in mice immunized with 106 irradiated tumor 85 cells 14 days prior to challenge. Protection is also observed if mice are immunized with C3H or C3HfeB/HeN (C3Hf) tumors originally induced by the same carcinogen as that used to induce tumor 85. The injection of carrageenan I h before challenge completely reverses the protection observed in immunized mice and tumors grow faster in carrageenan‐treated immunized mice than in normal mice. Two populations of cells obtained from cultures of spleen cells stimulated by tumor 85 cells appear to prevent tumor growth in vivo. One population, which is cytotoxic for tumor 85 cells in vitro, is nylon‐wool‐adherent and expresses Thy 1.2 The second population, which is not observed to be cytotoxic in a 51Cr release assay, is phagocytic.
Effects of carcinogen and/or mutagen on normal and gonadotropin‐primed ovaries of mice
Authors: Rao A. Ramesha
Published: February 2007

The influence of pregnant mare serum gonadotropin (PMSG) on the induction of ovarian tumors by carcinogen (DMBA) and/or mutagens (EMS and BMS) has been studied in Swiss albino mice. Priming of the ovaries of 6‐week‐old mice with PMSG (50 lU/mouse) 24 h before intragastric intubation of DMBA (5 mg/mouse) resulted in a significant increase in ovarian tumors when harvested 6 months after the treatment. A similar experiment done on 8‐week‐old mice yielded confirmatory results. Mutagens (EMS and BMS) failed, at given dose levels (200 mg/kg and 300 mg/kg body weight), to induce tumors in normal as well as PMSG‐primed ovaries. Nor could these mutagens enhance DMBA‐induced tumor incidences in normal or PMSG‐primed ovaries. Pretreatment of animals with PMSG‐enhanced DMBA‐induced oocyte depletion and also increased the DMBA‐3H activity in the ovaries. The augmentation of DMBA‐induced tumors in PMSG‐primed ovaries could be due to increased uptake of DMBA and increased depletion of oocytes. It is also possible that PMSG‐primed ovaries provided more proliferating granulosa cells (and macromolecules) for the interaction of DMBA (or its metabolites) and thereby increased the chances of cell transformation in the ovaries.
Cytostasis of tumor cell lines by granulocytes from cancer patients and normal human donors
Authors: Korec S. , Herberman R. B. , Cannon G. B. , Reid J. , Braatz J. A.
Published: February 2007

Granulocytes of normal human donors were previously shown to have cytostatic activity in vitro against a variety of tumor cell lines. In the present study, we have compared the levels of granulocyte‐mediated cytostatic activity in cancer patients and normal donors. In an initial study of 25 tumor‐bearing patients and 21 individuals with benign or no disease, decreased cytostatic activity was observed in 84% of the cancer patients. Nine cancer patients with no evidence of disease had reactivity in the normal range. Granulocytes separated by a one‐step method on a double Ficoll‐Percoll gradient showed decreased reactivity. This procedure eliminated the differences previously detected between tumorbearing patients and controls. Addition of either pooled normal AB human serum or autologous serum to the assay restored the reactivity. Only with autologous serum and not with allogeneic serum, were the differences between tumor‐bearing patients and controls again seen. Therefore, in a subsequent study, we examined the effect of serum on cytostasis by normal granulocytes that were isolated on double gradients. We observed lowered serum restorative activity (SRA) in 41 of the 46 (89%) tumor‐bearing patients tested. Fractionation of sera by Sephadex G‐200 chromatography indicated that SRA of both cancer patients and normal donors was in the 100,000 molecular weight region.
Tumoricidal activity of macrophages isolated from human ascitic and solid ovarian carcinomas: Augmentation by interferon, lymphokines and endotoxin
Authors: Peri Giuseppe , Polentarutti Nadia , Sessa Cristiana , Mangioni Costantino , Mantovani Alberto
Published: February 2007

Peripheral blood monocytes and macrophages from ascitic or solid tumors were obtained from 50 patients with advanced (Stage III or IV) ovarian carcinoma. Blood monocytes and peritoneal macrophages from 76 patients undergoing surgery for benign gynecological diseases were used as controls. Macrophages were 30% (range 0.2–62) and 2% (range 0.2–4) of mononuclear cell suspensions from ascitic and solid tumors, respectively. Cytolytic activity was measured as release of [3H]‐thy‐midine from prelabelled mKSATUS (TU5) target cells at an effector to target cell ratio of 20:1. Peripheral blood monocytes and tumor‐associated macrophages had baseline cytotoxicity lower than or similar to that of control peripheral blood and peritoneal macrophages respectively. In vitro exposure to partially purified human fibroblast interferon, lymphokine supernatants or endotoxin augmented the cytotoxicity of mononuclear phagocytes, and no significant difference was observed between control and ovarian cancer effector cells from peritoneal effusions. In four patients, macrophages were isolated from the solid tumor or from the malignant effusion and tested in parallel: in two out of four subjects, macrophages from the solid neoplasm showed defective cytotoxicity compared to ascites effector cells from the same subjet. When primary ovarian carcinoma cultures were used as targets, tumor cells from two out of five patients tested were relatively resistant to activated macrophage cytotoxicity. Thus, tumor‐associates macrophages from ascitic or solid ovarian neoplasms showed no evidence of activation, in terms of spontaneous cytotoxicity or responsiveness to stimuli: it appears unlikely that small numbers of non‐activated macrophages present within primary ovarian carcinomas act as a significant mechanism of restraint of neoplastic growth, at least at this anatomical site.
Biphasic depression of macrophage function after tumor transplantation
Authors: Normann Sigurd J. , Schardt Martin , Sorkin Ernst
Published: February 2007

Tumor bearing produces a biphasic depression of macrophage inflammatory responses. Macrophage accumulation was measured on nitrocellulose filters in DA rats transplanted with a syngeneic DMBA‐induced fibrosarcoma and in SJL/J mice transplanted with a firstgeneration histiocytic lymphoma. The early phase defect was observed 2–5 days and 4–12 days after tumor transplantation in rats and mice respectively. Although transient, its duration could be prolonged by increasing the number of tumor cells injected. An interval of normal responses separated this early defect from a second or late‐phase defect which began midway in the clinical course and persisted until death. Transplantation of syngeneic liver cells increased macrophage responses in DA rats but had no effect in SJL/J mice. The demonstration of a bisphasic anti‐inflammatory effect following tumor transplantation suggests that low doses of tumor cells are effective in inhibiting macrophages and that tumor bearing may alter macrophage responses by more than one mechanism.
Studies on lung tumours. V. Susceptibility of mice to dimethylnitrosamine‐induced tumour formation in relation toH‐2 haplotype
Authors: den Engelse L. , Oomen L. C. J. M. , Valk M. A. Vander , Hart A. A. M. , Dux A. , Emmelot P.
Published: February 2007

Male mice of the strain A/Sn, of its congeneic partner strain A.SW, C57BL/105cSnA (abbreviated: B10), and of two congeneic strains on a B10 background (B10.A and B10.AKM) were investigated for their susceptibility to lung tumour induction by dimethylnitrosamine (DMN) administered either by intraperitoneal injection or in the drinking water. Strain B10 (haplotypeH‐23) proved to be very resistant, whereas strains A/Sn (H‐2b) and A.SW (H‐2s) were highly susceptible. The introduction of the haplotypesH‐2aandH‐2min the resistant strain B10 resulted in a significant increase in sensitivity towards DMN‐induced lung tumour formation. Lung tumour incidences in male (B10.A × B10)F1, hybrids, receiving DMN in drinking water, were found to be intermediate between, and significantly different from, the incidences of identically‐treated parent strains B10.A and B10. Males of back‐cross (B10.A × B10) × B10 BC1proved to be of low susceptibility to lung tumour formation by DMN, tumour incidence being very low and not significantly different from that observed in identically‐treated B10 males. It is concluded that, at least in the model system of B10‐derived congeneic strains,H‐2haplotype is one of the factors important in determining susceptibility towards DMN‐induced lung tumours. Comparison of C3Hf (H‐2k), C3H/Sn (H‐2k) and the latter's congeneic strains C3H.B10 (H‐2b) and C3H.NB (H‐2p) of male mice showed that these strains were moderately susceptible to both lung tumour and hepatoma formation by DMN. Accordingly, the presence of anH‐2haplotype from a lung‐tumour‐resistant strain (H‐2b, B10) on the background of a strain of intermediate susceptibility (C3H) does not decrease susceptibility to lung tumour formation. The results were considered in the light of theH‐2haplotype dependence of spontaneous lung tumours, and consequently attention has been paid to the histological types of the induced and spontaneous lung tumours.
RNA oncovirus expression in N‐methyl‐N‐nitrosourea‐induced lymphomas in mice
Authors: Pintér A. , Börzsönyi M.
Published: February 2007

RNA oncovirus expression was investigated in thymic lymphomas induced by N‐methyl‐N‐nitrosourea (MNU) in (C57BL/6 × DBA/2)F1(BDF1) mice. Out of 15 newborn mice injected with 20 mg/kg MNU, five developed thymic tumours of T‐cell origin. Virus production of thymic cells from tumorous and normal animals was studied by an infectious center assay. All five tumours released ecotropic (mouse tropic) virus. No xenotropic or dualtropic mink cell focus‐inducing virus was found. No virus was obtained from thymus cells taken from six normal mice killed between 83 and 124 days; however, an ecotropic virus was cultured from the thymus of a 134‐dayold normal mouse. According to these results, the MNU‐induced thymic lymphoma development in BDF1, mice is accompanied by activation of endogenous ecotropic virus, whereas spontaneous activation also occurs in older mice.
Immunohistologic evidence for the role of antibody and macrophages in regression of the murine T1699 mammary adenocarcinoma
Authors: Key Marc , Haskill J. Stephen
Published: February 2007

The regression or progression of the T1699 murine mammary adenocarcinoma was analyzed with histologic and immunohistologic techniques to determine the tissue distribution of both macrophages and antitumor antibody. Changes in integrity of tumor blood vessels were apparent during tumor growth and regression. Tumors at early stages of growth were invaded in the capsule by multiple vascular branches which later permeated the tumor. Following the appearance of anti‐tumor antibody in the serum, these vessels often showed immune complex deposition which preceded vessel leakage, destruction and hemorrhage. After these changes, tumor cells appeared coated with antibody. Macrophages appeared predominantly in the tumor capsule during early stages of tumor growth, while at later stages they were observed within tumors most prominently near the edge of growing hemorrhagic and necrotic areas. As tumors regressed, connective tissue septation lined by macrophages became apparent. Phagocytosis of seemingly intact tumor cells was common and appeared to account for much of the loss in tumor cell numbers. In immunosuppressed animals (ATXBM, 450R) in which tumor progression always occurred, the above features were markedly diminished or absent. This model emphasizes the interplay of many factors in tumor regression. These include immune complex deposition, blood vessel destruction, macrophage infiltration and connective tissue development, all of which are associated with tumor regression and seem to be infrequent and/or inconsequential during progressive tumor growth.
Glycosphingolipids of K562 cells: A chemical and immunological analysis
Authors: Suzuki Akemi , Karol Robin A. , Kundu Samar K. , Marcus Donald M.
Published: February 2007

The K562 cell line, which was established from a patient with chronic myeloid leukemia in blast crisis, was thought to be myeloid, but recent data indicate that it is an undifferentiated erythroid cell line. We have found that the glycosphingolipid content of these cells differs considerably from that of mature erythrocytes. Globotetraosylceramide, the most abundant glycolipid of mature red cells, was not detected in K562 cells, and neither was globotriaosylceramide. The predominant neutral glycolipids of K562 cells are monohexaosyl‐ceramides, which are a mixture of glucosyl‐ and galactosylceramides, and lactotriaosyl‐ and lactoneote‐traosylceramides were also detected. Secondly, gangliosides which contain N‐acetylgalactosamine were much more abundant than those containing N‐acetylglucosamine in K562 cells, in contrast to erythrocytes. The most abundant ganglioside of K562 cells, GM2, is present in trace quantities in erythrocytes. A third major difference between these two cells lies in their relative proportions of neutral glycolipids and gangliosides. The molar ratio of neutral glycolipids/gangliosides is approximately 15:1 in erythrocytes and 1:1 in K562 cells. These striking differences between K562 cells and mature erythrocytes indicate that glycolipids may be useful cell surface markers of normal erythrocyte differentiation, and of erythroleukemias.
Regulation of gene expression by tumor promoters. II. Control of cell shape and developmental programs for macrophages and granulocytes in human myeloid leukemic cells
Authors: Liebermann Dan , Hoffman‐Liebermann Barbara , Sachs Leo
Published: February 2007

Regulation of the developmental programs for macrophages and granulocytes has been analysed, using two‐dimensional gel electrophorels of the cytoplasmic protein changes, in a human myeloid leukemic cell line (HL60) that can be induced to differentiate to macrophages by the macrophage and granulocyte‐inducing (MGI) protein and the tumor promoter 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA), and to granulocytes by dimethylsulfoxide (DMSO). Studies on the protein changes induced by the different inducers showed a similar developmental program for macrophage differentiation induced by MGI or TPA, which differed from the beginning from the granulocyte program induced by DMSO. Comparison with normal cells from human peripheral blood has shown that the developmental programs induced in the HL60 cells are relevant to the normal programs of differentiation for these two cell types. Unlike MGI and DMSO, TPA induces rapid attachment of the HL60 cells to the surface of the Petri dish. Combined treatment with TPA and DMSO showed cell attachment, extensive spreading of the cells, the regulation of specific proteins and expression of the macrophage program. The addition of TPA to cells induced for the granulocyte program by DMSO resulted in cell attachment and spreading and a switchover from the granulocyte to the macrophage program. The results indicate that cells in suspension can express either the macrophage or granulocyte program depending on the inducer, and that changes in cell shape associated with cell attachment induced by TPA can regulate specific proteins and restrict the developmental program to macrophages. It is suggested that the in vivo environment of cells in relation to the possibilities for cell adhesion, which can be regulated by tumor promotors, may play a major role in determining the developmental program of myeloid and other cell types.
Morbidity from cancer in La Paz, Bolivia
Authors: Ríos‐Dalenz Jaime , Correa Pelayo , Haenszel William
Published: February 2007

Data from a population‐based Cancer Registry in La Paz, Bolivia, are presented. The city is located at approximately 4,000 meters above sea level and has a strong cultural influence consisting of Aymará Indians immigrating from the altiplano. Incidence rates in females are high for cancer of the cervix, the gallbladder and the thyroid gland. Males display unusually high rates of testicular cancer. Stomach cancer rates are lower than among other Andean populations. Smoking‐related cancer and cancers related to sex‐hormones are lower than average in incidence. Cancer of the nasal mucosa and paranasal sinuses is unusually high in frequency.
Light‐induced chromatid damage in human skin fibroblasts in culture in relation to their neoplastic potential
Authors: Parshad Ram , Gantt Raymond , Sanford Katherine K. , Jones Gary M. , Camalier Richard F.
Published: February 2007

Skin fibroblasts from ataxia telangiectasia and xeroderma pigmentosum (XP) donors and from the XP sib (possible heterozygote), all genetically predisposed to a high risk of cancer, show an increased susceptibility to light‐induced chromatid breaks after culture in vitro. Light‐induced chromatid breaks were shown previously to result from generation of hydrogen peroxide (H2O2) during light exposure. The level of susceptibility attained is significantly higher than that observed in 13 lines of fibroblasts from normal skin of donors ranging in age from 3 days to 92 years or from fetal skin tested at various population doubling levels. Two lines of normal skin fibroblasts transformed by chemical carcinogens to neoplastic cells also show a significant increase in susceptibility as compared with their untransformed controls. These data indicate for human cells, as reported earlier for mouse cells, an association between enhanced susceptibility to light‐induced chromatid damage and neoplastic potential; this association is further supported by the high susceptibility of cells derived from a human adenocarcinoma. Two observations are consistent with the concept that the increased susceptibility does not result from greater initial damage to the DNA of the neoplastic cells. First, activities of the ubiquitous H2O2 scavenging enzyme, glutathione peroxidase, are similar in the paired normal and neoplastic cell populations. Second, cells of the paired lines are equally sensitive to DNA breakage by exogenous H2O2. The enhanced susceptibility associated with neoplastic potential may result from an impaired capacity to repair DNA rather than a greater initial sensitivity of the neoplastic cells to the damaging agent.
Establishment of attached and non‐attached cell lines from an uncommon human glioma
Authors: Westermark B. , Larsson E. , Brunk U. , Lubitz W. , Mark J.
Published: February 2007

A New cell line, U‐706, established from an uncommon human glioma (possibly giant‐cell glioblastoma) is reported in this communication. The tumor gave rise to two permanent sublines, one attached (U‐706M) and one non‐attached (U‐706S) cell line. The growth characteristics, chromosome banding pattern, electronmicroscopic picture and cell surface characteristics of the two sublines are described.
Suppressor pathways in tumor immunity: A requirement for Qa‐1 positive tumor‐bearer spleen t cells in suppression of the afferent immune response to tumor antigens
Authors: Mulé James J. , Stanton Thomas H. , Hellström Ingegerd , Hellström Karl Erik
Published: February 2007

Spleen cells from mice bearing large methylcholanthrene (MCA)‐induced sarcomas were injected intravenously into mice challenged in the hind footpads with heavily‐irradiated cells from the same or a different sarcoma. As measured by [3H]‐thymidine incorporation on day 5 or 6, cellular proliferation in the draining popliteal lymph nodes of these mice was significantly depressed as compared to control animals receiving normal spleen cells or medium intravenously. The suppression was found to be mediated by a Qa‐1‐positive, Thy‐1‐positive cell. It was relatively resistant to cyclophosphamide treatment (100 mg/kg). Furthermore, it had both antigen‐specific and non‐specific components. The findings are discussed in relation to a suppressor activator cellsuppressor acceptor cell pathway in the immunoregulation of tumor immunity.
Impairment of in vitro generation of cytotoxic or T suppressor lymphocytes by friend leukemia virus infection in mice
Authors: Garaci E. , Migliorati G. , Jezzi T. , Bartocci A. , Gioia L. , Rinaldi C. , Bonmassar E.
Published: February 2007

Spleen cells collected from DBA/2 (H‐2d) mice inoculated with the polycythemic variant of Friend‐Leukemia Virus Complex (FLV‐P) were tested for T‐dependent immune functions, such as the in vitro generation of cytotoxic T lymphocytes (CTL) and of non‐specific T suppressor lymphocytes (STL). CTL were generated against H‐2b splenocytes, and STL were obtained following a 5‐day lymphocyte culture without stimulator cells. A progressive and severe impairment of the generation of both CLT and STL was found from 2 weeks onward after infection, being almost totally abolished 3–4 weeks after virus challenge. Suppressor cells (SC) capable of inhibiting CTL generation was detected in FLV‐P bearing mice. Suppressor activity was unaffected by anti‐Thy 1.2 serum and complement but was removed following iron‐magnet depletion or passage through nylon‐wool column. Moreover complete recovery of the competence of CTL generation was attained when FLV‐P infected splenocytes were passed through nylon‐wool column. It is concluded that FLV‐P infection depresses T‐dependent cytotoxic and suppressor responses in mice, by the appearance of non‐T adherent phagocytic cells, capable of impairing CTL generation in vitro.
The usefulness of human tumor cell lines in the study of chemosensitivity. A study of malignant melanomas
Authors: Tveit Kjell Magne , Fodstad Øystein , Pihl Alexander
Published: February 2007

The chemosensitivity of human melanoma cells has been studied before and after continuous in vitro culture. Altogether, nine cell lines were studied, two derived from patients' biopsies, and seven from xenografts in athymic mice. The sensitivity to the agents DTIC (Dacarbazine), CCNU (Lomustine), procarbazine, vinblastine, abrin and ricin was assayed. Furthermore, in five cases the chemosensitivity of the cell lines was compared to that of tumors obtained by injecting the cell lines into athymic mice. In all cases the sensitivity was measured in an in vitro soft agar assay. Upon cultivation in vitro, two of the cell lines, one derived from a patient's metastasis and one from a xenograft in athymic mice, showed marked increases in sensitivity to some of the drugs, whereas sensitivity to other drugs showed little or no change. For the other cell lines small, but definite increases or decreases in chemosensitivity were observed. Permanent cultures showed the same chemosensitivity as early subcultures. The tumors formed by injecting the cell lines into athymic mice showed moderate changes in chemosensitivity, as compared to the cell lines in vitro. The data indicate that considerable changes in chemosensitivity may occur when cells are brought from in vivo to in vitro conditions and vice versa and that such changes may be highly specific. Therefore, although cell lines may be useful in some respects, they should be used with caution in attempts to evaluate quantitatively the sensitivity of human tumors to cancerostatic drugs.
Sister chromatid exchange in lymphoma lines and lymphoblastoid cell lines before and after heterotransplantation into nude mice
Authors: Fonatsch Christa , Kirchner Hartmut H. , Schaadt Michael , Günzel Manfred , Diehl Volker
Published: February 2007

The sister chromatid exchange (SCE) rates of cell lines derived from patients with different malignant and premalignant diseases were studied before and after intracerebral inoculation into nude mice and were compared to the SCE frequencies of cell lines from healthy controls. Lymphoma lines characterized by chromosomal markers as well as chromosomally normal lymphoblastoid cell lines were used. The SCE frequencies of nude mouse tumor‐derived cell lines did not show a homogeneous pattern. They were either as high as, or higher or lower than, the SCE levels of the original cell line. But all cell lines, karyotypically abnormal as well as normal, originating from patients with malignant and premalignant diseases, showed significantly higher SCE rates than the control lines from healthy donors.
Effects of human lymphoblastoid interferon on cultured breast cancer cells
Authors: Shibata Hideo , Taylor‐Papadimitriou Joyce
Published: February 2007

The effect of human interferon on growth and fibronectin production in a range of cultured breast cancer cell lines has been investigated. The cell lines differ in their sensitivity to interferon's growth‐inhibitory effect as determined from growth curves, but the degree of sensitivity varies according to the method of assay. When growth was measured in cultures seeded with fairly large numbers of cells, five out of seven lines examined showed a reduction of 50% or more in the number of attached cells after treatment for 8 days with 1,000 units/ml of interferon. Growth of the two cell lines least affected by interferon treatment in dense culture could, however, be markedly inhibited under conditions of clonal growth in agar or when sparsely seeded on plastic and this was due to inhibition of initiation of growth. In some breast epithelial lines, where the number of attached cells was regulated in part by cell shedding, it was found that interferon not only inhibited cell proliferation, but also increased cell shedding. To determine if interferon increased cell shedding by affecting fibronectin production, the total and cell associated fibronectin was estimated in control and interferon‐treated cultures. Four of 10 cell lines examined produced detectable amounts of fibronectin, and in only one of these lines, Hs578T derived from a carcino‐sarcoma, was the production and retention of fibronectin inhibited by interferon treatment. In those breast carcinoma lines which produced detectable amounts of fibronectin, the level of production and retention of the protein, expressed as a proportion of the total protein, did not change after interferon treatment, but showed an increase if expressed on a per cell basis. This is explained by the fact that the interferon‐treated cells showed an increase in cell volume.
Diploid human lymphoblastoid and burkitt lymphoma cell lines: Susceptibility to murine NK cells and heterotransplantation to nude mice
Authors: McCormick Kenneth J. , Giovanella Beppino C. , Klein George , Nilsson Kenneth , Stehlin John S.
Published: February 2007

Human lymphoid cell lines which had been classified on the basis of studies on clonality and morphological, chromosomal and functional parameters as lymphoblastoid cell lines (LCL) of presumed non‐neoplastic origin and Burkitt lymphoma (BL) lines of proven malignant origin, were tested for susceptibility to natural killer (NK) cells obtained from the spleens of athymic nude mice. The 20 lines included normal diploid LCL and aneuploid BL lines. All cells carried the Epstein‐Barr virus (EBV) genome. In addition, two EBV‐negative BL lines were tested. The pronase‐induced release of 14C‐DNA from 14C‐thymidine‐labelled target cells was used to assess the sensitivity of the cell lines to NK activity. When attempts were made to correlate the growth of the EBV‐positive LCL and the EBV‐positive BL cell lines in the subcutaneous space of adult nude mice with their susceptibility to NK cells, no significant correlation was observed. The EBV‐negative BL cell line, Ramos, however, could be transplanted subcutaneously in nude mice and was more resistant to NK activity than was the EBV‐negative BL cell line, BJAB, which cannot be transplanted subcutaneously. Growth of heterotransplanted EBV‐converted cell lines in the subcutaneous space of adult nude mice may be influenced by immune effectors other than NK cells.
Lysis of human B‐lymphocyte‐derived lymphoma/leukemia cells of established cell lines by interferon‐activated natural killer (NK) cells
Authors: Pattengale Paul K. , Gidlund Magnus , Nilsson Kenneth , Sundström Christer , Örn Anders , Wigzell Hans
Published: February 2007

Cultured cell lines derived from malignant Epstein‐Barr virus (EBV)‐negative B cells, and representative of the more common types of naturally occurring non‐Hodgkin lymphomas and related leukemias, were found to be sensitive to lysis by human natural killer (NK) cells. The observed lysis of such cell lines was mediated by a population of interferon‐augmentable, FcR‐positive, non‐adherent lymphoid cells, which were also able to kill the “standard” NK targets K562 and Molt‐4. When the NK susceptibility of the neoplastic, EBV‐negative B cells was compared to that of diploid, EBV‐carrying, non‐neoplastic B lymphoblastoid cell lines (BLCLs) and of the “standard” NK target K562, several distinct patterns were observed. The killing of the neoplastic B cell lines was significantly less than that of K562, but significantly greater than that of the EBV‐derived BLCLs of non‐neoplastic origin. An additional finding was a similar NK susceptibility profile for the neoplastic, true histiocytic cell line U‐937 (i.e., K562>U937>BLCLs). Furthermore, all cell lines, with the exception of the BLCLs, could effectively compete for the observed killing in cold target inhibition assays. The implications of these findings are discussed in relation to both neoplastic and non‐neoplastic targets of NK lysis.
Expression of SV40 T antigen polypeptides in cells biochemically transformed by plasmids containing the herpes simplex virus thymidine kinase gene and the genome of an SV40tsA mutant
Authors: Kit Saul , Otsuka Haruki , Qavi Hamida , Trkula David , Dubbs Del Rose
Published: February 2007

To study the expression of SV40 tsA genomes that had been non‐selectively introduced into mouse cells, SV40 tsA207 DNA was cleaved with BamH 1 and ligated to BamH 1‐cleaved plasmid pAGO DNA, which contains a functional HSV‐1 thymidine kinase (TK) gene in the form of a 2 kbp Pvu II fragment inserted at the Pvu II site of pBR322. Recombinant plasmids (11–12 kbp) were isolated and amplified in E. coli K12 strain RR1. Restriction nuclease analyses demonstrated that recombinant plasmids pSB15 and pSB10 contained intact SV40 genomes with the polarity of transcription oriented in the same direction (clockwise) or the opposite direction (counterclockwise), respectively, in relation to that of the HSV‐1 TK gene. C1a 1‐cleaved pSB10 and pSB15 DNAs were used to transform LM(TK−) cells to TK+. Serological and disc PAGE analyses showed that clonal lines transformed by these plasmids all expressed the selected marker, HSV‐1 TK. Molecular hybridization experiments showed that transformed clonal lines TF pSB10 C7 and TF pSB15 C10 had integrated intact SV40 genomes at one integration site, TF pSB10 C3 had integrated an SV40 genome with a small deletion near the BamH 1 site, but TF pSB15 C1 had integrated a plasmid from which most of the SV40 nucleotide sequences had been deleted. IF assays with hamster anti‐SV40 tumor sera showed that TF pSB10 C7 and TF pSB15 C10 strongly expressed SV40 T antigens in over 90% of the cells, TF pSB10 C3 expressed SV40 T antigens in a minority of the cells, and TF pSB15 C1 did not express SV40 T antigens at all. [35S]‐methionine labelling and immunoprecipitation experiments showed that, at 36.5°C: (1) TF pSB10 C7 and TF pSB15 C10 expressed 92K and 20K mol. wt. species of SV40 T antigens and 50–55K cellular protein; (2) expression of all three was reduced in TF pSB10 C3 cells; and (3) TF pSB15 C1 expressed none of the SV40 T antigens, nor did parental LM(TK−) or TF 8‐2 transformed cells (which contained the HSV‐1 TK gene but not SV40 DNA). At 40°C, labelling of the 50–55K cellular protein was markedly reduced in TF pSB10 C7 and pSB15 C10 cells. The results suggest that SV40 large T antigen (92K) induces and/ or stabilizes the 50–55K cellular protein in these mouse cells.
Rat mammary carcinoma cells secrete active collagenase and activate latent enzyme in the stroma via plasminogen activator
Authors: O'Grady Robert L. , Upfold Linda I. , Stephens Ross W.
Published: February 2007

A spontaneous mammary adenocarcinoma (AC) from an inbred female rat was investigated with regard to secretion of neutral proteases. Cultures of neoplastic epithelial cells derived from the tumour secreted an enzyme that fulfilled the criteria for a specific collagenase. In contrast to cultures of non‐neoplastic cells, tumour collagenase was present as an active enzyme, since treatment with trypsin or p‐aminophenylmercuric acetate (APMA) did not increase activity. The neoplastic cells were also prolific producers of plasminogen activator (PA). Dexamethasone (Dex) (10−6M) markedly reduced the levels of both enzymes. Addition of tranexamic acid (TA), an inhibitor of plasmin and of plasminogen activation, did not affect collagenase activity, even at 10−1M TA, nor did latent collagenase accumulate. Latent collagenase was secreted in culture by normal fibroblasts from neonatal rat lungs. This latent enzyme was activated by the addition of tumour cell medium plus plasminogen, but this effect was inhibited by the addition of TA. These results demonstrate that the neoplastic cells themselves secrete collagenase as an active enzyme. PA is also secreted, is not involved with tumour collagenase, but is capable, in the presence of plasminogen, of activating latent collagenase produced by the non‐neoplastic cells within the tumour or in the surrounding tissue. This tumour possesses potent collagenolytic ability in vitro which may be partly responsible for its rapid invasion in vivo.
Adjuvant reactivity predicts survival in patients with “high‐risk” primary malignant melanoma treated with systemic BCG
Authors: Cochran Alistair J. , Buyse Marc E. , Lejeune Ferdy J. , Macher Egon , Revuz Jacques , Rümke Philip
Published: February 2007

We report the prognostic importance of strength of reaction to BCG, tumor histology and clinical factors in patients with previously untreated high‐risk (Clark, III, IV and V) primary malignant melanoma. One hundred and one such patients received high‐dose BCG (1 × 108viable units) by Heaf gun as an adjuvant to standardized primary surgery according to EORTC Protocol 18741. Univariate analysis of disease‐free interval (DFI) indicates that the degree of maximum reaction to BCG (p= 0.0003), Breslow thickness (p= 0.0003) and Clark level (p= 0.002) are highly significant prognostic factors. When a multivariate model using Cox's proportional hazard regression was used for DFI, the degree of maximum reaction to BCG and Breslow thickness were by far the most significant criteria. A prognostic equation was obtained to predict DFI from maximum BCG reaction and Breslow thickness. From analysis of the “scores” calculated in this way it appears that the two variables act independently. This technique permits the determination of values that are predictive of DFI and discriminate between subgroups of patients with different DFI characteristics (5 groups,p< 0.0001). This exercise was repeated for survival and similar results were obtained. The degree of a patient's immune reaction to BCG administered therapeutically is of paramount importance in determining the likelihood of survival. This factor and the Breslow thickness can be integrated to produce a mathematical equation which accurately predicts survival for appropriately treated melanoma patients.