bluuebunny/crossref_metadata_2025 huggingface dataset:
Antitumor effect of arginine butyrate in conjunction with corynebacterium parvum and interferon
Authors: Chany Charles , Cerutti Italina
Published: February 2007

The antitumor effect of arginine butyrate, used alone or in conjunction with interferon (IFN), was studied using randomly selected Swiss mice inoculated i.p. with 106 180 TG Crocker tumor cells. The results of these different therapeutic regimens were estimated by tumor incidence at 10 days, by the time necessary to protect 50% of the animals, and by the final survival rate. Combined treatment by IFN and arginine butyrate was effective; but in order to compensate for IFN's immune repressive effects, a single injection of Corynebacterium parvum was administered in some experiments prior to IFN and/or arginine butyrate. After this immune potentiation, both IFN and arginine butyrate used separately significantly protected the animals. However, optimal results were obtained when a single C. parvum injection was followed by nine daily alternating shots of arginine butyrate and IFN.
Specific chromosome changes associated with viral transformation of rat glial cells
Authors: Kano‐Tanaka Kyoko , Tanaka Tatsuya
Published: February 2007

Karyotypes of three malignant cell lines derived from Wistar and WKA/Mk fetal rat glioblasts, transformed by murine sarcoma virus (MSV‐M‐os) as well as those of four cell lines derived from C6 glioma cells of Wistar origin, retransformed by MSV‐M‐os, were analyzed in early culture passages. The C6 line had a modal number of 42 chromosomes with a normal male karyotype, and only a minor population of cells with 43 chromosomes. The modal chromosome number in every transformed glial cell line shifted from 42 to 43. The G‐banding pattern revealed consistent chromosome abnormalities. Structural chromosome changes occurred in one chromosome No. 2 (2q‐) and in one No. 4 (4q+). The cells with a 43 chromosome karyotype showed trisomy of chromosome No. 12 and its heteromorphism, a finding also confirmed by silver staining. Identical chromosome changes were found in transformed C6 cell lines. A further interesting feature was that all malignant cells had different distribution patterns of silver‐stained nucleolar organizer regions (Ag‐NORs) among particular chromosomes (Nos. 3, 11 and 12) from normal cells, showing an increased frequency of chromosome No. 12 with Ag‐NORs. These results suggested that the gain and/or loss of specific segments involved in chromosomes Nos. 2, 4 and 12 contain(s) genes favorable to malignant transformation in rat glial cells.
Chromosome changes in butylnitrosourea (BNU)‐induced mouse leukemia
Authors: Carbonell F. , Seidel H. J. , Saks S. , Kreja L.
Published: February 2007

G‐banding analysis was carried out in 45 mice after exposure to the leukemogen butylnitrosourea (BNU). Of 27 animals without clinical signs of leukemia, 2 had chromosomal rearrangements (7%) while, of 18 leukemic mice, 5 showed abnormal karyotypes (28%). The chromosomal abnormalities were not random and showed preferential changes of chromosomes Nos. 14 and 15. The organ distribution of the chromosomal abnormalities showed a preferential involvement of the thymus with a secondary presence of chromosome anomalies in peripheral lymphoid organs and the bone marrow. The findings are discussed in relation to the recent reports on the specificity of trisomy 15 in murine leukemia and lymphoma.
Purification and functional characterization of a low molecular weight immune modulating factor produced by lewis lung carcinoma
Authors: Young M. Rita , Sundharadas G. , Cantarow Walter D. , Kumar P. Ravi
Published: February 2007

Previously, we reported that mouse tumors contain a low molecular weight factor which is capable of affecting in vitro properties of macrophages. We now describe the purification to homogeneity of the only factor with macrophage modulating activity from one of these tumors, Lewis lung carcinoma. The purified tumor factor appears to be a carboxylic acid and it retains all of the macrophage modulating properties which are characteristic of the unfractionated crude tumor extracts. This factor therefore reverses the spreading of macrophages, enhances the migration of macrophages out of capillary tubes and inhibits their chemotactic and tumoricidal activities. The purified tumor factor also inhibits immune responses of spleen cells. Specifically, proliferation of normal lymphocytes in response to mitogens and to alloantigens, as well as the generation of cytotoxic T lymphocytes in a mixed leukocyte culture, are suppressed when these cells are cultured in the presence of the purified tumor factor. The mixed leukocyte reaction of lymphoid cells obtained from mice which had been treated with the tumor factor is reduced compared to the response of lymphocytes obtained from normal mice. It is possible that there is a relation between production of this factor by tumor cells and survival of the tumor in a host.
Tumorigenicity of sarcoma cells is enhanced by the local environment of implanted foreign body
Authors: Vasiliev Ju. M. , Moizhess T. G.
Published: February 2007

The local effect of an implanted foreign body (polyvinyl chloride film) on the growth of transplanted syngeneic sarcoma cells was studied. Two cell lines derived from CBA mouse sarcomas induced by subcutaneously implanted polymer films were used. Small numbers of tumour cells were subcutaneously transplanted to CBA mice in several ways (1) as a suspension into normal tissue (control group); (2) as a suspension into the capsules around previously implanted polymer films; (3) attached to the surface of polymer films, and implanted with these films. The incidence of tumours was significantly increased and the time of their appearance was decreased in groups (2) and (3) as compared with the control group (1). Removal of the film from the capsule 24 h after the transplantation of sarcoma cells did not abolish the stimulation of tumor growth. It is concluded that the local environment of the implanted foreign body promotes the growth of sarcoma cells; similar promoting effects may play some role in the course of foreign body tumorigenesis.
Expression of intermediate filaments in soft‐tissue sarcomas
Authors: Miettinen M. , Lehto V.‐P. , Badley R. A. , Virtanen I.
Published: February 2007

Monospecific antibodies and indirect immunofluorescence microscopy were used to investigate the presence of cytoskeletal intermediate filaments of the keratin, vimentin and desmin types in 43 soft‐tissue sarcomas. The results showed that vimentin was present in the neoplastic cells of all types of soft‐tissue sarcomas studied, whereas keratin was absent, the only exception being the epithelial‐like cells in biphasic synovial sarcoma. The presence of desmin was confined to leiomyosarcomas and rhabdomyosarcomas, which usually showed desmin‐positivity. In addition, malignant fibrous histiocytomas occasionally displayed some desmin‐positive cells. Thus, determination of intermediate filaments is of aid in the histogenetical diagnosis of tumors, because keratin‐positivity largely excludes the possibility of a sarcoma, and desmin‐positivity aids in recognizing leiomyosarcomas and rhabdomyosarcomas.
Application of the micronucleus test to exfoliated cells of high cancer risk groups: Tobacco chewers
Authors: Stich Hans F. , Curtis J. Randall , Parida Bibhuti B.
Published: February 2007

Powdered tobacco (Khaini tobacco) with the addition of lime is commonly used by the residents of Bihar, India. The tobacco/lime mixture is usually placed on the inner side of the lower lip within the gingivolabial groove. About 42% of the users keep it at the front, the rest move the tobacco towards the left or right side within the oral cavity. Carcinomas (so‐called “Khaini cancers”) develop mainly at the site where the tobacco is in close contact with the mucosa. Scrapings of the mucosa were taken at sites where the tobacco is kept, then smears were prepared, stained with the Feulgen reaction and fast green, and screened for micronuclei which indicate the occurrence of chromosome aberrations in the dividing cell population of the basal layer. An elevated frequency of cells with micronuclei was found in the oral mucosa of all 27 examined Khaini tobacco users (Munda and Santal tribes) compared to that of non‐chewers of similar ethnic background and dietary habits. The induction of micronucleated mucosa cells seems to be due to genotoxic agents released from the tobacco/lime mixture. In vitro, an aqueous extract of the Khaini tobacco elicits chromosome aberrations and micronuclei in cultured human fibroblasts and Chinese hamster ovary (CHO) cells. No chromosome‐damaging effect was observed following the application of lime or calcium hydroxide (Ca(OH)2). The micronucleus test on exfoliated cells can provide evidence of carcinogen exposure in the tissue from which cancers will develop. This approach combines all the advantages of in vitro short‐term tests for genotoxic and carcinogenic agents with those of using an intact organism with all its defence mechanisms.
Human embryonal carcinoma cells in culture do not synthesize fibronectin until they differentiate
Authors: Andrews Peter W.
Published: February 2007

The expression of fibronectin by clones of 2102Ep, a human cell line derived from a testcular germ‐cell tumor, was studied. In high‐density cultures these cells retain an embryonal carcinoma phenotype and do not express the cell surface antigen SSEA‐1. They do not synthesize fibronectin. However, when grown at low densities, many of the cells appear to differentiate, as indicated by a change in their morphology and their expression of SSEA‐1. Such cultures also synthesize fibronectin. Further, when low‐density cultures were fractionated into SSEA‐1‐positive and SSEA‐1‐negative subpopulations by fluorescence‐activated cell sorting, fibronectin synthesis was confined to the SSEA‐1‐positive cells. The fibronectin produced by these cells exhibits an apparent molecular weight (261,000) slightly greater than that produced by diploid fibroblasts (250,000) and may represent an embyonic form. It is not laid down as an extracellular matrix and cannot be detected by immunofluorescence analysis of cell monolayers.
Human melanoma‐specific oncofetal antigen defined by a mouse monoclonal antibody
Authors: Liao Shuen‐Kuei , Clarke Bryan J. , Khosravi Mohammed , Kwong Pak C. , Brickenden Anne , Dent Peter B.
Published: February 2007

140.240, an IgG2a mouse monoclonal antibody raised against a cultured human melanoma cell line, was highly specific for melanoma cells as determined by direct and absorption analyses in a mixed hemadsorption assay. Supernatants of doubly cloned hybridomas producing antibody 140.240 reacted with all cultured and fresh melanomas tested but failed to react with a variety of carcinomas, sarcomas, lymphomas, leukemias and other tumors of neuroectodermal origin. This antibody did not react with B‐lymphoid cell lines, ruling out HLA‐DR specificity. Non‐reactivity of antibody 140.240 with peripheral blood lymphocytes obtained from the donor of the immunizing melanoma line excluded the possibility of detecting histocompatibility antigens. Nevus cells were also non‐reactive. However, antibody 140.240 did identify an antigenic determinant on tissue homogenates prepared from fetuses of 10–14 weeks' gestation. The antigen involved was shed by cultured melanoma lines and, by immunoprecipitation analysis of radiolabelled lysates, had a molecular weight of approximately 87kdal. Thus, the structure identified by monoclonal antibody 140.240 is a melanoma‐specific oncofetal antigen.
Immunoglobulins reactive to carcinoembryonic antigen and their relationship to the antigen in malignant ascitic fluid of ovarian carcinoma
Authors: Hill R. , Khoo S. K. , Daunter B. , Silburn P. A. , Mackay E. V.
Published: February 2007

Samples of malignant ascitic fluid from 30 patients with advanced ovarian carcinoma were examined for the presence of IgM antibodies to CEA and PEG‐precipitable proteins binding to 125I‐CEA. The IgM antibodies to CEA were measured by a solid‐phase radioimmunoassay using ovarian CEA. There was no correlation between the level of IgM antibodies to CEA and that of total IgM in the fluid. In 11 of 30 (37%) samples tested, significant amounts of IgM antibodies to CEA were found. The CEA‐binding proteins were measured by the ability of ascitic fluid to incorporate 125I‐colonic‐CEA into PEG‐precipitable complexes. In 9 of 39 (30%) samples, the precipitation was significant. There was no association between antibodies to the ABO and Lewis blood group factors and these antibodies to CEA. An inverse relationship was observed between the level of CEA and that of CEA‐binding proteins shown by the two assays. When 125I‐CEA was incubated with these “positive” samples, a high molecular weight fraction was demonstrated by chromatography. By contrast, in the “negative” samples, there was no incorporation of 125I‐CEA. These findings would indicate the presence of CEA‐reactive proteins possibly existing as immune‐complex‐like material in ascitic fluid of some patients.
A 6‐thioguanine‐resistant variant of the 13762 cell line which is no longer tumorigenic or metastatic
Authors: Ramshaw I. A. , Carlsen S. A. , Hoon D. , Warrington R. C.
Published: February 2007

A 6‐thioguanine resistant (TGR) variant of the highly tumorigenic and metastatic mammary adenocarcinoma cell line 13762 was obtained. This variant was no longer tumorigenic or metastatic in normal syngeneic rats but did grow as a primary tumor in irradiated animals. Our results suggest that the TGR cell line was rejected by an irradiation‐sensitive immunological mechanism. Although the TGR cells produced primary tumors in irradiated animals, there was no evidence of the extensive metastasis seen with the 13762 cells. This apparent inability to metastasize was confirmed by injecting the TGR cells intravenously. Whereas the 13762 cells produced large numbers of metastatic lung foci, there was no evidence of lung metastasis with the TGR cells, even in irradiated animals. Revertant cells for the 6‐thioguanine‐resistant phenotype were still non‐tumorigenic and non‐metastatic in normal rats, suggesting that 6‐thioguanine resistance is not associated with the altered tumorigenic phenotype. From the TGR variant, cell lines were selected with an increased ability to produce tumors in normal rats. Although some of these revertants were capable of producing limited lung metastases in normal animals, extensive metastases were always seen when the cells were injected into irradiated animals. Differences between the 13762 and the TGR variants were also found in their ability to produce plasminogen activator. The TGR cells released far less plasminogen activator in culture than the 13762 cells. This could be a contributing factor in their different metastatic potentials.
Immunotherapy of murine leukemia. VII. Prevention of friend leukemia virus‐induced immunosuppression by passive serum therapy
Authors: Genovesi Eugene V. , Livnat Daniella , Collins Jeffrey J.
Published: February 2007

Previous studies have suggested that the passive therapy of Friend leukemia virus (FLV)‐induced disease with chimpanzee anti‐FLV serum operates by reducing the level of infectious virus in the treated animal below the immunosuppressive threshold, thereby allowing the host to mount anti‐viral immune responses which are responsible for long‐term protection. The present study was undertaken to examine directly the effect of passive serum therapy on the marked immunosuppression induced by FLV in progressively infected mice, as well as to determine whether virus‐specific host cellular immune effector functions are augmented in serum‐protected animals. Using a variety of assays of host immunocompetence, including natural killing (NK), antibody‐dependent cellular cytotoxicity (ADCC) in vivo and in vitro induction of allogeneic killers, and mitogen blastogenesis, a marked compartmentalization of FLV immunodepression was observed in progressively infected DBA/2 mice, possibly reflecting the distribution of FLV target cells in various host lymphoid populations. Thus, spleen‐cell functions were suppressed most rapidly and to the greatest degree, followed by peritoneal cells and peripheral blood lymphocytes, while lymph node cells and thymocytes maintained normal levels of activity. In contrast, serum‐protected mice demonstrated no sign of FLV‐induced immunosuppression regardless of the host effector‐cell population or immune function examined. However, we were not able to identify host anti‐viral cellular immune functions which are significanly enhanced in serum‐protected animals; thus the specific role of the host immune system in the passive serum therapy of FLV‐induced disease remains undefined at the present time.
Tumorigenicity of tsA and wild‐type simian virus 40 transformed cells inoculated onto the chicken chorioallantoic membrane
Authors: Lehman John M. , Estes Patricia
Published: February 2007

This study compares the tumorigenicity of SV40 primary tumor cell lines, tsA and wild‐type SV40‐transformed Chinese hamster cells, at two temperatures, 37° C and 40.5° C, inoculated onto the chorioallantoic membrane of the chicken egg. The SV40 primary tumor cell lines varied in their efficiency of takes at 37° C from 78% for the H65–90B tumor line, 73% for the H80–7A and 25% for the H80‐4 line. At 40.5° C the H80‐4 was unable to form tumors; however, the H80–7A and H80‐4 produced 70% and 20% tumors respectively. Histologically, all CAM tumors were fibrosarcomas identical to the transplanted tumors, however, the tumor(s) at 40.5° C were smaller. Chinese hamster wild‐type SV40‐transformed cells were equally efficient (32%) at tumor production at both temperatures. The tsA‐SV40‐transformed Chinese hamster cells (A58 and A58–2) induced 34% tumors at 37° C and 9% tumors at 40.5° C. At 37° C these tumors were typical fibrosarcomas; however, the 40.5° C tumors were smaller and less cellular, resembling a more differentiated fibrosarcoma. Therefore, the tsA Chinese hamster transformed cells were less efficient at tumor induction at the non‐permissive temperature; however, the primary tumor lines also demonstrated a variability in tumorigenicity (H65–90B and H80–4). Possibly factors other than the temperature‐sensitive viral protein (big “T” antigen) may be involved in establishing a tumor on the chicken CAM.
Changes in antibody titers in cattle infected clinically and subclinically with bovine leukemia virus
Authors: Kono Yuji , Sentsui Hiroshi , Miyamoto Toru , Morozumi Kichizo , Sakamoto Yasuhiro
Published: February 2007

Changes in titers of antibodies to protein and glycoprotein antigens of bovine leukemia virus (BLV) were investigated by immunodiffusion in two groups of cattle. In one group of cattle (10 head) which developed enzootic bovine leukosis during the observation period of 3 years, seven showed a gradual increase in antibody titers following a period of level antibody titers that persisted for several months to several years. The titer was finally eight to 32 times higher than the initial titer. The remaining three showed little change in titer. Of the 10 animals with tumors, three showed a decrease in the titer when they were in extremis. In contrast, in the second group of cattle (110 head), which were infected with BLV subclinically, the change in the titers during 1 and 3 years ranged from no change to four times the lowest titer that was observed during the period. Of the cattle which had a low level of antibody to one of the BLV antigens, a few became negative reactors to the respective antigen.
Thymus independence of hybrid resistance against a panel of T‐cell lymphomas of H‐2b origin
Authors: Klein Gunnar O. , Kárre Klas , Kiessling Rolf , Klein George
Published: February 2007

Adult thymectomy, followed by whole‐body irradiation and reconstitution with fetal liver, was performed to study the T‐cell dependence of F1 hybrid resistance to a panel of lymphomas of H‐2b origin. Previously, the pattern of hybrid resistance against the same lymphomas was found to correlate with the pattern of NK‐activity in a spectrum of F1 hybrids (Kiessling et al., 1975). We now show that hybrid resistance against three lymphomas of C57BL/6 origin, P‐52–127–166, RBL‐5 and EL‐4 and against YLD, of C57L origin, is expressed in the absence of thymus. In another series of experiments, the effectors responsible for hybrid resistance to the transplanted lymphoma EL‐4 were studied by reconstituting thymectomized and non‐thymectomized C57BL mice with syngeneic bone marrow from NK‐deficient beige mutant or wild‐type C57BL donors. While the recipients of beige bone marrow had a clearly reduced tumor resistance, thymectomy did not decrease resistance further. This study supports the hypothesis that resistance to these lymphomas in F1 hybrids as well as in syngeneic mice is mainly mediated by natural killer cells.
Secretion of basement membrane collagen degrading enzyme and plasminogen activator by transformed cells – role in metastasis
Authors: Salo Tuula , Liotta Lance A. , Keski‐Oja Jorma , Turpeenniemi‐Hujanen Taina , Tryggvason Karl
Published: February 2007

The relationship of a basement membrane collagen degrading enzyme (BM collagenase) and plasminogen activator (PA) was studied in a number of non‐malignant and malignant human and murine cell lines. Several non‐malignant cell lines secreted significant amounts of PA but no detectable BM collagenase activity whereas the malignant cell lines, with one exception, secreted both enzymes. Therefore, the secretion of BM collagenase appears to be a characteristic of many malignant cells whereas PA is synthesized also by normal cells. The BM collagenase needed proteolytic activation for maximal activity indicating that it is secreted in a latent form. The addition of plasminogen to the culture medium of human fibrosarcoma cells (HT‐1080) resulted in maximal activation of the enzyme. Plasmin, but not plasminogen, increased the activity of partially purified enzyme protein. Accordingly, the activation of latent BM collagenase in vivo may be facilitated by PA through the conversion of plasminogen to plasmin. It is suggested that the secretion of BM collagenase concomtantly with PA is a prerequisite for metastasis.
Cancer of respiratory organs among workers at a nickel refinery in Norway second report
Authors: Magnus Knut , Andersen Aage , Høgetveit Arne Chr.
Published: February 2007

In a previous report (Pedersen et al., 1973) an excess risk of respiratory cancer among Norwegian nickel workers was demonstrated. The number of cancer cases was relatively small for the study of temporal changes in exposure. In this report the number of cancer cases increased by 70% through an extended follow‐up to 1979, and the results published previously were confirmed. Data on smoking habits of the employees at the nickel refinery have now become available. The interaction between smoking and occupational nickel exposure is assessed by comparing the excess risk of lung cancer caused by smoking in the study group and in a sample of the general population. It is shown that the interaction is closer to being additive than multiplicative. This observation has methodological implications for studying temporal changes in occupational exposure. These implications are discussed. No substantial reduction in occupational exposure at the nickel refinery can be observed as far as lung cancer is concerned. For nasal cancer, however, the risk is much smaller among those employed around 1960 than among those employed around 1930. The difference in trend of occupational risk for the two types of cancer cannot be explained by the data presented.
Paradoxical anti‐leukemic effects of plant‐derived tumor promoters on a human thymic lymphoblast cell line
Authors: Nakao Yoshinobu , Matsuda Shuichi , Kimoto Hiroyuki , Matsui Toshimitsu , Kobayashi Nobuhisa , Kishihara Michizo , Fujita Takuo , Watanabe Shaw , Ueda Kunihiro , Ito Yohei
Published: February 2007

Three different diterpen polyols and the teleocidin have antileukemic effects on the human thymic leukemia cell line HPB‐ALL by inducing phenotypic differentiation. We tested TPA (phorbol esters), mezerein (daphnane), milliamin (ingenol ester) and teleocidin B (teleocidins) as representative of the chemical structure of each principle and found that these agents have the similar biological activity of inducing phenotypic differentiation in HPB‐ALL cells. Moreover, competitive binding of [3H]PDB to cell‐surface receptors was significantly inhibited by these agents; n‐butyrate and phorbol per se did not inhibit the binding of [3H]PDB. Despite differences in the structure of the principles, these agents may have similarly acting side‐chain structures.
Morphological changes, cell aggregation and cell membrane alterations caused by phorbol 12,13‐dibutyrate in human blood lymphocytes
Authors: Patarroyo Manuel , Yogeeswaran Ganesa , Biberfeld Peter , Klein Eva , Klein George
Published: February 2007

Nanomolar concentrations of phorbol 12,13‐dibutyrate [P(Bu)2] were found to affect the morphology of human blood lymphocytes. Changes in the properties and the biochemical composition of the plasma membrane were particularly apparent. Light and electron microscopy (scanning and transmission) showed polarization of the cytoplasm, consistent with uropod formation, in the majority of the cells within 15 min of treatment. Ruffled membranes and cell‐to‐cell aggregation were observed within 2 h. Larger aggregates, long surface projections and signs of lymphocyte activation (lymphoblasts and mitotic figures) were detected after 24 and 48 h. Cell‐to‐cell aggregation was monitored by light transmission in an aggregometer and confirmed by light and electron microscopy. Aggregation occurred rapidly after the addition of the phorbol ester and was maximal within 1 h. Cells treated for 24 h formed large clumps. Only 44% of the cells remained single, compared with 97% in the untreated control. About 17% of the treated cells bound autologous untreated lymphocytes, as shown by conjugate formation between fluorescein‐labelled P(Bu)2 treated and untreated unlabelled cells. Synthesis and cell surface exposure of sialyl components were studied in untreated and 48 h P(Bu)2‐treated cells by metabolic labelling of sialic acid with the sialic‐acid‐specific precursor N‐acetyl‐[3H]‐mannosamine (ManNAc) followed by neuraminidase hydrolysis. Cells treated with P(Bu)2 for 48 h showed reduced incorporation of ManNAc and a two‐ to three‐fold reduction in neuraminidase‐releasable sialic acid, compared with untreated cells. Mild periodate oxidation followed by sodium borotritide labelling showed a 20–30% reduction in cell surface sialic acid in the phorboltreated cells. The degree of sialylation of galactosyl and N‐acetyl galactosamine residues in P(Bu)2‐treated cells, measured by galactose oxidase – sodium borotritide labelling of neuraminidase – treated versus untreated cells, showed a 15–16% reduction compared to controls. Study of glycosphingolipids showed a marked increase of [3H]‐galactose incorporation into major glycolipids with chromatographic mobilities of ceramide monohexoside, globoside, GM3, GM1, and GD1a in P(Bu)2 treated lymphocytes. There were no detectable qualitative or quantitative changes in glycoproteins, as judged by surface iodination and borotritide labelling. This suggests that the ganglioside compartment is responsible for the decreased surface sialic acid.
The effect of rutin‐N‐mustard on the survival of NK/Ly ascites tumour‐bearing mice
Authors: Molnár J. , Mucsi I. , Mándi Y. , Béládi I. , Földeák S. , Boda K.
Published: February 2007

A newly synthetized rutin derivative, rutin‐N‐mustard, showed a marked antiproliferative effect on NK/Ly ascites tumour cells in vivo. When administered i.p. or i.v., this compound increased the survival time of the animals, but oral administration had no such effect. The drug was not able to kill the tumour cells, since the chromium release from the rutin‐N‐mustard‐treated tumour cells was the same as in the case of the controls. Tumour growth was completely inhibited in the animals when the cells were pretreated with 100 mg/kg rutin‐N‐mustard before transplantation. The results also showed that rutin‐N‐mustard has little effect on the xenogenization of NK/Ly tumour cells. We presume that the antiproliferative action of rutin‐N‐mustard is due to its alkylating activity.
DNA virus‐transformed hamster cell – host effector cell interactions: Level of resistance to cytolysis correlated with tumorigenicity
Authors: Cook James L. , Hibbs John B. , Lewis Andrew M.
Published: February 2007

Spontaneously cytolytic hamster spleen cells and BCG‐activated hamster macrophages were used to examine susceptibilities to nonspecific effector cell‐induced lysis among 13 DNA virus‐transformed hamster cell lines exhibiting four different tumorigenic phenotypes. Hamster cells transformed by adenovirus type 12 (an oncogenic adenovirus serotype) or simian virus 40 (an oncogenic papovavirus) readily induced tumors in immunocompetent syngeneic hamsters and were relatively resistant to spleen‐cell‐induced lysis compared to cells transformed by adenovirus type 2 (a non‐oncogenic adenovirus serotype) which induced tumors only in immunoincompetent hosts. Simian virus 40‐transformed cells, which possess the unusual property of efficient tumor induction in allogeneic hosts, were uniquely resistant to lysis by activated macrophages. These differential patterns of susceptibility to cytolysis suggest an association between the level of transformed cell resistance to lysis by nonspecific host effector cells and the oncogenicity of the transforming virus. Furthermore, these data suggest that tumor‐cell properties, other than those commonly associated with neoplastic transformation, determine the level of susceptibility or resistance to host effector cell mechanisms.
Antitumor effects of interferon in mice injected with interferon‐sensitive and interferon‐resistant friend leukemia cells. II. Role of host mechanisms
Authors: Belardelli F. , Gresser I. , Maury C. , Maunoury M.‐T.
Published: February 2007

We have attempted to determine what host mechanisms are responsible for inducing a rapid decrease in the number of Friend leukemia cells (FLC) in the peritoneal cavity of interferon‐treated mice. By injecting radiolabelled FLC, we showed that there was a greater loss of radioactivity from individual interferon‐treated mice than from control mice. Thus, it was likely that fewer cells were recovered from the peritoneal cavity of interferontreated mice because of cell destruction. Treatment of mice with interferon limited to the period preceding tumor‐cell inoculation conferred some degree of antitumor activity, although this regimen was far less effective than when interferon treatment was initiated and continued daily after tumor‐cell inoculation. We have been unable to transfer any antitumor activity with peritoneal washings containing macrophages and lymphocytes from interferon‐treated donor mice to tumor‐inoculated recipient mice. Inoculation of silica particles i.p., which destroys macrophage function and may affect NK cell activity, did not abrogate interferon's antitumor activity. We suggest that interferon induces a host‐mediated antitumor effect by mechanisms which are not mediated by easily recoverable soluble factors or by cytotoxic cells. The nature of this potent interferon‐induced host mechanism remains unknown.
Intrapleural administration of OK432 in cancer patients: Activation of nk cells and reduction of suppressor cells
Authors: Uchida Atsushi , Micksche Michael
Published: February 2007

Twelve patients with carcinomatous pleural effusions were treated with single intrapleural (i.pl.) administration of OK432 on day 0 and the effects of i.pl. OK432 on natural killer (NK) cell activity were followed on day 7. Two patients showed no clinical evidence of therapeutic benefit from i.pl. OK432. In the other 10 patients, pleural effusions and/or tumor cells in the effusions had decreased or disappeared by day 7. NK cell activity was markedly low or absent in pleural effusions of untreated patients due to the presence of adherent effusion cells capable of suppressing the maintenance and interferon‐induced augmentation of NK cell activity. I.pl. injection of OK432 resulted in enhancement of NK cell activity and abrogation of NK suppressor cell activity in the effusions. On the other hand, blood NK cell activity was not consistently altered by i.pl. OK432. In vitro treatment of effusion mononu‐clear cells from untreated patients with OK432, but not with interferon, augmented NK cell activity. In addition, adherent effusion cells of untreated patients lost their NK suppressor function following in vitro OK432 treatment. These results suggest that i.pl. administration of OK432 will result in augmentation of NK cell activity and reduction of NK suppressor cell activity in pleural effusions, which could be responsible for the antitumor activity of i.pl. OK432.
Population distribution of placental benzo(α)pyrene metabolism in smokers
Authors: Gurtoo Hira L. , Williams Cynthia J. , Gottlieb Karen , Mulhern Aurelie I. , Caballes Lida , Vaught Jimmie B. , Marinello Anthony J. , Bansal Surendra K.
Published: February 2007

Human placental microsomes isolated from term placentas derived from nonsmoking women and women smoking I to 40 cigarettes a day were analyzed for the metabolism of benzo(a)pyrene measured as various metabolites by HPLC and/or as aryl hydrocarbon hydro‐xylase (AHH)6 activity. In accordance with other reports, AHH activity was several times higher in smokers than in nonsmokers. Regression analysis on 13 different placental tissues from women smoking from I to 40 cigarettes demonstrated a high correlation (r=0.8 to 0.9) between AHH activity (or the formation of benzo(a)pyrene phenols resolved by HPLC) versus the formation of the procarcinogenic benzo(a)pyrene‐7,8‐diol. Subsequent studies on placentas derived from 67 women who smoked 10 to 40 cigarettes per day demonstrated a definite dose‐response relationship between AHH activity and the number of cigarettes smoked/day. The dose‐response curve was sigmoidal in shape; however, when the data were plotted on a semi‐log scale the curve assumed a linear shape, reaching saturation of AHH induction beyond 20 to 25 cigarettes/day. While mean AHH activity was dependent upon the number of cigarettes smoked/ day, considerable interindividual variability in AHH (ranging more than 1,000‐fold in some cases) was observed among individuals with comparable smoking histories, i.e. smoking the same number of cigarettes. Population distribution suggested clustering of the population in the low‐AHH‐activity region while cord‐blood thiocyanate analysis and twin studies suggested that genetic factors contributed to a major portion of the inter‐individual variability in AHH activity observed among smokers.
Prediction of malignant melanoma recurrence by serumN‐acetylneuraminic acid
Authors: Silver Hulbert K. B. , Murray R. Nevin , Worth Ann J. , Salinas Fernando A. , Spinelli John J.
Published: February 2007

Since serum N‐acetylneuraminic acid (NANA) can serve as a relatively sensitive monitor of tumor burden, we wished to examine the relationship of NANA to other suggested prognostic factors for malignant melanoma. Eligible patients included 151 patients with stage‐l disease and 10 with stage‐ll regional lymphatic extension. A proportional hazards model was used to examine nine factors, of which five were not significant predictors of recurrence: age, sex, primary site, tumor diameter, and stage. Significant predictors included: measured depth p=7×10−7; anatomic depth (Clark level), p=7×10−4; NANA, p=0.003; and growth pattern (superficial spreading vs nodular), p=0.01. However, on multivariate analysis only two predictors were independent; measured depth and NANA. The latter could not be explained by non‐specific factors. The data were examined to define optimal test values for assignment of risk. According to this model, patients with lesions >l.75 mm and NANA <2μmol/ml have a more than 12‐fold greater risk of recurrence by 2 years than those with lesions ⩽1.75 mm and NANA ⩽2 μmol/ml.
Methods and mechanisms for the development of MTX resistance in human lymphoid cells
Authors: Alam A. , Geddes A. J. , North A. C. T.
Published: February 2007

Conditions are described for the development of methotrexate resistance in CCRF/CEM human lymphoid cells and an attempt is made to distinguish between those conditions that lead to methotrexate resistance through impairment of cellular transport of methotrexate and those that lead to resistance through enhanced production of dihydrofolate reductase. A restistant line showing a 200‐fold enhancement of dihydrofolate reductase has been obtained. The CCRF/CEM human cells are much more sensitive to methotrexate than are murine cells.
Elevation of serum placental alkaline phosphatase levels in cigarette smokers
Authors: Tonik Susan E. , Ortmeyer Ann E. , Shindelman Jeffrey E. , Sussman Howard H.
Published: February 2007

In an ongoing longitudinal study for tumor markers in breast cancer patients, levels of placental alkaline phos‐phatase (PAP) measured by RIA were found to be elevated in 34% of patients who smoked cigarettes as opposed to 5 % of non‐smoking subjects. A normal range was established (0‐2.14 ng/ml) using healthy non‐smoking females. In an expanded analysis by disease state, PAP levels were found to be elevated significantly (p<0.02) in the smoking groups of each category. This isoenzyme, when detected at elevated serum levels by RIA, was enzymatically active in 48% of the patients as analyzed by immunoenzymatic assay. One smoker with high PAP levels discontinued smoking following a myocardial infarction. Her PAP levels returned to normal within 2 months.
Chemotactic activity for mononuclear phagocytes of culture supernatants from murine and human tumor cells: Evidence for a role in the regulation of the macrophage content of neoplastic tissues
Authors: Bottazzi Barbara , Polentarutti Nadia , Balsari Andrea , Boraschi Diana , Ghezzi Pietro , Salmona Mario , Mantovani Alberto
Published: February 2007

Culture supernatants from 14 mouse solid tumors, 2 mouse lymphomas, 8 human solid tumor lines and 3 human leukemia‐lymphomas were examined for chemotactic activity in blind‐well chemotaxis chambers using murine peritoneal macrophages and human blood monocytes as indicator cells. Culture supernatants from various murine and human solid tumors had appreciable chemotactic activity for mononuclear phagocytes. Chemotactic activity was found in murine tumors of different histology and transplantation history, including autochthonous mammary carcinomas and chemically‐induced sarcomas. Chemotactic activity was not unique to neoplastic cells because is was detected also in supernatants of two preparations of mouse embryo fibroblasts and two human lung embryo fibroblast lines. Production of tumor‐derived chemo‐attractants did not require serum in the culture medium, was inhibited by the protein synthesis inhibitor Cycloheximide, but was unaffected by the DNA synthesis inhibitor Mitomycin C. Murine supernatants were active on human monocytes and vice‐versa. A first preliminary characterization of the chemotactic activity of the human sarcoma line 8387 revealed that it was not dialyzable, that most of the activity was retained at 56deg;C for 30 min, but not at 100deg;C, and that it was susceptible to proteolytic enzymes (trypsin and proteinase K) but unaffected by DNase and RNase. Upon fractionation on a Sephadex G‐75 column, the activity eluted in a single, relatively broad peak in the cytocrome C region, corresponding to an apparent molecular weight of about 12,000. In the heterogeneous series of murine solid tumors studied, a significant, though far from absolute, correlation (r=0.71, p=0.013) was found between chemotactic activity in culture supernatants (expressed as area under the chemotaxis titration curve) and the percentage of tumor‐associated macrophages. It is suggested that tumor‐derived chemotactic factor(s) play a role in the regulation of the macrophage content of neoplastic tissues.
Splenic variations affecting sarcomagenesis among mice of an inbred strain
Authors: Prehn Richmond T. , Karcher Christine A.
Published: February 2007

Among overtly identical mice of an inbred strain, some are relatively susceptible and some relatively resistant to sarcomagenesis by large concentrations of 3‐methyl‐cholanthrene (MCA) (Prehn, 1975a). Spleen cells from mice, subsequently shown to be relatively susceptible, conveyed a relative resistance to oncogenesis when transferred to irradiated recipients; spleen cells from mice, subsequently shown to be relatively resistant, conveyed to secondary hosts a relative susceptibility.
Natural host defence during oncogenesis. NK activity and dimethylbenzanthracene carcinogenesis
Authors: Ehrlich Rachel , Efrati Margalit , Malatzky Elinor , Shochat Lea , Eyal Aviva Bar , Witz Isaac P.
Published: February 2007

In this study we determined the effect of administering the chemical carcinogen dimethylbenzanthracene (DMBA) on NK activity mediated by murine splenocytes. The intragastric administration of six weekly l‐mg doses of DMBA to 2‐ to 3‐month‐old mice either following a pituitary graft or not, resulted in a tumor incidence which was higher than 60 %. The cellularity of the spleens decreased significantly after the third DMBA feeding and the NK activity of these spleens was selectively suppressed. There was no spontaneous reconstitution of the NK activity following cessation of DMBA treatment and during the entire tumor‐free period. The adoptive transfer of normal bone marrow, thymus or spleen cells did not restore NK activity in DMBA‐treated mice. The NK activity of DMBA‐fed mice could be augmented by interferon and by interferon inducers such as poly I:C and dsRNA from Us‐tilago virus. The effect of these biological response modifiers on NK activity was short‐lived but it was possible to restimulate this activity every 24h. Consecutive treatments of DMBA‐fed mice with poly I:C maintained a high level of NK activity for at least 3 weeks.
Liposome induction or enhancement of macrophage‐mediated cancer cell lysis
Authors: Jeannin Jean‐Fraņcois , Olsson Nils‐O. , Martin Françcois
Published: February 2007

Liposomes of different composition have been used to modify macrophage‐mediated destruction of syngeneic cancer cells through a modulation of membrane lipid content of macrophages and/or tumor cells. Dipalmitoylphos‐phatidylcholine (DPPC)1 liposomes induce cancer cell lysis by normal, non‐tumoricidal, peritoneal macrophages and enhance tumor cell destruction by BCG‐activated macrophages. This effect was produced by large and small unilamellar liposomes, which are in the 25,000 g supernatant of sonicated preparations. Addition of cholesterol or negative charges carried by dicetylphosphate supressed the effect of DPPC liposomes on macrophage‐mediated cytolysis. Enhancement of macrophage‐mediated tumor cell lysis was observed when both cancer cells and macrophages were incubated with DPPC liposomes, but not when macrophages and/or tumor cells were preincubated with liposomes prior to their coincubation. Liposomes did not promote the binding of the cancer cells to the macrophages. Liposomes could promote formation of phospholipid domains within the plasma membrane of both tumor cells and macrophages leading to the destruction of cancer cells through a temporary fusion with the macrophages.
In vivo generation and selection of variants with altered sensitivity to natural resistance (NR): A model of tumor progression
Authors: Chow Donna A. , Ray Manoranjan , Greenberg Arnold H.
Published: February 2007

The stability of a cloned murine tumor for sensitivity to NR was examined following growth in vivo in order to test the hypothesis that tumor progression proceeds through the generation and selection of variants. Clonal sensitivity to the [131l]‐dUrd elimination assay of NR was assessed for the L5178Y‐F9 tumor grown in syngeneic DBA/2 mice or maintained solely in tissue culture. Sub‐clones derived from a tumor obtained from the injection site 31/2 weeks after the s.c. inoculation of 25 cells were less sensitive to NR in comparison with subclones derived from cells grown only in vitro. Subclones from the cells grown in vivo exhibited increased heterogeneity in sensitivity to NR in addition to their expanded range of susceptibility to complement‐mediated lysis by CBA serum natural antibodies. The extent of the heterogeneity argues against tumor “adaptation” forming the basis for the phenotypic alteration while chromosomal studies eliminate the possibility that a new tumor was induced. These data support the hypothesis that tumor progression proceeds through the random generation of variants and host‐mediated selection for the proliferation of clones with an increased ability to survive.
Clonal development of lymphomas induced by rauscher leukemia virus
Authors: Reddy A. Lakshma , Fialkow Philip J.
Published: February 2007

The number of cells from which tumors induced by neonatal injection of Rauscher Leukemia virus (RLV) develop was investigated using F1 (C57BL/6 X Feral) female mice heterozygous at the X‐linked phosphoglycerate kinase (PGK) locus. Because of inactivation of one of the two X chromosomes in each somatic cell which occurs during embryogenesis in female mice, only one of the two PGK genes is active in each somatic cell. Thus, tumors that develop clonally in these mice exhibit one enzyme type, B or A, whereas those with a multicellular origin may exhibit both enzymes. Seventeen of 22 PGK heterozygous mice injected with RLV developed lymphosarcomas after an average latency of 38 weeks. Twelve of these lymphomas exhibit a single‐enzyme type, A or B. In three of five tumors with double‐enzyme phenotypes, the minor enzyme component comprised 20% or less of the total PGK activity, and histological examination revealed that these tumors contained a mixture of malignant and normal‐appearing cells, suggesting that the minor PGK component was not contributed by the malignant cells. In the two remaining lymphomas, the ratio of A:B PGK activity was close to l:l. However, lymphomas which developed in recipients after transplantation of cells from these two tumors into newborn mice showed only single‐enzyme PGK phenotypes, suggesting that the neoplastic cells in the primary tumors had single‐enzyme phenotypes. Thus, these results indicate that lymphosarcomas induced by RLV in mice develop clonally.
Relationship between the amounts of EBV‐DNA and ebna per cell, clonability and tumorigenicity in two EBV‐negative lymphoma lines and their EBV‐converted sublines
Authors: Ernberg I. , Klein G. , Giovanella B. C. , Stehlin J. , McCormick K. J. , Andersson‐Anvret M. , Åman P. , Killander D.
Published: February 2007

The effect of EBV‐conversion of two EBV‐negative lymphoma lines (Ramos and BJAB) on agarose clonability and tumorigenicity in nude mice was explored. The cloning frequency was increased in all 9 sublines investigated, between I.I and 4.9 times compared to the original “parental” lines. Tumorigenicity was increased in one out of 2 BJAB‐derived, EBV‐positive lines and in 3 of 6 Ramosderived lines, while it was decreased in 3 others. A strong positive correlation between the number of genomes/cell and the amount of EBNA/cell was detected, and in 7 of 9 converted lines the cloning frequency also correlated to the number of EBV genomes. On the other hand, no relation was established between the number of EBV‐genomes/cell, the amount of EBNA/cell and tumorigenicity.