bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractA 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

AbstractPrevious 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

AbstractThis 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

AbstractChanges 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

AbstractAdult 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

AbstractThe 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

AbstractIn 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

AbstractThree 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

AbstractNanomolar 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

AbstractA 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

AbstractSpontaneously 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

AbstractWe 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

AbstractTwelve 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

AbstractHuman 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

AbstractSince 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

AbstractConditions 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.