Lung injury elicited by a single intratracheal instillation of fibrogenic (quartz) and nuisance (anatase) dusts and/or weekly repeated instillation of CdCl2 solution combined with sinusoidal (50 Hz, 10 mT) magnetic field (MF) exposure was studied in male rats. Combined effects in bronchoalveolar lavage (BAL), rat lungs and regional lymph nodes after 4 months of MF exposure (1 h/5 days per week) were evaluated biochemically and by cytological and histopathological examination. Damage of cell membranes in the cell part of BAL due to MF exposure was not observed in the examined animal groups. Following MF exposure, decreased synthesis of collagen proteins (incorporation of [14C]proline) was demonstrated in lungs with quartz dust burden. Histological examination revealed differences in the lung tissue reaction suggesting the modification of the repair process due to MF exposure following experimental injury in both quartz and cadmium groups.

• MeSH
• alveolární makrofágy účinky léků   MeSH
• bronchoalveolární lavážní tekutina chemie   cytologie   MeSH
• chlorid kademnatý aplikace a dávkování   toxicita   MeSH
• elektromagnetická pole škodlivé účinky   MeSH
• intratracheální intubace MeSH
• křemen aplikace a dávkování   toxicita   MeSH
• krysa rodu Rattus MeSH
• lyzozomy účinky léků   enzymologie   MeSH
• plíce účinky léků   patologie   MeSH
• plicní fibróza etiologie   MeSH
• potkani Wistar MeSH
• prach MeSH
• titan aplikace a dávkování   toxicita   MeSH
• velikost orgánu účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chlorid kademnatý MeSH
• křemen MeSH
• prach MeSH
• titan MeSH
• titanium dioxide MeSH Prohlížeč

Experiments were designed to investigate a possible therapeutic role of interleukin-2 (IL-2) gene transfer in the model of murine (EL-4) leukaemia pretreated with cyclophosphamide. It has been found that i.p. pretreatment of the leukaemic mice with cyclophosphamide, followed by i.v. administration of irradiated cells, genetically engineered to produce IL-2 and used as a source of the cytokine (IR-IL-2 cells), cured a substantial percentage of the leukaemic mice. Neither treatment with cyclophosphamide nor administration of the IR-IL-2 cells alone had any significant therapeutic effect. Labelling of the EL-4 and IR-IL-2 cells with different fluorescent cell linkers followed by i.v. injection and detection of the labelled cells in cryostat sections of various organs has shown that both cell populations can be detected almost exclusively in the red pulp of the spleen, close to the white pulp nodules, thus providing the possibility of short-range local interactions among the IL-2-producing cells, IL-2-responsive defence effector cells and EL-4 leukaemia targets.

• MeSH
• cyklofosfamid farmakologie   MeSH
• experimentální leukemie terapie   MeSH
• genetická terapie * MeSH
• interleukin-2 účinky záření   terapeutické užití   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buňky kultivované MeSH
• technika přenosu genů MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cyklofosfamid MeSH
• interleukin-2 MeSH

The present study was designed to compare the tumour inhibitory effects of local therapy based on insertion of cloned IL-2, IL-4, or IL-6 genes into the genome of murine plasmacytoma X63-Ag8.653, followed by injection of the genetically modified cells to the vicinity of the parental plasmacytoma growing in syngeneic mice. It was also designed to investigate the effects of combined gene therapy with IL-2- and IL-6-producing plasmacytoma cells. It has been found that insertion of the IL-2 gene into the genome of X63-Ag8.653 cells can abrogate tumorigenicity of the transduced cells more effectively than insertion of the IL-4 or IL-6 gene. Peritumoral administration of the genetically modified plasmacytoma cells producing IL-6 (X63-h-IL-6) resulted in a therapeutic effect comparable with that of the IL-2-producing cells (X63-m-IL-2), whereas no substantial therapeutic effect of IL-4-producing cells (X63-m-IL4) was observed. The combined gene therapy with IL-2- and IL-6-producing cells did not give any additive or potentiated therapeutic effect.

• MeSH
• cytotoxicita imunologická MeSH
• genetická terapie * MeSH
• interleukin-2 genetika   terapeutické užití   MeSH
• interleukin-4 genetika   terapeutické užití   MeSH
• interleukin-6 genetika   terapeutické užití   MeSH
• interleukiny genetika   terapeutické užití   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nádorové buňky kultivované MeSH
• plazmocytom genetika   terapie   MeSH
• transfekce MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• interleukin-2 MeSH
• interleukin-4 MeSH
• interleukin-6 MeSH
• interleukiny MeSH

The present study was designed to examine the kinetics and function of peritoneal exudate cells (PEC) during local interleukin 2 (IL-2) gene therapy of the X63-Ag8.653 plasmacytoma growing in the peritoneal cavity. BALB/c mice were inoculated i.p. on day 0 with a tumorigenic dose of the syngeneic plasmacytoma and on day 1 with non-tumorigenic plasmacytoma cells carrying an inserted IL-2 gene and producing constitutively IL-2. At regular time intervals the experimental mice were sacrificed and their peritoneal exudate cells were used for phenotypic analysis and Cr-51 microcytotoxicity assay. On the first day after i.p. inoculation of the genetically modified plasmacytoma cells the percentage of Thy 1.2+, CD3+, TCR alphabeta+ T lymphocytes and NK+ cells in the peritoneal fluid dramatically increased. The levels of the positive cells continually decreased until day 11, when the values of normal, healthy mice were obtained. The percentage of Thy 1.2+ and CD3+ cells remained at these, or slightly lower values, until the end of the observation period. A similar, though more slowly descending kinetics was seen in the CD5+ cell population, whereas the CD8+ cells, compared to the controls, exhibited only a short-term peak between days 3 and 5, and the values of TCR alphabeta+ and NK+ cells exhibited a second peak between days 25 and 48. The percentage of TCR gammadelta+ cells showed a permanent, moderately elevated plateau from day 1 till the end of the observation period. In control, untreated mice, inoculated i.p. with the X63-Ag8.653 plasmacytoma, the kinetics of peritoneal exudate cells was different. A moderate, permanent elevation of all of the T and NK cell subsets examined occured during the observation period. In addition, the percentage of TCR alphabeta+, TCR gammadelta+ and NK+ cells further increased continually from day 11 till the end of the observation period. The cytolytic activity of the peritoneal exudate cells was examined in vitro concurrently with FACS phenotyping. Free tumour-specific killer cells generated in the peritoneal fluid due to the local IL-2 gene therapy were found only on day 6, and these cells were cytolytic for both, the parental X63-Ag8.653 and the genetically modified X63-m-IL-2 plasmacytoma cells.

• Publikační typ
• časopisecké články MeSH

Experiments were designed to compare the efficacy of recombinant IL-2 immunotherapy and IL-2 gene therapy of i.p. growing murine plasmacytoma X63-Ag8.653. The kinetics of peritoneal exudate mononuclear cells were monitored during the progression and gene therapy of the plasmacytoma, using cytofluorometric analysis and monoclonal antibodies against T and NK cell subsets. It has been found that the percentage of mice protected against plasmacytoma transplants was higher in mice treated by transfer of genetically manipulated IL-2-producing plasmacytoma cells as compared to the mice repeatedly injected with recombinant IL-2. Intraperitoneal inoculation of the X63-Ag8.653 plasmacytoma led in most of the inoculated mice to an increased percentage of NK+, ASGM1+, Thy 1.2+, CD3+ and TCR alpha beta+ cells in the peritoneal fluid. The presence of macroscopically detectable i.p. tumours was accompanied by a higher increase in the percentage of NK+ and TCR gamma delta+ cells. Local IL-2 gene therapy of the plasmacytoma either prevented or diminished an increase in the percentage of CD3+, Thy 1.2+ and TCR alpha beta+ lymphocytes.

• MeSH
• buněčná imunita MeSH
• buňky NK cytologie   MeSH
• genetická terapie metody   MeSH
• interleukin-2 genetika   terapeutické užití   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nádorové buňky kultivované MeSH
• plazmocytom imunologie   terapie   MeSH
• rekombinantní proteiny terapeutické užití   MeSH
• T-lymfocyty cytologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interleukin-2 MeSH
• rekombinantní proteiny MeSH

Local IL-2 administration prior to transplantation of murine sarcoma virus (MSV Harvey)-induced tumour MSVT2 provided a model of slowly growing tumours suitable for long-term investigation of the therapeutic efficacy of repeated IL-2 injection cycles. Challenge of mice with the dose of sarcoma cells, which was lethal for 20/20 untreated control recipients, revealed that 8/20 IL-2-pretreated mice were protected by the local IL-2 treatment and survival indefinitely. Nine out of twenty IL-2-pretreated mice died during the same time period as the control mice, i.e., during 36 days, and 3/20 IL-2 pretreated mice were tumour-negative until day 60, when incipient tumours arose. The three late tumours were used as a model to investigate the therapeutic efficacy of the new cycles of repeated local IL-2 administration. It was found that no resistance to IL-2 immunotherapy was induced by pretreatment of the late tumours and that the tumours were repeatedly susceptible to local IL-2 treatment. Spleen cells of the tumour-bearing mice, which were not cytotoxic for MSVT2 tumour cells in vitro, could be made cytotoxic by addition of exogenous IL-2.

• MeSH
• buňky K aktivované lymfokiny imunologie   MeSH
• cytotoxicita imunologická účinky léků   MeSH
• experimentální sarkom imunologie   terapie   MeSH
• inbrední kmeny myší MeSH
• infekce onkogenními viry imunologie   terapie   MeSH
• injekce subkutánní MeSH
• interleukin-2 aplikace a dávkování   terapeutické užití   MeSH
• Moloneyho virus myšího sarkomu * MeSH
• myši MeSH
• protinádorové látky aplikace a dávkování   terapeutické užití   MeSH
• retrovirové infekce imunologie   terapie   MeSH
• rozvrh dávkování léků MeSH
• slezina imunologie   MeSH
• transplantace nádorů MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interleukin-2 MeSH
• protinádorové látky MeSH

It has been previously found that local administration of Balb/c plasmacytoma cells transformed and made non-tumorigenic by insertion of the cloned murine interleukin-2 (IL-2) gene induced regressions of a variety of murine tumours including the original Balb/c plasmacytoma X63-Ag8.653 growing in syngeneic mice. The tumour-inhibitory effect of the plasmacytoma cells transformed by IL-2 cDNA and designated as X63-m-IL-2 was due to their high constitutive production of IL-2. Here we show that admixture of syngeneic spleen cells to the X63-m-IL-2 transformants substantially (P < 0.025) increased the antitumour efficacy of the transformants. Balb/c spleen cells co-cultivated with X63-m-IL-2 cells in vitro yielded predominantly Thy 1.2+, CD3+, LFA-1+ lymphocytes, cytolytic for the X63-Ag8.653 plasmacytoma as well as for other murine tumours, including the X63-m-IL-2 target cells.

• MeSH
• buňky NK účinky léků   fyziologie   MeSH
• DNA genetika   MeSH
• imunoterapie * MeSH
• interleukin-2 biosyntéza   genetika   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nádorová transformace buněk genetika   MeSH
• nádorové buňky kultivované MeSH
• nádory terapie   MeSH
• plazmocytom genetika   MeSH
• slezina cytologie   imunologie   MeSH
• transfekce * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA MeSH
• interleukin-2 MeSH

• MeSH
• interleukin-2 * MeSH
• lidé MeSH
• protinádorové látky * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• interleukin-2 * MeSH
• protinádorové látky * MeSH

It has been previously found that local administration of X63-m-IL-2 cells transformed by interleukin 2 (IL-2) cDNA and constitutively producing large quantities of IL-2 mediated regressions of murine plasmacytomas and 3-methyl-cholanthrene-induced sarcomas transplanted in syngeneic mice. Here we show that killer cells generated by cultivation of spleen cells in supernatants from X63-m-IL-2 cultures (LAK) or by co-cultivation of murine splenocytes with X63-m-IL-2 cells were cytolytic for natural killer (NK)-sensitive as well as NK-resistant target cells, including the IL-2-producing X63-m-IL-2 cells. Spleen cells cultured in X63-m-IL-2 supernatants or co-cultivated with X63-m-IL-2 cells yielded predominantly Thy 1.2+, CD3+, LFA-1+ lymphocytes. The in vitro results suggest that the LAK cells generated due to the IL-2 production by genetically engineered cells probably help to terminate the treatment by killing the IL-2 producers.

• MeSH
• aktivace lymfocytů * MeSH
• buněčné linie MeSH
• buňky K aktivované lymfokiny imunologie   MeSH
• cytotoxicita imunologická * MeSH
• DNA genetika   MeSH
• imunofenotypizace MeSH
• interleukin-2 biosyntéza   genetika   MeSH
• kultivované buňky MeSH
• myši MeSH
• průtoková cytometrie MeSH
• slezina imunologie   MeSH
• transfekce * MeSH
• transformované buněčné linie MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA MeSH
• interleukin-2 MeSH

Insertion of functional interleukin-2 (IL-2) gene into a plasmacytoma cell line X63-Ag8.653 substantially reduced tumorigenicity of the resulting cloned cells, designated as X63-m-IL-2. Peritumoral administration of the X63-m-IL-2 cells, producing constitutively large quantities of IL-2, resulted in regressions of established X63-Ag8.653 plasmacytomas growing in the peritoneal cavity of syngeneic mice. In vitro activation of BALB/c spleen cells by co-culture with X63-m-IL-2 cells or their supernatants gave rise to cytotoxic lymphocytes with lymphokine-activated killer (LAK) activity against syngeneic X63-Ag8.653 plasmacytoma and other tumor targets. In contrast, peritumoral administration of X63-Ag8.653 cells carrying an inserted interleukin-4 (IL-4) gene (designated X63-m-IL-4 cells) and producing constitutively large quantities of IL-4 did not result in a therapeutic effect. Moreover, the admixture of the X63-m-IL-4 and X63-m-IL-2 cells substantially diminished the X63-m-IL-2 cell-mediated therapeutic effect. Similarly, IL-4-containing supernatants generated from X63-m-IL-4 cell cultures substantially diminished LAK activation by X63-m-IL-2 cell produced supernatants.

• MeSH
• aktivace lymfocytů MeSH
• buňky K aktivované lymfokiny účinky léků   imunologie   MeSH
• imunoterapie metody   MeSH
• interleukin-2 biosyntéza   genetika   terapeutické užití   MeSH
• interleukin-4 biosyntéza   genetika   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nádorové buňky kultivované MeSH
• plazmocytom imunologie   MeSH
• transfekce * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interleukin-2 MeSH
• interleukin-4 MeSH