RESUMO
Hyperthermic purging of leukemic cells has been applied in clinical trials, although an accurate evaluation system to compare the effect on leukemia cells with that on normal hemopoietic cells has not been established. We evaluated the heat-sensitivity of murine leukemia cells, MK-8057, and compared differences in heat-sensitivity between surviving fractions of leukemic stem cells (leukemic spleen colony-forming units, L-CFU-S) and normal hemopoietic stem cells (spleen colony-forming units, CFU-S). Using the spleen colony assay, the survival fraction of L-CFU-S was compared with that of CFU-S after various hyperthermic treatments. One of the most efficient conditions, that is, hyperthermia at 42 degrees C for 3 h, allowed only 0.17% of L-CFU-S to survive, whereas 26.5% of normal CFU-S survived. Hyperthermia at 44 degrees C for 45 min further reduced the L-CFU-S (0.13%); however, the relative ratio of L-CFU-S to CFU-S was less than that at 42 degrees C for 3 h, because there was a larger reduction at 44 degrees C in normal CFU-S (5.1%). Recipient mice injected with MK-8057 cells treated with hyperthermia survived longer in proportion to the decreasing number of surviving L-CFU-S injected. This extension of the survival of recipient mice given MK-8057 cells after hyperthermia was also proportional to the estimated survival fraction of L-CFU-S. The survival fraction of MK-8057 cells after hyperthermia that was independently calculated through the extended survival of the recipients showed a good correlation with the surviving fraction of L-CFU-S, seen as the leukemic spleen colonies, at a correlation coefficient of r = 0.985. The number of surviving mice receiving the post-hyperthermic MK-8057 cells and the number of L-CFU-S calculated to have been injected had a relationship based on a Poisson distribution. Thus, the calculated results imply that the hyperthermia proportionally targets L-CFU-S, which are the only cells responsible for killing the recipient mice.
Assuntos
Células-Tronco Hematopoéticas/patologia , Temperatura Alta/uso terapêutico , Leucemia Megacarioblástica Aguda/patologia , Células-Tronco/patologia , Animais , Divisão Celular/fisiologia , Linhagem Celular , Sobrevivência Celular/fisiologia , Células-Tronco Hematopoéticas/fisiologia , Injeções , Leucemia Megacarioblástica Aguda/fisiopatologia , Masculino , Camundongos , Baço/citologia , Baço/fisiologia , Células-Tronco/fisiologiaRESUMO
A complex of an independent L chain from anti-mesotetrakis (4-carboxyphenyl) porphyrin (TCPP) monoclonal antibody 13-1 and TCPP Fe(III) was designated as L-zyme and shown to exhibit high peroxidase activity and high optimal reaction temperature (90 degrees C). Heat denaturation study and circular dichroism (CD) spectra analysis suggested that refolded structure of 13-1 L chain exhibited significantly reduced inactivation rate after heat treatment. The secondary structure of 13-1 L chain changed slightly by the encapsulation of TCPP Fe(III) and the complex was found to be less thermostable than the L chain alone. Furthermore, by characterization of truncated forms of the L chain, it was revealed that the hydrophobic region (115-146) and hydrophilic region (147-189) in CL are important for thermostability and activity, respectively. Tertiary structure of L-zyme was predicted by AbM. Comparison of residues of L-zyme with those in the active centre of known structure of the peroxidase from Arthromyces ramosus (ARP) indicated that His38(CDR1), His94(CDR3), Arg96(CDR3) of L-zyme are important residues for peroxidase activity. Moreover, the steric arrangements of these residues in both L-zyme and ARP are similar, respectively. Distance between proximal His and distal His in L-zyme is 9.09 A, whereas that of ARP is 7.8 A.
Assuntos
Anticorpos Monoclonais/metabolismo , Cadeias Leves de Imunoglobulina/metabolismo , Peroxidases/metabolismo , Porfirinas/imunologia , Animais , Anticorpos Catalíticos/química , Anticorpos Catalíticos/genética , Anticorpos Catalíticos/metabolismo , Anticorpos Monoclonais/química , Anticorpos Monoclonais/genética , Estabilidade Enzimática , Escherichia coli/genética , Temperatura Alta , Cadeias Leves de Imunoglobulina/química , Cadeias Leves de Imunoglobulina/genética , Ferro/metabolismo , Camundongos , Modelos Moleculares , Estrutura Molecular , Peroxidases/química , Peroxidases/genética , Porfirinas/metabolismo , Conformação Proteica , Desnaturação Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Deleção de SequênciaRESUMO
The CD8+ T cell clone 5F1 produces interleukin 10 (IL-10) and interferon gamma(IFN-gamma) in response to stimulation with a peptide corresponding to region 142-149 of bovine alpha(s1)-casein (p142-149). Ninety analog peptides derived from p142-149 with single amino acid substitutions of putative T cell receptor contact residues were prepared to examine whether production of IL-10 and IFN-gamma by 5F1 can be altered by stimulation with these peptides. We found that some peptides triggered only IL-10 production whereas others induced production of IFN-gamma alone or both of these cytokines. Peptides inducing IFN-gamma production triggered both cytotoxicity and a proliferative response, whereas peptides inducing production of IL-10 but not IFN-gamma triggered neither of these responses. Our results clearly demonstrate that the signaling pathway required for IL-10 production in CD8+ T cells differs from that required for IFN-gamma production. The distinct cellular signals for IL-10 production appear to be independent of those for cytotoxicity and the proliferative response of CD8+ T cells.
Assuntos
Linfócitos T CD8-Positivos/fisiologia , Interleucina-10/biossíntese , Peptídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Caseínas/imunologia , Caseínas/isolamento & purificação , Bovinos , Feminino , Interferon gama/biossíntese , Camundongos , Camundongos Endogâmicos C57BL , Peptídeos/imunologia , Mutação Puntual , Subpopulações de Linfócitos TRESUMO
The cytotoxic properties of hyperthermia combined with cis-diammine-dichroloplatinum(II) (CDDP), and recently developed platinum complexes, (Glycolato-O-O')diammineplatinum(II) (254-S), cis-1-1-cyclobutane-dicarboxylate-(R)-2-methyl-1-4-butanediammine platinum(II) (NK-121), cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA), and (-)-R-[2-(aminomethyl)pyrrolodine](1,1- cyclobutanedicarboxylato)-platinum(II)monohydrate (DWA-2114R) were studied in vitro in monolayer cultures and multicellular spheroids of HMV-I human malignant melanoma cells. Hyperthermia at 44 degrees C for 30 min was applied during the latter part of 1 hr drug exposure. Cell survival was compared after drug treatments in cells exposed or not exposed to heat. Cytotoxicity was assessed by clonogenic assays. In exponentially growing monolayer cultures, marked hyperthermic sensitization was observed by each of the five platinum complexes studied. The dose modifying factors obtained were almost the same in these drugs. Unlike monolayer cells, the spheroids were appreciably different with regard to hyperthermic sensitization among platinum complexes. The order of the magnitude was as follows: CDDP, DWA-2114R, 254-S, CBDCA, and NK-121. In the low dose region, however, 254-S was the most thermally sensitized. These results suggest that the microenvironment factor within spheroids may significantly affect the cytotoxicity of platinum complexes combined with hyperthermia. On the basis of these findings using spheroids, CDDP, DWA2114R, and 254-S appear to be promising platinum complexes for use with hyperthermia clinically as far as hyperthermic sensitization is concerned.
Assuntos
Antineoplásicos/farmacologia , Temperatura Alta , Melanoma/patologia , Compostos Organoplatínicos/farmacologia , Radiossensibilizantes/farmacologia , Carboplatina/análogos & derivados , Carboplatina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Humanos , Células Tumorais CultivadasRESUMO
PURPOSE: To assess the relationship between large intracranial vessel occlusive vasculopathy (vasculopathy) and radiation therapy, and to clarify the clinical efficacy of magnetic resonance (MR) imaging in the diagnosis and screening of the vasculopathy. METHODS AND MATERIALS: We retrospectively evaluated the medical records and serial MR images for 32 pediatric patients, in whom radiation therapy had been given to fields including the circle of Willis and major cerebral arteries. All children had periodically undergone follow-up neurologic assessment and MR imaging examinations at Kanagawa Children's Medical Center for more than one year after radiation therapy (range 1.3-14 years). Patients who had not remained free of tumor progression up to the time of final evaluation were excluded. RESULTS: Vasculopathy developed in 6 of 32 patients 2-13 years after radiation therapy. Three of them presented with transient ischemic attacks (TIA) and the other three showed infarctions without preceding TIA. Steno-occlusive changes of major cerebral arteries were identified by MR imaging in all six patients, but not obtained in the remaining 26 patients. In the patients with TIA, MR imaging demonstrated steno-occlusive changes at the time of TIA, before irreversible infarction. They have been doing well subsequent to encephaloduroarteriosynangiosis. In the three patients who presented infarction without preceding TIA, MR imaging did not demonstrate the vascular change before the onset of infarction, and two of them developed neurologic deficits. The mean exposure dose for the circle of Willis and major cerebral arteries in these six patients was significantly higher than that in the remaining 26 patients without this sequela (61 Gy vs. 50 Gy, p < 0.05). The mean age at radiation therapy of the six patients was lower, but the difference was not significant. CONCLUSION: The incidence of vasculopathy after radiation therapy has a considerable correlation with radiation dose and age at radiation therapy. MR examination is useful for the diagnostic evaluation of vasculopathy, and it is also effective in screening for vasculopathy in patients with TIA, and may be helpful in the prevention of neurologic sequela.
Assuntos
Neoplasias Encefálicas/radioterapia , Artérias Cerebrais/efeitos da radiação , Infarto Cerebral/diagnóstico , Imageamento por Ressonância Magnética , Adolescente , Fatores Etários , Infarto Cerebral/etiologia , Criança , Pré-Escolar , Círculo Arterial do Cérebro/efeitos da radiação , Feminino , Humanos , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/etiologia , Angiografia por Ressonância Magnética , Masculino , Estudos RetrospectivosRESUMO
Using plateau phase C3H 10T1/2 cells, we studied the effect of multiple-dose irradiation on the repair capacity of cells after further irradiation. Cells were irradiated with repeated doses of 2.5 Gy delivered two fractions per day at 6 to 7 hours interval. The cell survival after exposure to 1 to 9 fractions was lower above 5 fractions as compared to that predicted by calculating from single dose survival curve by assuming that cells retain their capacity to repair radiation damage after each fraction. Repair kinetics experiments showed that cells were less able to repair potentially lethal damage after test dose following multiple dose irradiations. There was, however, no difference in the ability to repair sublethal damage and potentially lethal damage sensitive to anisotonic treatment in preirradiated and untreated cells. Thus, it would appear that an enhancement of the lethal expression of potentially lethal damage of three types of damage may, at least in part, contribute to the difference between the cell survival curve after multiple fractions and that predicted by calculation.
Assuntos
Sobrevivência Celular/efeitos da radiação , Doses de Radiação , Animais , Comunicação Celular/efeitos da radiação , Divisão Celular/efeitos da radiação , Raios gama , Camundongos , Camundongos Endogâmicos C3HRESUMO
The pharmacokinetics of TAK-802, a potential agent of amelioration for voiding dysfunction, were investigated in rats, dogs and monkeys after a single oral administration of 14C-labeled TAK-802. The values of the bioavailability for the compound ranged from 10.2 to 19.9% and the extent of absorption of 14C were higher than the values for the bioavailability in the tested animals. TAK-802 and its related compounds distributed widely in the tissues including the target organ, the urinary bladder, in rats. TAK-802 was highly bound to the plasma proteins and the protein-binding % was independent of the spiked concentrations in all the species tested. Meanwhile, the erythrocyte distribution decreased significantly with the increase in the TAK-802 concentrations. After oral dosing, the dosed 14C was predominantly excreted into the feces of the test animals and the hepato-biliary route mainly contributed to the excretion of 14C in rats. The major components of 14C in the plasma and excreta were unidentified polar metabolites in the test animals. These results indicated that TAK-802 was extensively metabolized by first-pass metabolism during the absorption process and its related metabolites were excreted predominantly into the feces via the bile in the test animals. The concentration-dependent erythrocyte distribution was characterized as the most influential property on the pharmacokinetics of TAK-802. For the clinical safety in the development of TAK-802, the effect of the concentration-dependent erythrocyte distribution on the pharmacokinetics of TAK-802 in animals and humans should be addressed.
Assuntos
Inibidores da Colinesterase/farmacocinética , Pirróis/farmacocinética , Quinolonas/farmacocinética , Animais , Bile/metabolismo , Cães , Eritrócitos/metabolismo , Macaca fascicularis , Masculino , Ratos , Ratos Sprague-Dawley , Distribuição TecidualAssuntos
Braquiterapia/métodos , Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Recidiva Local de Neoplasia/radioterapia , Adulto , Idoso , Neoplasias Encefálicas/cirurgia , Terapia Combinada , Feminino , Glioblastoma/radioterapia , Glioblastoma/cirurgia , Glioma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Oligodendroglioma/radioterapia , Oligodendroglioma/cirurgiaRESUMO
Short-term results of chemo-hyperthermia of gastric carcinoma were reported. Complete regression was noted in 15%, partial regression in 42% of cases.
Assuntos
Antineoplásicos/uso terapêutico , Hipertermia Induzida , Neoplasias Gástricas/terapia , Humanos , Mitomicina , Mitomicinas/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Tegafur/uso terapêuticoRESUMO
A mitochondrial cox3 gene in the alkane yeast, Yarrowia lipolytica, encodes a subunit-3 protein of cytochrome c oxidase, and contains a 1044 base-pair-long intron, as compared with the corresponding intronless gene in Saccharomyces cerevisiae. The intron belongs to a group I intron as determined by the cDNA sequence for the splicing sites as well as the predicted RNA secondary structure. Remarkably, this intron could code for a protein of 206 amino-acid residues which showed 63% similarity with an RNA maturase encoded by the second intron of the mitochondrial apocytochrome b gene in S. cerevisiae. Both introns occurred within the conserved exon sequence, 5'-TT(G/C)AGGTGC-3', suggesting the possible transposition of a common ancestral intron.
Assuntos
Apoproteínas/genética , Grupo dos Citocromos b/genética , DNA Mitocondrial/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Proteínas Fúngicas/genética , Genes Fúngicos , Saccharomyces cerevisiae/genética , Saccharomycetales/genética , Leveduras/genética , Sequência de Aminoácidos , Sequência de Bases , Sequência Conservada , Citocromos b , Primers do DNA , Endorribonucleases/genética , Íntrons , Substâncias Macromoleculares , Mitocôndrias/metabolismo , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Nucleotidiltransferases/genética , Reação em Cadeia da Polimerase , RNA/biossíntese , Splicing de RNA , RNA Fúngico/biossíntese , RNA Fúngico/química , RNA Mitocondrial , Saccharomyces cerevisiae/enzimologia , Saccharomycetales/enzimologia , Homologia de Sequência de Aminoácidos , Leveduras/enzimologiaRESUMO
Modulation of CD8(+) T-cell responses specific for an exogenous antigen by epitope variants would be advantageous to develop a novel means of antigen-specific immune regulation. We have analyzed CD8(+) T-cell responses to single amino acid-substituted variants of a peptide corresponding to residues 142-149 (p142-149; LAYFYPEL) of alphas1-casein, a major milk allergen, which is a dominant determinant restricted by H-2Kb. An analog peptide L142I with a substitution of Ile for Leu at the nonanchor N-terminal residue induced more IFN-gamma secretion than p142-149 from specific CD8(+) T cells. Furthermore, L142I could prime CD8(+) T cells more efficiently in vivo, and these L142I-primed cells secreted more IFN-gamma than p142-149-primed CD8(+) T cells upon stimulation with p142-149 in vitro. These findings are mainly explained by the greater ability of L142I to form stable Kb-peptide complexes. These findings indicate that appropriate analog peptides may be useful as efficient inducers of CD8(+) T cells which recognize the parent peptide and secrete IFN-gamma, a potent inhibitor of Th2-dependent events, including IgE production.
Assuntos
Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Caseínas/imunologia , Caseínas/farmacologia , Epitopos/imunologia , Interferon gama/biossíntese , Oligopeptídeos/imunologia , Oligopeptídeos/farmacologia , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/farmacologia , Sequência de Aminoácidos , Animais , Caseínas/metabolismo , Bovinos , Epitopos/metabolismo , Feminino , Antígenos H-2/imunologia , Antígenos H-2/metabolismo , Interferon gama/imunologia , Interferon gama/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Oligopeptídeos/síntese química , Fragmentos de Peptídeos/metabolismo , Homologia de Sequência de Aminoácidos , Estimulação QuímicaRESUMO
A case of an extra-abdominal desmoid tumor in a 17-year-old female is reported. At the time of the first examination, the tumor was found to already involve the floor of the mouth, the submandibular region, both sides of the neck, the anterior chest wall and the mediastinum and hence was considered inoperable. The patient was treated by external irradiation and interstitial irradiation (Ir and Au). The therapeutic response was very slow, becoming noticeable 4 months after completion of the therapy and lasting for more than a year. Experience in this case indicates that in order for radiotherapy to prove successful in the treatment of desmoid tumor, it must be administered in relatively high doses. Since desmoid tumors reportedly have the potential for sarcomatous transformation, a long-term follow-up seems to be necessary in the management of patients with this neoplasm. It is considered that inoperable extra-abdominal desmoid tumors are a good indication for radiation therapy.
Assuntos
Braquiterapia , Fibroma/radioterapia , Neoplasias das Glândulas Salivares/radioterapia , Neoplasias da Glândula Submandibular/radioterapia , Adolescente , Feminino , Fibroma/patologia , Humanos , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/radioterapia , Neoplasias do Mediastino/secundário , Neoplasias Bucais/patologia , Neoplasias Bucais/radioterapia , Neoplasias Bucais/secundário , Invasividade Neoplásica , Dosagem Radioterapêutica , Neoplasias da Glândula Submandibular/patologiaRESUMO
Six patients with carcinoma of the vulva and 3 with carcinoma of the vagina following radiation therapy for cancer of the cervix were analyzed. The interval between irradiation and diagnosis of the second tumor varied from 5 to 23 years. Despite the lack of having detailed information on irradiation factors in all patients, circumstantial evidence from this study suggests that radiation therapy may have contributed to the development of carcinoma of the vulva and vagina in some of the patients. Close follow-up patients treated for squamous carcinoma of the genital tract must emphasize inspection for new lesions. The incidences previously reported in the literature are also reviewed for comparison.
Assuntos
Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias do Colo do Útero/radioterapia , Neoplasias Vaginais/epidemiologia , Neoplasias Vulvares/epidemiologia , Idoso , Braquiterapia , Feminino , Humanos , Japão , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas , Dosagem RadioterapêuticaRESUMO
Mitochondrial gene organization was studied in a dimorphic yeast, Yarrowia lipoltica. The gene order in a sequenced 6.6-kilobase region closely resembles that of the human mitochondrial genome in that ATP synthase subunit 8 and 6 genes are followed by genes for cytochrome c oxidase subunit 3 (which contains an intron), NADH-ubiquinone oxidoreductase subunit 4, and ATP synthase subunit 9. This region also contains tRNA genes decoding AUA, UGA, CUN and CCN codons, suggesting a unique mitochondrial translation. All the above genes are transcribed from the same DNA strand into multigenic RNAs, starting from a nonanucleotide sequence, 5'-ATATAAATA-3', similar to other yeast mitochondrial promoters.
Assuntos
Genes Fúngicos , ATPases Translocadoras de Prótons/biossíntese , ATPases Translocadoras de Prótons/genética , Saccharomycetales/enzimologia , Saccharomycetales/genética , Transcrição Gênica , Leveduras/enzimologia , Leveduras/genética , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Códon , Primers do DNA , DNA Mitocondrial/isolamento & purificação , DNA Mitocondrial/metabolismo , Éxons , Íntrons , Substâncias Macromoleculares , Mitocôndrias/enzimologia , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Oligodesoxirribonucleotídeos , RNA/biossíntese , RNA/isolamento & purificação , RNA Mitocondrial , RNA de Transferência/química , RNA de Transferência/genética , Mapeamento por RestriçãoRESUMO
Multi-institutional studies on clinical hyperthermia of deep-seated tumours were undertaken using 8 MHz radiofrequency capacitive heating devices (Thermotron RF-8) at seven institutions. Each institute was designated to treat specific organs. This paper contains the accumulations of the results obtained at different institutions charged for different tumours. Deep-seated tumours in the lung, stomach, pancreas, liver, urinary bladder and rectum were treated. A total of 177 cases examined from January 1985 to December 1988 included 96 cases (54%) treated with radiotherapy plus hyperthermia, among which 14 cases were pre-operative. Of 177 cases, 81 (46%) were treated with chemotherapy plus hyperthermia. Complete response (CR) and partial response (PR) were obtained in 80% of the cases with lung cancer, 39% with stomach cancer, 56% with liver cancer, 35% with pancreas cancer, 71% with urinary bladder cancer, 100% with primary rectal cancer, and 47% with recurrent rectal cancer. Thermometry was performed using two techniques; one is direct measurement of intratumour temperature in lung and liver cancers, the other is indirect measurement of intracavitary temperature for stomach, pancreas, urinary bladder and rectal cancers. Intratumour temperatures were measured in 30 of the 43 tumours of the lung and liver. The maximum tumour temperature was greater than 42 degrees C in 23 (77%) of the 30 tumours. Intracavitary temperatures were measured in 133 (99%) of the 134 tumours of stomach, pancreas, urinary bladder and rectum. An intracavitary temperature greater than 42 degrees C was obtained in 98 (73.7%) of the 133 tumours. The contribution of hyperthermia in improving the quality of life of patients under terminal care was also investigated. It was indicated that hyperthermia was one of the most effective treatment techniques for advanced or inoperable cases. In this study local control rate (LCR) was mainly discussed because the period of follow-up was only 3 years. Side-effects were observed in 37 cases (21%); main side-effects were fatty induration, pain during treatment and burn. However, no side-effects were severe enough to interrupt therapy.
Assuntos
Temperatura Alta/uso terapêutico , Neoplasias/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Neoplasias Pancreáticas/terapia , Neoplasias Retais/terapia , Neoplasias Gástricas/terapia , Neoplasias da Bexiga Urinária/terapiaRESUMO
The combination therapy of urinary bladder cancer with radiation and hyperthermia with bleomycin was investigated. Immediately following daily external irradiation (40 Gy/4 weeks), patients were irrigated with a solution of warmed saline (intravesical temperature, 42-43 degrees C) containing 30 micrograms/ml bleomycin. Of a total of 56 patients, complete responses were observed in 25, and partial responses in 21. Among T2-T3 cases, an 84% response rate was noted in combination therapy, whereas a 56% response rate was observed after radiation alone (50-70 Gy). The side-effects of the combination therapy were limited to reversible bladder irritation, and bladder capacity could be maintained within normal limits. These results suggest that combination therapy represents an effective conservative therapy for the management of bladder cancer.
Assuntos
Bleomicina/administração & dosagem , Carcinoma de Células de Transição/terapia , Temperatura Alta/uso terapêutico , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Adulto , Idoso , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/radioterapia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Bexiga Urinária/efeitos da radiação , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/radioterapiaRESUMO
Feeding of a whole casein diet, which abolished the α(s1)-casein-specific proliferation and IFN-γ productivity of CD(4+) T cells, did not affect the proliferative response of CD8(+) T cells with regard to the antigen dose response, cell dose response, kinetics of the proliferation and epitope specificity, as well as IFN-γ production. To assess the characteristics of the CD8(+) T cells, we established α(s1)-casein-specific CD8(+) T cell clones from both casein-fed and control mice. The established clones produced different amount of IFN-γ and IL-10, and one clone derived from the casein-fed mice produced a remarkable amount of IL-10. The clones from casein-fed mice produced considerable amounts of TGF-ß, while those from control mice produced only small amounts. The possible role of CD8(+) T cells in oral tolerance is discussed.
RESUMO
alpha s1-Casein-specific CD8+ T cell clones expressed the interleukin (IL)-4 receptor, although they did not secrete detectable IL-4. We found that IL-4 significantly enhanced the secretion of interferon (IFN)-gamma by these CD8+ T cell clones. IL-4 also enhanced the secretion of IFN-gamma induced by stimulating the immobilized anti-CD3 antibodies of polyclonal CD8+ T cells which had been isolated from lymph nodes and were stimulated in vitro with the immobilized anti-CD3 antibody and IL-2. In addition, IL-4 added at the time of this first in vitro stimulation induced strong IFN-gamma productivity, as well as IL-4 and IL-10 productivity, which were detectable upon restimulation of these cells. Results are discussed in relation to the inhibitory effects of IFN-gamma production on IL-4-producing cells.
Assuntos
Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Caseínas/metabolismo , Interferon gama/metabolismo , Interleucina-4/farmacologia , Animais , Antígenos CD/efeitos dos fármacos , Antígenos CD/metabolismo , Complexo CD3/farmacologia , Linfócitos T CD8-Positivos/imunologia , Caseínas/farmacologia , Células Clonais , Feminino , Interferon gama/efeitos dos fármacos , Interleucina-2/farmacologia , Linfonodos/citologia , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Interleucina/efeitos dos fármacos , Receptores de Interleucina/metabolismo , Receptores de Interleucina-4RESUMO
A joint clinical trial of hyperthermia using a newly developed 8-MHz radiofrequency (RF) capacitive heating device (Thermotron RF-8; developed in cooperation with Yamamoto Vinyter Co. of Osaka) was performed under collaboration of seven institutions. Radiation with 4 Gy twice a week for a total of 40 Gy or 2 Gy five times a week for a total of 50 Gy was delivered. After irradiation, hyperthermia at 42.5 degrees C +/- 0.5 degree C for 40 to 60 minutes was given twice a week for a total of 10 times. Tumors examined in this trial were located in various depths in the body, and included those which were considered refractory to conventional treatments or radioresistant such as malignant melanoma and soft tissue tumors. Of the 63 tumors treated, 52.4% showed complete regression (CR); 19.0% more than 80% regression (PRa); 20.6%, 80% to 50% regression (PRb); and 8.0% no regression (NR). Our joint clinical trial demonstrated that hyperthermia with the use of the Thermotron RF-8 is safe and effective in the treatment of radioresistant tumors located in superficial, subsurface, and in some cases deep regions, if the surface cooling is properly managed by the temperature-controlled saline pad and electrodes of appropriate size are paired.