RESUMO
BACKGROUND: CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) shows poor prognosis and frequent central nervous system (CNS) relapses under anthracycline-containing chemotherapy. The aim of this study was to determine the prognosis and CNS relapse incidence of CD5+ DLBCL in the rituximab era. PATIENTS AND METHODS: We analyzed 337 patients with CD5+ DLBCL who received chemotherapy with (R-chemotherapy group; n = 184) or without (chemotherapy group; n = 153) rituximab. RESULTS: No significant difference was found in clinical background comparisons between the two groups. In the R-chemotherapy group, 60% of the patients were older than 65 years at diagnosis. Both the complete response rate and overall survival (OS) were significantly better in the R-chemotherapy group (P = 0.0003 and P = 0.002, respectively). Multivariate analysis confirmed that chemotherapy without rituximab was associated with unfavorable OS. However, the probability of CNS relapse did not differ between the two groups (P = 0.89). The CNS relapse was strongly associated with short OS (P < 0.0001). In the R-chemotherapy group, 83% of patients who experienced CNS relapse had parenchymal disease. CONCLUSIONS: Our results indicate that rituximab improves the OS of patients with CD5+ DLBCL but does not decrease the CNS relapse rate. More effective treatments with CNS prophylaxis are needed for CD5+ DLBCL patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Antígenos CD5/metabolismo , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundário , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prednisona/administração & dosagem , Indução de Remissão , Estudos Retrospectivos , Rituximab , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagem , Adulto JovemRESUMO
We present here seven cases of idiopathic multicentric Castleman's disease (MCD) showing effusion at the initial clinical presentation. This series includes a high proportion of middle-aged and elderly females (5/7). Various autoantibodies were detected in six cases. Anemia (Hb < 10 g/dl) was detected in four cases, leukocytosis (WBC > 10 × 10(9)/l) in three and thrombycytopenia (<100 × 10(9)/l) in five. Positivity for C-reactive protein or elevated erythrocyte sedimentation rate was recorded in all seven cases. Elevated serum IgG level (>2000 mg/dl) was recorded in only three cases. Elevated serum interleukin-6 level was recorded in all four cases examined. At the onset of disease, four cases were associated with idiopathic thrombocytic purpura. During the course of disease, one case each was diagnosed as systemic sclerosis + Sjögren's syndrome (SJS) and SJS. Histologically, five lesions exhibited a mixed type of Castleman's disease, and one case each exhibited a hyaline-vascular type and plasma cell type. The non-neoplastic nature of the B-lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction. There were no human herpes type-8 virus-positive cells in any of the seven lesions. Good responsiveness to glucocorticoid therapy has been seen in all six cases treated. From a therapeutic perspective, it is important to discriminate this subtype of MCD.
Assuntos
Hiperplasia do Linfonodo Gigante , Exsudatos e Transudatos , Adulto , Idoso , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/imunologia , Hiperplasia do Linfonodo Gigante/patologia , Hiperplasia do Linfonodo Gigante/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de RemissãoRESUMO
Despite the outstanding results generally obtained with imatinib mesylate (IM) in the treatment of chronic myeloid leukemia (CML), some patients show a poor molecular response. To evaluate the relationship between steady-state trough plasma IM concentration (IM-C(min)) and clinical response in CML patients, we integrated data from six independent Japanese studies. Among 254 CML patients, the mean IM-C(min) was 1,010.5 ng/ml. Importantly, IM-C(min) was significantly higher in patients who achieved a major molecular response (MMR) than in those who did not (P = 0.002). Multivariate analysis showed that an MMR was associated with both age (odds ratio (OR) = 0.97 (0.958-0.995); P = 0.0153) and with IM-C(min) (OR = 1.0008 (1.0003-1.0015); P = 0.0044). Given that patients with IM-C(min) values >1,002 ng/ml had a higher probability of achieving an MMR in our large cohort (P = 0.0120), the data suggest that monitoring of IM levels in plasma may improve the efficacy of IM therapy for CML patients.
Assuntos
Povo Asiático , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/metabolismo , Piperazinas/farmacocinética , Piperazinas/uso terapêutico , Pirimidinas/farmacocinética , Pirimidinas/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzamidas , Estudos de Coortes , Feminino , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
This study was undertaken to establish reliable factors in order to identify chlamydial cervicitis among suspicious patients. Between January and December 2007, 406 patients who were suspected to have cervicitis due to clinical symptoms, were tested with polymerase chain reaction (PCR) for Chlamydia trachomatis (CT), vaginal pH and Nugent score (NS) in our University hospital and related clinics. During the same period, 67 patients who were diagnosed as having other sexually transmitted diseases (Neisseria gonorrhoeae (NG), Trichomonas vaginalis, Condyloma acuminatum and genital herpes) were also made to participate in this study. Eighty-nine women (22%) were positive for CT PCR. Bacterial vaginosis (BV)-positive women were tested positive for CT PCR (75/288), significantly higher than those without BV (6/66, P = 0.01). In addition, under 20-years old women were positive for CT PCR (24/57), significantly higher than those who were over 30 years old (16/113, P = 0.001). The proportion of patients with high NS (>7) in CT, NG and T. vaginalis cases were 75/89 (84.3%), 22/27 (81.5%) and 11/14 (78.6%), respectively. Whereas the high NS of the C. acuminatum and genital herpes groups were recorded at 7/14 (50%) and 4/12 (33.3%), respectively. Younger women with BV could be at a higher risk for STDs, especially for CT cervicitis.
Assuntos
Infecções por Chlamydia/diagnóstico , Chlamydia trachomatis/isolamento & purificação , Infecções Sexualmente Transmissíveis/diagnóstico , Cervicite Uterina/diagnóstico , Vaginose Bacteriana/diagnóstico , Adulto , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/microbiologia , Infecções por Chlamydia/fisiopatologia , Chlamydia trachomatis/classificação , Chlamydia trachomatis/genética , Feminino , Humanos , Concentração de Íons de Hidrogênio , Reação em Cadeia da Polimerase , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/etiologia , Infecções Sexualmente Transmissíveis/microbiologia , Cervicite Uterina/epidemiologia , Cervicite Uterina/microbiologia , Cervicite Uterina/fisiopatologia , Vagina/microbiologia , Vagina/fisiologia , Vaginose Bacteriana/epidemiologia , Vaginose Bacteriana/microbiologia , Adulto JovemRESUMO
The purpose of this study is to investigate the side effect in patients who survived for more than 5 years after initial treatment for invasive cervical cancer. Between January 1984 and December 1997, 341 patients underwent primary treatment for invasive cervical cancer. One hundred nine patients who underwent medical examinations at 5 years after primary treatment were reviewed. The patients were divided into three groups: radical surgery alone (group A), radiotherapy alone (group B), and radical surgery with postoperative radiotherapy (group C). Dysuria was seen in 8%, and positive catheterized urine culture was noted in about 20% of groups A and C. Hydronephrosis was seen in 2% and 9% of groups A and B, respectively. Colitis or ulcer detected by proctosigmoidoscopy was noted in 15%, 50%, and 43% of groups A, B, and C, respectively, frequently observed in radiotherapy group (P= 0.0029). Lymphocyst was still present in 6% of group A, and leg edema was noted in 14%, 6%, and 15% of groups A, B, and C, respectively. Long-standing abnormal findings including urinary and bowel complications were presented in this study. Periodic physical examination after treatment should be performed because complications existed over a long time.
Assuntos
Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Complicações Pós-Operatórias/epidemiologia , Lesões por Radiação/epidemiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Estudos de Coortes , Terapia Combinada/efeitos adversos , Feminino , Seguimentos , Humanos , Histerectomia/métodos , Imuno-Histoquímica , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidadeRESUMO
A case of Proteus syndrome is presented, in which severe hemihypertrophy of the left trunk and left lower extremity, scoliosis, endometriosis and huge bizarre-shaped body tumors were observed. Up to 22.6 kg of tumorous tissue was excised. This syndrome was first described in 1983. The name Proteus comes from a Greek mythical sea god who was able to change his body form freely. This syndrome has numerous features including hemihypertrophy, macrodactyly, various subcutaneous masses, scoliosis and other minor abnormalities. Although diagnostic criteria have been established for Proteus syndrome, which is very difficult to differentiate from other congenital hamartomatous syndromes, more case reports are needed to define such a rare disorder. Our patient is the 6th Japanese case in the English literature.
Assuntos
Síndrome de Proteu/patologia , Pele/patologia , Adolescente , Diagnóstico Diferencial , Feminino , HumanosRESUMO
Combination chemotherapy with paclitaxel and carboplatin every 4 weeks for 3 cycles was administered for recurrent glassy cell carcinoma of the uterine cervix in a 67-year-old Japanese female. The response rate was 56% under computed tomography (partial response). However, the effect was transient even with follow-up radiotherapy, and further cases need to be accumulated to determine a successful treatment modality.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/terapia , Neoplasias do Colo do Útero/terapia , Idoso , Carboplatina/uso terapêutico , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Nucléolo Celular/patologia , Núcleo Celular/patologia , Terapia Combinada , Citoplasma/patologia , Tubas Uterinas/cirurgia , Feminino , Humanos , Histerectomia , Excisão de Linfonodo , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/terapia , Ovariectomia , Paclitaxel/uso terapêutico , Radioterapia , Tomografia Computadorizada por Raios X , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologiaRESUMO
The object of this study was to determine the efficacy and safety of glycosylated recombinant human granulocyte colony-stimulating factor (rHuG-CSF; lenograstim) after combination chemotherapy consisting of ranimustine, vindesine, melphalan and prednisolone (MCNU-VMP). One hundred thirty-nine consecutive patients with newly diagnosed multiple myeloma (MM) were allocated at random to a lenograstim group (n = 70) or a placebo group (n = 69). Patients were treated with two cycles of MCNU-VMP, and either lenograstim (2 microg/kg daily, s.c.) or placebo was administered from the day neutrophils decreased to less than 1.000/microl and was discontinued when neutrophils exceeded 5,000/microl. The median duration of neutropenia (neutrophils under 1,000/microl) was significantly shorter for the lenograstim group than the placebo group (2 days vs 9 days in the first cycle; 1 day vs 13 days in the second cycle). The incidence of febrile neutropenia in the first cycle was significantly lower in the lenograstim group than in the placebo group (9.2% vs 30.4%). No life-threatening infections were observed in either group. The two cycles of MCNU-VMP therapy were completed in 90.8% of the patients, and a higher average relative dose intensity (ARDI; 0.94) was achieved in the lenograstim group. The tumor response rate of the lenograstim group (57.8%) was higher than that of the placebo group (43.1%), but the difference was not statistically significant (chi2 = 2.634, df = 1, P = 0.105). Lenograstim was well tolerated, and no unexpected adverse events occurred. Lenograstim proved effective in controlling chemotherapy-induced neutropenia in MM patients under MCNU-VMP therapy.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Neutropenia/tratamento farmacológico , Proteínas Recombinantes/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Distribuição de Qui-Quadrado , Método Duplo-Cego , Feminino , Humanos , Japão , Lenograstim , Masculino , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Compostos de Nitrosoureia/efeitos adversos , Prednisolona/efeitos adversos , Estatísticas não Paramétricas , Resultado do Tratamento , Vindesina/efeitos adversosRESUMO
Complete hydatidiform mole and coexistent fetus (CMCF) is a rare occurrence and is associated with an increased risk of persistent gestational trophoblastic diseases. The aim of this study was to reveal a potential risk factor and to determine optimum management of CMCF cases. Molar tissues are cytogenetically divided into two types, homozygous and heterozygous. The molar tissue of our case showed a 46, XY heterozygous complete mole. Genomic DNA was analyzed by the polymerase chain reaction using sets of unlabelled forward and Cy-5-labelled reverse primers for DNA marker loci. The patient developed persistent trophoblastic disease (PTD) with lung metastasis. Since 1980 there have been 13 reports (including our case) that cytogenetically revealed CMCF and clarified the clinical outcome. Nine of the 16 CMCF cases before 21 weeks of gestation and seven of the 12 CMCF cases after 22 weeks of gestation developed PTD. The incidence of PTD from CMCF was not related to the gestational age at termination or delivery. There were 10 case reports that analyzed the zygosity of a mole, heterozygous or homozygous. Two of six homozygous and three of four heterozygous moles in CMCF cases developed PTD. A heterozygous mole is thought to be a high risk factor for the incidence of PTD. Cytogenetic study is clinically useful for the optimum management of CMCF cases.
Assuntos
Mola Hidatiforme/diagnóstico , Adulto , Antineoplásicos/uso terapêutico , Gonadotropina Coriônica Humana Subunidade beta/sangue , DNA/análise , Feminino , Genótipo , Idade Gestacional , Heterozigoto , Humanos , Mola Hidatiforme/complicações , Mola Hidatiforme/genética , Cariotipagem , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Masculino , Metotrexato/uso terapêutico , Reação em Cadeia da Polimerase , Gravidez , Gravidez Múltipla , Tomografia Computadorizada por Raios X , Neoplasias Trofoblásticas/etiologia , Gêmeos , Ultrassonografia Pré-Natal , Neoplasias Uterinas/etiologiaRESUMO
The objectives of the present study were to evaluate whether a schedule-dependent pharmacokinetic and/or pharmacodynamic interaction exists between two sequences of docetaxel and doxorubicin administration and to determine the maximal tolerated dose (MTD) of this combination. Patients with chemotherapy-naïve metastatic or recurrent advanced breast cancer were enrolled. In the crossover design, tandem dose escalation of docetaxel and doxorubicin was performed. Docetaxel, in doses ranging from 50-70 mg/m2, was administered for 1 h by drip infusion either just before or after a 5-min bolus i.v. injection of doxorubicin at dosages from 40-50 mg/ m2. The sequence of drug administration was switched after the first course in each patient, and the sequence of drug administration thereafter depended on the patient's choice. Twenty-five patients were initially assessable for toxicity. The MTD in the sequence of doxorubicin after docetaxel was 40 and 50 mg/m2, respectively, with the dose-limiting toxicity of neutropenia. On the other hand, the MTD of the sequence of docetaxel after doxorubicin was 70 and 50 mg/m2, respectively. The dose-limiting toxicities in this sequence were neutropenia and diarrhea. Duration of grade 4 neutropenia in the sequence of docetaxel followed by doxorubicin was significantly longer than that in the alternate sequence (P = 0.0062). However, there was no difference in pharmacokinetic parameters of docetaxel, doxorubicin, and doxorubicinol between the two sequences. The sequence of 50 mg/m2 doxorubicin followed by 60 mg/m2 docetaxel is recommended for subsequent clinical trials for practical reasons.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Paclitaxel/análogos & derivados , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Taxoides , Adulto , Idoso , Análise de Variância , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Área Sob a Curva , Neoplasias da Mama/sangue , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Docetaxel , Relação Dose-Resposta a Droga , Doxorrubicina/farmacocinética , Doxorrubicina/toxicidade , Feminino , Humanos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neutropenia , Paclitaxel/farmacocinética , Paclitaxel/toxicidade , Fatores de TempoRESUMO
PURPOSE: RPR 109881A is a new semisynthetic taxoid compound that has a similar mechanism of action to docetaxel. The purpose of this phase I study was to characterize the maximum-tolerated dose (MTD), toxicity profile, pharmacokinetic profile, and antitumor effects of this agent. PATIENTS AND METHODS: Nineteen eligible patients with advanced solid tumors were enrolled. RPR 109881A was administered as a 1-hour intravenous infusion every 3 weeks at doses ranging from 15 to 75 mg/m(2). Pharmacokinetic evaluation was performed at the first cycle. RESULTS: Neutropenia (febrile neutropenia) and fatigue were dose-limiting toxicities at doses of 60 and 75 mg/m(2) and seemed to be dose-related. Both thrombocytopenia and anemia were infrequent. Nonhematologic toxicities were generally mild. Pharmacokinetic studies indicated that RPR 109881A plasma disposition was bi- or triphasic, with a high total plasma clearance, a large volume of distribution, and a long terminal half-life. The area under the concentration-time curve (AUC) and the peak concentration of RPR 109881A seemed to increase with increasing dose proportionally, suggesting linear pharmacokinetics. Urinary excretion over 48 hours was low, with a mean of 0.8 +/- 0.36% of the administered dose. A significant relationship existed between the percentage decrease of neutrophil counts and the AUC of RPR 109881A. Among 18 assessable patients, two partial and two minor responses were documented. CONCLUSION: RPR 109881A was found to be a well-tolerated and promising taxoid agent. The MTD was 75 mg/m(2), and the recommended dose for phase II study was 60 mg/m(2) as a 1-hour infusion every 3 weeks.
Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/farmacocinética , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Paclitaxel/efeitos adversos , Paclitaxel/farmacocinética , Taxoides , Adulto , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/análogos & derivadosRESUMO
BACKGROUND: Myxoid leiomyosarcoma is a rare variant of uterine sarcoma, exhibiting malignant biologic behavior despite the absence of cytologic atypia and of significant mitotic activity. CASE: A 20-year-old female was referred with a cystic pelvic mass. At laparotomy, the tumor, weighed 2,200 g and originating in the left lateral uterine wall, was removed. Microscopic examination revealed well-differentiated smooth muscle cells without atypia and with a few mitotic figures in the copious myxoid matrix, suggesting myxoid leiomyosarcoma. Three years following laparotomy, an irregular mass around the uterus was noted on sonographic examination, suggesting local recurrence. Two years and six months later, the second operation was performed, and a locally recurrent, multicystic tumor weighing 3,500 g was excised. The histopathology was similar to that of the primary tumor. Cytologic findings on imprint material from the tumor revealed a few isolated or sheet like small cells consisting of spindle and polygonal cells with round and oval nuclei. Cytologic atypia was also minimal. CONCLUSION: Myxoid leiomyosarcoma should be included in the differential diagnosis of smooth muscle neoplasia.
Assuntos
Leiomiossarcoma/patologia , Neoplasias Uterinas/patologia , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Laparotomia , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/cirurgia , Recidiva Local de Neoplasia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/cirurgiaRESUMO
To explore the pathogenesis in placental dysfunction and abruptio placentae, we analyzed the occurrence of placental cell apoptosis and the role of Fas and Fas ligand (L) in that process in an inflammatory placental dysfunction model of pregnant mice, using lipopolysaccharides (LPS). In the present study, Day 13 pregnant mice were injected i.p. with LPS (50 microg/kg) or saline as a control, and the placentas were isolated at various time points after the injection. Analysis of the isolated DNA in agarose-gel electrophoresis revealed a typical ladder pattern of bands consisting of 180-200 base pairs (bp), which is regarded as a hallmark of apoptosis. The intensity of the bands increased time-dependently, reaching a maximum level at 12 h after LPS injection. In accord with the biochemical data, histochemical analysis using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) revealed that nuclei positive for double-stranded DNA breaks were found in decidua, diploid trophoblasts in the basal zone, and spongiotrophoblasts. The number of positive nuclei was maximized at 12 h after LPS injection. As a next step, we investigated the possible involvement of Fas and Fas L in the induction of apoptosis of the placental cells after LPS injection. Western blot analysis indicated that LPS increased the expression of Fas and Fas L in the placenta by about 4-fold at 12 h and 18 h, respectively, after injection. The cells expressing Fas and Fas L were identified, using immunohistochemistry and nonradioactive in situ hybridization, as decidua, diploid trophoblasts in the basal zone, and spongiotrophoblasts. Furthermore, when the expression of 4-hydroxy-2-nonenal (HNE)-modified proteins was assessed to evaluate the relation of oxidative stress elicited by LPS to the induction of apoptosis, once again decidua, diploid trophoblasts in the basal zone, and spongiotrophoblasts were positive. Therefore, the placental dysfunction by LPS may be brought about by the Fas-mediated apoptosis of various placental cells in a paracrine/autocrine fashion, possibly under the influence of oxidative stress.
Assuntos
Apoptose , Lipopolissacarídeos/farmacologia , Glicoproteínas de Membrana/fisiologia , Placenta/citologia , Receptor fas/fisiologia , Aldeídos/farmacologia , Animais , Western Blotting , Reagentes de Ligações Cruzadas/farmacologia , DNA/análise , Proteína Ligante Fas , Feminino , Expressão Gênica , Hibridização In Situ , Marcação In Situ das Extremidades Cortadas , Glicoproteínas de Membrana/análise , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo , Gravidez , RNA Mensageiro/análise , Receptor fas/análise , Receptor fas/genéticaRESUMO
OBJECTIVE: To examine whether or not estrogens induced the expression of protein thiol/disulfide oxidoreductases such as protein disulfide isomerase (PDI), thioredoxin (Trx), Trx reductase, and glutaredoxin (Grx) in vascular endothelial cells. METHODS: The regenerative effects of the protein thiol/disulfide oxidoreductases, PDI, Trx and Grx, on oxidatively damaged proteins were assayed using H2O2-inactivated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a reporter enzyme. The induction of protein thiol/disulfide oxidoreductases and the accumulation of protein adducts generated by lipid peroxidation were examined by Western blotting in estrogen-treated bovine aortic endothelial cells (BAECs). RESULTS: Reduced PDI, Trx and Grx regenerated the H2O2-inactivated GAPDH in vitro. The levels of these protein disulfide oxidoreductases in BAECs were increased by pretreatment with 0.01-10 micromol/l 17beta-estradiol, the largest increase (about fourfold of the control) being found for PDI. Other sex hormones such as progesterone and testosterone did not affect the contents of these oxidoreductases in BAECs. 4-Hydroxy-2-nonenal (HNE)-protein adducts, which are generated by lipid peroxidation, were accumulated in BAECs exposed to paraquat, whereas the pretreatment of BAECs with 17beta-estradiol suppressed their accumulation. CONCLUSIONS: The estrogen-mediated induction of the protein thiol/disulfide oxidoreductases such as PDI, Trx, Trx reductase and Grx suggested a possible involvement of these oxidoreductases in the antioxidant protection of estrogen observed in the vascular system.
Assuntos
Antioxidantes/farmacologia , Endotélio Vascular/efeitos dos fármacos , Estradiol/farmacologia , Estresse Oxidativo , Oxirredutases , Proteína Dissulfeto Redutase (Glutationa)/biossíntese , Animais , Aorta , Bovinos , Células Cultivadas , Endotélio Vascular/metabolismo , Glutarredoxinas , Isomerases de Dissulfetos de Proteínas/metabolismo , Proteínas/metabolismo , Tiorredoxina Dissulfeto Redutase/metabolismo , Tiorredoxinas/metabolismoRESUMO
BACKGROUND: Cytologic findings of sarcoma botryoides were still equivocal because sarcoma botryoides of the uterine cervix is an extremely rare neoplasm, and few cases have been reported to date. CASE: A 17-year-old female was diagnosed with sarcoma botryoides of the uterine cervix. The entire vaginal canal was occupied with polypoid masses, which arose from the anterior lip of the uterine cervix, and the tumor was classified as group I (Intergroup Rhabdomyosarcoma Study). After wedge resection and six courses of combination chemotherapy, the tumor recurred in the same location of the cervix as the primary lesion. Touch smear of the polypoid mass formed loose clusters and also showed short spindle cells in a necrotic background. The nucleus of the tumor cells had a thin nuclear membrane, fine chromatin pattern and partly clear nucleolus, showing mild nuclear atypia. Immunohistochemically, some of the tumor cells showed positive staining for myoglobin and desmin. CONCLUSION: The cytologic findings of sarcoma botryoides of the female genital tract are typical features of nonepithelial malignant tumor. Immunohistochemical study is useful for the diagnosis of rhabdomyosarcoma.
Assuntos
Recidiva Local de Neoplasia/patologia , Rabdomiossarcoma Embrionário/patologia , Neoplasias do Colo do Útero/patologia , Adolescente , Biomarcadores , Feminino , Humanos , Imuno-Histoquímica , Rabdomiossarcoma Embrionário/metabolismo , Rabdomiossarcoma Embrionário/ultraestrutura , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/ultraestruturaRESUMO
Two groups of intermediate-to high-grade non-Hodgkin's lymphoma patients aged 65 years and over were enrolled in a dose-range study of CHOP therapy utilizing 5 doses (1/2, 7/12, 2/3, 5/6, full CHOP): 11 patients 65-79 years of age (group A) and 9 patients 80 years or older (group B). The patients were enrolled consecutively; the study was designed so that if 3 patients completed 3 cycles of CHOP on schedule without major problems, the next highest dose was administered. If 2 patients experienced any major problems during 6 cycles at a given dose, treatment was discontinued and the dose prior to that particular dose was regarded as the optimal dose. The 6 treatment cycles were completed by 3 of 3 (2/3 CHOP), 3 of 4 (5/6 CHOP), and 1 of 4 (full CHOP) group A patients; and by 3 of 3 (1/2 CHOP), 2 of 3 (7/12 CHOP) and 1 of 3 (2/3 CHOP) group B patients. The results indicated that the optimal doses for group A and B were five-sixths and seven-twelfths of the standard CHOP dose, respectively.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma não Hodgkin/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Humanos , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
The purpose of the present study was to investigate the correlation between tumor size and prognosis in stage IB and II cervical cancer and to elucidate the adequacy of new FIGO staging system for cervical cancer. The subjects included 128 patients with cervical cancer (stage IB = 86, IIA = 18, and IIB = 24) who had undergone radical hysterectomy. The largest tumor size of the pathology specimen was measured in two dimensions, and the correlation between tumor size and prognosis was investigated. In addition, tumor size of the pathology specimen was compared with the largest tumor diameter measured by MRI in stage IB cancers. Patients with a tumor size greater than 3 cm2 had a significantly worse 5-year survival rate (63%) when compared to those with tumor size no greater than 3 cm2 (96%) (P < 0.0001). Multivariate analysis revealed that independent prognostic factors were tumor size (P = 0.003) and lymph node metastasis (P = 0.015). By regression analysis, the largest tumor size of the pathology specimen was relatively well correlated with the largest tumor diameter by MRI in stage IB cancers; 3 cm2 of tumor size in the pathology specimen corresponded to 3.4 cm of tumor diameter by MRI. The adequacy of new FIGO staging system was considered relatively acceptable.
RESUMO
OBJECTIVE: To investigate the correlation between the development of low grade cervical intraepithelial neoplasia (LCIN) and human papillomavirus (HPV) infection in cases with long-term follow-up. STUDY DESIGN: Forty-three cases of LCIN were followed for more than five years with cytology, colposcopy and Vira Pap. Coexistence of HPV infection was sought using a simplified HPV detection kit, the Vira Pap method (Dot Blot hybridization). RESULTS: Regressive disease was noted in 21 cases, and persistent and progressive disease was noted in 22 cases. HPV DNA was negative in 81% (17 of 21) of regressive disease and positive in 55% (12 of 22) persistent and progressive disease. LCIN had disappeared in 17 (63%) of 27 cases negative for HPV DNA and was persistent or progressive in 12 (75%) of 16 cases positive for HPV DNA. CONCLUSION: The clinical course of LCIN correlates well with HPV infection.
Assuntos
Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções Tumorais por Vírus/epidemiologia , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Colposcopia , Sondas de DNA de HPV , DNA Viral/análise , Progressão da Doença , Feminino , Seguimentos , Humanos , Hibridização de Ácido Nucleico , Infecções por Papillomavirus/patologia , Infecções Tumorais por Vírus/patologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
Cadmium induces the expression of the 70 kDa heat shock protein (HSP70) and metallothionein (MT), both of which are considered to be associated with intracellular glutathione (GSH) metabolism in the cellular protection mechanism against cadmium-induced cellular injury. We determined the effects of N-acetyl-L-cysteine (NAC), which increases the intracellular GSH levels, on the induction of HSP70 and MT gene expression in a cultured cell line of human amniotic cells (WISH) exposed to CdCl2. The mRNA level of MT-II, a major isoform of MT genes, was more prominently increased than that of HSP70 when WISH cells were exposed to CdCl2 (5-15 microM, for 6 h). The treatment of WISH cells with 1.5 and 30 mM NAC for 2 h increased the intracellular GSH levels by 1.4- and 3.1-fold, respectively. Pretreatment of cells with 30 mM NAC significantly reduced both HSP70 and MT-II mRNA levels in the cells exposed to 50 microM CdCl2. This concentration of NAC also efficiently suppressed the cadmium-induced lethality. On the contrary, pretreatment with 1.5 mM NAC suppressed only the induction of HSP70 gene expression in the 50 microM CdCl2-treated cells, and did not inhibit the metal toxicity. However, this low concentration of NAC efficiently suppressed lipid peroxidation which was increased by 50 microM CdCl2. Furthermore, this low concentration of NAC also decreased the CdCl2-induced gene expression of HSP32 which represents a general response to oxidative stress. Taken together, NAC seems to have at least two concentration-dependent functions in WISH cells exposed to CdCl2; the low concentration of NAC can suppress the induction of HSP70 gene expression as well as the increase of lipid peroxidation via an antioxidant pathway, while the high concentration of NAC can suppress the induction of MT-II mRNA as well as cadmium-induced cell death. Our present data suggest that changes in intracellular redox status, as reflected by GSH concentration, have more important effects on the induction of HSP70 mRNA rather than that of MT-II mRNA in human amniotic cells exposed to cadmium.
Assuntos
Acetilcisteína/farmacologia , Cádmio/toxicidade , Proteínas de Choque Térmico HSP70/genética , Metalotioneína/genética , Acetilcisteína/administração & dosagem , Âmnio , Linhagem Celular , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Ten young adults (15-22 years of age) with acute lymphoblastic leukemia were treated with the protocol of internal medicine and pediatrics co-operative study group since 1989. All patients had complete remission within 5 weeks. Four of 6 patients of low risk group (less than 30,000/microliter of WBC count at diagnosis) and 1 of 4 patients of high risk group have continued the complete remission. Three patients relapsed in bone marrow (BM), and 2 patients in both BM and central nervous system (CNS). All patients could be treated without serious complications except for infection. We obtained the good results of treatment for the low risk group, but did not for the high risk group in this study. Little is known about acute lymphoblastic leukemia in young adults because these individuals are at the borderline age between internal medicine and pediatrics. Taken together with the psychologically distinct age of these patients, it is necessary to establish a closer relationship between internal medicine and pediatrics.