RESUMO
We investigated the difference in relationship between muscle strength and quality of life (QOL)/fatigue in long-term cancer survivors and healthy subjects. Thirty-six cancer survivors and 29 healthy subjects were assessed for body composition and bone status at the calcaneus using the Osteo Sono Assessment Index. Muscle strength was evaluated via handgrip and knee extensor strength. Health-related QOL was assessed using the Medical Outcome Study 36-item Short-Form Health Survey. Fatigue was measured using the brief fatigue inventory. Cancer survivors exhibited lower QOL scores in the physical functioning, physical role function, bodily pain and general health domains (p < .05). Grip and knee extension muscle strength in cancer survivors was positively correlated with the physical function and bodily pain of QOL (p < .05). The usual fatigue subscale score was only significantly higher in cancer survivors than in healthy subjects (p < .05). However, there were no correlations between muscle strength and fatigue in cancer survivors. Our results showed that muscle strength was an important factor for improving QOL in cancer survivors. We believe that the findings of this study will be relevant in the context of planning rehabilitation for cancer survivors.
Assuntos
Sobreviventes de Câncer , Fadiga/fisiopatologia , Nível de Saúde , Força Muscular , Neoplasias/fisiopatologia , Qualidade de Vida , Adulto , Estudos de Casos e Controles , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
In this study, we investigated the differences in physical activity before and after transplantation, and the relationship between physical activity and physical function and health-related quality of life (QOL) in 30 patients who underwent allogeneic haematopoietic stem cell transplantation (allo-HSCT). Duration and intensity of physical activity were quantified using a three-dimensional accelerometer. Physical function was quantified by handgrip and knee-extensor strength, with the 6-minute walk test (6MWT) used as a measure of exercise capacity. Health-related QOL was assessed using the 36-item Short-Form Health Survey. The proportion of daily activities performed at an intensity >3.0 metabolic equivalents (METs) increased significantly after allo-HSCT (p < .05). Daily activity time performed at an intensity of 1.6-2.9 METs significantly correlated only with left knee strength (p < .05). In contrast, the total number of daily steps and the proportion of activity performed at 1.6-2.9 METs and >3.0 METs were positively correlated with the 6MWT (p < .05). Additionally, physical functioning and general health subscales in health-related QOL positively correlated with daily activities performed at >3.0 METs (p < .05). Physical activity was associated with 6MWT and health-related QOL. These findings have implications for rehabilitation planning for patients undergoing allo-HSCT.
Assuntos
Exercício Físico/fisiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Adulto , Feminino , Força da Mão/fisiologia , Nível de Saúde , Humanos , Masculino , Força Muscular/fisiologia , Modalidades de Fisioterapia , Estudos Prospectivos , Qualidade de Vida , Transplante HomólogoAssuntos
Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/normas , Humanos , Kit de Reagentes para Diagnóstico , Padrões de Referência , Valores de ReferênciaRESUMO
OBJECTIVE: To assess the clinical negative predictive value (NPV) of multiparametric MRI (mp-MRI) for prostate cancer in a 5-year follow-up. MATERIALS AND METHODS: One hundred ninety-three men suspected of harboring prostate cancer with negative MRI findings were included. Patients with positive transrectal ultrasound (TRUS)-guided biopsy findings were defined as false-negative. Patients with negative initial TRUS-guided biopsy findings were followed up and only patients with negative findings by digital rectal examination, MRI, and repeat biopsy and no increase in PSA at 5-year follow-up were defined as "clinically negative". The clinical NPV of mp-MRI was calculated. For quantitative analysis, mean signal intensity on T2-weighted images and the mean apparent diffusion coefficient value on ADC maps of the initial MRI studies were compared between peripheral-zone (PZ) cancer and the normal PZ based on pathologic maps of patients who had undergone radical prostatectomy. RESULTS: The clinical NPV of mp-MRI was 89.6% for significant prostate cancer. Small cancers, prostatitis, and benign prostatic hypertrophy masking prostate cancer returned false-negative results. Quantitative analysis showed that there was no significant difference between PZ cancer and the normal PZ. CONCLUSION: The mp-MRI revealed a high clinical NPV and is a useful tool to rule out clinically significant prostate cancer before biopsy.
Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biópsia , Reações Falso-Negativas , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Ultrassonografia de IntervençãoRESUMO
This study aimed to investigate the safety and feasibility of physical therapy in cytopenic patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT), and to investigate the effect of physical therapy on physiological functions and quality of life (QOL) in allo-HSCT patients. The study cohort included 321 patients who underwent allo-HSCT. To investigate the safety and feasibility of physical therapy during cytopenia, patients were assigned to the physical therapy group (n = 227) or the control group (n = 94). To determine the effects of physical therapy, patients were divided according to the frequency with which they underwent physical therapy (n = 51 per group). Handgrip strength, knee extensor strength and a 6-min walk test were used as measures of physiological function. Short-Form 36 was used to assess QOL. The physical therapy group had higher rate of achieving engraftment and lower death rate than the control group (P < 0.05). After HSCT, the high-frequency physical therapy group showed significantly less decline than the low-frequency physical therapy group with respect to physical functioning of QOL (P < 0.01). Physical therapy is quite beneficial and can be performed safely and feasibly in cytopenic patients during allo-HSCT.
Assuntos
Neoplasias Hematológicas/reabilitação , Transplante de Células-Tronco Hematopoéticas , Pancitopenia , Modalidades de Fisioterapia/efeitos adversos , Adulto , Estudos de Coortes , Estudos de Viabilidade , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pancitopenia/etiologia , Qualidade de Vida , Transplante HomólogoRESUMO
AIM: To optimize low-kilovoltage (kV) computed tomography (CT) protocols using a hybrid iterative reconstruction (HIR) algorithm at 256-detector-row body CT. MATERIALS AND METHODS: Based on preliminary phantom studies, three different tube voltage protocols with an equal contrast-to-noise ratio (CNR) were developed. They were a conventional 120 kV protocol with filtered back-projection (FBP), an 80 kV protocol with HIR (a 160% increase in the tube current-time product and a 40% reduction in the contrast medium dose), and a 100 kV protocol with HIR (a 20% reduction in the tube current-time product and the contrast medium dose). The clinical study included 70 patients (34 women, 36 men; mean age 70.5 ± 9.1 years, range 44-92 years) who had undergone CT at 120 kV a mean of 148 ± 137 days before undergoing low kV contrast-enhanced body CT (80 kV with HIR, n = 35; 100 kV with HIR, n = 35). The estimated effective radiation dose (ED), image noise, and CNR were calculated and the visual image quality was scored on a four-point scale. RESULTS: Mean ED was 12.3, 8.4, and 15.4 mSv for the 80, 100, and 120 kV protocol, respectively, and significantly lower using the low kV protocols. There was no significant difference in the image noise and CNR between the low kV protocols with HIR and the 120 kV protocol with FBP, or in the visual scores among the three protocols. CONCLUSION: Without ensuing image-quality degradation, the radiation and contrast medium dose can be reduced with optimal contrast-enhanced CT protocols using a low kV technique and an HIR algorithm.
Assuntos
Algoritmos , Meios de Contraste/administração & dosagem , Iohexol/administração & dosagem , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Artefatos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagens de Fantasmas , Estatísticas não ParamétricasRESUMO
A 74-year-old female underwent surgical treatment for adenocarcinoma of the pancreatic head. Preoperative multi-detector row computed tomography (MD-CT) demonstrated tumor invasion into the accessory right colic vein and the branch of the middle colic artery (MCA), which was not detected by digital subtraction angiography. MD-CT showed anatomical variants in the left hepatic artery arising from the left gastric artery, and the right posterior hepatic artery arising from the superior mesenteric artery. Three-dimensional reconstruction CT generated a clear picture of the anatomy of the region concerned, which is essential for a safe operation. The MD-CT findings were highly consistent with the intraoperative findings. We have demonstrated that MD-CT is an important and highly accurate modality for pancreatic surgery.
Assuntos
Adenocarcinoma/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada Espiral , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Feminino , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgiaRESUMO
BACKGROUND AND PURPOSE: On diffusion-weighted imaging (DWI), metastatic tumors of the brain may exhibit different signal intensities (SI) depending on their histology and cellularity. The purpose of our study was to verify the hypotheses (1) that SI on DWI predict the histology of metastases and (2) that apparent diffusion coefficient (ADC) values reflect tumor cellularity. MATERIALS AND METHODS: We assessed conventional MR images, DWI, and ADC maps of 26 metastatic brain lesions from 26 patients, 13 of whom underwent surgery after the MR examination. Two radiologists performed qualitative assessment by consensus of the SI on DWI in areas corresponding to their enhancing portions. We measured the contrast-to-noise ratio (CNR) on T2-weighted images and normalized ADC (nADC) values, and compared them with tumor cellularity. RESULTS: The mean SI on DWI and the CNR on T2-weighted images were significantly lower in well differentiated than in poorly differentiated adenocarcinomas and lesions other than adenocarcinoma. The mean nADC value was significantly higher in well differentiated than poorly differentiated adenocarcinomas and lesions other than adenocarcinoma. All 3 small-cell carcinomas and 1 large-cell neuroendocrine carcinoma exhibited high SI on DWI. The nADC value showed a significant inverse correlation with tumor cellularity. There was no significant correlation between the CNR and tumor cellularity. CONCLUSION: The SI on DWI may predict the histology of metastases; well differentiated adenocarcinomas tended to be hypointense, and small- and large-cell neuroendocrine carcinomas showed hyperintensity. Their ADC values reflect tumor cellularity.
Assuntos
Neoplasias Encefálicas/secundário , Imagem de Difusão por Ressonância Magnética , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/secundário , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/secundário , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/secundário , Núcleo Celular/patologia , Meios de Contraste , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/secundário , Feminino , Previsões , Humanos , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeAssuntos
Carcinoma de Células em Anel de Sinete/diagnóstico , Neoplasias do Colo/diagnóstico , Colonoscopia , Adulto , Biópsia , Carcinoma de Células em Anel de Sinete/patologia , Neoplasias do Colo/patologia , Diagnóstico Diferencial , Feminino , Humanos , Mucosa Intestinal/patologia , Estadiamento de NeoplasiasRESUMO
Two experiments were conducted to determine effects of Juzen-taiho-to on endometrial carcinogenesis in mice. In the first experiment, Juzen-taiho-to treatment (2 weeks) decreased the levels of estradiol-17beta (E(2))-stimulated expression of c-fos/jun mRNA and their oncoproteins, determined by reverse transcription-polymerase chain reaction and Southern blot analysis, and the immunohistochemical method, in the uteri of ovarectomized mice. For the second experiment, 93 female ICR mice were given N-methyl-N-nitrosourea (MNU) solution (1 mg/100 g body weight) and normal saline (as controls) into their left and right uterine corpora, respectively, and were divided into four groups. Group 1 was given a diet containing 0.2% Juzen-taiho-to and 5 p.p.m. E(2). Group 2 was given a diet containing 5 p.p.m. E(2) alone. Group 3 was given a diet containing 0.2% Juzen-taiho-to alone. Group 4 was kept on the basal diet alone and treated as a control. Juzen-taiho-to treatment significantly decreased incidences of the uterine endometrial atypical (P<0.01), complex (P<0.05) and simple hyperplasias (P<0.01), under estrogenic stimulation. It is suggested that Juzen-taiho-to has an inhibitory effect on E2-related endometrial carcinogenesis in mice, relevantly through suppression of estrogen-induced c-fos/jun-expression.
Assuntos
Anticarcinógenos/uso terapêutico , Carcinógenos , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias do Endométrio/induzido quimicamente , Neoplasias do Endométrio/prevenção & controle , Estradiol/metabolismo , Metilnitrosoureia , Animais , Southern Blotting , Peso Corporal/efeitos dos fármacos , Feminino , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos ICR , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Útero/metabolismoAssuntos
Antígeno CA-19-9/análise , Cistos/química , Doenças Renais Císticas/sangue , Adulto , Fatores Etários , Humanos , MasculinoRESUMO
Short and long-term experiments were designed to determine effects of danazol on estrogen-related endometrial carcinogenesis in mice. The short-term assays showed that danazol decreased expression levels of c-fos/jun mRNA and their oncoproteins induced by estradiol-17beta (E2). For the long-term assay, 85 female ICR mice were given N-methyl-N-nitrsourea solution into their uterine corpora. The animals were divided into three groups as follows: Group 1, E2-diet (5 ppm) plus danazol (2 mg/body (s.c.), every 4 weeks); Group 2, E2-diet alone, Group 3, basal diet alone. At 30 weeks, incidences of atypical and complex endometrial hyperplasia were significantly decreased by danazol-treatment. These results suggest that danazol has preventive effects on estrogen-related endometrial carcinogenesis in mice, through the suppression of estrogen-induced c-fos/jun-expression.
Assuntos
Danazol/uso terapêutico , Neoplasias do Endométrio/prevenção & controle , Antagonistas de Estrogênios/uso terapêutico , Administração Oral , Alquilantes/toxicidade , Animais , Neoplasias do Endométrio/induzido quimicamente , Neoplasias do Endométrio/metabolismo , Estradiol/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Imuno-Histoquímica , Metilnitrosoureia/toxicidade , Camundongos , Camundongos Endogâmicos ICR , Antígeno Nuclear de Célula em Proliferação/análise , Proteínas Proto-Oncogênicas c-fos/análise , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-jun/análise , Proteínas Proto-Oncogênicas c-jun/genética , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Útero/química , Útero/patologiaRESUMO
Chronic fatigue occurring in previously healthy children and adolescents is one of the most vexing problems encountered by pediatric practitioners. We report three cases, 11, 12 and 13-year-old children, with chronic fatigue syndrome (CFS). They initially developed a low grade fever and generalized fatigue, followed by sleep disturbance and psychosomatic symptoms, and their performance ability deteriorated. They were diagnosed as having CFS on the basis of criteria. To investigate the brain function in CFS patients, we examined the regional cerebral blood flow by single-photon emission-computed tomography (SPECT) with 111 MBq [123I]-iodoamphetamine (123I-IMP) or xenon-computed tomography (Xe-CT), and brain metabolic levels by MR spectroscopy (MRS). Blood flow, expressed as the corticocerebellar ratio (CCR), in the left temporal and occipital lobes was markedly lower in cases 2 and 3 than that in healthy subjects reported by another investigator. In case 1, however, blood flow in the left basal ganglia and thalamus was markedly higher than in healthy subjects. The MR spectroscopy (MRS) study revealed remarkable elevation of the choline/creatine ratio in the patients with CFS. None of our patients exhibited evidence of focal structural abnormalities on MRI. These findings suggest that the various clinical symptoms in CFS patients may be closely related to an abnormal brain function.
Assuntos
Síndrome de Fadiga Crônica/diagnóstico por imagem , Síndrome de Fadiga Crônica/metabolismo , Adolescente , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Circulação Cerebrovascular/fisiologia , Criança , Síndrome de Fadiga Crônica/fisiopatologia , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
PURPOSE: To identify features useful for differentiation between malignant and benign breast neoplasms using multivariate analysis of findings by MR imaging. MATERIAL AND METHODS: In a retrospective analysis, 61 patients with 64 breast masses underwent MR imaging and the time-signal intensity curves for precontrast dynamic postcontrast images were quantitatively analyzed. Statistical analysis was performed using a logistic regression model, which was prospectively tested in another 34 patients with suspected breast masses. RESULTS: Univariate analysis revealed that the reliable indicators for malignancy were first the appearance of the tumor border, followed by the washout ratio, internal architecture after contrast enhancement, and peak time. The factors significantly associated with malignancy were irregular tumor border, followed by washout ratio, internal architecture, and peak time. For differentiation between benignity and malignancy, the maximum cut-off point was to be found between 0.47 and 0.51. In a prospective application of this model, 91% of the lesions were accurately discriminated as benign or malignant lesions. CONCLUSION: Combination of contrast-enhanced dynamic and postcontrast-enhanced MR imaging provided accurate data for the diagnosis of malignant neoplasms of the breast. The model had an accuracy of 91% (sensitivity 90%, specificity 93%).
Assuntos
Neoplasias da Mama/diagnóstico , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Neoplasias da Mama/patologia , Distribuição de Qui-Quadrado , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Effects of Reiousan, a crude drug preparation consisting of bezoar and ginseng, on blood rheology were studied. Reiousan improved the deformability of rat erythrocytes exposed to hyperosmorality and treated with phenylhydrazine. The ATP depletion in erythrocytes, the polybrene-induced erythrocyte aggregation and the oxidation of low density lipoprotein were suppressed by Reiousan. Oral administration of Reiousan also improved the erythrocyte deformability in phenylhydrazine-treated rats and delayed the thromboembolic death induced by arachidonic acid in mice. These results suggest that Reiousan has an ameliorative effect on blood rheology related to "Oketsu" syndrome in Kampo diagnostics.
Assuntos
Circulação Sanguínea/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Panax , Plantas Medicinais , Trifosfato de Adenosina/sangue , Animais , Depressão Química , Agregação Eritrocítica/efeitos dos fármacos , Deformação Eritrocítica/efeitos dos fármacos , Eritrócitos/metabolismo , Humanos , Técnicas In Vitro , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Ratos , Ratos WistarRESUMO
Short- and long-term experiments were conducted to examine the effects of Glycyrrhizae radix (Gl radix) extract on mouse endometrial carcinogenesis. Gl radix treatment (2 weeks) decreased the levels of c-fos/jun mRNA and the corresponding oncoproteins induced by estradiol-17 beta (E2) in castrated mice uteri, as determined by reverse transcription-polymerase chain reaction and Southern blot analysis, and immunohistochemical methods, respectively. For the long-term assays, 98 female ICR mice were given N-methyl-N-nitrosourea (MNU) solution (1 mg/100 g body wt.) and normal saline (as controls) into their left and right uterine corpora, respectively. They were divided into four groups as follows: group 1 was given 0.625% Gl radix- and 5 ppm E2-containing diet; group 2, 5 ppm E2-containing diet; group 3, 0.625% Gl radix-containing diet; and group 4, the basal diet alone. Gl radix treatment significantly decreased uterine weights and the incidences of uterine endometrial atypical hyperplastic and malignant lesions. It is suggested that Gl radix has inhibitory effects on E2-related endometrial carcinogenesis in mice, through suppression of estrogen-induced c-fos/jun-expressions.
Assuntos
Anticarcinógenos , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias do Endométrio/prevenção & controle , Fitoterapia , Plantas Medicinais/uso terapêutico , Animais , Testes de Carcinogenicidade , Neoplasias do Endométrio/induzido quimicamente , Neoplasias do Endométrio/metabolismo , Estrogênios , Feminino , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos ICR , Proteínas Oncogênicas v-fos/metabolismo , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-jun/metabolismoRESUMO
BACKGROUND AND PURPOSE: Although abnormal hyperintensities are frequently observed at or around the optic radiation in elderly subjects, no previous reports have mentioned the clinical significance and pathologic changes of these hyperintensities. We evaluated the hyperintensity patterns of the optic radiation and its surrounding structures on T2-weighted MR images and compared these findings with pathologic observations and visual field measurements. METHODS: High-resolution coronal T2-weighted MR images of 102 consecutive patients (51-84 years old) were evaluated retrospectively for the presence and morphology of hyperintensities of the optic radiation (204 sides) and its surrounding structures. Pathologic specimens were obtained from 25 other patients (60-91 years old) who had died of nonneurologic causes. The histopathologic changes of the optic radiation and its surrounding structures were evaluated and correlated with the MR findings. Finally, MR findings and visual field measurements were correlated in 46 elderly volunteers (70-91 years old). RESULTS: Hyperintensities of the optic radiation or its surrounding structures or both were observed on 125 sides (93%) of 67 patients (61%), and linear/laminar hyperintensity of the optic radiation and the tapetum was the characteristic finding. Eleven (44%) of 25 pathologic specimens exhibited pallor of three anatomic layers (the external sagittal stratum or the optic radiation, the internal sagittal stratum, and the tapetum). No subjects with hyperintensity of the optic radiation had visual field abnormalities. CONCLUSION: Linear/laminar hyperintensity of the optic radiation and tapetum on T2-weighted images is common in elderly subjects, and may reflect differences in the internal structures and in the water content of three anatomic structures. Hyperintensities of this region did not cause visual field abnormalities in a group of elderly volunteers.
Assuntos
Envelhecimento/fisiologia , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Vias Visuais/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nervo Óptico/fisiologia , Campos Visuais/fisiologiaRESUMO
Recent studies of intracellular signal transduction mechanisms for the transforming growth factor-beta (TGF-beta) superfamily have focused on Smad proteins, but have paid little attention to mitogen-activated protein (MAP) kinase cascades. Here we demonstrate that growth/differentiation factor-5 (GDF-5), but neither bone morphogenetic protein-2 (BMP-2) nor TGF-beta1, fully promotes the early phase of the chondrogenic response by inducing cellular condensation followed by cartilage nodule formation in a mouse chondrogenic cell line, ATDC5. We investigated which, if any, of the three major types of MAP kinase plays a functional role in the promotion of chondrogenesis induced by GDF-5. GDF-5 induced phosphorylation of p38 MAP kinase and extracellular signal-regulated kinase (ERK) but not that of c-Jun N-terminal kinase (JNK). The phosphorylation of p38 MAP kinase was also induced by BMP-2 and TGF-beta1. An inhibitor of p38 and p38 beta MAP kinase, SB202190, showed complete inhibition of cartilage nodule formation but failed to affect alkaline phosphatase (ALP) activity induced by GDF-5. Expression of the type II collagen gene, a hallmark of chondrogenesis in vertebrates, was also induced by GDF-5 treatment and strongly suppressed by SB202190. On the other hand, although an inhibitor of MAP/ERK kinase, PD98059, inhibited the rapid phosphorylation of ERK by GDF-5, it inhibited neither ALP activity nor cartilage nodule formation induced by GDF-5. These results strongly suggest that the p38 MAP kinase cascade is involved in GDF-5 signaling pathways and that a role of the p38 MAP kinase pathway is necessary over a longer period to promote chondrogenesis in ATDC5 cells.
Assuntos
Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Condrogênese/efeitos dos fármacos , Substâncias de Crescimento/farmacologia , Quinases de Proteína Quinase Ativadas por Mitógeno , Proteínas Quinases Ativadas por Mitógeno , Fosfatase Alcalina/metabolismo , Animais , Proteína Morfogenética Óssea 2 , Proteínas Morfogenéticas Ósseas/farmacologia , Proteínas Quinases Dependentes de Cálcio-Calmodulina/antagonistas & inibidores , Carcinoma Embrionário , Cartilagem/efeitos dos fármacos , Cartilagem/metabolismo , Diferenciação Celular/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Colágeno/genética , Relação Dose-Resposta a Droga , Indução Enzimática/efeitos dos fármacos , Fator 5 de Diferenciação de Crescimento , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno , MAP Quinase Quinase 1 , Camundongos , Fosforilação/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/farmacologia , Células Tumorais Cultivadas , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
201Tl-SPECT was performed to diagnose the malignancy of bone and soft tissue tumors by visual and quantitative assessment in 48 patients (17 malignant lesions and 31 benign lesions). SPECT images were obtained in the early phase (15 min after injection) and the delayed phase (240 min). By visual assessment a tumor was considered malignant if high accumulation was found in the tumor in the early phase and the accumulation was confirmed in the delayed phase. Tumors which did not meet these criteria were considered benign. For quantitative assessment, the ROI (region of interest) accumulation ratios of the tumor to the contralateral normal tissue in the early phase (ER) and in the delayed phase (DR), the ROI accumulation ratio of the delayed phase to the early phase of the tumor (Td/Te), and the ROI accumulation ratio of the delayed phase to the early phase of the contralateral normal tissue (Nd/Ne) were obtained. Sixteen patients with malignant tumors each had a high accumulation each but 12 of 31 benign lesions had no high accumulation on visual assessment. Furthermore, the accuracy was 85.4%, sensitivity 94.1%, and specificity 80.6%. Quantitative assessment was performed for 36 cases of high accumulation. The ER of malignant and benign lesions was 5.51 +/- 3.73 and 2.75 +/- 2.17, respectively, and the ER of malignant lesions was significantly higher than that of benign lesions. The DR did not demonstrate a significant difference. If the tumor having an ER greater than 3.9 was assumed to be malignant, the accuracy for differentiating malignant lesions from benign lesions was 85.4%. The Td/Te of benign lesions (0.97 +/- 0.28) was higher than that of malignant lesions (0.77 +/- 0.09). The Nd/Ne of normal tissue which contained muscles in both lesions were higher than 1.4. In conclusion, 201Tl-SPECT was very useful for the differential diagnosis of benign or malignant bone and soft tissue tumors. The ER was important for quantitative assessment, but a delayed image was necessary for visual assessment.
Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias de Tecidos Moles/diagnóstico por imagem , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cintilografia , Radioisótopos de TálioRESUMO
We performed molecular biological studies as well as immunohistochemical analysis of three cases of giant cell carcinoma of the pancreas. Histologically, one case was a pleomorphic giant cell carcinoma consisting of pleomorphic giant/ small cells and spindle cells, one an osteoclast-like giant cell tumor composed of osteoclastoid giant cells and pleomorphic small cells, and one a pleomorphic giant cell carcinoma with osteoclastoid giant cells. Immunohistochemically, pleomorphic giant cells and small pleomorphic cells were positive for epithelial and mesenchymal markers throughout the cases. Osteoclastoid cells were strongly positive for PG-M1 (CD68), but negative for lysozyme and epithelial markers. Pleomorphic spindle cells showed the same immunoreactivity as pleomorphic giant/small cells. Genetically, all cases contained a mutation in the K-ras (codons 12, 13) oncogene, but neither p53 (exons 5-8) nor p16INK4 (exons 1, 2) gene mutations were found in any case. Furthermore, Loss of heterozygosity (LOH) of the p53, p161NK4. APC, and DPC4 gene loci was not found in any of the cases. Immunohistochemical study demonstrated this tumor to be of epithelial origin with mesenchymal differentiation. Genetically, initiation of the tumor is similar to that of usual ductal adenocarcinoma, but progression might be rather different. The peculiar histologic and biologic features of this tumor would be the result of changes in other functional genes.