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1.
Kyobu Geka ; 62(9): 812-5, 2009 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-19670785

RESUMO

A 78-year-old man had non-small cell lung cancer (NSCLC) in the left upper lobe (squamous cell carcinoma, cT1N0M0). He preferred less invasive treatment and undertook stereotactic radiotherapy (SRT)[48 Gy/4 Fr] because his forced expiratory volume in 1 second percent (FEV1.0%) was 53.50%. The therapeutic effect was partial response and the adverse reaction was dermatitis (grade 1). Seven months after SRT, local recurrence was detected. The tumor was growing from 3 x 5 mm to 25 x 25 mm in size. Nine months after SRT, left upper lobectomy was performed successfully unaffected by SRT. He is doing well 14 months after the operation without any signs of recurrence. This case might help develop a new strategy for the treatment of stage I NSCLC. It is that patients with stage I NSCLC have SRT as 1st line treatment, and if local recurrence is observed after SRT, lobectomy may be performed.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/cirurgia , Pneumonectomia , Idoso , Humanos , Masculino , Técnicas Estereotáxicas
2.
Biochim Biophys Acta ; 1396(3): 242-4, 1998 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-9545571

RESUMO

A novel full-length human cDNA homologous to Glia Maturation Factor-beta (GMF-beta) gene was isolated. Sequence analysis of the entire cDNA revealed an open reading frame of 426 nucleotides with a deduced protein sequence of 142 amino acid residues. The deduced amino acid sequences of its putative product is highly homologous to human GMF-beta (82% identity) and named for GMF-gamma. Northern blot analysis indicated that a message of 0.9 kb long, but not 4.1 kb of GMF-beta, is predominantly expressed in human lung, heart, and placenta.


Assuntos
DNA Complementar/isolamento & purificação , Proteínas do Tecido Nervoso/genética , Homologia de Sequência de Aminoácidos , Sequência de Aminoácidos , Sequência de Bases , Northern Blotting , Encéfalo , Clonagem Molecular , Feto , Fator de Maturação da Glia , Humanos , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/isolamento & purificação , Especificidade de Órgãos/genética
3.
J Tissue Eng Regen Med ; 9(1): 24-30, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23165985

RESUMO

The authors aimed to repair and regenerate articular cartilage with layered chondrocyte sheets, produced using temperature-responsive culture dishes. The purpose of this study was to investigate the humoral factors produced by layered chondrocyte sheets. Articular chondrocytes and synovial cells were harvested during total knee arthroplasty. After co-culture, the samples were divided into three groups: a monolayer, 7 day culture sheet group (group M); a triple-layered, 7 day culture sheet group (group L); and a monolayer culture group with a cell count identical to that of group L (group C). The secretion of collagen type 1 (COL1), collagen type 2 (COL2), matrix metalloproteinase-13 (MMP13), transforming growth factor-ß (TGFß), melanoma inhibitory activity (MIA) and prostaglandin E2 (PGE2) were measured by enzyme-linked immunosorbent assay (ELISA). Layered chondrocyte sheets produced the most humoral factors. PGE2 expression declined over time in group C but was significantly higher in groups M and L. TGFß expression was low in group C but was significantly higher in groups M and L (p<0.05). Our results suggest that the humoral factors produced by layered chondrocyte sheets may contribute to cartilaginous tissue repair and regeneration.


Assuntos
Condrócitos/citologia , Imunidade Humoral/fisiologia , Membrana Sinovial/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho , Cartilagem Articular/citologia , Técnicas de Cultura de Células , Técnicas de Cocultura , Meios de Cultura , Dinoprostona/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Teste de Materiais , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Temperatura , Fator de Crescimento Transformador beta/metabolismo
4.
Int J Radiat Oncol Biol Phys ; 48(4): 1081-7, 2000 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11072166

RESUMO

PURPOSE: To determine the survival of pancreatic cancer patients treated with intraoperative radiotherapy (IORT) and/or external beam radiation therapy (EBRT) following macroscopically curative resection. METHODS AND MATERIALS: One hundred and thirty-eight patients with pancreatic cancer who had undergone potentially curative total or regional pancreatectomy between 1980 and 1997 were retrospectively analyzed. Among the 138 patients, 98 had a pathologically negative surgical margin and the remaining 40 patients had a positive surgical margin. The usual EBRT dose was 45-55 Gy with a daily fraction of 1.5-2.0 Gy. The median IORT dose was 25 Gy in a single fraction. RESULTS: The 2-year cause-specific survival rate of patients with pathologically negative surgical margins was 19%, and that of patients with positive margins was 4% (p < 0.005). Although the median survival time (MST) of patients with negative margins treated with IORT and EBRT was significantly longer than that of those treated with operation alone (17 vs. 11 months), no significant difference in survival curves was observed. In patients with positive surgical margins in peripancreatic soft tissue, the difference between the survival curve of patients treated with surgery alone and that of those treated with surgery and radiation therapy was borderline significant (p < 0.10). Patients receiving intraarterial or intraportal infusion chemotherapy had significantly improved survival rates compared with those who did not receive it (p < 0.05). CONCLUSION: Although the MST was longer in patients with negative margins receiving IORT and EBRT than in those receiving no radiation, improved long-term survival by IORT and/or EBRT was not suggested. In patients with positive margins, our results obtained by IORT/EBRT were encouraging. Randomized studies with much higher patient numbers are necessary to define the role of IORT in curatively resected pancreatic cancer.


Assuntos
Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Infusões Intra-Arteriais , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Pancreatectomia/métodos , Neoplasias Pancreáticas/mortalidade , Dosagem Radioterapêutica , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de Sobrevida
5.
Int J Radiat Oncol Biol Phys ; 48(1): 153-60, 2000 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-10924985

RESUMO

PURPOSE: We re-evaluated histopathological specimens of head and neck early-stage extranodal non-Hodgkin's lymphoma (NHL) using the revised European and American lymphoma (REAL) classification, and also investigated the relationship between the clinical characteristics and histopathological classification in an attempt to evaluate the usefulness of this new classification system in selecting treatment modalities. MATERIALS AND METHODS: Between 1979 and 1995, 117 patients with histologically confirmed stages I and II NHL of head-and-neck extranodal regions were treated. Of these patients, 110 specimens were available for re-evaluation. Sixty-four patients had Stage I, and 46 had Stage II diseases. All but 3 had received radiation therapy, and 59 patients were also treated with intensive combination chemotherapy. RESULTS: There were 32 extranodal marginal-zone B-cell lymphomas, 57 diffuse large B-cell lymphomas, 11 peripheral T/NK-cell lymphomas, and 10 others. The 5- and 10-year cause-specific survival rates for all patients were 72% and 62%, respectively. Patients with extranodal marginal-zone B-cell lymphoma or other low-grade B-cell lymphomas demonstrated higher survival rates than patients with other lymphomas. Patients with peripheral T/NK lymphomas showed the lowest survival rate. CONCLUSION: The REAL classification accurately indicated the prognosis of patients with NHL. These results suggest that appropriate treatment modalities can be selected using this classification.


Assuntos
Neoplasias de Cabeça e Pescoço/classificação , Linfoma não Hodgkin/classificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Linfoma de Células B/classificação , Linfoma de Células B/patologia , Linfoma de Células B/terapia , Linfoma Difuso de Grandes Células B/classificação , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Linfoma de Células T/classificação , Linfoma de Células T/patologia , Linfoma de Células T/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Taxa de Sobrevida
6.
Int J Radiat Oncol Biol Phys ; 51(1): 87-93, 2001 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-11516856

RESUMO

PURPOSE: To evaluate the outcome and adverse effects in patients with osteosarcoma treated with very high-dose definitive intraoperative radiotherapy (IORT), with the intention of saving the affected limb. METHODS AND MATERIALS: Thirty-nine patients with osteosarcoma in their extremities were treated with definitive IORT. The irradiation field included the tumor plus an adequate wide margin and excluded the major vessels and nerves. Forty-five to 80 Gy of electrons or X-rays were delivered. The median follow-up of the surviving patients was 124 months. RESULTS: The cause-specific and relapse-free 5-year survival rate was 50% and 43%, respectively. Distant metastasis developed in 23 patients; 19 died and 4 were alive for >10 years. Nine local recurrences were found 4-29 months after IORT in the affected limb. No radiation-induced skin reaction or nerve palsy was observed in the patients treated with X-rays. Experiments using phantoms also confirmed that the scatter dose was below the toxic level in the IORT setting with X-rays. CONCLUSIONS: Very high-dose definitive IORT combined with preventive nailing and chemotherapy appeared to be a promising quality-of-life-oriented alternative to treating patients with osteosarcomas in the extremities, although the problem of recurrences from the surrounding unirradiated soft tissue remains to be solved.


Assuntos
Neoplasias Ósseas/radioterapia , Extremidades , Osteossarcoma/radioterapia , Adolescente , Adulto , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Criança , Terapia Combinada , Feminino , Neoplasias Femorais/mortalidade , Neoplasias Femorais/patologia , Neoplasias Femorais/radioterapia , Humanos , Úmero , Ílio , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Dosagem Radioterapêutica , Tíbia , Resultado do Tratamento
7.
Int J Radiat Oncol Biol Phys ; 39(1): 39-49, 1997 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-9300738

RESUMO

PURPOSE: Clinical results of intraoperative radiotherapy (IORT) and/or external beam radiotherapy (EBRT) for both resectable and unresectable pancreatic cancer were analyzed. METHODS AND MATERIALS: Between 1980 and 1995, 332 patients with pancreatic cancer were treated with surgery and/or radiation therapy (RT). Of the 332 patients, 157 patients were treated with surgical resection of pancreatic tumor, and the remaining 175 patients had unresectable pancreatic tumors. Among the 157 patients with resected pancreatic cancer, 62 patients were not treated with RT, while 40 patients were treated with EBRT alone (mean RT dose; 46.3 Gy) and 55 patients with IORT (25.2 Gy) +/- EBRT (44.0 Gy). On the other hand, among the 175 patients with unresectable pancreatic cancer, 58 patients were not treated with RT, 46 patients were treated with EBRT alone (39.2 Gy), and the remaining 71 patients with IORT (29.3 Gy) +/- EBRT (41.2 Gy). RESULTS: For 87 patients with curative resection, the median survival times (MSTs) of the no-RT, the EBRT, and the IORT +/- EBRT groups were 10.4, 13.0, and 15.5 months, respectively, without significant difference. For 70 patients with noncurative resection, the MSTs of the no-RT, the EBRT, and the IORT +/- EBRT groups were 5.3, 8.7, and 6.5 months, respectively. When the EBRT and the IORT +/- EBRT groups were combined, the survival rate was significantly higher than that of the no RT group for noncuratively resected pancreatic cancers (log rank test; p = 0.028). The 2-year survival probability of the IORT +/- EBRT group (16%) was higher than that of the EBRT group (0%). For unresectable pancreatic cancer, the MSTs of 52 patients without distant metastases were 6.7 months for palliative surgery alone, 7.6 months for EBRT alone, and 8.2 months for IORT +/- EBRT. The survival curve of the IORT +/- EBRT group was significantly better than that of the no-RT group (p < 0.05), and the difference between the IORT +/- EBRT and the EBRT alone groups was marginally significant (p = 0.056). In addition, the 2-year survival probability for the IORT +/- EBRT group was 14%, while no 2-year survival was observed in the no RT or the EBRT groups. Multivariate analysis using the Cox proportional hazards model revealed that tumor size, stage (Stages 1, 2 vs. Stages 3, 4), and curability of resection were significant variables for resectable pancreatic cancer, while distant metastases and performance of IORT were significant variables for unresectable pancreatic cancer. The dose of EBRT was a marginally significant factor for both resectable and unresectable tumors (both p = 0.06). In terms of complications, ulcers of gastrointestinal tract were noted in 14% of the 126 patients treated with IORT. CONCLUSION: Although prolongation of the MST by IORT was not remarkable, long survivals (>2 years) were obtained by IORT +/- EBRT for noncuratively resected and unresectable pancreatic cancer. IORT combined with EBRT is indicated for noncurative resected or unresectable pancreatic cancer without distant metastases.


Assuntos
Neoplasias Pancreáticas/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Lesões por Radiação/epidemiologia , Análise de Sobrevida
8.
Int J Radiat Oncol Biol Phys ; 50(4): 889-98, 2001 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-11429216

RESUMO

PURPOSE: To evaluate the daily setup accuracy and the reduction of respiratory tumor movement using a body frame in conformal therapy for solitary lung tumor. METHODS AND MATERIALS: Eighteen patients with a solitary lung tumor underwent conformal therapy using a body frame. The body shell of the frame was shaped to the patient's body contour. The respiratory tumor movement was estimated using fluoroscopy, and if it was greater than 5 mm, pressure was applied to the patient's abdomen with the goal of minimizing tumor movement. CT images were then obtained, and a treatment planning was made. A total dose of 40 or 48 Gy was delivered in 4 fractions. Portal films were obtained at each treatment, and the field displacements between them and the simulation films were measured for daily setup errors. The patients were repositioned if the setup error was greater than 3 mm. Correlations were analyzed between patient characteristics and the tumor movement, or the tumor movement reduction and the daily setup errors. RESULTS: Respiratory tumor movement ranged from 0 to 20 mm (mean 7.7 mm). The abdominal press reduced the tumor movement significantly from a range of 8 to 20 mm to a range of 2 to 11 mm (p = 0.0002). Daily setup errors were within 5 mm in 90%, 100%, and 93% of all verifications in left-right, anterior-posterior, and cranio-caudal directions, respectively. Patient repositioning was performed in 25% of all treatments. No significant correlation was detected between patient characteristics and tumor movement, tumor movement reduction, and the daily setup errors. CONCLUSIONS: The abdominal press was successful in reducing the respiratory tumor movement. Daily setup accuracy using the body frame was acceptable. Verification should be performed at each treatment in hypofractionated conformal therapy.


Assuntos
Imobilização , Neoplasias Pulmonares/radioterapia , Radioterapia Conformacional/instrumentação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Respiração
9.
Int J Radiat Oncol Biol Phys ; 34(5): 1105-11, 1996 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-8600094

RESUMO

PURPOSE: To introduce the process of developing an integrated radiotherapy network. METHODS AND MATERIALS: We developed a new radiotherapy treatment-planning system in 1987 that we named the Computer Tomography (CT) simulator. CT images were immediately transported to multiimage monitors and to a planning computer, and treatment planning could be performed with the patient lying on the CT couch. The results of planning were used to guide a laser projector, and radiation fields were projected onto the skin of the patient. Since 1991, an integrated radiotherapy network system has been developed, which consists of a picture archiving and communicating system (PACS), a radiotherapy information database, a CT simulator, and a linear accelerator with a multileaf collimator. RESULTS: Clinical experience has been accumulated in more than 1,000 patients. Based on our 7 years of experience, we have modified several components of our original CT simulator and have developed a second generation CT simulator. A standard protocol has been developed for communication between the CT scanner, treatment planning computer, and radiotherapy apparatus using the Ethernet network. As a result, treatment planning data can be transported to the linear accelerator within 1 min after completion of treatment planning. CONCLUSION: This system enables us to make optimal use of CT information and to devise accurate three-dimensional (3D) treatment-planning programs. Our network also allows for the performance of fully computer-controlled dynamic arc conformal therapy.


Assuntos
Redes de Comunicação de Computadores/organização & administração , Simulação por Computador , Sistemas de Informação em Radiologia/organização & administração , Planejamento da Radioterapia Assistida por Computador/organização & administração , Tomografia Computadorizada por Raios X
10.
J Histochem Cytochem ; 34(11): 1385-8, 1986 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3534076

RESUMO

Immunohistochemical localization of ornithine aminotransferase (L-ornithine: 2-oxo-acid aminotransferase, EC 2.6.1.13), a mitochondrial enzyme whose hereditary absence induces gyrate atrophy of the choroid and retina, was elucidated by a direct immunoperoxidase method using Fab'-horseradish peroxidase conjugates. In immunodiffusion studies, the antibodies raised with the re-crystallized enzyme were highly specific to ornithine aminotransferase. To show localization of ornithine aminotransferase in normal rat tissues, clear immunohistochemical staining of this enzyme through the inner mitochondrial membrane in paraffin sections was achieved with Fab'-horseradish peroxidase conjugates. Strong immunoreactivity was present in cerebral neurons, hepatocytes, and epithelial cells of renal tubuli, gut mucous membranes, and ocular tissues. Specific distribution of ornithine aminotransferase was found in ependymal cell groups: namely, epithelial cells of the choroid plexus, pigmented and nonpigmented epithelial cells of the ciliary body. and Müller cells and pigment epithelium of the retina.


Assuntos
Peroxidase do Rábano Silvestre , Fragmentos Fab das Imunoglobulinas/imunologia , Ornitina-Oxo-Ácido Transaminase/análise , Peroxidases , Transaminases/análise , Animais , Encéfalo/enzimologia , Sistema Digestório/enzimologia , Olho/enzimologia , Histocitoquímica , Técnicas Imunoenzimáticas , Rim/enzimologia , Fígado/enzimologia , Ratos , Ratos Endogâmicos
11.
Radiother Oncol ; 57(2): 237-42, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11054528

RESUMO

BACKGROUND AND PURPOSE: Image distortion is one of the major drawbacks of magnetic resonance (MR) imaging for use in radiotherapy treatment planning (RTTP). In this study, the reproducibility of MR imaging distortion was evaluated by repeated phantom measurements. MATERIALS AND METHODS: A grid-pattern acrylic phantom was scanned with a 0.2-Tesla permanent magnetic unit. We repeated a series of scans three times to evaluate the reproducibility of the distortion. In each series, co-ordinates at 432 intersections of the grid were measured for both T1- and T2-weighted spin-echo (SE) pulse sequences. Positional displacements and their variations at the intersections were calculated. RESULTS: Averages of the displacements were distributed between 1.58 and 1.74 mm, and maximum values (MAX) between 12.6 and 15.0 mm. Within 120 mm of the image center, the average values ranged from 0.73 to 0.80 mm, and from 3.4 to 5.0 mm for MAX. The absolute values of the positional variations among three series were distributed between 0.41 and 0.88 mm for average values, and between 1.4 and 4.5 mm for MAX. CONCLUSIONS: The positional variations were mostly within 3 pixels, and most of the positional displacements within the radius of 120 mm of the image center were 2 mm or less. Therefore, it will be possible to use this MR system in RTTP under limited situations, although careful applications are required for RTTP of the body. The development of a computer program to correct image distortion is expected.


Assuntos
Artefatos , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/instrumentação , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador/métodos , Desenho de Equipamento , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
12.
Radiother Oncol ; 50(2): 151-6, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10368038

RESUMO

PURPOSE: To assess errors resulting from manual transfer of contour information for three-dimensional (3-D) target reconstruction, and to determine variations in target volume delineation of brain tumours by different radiation oncologists. MATERIALS AND METHODS: Images of 18 patients with intracranial astrocytomas were used for retrospective treatment planning by five radiation oncologists. In this study, the target outline was delineated on sequential CT slices by an experienced radiation oncologist. Thereafter, the target outline was manually reconstructed by five radiation oncologists onto an A-P or lateral scout film. The same target outline was also reconstructed as a projection using the Beam's-eye view capability on a CT simulator unit. The two target outlines were compared by encompassing each shape with the smallest rectangle. The manually-reconstructed radiation field was termed 'Field manually established on X-ray film (F-X)', and the automatically-established field was termed 'Field established by CT simulator (F-CT)'. In a second part of this study, four radiation oncologists defined contours from contrast enhanced CT images of nine patients with intracranial astrocytomas. The CT images of these nine cases included five pre-operative cases and four post-operative cases. Both gross tumour volume (GTV) and clinical target volume (CTV) were outlined on sequential CT slices. The target outlines for the four radiation oncologists were compared by identifying the smallest rectangular field surrounding the projection of these contours. The field established by each radiation oncologist was termed 'Field of target volume (F-TV)', and the overlapping portion of the four F-TVs for each case was termed 'Overlapped field of the target volume (Fo-TV)'. RESULTS: The average distance between the isocentres of F-X and F-CT was 0.6 +/- 0.4 cm (mean +/- SD). The average ratio of the area of F-X divided by the area of F-CT was 1.04 +/- 0.12. The area of F-X was wider than the area of F-CT for four of the five oncologists. The ratio of the area of F-TV divided by the area of Fo-TV was calculated. The average ratio was relatively greater for CTV (2.07 in pre-operative cases and 2.11 in post-operative cases) than for GTV (1.12 in pre-operative cases and 1.41 in post-operative cases). Among radiation oncologists, variations in the delineation of GTV were smaller than those of CTV. CONCLUSIONS: When using an X-ray simulator in treatment planning, errors resulting from the manual transfer of CT contour information to planar radiographs must be considered. When computer techniques are used to project contours onto radiographs errors resulting from individual variations when performing the contouring must be considered.


Assuntos
Astrocitoma/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X , Astrocitoma/radioterapia , Neoplasias Encefálicas/radioterapia , Humanos , Variações Dependentes do Observador , Reprodutibilidade dos Testes
13.
Biochem Pharmacol ; 48(2): 426-8, 1994 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-8053939

RESUMO

7-Substituted 5-methyl-2-isopropylamino-4H-3,1-benzoxazin-4-ones (BOZNs) were prepared and tested as inhibitors of human sputum elastase (HSE). The BOZNs with certain amino acid residues at the 7-position proved to be potent inhibitors of HSE. Some of the compounds also showed a high selectivity for HSE versus chymotrypsin. In a hamster model in which acute injury was induced by intratracheal administration of HSE (1.0 mg/kg), these compounds, when administered intratracheally (1.0 mg/kg) either 30 or even 240 min before challenge with HSE, significantly suppressed pulmonary hemorrhage. These findings suggest that 7-substitution of BOZN by amino acid residues can produce strong and HSE-specific inhibitors, with potential use in elastase-mediated disorders.


Assuntos
Leucócitos/enzimologia , Oxazinas/farmacologia , Elastase Pancreática/antagonistas & inibidores , Escarro/enzimologia , Animais , Cricetinae
14.
Chest ; 119(3): 768-75, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11243955

RESUMO

BACKGROUND: Endotracheal/endobronchial metastases (EEMs) from nonpulmonary neoplasms are rare. However, their definition and developmental modes have not yet been fully elucidated. METHODS: EEMs were defined as documented nonpulmonary neoplasms metastatic to the subsegmental or more proximal central bronchus, in a bronchoscopically visible range. The clinical and pathologic features of 16 cases were reviewed, with special emphasis on the developmental modes based on five criteria: location in the tracheobronchial tree, number of lesions, laterality of lesions, depth of lesions, and relationship with the associated bronchus. RESULTS: The developmental modes were proposed on the basis of the above five criteria as follows: type I, direct metastasis to the bronchus; type II, bronchial invasion by a parenchymal lesion; type III, bronchial invasion by mediastinal or hilar lymph node metastasis; and type IV, peripheral lesions extended along the proximal bronchus. Primary tumors included colorectal in six patients, breast in three patients, uterus in two patients, osteosarcoma of the bone in two patients, and maxillary, larynx, and parotid carcinoma in one patient each, respectively. The mean recurrence interval was 65.3 months. The developmental modes were as follows: type I, five patients; type II, one patient; type III, four patients; and type IV, nine patients. Three patients underwent surgical resection. One patient has remained well for 5 years after operation. Median and mean survival times were 9 months and 15.5 months, respectively. CONCLUSION: The mean recurrence interval was long at 65.3 months, but the mean survival time was short at 15.5 months. Type I accounted for only 5 of 16 patients. Type II was found in only one patient. It is thought that this type is a rare form. Type IV affected nine patients. Treatment plans must be individualized, because in some cases, long-term survival can be expected.


Assuntos
Neoplasias Brônquicas/secundário , Neoplasias da Traqueia/secundário , Neoplasias Ósseas/patologia , Neoplasias da Mama/patologia , Neoplasias Brônquicas/mortalidade , Neoplasias Colorretais/patologia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Neoplasias da Traqueia/mortalidade , Neoplasias Uterinas/patologia
15.
Neurosci Res ; 39(2): 205-12, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11223466

RESUMO

We have established a new line of immortalized rat astrocytes through transfection of plasmid pSV3-neo encoding the large T antigen of simian virus 40 into normal astrocytes. One of these immortalized astrocytes (ACT-57) with a flat and polygonal cell shape, exhibited stable growth in a chemically defined medium (modified N-2 medium) as well as in medium containing ordinary serum. ACT-57, retained a detectable level of expression of glial fibrillary acidic protein (GFAP) and its mRNA, and exhibited a stronger expression of nerve growth factor (NGF) mRNA than that of normal rat astrocytes or C6 glioma cells. NGF mRNA was significantly up-regulated by phorbol ester (12-O-tetradecanoylphorbol 13-acetate, TPA) and gamma-amino-n-butyric acid (GABA) but not by hydrocortisone. None of stimulants (TPA, dibutyryl cyclic AMP (db-cAMP), hydrocortisone, L-glutamate, carbacol, GABA, dopamine, or isoproterenol) changed the expression level of either brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3). There was a discrete difference between ACT-57 and normal astrocytes in the response to GABA and isoproterenol. These findings imply that normal cortical astrocytes possess a functional heterogeneity whereas the clonal astrocyte, ACT-57, does not, indicating that ACT-57 cells may be useful for in vitro studies of neuron-astrocyte interactions involving the induction of neurotrophic factors such as NGF.


Assuntos
Astrócitos/citologia , Astrócitos/metabolismo , Fator de Crescimento Neural/genética , Transcrição Gênica , Animais , Encéfalo/citologia , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Técnicas de Cultura de Células/métodos , Células Cultivadas , Embrião de Mamíferos , Cariotipagem , Neurotrofina 3/genética , RNA Mensageiro/genética , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa
16.
Oncol Rep ; 7(4): 773-6, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10854542

RESUMO

Initial clinical results of concurrent chemoradiotherapy combined with high-dose intraoperative radiotherapy (IOR) for locally advanced pancreatic cancer were analyzed. Between June 1996 and May 1999, 6 patients with locally advanced pancreatic cancer without distant metastasis were treated with preoperative concurrent chemoradiotherapy followed by IOR. Preoperative radiation therapy was given by the dynamic arc conformal technique with a daily fraction of 1.8 Gy to a total dose of 45 Gy in 5 weeks. Cisplatin (5 mg/day for 4 weeks) and 5-fluorouracil (250 mg/day for 5 weeks) were administered continuously during preoperative radiation therapy. IOR as a single dose of 28 or 30 Gy was given to the gross tumor volume using electron beams of 15- to 22-MeV. Concurrent chemoradiotherapy was well tolerated, although all of the patients complained of nausea and fatigue. Two patients developed grade III leukopenia. No other serious acute toxicity was noted. The median survival time of the 6 patients was 17.5 months, which was significantly longer than that of our historical control treated with external radiation therapy with IOR (8 months), although the difference in survival was borderline significant (p=0.068). Concurrent chemoradiotherapy followed by high-dose IOR was well tolerated in patients with locally advanced pancreatic cancer, and the initial clinical results appeared promising.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/terapia , Radioterapia Conformacional , Adulto , Idoso , Cisplatino/administração & dosagem , Terapia Combinada/efeitos adversos , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/cirurgia , Análise de Sobrevida , Fatores de Tempo
17.
Am J Clin Oncol ; 24(1): 71-6, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11232954

RESUMO

The clinical results of definitive chemoradiotherapy for oropharyngeal carcinoma were retrospectively analyzed. Thirty-one patients with oropharyngeal carcinoma who received definitive radiation therapy between January 1986 and June 1998 were analyzed. The median age was 61 years. All patients had squamous cell carcinoma. According to the Union International Contre le Cancer 1997 classification system, stage I, II, III, IVA, and IVB were 1,0, 9, 14, and 7, respectively. Regarding the primary site, 23 tumors were in the lateral wall, whereas 2 were in the superior wall, and 3 each were in the anterior and posterior walls. The median total dose was 66 Gy, with a range of 60 Gy to 74.4 Gy. The overall treatment time ranged from 39 days to 113 days, with a median of 50 days. Seven patients underwent hemilateral radical neck dissection. Fourteen patients received concurrent chemotherapy using weekly cisplatin (50 mg/d) at least three times. The 5-year overall and cause-specific survival (CSS) rates were 55% and 62%, respectively. All local recurrences occurred within 2 years. The CSS rate in patients with lateral or superior wall origin was significantly superior to that of patients with anterior or posterior wall origin (p < 0.05). The 3-year CSS rate was 83% for patients treated with concurrent chemoradiotherapy using weekly cisplatin at least 3 times, whereas that was 53% for the remaining patients (p < 0.05). No serious adverse effects were observed. It is concluded that definitive concurrent chemoradiotherapy using weekly cisplatin for oropharyngeal carcinoma appear promising.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Cisplatino/uso terapêutico , Neoplasias Orofaríngeas/tratamento farmacológico , Neoplasias Orofaríngeas/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Carcinoma de Células Escamosas/patologia , Cisplatino/efeitos adversos , Terapia Combinada , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/patologia , Radioterapia/efeitos adversos , Estudos Retrospectivos , Taxa de Sobrevida
18.
Am J Clin Oncol ; 23(5): 499-505, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11039512

RESUMO

This study evaluated the results of breast-conserving therapy (BCT). Nine hundred six patients who underwent BCT at our hospital between November 1987 and February 1998 were analyzed. The mean age was 48 years. According to the Union Internationale Contre le Cancer 1997 classification system, stages 0, I, IIA, IIB, IIIA, and IIIB were 37, 400, 344, 117, 7, and 1, respectively. Radiation therapy consisted of 50 Gy to the ipsilateral whole breast. Boost irradiation of 10 Gy was administered to 186 of 231 patients with close or positive margins. Nearly all patients received adjuvant chemohormonal therapy with tamoxifen and 5-fluorouracil or its derivatives for 2 years. The minimum and median follow-up periods were 18 and 52 months, respectively. The 5-year overall survival, cause-specific survival, local recurrence-free survival, and disease-free survival rates were 97.3%, 98.4%, 98.1%, and 91.5%, respectively. Local recurrence in preserved breast occurred in 20 patients 7 to 86 months after surgery. Multivariate analysis revealed that the most predictive factor for disease-free survival rates and distant failures was the number of pathologically positive lymph nodes (p < 0.0001), and that the factor for local failure was marginal status (p = 0.005). This study demonstrated that BCT was suitable for the treatment of early-stage breast cancer with its reasonable survival rates and acceptable toxicity.


Assuntos
Neoplasias da Mama/cirurgia , Mastectomia Segmentar , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Análise de Sobrevida
19.
Am J Clin Oncol ; 22(1): 97-102, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10025392

RESUMO

The effects of transcatheter intraarterial infusion of anticancer drugs on the prognosis of cervical cancer were retrospectively studied. Two or three sessions of transcatheter arterial infusion therapy were performed for 68 patients with primary uterine cervical cancer. The number of patients with stage I, II, III, or IV disease were 13, 22, 24, and 9, respectively. Patients with squamous cell carcinoma comprised 3, 17, 17, and 5 of the respective groups, and the patients with stage I and II disease had either adenocarcinoma or adenosquamous carcinoma, or bulky tumor (>4 cm). The drugs infused were cisplatin (60-70 mg/m2), doxorubicin hydrochloride (30-40 mg/m2), mitomycin (15 mg/m2), and 5-fluorouracil (500 mg/body). They were infused via the bilateral internal iliac arteries. Fifty-eight of the 68 patients (85%) received a radical hysterectomy after transcatheter arterial infusion: 12 of 13 with stage I disease, 21 of 22 with stage II disease, 20 of 24 with stage III disease, and five of nine with stage IV disease. Two patients with stage III disease received radical radiotherapy. The other eight patients (one with stage I disease, one with stage II disease, two with stage III disease, and four with stage IV disease) did not receive an operation after transcatheter arterial infusion because they had distant metastases at the time of operation. Thirty-two of 58 patients (56%) received postoperative radiotherapy. The complete histologic response rates (no active cancer cells) after transcatheter arterial infusion were: 2 of 12 patients with stage I disease, 3 of 21 patients with stage II disease, 5 of 20 patients with stage III disease, and one of five patients with stage IV disease. Tumors with squamous cell carcinoma disappeared at a significantly better rate (10/36, 28%) than did tumors with adenocarcinoma or adenosquamous cell carcinoma (1/22, 5%; p < 0.05). The overall 5-year survival rates of the patients with stages I, II, and III disease were 92.3%, 62.2%, and 71%, respectively. The 5-year survival rates of the patients who underwent surgery with stage I, II, and III disease were 100%, 66.3%, and 71.5%, respectively. Leukocytopenia and thrombocytopenia occurred as an acute complication in 75% and 79% of the patients, respectively. As a late complication, ileus occurred in 7%. Transcatheter arterial infusion may improve the prognosis of patients with cervical cancer without increasing the incidence of late complications.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Infusões Intra-Arteriais , Neoplasias do Colo do Útero/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Feminino , Humanos , Histerectomia , Artéria Ilíaca , Imageamento por Ressonância Magnética , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias do Colo do Útero/patologia
20.
J Agric Food Chem ; 49(2): 736-40, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11262021

RESUMO

A three-dimensional (3D) visualization technique for the compound distribution in a rice kernel was developed. This technique is a combination of sectioning, staining, and digital image postprocessing. By using a special microtome system with adhesive tapes, a set of sequential sections of a rice kernel, which can be preserved with their own set of relative position data, was obtained. A single set of sequential sections was stained by various chemical techniques for the visualization of protein, starch, or lipid content. Each stained section was digitally captured using a CCD imaging device. As the stained areas represent areas containing dye-target complex, the distribution of each compound in the section was visualized in two dimensions. The digitally captured images of a single set of sequential sections were reconstructed to produce a 3D plotting image. As a result, the distributions of various compounds in a rice kernel could be visualized in a new 3D model.


Assuntos
Oryza/química , Oryza/citologia , Sementes/química , Sementes/citologia , Corantes , Técnicas Histológicas , Processamento de Imagem Assistida por Computador/métodos
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