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1.
Neuropathol Appl Neurobiol ; 46(2): 111-124, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31179566

RESUMO

AIMS: Alterations in microenvironments are a hallmark of cancer, and these alterations in germinomas are of particular significance. Germinoma, the most common subtype of central nervous system germ cell tumours, often exhibits massive immune cell infiltration intermingled with tumour cells. The role of these immune cells in germinoma, however, remains unknown. METHODS: We investigated the cellular constituents of immune microenvironments and their clinical impacts on prognosis in 100 germinoma cases. RESULTS: Patients with germinomas lower in tumour cell content (i.e. higher immune cell infiltration) had a significantly longer progression-free survival time than those with higher tumour cell contents (P = 0.03). Transcriptome analyses and RNA in-situ hybridization indicated that infiltrating immune cells comprised a wide variety of cell types, including lymphocytes and myelocyte-lineage cells. High expression of CD4 was significantly associated with good prognosis, whereas elevated nitric oxide synthase 2 was associated with poor prognosis. PD1 (PDCD1) was expressed by immune cells present in most germinomas (93.8%), and PD-L1 (CD274) expression was found in tumour cells in the majority of germinomas examined (73.5%). CONCLUSIONS: The collective data strongly suggest that infiltrating immune cells play an important role in predicting treatment response. Further investigation should lead to additional categorization of germinoma to safely reduce treatment intensity depending on tumour/immune cell balance and to develop possible future immunotherapies.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/imunologia , Linhagem da Célula/imunologia , Germinoma/diagnóstico , Germinoma/imunologia , Neoplasias Encefálicas/metabolismo , Perfilação da Expressão Gênica , Germinoma/metabolismo , Humanos , Prognóstico , Transcriptoma , Microambiente Tumoral/imunologia
2.
Neuropathol Appl Neurobiol ; 42(3): 279-90, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26111727

RESUMO

AIMS: Primary central nervous system lymphoma (PCNSL) manifest aggressive clinical behaviour and have poor prognosis. Although constitutive activation of the nuclear factor-κB (NF-κB) pathway has been documented, knowledge about the genetic alterations leading to the impairment of the NF-κB pathway in PCNSLs is still limited. This study was aimed to unravel the underlying genetic profiles of PCNSL. METHODS: We conducted the systematic sequencing of 21 genes relevant to the NF-κB signalling network for 71 PCNSLs as well as the pyrosequencing of CD79B and MYD88 mutation hotspots in a further 35 PCNSLs and 46 glioblastomas (GBMs) for validation. RESULTS: The results showed that 68 out of 71 PCNSLs had mutations in the NF-κB gene network, most commonly affecting CD79B (83%), MYD88 (76%), TBL1XR1 (23%), PRDM1 (20%) and CREBBP1 (20%). These mutations, particularly CD79B and MYD88, frequently coincided within each tumour in various combinations, simultaneously affecting diverse pathways within the network. No GBMs had hotspot mutation of CD79B Y196 and MYD88 L265. CONCLUSIONS: The prevalence of CD79B and MYD88 mutations in PCNSLs was considerably higher than reported in systemic diffuse large B-cell lymphomas. This observation could reflect the paucity of antigen stimuli from the immune system in the central nervous system (CNS) and the necessity to substitute them by the constitutive activation of CD79B and MYD88 that would initiate the signalling cascades. These hotspot mutations may serve as a genetic hallmark for PCNSL serving as a genetic marker for diagnose and potential targets for molecular therapy.


Assuntos
Antígenos CD79/genética , Neoplasias do Sistema Nervoso Central/genética , Linfoma Difuso de Grandes Células B/genética , Fator 88 de Diferenciação Mieloide/genética , Idoso , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase
3.
Jpn J Clin Oncol ; 31(6): 246-50, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11463801

RESUMO

BACKGROUND: The aim of this study was to examine the effectiveness of radio-chemotherapy using nimustine hydrochloride (ACNU) and etoposide (VP-16) for malignant gliomas. METHODS: From 1985 through 1998, 33 consecutive patients with supratentorial malignant gliomas were treated by a single protocol. The mean age was 45.8 years (range 12-76 years). The median Karnofsky performance score was 80 (range 60-100). There were 14 anaplastic astrocytomas (AA) and 19 glioblastomas (GBM). Following surgery, 60 Gy of radiotherapy combined with an adjuvant chemotherapy using ACNU (80 mg/m(2) i.v. days 1 and 36) and etoposide (80 mg/m(2) i.v. days 2, 3, 37 and 38) was administered. On completion of the initial radio-chemotherapy, a single cycle of the same chemotherapy was repeated every 6-8 weeks until tumor progression or for 2 years at the maximum. RESULTS: All 33 patients tolerated treatment. We observed complete response in five cases (15%), partial response in nine (27%), no change in 11 (33%) and progressive disease in eight (24%). The response rate (>50% reduction) was therefore 42.4%. Median progression-free survival (PFS) for all 33 patients was 8.4 months: 7.8 months for GBMs and 13.5 months for AAs. There was no significant difference in PFS between GBM and AA patients (p = 0.14). The median survival time of all 33 patients was 21.1 months: 16.2 months for GBMs and 49.9 months for AAs. The difference in survival between AA and GBM was statistically significant (p = 0.0019). Myelosuppression appeared in 11 patients: grade 2 hematological toxicity in 10 cases (30%) and grade 3 in one case (3%). We did not observe any gastrointestinal toxicity. Multivariate analysis showed that age and initial histological grade had independent prognostic significance. CONCLUSION: RT with ACNU and etoposide are feasible and well tolerated and the treatment results were comparable to the best results reported in the literature.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Glioma/tratamento farmacológico , Glioma/radioterapia , Neoplasias Supratentoriais/tratamento farmacológico , Neoplasias Supratentoriais/radioterapia , Adolescente , Adulto , Idoso , Criança , Terapia Combinada , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nimustina/administração & dosagem , Projetos Piloto , Prognóstico
4.
Int J Radiat Oncol Biol Phys ; 48(5): 1389-93, 2000 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-11121638

RESUMO

PURPOSE: To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) for brain metastases from renal cell carcinoma (RCC). METHODS AND MATERIALS: From May 1983 to September 1998, 35 patients with brain metastases from RCC underwent radiotherapy at the National Cancer Center Hospital, Tokyo; 10 patients treated initially with FSRT (FSRT group); 11 with surgery followed by conventional radiotherapy (S/CR group); and 14 with conventional radiotherapy (CR group). Survival and local control rates were determined for patients who had an ECOG performance status of 0-2. RESULTS: Overall median survival rate was 18 months, and actuarial 1- and 2-year survival rates were 57.6% and 31.0%, respectively. Median survival rates were 25.6 months for the FSRT group, 18.7 months for the S/CR group, and 4.3 months for the CR group. Significant prognostic factors associated with survival were age less than 60 years and good performance status. In patients treated with FSRT, imaging studies revealed that 21 of 24 tumors (88%) were locally controlled during a median follow-up time of 5.2 months (range 0.5-68). Actuarial 1- and 2-year local control rates were 89.6% and 55.2%, respectively. No patient suffered from acute or late complications during and following FSRT. CONCLUSIONS: FSRT offers better tumor control and prolonged survival over the S/CR or CR groups, and should be considered as primary treatment for brain metastases from RCC. Patients under 60-years-old and those with a good performance status at the beginning of radiotherapy had a better prognosis.


Assuntos
Neoplasias Encefálicas/cirurgia , Carcinoma de Células Renais/cirurgia , Neoplasias Renais , Radiocirurgia/métodos , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Humanos , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida
6.
Breast Cancer ; 7(2): 153-6, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11029788

RESUMO

We report 7 rare cases of recurrent breast cancers who presented with central nervous system (CNS) metastases as the initial relapse site without any other organ metastases. The average age of the patients at surgery was 42.6 years old of age (median 45:range 32-60), and 6 of the 7 cases (86%) were premenopausal. The mean disease-free period was 25.7 months (median 22, range 2-60 months). The primary tumors were all invasive ductal carcinomas. The estrogen receptor and progesterone receptor status of the 3 tumors available for study were all negative. The metastatic CNS lesions included the cerebrum (4 cases), cerebellum, cervical spinal cord, and meninges. In 6 out of these 7 cases (86%), the CNS metastasis was the initial recurrent lesion. Multidisciplinary treatments including surgery, radiotherapy and systemic or intrathecal chemotherapy were given. Although the mean survival time from clinical manifestations of the metastases of the 4 deceased patients was 20 months (median 20.5; range 6-33), one patient treated with surgery and radiotherapy is been still alive18 years later. These cases were also notable for the fact that the only metastatic site was in the CNS only during the entire clinical course, except for 2 cases, one with ocular adnexa metastasis, and the other with cervical lymph node metastasis. Premenopausal patients with negative hormone receptor status are more likely to develop this type of recurrence, regardless of the histological type. It is necessary to pay attention to neurological symptoms and signs during follow-up of breast cancer patients.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Neoplasias do Sistema Nervoso Central/secundário , Adulto , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Pré-Menopausa , Receptores de Estrogênio/análise , Receptores de Progesterona/análise
7.
J Neurosurg ; 92(2): 338-41, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10659023

RESUMO

The authors present the clinical, radiological, and pathological features of a malignant intracerebral nerve sheath tumor that occurred in the right parietooccipital lobe of a 4-year-old girl. Computerized tomography scanning and magnetic resonance imaging demonstrated a 5x5x4-cm multiloculated mass with considerable enhancement of the irregularly shaped septa and clearly calcified areas within the mass. Among five cases reported in the literature, this patient is the youngest and represents the first case in which there is radiological evidence of intratumoral calcification.


Assuntos
Neoplasias Encefálicas/cirurgia , Calcinose/cirurgia , Neoplasias de Bainha Neural/cirurgia , Lobo Occipital/cirurgia , Lobo Parietal/cirurgia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Calcinose/diagnóstico , Calcinose/patologia , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Microscopia Eletrônica , Neoplasias de Bainha Neural/diagnóstico , Neoplasias de Bainha Neural/patologia , Lobo Occipital/patologia , Lobo Parietal/patologia , Tomografia Computadorizada por Raios X
9.
Jpn J Clin Oncol ; 29(5): 252-5, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10379337

RESUMO

A 68-year-old man with metastatic brain tumors from adenoendocrine carcinoma of the common bile duct is reported. A common bile duct tumor and a metastatic liver tumor had been resected 6 years and 3 years prior to admission, respectively. Microscopically they showed two components; moderately differentiated tubular adenocarcinoma and neuroendocrine carcinoma. He presented with headache and vomiting and MRI revealed two metastatic brain tumors. They were successfully resected and radiotherapy was carried out. Histological diagnosis of the metastatic brain tumors was neuroendocrine carcinoma, but carbohydrate antigen (CA)-19-9 and carcinoembryonic antigen (CEA)-immunoreactive cells were observed without glandular pattern. Immunohistochemically serotonin and pancreatic polypeptide were detected, but somatostatin was not. As the endocrine cells demonstrated in the normal extrahepatic bile ducts are only somatostatin-containing D cells, these cells are considered to originate as part of a metaplastic process. To our knowledge, this represents the second case of adenoendocrine carcinoma of the common bile duct.


Assuntos
Adenocarcinoma/secundário , Neoplasias Encefálicas/secundário , Carcinoma Neuroendócrino/secundário , Neoplasias do Ducto Colédoco/patologia , Neoplasias Primárias Múltiplas , Adenocarcinoma/diagnóstico , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico , Carcinoma Neuroendócrino/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios X
11.
J Neurooncol ; 44(2): 169-73, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10619501

RESUMO

A 57-year-old male with pineal ganglioneuroblastoma was reported. The tumor was composed of a predominant ganglioneuromatous component and a small neuroblastic component. Primary ganglioneuroblastoma of the pineal region is extremely rare. To our knowledge, only three cases have been documented. This case may have a good prognosis because there is a predominant ganglioneuromatous component defined by both neurofilament triplet proteins and synaptophysin. The clinical significance of the neuronal differentiation in the present case and pathological considerations are discussed.


Assuntos
Neoplasias Encefálicas/diagnóstico , Ganglioneuroblastoma/diagnóstico , Glândula Pineal , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Ganglioneuroblastoma/metabolismo , Ganglioneuroblastoma/patologia , Ganglioneuroblastoma/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
12.
Jpn J Clin Oncol ; 29(11): 527-34, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10678554

RESUMO

BACKGROUND: In addition to traditional modalities such as surgical intervention and radiotherapy, chemotherapy is a common therapeutic method for human malignant brain tumors. However, the effectiveness of chemotherapy is frequently hampered by cancer cell chemoresistance, resulting in an unsatisfactory outcome. To overcome this disadvantage, the proper selection of efficacious anticancer agents is required. METHODS: The expression levels of chemoresistance-related genes, MGMT, mdr1, MRP, MTIIA and GST-pi, in 28 surgical specimens of human brain tumors and in 10 human glioma cell lines were examined by Northern blot analysis. In addition, the SD10 values of human glioma cell lines against ACNU, CDDP, ADM and VP16 were estimated by a cell survival assay. RESULTS: The expression levels of each of the chemoresistance-related genes, except MRP, were generally higher in brain tumors than those in non-neoplastic brain tissues. MGMT expression correlated exclusively with ACNU resistance in all glioma cell lines examined (p = 0.0002). The transcriptional level of mdr1 in the tumor cells correlated with the SD10 values of VCR (p = 0.04) and ADM (p = 0.034). In contrast, the expression levels of MTIIA and GST-pi did not correlate with resistance to any of the drugs tested. A correlation of MRP mRNA expression with multidrug resistance was not apparent in the 10 cell lines tested. CONCLUSIONS: The data indicate that knowledge of the expression levels of MGMT and mdr1 may be particularly useful for a more rational selection of drugs which are not influenced by these resistance genes and which have improved efficacy against human brain tumors.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Encefálicas/genética , Genes MDR , Glioma/genética , Glicoproteínas de Membrana , Antígenos CD/análise , Antígenos CD/genética , Neoplasias Encefálicas/patologia , Cisplatino/farmacologia , Doxorrubicina/farmacologia , Etoposídeo/farmacologia , Glioma/patologia , Humanos , Nimustina/farmacologia , RNA Mensageiro/análise , Tetraspanina 29 , Células Tumorais Cultivadas/efeitos dos fármacos
13.
Jpn J Clin Oncol ; 28(10): 626-30, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9839504

RESUMO

Solitary plasmacytoma of the skull is very rare and only 35 cases have been reported in the English literature. It remains controversial whether solitary plasmacytoma of the skull is essentially identical with solitary plasmacytoma of bone or not. Solitary plasmacytoma of bone including solitary plasmacytoma of the skull is characterized by a radiologically solitary bone lesion, neoplastic plasma cells in the biopsy specimen, fewer than 5% plasma cells in bone marrow, less than 2.0 g/dl monoclonal protein in the serum when present and negative urine test for Bence Jones protein (monoclonal light chain). Solitary plasmacytoma of bone tends to disseminate or progress to multiple myeloma even as long as 7-23 years after presentation. We report the first case of solitary plasmacytoma of the skull in which both beta2-microglobulin for detection of early renal disturbance and neoplastic plasma cell labeling index for detection of DNA synthesis were examined in order to predict the clinical course of solitary plasmacytoma of the skull.


Assuntos
Plasmocitoma/diagnóstico , Neoplasias Cranianas/diagnóstico , Feminino , Gadolínio DTPA , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Plasmocitoma/patologia , Prognóstico , Neoplasias Cranianas/patologia , Microglobulina beta-2/análise
14.
Int J Radiat Oncol Biol Phys ; 42(5): 989-94, 1998 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-9869220

RESUMO

PURPOSE: To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) in patients with small intracranial malignancies. METHODS AND MATERIALS: From July 1991 to March 1997, 80 patients with a total of 121 brain or skull-base tumors were treated with FSRT alone, and were followed for periods ranging from 3 to 62 months (median 9.8). The majority of patients received 42 Gy in 7 fractions over 2.3 weeks, but in July 1993, protocols using smaller fraction doses were introduced for patients whose radiation-field diameters were larger than 3 cm or whose tumors were close to critical normal tissues. RESULTS: For 64 patients with metastatic brain tumors the overall median survival was 8.3 months and 1-year actuarial survival rate was 33%. Significant prognostic factors were: the presence of extracranial tumors, pre-treatment performance status, and the lung as a primary site. Patients without extracranial tumors prior to FSRT had a median survival of 21.2 months. For seven patients with high-grade glioma, 1-year actuarial local control rate was 75%, with a median survival of 10.3 months. For patients with skull-base tumors the local control was achieved in 6 of 6 patients (100%), with a median survival of 30.7 months. No one suffered from acute complications, but three patients, two of whom had undergone FSRT as the third course of radiotherapy, developed late radiation injuries. CONCLUSION: Overall high local control and low morbidity rates suggest that FSRT is an effective and safe modality, even for those with a history of prior irradiation. However, patients with risk factors should be treated with smaller fraction doses.


Assuntos
Neoplasias Encefálicas/cirurgia , Glioma/cirurgia , Radiocirurgia , Análise de Variância , Neoplasias Encefálicas/secundário , Fracionamento da Dose de Radiação , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida
15.
Int J Radiat Oncol Biol Phys ; 40(5): 1151-5, 1998 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-9539571

RESUMO

PURPOSE: We evaluated the feasibility of fractionated stereotactic radiotherapy for small intracranial recurrences after conventional radiotherapy. METHODS AND MATERIALS: Nineteen patients who had initially undergone conventional radiotherapy to intracranial lesions, receiving a median total dose of 50 Gy in 5 weeks, were retreated with stereotactic radiotherapy for their recurrences and received a median total dose of 42 Gy in seven fractions over 2.3 weeks. RESULTS: Of the 19 patients, 15 achieved local control 3-51 months after reirradiation. No patient suffered from acute reaction, but one patient with a history of extensive radiotherapy developed progressive radionecrosis 9 months after reirradiation. CONCLUSIONS: Fractionated stereotactic radiotherapy of intracranial recurrences appears to be effective in achieving in local control with negligible morbidity. We believe it merits further investigation in a prospective study.


Assuntos
Neoplasias Encefálicas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Radiocirurgia , Neoplasias da Base do Crânio/cirurgia , Adulto , Neoplasias Encefálicas/radioterapia , Criança , Estudos de Viabilidade , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/radioterapia , Neoplasias da Base do Crânio/secundário
16.
Neurosurg Focus ; 5(1): e7, 1998 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-17140188

RESUMO

The authors conducted a multiinstitutional phase II study to establish a postsurgical combined chemotherapy and radiation therapy regimen for patients with primary germ cell tumors of the brain. After surgical debulking of the tumor and histological verification, patients were divided into three therapeutic groups: good prognosis, intermediate prognosis, and poor prognosis. Patients received two kinds of chemotherapy (three courses) prior to receiving radiation therapy: carboplatin-etoposide combination ([CARB-VP]: carboplatin 450 mg/m(2) on Day 1, etoposide 150 mg/m(2) on Days 1-3) or ifosphamide-cisplatin-etoposide combination ([ICE]: ifosphamide 900 mg/m(2), cisplatin 20 mg/m(2), and etoposide 60 mg/m(2) on Days 1-5). Patients in the good prognosis group (those with germinomas) were treated with CARB-VP followed by local radiation therapy (24 Gy). Patients in the intermediate prognosis group received CARB-VP followed by local radiation therapy (50 Gy); they received five additional chemotherapy treatments. Patients in the poor prognosis group received ICE followed by whole craniospinal radiation therapy; they also received five additional chemotherapy treatments. Eighty-two patients were evaluated. For the 56 patients with germinomas, a 93% rate of complete remission after treatment was achieved. The remission rate was 76% for 21 patients in the intermediate prognosis group, and no recurrence was detected during a median follow-up period of 2.6 years. In the group of five patients with poor prognosis, the disease in three patients progressed during chemotherapy or radiation therapy and they died within 6 months. There were no serious complications in the surviving patients. The authors found their treatment protocols to be currently effective for patients with germinomas and those with an intermediate prognosis.

17.
Neurosurgery ; 41(2): 434-40; discussion 440-1, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9257312

RESUMO

OBJECTIVE: A derivative of chloroethylnitrosoureas, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), is a drug of choice for the chemotherapy of human malignant brain tumors. However, the cytocidal effect of ACNU is effectively repressed through repair of ACNU-mediated deoxyribonucleic acid lesions by O6-methylguanine-deoxyribonucleic acid methyltransferase (MGMT). Because a variety of human tumors, including brain tumors, contain high levels of MGMT activity, we investigated the effect of antisense ribonucleic acid (RNA) complementary to MGMT messenger RNA on ACNU resistance in tumor cells. METHODS: We established a stable ACNU-resistant clone, C6AR, from the rat glioma cell line C6 exposed to a stepwise increasing concentration of ACNU. We transfected a plasmid deoxyribonucleic acid-encoding antisense MGMT RNA under the control of the human metallothionein promoter into C6AR cells and determined the effect of the antisense RNA on ACNU resistance of tumor cells by a colony-forming efficiency assay. RESULTS: C6AR cells expressed abundant MGMT messenger RNA, although the transcription level of the MGMT gene in parental C6 cells was below the lower limits of detection under the same assay conditions. ACNU resistance of C6AR cells was significantly repressed by transfected gene-dependent antisense MGMT RNA expression that resulted in decreased survival of the tumor cells. CONCLUSION: ACNU resistance resulting from the expression of MGMT in rat glioma cells is significantly overcome by the expression of antisense MGMT RNA. This result suggests that the antisense MGMT RNA system might be a useful strategy for overcoming ACNU resistance in the treatment of intractable malignant gliomas.


Assuntos
Elementos Antissenso (Genética)/uso terapêutico , Glioma/terapia , Metiltransferases/genética , RNA Complementar/uso terapêutico , RNA Mensageiro/genética , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Glioma/genética , Glioma/patologia , Nimustina/efeitos adversos , Nimustina/uso terapêutico , O(6)-Metilguanina-DNA Metiltransferase , Biossíntese de Proteínas , Ratos , Transfecção , Células Tumorais Cultivadas
18.
Gan To Kagaku Ryoho ; 24(6): 657-65, 1997 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-9126301

RESUMO

In radiotherapeutic management for pediatric tumors, we have to pay more attention to confinement of higher dose to the target volume than for adult tumors, in order that the risk of untoward normal tissue complications dose not increase, such as growth retardation. Two current approaches performing in our department to match this purpose are presented, namely, perioperative brachytherapy and fractionated stereotactic radiotherapy (F-SRT). In perioperative brachytherapy for bone and soft tissue sarcoma, plastic guide tubes for introducing radioactive sources are placed in the residual tumor bed or at the margins during the surgery, and patients are treated by high-dose-rate brachytherapy after surgery. Patients are not restricted in radioprotective area, and the overall treatment period is short enough. F-SRT is used either as the boost of conventional brain radiotherapy in primary brain neoplasms, or as hypofractionated F-SRT for control of metastatic brain tumors, with nearly perfect local control and maintenance of good quality of life. F-SRT is planned in 3-dimensional fashion from computed tomography images. Easily detachable, relocatable cast made for F-SRT is useful in pediatric patients.


Assuntos
Braquiterapia/métodos , Neoplasias Encefálicas/radioterapia , Técnicas Estereotáxicas , Neoplasias Encefálicas/fisiopatologia , Criança , Humanos , Dosagem Radioterapêutica , Sarcoma/radioterapia , Neoplasias de Tecidos Moles/radioterapia
19.
Surg Neurol ; 45(3): 219-29, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8638217

RESUMO

BACKGROUND: Two rare cases of triple primary malignant neoplasms (PMN), including malignant brain tumors, which were glioblastoma multiformes, are described. METHODS: The clinical characteristics and underlying genetic alterations in triple or more PMN, including malignant brain tumors are discussed with intensive review of the literature. RESULTS: The first patient, a 77-year-old male, suffered metachronously from tubular adenocarcinoma of the stomach, transitional cell carcinoma of the bladder, and glioblastoma in the brain. This glioblastoma had loss of heterozygosity in exons 7-8 in p53 gene. The second patient, a 68-year-old male, developed papillary adenocarcinoma of the lung, adenocarcinoma of the rectum, and glioblastoma in the brain during a period of 7 years. In 42 such cases described in the literature, age distribution demonstrated two characteristic peaks, one in the third decade and the other over 50 years of age. The younger group consisted mainly of Turcot's syndrome, and of a case of Li-Fraumeni familial cancer syndrome. On the other hand, neither of these hereditary cancer syndromes were contained in the elder group. Regarding the site of PMN, colorectal cancers were associated most frequently with malignant brain tumors, followed by stomach cancers, and thyroid cancers. Malignant brain tumors, mostly glioblastoma multiforme, tend to occur as the last tumor of triple or more PMN. CONCLUSIONS: These results suggest that genetic background might play an important role in tumorigenesis of PMN in the younger group, whereas epigenetic factors would be more important in the older group. Characteristic organ association and factors influencing carcinogenesis, such as aging, environmental carcinogens, and underlying genetic alterations in these tumors are further discussed.


Assuntos
Polipose Adenomatosa do Colo/epidemiologia , Neoplasias Encefálicas/epidemiologia , Glioblastoma/epidemiologia , Neoplasias Primárias Múltiplas/epidemiologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adulto , Distribuição por Idade , Idoso , Neoplasias Encefálicas/patologia , Neoplasias da Mama/epidemiologia , Carcinoma de Células de Transição/epidemiologia , Comorbidade , Feminino , Glioblastoma/patologia , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/patologia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Neoplasias da Bexiga Urinária/epidemiologia
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