RESUMO
The Kansai BNCT Medical Center has a cyclotron based epithermal neutron source for clinical Boron Neutron Capture Therapy. The system accelerates a proton to an energy of 30 MeV which strikes a beryllium target producing fast neutrons which are moderated down to epithermal neutrons for BNCT use. While clinical studies in the past have shown BNCT to be highly effective for malignant melanoma of the skin, to apply BNCT for superficial lesions using this system it is necessary to shift the thermal neutron distribution so that the maximum dose occurs near the surface. A dose distribution shifter was designed to fit inside the collimator to further moderate the neutrons to increase the surface dose and reduce the dose to the underlying normal tissue. Pure polyethylene was selected, and a Monte Carlo simulation was performed to determine the optimum thickness of the polyethylene slab. Compared with the original neutron beam, the shifter increased the thermal neutron flux at the skin by approximately 4 times. The measured and simulated central axis depth distribution and off axis distribution of the thermal neutron flux were found to be in good agreement. Compared with a 2 cm thick water equivalent bolus, a 26% increase in the thermal neutron flux at the surface was obtained, which would reduce the treatment time by approximately 29%. The DDS is a safe, simple and an effective tool for the treatment of superficial tumours for BNCT if an initially fast neutron beam requires moderation to maximise the thermal neutron flux at the tissue surface.
Assuntos
Terapia por Captura de Nêutron de Boro , Neoplasias , Humanos , Método de Monte Carlo , Nêutrons , Imagens de FantasmasRESUMO
Boron neutron capture therapy (BNCT) is high linear energy transfer (LET) radiation and tumor-selective radiation that does not cause serious damage to the surrounding normal tissues. BNCT might be effective and safe in patients with inoperable, locally advanced head and neck cancers, even those that recur at previously irradiated sites. However, carotid blowout syndrome (CBS) is a lethal complication resulting from malignant invasion of the carotid artery (CA); thus, the risk of CBS should be carefully assessed in patients with risk factors for CBS after BNCT. Thirty-three patients in our institution who underwent BNCT were analyzed. Two patients developed CBS and experienced widespread skin invasion and recurrence close to the carotid artery after irradiation. Careful attention should be paid to the occurrence of CBS if the tumor is located adjacent to the carotid artery. The presence of skin invasion from recurrent lesions after irradiation is an ominous sign of CBS onset and lethal consequences.
Assuntos
Terapia por Captura de Nêutron de Boro/efeitos adversos , Artérias Carótidas/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Ruptura Espontânea/etiologia , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: In this Tamoxifen Exemestane Adjuvant Multinational Japan sub-study, we evaluated the time course of changes in serum lipids in postmenopausal women with hormone-sensitive early breast cancer treated with exemestane, anastrozole, or tamoxifen for postoperative adjuvant therapy. PATIENTS AND METHODS: A total of 154 breast cancer patients were assigned to receive exemestane, anastrozole, or tamoxifen in this randomized open-label study. Serum lipid parameters including triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured during 1 year of treatment. RESULTS: TC and LDL-C rapidly decreased in patients treated with tamoxifen at 3 months. Compared with anastrozole and exemestane patients, TC and LDL-C were significantly lower at all assessment time points in tamoxifen patients (P < 0.05). TG increased in tamoxifen patients; it was significantly higher compared with exemestane patients at all assessment time points (P < 0.05). HDL-C slightly decreased in exemestane patients; it was significantly lower compared with anastrozole patients at 3 months and 1 year (P = 0.0179 and 0.0013, respectively). CONCLUSION: Changes of lipid profiles in Japanese postmenopausal women treated with tamoxifen were relatively favorable, while exemestane and anastrozole had no clinically significant effect on the serum lipids.
Assuntos
Androstadienos/uso terapêutico , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Lipídeos/sangue , Neoplasias Hormônio-Dependentes/sangue , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Nitrilas/uso terapêutico , Tamoxifeno/uso terapêutico , Triazóis/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anastrozol , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Japão , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Hormônio-Dependentes/patologia , Pós-Menopausa/sangue , Triglicerídeos/sangueRESUMO
BACKGROUND: Use of aromatase inhibitors in women with postmenopausal breast cancer accompanies risks of bone loss. We evaluated changes in bone mineral density (BMD) and bone turnover markers in patients treated with exemestane, anastrozole or tamoxifen for hormone-sensitive postmenopausal early breast cancer. PATIENTS AND METHODS: Sixty-eight patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational Japan bone substudy were randomly assigned to receive tamoxifen, exemestane or anastrozole. During a 2-year study period, lumbar spine BMD was measured using dual-energy X-ray absorptiometry, and urinary type I collagen cross-linked N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP) were also measured. RESULTS: BMD at 2 years of treatment was higher in tamoxifen patients compared with exemestane and anastrozole patients; however, the intergroup difference was not significant (p = 0.2521 and p = 0.0753, respectively). BMD was higher in exemestane patients compared with anastrozole patients; however, the intergroup difference was not significant (p = 0.7059 and p = 0.8134, respectively). NTX and BAP were significantly lower in tamoxifen patients compared with exemestane and anastrozole patients at 1 and 2 years of treatment (p < 0.05). CONCLUSION: Tamoxifen may provide better bone protection compared with exemestane or anastrozole. The effect of exemestane and anastrozole on bone loss may be comparable in Japanese postmenopausal women.
Assuntos
Androstadienos , Antineoplásicos , Densidade Óssea/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Nitrilas , Tamoxifeno , Triazóis , Idoso , Idoso de 80 Anos ou mais , Anastrozol , Androstadienos/efeitos adversos , Androstadienos/farmacologia , Androstadienos/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Reabsorção Óssea , Osso e Ossos/efeitos dos fármacos , Feminino , Humanos , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Pós-Menopausa , Tamoxifeno/efeitos adversos , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Triazóis/efeitos adversos , Triazóis/farmacologia , Triazóis/uso terapêuticoRESUMO
We studied 52 patients, each with a lumbosacral transitional vertebra. Using MRI we found that the lumbar discs immediately above the transitional vertebra were significantly more degenerative and those between the transitional vertebrae and the sacrum were significantly less degenerative compared with discs at other levels. We also performed an anatomical study using 70 cadavers. We found that the iliolumbar ligament at the level immediately above the transitional vertebra was thinner and weaker than it was in cadavers without a lumbosacral transitional vertebra. Instability of the vertebral segment above the transitional vertebra because of a weak iliolumbar ligament could lead to subsequent disc degeneration which may occur earlier than at other disc levels. Some stability between the transitional vertebra and the sacrum could be preserved by the formation of either an articulation or by bony union between the vertebra and the sacrum through its transverse process. This may protect the disc from further degeneration in the long term.
Assuntos
Disco Intervertebral/patologia , Vértebras Lombares/patologia , Doenças da Coluna Vertebral/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Cadáver , Feminino , Humanos , Ílio , Instabilidade Articular/fisiopatologia , Ligamentos Articulares/patologia , Região Lombossacral , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Sacro , Fatores SexuaisRESUMO
AIMS: Accurate evaluation of sentinel nodes is of clinical importance to avoid further surgery for axillary node dissection. A prospective study was carried out to investigate the feasibility and accuracy of touch imprint cytology (TIC) and touch imprint immunohistochemistry (TIHC). METHODS: Two hundred and five sentinel nodes from consecutive 118 patients with primary breast cancer were studied after successful identification of sentinel nodes. Sentinel nodes were sectioned at 2 mm intervals and imprint specimens prepared from all cut surfaces were subjected to Papanicolaou staining and immunohistochemical staining using anti-cytokeratin antibody. RESULTS: Forty-nine sentinel nodes from 40 patients were positive by permanent section. The sensitivity of TIC was 84% (41/49) per sentinel node and 83% (33/40) on a per patient basis. The sensitivity of TIHC was 86% (42/49) per sentinel node and 83% (33/40) on a per patient basis. When the results of TIC and TIHC were combined, the sensitivity was 88% (43/49) per sentinel node and 85% (34/40) on a per patient basis. Among the 156 negative sentinel nodes, four sentinel nodes from four different patients were consistently positive by TIC and TIHC, but only one patient out of 78 node-negative patients was upstaged. CONCLUSIONS: Touch imprint cytology is sufficiently sensitive for intraoperative evaluation of sentinel nodes. A slight improvement in the sensitivity is expected when immunohistochemistry is used. The combination of these methods provides better sensitivity than either method alone.
Assuntos
Neoplasias da Mama/patologia , Biópsia de Linfonodo Sentinela/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Citodiagnóstico/métodos , Feminino , Humanos , Imuno-Histoquímica , Período Intraoperatório , Metástase Linfática/diagnóstico , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: This study was conducted to investigate the efficacy and toxicity of weekly docetaxel administration in patients with metastatic breast cancer. PATIENTS AND METHODS: Thirty-seven women were treated with 1 h infusions of docetaxel at 40 mg/m2/week after pre-medication with 8 mg dexamethazone. Each cycle consisted of three consecutive weekly treatments followed by a 1 week rest. All patients were assessed for toxicity; five patients were not assessable for clinical response, time to progression (TTP) and overall survival (OS) because of early treatment failure, but they were included in intention-to-treat analysis. RESULTS: Patients received a median of four cycles (range, 1-9), with a median dose intensity of 28 mg/m2/week (range 22-30) and a median relative dose intensity of 0.95 (range 0.73-1.0). No patients showed complete response, whereas 14 had partial response, which accounted for 38% of objective response rate [95% confidence interval (CI) 22% to 53%]. In addition, three patients (8%, 95% CI 0% to 17%) had stable disease over 6 months. Clinical responses were achieved at a median of three cycles (range 1-4 cycles). The median TTP and OS were 5 and 12 months, respectively. The weekly docetaxel regimen was generally well tolerated. About half of the patients experienced grade > or = 1 neutropenia; only 19% had grade 3/4 neutropenia, including one case of grade 4. No febrile neutropenia was observed and fluid retention syndrome was uncommon. Non-hematologic toxicity, however, such as asthenia/fatigue, nail damage, tearing or hearing disorders, was seen with successive treatment cycles. CONCLUSIONS: Weekly docetaxel at 40 mg/m2/week is an active and feasible regimen for patients with metastatic breast cancer.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/análogos & derivados , Paclitaxel/uso terapêutico , Taxoides , Adulto , Idoso , Docetaxel , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Paclitaxel/efeitos adversos , Resultado do TratamentoRESUMO
Epstein-Barr virus (EBV) infection has been associated with infectious mononucleosis, EBV-associated hemophagocytic syndrome (EBV-AHS), chronic active EBV infection (CAEBV), lymphomas, inflammatory pseudotumor, lymphomatoid granulomatosis, and nasopharyngeal carcinoma. EBV-AHS and CAEBV are more lethal than infectious mononucleosis with imaging findings of gallbladder wall thickening, pleural effusion, cardiomegaly, and hepatomegaly. EBV infection is also associated with benign and malignant tumors.
Assuntos
Infecções por Vírus Epstein-Barr/diagnóstico , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/diagnóstico por imagem , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr/diagnóstico por imagem , Feminino , Granuloma de Células Plasmáticas/diagnóstico , Granuloma de Células Plasmáticas/diagnóstico por imagem , Histiocitose de Células não Langerhans/diagnóstico , Histiocitose de Células não Langerhans/diagnóstico por imagem , Humanos , Lactente , Mononucleose Infecciosa/diagnóstico , Mononucleose Infecciosa/diagnóstico por imagem , Japão , Granulomatose Linfomatoide/diagnóstico , Granulomatose Linfomatoide/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
To identify differentially expressed genes in hepatocarcinogenesis, we performed differential display analysis using surgically resected hepatocellular carcinoma (HCC) and adjacent non-tumorous liver tissues. We identified four cDNA fragments upregulated in HCC samples, encoding antisecretory factor-1 (AF), gp96, DAD1 and CDC34. Northern blot analysis demonstrated that these mRNAs were expressed preferentially in HCCs compared with adjacent non-tumorous liver tissues or normal liver tissues from non-HCC patients. The expression of these mRNAs was increased along with the histological grading of HCC tissues. These mRNA levels were also high in three human HCC cell lines (HuH-7, HepG2 and HLF), irrespective of the growth state. We also demonstrate that sodium butyrate, an inducer of differentiation, downregulated the expression of AF and gp96 mRNAs, supporting in part our pathological observation. Immunohistochemical analysis revealed that gp96 and CDC34 proteins were preferentially accumulated in cytoplasm and nuclei of HCC cells, respectively. Overexpression of these genes could be an important manifestation of HCC phenotypes and should provide clues to understand the molecular basis of hepatocellular carcinogenesis.
Assuntos
Antígenos de Neoplasias/genética , Carcinoma Hepatocelular/genética , Ligases/genética , Neoplasias Hepáticas/genética , Proteínas de Membrana/genética , RNA Mensageiro/metabolismo , Complexos Ubiquitina-Proteína Ligase , Adulto , Idoso , Ciclossomo-Complexo Promotor de Anáfase , Antígenos de Neoplasias/metabolismo , Proteínas Reguladoras de Apoptose , Northern Blotting , Carcinoma Hepatocelular/patologia , DNA Complementar/isolamento & purificação , Progressão da Doença , Feminino , Marcadores Genéticos , Humanos , Imuno-Histoquímica , Ligases/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , RNA Mensageiro/análise , Células Tumorais Cultivadas , Enzimas de Conjugação de Ubiquitina , Ubiquitina-Proteína Ligases , Regulação para CimaRESUMO
Although it is known that the pathogenic mechanism of Helicobacter pylori involves the stimulated production of interleukin-8 (IL-8) as an inflammatory mediator, the details of the pathway remain unclear. The role of mitogen-activated protein kinase (MAPK) in IL-8 production by H. pylori has been examined in an in vitro study. IL-8 mRNA expression in gastric epithelial cells (MKN 28) was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). IL-8 production was examined by ELISA. The activation of p38 MAPK was assessed by western blotting. Neither IL-8 mRNA nor activated p38 MAPK or p44/42 MAPK was detected in cells not treated with H. pylori. In contrast, incubation of cells with H. pylori, or IL-1beta, or both, clearly stimulated the expression of IL-8 mRNA within 60 min in a concentration-dependent manner. Phosphorylation of p38 MAPK and p44/p42 MAPK, as well as IL-8 production, occurred within 30 min and 24 hr after co-culturing MKN 28 cells with H. pylori and IL-1beta, respectively. Pretreatment of cells with MAPK inhibitors [1-[7-(4-fluorophenyl)-1,2,3,4-tetra-hydro-8-pyridylpyrazolo[5,1-c][1,2,4]triazin-2-yl]-2-phenylethanedione sulfate monohydrate (FR167653), 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)imidazole (SB203580), or 2-(2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one (PD98059)] significantly inhibited IL-8 production stimulated by H. pylori or IL-1beta or both. The combination of H. pylori and IL-1beta additively stimulated IL-8 production. The additive effect of H. pylori and IL-1beta on IL-8 production was inhibited by treatment with a p38 MAPK inhibitor. It was revealed that the culturing of MKN 28 cells with H. pylori significantly stimulates IL-8 production to a degree sufficient for induction of neutrophil chemotaxis via activation of p38 and p44/42 MAPK.
Assuntos
Helicobacter pylori/fisiologia , Interleucina-1/metabolismo , Interleucina-8/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator 2 Ativador da Transcrição , Anti-Inflamatórios não Esteroides/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Ativação Enzimática , Inibidores Enzimáticos , Humanos , Interleucina-8/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Pirazóis/farmacologia , Piridinas/farmacologia , RNA Mensageiro/metabolismo , Fatores de Tempo , Fatores de Transcrição/metabolismo , Células Tumorais Cultivadas , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
In this report, we describe a rare case of a malignant transformation in an ancient schwannoma arising in the right side of the neck of a 51-year-old man. The patient was referred to our hospital because of a mass that had been present for three years. The mass, measuring about 4 x 2 cm, was elastic and hard, relatively well demarcated, and movable upon palpation. Aspiration cytology was performed, but the diagnosis was unclear histologically. The patient was placed under general anesthesia and the tumor was totally excised. The tumor, which was easily excised, was connected to the sympathetic nerve at both poles. The histological diagnosis was a malignant transformation in an ancient schwannoma. The patient showed no clinical manifestations suggesting neurofibromatosis. Three months after the operation, a recurrent tumor, which was not resectable, was discovered extending deep into the skull base. The patient underwent two operations and two courses of radiation therapy, but the tumor metastasized to the lung and liver. He died of pulmonary failure eleven months after the initial treatment.
Assuntos
Neoplasias de Cabeça e Pescoço/patologia , Neurilemoma/patologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
To investigate the feasibility of repeated gene transfection in suicide gene therapy against human solid tumors by a combination of 5- fluorocytosine (5-FC) and its converting enzyme, cytosine deaminase (CD), we repeatedly transfected the yeast CD gene into the human pancreatic cancer cell line BXPC3 using the hemagglutinating virus of Japan-liposome in a new gene transfer method. The in vivo growth of the s.c. transplanted BXPC3 tumor in nude mice given CD-gene transfection was significantly suppressed by i.p. injection of 5-FC when compared with tumors treated with the control vector. Furthermore, the tumor transfected with the CD gene during a 7-day interval was suppressed much more than that of a single transfection. These results suggest that repeated transfection of the suicide gene together with the combination of 5-FC and the yeast CD gene using the hemagglutinating virus of Japan-liposome gene transfer method may be useful for the treatment of human solid tumors, including pancreatic cancer.
Assuntos
Terapia Genética/métodos , Nucleosídeo Desaminases/genética , Neoplasias Pancreáticas/terapia , Respirovirus/genética , Animais , Antimetabólitos Antineoplásicos/farmacocinética , Antimetabólitos Antineoplásicos/farmacologia , Divisão Celular/efeitos dos fármacos , Citosina Desaminase , Estudos de Viabilidade , Feminino , Flucitosina/farmacocinética , Flucitosina/farmacologia , Fluoruracila/farmacocinética , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Humanos , Injeções Intralesionais , Lipossomos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nucleosídeo Desaminases/biossíntese , Nucleosídeo Desaminases/metabolismo , Neoplasias Pancreáticas/patologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
DNA damage induced by irradiation causes overexpression of the p53 gene, and subsequently the upregulation of p53 downstream genes involved in cell cycle modification. Irradiated malignant cells which possess wild-type p53 have been known to undergo G1 arrest due to p21/Cip1/Waf1 upregulation. Other p53 downstream genes related to the modification of the cell cycle such as gadd45 may cause G2 arrest. Many of the genes which regulate the cell cycle progression have been identified, including the G1 phase specific ink4 family of cyclin-dependent kinase inhibitors (CDK-I), another group of CDK-Is, which affect the cyclin-CDK complexes ubiquitously, and S/G2 accelerator genes. The sequential changes in these cell cycle regulator genes after irradiation has not been clarified. We analyzed the appearance of the apoptotic fraction and cell cycle perturbation after irradiation using KB, a human squamous cell carcinoma line derived from oral floor, and examined the alteration of gene expression for cell cycle regulator genes. The KB cells proceeded to undergo apoptosis in a time and dose dependent manner after irradiation and showed G2 arrest accompanied by upregulation of p53, ubiquitous CDK-Is, and S and G2 accelerator genes.
Assuntos
Carcinoma de Células Escamosas/patologia , Proteínas de Ciclo Celular/biossíntese , DNA de Neoplasias/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Células KB/efeitos da radiação , Neoplasias Bucais/patologia , Proteínas de Neoplasias/biossíntese , Proteínas de Saccharomyces cerevisiae , Proteínas Supressoras de Tumor , Apoptose/genética , Apoptose/efeitos da radiação , Ciclo Celular/genética , Ciclo Celular/efeitos da radiação , Proteínas de Ciclo Celular/genética , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Inibidor de Quinase Dependente de Ciclina p21 , Inibidor de Quinase Dependente de Ciclina p27 , Quinases Ciclina-Dependentes/biossíntese , Quinases Ciclina-Dependentes/genética , Ciclinas/biossíntese , Ciclinas/genética , Dano ao DNA , DNA de Neoplasias/genética , Proteínas Fúngicas/biossíntese , Proteínas Fúngicas/genética , Fase G2/efeitos da radiação , Genes p16 , Genes p53 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Células KB/metabolismo , Proteínas Associadas aos Microtúbulos/biossíntese , Proteínas Associadas aos Microtúbulos/genética , Proteínas Motores Moleculares , Proteínas de Neoplasias/genética , Biossíntese de Proteínas , Proteínas/genética , Proteínas Quinases Associadas a Fase S , Proteína Supressora de Tumor p53/biossíntese , Proteínas GADD45RESUMO
CD56(+)T cells and CD56(+)natural killer (NK) cells are abundant in the human liver. The aim of this study was the further characterization of these cells in the liver with or without hepatitis C virus (HCV) infection. Liver mononuclear cells (MNC) were isolated from liver specimens obtained from the patients during abdominal surgery. In addition to a flow cytometric analysis, liver MNC and PBMC were cultured with the immobilized anti-CD3 Ab, IL-2, or a combination of IL-2 and IL-12 and their IFN-gamma production and the antitumor cytotoxicity were assessed. The liver MNC of HCV (-) patients contained 20% CD56(+)T cells whereas the same proportions decreased to 11% in chronic hepatitis livers and to 5% in cirrhotic livers. The proportion of NK cells also decreased in the cirrhotic livers. On the other hand, the populations of these cells in PBMC did not significantly differ among patient groups. The IFN-gamma production and the cytotoxicity against K562 cells, Raji cells, and a hepatocellular carcinoma, HuH-7 cells, greatly decreased in the cirrhotic liver MNC. In contrast, the cytotoxicity in PBMC did not significantly differ among the patient groups and was lower than that in the liver MNC of HCV (-) patients. CD56(+)T cells and NK cells but not regular T cells purified from liver MNC cultured with cytokines showed potent cytotoxicities against HuH-7 cells. These results suggest that a decreased number of CD56(+)T cells and NK cells in cirrhotic livers may be related to their susceptibility to hepatocellular carcinoma.
Assuntos
Antígeno CD56/análise , Carcinoma Hepatocelular/etiologia , Hepatite C/complicações , Células Matadoras Naturais/patologia , Cirrose Hepática/complicações , Neoplasias Hepáticas/etiologia , Linfócitos T/patologia , Idoso , Anticorpos/farmacologia , Complexo CD3/imunologia , Suscetibilidade a Doenças , Feminino , Hepatite C/patologia , Humanos , Interferon gama/biossíntese , Interleucina-2/farmacologia , Células Matadoras Naturais/imunologia , Fígado/patologia , Cirrose Hepática/imunologia , Cirrose Hepática/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Monócitos/patologia , Monócitos/fisiologia , Fenótipo , Linfócitos T/imunologiaRESUMO
In the presence of excess amounts of fluorine, a physiological divalent cation, magnesium (Mg(2+)), forms a novel phosphate analogue, magnesium fluoride (MgFn). Park et al. [Biochim. Biophys. Acta 1430, 127-140 (1999)] previously demonstrated that MgADP. MgFn forms a complex with myosin subfragment-1 (S-1), and the S-1.ADP. MgFn ternary complex mimics a transient state in the activity cycle of ATPase. In the present study, localized conformations in the regions of highly reactive cysteine and lysine residues, Cys 707 (SH1), Cys 697 (SH2), and Lys 83 (RLR), which change their conformations markedly during ATP hydrolysis, were studied using fluorescent probes and chemical modification. The global shape of the complex was also studied using small angle X-ray solution scattering and compared it with other previously reported myosin.ADP. fluorometal ternary complexes. The results suggest that the overall conformation and localized functional regions of the complex are quite similar to those in the presence of ATP, indicating that the complex mimics the M(**).ADP.P(i) steady state.
Assuntos
Difosfato de Adenosina/química , Fluoretos/química , Compostos de Magnésio/química , Subfragmentos de Miosina/química , Subfragmentos de Miosina/metabolismo , Síncrotrons , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/metabolismo , Naftalenossulfonato de Anilina/química , Naftalenossulfonato de Anilina/metabolismo , Animais , Sítios de Ligação , Galinhas , Corantes Fluorescentes/metabolismo , Fluoretos/metabolismo , Compostos de Magnésio/metabolismo , Modelos Moleculares , Músculo Esquelético/química , Oxidiazóis/química , Oxidiazóis/metabolismo , Maleabilidade , Ligação Proteica , Conformação Proteica , Espalhamento de Radiação , Soluções , Espectrometria de Fluorescência , Ácido Trinitrobenzenossulfônico/química , Ácido Trinitrobenzenossulfônico/metabolismo , Raios XRESUMO
We studied 23 patients with spondylolysis of the fifth lumbar vertebra (L5) and 20 with spondylolytic spondylolisthesis at this level. All were more than 40 years of age. The transverse processes at L5 were significantly wider in the former group than in the latter. We also dissected 56 cadavers to study the morphological relationship between the transverse process of L5 and the iliolumbar ligament, and found that the wider transverse process is associated with increased width of the posterior band of the iliolumbar ligament. If a patient with pars defects has wide transverse processes at L5, the lumbosacral junction may be stabilised by wide posterior bands of the iliolumbar ligament and the fifth lumbar vertebra by the ligament, preventing anterior displacement.
Assuntos
Ílio , Ligamentos Articulares/patologia , Vértebras Lombares/patologia , Espondilolistese/etiologia , Espondilolistese/patologia , Espondilólise/etiologia , Espondilólise/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antropometria , Fenômenos Biomecânicos , Cadáver , Feminino , Humanos , Ligamentos Articulares/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Radiografia , Análise de Regressão , Fatores de Risco , Caracteres Sexuais , Espondilolistese/classificação , Espondilolistese/diagnóstico por imagem , Espondilólise/classificação , Espondilólise/diagnóstico por imagemRESUMO
Several studies have demonstrated elevated expression of translation factor mRNAs in malignant tissues. In this study, using primary human hepatocellular carcinoma (HCC) tissues, we examined gene expression of translation factors, including 2 eukaryotic initiation factors (eIFs-4A1, -4E), 4 elongation factors (eEFs-1 alpha, -1 gamma, -1 delta, and -2) and 10 ribosomal proteins (Rps P1, P2, S10, L35, L5, L39, L9, L6, S3a and S17), whose mRNA expression has never been examined in HCC. Our results demonstrated that all the mRNAs examined were up-regulated in HCC tissues. Among 7 HCC tissues of different histological grades, the expression of these mRNAs remained at basal levels in a well to moderately differentiated (W/M-) HCC, was coordinately up-regulated in moderately differentiated (M-) HCCs. In moderately to poorly differentiated (M/P-) HCCs, the expression of eEFs-1 gamma, -1 delta, -2, Rps P0 and L9 mRNAs was further up-regulated along with the histological grading. These results therefore suggest that coordination and specific activation of translation factor genes might be involved in the process of liver carcinogenesis.
Assuntos
Carcinoma Hepatocelular/metabolismo , Regulação da Expressão Gênica , Neoplasias Hepáticas/metabolismo , Biossíntese de Proteínas , RNA Mensageiro/análise , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Fatores de Alongamento de Peptídeos/genética , Fatores de Iniciação de Peptídeos/genética , Proteínas Ribossômicas/genéticaRESUMO
There is evidence to suggest that CDC25B phosphatase is an oncogenic protein. To elucidate the role of CDC25B in colorectal carcinoma, we examined the expression of CDC25B at the mRNA and protein levels. Reverse transcription-PCR assay indicated that CDC25B was overexpressed in tumor tissues relative to normal mucosa in 6 of 10 cases. Using immunohistochemistry, we identified high expression of CDC25B in 77 of 181 colorectal cases (43%). Univariate analysis showed that high expression was a significant predictor for poor prognosis compared with low expression (5-year survival rate; 59% versus 82%, respectively; P < 0.0001). Multivariate analysis indicated that CDC25B was an independent prognostic marker (risk ratio for death, 3.7; P < 0.0001) even after controlling for various factors such as lymph node metastasis, tumor size, degree of differentiation, and depth of invasion. Furthermore, the level of CDC25B expression clearly predicted the outcome of patients with Dukes' B and Dukes' C tumors. On the other hand, CDC25A mRNA was overexpressed in 9 of 10 colorectal cancer cases, and immunohistochemistry for CDC25A showed high expression in 52 of 111 cases (47%), but no significant correlation with prognosis. Our findings suggest that CDC25B is a novel independent prognostic marker of colorectal carcinoma and that it may be clinically useful for selecting patients who could benefit from adjuvant therapy.
Assuntos
Carcinoma/diagnóstico , Carcinoma/enzimologia , Proteínas de Ciclo Celular/biossíntese , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/enzimologia , Fosfatases cdc25/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Western Blotting , Carcinoma/mortalidade , Colo/metabolismo , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/biossíntese , Masculino , Pessoa de Meia-Idade , Mucosa/metabolismo , Análise Multivariada , Prognóstico , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The aim of this study was to search for specific and sensitive mRNA markers or a combination of markers for RT-PCR detection of micrometastases in axillary lymph nodes (LNs) from patients with breast cancer. LNs (n=177) from 17 patients were examined with Cytokeratin20 (CK20), melanoma-associated genes (MAGE1, MAGE3), carcinoembryonic antigen (CEA), prostate-specific antigen (PSA), mammaglobin (MGB1) and mammaglobin B (MGB2) as molecular markers. CK20, MAGE1 and MAGE3 were slightly positive in primary tumors and CEA, PSA, MGB1 and MGB2 were highly positive. MGB1 and MGB2 were 100% positive in HE-positive LNs while CEA and PSA were only 35.7% and 57.1% positive. MGB1 and MGB2 were also 30.1% and 17.8% positive in HE-negative nodes. Thus, MGB1 and MGB2 are specific and a combination of the two should be useful for detection of micrometastases in axillary LNs of breast cancer patients.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Metástase Linfática/patologia , RNA Mensageiro/análise , Biomarcadores Tumorais/genética , Neoplasias da Mama/cirurgia , Primers do DNA , Feminino , Marcadores Genéticos , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Pós-Menopausa , Pré-Menopausa , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Sensibilidade e Especificidade , Células Tumorais CultivadasRESUMO
The role of pre- and intraoperative procedures for the localization of insulinomas has been extensively debated. We report a case of successful treatment using preoperative selective intra-arterial calcium injection and intraoperative glucose monitoring. A 12-year-old boy with hypoglycemic attacks had a large insulinoma in the head of the pancreas on computed tomography. Preoperative selective angiography combined with arterial stimulation-venous sampling (ASVS) by intra-arterial injection of calcium revealed no other insulinomas in the body and tail of the pancreas. Elevation of serum glucose on intraoperative monitoring confirmed complete enucleation of the insulinoma. Preoperative ASVS can accurately localize an insulinoma, and may help to increase the success rate of surgery and avoid blind pancreatectomy.