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1.
Proc Natl Acad Sci U S A ; 121(4): e2317283121, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38227666

RESUMO

Despite many clinical trials, CAR-T cells are not yet approved for human solid tumor therapy. One popular target is mesothelin (MSLN) which is highly expressed on the surface of about 30% of cancers including mesothelioma and cancers of the ovary, pancreas, and lung. MSLN is shed by proteases that cleave near the C terminus, leaving a short peptide attached to the cell. Most anti-MSLN antibodies bind to shed MSLN, which can prevent their binding to target cells. To overcome this limitation, we developed an antibody (15B6) that binds next to the membrane at the protease-sensitive region, does not bind to shed MSLN, and makes CAR-T cells that have much higher anti-tumor activity than a CAR-T that binds to shed MSLN. We have now humanized the Fv (h15B6), so the CAR-T can be used to treat patients and show that h15B6 CAR-T produces complete regressions in a hard-to-treat pancreatic cancer patient derived xenograft model, whereas CAR-T targeting a shed epitope (SS1) have no anti-tumor activity. In these pancreatic cancers, the h15B6 CAR-T replicates and replaces the cancer cells, whereas there are no CAR-T cells in the tumors receiving SS1 CAR-T. To determine the mechanism accounting for high activity, we used an OVCAR-8 intraperitoneal model to show that poorly active SS1-CAR-T cells are bound to shed MSLN, whereas highly active h15B6 CAR-T do not contain bound MSLN enabling them to bind to and kill cancer cells.


Assuntos
Neoplasias Pancreáticas , Receptores de Antígenos Quiméricos , Feminino , Humanos , Linhagem Celular Tumoral , Proteínas Ligadas por GPI/metabolismo , Mesotelina , Neoplasias Pancreáticas/tratamento farmacológico , Linfócitos T/metabolismo
3.
Minerva Chir ; 63(3): 241-7, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18577911

RESUMO

The authors report a new familial case of alpha-1- antitrypsin (AAT) deficiency with severe pulmonary emphysema and hemoptysis. A severely reduced serum AAT level of the proband, a 56-year-old farmer's wife and her sister were observed. Mutation analysis of the AAT gene was performed using allele-specific polymerase chain reaction (PCR) analysis followed by direct sequencing. The proband and her younger sister proved to be homozygous for PISiiyama. Although home oxygen therapy was induced in addition to previous medications including bronchodilators and cardiovascular conditioning, the proband's rate of decline of forced expiratory volume at one second (FEV1) was progressing. Lung transplantation was therefore advisable for the patient. Clinical analysis on Japanese cases reported in the literature shows that the rate of decline of FEV1 is one of the most convenient prognostic factors to find proper timing for surgical intervention. Lung transplantation is one of the best reliable current therapies to improve quality of life of severely impaired patients.


Assuntos
Transplante de Pulmão , Enfisema Pulmonar/etiologia , Deficiência de alfa 1-Antitripsina , alfa 1-Antitripsina/genética , Feminino , Volume Expiratório Forçado , Hemoptise/etiologia , Homozigoto , Humanos , Pessoa de Meia-Idade , Mutação , Linhagem , Reação em Cadeia da Polimerase , Prognóstico , Enfisema Pulmonar/diagnóstico por imagem , Qualidade de Vida , Radiografia Torácica , Tomografia Computadorizada por Raios X , Deficiência de alfa 1-Antitripsina/complicações , Deficiência de alfa 1-Antitripsina/genética
4.
Oncogene ; 26(8): 1178-87, 2007 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-16924234

RESUMO

Anaplastic thyroid cancer (ATC) is one of the most lethal of all human tumors, but cytogenetic information concerning ATC is extremely limited. Using our in-house array-based comparative genomic hybridization and 14 ATC cell lines with further fluorescence in situ hybridization analysis, we demonstrated amplification of the DUSP26 gene, known by another report as MAP kinase phosphatase-8. DUSP26 was overexpressed in ATC cell lines and primary ATC tumor samples. When overexpressed, either exogenously or endogenously, DUSP26 promoted growth of the ATC cells. DUSP26 encodes a protein containing a dual-specificity phosphatase domain that can dephosphorylate itself. DUSP26 effectively dephosphorylates p38 and has a little effect on extracellular signal-regulated kinase in ATC cells. DUSP26 protein formed a physical complex with p38, and promoted survival of ATC cells by inhibiting p38-mediated apoptosis. Our findings suggest that DUSP26 may act as an oncogene in ATC, and might be a useful diagnostic marker and therapeutic target of this disease.


Assuntos
Carcinoma/patologia , Amplificação de Genes , Proteínas Tirosina Fosfatases/genética , Neoplasias da Glândula Tireoide/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Apoptose/genética , Carcinoma/enzimologia , Carcinoma/genética , Caspase 3/genética , Linhagem Celular Tumoral , Proliferação de Células , Clonagem Molecular , Fosfatases de Especificidade Dupla , Humanos , Hibridização in Situ Fluorescente , Fosfatases da Proteína Quinase Ativada por Mitógeno , Proteínas Tirosina Fosfatases/antagonistas & inibidores , Proteínas Tirosina Fosfatases/metabolismo , RNA Interferente Pequeno/farmacologia , Neoplasias da Glândula Tireoide/enzimologia , Neoplasias da Glândula Tireoide/genética , Proteínas Quinases p38 Ativadas por Mitógeno/análise , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
5.
J Cancer Res Clin Oncol ; 133(4): 213-8, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17072649

RESUMO

PURPOSE: Ansaplastic thyroid cancer (ATC) is one of the most lethal malignancies, but the carcinogenic mechanism of ATC has not been clarified. Recently, we performed a cDNA microarray analysis and identified transmembrane protein 34 (TMEM34) that down-regulated in anaplastic thyroid cancer cell lines (ACL)s as compared to normal thyroid tissues. METHODS: To investigate the role of TMEM34 in ATC carcinogenesis, we examined expression levels of TMEM34 in ACLs as well as differentiated thyroid cancers (DTC)s and normal human tissues. To explore the effect of TMEM34 in ATC development, cell-growth assays with KTA2 cells were performed. RESULTS: Expression of TMEM34 was down-regulated in all 11 ACLs, as compared to either normal thyroid tissues or cell lines derived from papillary or follicular thyroid cancers. TMEM34 was expressed ubiquitously in normal human tissues tested. Transfection of TMEM34 into KTA2 cells led to inhibition of cell growth. CONCLUSIONS: Our findings suggest that TMEM34 might be a tumor suppressor gene, associated with the development of ATC from DTC.


Assuntos
Carcinoma/genética , Processos de Crescimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Proteínas de Membrana/metabolismo , Neoplasias da Glândula Tireoide/genética , Proteínas Supressoras de Tumor/metabolismo , Carcinoma/metabolismo , Carcinoma/patologia , Linhagem Celular Tumoral , Clonagem Molecular , Primers do DNA , Regulação para Baixo , Perfilação da Expressão Gênica/métodos , Humanos , Proteínas de Membrana/química , Análise de Sequência com Séries de Oligonucleotídeos/métodos , RNA Neoplásico/genética , RNA Neoplásico/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Transfecção , Proteínas Supressoras de Tumor/química
6.
Ann Oncol ; 17(11): 1615-9, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16600983

RESUMO

Peritoneal mesothelioma is a rare cancer of the peritoneum with about 250 new cases diagnosed each year in the United States. It is the second most common site for mesothelioma development and accounts for 10-20% of all mesotheliomas diagnosed in the United States. A meeting sponsored by the NIH Office of Rare Diseases was held in Bethesda, Maryland on September 13 and 14, 2004. The objective of this meeting was to review the epidemiology, biology and current surgical and medical management of peritoneal mesothelioma. In addition, the meeting also discussed clinical and pre-clinical evaluation of novel treatments for mesothelioma as well as ongoing laboratory research to better understand this disease. This report summarizes the proceedings of the meeting as well as directions for future clinical and basic research.


Assuntos
Mesotelioma/patologia , Mesotelioma/terapia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Mesotelioma/epidemiologia , Mesotelioma/genética , National Institutes of Health (U.S.) , Neoplasias Peritoneais/epidemiologia , Neoplasias Peritoneais/genética , Estados Unidos
7.
Ann Oncol ; 17(5): 842-7, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16524972

RESUMO

BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. RESULTS: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P < 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes' stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P < 0.001). Patients with Dukes' C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. CONCLUSIONS: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/genética , Mutação , Proteína Supressora de Tumor p53/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Idoso , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Análise Mutacional de DNA , Éxons , Feminino , Seguimentos , Humanos , Agências Internacionais , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Taxa de Sobrevida
8.
Kyobu Geka ; 58(9): 787-93, 2005 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-16104563

RESUMO

A 50-year-old man with continuous hemosputa and large hematoma of left upper lobe contiguous to bilateral emphysematous bullous disease was admitted for surgery to stop hemorrhage and to resect left lung hematoma and multiple bullae. Bullectomy and neodymium yttrium aluminum garnet (Nd-YAG) laser irradiation to bullae of left upper lobe performed successfully with maximum preserved pulmonary function of it. Pathological examination, however, revealed anaplastic carcinoma inside bulla of S(1+2)c with minimal invasion into adhered parietal pleura (p 3). Left upper lobectomy was carried out with complete mediastinal lymph node dissection (ND 2 b). The final pathological diagnosis was large cell carcinoma of left S(1+2)c with the staging pT3N0M0 and stage II. The patient lives actively in daily life more than 7 years without any recurrence. Clinical analysis of Japanese 20 cases of lung carcinoma with initial signs of hemosputa and/or hemoptysis contiguous to emphysematous bullae elucidate following important facts. Hemosputa and hemoptysis play important role for early finding and diagnosis of lung cancer contiguous to bullous disease, especially in patients of early clinical stage with or without computed tomography (CT) exams and promise to better surgical prognosis and survivals as compared with non hemosputa ones.


Assuntos
Vesícula/cirurgia , Carcinoma de Células Grandes/diagnóstico , Hematoma/cirurgia , Pneumopatias/cirurgia , Neoplasias Pulmonares/diagnóstico , Pneumonectomia , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/cirurgia , Hemoptise/cirurgia , Humanos , Fotocoagulação a Laser , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Enfisema Pulmonar/complicações
9.
Br J Cancer ; 92(12): 2216-24, 2005 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-15956966

RESUMO

Anaplastic thyroid cancer (ATC) is one of the most fulminant and foetal diseases in human malignancies. However, the genetic alterations and carcinogenic mechanisms of ATC are still unclear. Recently, we investigated the gene expression profile of 11 anaplastic thyroid cancer cell lines (ACL) and significant decreased expression of haemoglobin beta (HBB) gene in ACL. Haemoglobin beta is located at 11p15.5, where loss of heterozygosity (LOH) was reported in various kinds of cancers, including ATC, and it has been suggested that novel tumour suppressor genes might exist in this region. In order to clarify the meaning of decreased expression of HBB in ATC, the expression status of HBB was investigated with ACL, ATC, papillary thyroid cancer (PTC) and normal human tissues. Haemoglobin beta showed significant decreased expression in ACLs and ATCs; however, in PTC, HBB expressed equal to the normal thyroid gland. In addition, HBB expressed in normal human tissues ubiquitously. To validate the tumour-suppressor function of HBB, cell growth assay was performed. Forced expression of HBB in KTA2 cell, which is a kind of ACL, significantly suppressed KTA2 growth. The mechanism of downregulation of HBB in ATC is still unclear; however, our results suggested the possibility of HBB as a novel tumour-suppressor gene.


Assuntos
Carcinoma/genética , Globinas/genética , Neoplasias da Glândula Tireoide/genética , Carcinoma/patologia , Linhagem Celular Tumoral , Proliferação de Células , Perfilação da Expressão Gênica , Genes Supressores de Tumor , Hemoglobinas/genética , Humanos , Neoplasias da Glândula Tireoide/patologia
10.
Endocr Relat Cancer ; 12(1): 65-73, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15788639

RESUMO

We have been investigating gene-expression profiles in estrogen receptor (ER)-negative breast cancers to identify molecules involved in breast carcinogenesis and to select genes or gene products that might be useful as diagnostic markers or targets for new molecular therapies. Here we report evidence that the gene encoding retinoic acid-induced protein 3 (RAI3) is a potential molecular target for treatment of breast cancers. Using quantitative reverse transcription-PCR (RT-PCR), we documented increased expression of RAI3 in 19 of 25 primary breast cancers and in 6 of 11 breast-cancer cell lines examined, by comparison with normal mammary-gland tissue. Treatment of human embryonic kidney (HEK293) cells with siRNA against RAI3 suppressed expression of RAI3 and also suppressed cell growth. Transfection of siRNA into breast-cancer cell lines MCF7 and T47D also suppressed RAI3 mRNA and growth of the cancer cells. Because our data imply that up-regulation of RAI3 function is a frequent feature of breast carcinogenesis, we suggest that selective suppression of signal from RAI3 might hold promise for development of a new strategy for treating breast cancers.


Assuntos
Neoplasias da Mama/terapia , RNA Interferente Pequeno/farmacologia , Receptores de Estrogênio/metabolismo , Receptores Acoplados a Proteínas G/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Células Cultivadas , Feminino , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Glândulas Mamárias Humanas/citologia , Glândulas Mamárias Humanas/metabolismo , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/farmacologia , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
11.
Endocr Relat Cancer ; 11(4): 843-54, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15613457

RESUMO

Little is known about the genetic mechanisms of anaplastic thyroid cancer (ATC). This is the most virulent of all human malignancies, and it is believed to result from transformation of differentiated thyroid cancers. To identify a set of genes involved in the development of ATC, we investigated expression profiles of 11 cell lines derived from ATC using a cDNA microarray representing 25 344 genes. Semi-quantitative RT-PCR experiments carried out for some genes that had shown altered expression on the microarray verified frequent over-expression of destrin, HSPA8, stathmin, LDH-A, ATP5A1, PSMB6, B23, HDP-1 and LDH-B, and frequent under-expression of thyroglobulin, PBP and c-FES/FPS genes among the cell lines and also among ten primary ATCs. In addition to mRNA expression studies, up-regulation of GDI2, destrin and stathmin were confirmed with immunohistochemical analysis. The extensive list of genes identified provides valuable information towards understanding the development of ATC, and provides a source of possible biomarkers for diagnosis and/or molecular targets for the development of novel drugs to treat ATC.


Assuntos
Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , RNA Mensageiro/análise , RNA Neoplásico/análise , Neoplasias da Glândula Tireoide/genética , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Humanos , Japão , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Glândula Tireoide
12.
J Hepatobiliary Pancreat Surg ; 10(6): 425-7, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14714162

RESUMO

BACKGROUND/PURPOSE: Radiofrequency ablation (RFA) and microwave coagulation therapy (MCT) have been gaining acceptance as a standard method in the management strategy of liver cancer, for reasons of minimally invasive techniques and effective results. We present our experience of RFA and MCT in patients with liver cancer, and analyze retrospectively the advantages and disadvantages of both of the percutaneous and laparoscopic approaches. METHODS: Thirty-two consecutive patients (23 men and 9 women) with 19 hepatocellular carcinomas (HCC), 12 metastatic liver cancers, and recurrent cholangiocellular carcinoma (CCC), were enrolled in this study. Out of these 32 patients, as a prior laparotomy, 19 underwent hepatectomy, colectomy, gastrectomy or cholecystectomy, and 15 were treated with the laparoscopic approach, 17 treated with the percutaneous approach, and 2 treated with the combined approach of those two. All of these procedures were carried out under general anesthesia with ultrasound guidance. Seven and 30 days after these procedures, an assessment helical computed tomography was done. RESULTS: No sign of the residual tissues was noted in all patients except only one case. CONCLUSIONS: The percutaneous approach was thought to be a more practical and less invasive method regardless previous laparotomy. For the laparoscopic approach, tumors located at the hepatic surface or margin were preferable candidates.


Assuntos
Ablação por Cateter/métodos , Laparoscopia , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Carcinoma Hepatocelular/cirurgia , Colangiocarcinoma/cirurgia , Feminino , Humanos , Neoplasias Hepáticas/secundário , Masculino , Micro-Ondas/uso terapêutico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Resultado do Tratamento
13.
Dis Esophagus ; 15(3): 226-31, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12444995

RESUMO

The aim of this study was to evaluate the effect of preoperative chemotherapy on metastatic lymph nodes and on the outcome of patients who underwent esophagectomy for advanced squamous cell carcinoma of the esophagus. Fifty-nine patients with potentially resectable squamous cell carcinoma of the esophagus were studied. Twenty patients (group A) were treated by preoperative chemotherapy with cisplatin, 5-fluorouracil, and leucovorin, followed by surgery. Thirty-nine patients underwent surgery alone (group B). A total of 2591 resected lymph nodes were histologically evaluated for metastasis and the effect of chemotherapy. The metastasis rate in the resected lymph nodes, the number of metastatic lymph nodes, and outcome of the patients were statistically analyzed between groups. In group A, the clinical and pathological response rates were 75% and 75% respectively. The metastasis rate in the resected lymph nodes was significantly higher in group B (P < 0.01). The mean number of metastatic lymph nodes was significantly lower in group A (P < 0.05). Furthermore, the mean number of metastatic lymph nodes was significantly lower in the chemotherapy responders than in non-responders. The survival rate in group A was better than in group B (P = 0.07). Preoperative chemotherapy reduced the number of metastatic lymph nodes and may contribute to improving the outcome of the patients who have undergone esophagectomy for squamous cell carcinoma of the esophagus.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/secundário , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Linfonodos/patologia , Adulto , Idoso , Biópsia por Agulha , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Estudos de Casos e Controles , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Esofagectomia/métodos , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Pré-Operatórios , Probabilidade , Prognóstico , Estatísticas não Paramétricas , Análise de Sobrevida , Resultado do Tratamento
14.
Dis Esophagus ; 15(3): 237-41, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12444997

RESUMO

A 63-year-old man presented to our hospital with persistent dysphagia. Radiologic and endoscopic examination disclosed a 2.0-cm exophytic tumor in the middle third of the esophagus. An endscopically obtained biopsy specimen was found to represent undifferentiated small cell carcinoma. Computed tomography of the chest, abdomen, and cervical region was performed, as were gallium and bone scintigraphy. Metastasis to an adjacent lymph node was detected, without metastasis to distant organs. After neoadjuvant chemotherapy with carboplatin (CBDCA) (400 mg/m2) and etoposide (VP-16) (100 mg/m2), endoscopy and barium-swallow esophagography showed regression. Thoracic esophagectomy then was performed with mediastinal, abdominal and cervical lymph node dissection. The resected tumor was polypoid, measuring 0.5 x 0.5 cm. The lesion consisted mainly of small anaplastic cells, but included a small focus of squamous cell carcinoma. The patient has survived for more than 7 months with no further treatment and no evidence of recurrent disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/cirurgia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Linfonodos/patologia , Biópsia por Agulha , Carboplatina/administração & dosagem , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/secundário , Quimioterapia Adjuvante , Neoplasias Esofágicas/patologia , Esofagectomia/métodos , Esofagoscopia , Etoposídeo/administração & dosagem , Seguimentos , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Pré-Operatórios , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Hepatogastroenterology ; 49(46): 984-8, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12143259

RESUMO

BACKGROUND/AIMS: In patients with esophageal varices, we investigated the impact on long-term outcome of combining interventional radiologic procedures with endoscopic therapy. METHODOLOGY: Of 133 patients with esophageal varices, 86 were treated with endoscopic therapy alone and 47 underwent endoscopic therapy in addition to interventional radiologic procedures. End-points considered during 5-years of follow-up included recurrent bleeding and retreatment. RESULTS: Bleeding rates were 24.4% in the endoscopy group and 25.4% in the combined therapy group. Retreatment rates at 1, 3, and 5 years for the endoscopy group versus the combined therapy group were 40.7% versus 30.3%, 72.0% versus 67.5%, and 88.2% versus 80.5%, respectively, representing no significant difference between two groups. However, cumulative retreatment rates in Child's class C cases were significantly lower in the combined therapy group than in the endoscopy group (P = 0.025). Patients who had combined therapy which included all embolizing techniques showed significantly lower retreatment rates than patients treated with endoscopy alone (P = 0.05). CONCLUSIONS: In combination, interventional radiologic and endoscopic therapies are highly effective and can improve long-term outcome in patients with esophageal varices, especially those with poor liver function and those who undergo embolization by all techniques.


Assuntos
Embolização Terapêutica/métodos , Varizes Esofágicas e Gástricas/terapia , Esofagoscopia/métodos , Hemorragia Gastrointestinal/terapia , Escleroterapia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia , Terapia Combinada , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Feminino , Hemorragia Gastrointestinal/diagnóstico por imagem , Humanos , Ligadura/métodos , Masculino , Pessoa de Meia-Idade , Portografia , Baço/irrigação sanguínea , Resultado do Tratamento
20.
J Surg Oncol ; 78(3): 208-14, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11745809

RESUMO

BACKGROUND AND OBJECTIVES: Cyclin D1 is known to play important roles in the G1/S check-point of the cell cycle. We investigated the correlation between cyclin D1 overexpression and clinical characteristics to clarify its prognostic significance in patients with esophageal cancer. METHODS: From 1991 to 1998, cyclin D1 was investigated in esophageal cancers from 86 patients who underwent esophagectomy. Overexpression of cyclin D1 was demonstrated using an immunohistochemical method. RESULTS: Overexpression of cyclin D1 was found in 23 (26.7%) of 86 cases. Overexpression of cyclin D1 correlated with lymph node metastasis (P = 0.0083) and lymphatic vessel invasion (P = 0.018). Cyclin D1 overexpression may indicate resistance to chemotherapy. The patients with cyclin D1 overexpression had a significantly lower survival rate than those without overexpression (P = 0.013). The multivariate analysis revealed cyclin D1 overexpression to be an important prognostic factor in patients with esophageal cancer. CONCLUSIONS: Immunohistochemical examination of cyclin D1 expression may provide important prognostic information in univariate and multivariate analysis and may be necessary for determining therapeutic strategies for esophageal cancer.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Ciclina D1/biossíntese , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas/patologia , Ciclo Celular , Neoplasias Esofágicas/patologia , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Análise de Sobrevida
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