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1.
Intern Med ; 58(24): 3551-3555, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31434823

RESUMO

Treatment involving the insertion of an implantable cardioverter defibrillator and cardiac resynchronization therapy devices has markedly improved the prognosis of cardiac sarcoidosis. However, the prognosis remains poor in patients with advanced cardiac dysfunction or heart failure. We herein report the clinical course and histopathological findings of the autopsied heart of a patient with cardiac sarcoidosis with long-term refractory heart failure.

2.
Int Heart J ; 60(4): 788-795, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31353344

RESUMO

Severe ventricular arrhythmias such as high-grade atrioventricular block and ventricular tachycardia may cause lethal conditions or sudden death in patients with cardiac sarcoidosis (CS). Physicians should examine patients carefully for these conditions and treat them appropriately. As arrhythmias are being better diagnosed and treated, physicians are increasingly aware of atrial arrhythmias, which have not been focused upon as CS-related conditions, in patients with CS. This article reports a case of atrial flutter in sarcoidosis, and discusses literature findings on atrial arrhythmias and atrial involvement of CS. It is highly likely that atrial arrhythmia and supraventricular conduction disorder associated with or caused by CS are more common than previously thought. Physicians should pay careful attention for these conditions in the diagnosis and treatment of CS.


Assuntos
Fibrilação Atrial/etiologia , Flutter Atrial/etiologia , Cardiomiopatias/complicações , Átrios do Coração/fisiopatologia , Sarcoidose/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Flutter Atrial/diagnóstico , Flutter Atrial/cirurgia , Cardiomiopatias/diagnóstico , Cardiomiopatias/fisiopatologia , Ablação por Cateter , Ecocardiografia , Eletrocardiografia Ambulatorial , Átrios do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Sarcoidose/diagnóstico , Sarcoidose/fisiopatologia
3.
J Thorac Oncol ; 12(3): 477-490, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27867002

RESUMO

INTRODUCTION: Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy in which the mitogen-activated protein kinase pathway plays a critical role in the regulation of tumorigenesis. Hyaluronic acid (HA) is a major component of the extracellular matrix, and elevated HA levels with a concurrent increase in malignant properties are associated with MPM. METHODS: We evaluated the effects of trametinib, a mitogen-activated protein kinase (MEK) inhibitor, and 4-methylumbelliferone (4-MU), an HA synthesis inhibitor, alone and in combination on MPM cells in vitro and in vivo. We studied the effects of trametinib, 4-MU, and their combination on MPM cells by using cell viability assays, Western blot analysis, and a mouse xenograft model. RESULTS: Trametinib and 4-MU exhibited antiproliferative activity in MPM cells. Trametinib blocked MEK-dependent extracellular signal-regulated kinase (ERK) phosphorylation and decreased CD44 expression in a concentration-dependent manner. Trametinib inhibited the expression of Fra-1 (the activator protein 1 [AP1] component), inhibited ERK phosphorylation, and decreased CD44 expression. 4-MU inhibited ERK phosphorylation but not CD44 expression. In a mouse xenograft model, trametinib and 4-MU alone suppressed tumor growth compared with a control. The combination had a greater inhibitory effect than either monotherapy. Immunohistochemical analysis showed that trametinib treatment alone significantly reduced expression of programmed cell death 1 ligand 1. Furthermore, the combination of trametinib and 4-MU resulted in higher expression of programmed cell death 1 and programmed cell death 1 ligand 1 than did the 4-MU treatment alone. CONCLUSIONS: Our results suggest that trametinib and 4-MU are promising therapeutic agents in MPM and that further study of the combination is warranted.


Assuntos
Antígeno B7-H1/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Receptores de Hialuronatos/química , Himecromona/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Neoplasias Pleurais/tratamento farmacológico , Receptor de Morte Celular Programada 1/metabolismo , Piridonas/farmacologia , Pirimidinonas/farmacologia , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Indicadores e Reagentes/farmacologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Mesotelioma/metabolismo , Mesotelioma/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pleurais/metabolismo , Neoplasias Pleurais/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Hinyokika Kiyo ; 62(10): 553-556, 2016 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-27919132

RESUMO

A 70-year-old man was referred to our department for further examination and treatment of a painless penile mass of about 2cm. The patient first noticed the mass onlya few weeks before presentation. Diagnostic biopsy was interpreted as leiomyosarcoma. Through systemic examinations the clinical stage of his disease was diagnosed as cT2N0M0 and we performed total penectomy. Histopathological examination for the totallyresected tissue disclosed the concomitant presence of regions compatible to squamous cell carcinoma and the results of immunohistochemistrywere compatible with the diagnosis of squamous cell carcinoma, sarcomatoid subtype of the penis. One month after the surgery, multiple metastases to left inguinal lymph nodes and lungs developed, for which systemic chemotherapy by doxorubicin was ineffective and the patient died of respiratoryinsufficiencyfive months after presentation.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Penianas/patologia , Idoso , Antibióticos Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/cirurgia , Doxorrubicina/uso terapêutico , Evolução Fatal , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Neoplasias Penianas/tratamento farmacológico , Neoplasias Penianas/cirurgia
5.
J Toxicol Pathol ; 27(3-4): 205-15, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25378805

RESUMO

Food allergies are driven by aberrant T helper (Th) 2 cells. Lipopolysaccharide (LPS) influences the development of Th2-mediated diseases, but its role in food allergy and tolerance remains unclear. To address this issue, we established mouse models presenting allergic or tolerant responses to ovalbumin (OVA). Mice sensitized with crude OVA developed Th2 responses including acute diarrhea, increases in serum OVA-specific IgE, dominant production of serum OVA-specific IgG1, increases in Th2-type cytokines and proliferation of mast cells in duodenal and colonic tissues. Sensitization of mice with crude OVA and LPS abrogated Th2-type responses observed in allergic mice. The level of OVA-specific proliferation in mesenteric lymph node CD4(+) T cells was comparable in allergic and tolerant mice, indicating that the tolerance is not caused by anergy and apoptosis of antigen-primed T cells. Expression of Th1- and Th2-type cytokines was suppressed in whole spleen cells and/or purified spleen CD4(+) T cells of tolerant mice, indicating that the tolerance was not caused by the shift from Th2 to Th1. On the other hand, interleukin (IL)-10, a regulatory cytokine produced by regulatory T cells, was upregulated in whole spleen cells and purified spleen CD4(+) T cells of tolerant mice. Furthermore, spleen CD4(+) T cells from tolerant mice suppressed the growth of CD4(+) T cells from DO11.10 mice in co-culture. These results indicate that tolerance is induced in allergic mice by simultaneous exposure to LPS during sensitization with OVA and that a population of T cells producing IL-10 plays an important role in the tolerance induction.

6.
Int Surg ; 99(5): 577-83, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25216424

RESUMO

Abstract A 78-year-old man was admitted to our hospital with right upper abdominal pain and fever. His general condition was poor. The laboratory data showed severe inflammatory reactions. Computed tomography revealed an irregular tumor in the gallbladder. (18)F-fluorodeoxy-glucose positron emission tomography (FDG-PET) showed high uptake by the tumor, with diffuse uptake in the spine. Based on the elevated leukocyte count and FDG-PET findings, a granulocyte-colony stimulating factor (G-CSF)-producing tumor was diagnosed (G-CSF 120 pg/mL). We performed cholecystectomy with central bisegmentectomy of the liver, lymph node dissection and right hemicolectomy. Histologically, the tumor was an adenosquamous cell carcinoma of the gallbladder. Immunohistochemical staining of the tumor cells was positive for G-CSF. Postoperatively, the general condition of the patient was improved. The fever subsided, the leukocyte count and serum G-CSF level normalized, and FDG-PET showed no uptake in the spine postoperatively. The patient showed no signs of recurrence at 27 months after undergoing surgery. FDG-PET is a useful method for diagnosing G-CSF-producing gallbladder carcinoma. Aggressive curative resection for G-CSF-producing gallbladder carcinoma may improve patients' general condition and prognosis.


Assuntos
Carcinoma Adenoescamoso/metabolismo , Neoplasias da Vesícula Biliar/metabolismo , Fator Estimulador de Colônias de Granulócitos/biossíntese , Idoso , Carcinoma Adenoescamoso/diagnóstico , Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/cirurgia , Colecistectomia , Fluordesoxiglucose F18 , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Imuno-Histoquímica , Masculino , Tomografia por Emissão de Pósitrons
7.
J Clin Immunol ; 34 Suppl 1: S35-45, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24793544

RESUMO

IgM exists as both a monomer on the surface of B cells and a pentamer secreted by plasma cells. Both pre-immune "natural" and antigen-induced "immune" IgM antibodies are important for protective immunity and for immune regulation of autoimmune processes by recognizing pathogens and self-antigens. Effector proteins interacting with the Fc portion of IgM, such as complement and complement receptors, have thus far been proposed but fail to fully account for the IgM-mediated protection and regulation. A major reason for this deficit in our understanding of IgM function seems to be lack of data on a long elusive Fc receptor for IgM (FcµR). We have recently identified a bona fide FcµR in both humans and mice. In this article we briefly review what we have learned so far about FcµR.


Assuntos
Linfócitos B/imunologia , Imunoglobulina M/imunologia , Receptores Fc/imunologia , Animais , Autoantígenos/imunologia , Humanos , Imunomodulação , Camundongos , Receptores Fc/isolamento & purificação
8.
Int J Clin Oncol ; 17(1): 33-9, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22237726

RESUMO

Malignant pleural mesothelioma (MPM) remains suffering poor prognosis in spite of recent diagnostic and therapeutic progress. Although there is currently no established evidence, early diagnosis and early intervention may play a key role to improve prognosis of MPM, similarly to other malignancies. As pleural effusion is usually the first clinical sign of MPM, pleural effusion cytology is often the first diagnostic examination to be carried out. Since the sensitivity of pleural effusion cytology is approximately 60%, however, false-negative diagnosis is given to almost half of true MPM patients at this clinical step. One practical way to reduce the number of misdiagnosed MPM is to encourage performing thoracoscopic pleural biopsy unless definitive diagnosis other than MPM is established. There still remain a considerable number of patients with radiological/thoracoscopic T0 MPM who are misdiagnosed with nonspecific pleuritis after a complete investigation including thoracoscopic biopsies. Such patients will turn out to be malignant during follow-up period, although they have the best opportunity for long-term survival if only early therapeutic intervention is given. Currently, we are performing diagnostic total parietal pleurectomy in highly selected patients, who are characterized with strong clinical suspicion, positive pleural effusion cytology but uncertain pathological diagnosis, excellent cardiopulmonary reserve, and with written informed consent for highly invasive diagnostic surgery for pathologically unproven disease.


Assuntos
Detecção Precoce de Câncer , Mesotelioma/diagnóstico , Pleura/cirurgia , Neoplasias Pleurais/diagnóstico , Humanos , Mesotelioma/patologia , Mesotelioma/cirurgia , Estadiamento de Neoplasias , Derrame Pleural Maligno/patologia , Neoplasias Pleurais/patologia , Neoplasias Pleurais/cirurgia , Prognóstico
9.
Int J Clin Oncol ; 17(1): 40-7, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22237727

RESUMO

Malignant mesothelioma is an asbestos-related malignancy that arises primarily from mesothelial cells on the serosal surfaces of the pleural, peritoneal, and pericardial cavities. Malignant pleural mesothelioma (MPM) is most common, and its incidence is dramatically increasing worldwide as a result of widespread use of asbestos. Morphological discrimination between MPM and reactive mesothelial hyperplasia is difficult, and the most reliable pathological criterion for malignancy is mesothelial proliferation invading deeply into subpleural adipose tissues. To establish radical cure of MPM, it is crucial to find early-stage MPM of epithelial type, in which mesothelial proliferation is localized on the serosal surface of parietal pleura or limited within the submesothelial fibrous tissues of parietal pleura. The initial clinical presentation for patients with MPM is frequently dyspnea and/or chest pain due to large pleural effusion, and cytological analysis of pleural effusions is valuable to find patients with early-stage MPM of epithelial type. Recently, cytological features of MPM in pleural effusion, molecular markers for MPM, and genetic alternations of MPM have been reported. In this review, we discuss major issues on pathological and molecular biological approaches for diagnosis of early-stage MPM of epithelial type.


Assuntos
Biomarcadores Tumorais/metabolismo , Detecção Precoce de Câncer , Mesotelioma/metabolismo , Mesotelioma/patologia , Neoplasias Pleurais/metabolismo , Neoplasias Pleurais/patologia , Biomarcadores Tumorais/genética , Genes p16 , Humanos , Mesotelioma/genética , Estadiamento de Neoplasias , Neurofibromina 2/genética , Neurofibromina 2/metabolismo , Derrame Pleural Maligno/patologia , Neoplasias Pleurais/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo
10.
Ann Thorac Cardiovasc Surg ; 17(1): 71-3, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21587134

RESUMO

Alveolar adenoma is a rare pulmonary neoplasm. This report describes a case of alveolar adenoma of the lung in a 61-year-old woman. A chest X-ray demonstrated a solitary round pulmonary nodule. After six years of observation, this lesion had increased in size. Thoracoscopic left upper segmentectomy was performed on account of a possible low-grade malignant tumor. Histologically, the neoplastic epithelial cells, which had the appearance of proliferative type II pneumocytes, revealed no evidence of malignancy. These findings indicated that the tumor is alveolar adenoma of the lung. The course of disease remains uneventful, one year after the resection.


Assuntos
Adenoma/patologia , Neoplasias Pulmonares/patologia , Alvéolos Pulmonares/patologia , Nódulo Pulmonar Solitário/patologia , Adenoma/cirurgia , Células Epiteliais Alveolares/patologia , Biópsia , Proliferação de Células , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Pessoa de Meia-Idade , Pneumonectomia , Alvéolos Pulmonares/cirurgia , Nódulo Pulmonar Solitário/cirurgia , Toracoscopia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
11.
Pathology ; 43(1): 36-9, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21240063

RESUMO

AIMS: Perianal fistulae are often observed in patients with Crohn's disease (CD), although the development of associated adenocarcinomas is very rare. The origin of adenocarcinomas in perianal fistulae associated with CD remains controversial and includes adjacent anal glands or rectal mucosa. Here, we attempted to determine the origin. METHODS: We performed immunohistochemical analysis on seven cases of adenocarcinomas in perianal fistulae associated with CD using antibodies against mucins (MUCs), cytokeratins (CKs) and the intestine-specific transcription factor CDX2. RESULTS: MUC2 and CK20 were expressed in all seven adenocarcinomas examined. MUC5AC/CLH2, MUC5AC/HGM and CDX2 were positive in four (57%), five (71%), and five (71%) adenocarcinomas, respectively. These proteins were positive in rectal mucosa, and negative in the anal glands. Six of seven adenocarcinomas (86%) were negative for CK7. CK7 was expressed in the anal glands, but not in rectal mucosa. CONCLUSIONS: Adenocarcinomas in perianal fistulae associated with CD showed immunohistochemical phenotypes similar to those of rectal-type mucosa, rather than the anal glands. The adenocarcinomas might originate from cells migrating from the adjacent rectal mucosa to the CD-associated perianal fistulae.


Assuntos
Adenocarcinoma/patologia , Canal Anal/patologia , Doença de Crohn/patologia , Fístula Retal/patologia , Neoplasias Retais/patologia , Reto/patologia , Adenocarcinoma/complicações , Adenocarcinoma/metabolismo , Adulto , Canal Anal/metabolismo , Biomarcadores Tumorais/metabolismo , Doença de Crohn/complicações , Doença de Crohn/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Fístula Retal/etiologia , Fístula Retal/metabolismo , Neoplasias Retais/complicações , Neoplasias Retais/metabolismo , Reto/metabolismo
12.
Cancer Sci ; 102(3): 648-55, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21205078

RESUMO

Malignant pleural mesothelioma is a refractory tumor with increasing incidence. In the present study, we established six mesothelioma cell lines possessing two allele deletions of the p16(INK4A) gene and one allele deletion of the neurofibromatosis type 2 gene, MM16, MM21, MM26, MM35, MM46 and MM56, from pleural effusion fluids or surgically resected tumors of Japanese patients. MM21, MM26 and MM46 cells failed to develop tumors in BALB/c-nude mice following subcutaneous inoculation. MM16 and MM35 cells slowly generated tumors at the site of subcutaneous inoculation in BALB/c-nude mice, but lost the expression of mesothelioma-related markers such as calretinin, D2-40 and Wilms' tumor 1 in the subcutaneous tumors. On the other hand, MM56 cells rapidly generated tumors with the expression of calretinin and D2-40 in BALB/c-nude mice following subcutaneous inoculation. In addition, orthotopic implantation of MM56 cells into BALB/c-nude mice developed diffusely growing thoracic tumors by 3 weeks after implantation. Pleural effusions were observed in these mice 4 weeks after implantation. Thoracic tumors invaded aggressively into the chest wall 5 weeks after implantation and often metastasized into the lung, rib, peritoneum and pericardial cavity. On the pleural surface, MM56 cells were growing as single or multiple cell layers with the reactive mesothelium of recipient mice. These results indicate that MM56 cells can behave in a manner characteristic of human malignant pleural mesothelioma in the thoracic cavity of BALB/c-nude mice. The in vivo model using MM56 cells may be useful for studying the biological behavior of malignant pleural mesothelioma and developing its diagnostic and therapeutic strategies.


Assuntos
Mesotelioma/patologia , Neoplasias Pleurais/patologia , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Feminino , Genes da Neurofibromatose 2 , Genes p16 , Humanos , Imuno-Histoquímica , Masculino , Mesotelioma/química , Mesotelioma/genética , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Transplante de Neoplasias , Neoplasias Pleurais/química , Neoplasias Pleurais/genética , Transplante Heterólogo
13.
Acta Otolaryngol ; 131(3): 323-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21142741

RESUMO

CONCLUSIONS: CD44 expression in hypopharyngeal squamous cell carcinomas (SCCs) is closely associated with poor prognosis for patients. CD44 may serve as a prognostic marker for hypopharyngeal SCCs. OBJECTIVES: CD44, an adhesion molecule binding to extracellular matrix, is believed to participate in the progression of malignancies. To clarify the role of CD44 in the progression of hypopharyngeal SCCs, we examined CD44 expression in relation to clinical parameters in hypopharyngeal SCCs. METHODS: Biopsy specimens of hypopharyngeal SCCs were collected from 40 untreated patients, and their CD44 expression was examined immunohistochemically. Hypopharyngeal SCCs were classified into two groups: CD44-low SCCs comprising < 50% CD44-positive tumor cells and CD44-high SCCs comprising ≥ 50% CD44-positive tumor cells. The relation between CD44 expression and various parameters (clinical T and N stages, distant metastasis, and pathological T and N stages) was analyzed by Fisher's exact test. The relation between CD44 expression and the 5-year disease-free survival (DFS) rate was also analyzed by log rank test. RESULTS: The CD44 expression in hypopharyngeal SCCs was related to pathological N stage, but not to clinical T and N stages and pathological T stage, of the patients. Distant metastasis during the follow-up occurred more frequently in patients with CD44-high SCCs than those with CD44-low SCCs. The 5-year DFS was significantly lower in the former than in the latter.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Receptores de Hialuronatos/metabolismo , Neoplasias Hipofaríngeas/metabolismo , Adulto , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Neoplasias Hipofaríngeas/diagnóstico , Neoplasias Hipofaríngeas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
14.
Pathol Res Pract ; 206(12): 846-50, 2010 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-20846793

RESUMO

Ulcerative colitis (UC) complicated by colonic lymphoma is rare, although UC is often accompanied by adenocarcinoma of the colon. A concurrent existence of adenocarcinoma and lymphoma in a patient with UC is extremely rare, and has not yet been analyzed at the molecular level. We report a 64-year-old female patient with concomitant adenocarcinoma and diffuse large B-cell lymphoma (DLBCL) in the colon of UC. The genetic changes in these two neoplasms were analyzed. The colon adenocarcinomas had a mutation in MSH6 gene, DNA methylation in CDKN2A gene, and increased microsatellite instability (MSI), although these genetic changes were not recognized in either DLBCL or non-neoplastic UC mucosa. The DLBCL was diagnosed as primary colonic lymphoma, and confirmed Epstein-Barr virus (EBV) infection. The adenocarcinomas and the non-neoplastic UC mucosa were EBV-negative. Our case presented here clearly shows that the development of adenocarcinoma and lymphoma in the colon with UC was caused by individual mechanisms.


Assuntos
Adenocarcinoma/genética , Colite Ulcerativa/patologia , Neoplasias do Colo/genética , Proteínas de Ligação a DNA/genética , Genes p16 , Herpesvirus Humano 4 , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/virologia , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Linfócitos B/patologia , Colite Ulcerativa/complicações , Colite Ulcerativa/genética , Neoplasias do Colo/complicações , Neoplasias do Colo/patologia , Metilação de DNA , Análise Mutacional de DNA , DNA de Neoplasias , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Feminino , Herpesvirus Humano 4/isolamento & purificação , Humanos , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/genética , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mutação , Prednisolona/uso terapêutico
15.
Mod Pathol ; 23(11): 1458-66, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20657552

RESUMO

Malignant pleural mesothelioma is a refractory tumor with poor prognosis associated with asbestos exposure. Pleural effusion is frequently observed in patients with malignant pleural mesothelioma, and cytological analysis is effective to detect malignant pleural mesothelioma. However, cytological discrimination between malignant pleural mesothelioma and reactive mesothelium is often difficult. Increased expression of CD146, a cell adhesion molecule, has been reported to be closely associated with an advanced stage of malignant melanoma, prostate cancer, and ovarian cancer. In this study, to evaluate the diagnostic utility of CD146 for discrimination between malignant pleural mesothelioma and reactive mesothelium, we examined immunocytochemical expression of CD146 in malignant pleural mesothelioma and reactive mesothelium using two clones of CD146 antibody, OJ79 and EPR3208, on smear specimens of effusion fluids. Immunocytochemical stains were semiquantitatively scored on the basis of immunostaining intensity (0, negative; 1, weak positive; 2, moderate positive; and 3, strong positive). CD146 expression was detected in 15 of 16 malignant pleural mesothelioma with median immunostaining score of 3 by OJ79, and in 19 of 21 malignant pleural mesothelioma with median immunostaining score of 2 by EPR3208. Strong immunoreactivity of CD146 was observed at the apposing surfaces of cell-cell interactions on the plasma membrane of mesothelioma cells. In addition, one OJ79-negative case of malignant pleural mesothelioma was positive for CD146 by EPR3208 and two EPR3208-negative cases of malignant pleural mesothelioma were CD146 positive by OJ79, showing that all 23 malignant pleural mesothelioma cases were positive for CD146 by either OJ79 or EPR3208. On the other hand, CD146 expression was undetectable in all reactive mesothelium cases by OJ79 and EPR3208. The sensitivity of OJ79 and EPR3208 was 94 and 90%, respectively, and the specificity was 100% for both clones. We propose that CD146 is a sensitive and specific immunocytochemical marker enabling differential diagnosis of malignant pleural mesothelioma from reactive mesothelium.


Assuntos
Biomarcadores Tumorais/análise , Epitélio/imunologia , Imuno-Histoquímica , Mesotelioma/imunologia , Derrame Pleural Maligno/imunologia , Neoplasias Pleurais/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno CD146/análise , Diagnóstico Diferencial , Epitélio/patologia , Feminino , Humanos , Japão , Masculino , Mesotelioma/patologia , Pessoa de Meia-Idade , Derrame Pleural Maligno/patologia , Neoplasias Pleurais/patologia , Valor Preditivo dos Testes , Sensibilidade e Especificidade
16.
Lung Cancer ; 68(3): 498-500, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20307913

RESUMO

The diagnosis of multiple primary lung cancer is sometimes difficult when multiple lung tumors with the same histologic type are identified. We now present a case of synchronous double primary lung adenocarcinomas (one in the right upper lobe and another in the right middle lobe) diagnosed based on mutational analysis of the epidermal growth factor receptor (EGFR) gene, although clinico-pathological findings suggested the diagnosis of intrapulmonary metastasis. After complete resection, pathological sections revealed the similar pathological features of two adenocarcinomas and unexpected subcarinal nodal metastasis. As the L858R mutation within exon 21 of the EGFR gene was identified in the middle-lobe tumor and the subcarinal node but not in the upper-lobe tumor, we diagnosed as double primary cancers. Local mediastinal recurrence after operation has been well-controlled with administration of gefitinib, a EGFR-tyrosine kinase inhibitor, and mutational analysis of the EGFR gene provided important information not only in the diagnosis of double primary cancers but also in decision-making of selection of chemotherapeutic agent.


Assuntos
Adenocarcinoma/diagnóstico , Fator de Crescimento Epidérmico/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/fisiopatologia , Adenocarcinoma/terapia , Idoso , Análise Mutacional de DNA , Diagnóstico Diferencial , Fator de Crescimento Epidérmico/antagonistas & inibidores , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/terapia , Metástase Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/fisiopatologia , Neoplasias Primárias Múltiplas/terapia , Pneumonectomia , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Radiografia Torácica
17.
Lung Cancer ; 67(2): 244-7, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19880210

RESUMO

Well-differentiated papillary mesothelioma (WDPM) is an uncommon tumor with a papillary architecture, bland cytologic features, a tendency toward superficial spread without invasion, and good prognosis with prolonged survival. WDPM occurs primarily in the peritoneum of women, but also rarely in the pleura. We here report a case of 48-year-old woman who developed WDPM in the pleura with no history of asbestos exposure. Tumors were multifocal and widespread with a velvety appearance on the surface of parietal and visceral pleurae resected by extrapleural pneumonectomy (EPP). Tumors showed papillary structures with fibrovascular cores and lined by epithelioid cells. Immunohistochemically, these epithelioid tumor cells were positive for epithelial membrane antigen (EMA), a marker of malignant mesothelioma, with more than 50% positive for p53. Tumor cells microinvaded into subpleural parenchyma of the lung and minimally spread to adipose tissues of the mediastinal lesion. In addition, tumor cells invaded into the chest wall with a trabecular or glandular architecture. Based on these findings, this case is pathologically considered as WDPM of the pleura with malignant potential.


Assuntos
Mesotelioma/patologia , Neoplasias Pleurais/patologia , Parede Torácica/patologia , Feminino , Humanos , Imuno-Histoquímica , Achados Incidentais , Mesotelioma/metabolismo , Mesotelioma/cirurgia , Pessoa de Meia-Idade , Mucina-1/metabolismo , Derrame Pleural Maligno/patologia , Neoplasias Pleurais/metabolismo , Neoplasias Pleurais/cirurgia , Pneumonectomia
18.
J Exp Med ; 206(12): 2779-93, 2009 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-19858324

RESUMO

Although Fc receptors (FcRs) for switched immunoglobulin (Ig) isotypes have been extensively characterized, FcR for IgM (FcmuR) has defied identification. By retroviral expression and functional cloning, we have identified a complementary DNA (cDNA) encoding a bona fide FcmuR in human B-lineage cDNA libraries. FcmuR is defined as a transmembrane sialoglycoprotein of approximately 60 kD, which contains an extracellular Ig-like domain homologous to two other IgM-binding receptors (polymeric Ig receptor and Fcalpha/muR) but exhibits an exclusive Fcmu-binding specificity. The cytoplasmic tail of FcmuR contains conserved Ser and Tyr residues, but none of the Tyr residues match the immunoreceptor tyrosine-based activation, inhibitory, or switch motifs. Unlike other FcRs, the major cell types expressing FcmuR are adaptive immune cells, including B and T lymphocytes. After antigen-receptor ligation or phorbol myristate acetate stimulation, FcmuR expression was up-regulated on B cells but was down-modulated on T cells, suggesting differential regulation of FcmuR expression during B and T cell activation. Although this receptor was initially designated as Fas apoptotic inhibitory molecule 3, or TOSO, our results indicate that FcmuR per se has no inhibitory activity in Fas-mediated apoptosis and that such inhibition is only achieved when anti-Fas antibody of an IgM but not IgG isotype is used for inducing apoptosis.


Assuntos
Proteínas Reguladoras de Apoptose/imunologia , Linfócitos B/imunologia , Imunoglobulina M/imunologia , Proteínas de Membrana/imunologia , Receptores Fc/imunologia , Linfócitos T/imunologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Apoptose/imunologia , Proteínas Reguladoras de Apoptose/genética , Carcinógenos/farmacologia , Linhagem Celular , DNA Complementar/genética , DNA Complementar/imunologia , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/genética , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Receptores Fc/genética , Acetato de Tetradecanoilforbol/farmacologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Regulação para Cima/imunologia , Receptor fas/genética , Receptor fas/imunologia
19.
Pancreas ; 38(5): 558-64, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19287335

RESUMO

OBJECTIVE: Mucinous cystic neoplasm (MCN) and intraductal papillary mucinous neoplasm of the branch duct type (IPMN-BD) differ in biological and clinical behaviors, but MCN is often misdiagnosed as IPMN-BD. The purpose of this study was to find useful markers for the differential diagnosis of MCN and IPMN-BD. METHODS: Immunohistochemically, the expression of the 2 types of mucin (MUC) 1 (MUC1/DF3 and MUC1/CORE), MUC2, MUC5AC, MUC6, human gastric mucin (HGM), caudal-related homeobox transcription factor 2 (CDX2), CD10, cytokeratin (CK) 7, and CK20 was examined in 7 cases of MCN and 16 cases of IPMN-BD. RESULTS: Expression frequencies in MCN and IPMN-BD were 100% versus 44% for MUC1/DF3, 86% versus 31% for MUC1/CORE, 57% versus 19% for MUC2, 86% versus 100% for MUC5AC, 57% versus 88% for MUC6, 86% versus 100% for HGM, 57% versus 0% for CDX2, 71% versus 0% for CD10, 100% versus 69% for CK7, and 86% versus 6% for CK20. CONCLUSIONS: Mucin 1/DF3, MUC1/CORE, CDX2, CD10, and CK20 were expressed significantly more frequently in MCN than in IPMN-BD. In particular, CD10 and CK20 showed marked differences in immunohistochemical sensitivity and specificity between MCN and IPMN-BD. It is therefore proposed that CD10 and CK20 may be used for the differential diagnosis of MCN and IPMN-BD.


Assuntos
Carcinoma Ductal Pancreático/patologia , Carcinoma Papilar/patologia , Cistadenocarcinoma Mucinoso/patologia , Queratina-20/análise , Neprilisina/análise , Neoplasias Pancreáticas/patologia , Idoso , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Papilar/metabolismo , Cistadenocarcinoma Mucinoso/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Queratina-7/análise , Masculino , Pessoa de Meia-Idade , Mucina-5AC/análise , Mucina-1/análise , Mucina-2/análise , Mucina-6/análise , Neoplasias Pancreáticas/metabolismo
20.
World J Gastrointest Oncol ; 1(1): 69-73, 2009 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-21160777

RESUMO

AIM: To explore useful prognostic factors for mucinous adenocarcinoma (MAC) in the colon and rectum. METHODS: MAC was divided into low- and high-grade types based on the degree of structural differentiation; low-grade MAC arisen from well to moderately differentiated adenocarcinoma and papillary carcinoma, and high-grade MAC from poorly differentiated adenocarcinoma and signet ring cell carcinoma. Immunohistochemically, the expression of 2 types of MUC1 (MUC1/DF and MUC1/CORE), MUC2, 2 types of MUC5AC (MUC5AC/CHL2 and HGM), MUC6, CDX2, and CD10 was examined in 16 cases of MAC consisting of 6 low- and 10 high-grade types. RESULTS: MUC1/DF3 was expressed in 3 of 6 low-grade MAC (50%) and 10 of 10 high-grade MAC (100%). MUC1/CORE was expressed in 1 of 6 low-grade MAC (16.7%) and 7 of 10 high-grade MAC (70%). MUC2 was expressed in all MAC regardless of the grade. MUC5AC was expressed in 6 of 6 low-grade MAC (100%) and 4 of 10 high-grade MAC (40%). HGM was expressed in 5 of 6 low-grade MAC (83.3%) and 6 of 10 high-grade MAC (60%). Expression of MUC6 and CD10 was undetected in all MAC regardless of the grade. CDX2 was expressed in 5 of 6 low-grade MAC (83.3%) and 7 of 10 high-grade MAC (70%). Taken together, MUC1/DF3 was expressed significantly more frequently in high-grade MAC than in low-grade, and MUC5AC/CHL2 was expressed significantly more frequently in low-grade MAC than in high-grade. CONCLUSION: It is proposed that MUC1/DF3 and MUC5AC/CHL2 immunostaining is useful to discriminate high-grade MAC from low-grade MAC.

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