RESUMO
An elderly woman with rheumatoid arthritis (RA) presented with a chief complaint of abdominal pain and diarrhoea while undergoing treatment with low-dose corticosteroids and abatacept. Endoscopic and histopathological findings revealed manifestations of ulcerative colitis (UC). An intermediate dose of corticosteroids and 5-aminosalicylic acid were administered. Abatacept was discontinued; the anti-TNF biologic, golimumab, was administered for treatment of both RA and UC. However, colitis worsened in response to this therapeutic regimen. Colonoscopy revealed severe mucosal lesions; larvae were detected in samples taken from multiple shallow mucosal ulcers. The patient was diagnosed with Strongyloides stercoralis colitis based on the results of an anti-parasite antibody test and examination of the larval DNA. Furthermore, serology revealed a positive test for antibodies against human T-cell leukaemia virus type 1 (HTLV-1). Immunosuppressive treatment was terminated; ivermectin was administered, which resulted in improvements in colitis symptoms within a few weeks. There are several published reports describing S. stercoralis colitis as a lethal mimic of UC. Corticosteroid and anti-TNF therapies have been reported as among the major risk factors associated with strongyloidiasis in patients with HTLV-1 infection. Therefore, HTLV-1 and Strongyloides infections may be considered in cases of new-onset gastrointestinal symptoms during immunosuppressive therapy, particularly in HTLV-1-endemic regions.
Assuntos
Artrite Reumatoide/complicações , Colite Ulcerativa/induzido quimicamente , Infecções por HTLV-I/complicações , Imunossupressores/efeitos adversos , Strongyloides stercoralis/isolamento & purificação , Estrongiloidíase/complicações , Idoso , Animais , Antiparasitários/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Colite Ulcerativa/patologia , Feminino , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/tratamento farmacológico , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Ivermectina/uso terapêutico , Estrongiloidíase/diagnóstico , Estrongiloidíase/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
BACKGROUND: Oral adjuvant chemotherapy without hospitalization might reduce the physiological and psychological burden on patients if effectiveness could be guaranteed. We conducted a multicenter feasibility study using S-1, an oral derivative of 5-fluorouracil, as postoperative adjuvant chemotherapy in patients with curatively resected pathologically stage IB-IIIA non-small-cell lung cancer. PATIENTS AND METHODS: Adjuvant chemotherapy comprised 8 courses (4-week administration, 2-week withdrawal) of S-1 at 80-120 mg per day. Fifty-one patients from 7 institutions were enrolled in this pilot study, from June 2005 to March 2007. The primary end point was the completion rate of scheduled adjuvant chemotherapy. Secondary end points were the incidence and grade of adverse reactions. RESULTS: Fifty patients were eligible. The completion rate for the planned 8 courses of S-1 administration was 72.0% (36 patients). Total percentage administration amount was 71.1%. Grade 3 adverse reactions such as neutropenia (4.0%), anorexia (4.0%), thrombopenia (2.0%), anemia (2.0%), elevated total bilirubin (2.0%), hypokalemia (2.0%), nausea (2.0%), and diarrhea (2.0%) were observed, but no grade 4 adverse effects were encountered. Overall and relapse-free survival rates at 3 years were 87.7% and 69.4%, respectively. CONCLUSIONS: Postoperative 1-year administration of S-1 seems feasible as oral adjuvant chemotherapy for lung cancer. The oral formulation and low incidence of adverse reactions permit treatment on an outpatient basis. The present study would be reasonable to follow up with a properly powered phase III trial.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Tegafur/uso terapêutico , Administração Oral , Idoso , Assistência Ambulatorial/métodos , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante/métodos , Terapia Combinada , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Incidência , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Resultado do TratamentoRESUMO
Lung cancer commonly occurs in individuals who are 60 years of age or older. Lung cancer in patients younger than 40 years of age is rare and is often advanced when discovered. However, the biological features of lung cancer in young adults have not yet been fully elucidated. This study was conducted to determine the role of p53 expression and neoangiogenesis in lung adenocarcinomas of young patients. Lung adenocarcinomas, which were surgically resected from 20 patients younger than 40 years of age between 1977 and 1996, were compared with lung adenocarcinomas selected with random sampling from 45 patients older than 60 years of age. The expression of p53, vascular endothelial growth factor (VEGF), CD34, a marker for vascular endothelial cells, and proliferating cell nuclear antigen (PCNA) were studied immunohistochemically in both young and elderly patient groups. Lung adenocarcinomas with p53-positive staining showed higher expression of VEGF protein than p53-negative tumors in both the young and the elderly groups. However, the intratumoral microvessel count was significantly higher in the p53-positive young group than in the elderly group. The percentage of VEGF-positive cells correlated significantly with intratumoral microvessel counts in the young group. The survival rate tended to be poorer in patients with a high VEGF labeling index and p53-positive staining than in other young patients. Lung adenocarcinoma occurring in young patients tends to have a poorer prognosis, and angiogenesis of lung adenocarcinoma in young patients is more closely correlated with p53 expression than in elderly patients.
Assuntos
Adenocarcinoma/irrigação sanguínea , Adenocarcinoma/metabolismo , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/metabolismo , Neovascularização Patológica/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Adulto , Distribuição por Idade , Idoso , Antígenos CD34/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Microvasos/metabolismo , Microvasos/patologia , Pessoa de Meia-Idade , Antígeno Nuclear de Célula em Proliferação/metabolismo , Análise de Regressão , Análise de Sobrevida , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
PURPOSE: The treatment strategy for patients with non-small-cell lung cancer (NSCLC) involving ipsilateral mediastinal lymph nodes is still controversial. We performed a phase II feasibility study of induction chemotherapy followed by surgery for patients with pathologic N2 NSCLC. PATIENTS AND METHODS: Patients with mediastinoscopy- positive stage IIIA N2 NSCLC received 2 cycles of cisplatin 80 mg/m2, vinorelbine 25 mg/m2, and mitomycin-C 8 mg/m2. Patients without progressive disease underwent thoracotomy and lobectomy with lymph node dissections 2-4 weeks later. RESULTS: From January 2000 to July 2004, 24 eligible patients (15 men, 9 women) were enrolled. Induction chemotherapy was completed as planned in 23 patients (95.8%). Hematological toxicity was the primary grade 3/4 toxicity. Twelve (50%) patients achieved a partial response. Twenty-three patients underwent surgical resection, and complete resection was achieved in 22 patients (95.7%). There were no surgery-related deaths. Pathologic complete response in metastatic lymph nodes was achieved in 5 patients. With a median follow-up of 5.4 years (range, 2.88-7.7 years), the estimated 5-year survival was 51.8% (95% CI, 41.3-62.3) and progression-free survival was 46.6% (95% CI, 36-57.2). CONCLUSION: Induction chemotherapy followed by surgery for patients with pathologic N2 NSCLC was feasible and associated with high response to lymph node metastasis and good survival.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Cisplatino/administração & dosagem , Terapia Combinada , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Estadiamento de Neoplasias , Cooperação do Paciente , Taxa de Sobrevida , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , VinorelbinaRESUMO
Broncholithiasis is frequently associated with hemoptysis and infection. The most common cause of the disease is the presence of calcified material in a bronchus or in a cavity communicating with a bronchus. We present two cases of broncholithiasis treated by surgery. Case 1 involves a 57-year-old woman who presented with cough and bloody sputum. She had suffered from recurrent pneumonia in the left lower lobe caused by broncholithiasis for 2 years. We performed left S6 segmentectomy with bronchoplasty after unsuccessful bronchoscopic removal. Case 2 is a 65-year-old man who had had hilar tuberculous lymphoadenopathy at the age of 20. Recently he had suffered from recurrent bloody sputum and pulmonary suppuration for 3 years. We performed right upper lobectomy because the right B3 was occluded by inflammatory granulation with calcification. Postoperatively, these two patients have been alive and well with no complications. The indications of surgery for broncholithiasis include a difficult bronchoscopic broncholithectomy, massive hemoptysis, and irreversible complications such as chronic pulmonary suppurative disease.
Assuntos
Broncopatias/cirurgia , Litíase/cirurgia , Procedimentos Cirúrgicos Pulmonares , Idoso , Broncopatias/etiologia , Feminino , Humanos , Litíase/complicações , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
A region encompassing the rat aldolase B gene (aldB) promoter acts as a chromosomal origin of DNA replication (origin) in rat aldolase B-nonexpressing hepatoma cells. To examine replicator function of the aldB origin, we constructed recombinant mouse cell lines in which the rat aldB origin and the mutant derivatives were inserted into the same position at the mouse chromosome 8 by cre-mediated recombination. Nascent strand abundance assays revealed that the rat origin acts as a replicator at the ectopic mouse locus. Mutation of site C in the rat origin, which binds an Orc1-binding protein AlF-C in vitro, resulted in a significant reduction of the replicator activity in the mouse cells. Chromatin immunoprecipitation (ChIP) assays indicated that the reduction of replicator activity was paralleled with the reduced binding of AlF-C and Orc1, suggesting that sequence-specific binding of AlF-C to the ectopic rat origin leads to enhanced replicator activity in cooperation with Orc1. Involvement of AlF-C in replication in vivo was further examined for the aldB origin at its original rat locus and for a different rat origin identified in the present study, which contained an AlF-C-binding site. ChIP assays revealed that both replication origins bind AlF-C and Orc1. We think that the results presented here may represent one mode of origin recognition in mammalian cells.
Assuntos
Frutose-Bifosfato Aldolase/genética , Complexo de Reconhecimento de Origem/metabolismo , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Animais , Sítios de Ligação , Ligação Competitiva , Imunoprecipitação da Cromatina , Cromossomos/metabolismo , Clonagem Molecular , Ensaio de Desvio de Mobilidade Eletroforética , Frutose-Bifosfato Aldolase/metabolismo , Glutationa Transferase/metabolismo , Integrases , Células L , Camundongos , Dados de Sequência Molecular , Mutagênese Insercional , Ligação Proteica , Ratos , Proteínas Recombinantes/metabolismo , Recombinação Genética , Fatores de Transcrição/químicaRESUMO
We report a case of N 3 gastric cancer successfully treated by TS-1 followed by curative resection. The patient was a 64-year-old male. Gastrointestinal endoscopic examination showed advanced gastric cancer. Examination by computed tomography revealed gastric cancer and swollen para-aortic lymph nodes. This patient was treated by neoadjuvant chemotherapy with oral administration of TS-1 (120 mg/day, day 1-28 with 2 weeks rest). After 3 courses of TS-1, the primary lesion and swollen lymph nodes were remarkably reduced. This chemotherapy enabled pancreatoduodenectomy with D 3 lymph node dissection in curative resection. The pathological diagnosis was por, pT 2, pMP and pap, pT 1, pSM 2, pPM(-), pDM(-), pN 1, pStage II and curability A. This neoadjuvant chemotherapy regimen seems to be an effective and promising therapy for patients with advanced gastric cancer.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/administração & dosagem , Gastrectomia , Excisão de Linfonodo , Linfonodos/patologia , Ácido Oxônico/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Tegafur/administração & dosagem , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Administração Oral , Quimioterapia Adjuvante , Terapia Combinada , Esquema de Medicação , Combinação de Medicamentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pancreaticoduodenectomia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
Three new rearranged vibsane-type diterpenes, neovibsanin F (1), 14-epi-neovibsanin F (2), and 14-epi-18-oxoneovibsanin F (3), have been isolated from the leaves of Viburnum suspensum, and their structures were elucidated on the basis of spectroscopic data and comparison with those of previously reported vibsane-type diterpenes.
Assuntos
Antineoplásicos Fitogênicos , Diterpenos , Plantas Medicinais/química , Viburnum/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/classificação , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Artemia/efeitos dos fármacos , Diterpenos/química , Diterpenos/classificação , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células KB , Estrutura Molecular , Folhas de Planta/químicaRESUMO
We describe a novel pharmacological activity of the gentian root, an ingredient of Chinese medicines. Root extract from Gentiana triflora triggered cell death of human Daudi cells in culture. In addition, daily administration of the extract to mice inhibited growth of implanted solid tumors. Extract treatment of cultured cells resulted in the appearance of shranken, fragmented, or condensed cell and nuclear morphologies, and in chromosomal DNA degradation. But, the extract-treated cells did not show DNA fragmentation, which exhibits a nucleosome ladder, suggesting that extract-triggered cell death is not mediated through a typical apoptotic pathway.
Assuntos
Gentiana/química , Neoplasias/patologia , Raízes de Plantas/química , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Forma Celular , Transplante de Células , Masculino , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
The rat aldolase B promoter acts as a replication origin in vivo, as well as an autonomously replicating sequence (ARS). Here, we examined roles of a polypurine stretch (site PPu) in this origin, which is indispensable to the ARS activity. Purification of site PPu-binding protein revealed that site PPu binds Puralpha and Purbeta, i.e., single-stranded DNA-binding proteins whose roles in replication have been implicated, but less clear. Biochemical analyses showed that site PPu even in a longer DNA fragment is unstable in terms of double-helix, implying that Puralpha/beta may stabilize single-stranded state. Deletion of site PPu from the origin DNA, which was ectopically positioned in the mouse chromosome, significantly reduced replicator activity. Chromatin immunoprecipitation experiments showed that deletion of site PPu abolishes binding of the Puralpha/beta proteins to the origin. These observations suggest functional roles of site PPu and Puralpha/beta proteins in replication initiation.
Assuntos
Replicação do DNA/fisiologia , Proteínas de Ligação a DNA/metabolismo , Frutose-Bifosfato Aldolase/biossíntese , Frutose-Bifosfato Aldolase/genética , Origem de Replicação/genética , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Animais , Sítios de Ligação/genética , Linhagem Celular Tumoral , Frutose-Bifosfato Aldolase/metabolismo , Células L , Camundongos , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Regiões Promotoras Genéticas , Ratos , Origem de Replicação/fisiologiaRESUMO
We report a case of Castleman disease which originated from the inter-lobar lymph node, with a review of literatures. A 19-year-old woman complaining of cough was pointed out to have an abnormal shadow in the left lung field on chest X-ray. Chest computed tomography (CT) and magnetic resonance imaging (MRI) with enhancement revealed a homogeneous mass lesion at the left inter-lobar portion of the lung. Bronchoscopic findings demonstrated mucosal telangiectasis of the left lower bronchus. We performed the usual axillary thoracotomy and succeeded in extirpation of the tumor without large amount of bleeding. The tumor was elastic and hard, and 70 x 55 x 45 mm in size. Her postoperative course was uneventful and she was discharged on the 12th postoperative day.