RESUMO
This study was a prospective single arm trial conducted in Zhejiang Jinhua Guangfu hospital from February 2018 to June 2020. A total of 39 patients (32 males and 7 females) with esophageal cancer, aged from 44 to 82 (69±9) years were enrolled. Diffusion weighted magnetic resonance imaging(MR-DWI) was implemented to evaluate the changes of apparent diffusion coefficient(ADC) value before and after chemoradiotherapy. The results showed that the ADC value after chemoradiotherapy was higher than that before treatment[(2.03±0.42)×10⻳ mm 2/s vs (1.60±0.28)×10⻳ mm2/s], and there was a positive correlation between the increase of ADC value and the prognosis of patients.
Assuntos
Neoplasias Esofágicas , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Imagem de Difusão por Ressonância Magnética , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/terapia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos ProspectivosRESUMO
OBJECTIVE: To detect Mycobacterium tuberculosis (MTB) and rifampin resistance of the clinical specimens in children by Xpert MTB DNA and resistance to rifampicin(MTB/RIF) detection system, and evaluate the application value of this method in children with tuberculosis. METHOD: Data of 109 children cases of clinically suspected tuberculosis were collected (including 46 gastric lavage aspirate, 19 sputum, 10 fine needle aspiration biopsy, 4 pus, 14 cerebrospinal fluid, 11 Serous membrance fluid, 1 marrow, 3 stool, 1 urine specimens)between April 2014 and March 2015. All specimens were detected by smear fluorescence staining microscopy, MGIT 960 BACTEC liquid culture, Xpert MTB/RIF assay and T-SPOT.TB test respectively. The sensitivity and specificity of Xpert MTB/RIF assay were analyzed in those clinical specimens. RESULT: The sensitivity and specificity of the Xpert MTB/RIF assay for MTB detection in childhood tuberculosis clinical specimen were 28.6% and 87.5%. The sensitivity of 65 pulmonary tuberculosis(46 gastric lavage aspirate, 19 sputum) which included gastric lavage aspirates and sputum was 33.3% and 57.1%, the specificity of the two was 100.0%. In 44 extrapulmonary tuberculosis, the sensitivity of the pus and the puncture fluid was higher and approached 100.0%. The detection rate of the cerebrospinal fluid and serous cavity effusion was very low. The sensitivity was 100.0% in smear-positive and culture-positive samples and only 30.8% to 50.0% in smear-negative and culture-positive samples. The sensitivity and specificity of Xpert MTB/RIF assay to detect rifampin resistance were 100.0%. In clinical samples, the sensitivity of Xpert MTB/RIF assay was higher than that of smear fluorescence staining microscopy, but the difference was not statistically significant (χ(2)=0, P>0.05). The result was equivalent to that of MGIT 960 BACTEC liquid culture (28.6% vs. 27.3%, χ(2)=2.50, P>0.05), and far below that of T-SPOT.TB(28.6% vs 59.7%, χ(2)=13.92, P<0.05). CONCLUSION: Xpert MTB/RIF assay did not show obvious advantage in childhood tuberculosis, especially in serous cavity effusion and cerebrospinal fluid, but the advantages of detecting tuberculosis rapidly and resistance to rifampin can provide help for the clinical diagnosis and treatment in childrenhood tuberculosis.
Assuntos
Farmacorresistência Bacteriana , Técnicas de Diagnóstico Molecular/métodos , Tuberculose Pulmonar/diagnóstico , Tuberculose/diagnóstico , Criança , DNA Bacteriano/isolamento & purificação , Humanos , Mycobacterium tuberculosis/efeitos dos fármacos , Rifampina/farmacologia , Sensibilidade e Especificidade , Escarro/microbiologiaRESUMO
The susceptibility to glioma is not well understood. It has been suggested that the X-ray cross complementing group 3 (XRCC3) gene influences the capacity to repair DNA damage, leading to increased glioma susceptibility. In this study, we evaluated the relationship between XRCC3 mutations and glioma risk. Genotypes were assessed in 389 Chinese glioma patients and 358 healthy controls. XRCC3 Thr241Met (rs861539) and 2 additional polymorphisms, rs3212112 (c.774+19T>G) and rs1799796 (c.562-14A>G), were directly sequenced. The frequency of the rs861539 T allele was significantly lower in the glioma group than in healthy controls [11.1 vs 17.7%, odds ratio = 0.62 (0.48-0.80), P < 0.001]; the frequencies of the CT or CT+TT genotypes differed between groups (18.5 vs 31%, 20.3 vs 33.2%, respectively). The frequency of the rs3212112 G allele was significantly higher in the glioma group than in healthy controls [15.8 vs 5.3%, odds ratio = 2.94 (2.07-4.17), P < 0.001]. The frequencies of the GT or TG+GG genotypes differed between groups (25.4 vs 7.8%, 28.5 vs 9.2%, respectively). This study demonstrates that the rs861539 and rs3212112 polymorphisms in the XRCC3 gene may influence the risk of glioma development in Chinese populations.
Assuntos
Neoplasias Encefálicas/genética , Reparo do DNA , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Glioma/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Povo Asiático , Neoplasias Encefálicas/etnologia , Neoplasias Encefálicas/patologia , Estudos de Casos e Controles , Feminino , Expressão Gênica , Frequência do Gene , Genótipo , Glioma/etnologia , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Análise de Sequência de DNARESUMO
This retrospective study aimed to observe the clinicopathological features and immunological phenotypes, and explore effective treatment and prognosis for 12 Chinese Han patients with acquired immunodeficiency syndrome-related cutaneous Kaposi's sarcoma. All 12 patients were human immunodeficiency virus-positive, and underwent the standard highly active antiretroviral therapy (HAART). Skin lesions mainly presented as purple, or rufous papules, or plaques; skin biopsy showed diffuse or flaky infiltration of spindle cells, active proliferation of slit-like vasculature, erythrocyte exudation, hemosiderin deposition, and inflammatory cell infiltration. Immunohistochemical analysis showed the expression of Ubiquitin C-terminal hydrolase L1 (+), and CD31 (+) in T-cells; factor VIII (+) and HHF-35 (+) in the proliferating vascular endothelial cells; vimentin (+) and S-100 protein (-) in the vessel wall; and CD34 (+++) in the spindle cells of 6 cases, with 1 case of negative CD34 expression. Four patients with confined lesions underwent surgery and microwave therapy, and received a favorable prognosis. Two patients with limited lesions underwent microwave therapy, and the lesions subsided. Of six patients with widely distributed sarcomas, five underwent microwave therapy and one received combined chemotherapy; five attained significant efficacy, and one died. There were no significant differences in the clinicopathological features and immunological phenotypes between the Chinese Han patients and those from other populations. Along with basal HAART, patients in early stages, with sarcomas <2 cm in diameter should undergo surgery and microwave therapy, while patients with sarcomas >2 cm in diameter should undergo chemotherapy and microwave therapy.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/radioterapia , Terapia Antirretroviral de Alta Atividade/métodos , Sarcoma de Kaposi/tratamento farmacológico , Sarcoma de Kaposi/radioterapia , Pele/patologia , Infecções Oportunistas Relacionadas com a AIDS/patologia , Infecções Oportunistas Relacionadas com a AIDS/cirurgia , Adulto , Antígenos CD34/genética , Antígenos CD34/metabolismo , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/patologia , Vasos Sanguíneos/efeitos da radiação , Procedimentos Cirúrgicos Dermatológicos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Células Endoteliais/efeitos da radiação , Fator VIII/genética , Fator VIII/metabolismo , Feminino , Expressão Gênica , HIV/efeitos dos fármacos , HIV/crescimento & desenvolvimento , Humanos , Masculino , Micro-Ondas/uso terapêutico , Pessoa de Meia-Idade , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Prognóstico , Estudos Retrospectivos , Proteínas S100/genética , Proteínas S100/metabolismo , Sarcoma de Kaposi/patologia , Sarcoma de Kaposi/cirurgia , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Linfócitos T/efeitos dos fármacos , Linfócitos T/patologia , Linfócitos T/efeitos da radiação , Resultado do Tratamento , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Vimentina/genética , Vimentina/metabolismoRESUMO
BACKGROUND: Breast cancer is categorized into two broad groups: estrogen receptor positive (ER+) and ER negative (ER-) groups. Previous study proposed that under trastuzumab-based neoadjuvant chemotherapy, tumor initiating cell (TIC) featured ER- tumors response better than ER+ tumors. Exploration of the molecular difference of these two groups may help developing new therapeutic strategies, especially for ER- patients. MATERIALS AND METHODS: With gene expression profile from the Gene Expression Omnibus (GEO) database, we performed partial least squares (PLS) based analysis, which is more sensitive than common variance/regression analysis. RESULTS: We acquired 512 differentially expressed genes. Four pathways were found to be enriched with differentially expressed genes, involving immune system, metabolism and genetic information processing process. Network analysis identified five hub genes with degrees higher than 10, including APP, ESR1, SMAD3, HDAC2, and PRKAA1. CONCLUSIONS: Our findings provide new understanding for the molecular difference between TIC featured ER- and ER+ breast tumors with the hope offer supports for therapeutic studies.
Assuntos
Neoplasias da Mama/genética , Receptores de Estrogênio/genética , Anticorpos Monoclonais Humanizados/farmacologia , Neoplasias da Mama/tratamento farmacológico , Feminino , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Análise dos Mínimos Quadrados , Terapia Neoadjuvante/métodos , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética , TrastuzumabRESUMO
Hepatocarcinoma represents one of the most malignant cancer types. Esophageal cancer-related gene 2 (ECRG2) is found to be critical in the process of carcinogenesis. It regulates urokinase-type plasmin activator receptor and extracellular matrix function and its polymorphism in exon 4 is associated with cancer relapse. To explore new strategies to fight against cancer, here we first systematically evaluated the therapeutic potential as a biological tool using adenoviral vector (Ad-ECRG2). Ad-ECRG2 is exogenously expressed in cytoplasm and is potent to suppress the growth of cancer cell by inducing apoptosis as effective as Ad-p53. Ad-ECRG2 is able to suppress the invasion and adhesion of cancer cells at low titers. It alters the expression of a panel of cancer-related molecules, including nuclear factor-kB, matrix metalloproteinase 2 and E-cadherin, contributing to reverse malignancy phenotype of cancer cells. In vivo experiments show a significant inhibition of cancer growth by intratumoral Ad-ECRG2 administration. No evident toxicity was observed in the model animal during the study. We concluded that ECRG2 is a potential molecular target in biological therapy strategies for cancer treatment.
Assuntos
Adenoviridae/genética , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Proteínas Secretadas Inibidoras de Proteinases/genética , Inibidores de Serina Proteinase/genética , Adenoviridae/metabolismo , Animais , Apoptose/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Adesão Celular/genética , Linhagem Celular Tumoral , Vetores Genéticos/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Células MCF-7 , Camundongos , Proteínas Secretadas Inibidoras de Proteinases/biossíntese , Inibidores de Serinopeptidase do Tipo Kazal , Inibidores de Serina Proteinase/biossíntese , Transfecção/métodos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: Abundant evidence has demonstrated that long-term cytokine-mediated inflammation is a risk factor for obesity and type 2 diabetes mellitus (T2DM). Our previous study reveals a significant association between promoter polymorphisms of Th2-derived cytokine interleukin-4 (IL-4) and T2DM, which suggests possible roles of IL-4 in metabolism. In this study, we focused on examining the putative regulation of glucose and lipid metabolism by IL-4. METHODS: C57BL/6 mice were intraperitoneally injected with either adenovirus containing full-length IL-4 encoding gene (AdIL-4) or recombinant IL-4 for mimicking the status of transient and long-term IL-4 overexpression, respectively, and the effects of the overexpressed IL-4 to glucose/lipid metabolism and insulin sensitivity were subsequently investigated. RESULTS: Our results reveal that IL-4 improves insulin sensitivity and glucose tolerance through upregulating Akt phosphorylation while attenuating GSK-3ß activities. IL-4 is also involved in lipid metabolism by inhibiting lipid accumulation in fat tissues, which lead to decreased weight gain and fat mass. CONCLUSIONS: Our results suggest that IL-4 regulates glucose and lipid metabolism by promoting insulin sensitivity, glucose tolerance and inhibiting lipid deposits. This study uncovers the novel roles of IL-4 in metabolism and provides new insights in the interaction between cytokines/immune responses, insulin sensitivity and metabolism.
Assuntos
Glicemia/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Resistência à Insulina , Interleucina-4/metabolismo , Metabolismo dos Lipídeos , Obesidade/metabolismo , Animais , Regulação da Expressão Gênica/genética , Teste de Tolerância a Glucose , Glicogênio Sintase Quinase 3 beta , Humanos , Resistência à Insulina/genética , Metabolismo dos Lipídeos/genética , Camundongos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Central diabetes insipidus (CDI), secondary to pituitary metastatic lesions, is uncommon; however, lung and breast cancer are the commonest malignancies to have metastases to the pituitary. Early management of systemic chemotherapy and pituitary irradiation might improve the prognosis of patients. AIMS: To investigate the clinical features, diagnosis, and management of CDI caused by lung cancer metastasis to the pituitary glands. MATERIALS AND METHODS: We retrospectively reviewed 10 patients who had CDI as their first symptom before their lung cancers were diagnosed. Their clinical presentations, anterior pituitary gland function, sellar magnetic resonance imaging (MRI), management, and prognosis were described. SETTINGS AND DESIGN: This retrospective cross-sectional clinical study was conducted in a medical college hospital. RESULTS: The patient's mean age was 58.6±7.8 years. Diabetes insipidus was the main complaint when they were referred to our hospital. MRI revealed specific dumbbell-shaped masses in the sella turcica in five patients. In seven patients whose hormones were measured, the levels of hormones from adenohypophysis were abnormally low in six patients. The main treatments included surgery, systemic chemotherapy, and sellar irradiation. Although nine patients had poor prognoses, one patient has survived for more than 3 years, suggesting benefit from early diagnosis and treatment. CONCLUSIONS: New-onset CDI might be the only symptom presented by the patients with pituitary metastasis (PM) from lung cancer. Dumbbell-shaped sellar masses in MRI are prone to the diagnosis of PM. A thorough examination for primary cancer should be carried out in these aged and elderly patients.
Assuntos
Adenocarcinoma/secundário , Diabetes Insípido/diagnóstico , Neoplasias Pulmonares/patologia , Neoplasias Hipofisárias/secundário , Carcinoma de Pequenas Células do Pulmão/secundário , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/terapia , Adulto , Idoso , Diabetes Insípido/etiologia , Diabetes Insípido/terapia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/terapia , Radiografia , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/terapiaRESUMO
Interleukin-27 (IL-27) is a novel cytokine of the IL-6/12 family with a broad range of immune regulation properties, which has been considered as a potential therapeutic agent for immune diseases and cancers. However, little is known about the effect of IL-27 on human neutrophils before its clinical administration. In this study, we investigated the effects of IL-27 on human neutrophil functions including adhesion, reactive oxygen species (ROS)/cytotoxic granule components production, inflammatory cytokines production, major histocompatibility complex (MHC) molecules expression and neutrophils' survival. We showed that IL-27 receptor complex, WSX-1/TCCR and gp130, is constitutively expressed on human neutrophils. In vitro, IL-27 suppressed neutrophil adhesion in response to fMLP, which might depend on the down-regulation of Mac-1. IL-27 also suppressed lipopolysaccharide-induced ROS production and attenuated cytotoxic granule components production in the cytoplasm of human neutrophils. In addition, IL-27 enhanced the production of IL-1ß but not TNF-α from neutrophils. However, IL-27 failed to regulate the expression of MHC molecules and the survival of human neutrophils. In conclusion, our data demonstrate that IL-27 mainly down-modulates human neutrophil function, which might extend our understanding of the role of IL-27 in the innate immune response.
Assuntos
Citocinas/metabolismo , Interleucinas/farmacologia , Neutrófilos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Adesão Celular/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/ultraestrutura , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Receptor gp130 de Citocina/genética , Receptor gp130 de Citocina/metabolismo , Grânulos Citoplasmáticos/efeitos dos fármacos , Grânulos Citoplasmáticos/metabolismo , Citometria de Fluxo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Antígeno-1 Associado à Função Linfocitária/genética , Antígeno-1 Associado à Função Linfocitária/metabolismo , Antígeno de Macrófago 1/genética , Antígeno de Macrófago 1/metabolismo , Microscopia Eletrônica de Transmissão , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Neutrófilos/citologia , Neutrófilos/metabolismo , Receptores de Interleucina/genética , Receptores de Interleucina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Gastrointestinal stromal tumors (GISTs) possess a wide spectrum of biological properties, from indolent to highly aggressive. In this study, we evaluated a set of clinical and pathological parameters for their predicative values for malignancy of GISTs by retrospective reviews of tumor specimens and their relevant medical records from 840 patients. All GIST cases were first assigned as malignant if they met any of the following criteria: gross spreads, including liver metastassis and/or peritoneal dissemination, microscopic spreads, including lymph node metastasis, infiltrations to vascular, fat, nerve and muscularis mucosal tissues, or relapse. The remaining cases were recorded as biological behavior uncertain. This initial assignment revealed a set of five morphological features to be associated with malignancy. They were: mitotic counts greater than 10 per 50HPFs (P<0.0001), muscularis propria infiltration (P<0.0001), coagulative necrosis (P<0.0001), perivascular growth pattern (P=0.005), and severe nuclear atypia (P=0.014). Therefore, a new classification system, including criteria of 2 gross spreads, 5 microscopic spreads, and 5 histopathological parameters was developed. All the GIST cases were re-classified into a group of 485 malignant tumors, and a group of 355 nonmalignant tumors. Patient follow-up data revealed 5-year disease-free and overall survival rates as high as 99.3% and 100% for the nonmalignant group, but low rates of 43.9% and 59.7% for the malignant group. These results demonstrated a correlation of the new classification with clinical outcomes. Therefore, this set of 12 parameters has predictive values for malignancy of GISTs, and is potentially useful in the grading of the tumors.
Assuntos
Tumores do Estroma Gastrointestinal/classificação , Tumores do Estroma Gastrointestinal/patologia , Invasividade Neoplásica/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Tumores do Estroma Gastrointestinal/mortalidade , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , PrognósticoRESUMO
BACKGROUND: Insulin-like growth factor II mRNA-binding protein (IMP) 3 is expressed in embryonic tissues and multiple cancers. The aim was to establish the prognostic value of IMP-3 expression in gastric adenocarcinoma. METHODS: IMP-3 expression in resected gastric adenocarcinomas was analysed by immunohistochemistry. RESULTS: IMP-3 was expressed in 183 (58.1 per cent) of 315 tumours. Expression was associated with older age (P < 0.001), larger tumour size (P = 0.009), deep tumour invasion (P < 0.001) and lymph node metastasis (P < 0.001). IMP-3-positive tumours were associated with poorer 5-year survival than negative tumours at all stages (stage I, 82 versus 97 per cent; stage II, 55 versus 78 per cent; stage III and IV, 11 versus 25 per cent; P = 0.005, P = 0.033 and P = 0.036 respectively). Multivariable analysis identified IMP-3 (hazard ratio (HR) 1.93), depth of tumour invasion (HR 3.69, 9.77 and 10.69 for pathological tumour stage (pT) 2, pT3 and pT4 respectively versus pT1), and lymph node metastasis (HR 1.57, 3.29 and 3.40 for pathological node stage (pN) 1, pN2 and pN3 respectively versus pN0) as independent prognostic factors. CONCLUSION: IMP-3 expression correlates with the metastatic potential of gastric adenocarcinoma and is an independent prognostic factor.
Assuntos
Adenocarcinoma/metabolismo , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , RNA Mensageiro/metabolismo , Fatores de Risco , Neoplasias Gástricas/mortalidadeRESUMO
Recent advances suggest human umbilical cord is a new source for stem cells. Our laboratory has established a method to readily isolate and expand stem cells from human umbilical cord tissues. The aim of this study was to investigate the therapeutic potential of human umbilical cord-derived stem (UCDS) cells in ischemic diseases. The UCDS cells were characterized by flow cytometry and differentiation into osteogenic and adipogenic cells. Unilateral hind limb ischemia was surgically induced by femoral artery ligation in nude mice. The animals were intramuscularly injected with 10(6) UCDS cells or control phosphate-buffered saline. Blood perfusion of ischemic limbs was detected by laser Doppler perfusion imaging. Transplantation of UCDS cells to the ischemic limbs of nude mice significantly improved the blood flow to the affected limbs. Thus, transplantation of UCDS cells may potentially be a promising treatment for human ischemic diseases.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Membro Posterior/irrigação sanguínea , Isquemia/terapia , Animais , Humanos , Masculino , Camundongos , Camundongos Nus , Transplante Heterólogo , Cordão UmbilicalRESUMO
AIMS: Thirty-three cases of gastrointestinal schwannomas were analysed to elucidate their peculiar clinicopathological, immunohistochemical and ultrastructural features. METHODS AND RESULTS: The patients were 16 men and 17 women, whose ages ranged from 27 to 81 years (median 52.6 years). Tumour size ranged from 10 to 120 mm in diameter. Follow-up in 23 cases from 6 months to 13 years showed no recurrences or metastases. Microscopically, all tumours were composed of spindle cells with focal epithelioid cells in four cases. In all cases except one, there were peripheral cuff-like lymphoid aggregates. Immunohistochemically, tumours were strongly positive for S100 protein and vimentin, the tumours were variably positive for nestin (78.8%, 26/33) and glial fibrillary acidic protein (63.6%, 21/33), three tumours had CD34+ cells, but all were negative for CD117, alpha-smooth muscle actin and desmin. Ultrastructurally, the tumours were composed of elongated spindle shaped cells with prominent parallel membranous structures. CONCLUSIONS: Gastrointestinal schwannomas have characteristic histological features, especially the presence of a lymphoid cuff, that are different from their soft tissue and central nervous system counterparts. Gastrointestinal tract schwannomas behave in a benign fashion.
Assuntos
Neoplasias Gastrointestinais/patologia , Neurilemoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34/análise , Análise Mutacional de DNA , Feminino , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/metabolismo , Proteína Glial Fibrilar Ácida/análise , Humanos , Imuno-Histoquímica , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Neurilemoma/metabolismo , Neurilemoma/ultraestrutura , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas S100/análise , Vimentina/análiseRESUMO
PURPOSE: We studied the cross-resistance and combined cytotoxic effects of cisplatin and paclitaxel in bladder cancer cells in vitro. MATERIALS AND METHODS: The cytotoxicity of the 2 agents alone or in combination were studied in the bladder cancer cell line NTUB1 and the 2 sublines NTUB1/P, which is cisplatin resistant, and NTUB1/T, which is paclitaxel resistant, using the microculture tetrazolium assay. Schedule dependence of the 2-drug combination was assayed using 3 treatment schedules, including 1 concurrent and 2 sequential exposures. RESULTS: The mean cisplatin concentration plus or minus standard error of the means inhibiting 50% of the growth of NTUB1, NTUB1/P and NTUB1/T was 1.9 +/- 0.19, 19.3 +/- 2.33 and 2.1 +/- 0.15 microM., respectively, and the mean paclitaxel concentration inhibiting 50% of the growth of the 3 cell lines was 30 +/- 3.9, 1,033 +/- 120 and 110 +/- 15 nM., respectively. NTUB1/P had strong cross-resistance to paclitaxel. In contrast, NTUB1/T was as sensitive as NTUB1 to cisplatin. On median effect analysis the combined effects of the 2 agents given concurrently were sub-additive in the low fraction affected range of 0.1 to 0.3 and additive in the median to high fraction affected range of 0.4 to 1.0 in the 3 cell lines. Combined cytotoxicity was more synergistic when paclitaxel was given 24 hours earlier than cisplatin. The effects were less synergistic when cisplatin was given before paclitaxel. This phenomenon was noted in sensitive and resistant cells. CONCLUSIONS: In our bladder cancer cell model cisplatin resistant cells have strong cross-resistance to paclitaxel, whereas paclitaxel resistant cells are sensitive to cisplatin. The combined effects may be optimized by sequential use of the 2 agents, preferably paclitaxel given 24 hours before cisplatin. Our results have clinical implications for the treatment of bladder cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma de Células de Transição/tratamento farmacológico , Cisplatino/farmacologia , Paclitaxel/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Sinergismo Farmacológico , Humanos , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Terapia de Salvação , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
We explored the mechanisms of cisplatin resistance in a series of bladder transitional carcinoma cells that are either sensitive or progressively resistant to cisplatin. Resistant lines were raised by chronic exposure of the parental cells to progressively increased concentrations of cisplatin. The cisplatin IC50s of the sensitive and the three resistant cells were 4.3, 25.0, 40.4, and 52.2 microM, respectively. The expressions of glutathione S-transferase pi (GST-pi) and multidrug resistance-associated protein (MRP) were enhanced in a dose-response manner as cells acquired progressive cisplatin resistance. Expression of mdr-1 transcript was detected in the three resistant lines but not in the sensitive line. Glutathione contents were increased in resistant cells, yet the trend of increase did not reach statistical significance (p = 0.061). In conclusion, transitional carcinoma cells may gain cisplatin resistance through multiple pathways including up-regulation of GST-pi, MRP and possibly mdr-1. Glutathione contents may play a less significant role in cisplatin chemoresistance.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos/farmacologia , Carcinoma de Células de Transição/tratamento farmacológico , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Glutationa Transferase/metabolismo , Isoenzimas/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Antineoplásicos/metabolismo , Western Blotting/métodos , Cisplatino/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Glutationa/metabolismo , Glutationa S-Transferase pi , Glutationa Transferase/genética , Isoenzimas/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais CultivadasAssuntos
Neoplasias Esofágicas/genética , Genes Supressores de Tumor/genética , Oncogenes/genética , Animais , Carcinógenos/farmacologia , China/epidemiologia , Dimetilnitrosamina/análogos & derivados , Dimetilnitrosamina/farmacologia , Neoplasias Esofágicas/induzido quimicamente , Neoplasias Esofágicas/epidemiologia , Humanos , Perda de Heterozigosidade , MutaçãoRESUMO
OBJECTIVES: To investigate mitochondrial DNA (mtDNA) mutations in human detrusor after partial bladder outlet obstruction (BOO) and correlate the findings with the results of urodynamic studies. METHODS: Sixty-two male patients with and without BOO were recruited and assessed by the International Prostate Symptom Score, a quality-of-life assessment index, and sonography. The severity of partial BOO was determined by pressure-flow study with an International Continence Society (ICS) nomogram. Random detrusor biopsies obtained cystoscopically were analyzed by polymerase chain reaction (PCR) techniques to detect possible mtDNA deletions. Primer-shift PCR and DNA sequencing were then performed to characterize specific mtDNA deletions. A semiquantitative PCR method was used to determine the proportion of the deleted mtDNA in detrusor. Finally, the mtDNA deletion and the urodynamic results were compared statistically. RESULTS: A 4977-bp mtDNA deletion was identified in the human detrusor. Its incidence and proportion were found to increase after partial BOO (P = 0.005 and 0.012, respectively). The incidence of the mtDNA deletion was 4.2% (1 of 24) in the unobstructed group, 27.8% (5 of 18) in the equivocal group, and 40% (8 of 20) in the obstructed group. The mean proportion of the 4977-bp deleted mtDNA was 23.7 and 12.7 times higher in the obstructed and equivocal groups, respectively, compared with that of the unobstructed group. CONCLUSIONS: We found mtDNA with the 4977-bp deletion in human detrusor and an increase of this deletion after partial BOO. This molecular change might account for the previous observations of mitochondrial functional impairment and voiding dysfunction after partial BOO.
Assuntos
Deleção Cromossômica , DNA Mitocondrial/genética , Obstrução do Colo da Bexiga Urinária/genética , Urodinâmica/genética , Idoso , Biópsia , Análise Mutacional de DNA , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Bexiga Urinária/patologia , Bexiga Urinária/fisiopatologia , Obstrução do Colo da Bexiga Urinária/patologia , Obstrução do Colo da Bexiga Urinária/fisiopatologia , Urodinâmica/fisiologiaRESUMO
PURPOSE: We correlated ultrastructural changes in mitochondria in the human detrusor with the severity of partial bladder outlet obstruction on urodynamics. MATERIALS AND METHODS: We recruited into the study 52 men with and without bladder outlet obstruction symptoms. The severity of partial bladder outlet obstruction was determined by pressure flow study. Random detrusor biopsy specimens obtained by cystoscopy were fixed immediately and processed for transmission electron microscopic observation. Random areas were photographed for further morphological and morphometric analysis using mitochondrial damage score and stereological principles. RESULTS: Mitochondrial damage score and mean mitochondrial volume strongly correlated with the urodynamic severity of partial bladder outlet obstruction, while mitochondrial volume density, surface density of the mitochondrial outer membrane and number of mitochondria per unit of cytoplasm area did not significantly correlate with severity. CONCLUSIONS: Detrusor mitochondrial swelling and structural destruction increased with the severity of partial bladder outlet obstruction. These changes may be associated with impaired mitochondrial function and oxidative metabolism after partial bladder outlet obstruction. Detrusor mitochondrial damage may explain voiding dysfunction after partial bladder outlet obstruction develops.
Assuntos
Mitocôndrias Musculares/ultraestrutura , Músculo Liso/ultraestrutura , Obstrução do Colo da Bexiga Urinária/patologia , Obstrução do Colo da Bexiga Urinária/fisiopatologia , Bexiga Urinária/ultraestrutura , Urodinâmica , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
The effects of mifepristone on production of leukemia inhibitory factor (LIF) and uterine receptivity in rabbits was studied. In ovariectomized rabbits, LIF protein was at an undetectable level in control (score = 0), and upregulated by progesterone alone (score = 4). Estrogen had no additive effect, and may even have had a slightly negative effect when the rabbits were treated with both estrogen and progesterone (score = 3). Meanwhile, mifepristone obviously inhibited the stimulation of progesterone on the production of LIF in rabbit uterus (score = 1). The results also showed that LIF protein has a beneficial effect on uterine receptivity and mifepristone prevents this effect. The transfer of embryos to LIF-treated recipients significantly increased pregnancy (70%) and implantation rate (31%) as compared with control (pregnant rate = 50% and implantation rate = 17%). The transfer of embryos to LIF and mifepristone-treated recipients significantly decreased pregnancy (30%) and implantation rate (9%). The results of this study suggest that mifepristone prevented the effects of progesterone on LIF production and the beneficial effect of LIF on uterine receptivity.