Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 116
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Hong Kong Med J ; 30(3): 233-240, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38825732

RESUMO

The surgical management of obesity in Hong Kong has rapidly evolved over the past 20 years. Despite increasing public awareness and demand concerning bariatric and metabolic surgery, service models generally are not standardised across bariatric practitioners. Therefore, a working group was commissioned by the Hong Kong Society for Metabolic and Bariatric Surgery to review relevant literature and provide recommendations concerning eligibility criteria for bariatric and metabolic interventions within the local population in Hong Kong. The current position statement aims to provide updated guidance regarding the indications and contraindications for bariatric surgery, metabolic surgery, and bariatric endoscopic procedures.


Assuntos
Cirurgia Bariátrica , Obesidade , Humanos , Cirurgia Bariátrica/normas , Cirurgia Bariátrica/métodos , Hong Kong , Obesidade/cirurgia , Adulto , Endoscopia/métodos , Endoscopia/normas , Sociedades Médicas , Obesidade Mórbida/cirurgia
2.
Br J Surg ; 108(5): 554-565, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-34043776

RESUMO

BACKGROUND: Bariatric surgery can be effective in weight reduction and diabetes remission in some patients, but is expensive. The costs of bariatric surgery in patients with obesity and type 2 diabetes mellitus (T2DM) were explored here. METHODS: Population-based retrospectively gathered data on patients with obesity and T2DM from the Hong Kong Hospital Authority (2006-2017) were evaluated. Direct medical costs from baseline up to 60 months were calculated based on the frequency of healthcare service utilization and dispensing of diabetes medication. Charlson Co-morbidity Index (CCI) scores and co-morbidity rates were measured to compare changes in co-morbidities between surgically treated and control groups over 5 years. One-to-five propensity score matching was applied. RESULTS: Overall, 401 eligible surgical patients were matched with 1894 non-surgical patients. Direct medical costs were much higher for surgical than non-surgical patients in the index year (€36 752 and €5788 respectively; P < 0·001) mainly owing to the bariatric procedure. The 5-year cumulative costs incurred by surgical patients were also higher (€54 135 versus €28 603; P < 0·001). Although patients who had bariatric surgery had more visits to outpatient and allied health professionals than those who did not across the 5-year period, surgical patients had shorter length of stay in hospitals than non-surgical patients in year 2-5. Surgical patients had significantly better CCI scores than controls after the baseline measurement (mean 3·82 versus 4·38 at 5 years; P = 0·016). Costs of glucose-lowering medications were similar between two groups, except that surgical patients had significantly lower costs of glucose-lowering medications in year 2 (€973 versus €1395; P = 0.012). CONCLUSION: Bariatric surgery in obese patients with T2DM is expensive, but leads to an improved co-morbidity profile, and reduced length of hospitalization.


Assuntos
Cirurgia Bariátrica/economia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Obesidade/economia , Assistência Ambulatorial/economia , Assistência Ambulatorial/estatística & dados numéricos , Estudos de Casos e Controles , Comorbidade , Diabetes Mellitus Tipo 2/economia , Serviço Hospitalar de Emergência/economia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hong Kong/epidemiologia , Humanos , Hipoglicemiantes/economia , Hipoglicemiantes/uso terapêutico , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Obesidade/cirurgia , Visita a Consultório Médico/economia , Visita a Consultório Médico/estatística & dados numéricos , Estudos Retrospectivos
3.
Med J Malaysia ; 76(1): 107-109, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33510120

RESUMO

Dengue fever is one of the commonest tropical disease in the tropics. It can present with mild acute febrile illness to severe organ failure. Reported neurological complications of dengue include dengue encephalopathy, encephalitis, transverse myelitis and intracranial haemorrhage. Intracranial haemorrhage in dengue can present as subdural haematoma, extradural haematoma, intracerebral haemorrhage and subarachnoid haemorrhage. We report here a case of subarachnoid haemorrhage in a patient with severe dengue. Our patient was a 30-year-old man who presented with acute febrile illness. He subsequently developed plasma leakage and upper gastrointestinal bleeding. He then had reduced conscious level. Computed tomography of his brain showed subarachnoid haemorrhage. He eventually succumbed to his illness.


Assuntos
Dengue , Encefalite , Dengue Grave , Hemorragia Subaracnóidea , Adulto , Dengue/complicações , Febre , Hematoma Subdural , Humanos , Masculino , Dengue Grave/complicações , Dengue Grave/diagnóstico , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/etiologia
4.
Br J Surg ; 103(11): 1476-86, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27511444

RESUMO

BACKGROUND: Radiofrequency ablation (RFA) is an emerging treatment for primary aldosteronism owing to aldosterone-producing adenoma. Whether RFA could be an alternative treatment to laparoscopic adrenalectomy is unknown. METHODS: This was a retrospective comparative study in patients with aldosterone-producing adenoma undergoing either laparoscopic adrenalectomy or CT-guided percutaneous RFA between 2004 and 2012. Short-term outcomes and long-term resolution rates of primary aldosteronism (normalized aldosterone to renin ratio), hypokalaemia and hypertension (BP lower than 140/90 mmHg without antihypertensive medical therapy) were evaluated. RESULTS: Some 63 patients were included, 27 in the laparoscopic adrenalectomy group and 36 in the RFA group. RFA was associated with shorter duration of operation (median 12 versus 124 min; P < 0·001), shorter hospital stay (2 versus 4 days; P < 0·001), lower analgesic requirements (13 of 36 versus 23 of 27 patients; P < 0·001) and earlier resumption of work (median 4 versus 14 days; P = 0·006). Morbidity rates were similar in the two groups. With median follow-up of 5·7 (range 1·9-10·6) years, resolution of primary aldosteronism was seen in 33 of 36 patients treated with RFA and all 27 patients who had laparoscopic adrenalectomy (P = 0·180). Hypertension was resolved less frequently after treatment with RFA compared with laparoscopic adrenalectomy (13 of 36 versus 19 of 27 patients; P = 0·007). Hypokalaemia was resolved in all patients. CONCLUSION: For patients with aldosterone-producing adenoma the efficacy of resolution of primary aldosteronism and hypertension was inferior after treatment with RFA compared with laparoscopic adrenalectomy.


Assuntos
Adenoma/cirurgia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Laparoscopia/métodos , Terapia a Laser/métodos , Adenoma/diagnóstico , Adenoma/metabolismo , Adolescente , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/metabolismo , Adulto , Assistência ao Convalescente , Idoso , Idoso de 80 Anos ou mais , Aldosterona/metabolismo , Feminino , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirurgia , Hipertensão/etiologia , Hipertensão/cirurgia , Tempo de Internação/estatística & dados numéricos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
8.
Br J Cancer ; 112(11): 1751-9, 2015 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-25906045

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancer in women globally. This subtype often has early and high recurrence rates resulting in poor survival, partially due to lack of targeted therapies. Therefore, there is an urgent need to identify TNBC-specific biomarkers for early diagnosis and treatment monitoring, and to develop more effective targeted therapy. METHODS: By using miRCURY LNA array platform, we compared the differential miRNA expressions in plasma of patient with TNBC (n=5) and non-TNBC (n=5), as well as healthy controls (n=5). Potential miRNAs were then validated in a large cohort of patients by real-time PCR. RESULTS: Ten putative miRNAs from the microarray data that differentially expressed between non-TNBC and healthy controls were identified. In the screening phase (n=90), we selected five miRNAs (miR-92a-3p, miR-342-3p, miR-16, miR-21 and miR-199a-5p) that could discriminate TNBC from non-TNBC for further validation. Results showed that miR-16, miR-21 and miR-199a-5p were underexpressed in TNBC when compared with non-TNBC, and were further validated in a large cohort (n=252). In addition, post-operative plasma levels of miR-16, miR-21 and miR-199a-5p were significantly restored when compared with pre-operative plasma of TNBC. Plasma miR-199a-5p expression in TNBC had significant difference when compared with non-TNBC and healthy controls, the receiver-operator characteristics curve analysis revealed the highest area under curve (AUC=0.8838) among all. The expression levels were associated with TNM stage and tumour subtypes. CONCLUSIONS: Our data suggest that miR-199a-5p could be a TNBC-specific marker with diagnostic value and provide insights into targeted therapy in the treatment of TNBC.


Assuntos
Diagnóstico Precoce , MicroRNAs/sangue , Neoplasias de Mama Triplo Negativas/sangue , Adulto , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Pessoa de Meia-Idade , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
9.
Br J Surg ; 102(2): e158-68, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25627130

RESUMO

BACKGROUND: Mesenchymal stem cells are proposed to facilitate repair of organ injuries. The aim of this study was to investigate whether local injection of mesenchymal stem cells could accelerate healing of sutured gastric perforations. METHODS: Sutured gastric perforations in rats were treated either with local injection of mesenchymal stem cells (injected MSC group) or by topically spraying with fibrin glue containing mesenchymal stem cells (sprayed MSC group). Controls were treated by local injection of saline or topical spray of fibrin glue without mesenchymal stem cells. Healing of sutured gastric perforations was assessed on days 3, 5 and 7. RESULTS: Local injection of mesenchymal stem cells significantly promoted the healing of gastric perforations, with the highest pneumatic bursting pressure (mean(s.e.m.) 112·3(30·2) mmHg on day 5 versus 71·2(17·4) mmHg in saline controls; P = 0·001), minimal wound adhesions, and lowest incidence of wound dehiscence (3, 6, 5 and 1 animal on day 5 in control, fibrin, sprayed MSC and injected MSC groups respectively; n = 10 per group) and abdominal abscess (2, 2, 1 and no animals respectively on day 5). Histological examination showed that gastric perforations in the injected MSC group displayed reduced inflammation, and increased granulation and re-epithelialization. Sutured gastric perforations in the injected MSC group showed decreased expression of interleukin 6, and increased expression of transforming growth factor ß1 and epithelial proliferating cell nuclear antigen, compared with the other groups. CONCLUSION: Local injection of mesenchymal stem cells was more effective than topical application, and enhanced the healing of sutured gastric perforations by an anti-inflammatory process, enhanced cellular proliferation and earlier onset of granulation. Surgical relevance Abnormal healing of gastric perforation may cause morbidity and increase the risk of death. Adipose tissue-derived mesenchymal stem cells have been found to promote the healing of organ injuries through cellular differentiation and secretion of cytokines that stimulate cellular proliferation and angiogenesis, and suppress inflammation. This study explored the therapeutic potential of such mesenchymal stem cells for promotion of the healing of sutured gastric perforations. Mesenchymal stem cells delivered by local injection significantly enhanced the healing of gastric perforations with reduced severity of wound adhesion, and a decreased incidence of wound dehiscence and abdominal abscess. The increased expression of transforming growth factor ß1, proliferating cell nuclear antigen and reduced level of interleukin 6 provide evidence for enhancement of the healing process. Engrafted mesenchymal stem cells expressed α-smooth muscle actin as a marker of myofibroblasts. This preclinical study indicates that local injection of allogeneic adipose tissue-derived mesenchymal stem cells may have a potential therapeutic role in enhancing the healing of peptic ulcer disease and prevention of ulcer-related complications.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Cicatrização/fisiologia , Tecido Adiposo/citologia , Tecido Adiposo/transplante , Administração Tópica , Animais , Diferenciação Celular/fisiologia , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Feminino , Adesivo Tecidual de Fibrina/administração & dosagem , Gastrite/metabolismo , Injeções , Perfuração Intestinal/patologia , Perfuração Intestinal/terapia , Células-Tronco Mesenquimais/citologia , Pressão , Ratos Sprague-Dawley , Gastropatias/patologia , Gastropatias/terapia , Deiscência da Ferida Operatória , Técnicas de Sutura , Adesivos Teciduais/administração & dosagem , Fator de Crescimento Transformador beta1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Ann Oncol ; 24(1): 165-71, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22887465

RESUMO

BACKGROUND: The aim of this study was to report on the 5-year survival outcomes of patients with resectable esophageal carcinoma who were treated by definitive chemoradiotherapy (CRT) or standard esophagectomy. PATIENTS AND METHODS: Between July 2000 and December 2004, 81 patients with resectable squamous cell carcinoma of the mid- or lower thoracic esophagus were randomized to receive esophagectomy or definitive CRT. The primary outcome was the overall survival and secondary outcomes included disease-free survival, morbidities and mortalities. RESULTS: Forty-five patients received esophagectomy and 36 patients were treated by definitive CRT. The overall 5-year survival favors CRT but the difference did not reach statistical significance (surgery 29.4% and CRT 50%, P=0.147). A trend to improved 5-year survival was observed for patients suffering from node-positive disease (P=0.061). The 5-year disease-free survival also showed a trend to significance favoring CRT (P=0.068), particularly for patients suffering from node-positive disease (P=0.017). Both the stage of the disease and albumin level were significant predictors to mortality and disease-free survival. CONCLUSIONS: Definitive CRT for squamous esophageal carcinoma resulted in comparable long-term survival to surgery. Further large-scale studies would be required to further investigate the role of CRT in node-positive patients. Clinicaltrials.gov identifier: NCT01032967.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Análise de Sobrevida , Carcinoma de Células Escamosas/cirurgia , Terapia Combinada , Neoplasias Esofágicas/cirurgia , Humanos , Estudos Prospectivos
11.
Dis Esophagus ; 26(3): 231-6, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22624653

RESUMO

Achalasia is a rare primary motility disorder of esophagus; treatments include endoscopic balloon dilatation (EBD) and laparoscopic Heller's cardiomyotomy (LC). This study compared EBD versus LC for treatment of achalasia with focus on quality of life (QoL) and prevalence of post-treatment gastroesophageal reflux disease. This was a retrospective cohort study of all patients diagnosed with achalasia older than 16 treated with either EBD or LC from January 1998 to April 2008. Patients' demographic data, comorbidities, postintervention GERD symptoms, QoL, recurrence of dysphagia, reintervention rate, hospital stay, and time to resumption of diet were collected. Sixty-eight patients were recruited into the study (EBD n= 50; LC n= 18). A significant improvement in QoL was found in patients undergoing LC (0.917 vs. 0.807, P= 0.006). A higher proportion of patients treated with EBD developed post-treatment gastroesophageal reflux symptoms (60.5% vs. 43.8%) when compared with LC, although statistically insignificant (P= 0.34). Patients treated with balloon dilatation had a greater percentage of recurrence of dysphagia (55.1% vs. 26.7%; P= 0.235) and need of reintervention (42.1% vs. 9.1%; P= 0.045). However, these patients had a shorter median hospital stay (1d [range 0-4]) and earlier resumption of diet (0d [range 0-3]). Although EBD is associated with a quicker perioperative recovery, LC accomplished a better QoL, lower incidence of recurrence of dysphagia, and need of reintervention after treatment for achalasia.


Assuntos
Cárdia/cirurgia , Cateterismo/métodos , Transtornos de Deglutição/prevenção & controle , Acalasia Esofágica/cirurgia , Esofagoscopia/métodos , Laparoscopia/métodos , Qualidade de Vida , Adulto , Estudos de Coortes , Dieta , Dilatação/métodos , Acalasia Esofágica/psicologia , Acalasia Esofágica/terapia , Feminino , Seguimentos , Refluxo Gastroesofágico/etiologia , Hospitalização , Humanos , Tempo de Internação , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Recidiva , Retratamento , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
12.
Int Nurs Rev ; 60(4): 501-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24131252

RESUMO

BACKGROUND: Nurses in the general ward are faced with patients who are at high risk of clinical deterioration. Having the key role in performing routine vital signs monitoring, non-registered nurses such as enrolled nurses are the front line nurses who play a pivotal role in detecting and responding to the deteriorating ward patient. AIMS: (1) To explore the experience of enrolled nurses with deteriorating patients in pre-cardiac arrest situations and (2) to identify strategies to enhance their role in caring for deteriorating ward patients. METHOD: A qualitative study using critical incident technique was conducted. Fifteen enrolled nurses who had encountered deteriorating ward patients were interviewed. Data were analysed using content analysis. FINDINGS: Three themes emerged describing enrolled nurse's experience with deteriorating patients: recognizing deterioration, responding to deterioration and taking responsibility. Two themes, including educational development and modifying clinical processes, were strategies identified to enhance the ability of enrolled nurses in recognizing and managing deteriorating patients. CONCLUSION: The study highlighted a need to enhance the ability of front line nurses in recognizing and responding to patient deterioration through nursing education and modifications of clinical processes. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nursing education could focus on increasing the awareness of the importance of performing complete vital signs monitoring and undertaking accurate interpretation of vital signs. Strategies to improve clinical processes could include the need for registered nurses to provide supervision of enrolled nurses in the interpretation of vital signs readings and share the responsibility of performing vital signs monitoring.


Assuntos
Competência Clínica , Avaliação em Enfermagem , Análise e Desempenho de Tarefas , Sinais Vitais , Progressão da Doença , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pesquisa Qualitativa , Singapura
13.
Diabetes Obes Metab ; 14(4): 372-4, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22050632

RESUMO

Bariatric surgery has recently been considered as an option for treatment of type 2 diabetes mellitus (T2DM). We assessed the effect of laparoscopic gastric banding and laparoscopic sleeve gastrectomy in a cohort of 39 T2DM Chinese patients with body mass index (BMI) over 30 kg/m(2) . Their mean body weights and BMI before surgery were 108 kg and 40 kg/m(2) , respectively, and 18 patients (46%) had suboptimal diabetic control (HbA1c >7%). After a mean follow-up of 27 months, 4 of 11 insulin-dependent patients (36%) were able to stop their insulin therapy, and 18 patients (46%) achieved remission of T2DM (HbA1c <6.5% without the use of medication). Glycaemic control remained poor in only nine other patients (27%). Logistic regression analysis showed that a short history of T2DM and high BMI could predict remission of diabetes after restrictive procedures. Our results suggest that restrictive surgery can significantly improve glycaemic control in obese T2DM patients.


Assuntos
Diabetes Mellitus Tipo 2/cirurgia , Gastrectomia , Gastroplastia , Obesidade Mórbida/cirurgia , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , China/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Seguimentos , Gastrectomia/métodos , Gastroplastia/métodos , Hemoglobinas Glicadas/metabolismo , Humanos , Modelos Logísticos , Masculino , Obesidade Mórbida/sangue , Obesidade Mórbida/epidemiologia , Indução de Remissão , Resultado do Tratamento , Redução de Peso
14.
Med J Malaysia ; 67(2): 151-4, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22822633

RESUMO

In-centre intermittent peritoneal dialysis (IPD), a decade-old modality commonly associated with acute (stab) PD, continues to play an undeniably important role of providing "temporary" renal replacement therapy (RRT) in Malaysia. In our center, IPD is commenced after insertion of Tenckhoff catheter by interventional nephrologists as an interim option until a definitive RRT is established. This study aims to describe our experience and evaluate the viability of this modality as a bridging therapy. We retrospectively analyzed 39 IPD patients from January 2007 to December 2009; looking at demographics, cause of end-stage renal disease, duration on the program, length of hospitalization, PD-related infection profile, biochemical parameters and clinical outcomes. We accumulated a total experience of 169 patient-months, the average age of patients was 54.6 +/- 11.6 years, 84.6% of them diabetics. The median duration of a patient in the program was 88 days with accumulated in-hospital stay of 45 days. Eventually 48.7% of the patients secured placement for long-term haemodialysis while 20.5% were converted to CAPD. The mortality rate was 7.7% while the peritonitis rate was at 1 per 18.8 patient months. Our study shows that IPD is a viable interim option with a low infection rate and good clinical outcome.


Assuntos
Falência Renal Crônica/terapia , Diálise Peritoneal/métodos , Feminino , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/mortalidade , Tempo de Internação/estatística & dados numéricos , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/mortalidade , Radiografia Intervencionista , Terapia de Substituição Renal , Estudos Retrospectivos , Resultado do Tratamento
15.
Endoscopy ; 42(4): 338-41, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20146165

RESUMO

A newly designed insulated angulotome was evaluated in a series of patients in whom biliary cannulation using conventional methods had failed and who required precut sphincterotomy. The new device consists of an insulated glass tip to prevent excessive electrocautery flow, and angulation to facilitate elevation of the papillary roof on cutting. A prospective series of patients with cholangitis or obstructive jaundice with failed biliary cannulation were recruited. The success of cannulation and complications following endoscopic retrograde cholangiopancreatography were analyzed. A total of 13 patients underwent precut sphincterotomy using the insulated angulotome. The immediate success of gaining biliary access after failed cannulation was 100 %. The mean size of the common bile duct on ultrasonography was 8.1 mm. The mean time to achieve biliary cannulation was 9 minutes 4 seconds, and there was no perforation or bleeding. This case series showed that precut sphincterotomy with the insulated angulotome can be safely performed without major complications.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/instrumentação , Esfinterotomia Endoscópica/instrumentação , Cateterismo , Ducto Colédoco/cirurgia , Humanos
17.
Gut ; 58(10): 1375-81, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19201770

RESUMO

OBJECTIVE: MicroRNAs (miRNAs) have been shown to offer great potential in the diagnosis of cancer. We investigated whether plasma miRNAs could discriminate between patients with and without colorectal cancer (CRC). METHODS: This study was divided into three phases: (1) marker discovery using real-time PCR-based miRNA profiling on plasma, corresponding cancerous and adjacent non-cancerous colonic tissues of five patients with CRC, along with plasma from five healthy individuals as controls; (2) marker selection and validation by real-time quantitative RT-PCR on a small set of plasma; and (3) independent validation on a large set of plasma from 90 patients with CRC, 20 patients with gastric cancer, 20 patients with inflammatory bowel disease (IBD) and 50 healthy controls. RESULTS: Of the panel of 95 miRNAs analysed, five were upregulated both in plasma and tissue samples. All the five miRNAs were validated on the plasma of 25 patients with CRC and 20 healthy controls. Both miR-17-3p and miR-92 were significantly elevated in the patients with CRC (p<0.0005). The plasma levels of these markers were significantly reduced after surgery in 10 patients with CRC (p<0.05). Further validation with an independent set of plasma samples (n = 180) indicated that miR-92 differentiates CRC from gastric cancer, IBD and normal subjects. This marker yielded a receiver operating characteristic curve area of 88.5%. At a cut-off of 240 (relative expression in comparison to RNU6B snRNA), the sensitivity was 89% and the specificity was 70% in discriminating CRC from control subjects. CONCLUSION: MiR-92 is significantly elevated in plasma of patients with CRC and can be a potential non-invasive molecular marker for CRC screening.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/diagnóstico , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/metabolismo , Células Neoplásicas Circulantes/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
Br J Cancer ; 101(4): 699-706, 2009 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-19638978

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are 19-25-nucleotides regulatory non-protein-coding RNA molecules that regulate the expressions of a wide variety of genes, including some involved in cancer development. In this study, we investigated the possible role of miR-143 in colorectal cancer (CRC). METHODS: Expression levels of human mature miRNAs were examined using real-time PCR-based expression arrays on paired colorectal carcinomas and adjacent non-cancerous colonic tissues. The downregulation of miR-143 was further evaluated in colon cancer cell lines and in paired CRC and adjacent non-cancerous colonic tissues by qRT-PCR. Potential targets of miR-143 were defined. The functional effect of miR-143 and its targets was investigated in human colon cancer cell lines to confirm miRNA-target association. RESULTS: Both real-time PCR-based expression arrays and qRT-PCR showed that miR-143 was frequently downregulated in 87.5% (35 of 40) of colorectal carcinoma tissues compared with their adjacent non-cancerous colonic tissues. Using in silico predictions, DNA methyltranferase 3A (DNMT3A) was defined as a potential target of miR-143. Restoration of the miR-143 expression in colon cell lines decreased tumour cell growth and soft-agar colony formation, and downregulated the DNMT3A expression in both mRNA and protein levels. DNMT3A was shown to be a direct target of miR-143 by luciferase reporter assay. Furthermore, the miR-143 expression was observed to be inversely correlated with DNMT3A mRNA and protein expression in CRC tissues. CONCLUSION: Our findings suggest that miR-143 regulates DNMT3A in CRC. These findings elucidated a tumour-suppressive role of miR-143 in the epigenetic aberration of CRC, providing a potential development of miRNA-based targeted approaches for CRC therapy.


Assuntos
Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/metabolismo , Western Blotting , Linhagem Celular Tumoral , DNA Metiltransferase 3A , Regulação para Baixo , Inativação Gênica , Humanos , MicroRNAs/genética , RNA Interferente Pequeno , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
Br J Cancer ; 101(4): 691-8, 2009 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-19672268

RESUMO

BACKGROUND: Retinoic acid-regulated nuclear matrix-associated protein (RAMP) is a WD40 repeat-containing protein that is involved in various biological functions, but little is known about its role in human cancer. This study aims to delineate the oncogenic role of RAMP in gastric carcinogenesis. METHODS: RAMP expression was examined by real-time quantitative RT-PCR, immunohistochemistry and western blotting. Inhibition of RAMP expression was performed by siRNA-mediated knockdown. The functional effects of RAMP on cell kinetics were measured by cell viability assay, colony formation assay and flow cytometry. Cell lines stably expressing RAMP were established to investigate the oncogenic effects of RAMP in vitro. RESULTS: Ramp was readily expressed in all seven gastric cancer cell lines and was significantly increased in human gastric cancer tissues when compared with their adjacent non-cancerous tissues (P<0.001). In keeping with this, expression of RAMP protein was higher in gastric cancer tissues compared with their adjacent non-cancerous tissues, whereas moderate protein expression were noted in intestinal metaplasia. Knockdown of RAMP in gastric cancer cells significantly reduced cell proliferation (P<0.01) and soft agar colony formation (P<0.001), but induced apoptosis and G(2)/M arrest. In additional, knockdown RAMP induced cell apoptosis is dependent on functional accumulation of p53 and p21 and induction of cleaved caspases-9, caspases-3 and PARP. Strikingly, overexpression of RAMP promoted anchorage-independent cell growth in soft agar. CONCLUSION: Our findings demonstrate that RAMP plays an oncogenic role in gastric carcinogenesis. Inhibition of RAMP may be a promising approach for gastric cancer therapy.


Assuntos
Biomarcadores Tumorais/análise , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Apoptose/fisiologia , Western Blotting , Linhagem Celular Tumoral , Citometria de Fluxo , Expressão Gênica , Humanos , Imuno-Histoquímica , RNA Mensageiro/análise , RNA Interferente Pequeno , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise Serial de Tecidos , Ubiquitina-Proteína Ligases
20.
Br J Cancer ; 99(12): 2083-7, 2008 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-18985039

RESUMO

Tumour suppressor genes (TSGs) were frequently inactivated through promoter hypermethylation in gastric carcinoma as well as pre-malignant gastric lesions, suggesting that promoter hypermethylation can be used as a marker to define novel TSGs and also biomarkers for early detection of gastric cancer. In an effort to search for such genes aberrantly methylated in gastric cancer development, fibulin 1 (FBLN1) was found as a candidate TSG epigenetically downregulated in gastric cancer. FBLN1 expression was downregulated in all of gastric cancer cell lines used (100%, 7 out of 7) and the primary gastric carcinoma tissues (84%, 86 out of 102) and significantly restored after pharmacological demethylation. Hypermethylation of the FBLN1 promoter was frequently (71%, 5 out of 7) detected in gastric cancer cell lines and primary gastric carcinoma tissues. Ectopic expression of FBLN1 led to the growth inhibition of gastric cancer cells through the induction of apoptosis. In summary, FBLN1 was identified as a novel candidate TSG epigenetically downregulated in gastric cancer.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Metilação de DNA/genética , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/genética , Regiões Promotoras Genéticas/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Idoso , Compostos Aza/farmacologia , Proteínas de Ligação ao Cálcio/genética , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Masculino , Neoplasias Gástricas/patologia , Regulação para Cima/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA