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1.
Clin Radiol ; 73(3): 324.e9-324.e18, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29195659

RESUMO

AIM: To investigate the accuracy of cardiac magnetic resonance (CMR) tissue tracking (CMR-TT) and speckle tracking echocardiography (STE) against CMR determined right ventricular (RV) ejection fraction (RVEF) and to identify an optimal cut-off value for STE and CMR-TT to determine RVEF <45% and compare this to other conventional methods for estimating RVEF in dilated cardiomyopathy (DCM) patients. MATERIALS AND METHODS: Twenty-nine DCM patients were recruited prospectively. CMR and echocardiography were performed within 48 hours and four-chamber views were used for strain analysis. Contoured CMR short axis images provided RVEF. Intraclass correlation coefficient (ICC), bias, levels of agreement, and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: CMR-TT RV free-wall longitudinal strain (FLS) and STE RV global longitudinal strain (GLS) showed the best correlation with RVEF (r=-0.68, r=-0.82, p<0.001 respectively). There was moderate correlation between echocardiography RV GLS and CMR RV FLS (r=0.64, p<0.001). CMR-TT FLS showed excellent intra-observer and interobserver reliability (ICC=0.980; ICC=0.968 respectively). STE GLS correlated better with RVEF than with peak systolic annular velocity (S'; r=0.45), tricuspid annular plane systolic excursion (TAPSE; r=0.56), and fractional area change (FAC; r=0.78). CMR-TT RV FLS had better correlation with RVEF than CMR TAPSE (r=0.69 versus 0.40). ROC analysis demonstrated the optimal cut-off value for CMR-TT RV FLS and STE GLS in detection of RVEF <45% was ≥-24.4% (area under the curve=0.87, 100% sensitivity, 66.7% specificity) and ≥-20.9% (area under the curve=0.88, 100% sensitivity, 60% specificity) respectively. CONCLUSION: CMR-TT FLS and STE GLS showed potential to provide rapid assessment of RV function and had superior correlation with RVEF compared to conventional parameters.


Assuntos
Ecocardiografia/métodos , Imagem Cinética por Ressonância Magnética/métodos , Função Ventricular Direita , Idoso , Feminino , Humanos , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes
2.
BMC Cancer ; 12: 324, 2012 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-22846379

RESUMO

BACKGROUND: Prostate cancer is the most commonly diagnosed non-melanoma cancer among men. Androgen deprivation therapy (ADT) has been the core therapy for men with advanced prostate cancer. It is only in recent years that clinicians began to recognize the cognitive-psychosocial side effects from ADT, which significantly compromise the quality of life of prostate cancer survivors. The objectives of the study are to determine the efficacy of a simple and accessible home-based, walking exercise program in promoting cognitive and psychosocial functions of men with prostate cancer receiving ADT. METHODS: A 6-month prospective, single-blinded, randomized controlled trial will be conducted to compare the Exercise Group with the Control Group. Twenty men with prostate cancer starting ADT will be recruited and randomly assigned to one of the two groups: the Exercise Group will receive instructions in setting up an individualized 6-month home-based, walking exercise program, while the Control Group will receive standard medical advice from the attending physician. The primary outcomes will be psychosocial and cognitive functions. Cognitive functions including memory, attention, working memory, and executive function will be assessed using a battery of neurocognitive tests at baseline and 6 months. Psychosocial functions including depression, anxiety and self-esteem will be assessed at baseline, 3 and 6 months using the Center for Epidemiological Studies Depression Scale, Spielberger State-Trait Anxiety Inventory, and Rosenberg Self-Esteem Scale. DISCUSSION: The significance of the cognitive-psychosocial side effects of ADT in men with prostate cancer has only been recently recognized, and the management remains unclear. This study addresses this issue by designing a simple and accessible home-based, exercise program that may potentially have significant impact on reducing the cognitive and psychosocial side effects of ADT, and ultimately improving the health-related quality of life in men with prostate cancer receiving ADT. TRIAL REGISTRATION: NCT00856102.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Cognição/fisiologia , Terapia por Exercício/métodos , Neoplasias da Próstata/terapia , Caminhada/fisiologia , Terapia Combinada , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Neoplasias da Próstata/fisiopatologia , Neoplasias da Próstata/psicologia , Método Simples-Cego , Ajustamento Social , Fatores de Tempo , Resultado do Tratamento
3.
BMC Cancer ; 12: 103, 2012 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-22436542

RESUMO

BACKGROUND: Androgen deprivation therapy (ADT) is the mainstay therapy for men with prostate cancer. However, there are musculoskeletal side effects from ADT that increase the risk for osteoporosis and fracture, and can compromise the quality of life of these individuals. The objectives of this study are to determine the efficacy of a home-based walking exercise program in promoting bone health, physical function and quality of life in men with prostate cancer receiving ADT. METHODS/DESIGN: A 12-month prospective, single-blinded, randomized controlled trial will be conducted to compare the Exercise Group with the Control Group. Sixty men with prostate cancer who will be starting ADT will be recruited and randomly assigned to one of the two groups: the Exercise Group will receive instructions in setting up an individualized 12-month home-based walking exercise program, while the Control Group will receive standard medical advice from the attending physician. A number of outcome measures will be used to assess bone health, physical function, and health-related quality of life. At baseline and 12 months, bone health will be assessed using dual-energy X-ray absorptiometry. At baseline and every 3 months up to 12 months, physical function will be evaluated using the Functional Assessment of Chronic Illness Therapy - Fatigue Scale, Activities-specific Balance Confidence Scale, Short Physical Performance Battery, and Six-Minute Walk Test; and health-related quality of life will be assessed using the Functional Assessment of Cancer Therapy Prostate Module and the Medical Outcomes Study 12-item Short Form Health Survey Version 2. A mixed multiple analysis of variance will be used to analyze the data. DISCUSSION: Musculoskeletal health management remains a challenge in men with prostate cancer receiving ADT. This study addresses this issue by designing a simple and accessible home-based walking exercise program that will potentially have significant impact on reducing the risk of fracture, promoting physical function, and ultimately improving the health-related quality of life in men with prostate cancer receiving ADT. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00834392.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Terapia por Exercício , Doenças Musculoesqueléticas/prevenção & controle , Neoplasias da Próstata/tratamento farmacológico , Absorciometria de Fóton , Análise de Variância , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Composição Corporal/fisiologia , Índice de Massa Corporal , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Humanos , Masculino , Projetos Piloto , Estudos Prospectivos , Neoplasias da Próstata/fisiopatologia , Qualidade de Vida , Método Simples-Cego , Caminhada
4.
Hong Kong Med J ; 17(2): 96-104, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21471588

RESUMO

OBJECTIVE: To identify predictive factors for mortality of patients with upper limb necrotising fasciitis. DESIGN: Retrospective study. SETTING: Six hospitals in Hong Kong. PATIENTS: Clinical records of 29 patients treated in the hospitals were traced and analysed. MAIN OUTCOME MEASURES: Possible predictive factors for mortality as evaluated by application of Fisher's test. RESULTS: Overall mortality was 28%. Digital infections conferred a lower mortality, but progressive necrosis necessitated amputation. Vibrio vulnificus was the commonest organism identified in association with marine injury and in patients with cirrhosis. Prognostic indicators with decreasing significance include deranged renal and liver function, thrombocytopaenia, proximal involvement (elbow or above) initially, and presence of hypotension upon admission. CONCLUSION: With a P value of less than 0.05, deranged renal and liver function, thrombocytopaenia, initial proximal involvement, and hypotension on admission were predictors of mortality in necrotising fasciitis affecting the upper limbs. The ALERTS (Abnormal Liver function, Extent of infection, Renal impairment, Thrombocytopenia, and Shock) score with a cutoff of 3 appeared to predict mortality.


Assuntos
Fasciite Necrosante/mortalidade , Fasciite Necrosante/complicações , Fasciite Necrosante/tratamento farmacológico , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Extremidade Superior
5.
Accid Anal Prev ; 142: 105565, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32361475

RESUMO

In this study, a virtual-reality (VR) pedestrian simulation method was used to evaluate the risks to pedestrians crossing streets in a traffic system with driving rules that were unfamiliar to them. Pedestrians from mainland China (which has a right-side driving (RD) system) and Hong Kong (which has a left-side driving (LD) system) were studied. Significant differences were observed between pedestrians from the different locations in terms of the direction in which the pedestrians habitually first looked before crossing. When exposed to an unfamiliar driving rule (i.e., traffic coming from an inconsistent direction in terms of participants' habitual driving system), the odds of participants from mainland China making an error in their looking behavior were 2.93 times those when exposed to a familiar driving rule. Road markings and traffic sound did not improve these participants' looking behavior. The results also show a negative correlation between inattentive looking behavior and time to collision (significant at the 1% level), as these errors lead to a shorter time to collision and increased the risk to pedestrians. The results of this study confirmed the risks for pedestrians traveling to places with unfamiliar driving rules and confirmed the existence of habitual looking behavior, and therefore provide evidence of the need for future studies to improve this problem. These may help decision makers take the risks of pedestrians from different driving rules into consideration in future traffic policymaking or traffic-facility improvements. The use of a VR simulation-based approach in this study provided a safe and controllable way to trial interventions and potential improvements without risking injury to participants, and thus may also be used for similar future studies.


Assuntos
Condução de Veículo/legislação & jurisprudência , Pedestres/psicologia , Acidentes de Trânsito/prevenção & controle , Adulto , China , Tomada de Decisões , Feminino , Hong Kong , Humanos , Masculino , Realidade Virtual , Adulto Jovem
6.
J Am Chem Soc ; 131(45): 16461-71, 2009 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-19845339

RESUMO

The basic characteristics of nanowire growth driven by screw dislocations were investigated by synthesizing hierarchical lead sulfide (PbS) nanowire "pine trees" using chemical vapor deposition of PbCl(2) and S precursors and systematically observing the effects of various growth parameters, such as hydrogen flow, temperature, pressure, and the growth substrates employed. Statistical surveys showed that the growth rate of the dislocation-driven trunk is about 6 mum/min and that of the vapor-liquid-solid (VLS) driven branch nanowire is about 1.2 mum/min under the typical reaction conditions at 600 degrees C, 900 Torr, and a hydrogen flow rate of 1.5 sccm. The onset of hydrogen flow plus the presence of fresh silicon have been identified as the critical ingredients for generating PbS nanowire trees reproducibly. To explain the experimental findings in the context of classical crystal growth theory, the former is suggested to create a spike in supersaturation of the actual sulfur precursor H(2)S and initiate dislocations with screw components that then propagate anisotropically to form the PbS nanowire trunks. Maintaining suitable hydrogen flow provides a favorable low supersaturation that promotes dislocation-driven trunk nanowire growth and enables the simultaneous VLS nanowire growth of branches. Furthermore, thermodynamic consideration and experiments showed that silicon fortuitously controls the supersaturation by reversibly reacting with H(2)S to form SiS(2) and that SiS(2) can also be a viable precursor for PbS nanowire growth. The key requirements of screw dislocation-driven nanowire growth are summarized. This study provides some general guidelines for further nanowire growth driven by screw dislocations.


Assuntos
Nanofios/química , Sulfetos/síntese química , Hidrogênio/química , Chumbo/química , Teste de Materiais , Tamanho da Partícula , Pressão , Silício/química , Sulfetos/química , Propriedades de Superfície , Temperatura
7.
Stud Health Technol Inform ; 122: 654-6, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17102343

RESUMO

With the growth of the ageing population in Hong Kong, healthcare professionals believe that there will be a great demand of healthcare service at the community level. In 2000, the first prototype of telehealth system was developed, tested and validated by the School of Nursing, The Hong Kong Polytechnic University. With the advancement of information technology and inexpensive video- conference facility, an inter-clinic patient-centered healthcare information system has been evolved and used by a number of satellite clinics since 2003. In order to foster the importance of personal healthcare education at the community level, different versions of the telehealth system were designed and developed for school children and teenagers. Now the research team is focusing on the development of the pocket PC's version. Experience on the deployment of such technology-intensive system in healthcare was discussed in this paper.


Assuntos
Difusão de Inovações , Telemedicina/instrumentação , Hong Kong , Humanos
8.
Am J Phys Med Rehabil ; 95(8): 561-70, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26829081

RESUMO

OBJECTIVE: The aim of this study was to examine the effects of a 6-week community-based physical activity (PA) intervention on physical function-related risk factors for falls among 56 breast cancer survivors (BCS) who had completed treatments. DESIGN: This was a single-group longitudinal study. The multimodal PA intervention included aerobic, strengthening, and balance components. Physical function outcomes based on the 4-meter walk, chair stand, one-leg stance, tandem walk, and dynamic muscular endurance tests were assessed at 6-week pre-intervention (T1), baseline (T2), and post-intervention (T3). T1 to T2 and T2 to T3 were the control and intervention periods, respectively. RESULTS: All outcomes, except the tandem walk test, significantly improved after the intervention period (P < 0.05), with no change detected after the control period (P > 0.05). Based on the falls risk criterion in the one-leg stance test, the proportion at risk for falls was significantly lower after the intervention period (P = 0.04), but not after the control period. CONCLUSIONS: A community-based multimodal PA intervention for BCS may be efficacious in improving physical function-related risk factors for falls, and lowering the proportion of BCS at risk for falls based on specific physical function-related falls criteria. Further larger trials are needed to confirm these preliminary findings.


Assuntos
Acidentes por Quedas/prevenção & controle , Neoplasias da Mama/fisiopatologia , Exercício Físico/fisiologia , Sobreviventes , Idoso , Teste de Esforço , Feminino , Humanos , Estudos Longitudinais , Força Muscular/fisiologia , Equilíbrio Postural/fisiologia
9.
Oncogene ; 19(20): 2398-403, 2000 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-10828881

RESUMO

Maspin, a member of the serpin family of protease inhibitors, is known to have tumor-suppressor functions. However, the association between its expression level and survival has not been demonstrated in human cancer. Using the immunohistochemical technique to examine the expression levels of maspin in 44 cases of oral squamous cell carcinoma (SCC), we found that 66% of the cases expressed low to intermediate levels of maspin and 34% of the cases expressed high levels of maspin. We further examined maspin protein expression in a series of six SCC cell lines from the head and neck, and found that all but one expressed low or no maspin protein. We also compared the clinicopathological features of the oral SCC cases with the maspin expression level, and found that high maspin expression was associated with the absence of lymph node metastasis. More importantly, we showed that higher maspin expression was significantly associated with better rates of overall survival, suggesting that high maspin expression may be a favorable prognostic marker for oral SCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias Bucais/metabolismo , Proteínas/metabolismo , Serpinas/metabolismo , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Feminino , Genes Supressores de Tumor , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Análise de Sobrevida , Células Tumorais Cultivadas
10.
Oncogene ; 16(22): 2855-63, 1998 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-9671406

RESUMO

We have previously shown that emodin suppresses tyrosine kinase activity of HER-2/neu-encoded p185neu receptor tyrosine kinase. In this study, we examine the relationship between the chemical structure and the activity of emodin and nine derivatives, and identified that one methyl, one hydroxy, and one carbonyl functional groups are critical for the biological activities of emodin. We also found that one of the derivatives 10-(4-acetamidobenzylidene)-9-anthrone (DK-V-47) is more effective than emodin in repressing the tyrosine phosphorylation of p185neu and in inhibiting the proliferation and transformation of HER-2/neu-overexpressing human breast cancer cells. Using mutation-activated HER-2/neu transformed 3T3 cells, we also investigated whether emodin and DK-V-47 can inhibit malignant transformation induced solely by the HER-2/neu oncogene. We found that DK-V-47 is more potent than emodin in suppressing transformation phenotypes of activated HER-2/neu transformed 3T3 cells including anchorage-dependent and -independent growth, metastasis-associated properties. These results clearly indicate that the inhibition of p185neu tyrosine kinase by both emodin and DK-V-47 is capable of suppressing the HER-2/neu associated transformed phenotypes including the ability to induce metastatic potential. Our results also support the chemotherapeutic implications of the use of either emodin or DK-V-47 to target HER-2/neu-overexpressing cancer cells.


Assuntos
Transformação Celular Neoplásica , Emodina/análogos & derivados , Emodina/farmacologia , Inibidores Enzimáticos/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Receptor ErbB-2/antagonistas & inibidores , Células 3T3 , Animais , Neoplasias da Mama , Divisão Celular/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Emodina/química , Feminino , Fase G1 , Humanos , Camundongos , Estrutura Molecular , Metástase Neoplásica/prevenção & controle , Fosforilação , Receptor ErbB-2/metabolismo , Fase de Repouso do Ciclo Celular , Relação Estrutura-Atividade , Células Tumorais Cultivadas
11.
Biochim Biophys Acta ; 548(3): 565-78, 1979 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-228716

RESUMO

The reduction of acetylated, fully succinylated and dicarboxymethyl horse cytochromes c by the radicals CH3CH(OH), CO2.-, O2.-, and e-aq' and the oxidation of the reduced cytochrome c derivatives by Fe(CN)3-6 were studied using the pulse radiolysis technique. Many of the reactions were also examined as a function of ionic strength. By obtaining rate constants for the reactions of differently charged small molecules redox agents with the differently charged cytochrome c derivatives at both zero ionic strength and infinite ionic strength, electrostatic and conformational contributions to the electron transfer mechanism were effectively partioned from each other in some cases. In regard to cytochrome c electron transfer mechanism, the results, especially those for which conformational influences predominate, are supportive of the electron being transferred in the heme edge region.


Assuntos
Grupo dos Citocromos c , Acetilação , Animais , Grupo dos Citocromos c/metabolismo , Transporte de Elétrons , Ferricianetos , Cavalos , Cinética , Matemática , Miocárdio , Oxirredução , Ligação Proteica , Conformação Proteica , Succinatos
12.
J Am Coll Cardiol ; 32(6): 1701-8, 1998 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-9822099

RESUMO

OBJECTIVES: We examined the relationship among viability assessment by dobutamine echocardiography (DE), positron emission tomography (PET) and thallium-201 single-photon emission computed tomography (TI-SPECT) to the degree of fibrosis. BACKGROUND: DE, PET and TI-SPECT have been shown to be sensitive in identifying viability of asynergic myocardium. However, PET and TI-SPECT indicated viability in a significant percentage of segments without dobutamine response or functional improvement after revascularization. METHODS: Twelve patients with coronary artery disease and severely reduced left ventricular function (EF 14.5+/-5.2%) were studied with DE prior to cardiac transplantation: 5 had additional PET and 7 had TI-SPECT studies. Results of the three techniques were compared to histologic findings of the explanted hearts. RESULTS: Segments with >75% viable myocytes by histology were determined to be viable in 78%, 89% and 87% by DE, PET and TI-SPECT; those with 50-75% viable myocytes in 71%, 50% and 87%, respectively. Segments with 25-50% viable myocytes showed response to dobutamine in only 15%, but were viable in 60% by PET and 82% by TI-SPECT. Segments with <25% viable myocytes responded to dobutamine in 19%; however, PET and TI-SPECT demonstrated viability in 33% and 38%, respectively. Discrepant segments without dobutamine response but viability by PET and SPECT had significantly more viable myocytes by pathology than did those classified in agreement to be nonviable but had significantly less viable myocytes than those classified in agreement to be viable (p < .001). CONCLUSIONS: These findings suggest that contractile reserve as evidenced by a positive dobutamine response requires at least 50% viable myocytes in a given segment whereas scintigraphic methods also identify segments with less viable myocytes. Thus, the methods may provide complementary information: Nuclear techniques appear to be highly sensitive for the detection of myocardial viability, and negative tests make it highly unlikely that a significant number of viable myocytes are present in a given segment. Conversely, dobutamine echo may be particularly useful for predicting recovery of systolic function after revascularization.


Assuntos
Doença das Coronárias/diagnóstico , Ecocardiografia , Sobrevivência de Tecidos , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada de Emissão , Idoso , Cardiotônicos , Doença das Coronárias/patologia , Doença das Coronárias/cirurgia , Dobutamina , Coração/diagnóstico por imagem , Transplante de Coração , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Radiografia , Radioisótopos de Tálio , Sobrevivência de Tecidos/fisiologia
13.
Clin Cancer Res ; 5(2): 343-53, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10037184

RESUMO

Overexpression of the HER-2/neu proto-oncogene, which encodes the tyrosine kinase receptor p185neu, has been observed in tumors from breast cancer patients. We demonstrated previously that emodin, a tyrosine kinase inhibitor, suppresses tyrosine kinase activity in HER-2/neu-overexpressing breast cancer cells and preferentially represses transformation phenotypes of these cells in vitro. In the present study, we examined whether emodin can inhibit the growth of HER-2/neu-overexpressing tumors in mice and whether emodin can sensitize these tumors to paclitaxel, a commonly used chemotherapeutic agent for breast cancer patients. We found that emodin significantly inhibited tumor growth and prolonged survival in mice bearing HER-2/neu-overexpressing human breast cancer cells. Furthermore, the combination of emodin and paclitaxel synergistically inhibited the anchorage-dependent and -independent growth of HER-2/neu-overexpressing breast cancer cells in vitro and synergistically inhibited tumor growth and prolonged survival in athymic mice bearing s.c. xenografts of human tumor cells expressing high levels of p185neu. Both immunohistochemical staining and Western blot analysis showed that emodin decreases tyrosine phosphorylation of HER-2/neu in tumor tissue. Taken together, our results suggest that the tyrosine kinase activity of HER-2/neu is required for tumor growth and chemoresistance and that tyrosine kinase inhibitors such as emodin can inhibit the growth of HER-2/neu-overexpressing tumors in mice and also sensitize these tumors to paclitaxel. The results may have important implications in chemotherapy for HER-2/neu-overexpressing breast tumors.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Antineoplásicos/uso terapêutico , Emodina/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Neoplasias Mamárias Experimentais/tratamento farmacológico , Paclitaxel/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Receptor ErbB-2/biossíntese , Animais , Divisão Celular/efeitos dos fármacos , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Neoplasias Mamárias Experimentais/metabolismo , Camundongos , Camundongos Nus , Transplante de Neoplasias , Fosforilação/efeitos dos fármacos , Proto-Oncogene Mas , Células Tumorais Cultivadas , Tirosina/metabolismo
14.
Clin Cancer Res ; 3(1): 3-9, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9815530

RESUMO

Overexpression of c-erbB-2 (also known as HER-2/neu) has been found in many human cancers, including head and neck squamous cell carcinoma (SCC). We therefore examined expression of the oncoprotein in oral SCC primary tumor samples and compared its relationship with clinical stages and survival rate. Out of 80 cases of oral SCC, high expression level (++ or +++) of c-erbB-2 was found in 41 cases. Of the 80 cases with follow-up information, 39 were further investigated for the correlation of expression level of c-erbB-2 and survival rate. Overexpression of the oncoprotein was significantly correlated with shorter overall survival, and the patients with low and no expression of c-erbB-2 had much higher survival rates. Overexpression of c-erbB-2 was also significantly correlated with nodal stage and metastasis. We found that high expression level of c-erbB-2 was frequently detected in oral cancer cell lines but not in the other head and neck SCC cell lines. Thus, we conclude that overexpression of c-erbB-2 is a frequent event in oral SCC and is correlated with poor survival and may be used as a poor prognostic factor.


Assuntos
Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias Bucais/genética , Receptor ErbB-2/genética , Adolescente , Adulto , Idoso , Western Blotting , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Criança , Terapia Combinada , Feminino , Marcadores Genéticos , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Neoplasias Bucais/terapia , Prognóstico , Receptor ErbB-2/biossíntese , Estudos Retrospectivos , Análise de Sobrevida , Células Tumorais Cultivadas
15.
Clin Cancer Res ; 5(12): 4164-74, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10632356

RESUMO

In a series of 111 patients with squamous cell carcinoma (SCC), we used immunohistochemistry to examine the expression levels of four epidermal growth factor receptor (EGFR) family members (EGFR, HER-2/neu, HER-3, and HER-4). Expression of the EGFR members was not significantly associated with tumor size. However, their expressions (except for HER-4) were significantly associated with the presence of lymph node metastasis, and all of them were significantly associated with distant metastasis. We further examined the association between the expression levels of the EGFR members and the survival rates in 47 oral SCC patients whose detailed clinical follow-ups were available. The expression of all EGFR members was significantly associated with shortened patient survival, and the association was strongest for HER-2/neu. Furthermore, the combination of HER-2, HER-3, and EGFR but not HER-4 significantly improved the predicting power. The expression level of HER-2/neu was significantly correlated with that of EGFR or HER-3. Similar coexpression patterns were also observed in three oral SCC cell lines studied, but not in four other head and neck SCC cell lines. Taken together, these results indicated that expression levels of EGFR, HER-2/ neu, and HER-3 may help predict the outcome of patients with oral SCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Receptores ErbB/biossíntese , Neoplasias Bucais/metabolismo , Receptor ErbB-2/biossíntese , Receptor ErbB-3/biossíntese , Adolescente , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Neoplasias Bucais/terapia , Valor Preditivo dos Testes , Prognóstico , Receptor ErbB-4 , Análise de Sobrevida , Resultado do Tratamento , Células Tumorais Cultivadas
16.
Ann Acad Med Singap ; 34(1): 52-9, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15726220

RESUMO

This article presents clinical data which suggest that the current dosage of losartan 50 to 100 mg/day may not be the optimum in many cases, especially if used as monotherapy in the treatment of proteinuria and we may have to increase to 200 mg/day. However, about 30% of patients cannot take angiotensin-converting enzyme inhibitor (ACEI) because of the side effect of cough. To potentiate the anti-proteinuric effect of losartan, especially for patients who do not adhere to a low salt diet, a 12.5-mg dose of hydro-chlorothiazide may further decrease proteinuria. The main message of this article is that we would have to, in many instances, increase the dose of losartan to a minimum of 100 mg/day or 100 mg twice a day for some patients for optimal therapy. The second message is to monitor the creatinine clearance test (CCT) and to start therapy when CCT is reduced and not wait for serum creatinine to rise to abnormal levels (renal impairment) before starting therapy. The first group involves half a dozen patients with hypertension but no proteinuria. Therapy with losartan is shown to improve the renal function. This data suggest that losartan, apart from its use in reduction of proteinuria, can be used in patients with mild renal impairment without proteinuria to reverse the mild renal impairment and preserve renal function. The second group deals with 3 patients with low creatinine clearance. After a followup period of an average of 3 years, they all developed renal impairment. In another 6 patients, the data suggest that we should perhaps treat patients with low CCT as soon as possible and with dose ranging from 100 to 200 mg/day if necessary, to derive maximum beneficial effect. The third group highlights 5 patients with high CCT due to glomerular hyperfiltration. With time, the high CCT decreases and renal impairment sets in. The data suggest that patients with high CCT should be treated early to prevent renal impairment. The fourth group illustrates 6 patients where their proteinuria was markedly reduced with the increase of losartan from 100 mg/day to 200 mg/day, suggesting that losartan 200 mg/day is probably the optimum dose. In conclusion, apart from its traditional usage in reduction of proteinuria to retard progression to renal failure, the data suggest that losartan is also indicated in patients with renal impairment in the absence of proteinuria; patients with low CCT, patients with high CCT and patients who do not respond to a dosage of 100 mg/day should have the dosage increased to 100 mg twice daily to increase efficacy of losartan. It is hoped that with these new and earlier indications as well as increased dosage of losartan starting with 100 mg, whenever possible, and increasing to 200 mg/day, if there is no response, we can prevent more patients from developing renal failure. Based on these observations, further randomised controlled trials should be designed to address these issues.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Creatinina/sangue , Taxa de Filtração Glomerular/fisiologia , Losartan/administração & dosagem , Insuficiência Renal/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteinúria/sangue , Proteinúria/prevenção & controle , Insuficiência Renal/sangue , Insuficiência Renal/fisiopatologia , Resultado do Tratamento
17.
Semin Oncol ; 26(4 Suppl 12): 51-9, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10482194

RESUMO

The HER-2/neu (also known as c-erbB-2) oncogene is the second member of the epidermal growth factor receptor family. It is overexpressed in many different types of human cancers, including breast, ovarian, lung, gastric, and oral cancers. Overexpression of HER-2/neu in breast cancer has been associated with poor overall survival and has been shown preclinically to enhance malignancy and the metastatic phenotypes. Although discrepancies exist between different studies, HER-2/ neu overexpression seems to induce chemoresistance in certain experimental conditions. Many studies have convincingly shown that repression of HER-2/neu suppresses the malignant phenotypes of HER-2/neu-overexpressing cancer cells. These findings strongly suggest that HER-2/neu may serve as an excellent target for developing anticancer agents specific for HER-2/neu-overexpressing cancer cells. HER-2/neu-encoded p185 protein is a receptor tyrosine kinase that can be associated with multiple signal transduction pathways. However, it is not yet clear how a specific signal pathway may correspond to a specific biological response. This report reviews basic information on signal transduction of HER-2/neu receptor tyrosine kinase and summarizes our approaches to targeting HER-2/neu-overexpressing cancer cells. The HER-2/neu promoter was targeted using cationic liposomes or an adenovirus vector to deliver the adenovirus-5 EIA gene products and a nontransformed mutant of the SV40 large T antigen into the tumor-bearing mice. This resulted in suppression of the tumor growth and prolongation of survival. For repressing the function of HER-2/neu we used emodin, a tyrosine kinase inhibitor. This agent can inhibit the tyrosine kinase activity of HER-2/neu and preferentially block the growth of the HER-2/neu-overexpressing human breast cancer cells in tissue culture as well as in nude mice.


Assuntos
Neoplasias/metabolismo , Receptor ErbB-2/fisiologia , Animais , Expressão Gênica , Genes erbB-2 , Humanos , Neoplasias/genética , Neoplasias/patologia , Proteínas Tirosina Quinases , Transdução de Sinais
18.
Thromb Res ; 38(3): 201-6, 1985 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-3895560

RESUMO

Antithrombin III (AT III) is increased in situations where there is increased platelet turnover. Plasma AT III levels measured in 39 renal transplant recipients were significantly higher than in 20 healthy subjects (p less than 0.001) and 20 patient controls (p less than 0.025). AT III levels were significantly correlated with the patients' platelet counts (r = 0.4, p less than 0.02). Transplant patients with less than 1 year follow up had significantly higher AT III levels than patients with more than 1 year follow up (p less than 0.01). All 5 patients with transplant rejection in the study had elevated plasma AT III levels. The data suggest that elevation of plasma AT III may be related to graft rejection.


Assuntos
Antitrombina III/análise , Transplante de Rim , Adulto , Creatinina/sangue , Feminino , Seguimentos , Rejeição de Enxerto , Humanos , Imunossupressores/uso terapêutico , Masculino , Contagem de Plaquetas , Fatores de Tempo
19.
Thromb Res ; 40(4): 483-7, 1985 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-4082121

RESUMO

Plasma Antithrombin III (A T III) was measured in 97 patients with IgA nephritis, 30 patients with non IgA idiopathic mesangial proliferative glomerulonephritis and 40 healthy subjects. The mean plasma A T III levels in the patients with IgA nephritis (105 +/- 10%) was significantly higher than those of normal controls (96 +/- 5%) (p less than 0.0005). The mean plasma A T III levels in the patients with non IgA nephritis (101 +/- 10%) was not different from those of the normal controls or the patients with IgA nephritis. A T III levels were significantly correlated with proteinuria (p less than 0.0001), segmental sclerosis (p less than 0.001), crescents (p less than 0.01), medial hypertrophy (p less than 0.001) and intensity of IgA staining on IMF (p less than 0.02). Patients with IgA nephritis with raised A T III levels had significantly more proteinuria (p less than 0.003), more segmental sclerosis (p less than 0.007) as well as a greater intensity of IgA staining on IMF (p less than 0.02) when compared to patients with normal A T III levels. The data suggest that raised plasma A T III levels may serve as a prognostic marker in IgA nephritis.


Assuntos
Antitrombina III/análise , Glomerulonefrite por IGA/sangue , Feminino , Hematúria , Humanos , Masculino , Síndrome Nefrótica/sangue , Proteinúria , Valores de Referência
20.
Clin Nephrol ; 36(2): 60-6, 1991 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1934661

RESUMO

This study is a 5-year post trial assessment of patients with IgA nephritis who entered a 3-year prospective controlled trial of cyclophosphamide, dipyridamole (D) and low-dose warfarin (W). Patients entered the trial from 1979 to 1981 and the trial ended in 1984 with those in the treatment group having more stable renal function and less proteinuria compared to the control group. Present reassessment of the patients in 1989 showed no difference in the renal function between those in the treatment group (n = 27) and the control group (n = 21). 6 patients in the treatment group and 7 in the control group were in ESRF. At the conclusion of the trial in 1984, among the 27 patients in the original treatment group, 13 patients elected to continue with D + W while the other 14 patients chose to cease therapy and therefore served as the new control group. 5 years later, renal function in the new treatment group (n = 13) was significantly stable compared to the new control group (n = 14), (serum creatinine 1.4 +/- 0.7 versus 4.4 +/- 3.2 mg/dl, p less than 0.01). Furthermore, all the 6 patients with ESRF in the original treatment group of 27 patients were from the new control group (n = 14) where treatment with D + W had been ceased. None of the patients still on D + W are in ESRF.


Assuntos
Ciclofosfamida/uso terapêutico , Dipiridamol/uso terapêutico , Glomerulonefrite por IGA/tratamento farmacológico , Varfarina/uso terapêutico , Adulto , Quimioterapia Combinada , Feminino , Seguimentos , Glomerulonefrite por IGA/epidemiologia , Humanos , Testes de Função Renal , Masculino , Estudos Prospectivos , Fatores de Tempo
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