Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 127
Filtrar
1.
Ann Oncol ; 35(6): 537-548, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38844309

RESUMO

BACKGROUND: Nivolumab plus ipilimumab demonstrated promising clinical activity and durable responses in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC) in the CheckMate 040 study at 30.7-month median follow-up. Here, we present 5-year results from this cohort. PATIENTS AND METHODS: Patients were randomized 1 : 1 : 1 to arm A [nivolumab 1 mg/kg plus ipilimumab 3 mg/kg Q3W (four doses)] or arm B [nivolumab 3 mg/kg plus ipilimumab 1 mg/kg Q3W (four doses)], each followed by nivolumab 240 mg Q2W, or arm C (nivolumab 3 mg/kg Q2W plus ipilimumab 1 mg/kg Q6W). The primary objectives were safety, tolerability, investigator-assessed objective response rate (ORR), and duration of response (DOR) per RECIST version 1.1. RESULTS: A total of 148 patients were randomized across treatment arms. At 60-month minimum follow-up (62.6-month median follow-up), the ORR was 34% (n = 17), 27% (n = 13), and 29% (n = 14) in arms A, B, and C, respectively. The median DOR was 51.2 months [95% confidence interval (CI) 12.6 months-not estimable (NE)], 15.2 months (95% CI 7.1 months-NE), and 21.7 months (95% CI 4.2 months-NE), respectively. The median overall survival (OS) was 22.2 months (34/50; 95% CI 9.4-54.8 months) in arm A, 12.5 months (38/49; 95% CI 7.6-16.4 months) in arm B, and 12.7 months (40/49; 95% CI 7.4-30.5 months) in arm C; 60-month OS rates were 29%, 19%, and 21%, respectively. In an exploratory analysis of OS by response (6-month landmark), the median OS was meaningfully longer for responders versus nonresponders for all arms. No new safety signals were identified with longer follow-up. There were no new discontinuations due to immune-mediated adverse events since the primary analysis. CONCLUSIONS: Consistent with the primary analysis, the arm A regimen of nivolumab plus ipilimumab continued to demonstrate clinically meaningful responses and long-term survival benefit, with no new safety signals in patients with advanced HCC following sorafenib treatment, further supporting its use as a second-line treatment in these patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Ipilimumab , Neoplasias Hepáticas , Nivolumabe , Sorafenibe , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Seguimentos , Ipilimumab/administração & dosagem , Ipilimumab/efeitos adversos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Sorafenibe/administração & dosagem , Sorafenibe/efeitos adversos , Sorafenibe/uso terapêutico
2.
Ann Oncol ; 35(4): 381-391, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38151184

RESUMO

BACKGROUND: Patients with advanced hepatocellular carcinoma (aHCC) have a poor prognosis and high mortality. Nivolumab monotherapy demonstrated clinical benefit with an acceptable safety profile in patients with aHCC in the CheckMate 040 study. Five-year follow-up of the sorafenib-naive and sorafenib-experienced groups of CheckMate 040 is presented here. PATIENTS AND METHODS: Patients received nivolumab monotherapy at dose levels of 0.1-10.0 mg/kg (dose-escalation phase) or 3 mg/kg (dose-expansion phase) every 2 weeks until disease progression or unacceptable toxicity. Primary endpoints were safety and tolerability (dose escalation), and objective response rate (ORR) by blinded independent central review (BICR) and by investigator as per RECIST version 1.1 (dose expansion). RESULTS: Eighty sorafenib-naive and 154 sorafenib-experienced patients were treated. Minimum follow-up in both groups was 60 months. ORR as per BICR was 20% [95% confidence interval (CI) 12% to 30%] and 14% (95% CI 9% to 21%) in the sorafenib-naive and sorafenib-experienced groups, respectively. Responses occurred regardless of HCC etiology or baseline tumor cell programmed death-ligand 1 (PD-L1) expression levels. Median overall survival (OS) was 26.6 months (95% CI 16.6-30.6 months) and 15.1 months (95% CI 13.0-18.2 months) in sorafenib-naive and sorafenib-experienced patients, respectively. The 3-year OS rates were 28% in the sorafenib-naive and 20% in the sorafenib-experienced groups; 5-year OS rates were 14% and 12%, respectively. No new safety signals were identified; grade 3/4 treatment-related adverse events were observed in 33% and 21% of patients in the sorafenib-naive and sorafenib-experienced groups, respectively. Biomarker analyses showed that baseline PD-L1 expression ≥1% was associated with higher ORR and longer OS compared with PD-L1 <1%. In the sorafenib-naive group, patients with OS ≥3 years exhibited higher baseline CD8 T-cell density compared with those with OS <1 year. CONCLUSION: With 5 years of follow-up, nivolumab monotherapy continued to provide durable clinical benefit with manageable safety in sorafenib-naive and sorafenib-experienced patients with aHCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Nivolumabe/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Sorafenibe/uso terapêutico , Antígeno B7-H1/metabolismo , Seguimentos , Neoplasias Hepáticas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ipilimumab/uso terapêutico
5.
Hong Kong Med J ; 23(1): 19-27, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27779099

RESUMO

INTRODUCTION: The treatment of ductal carcinoma in situ has been widely reported in the western and other Asian countries, but the relevant data in Hong Kong are relatively limited. This study aimed to evaluate the latest detection and treatment pattern for ductal carcinoma in situ in Hong Kong so as to guide planning of future service provision. METHODS: This was a retrospective case series study. A total of 573 patients who registered with the Hong Kong Breast Cancer Registry, and were diagnosed and treated in Hong Kong from January 2001 to December 2011 were reviewed. RESULTS: Compared with invasive breast cancer patients, patients with ductal carcinoma in situ were younger (median, 48.6 vs 50.3 years; P<0.001), had a higher education level (P<0.001), had a higher total monthly family income (P<0.001), and more common breast-screening habits (P<0.001). Significantly more patients with ductal carcinoma in situ underwent breast-conserving surgery than their invasive cancer counterparts (55.8% vs 36.7%; P<0.001). The percentage of screen-detected ductal carcinoma in situ was relatively lower than that reported in other studies, but was still much higher than that in invasive breast cancer patients (29.0% vs 4.7%; P<0.001). Screen-detected patients with ductal carcinoma in situ tended to choose a private hospital instead of a public hospital for treatment (P=0.05) and to undergo breast-conserving surgery (P=0.02). With a median follow-up of 3 years, the crude local recurrence rate after mastectomy and breast-conserving surgery was 0.4% and 3.3%, respectively; 44% of recurrent tumours had developed invasive components. No regional recurrence, distant recurrence, or cancer-related deaths were recorded. CONCLUSIONS: In the absence of a population-based breast screening programme in Hong Kong, ductal carcinoma in situ is more frequently found in the higher social classes and managed in the private sector. The clinical outcome of ductal carcinoma in situ is excellent and more than half of the patients can be successfully managed with breast-conserving surgery.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Carcinoma Intraductal não Infiltrante/epidemiologia , Carcinoma Intraductal não Infiltrante/terapia , Recidiva Local de Neoplasia/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Terapia Combinada , Feminino , Hong Kong/epidemiologia , Humanos , Renda , Programas de Rastreamento/estatística & dados numéricos , Mastectomia Segmentar , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Adulto Jovem
6.
Hong Kong Med J ; 23(6): 622-34, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29170361

RESUMO

Polycystic ovary syndrome is the most common endocrine disorder among women of reproductive age. Although traditionally viewed as a reproductive disorder, there is increasing appreciation that it is associated with significantly increased risk of cardiometabolic disorders. Women with polycystic ovary syndrome may present to clinicians via a variety of different routes and symptoms. Although the impact on reproduction predominates during the reproductive years, the increased cardiometabolic problems are likely to become more important at later stages of the life course. Women with polycystic ovary syndrome have an approximately 2- to 5-fold increased risk of dysglycaemia or type 2 diabetes, and hence regular screening with oral glucose tolerance test is warranted. Although the diagnostic criteria for polycystic ovary syndrome are still evolving and are undergoing revision, the diagnosis is increasingly focused on the presence of hyperandrogenism, with the significance of polycystic ovarian morphology in the absence of associated hyperandrogenism or anovulation remaining uncertain. The management of women with polycystic ovary syndrome should focus on the specific needs of the individual, and may change according to different stages of the life course. In view of the clinical manifestations of the condition, there is recent debate about whether the current name is misleading, and whether the condition should be renamed as metabolic reproductive syndrome.


Assuntos
Síndrome Metabólica/complicações , Síndrome do Ovário Policístico/complicações , Feminino , Humanos , Sobreviventes
7.
Ann Oncol ; 26(12): 2457-63, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26386123

RESUMO

BACKGROUND: The efficacy and safety of axitinib, a potent and selective vascular endothelial growth factor receptors 1-3 inhibitor, combined with best supportive care (BSC) was evaluated in a global, randomized, placebo-controlled phase II trial in patients with locally advanced or metastatic hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Patients with HCC and Child-Pugh Class A who progressed on or were intolerant to one prior antiangiogenic therapy were stratified by tumour invasion (presence/absence of extrahepatic spread and/or vascular invasion) and region (Asian/non-Asian) and randomized (2:1) to axitinib/BSC (starting dose 5 mg twice-daily) or placebo/BSC. The primary end point was overall survival (OS). RESULTS: The estimated hazard ratio for OS was 0.907 [95% confidence interval (CI) 0.646-1.274; one-sided stratified P = 0.287] for axitinib/BSC (n = 134) versus placebo/BSC (n = 68), with the median (95% CI) of 12.7 (10.2-14.9) versus 9.7 (5.9-11.8) months, respectively. Results of prespecified subgroup analyses in Asian versus non-Asian patients or presence versus absence of tumour invasion were consistent with the overall population. Improvements favouring axitinib/BSC (P < 0.01) were observed in secondary efficacy end point analyses [progression-free survival (PFS), time to tumour progression (TTP), and clinical benefit rate (CBR)], and were retained among Asian patients in the prespecified subgroup analyses. Overall response rate did not differ significantly between treatments and patient-reported outcomes favoured placebo/BSC. Most common all-causality adverse events with axitinib/BSC were diarrhoea (54%), hypertension (54%), and decreased appetite (47%). Baseline serum analyses identified potential new prognostic (interleukin-6, E-selectin, interleukin-8, angiopoietin-2, migration inhibitory factor, and c-MET) or predictive (E-selectin and stromal-derived factor-1) factors for survival. CONCLUSIONS: Axitinib/BSC did not improve OS over placebo/BSC in the overall population or in stratification subgroups. However, axitinib/BSC resulted in significantly longer PFS and TTP and higher CBR, with acceptable toxicity in patients with advanced HCC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01210495.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Imidazóis/uso terapêutico , Indazóis/uso terapêutico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Cuidados Paliativos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Axitinibe , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Cuidados Paliativos/tendências , Taxa de Sobrevida/tendências , Resultado do Tratamento
8.
Br J Cancer ; 111(9): 1765-71, 2014 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-25233396

RESUMO

BACKGROUND: The detection of microRNA (miRNA) dysregulation in stool is a novel approach for the diagnosis of colorectal carcinoma (CRC). The aim of this study is to investigate the use of miR-221 and miR-18a in stool samples as non-invasive biomarkers for CRC diagnosis. METHODS: A miRNA expression array containing 667 miRNAs was performed to identify miRNA dysregulation in CRC tissues. We focused on miR-221 and miR-18a, two significantly upregulated miRNAs which were subsequently verified in 40 pairs of CRC tissues and 595 stool samples (198 CRCs, 199 polyps and 198 normal controls). RESULTS: miR-221 and miR-18a were upregulated in the miRNA expression array. miR-221 and miR-18a levels were also significantly higher in 40 CRC tumours compared with their respective adjacent normal tissues. In stool samples, miR-221 and miR-18a showed a significant increasing trend from normal controls to late stages of CRC (P<0.0001). The levels of stool miR-221 and miR-18a were both significantly higher in subjects with stages I+II (miR-221: P<0.0001, miR-18a: P<0.0001) and stages III+IV of CRC (miR-221: P=0.0004, miR-18a: P<0.0001) compared with normal controls. The AUC of stool miR-221 and miR-18a were 0.73 and 0.67 for CRC patients as compared with normal controls, respectively. No significant differences in stool miR-221 and miR-18a levels were found between patients with proximal and distal CRCs. The use of antibiotics did not influence stool miRNA-221 and miRNA-18a levels. CONCLUSIONS: Stool-based miR-221 can be used as a non-invasive biomarker for the detection of CRC.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Fezes/química , MicroRNAs/genética , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Curva ROC
9.
Psychooncology ; 22(12): 2831-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24038545

RESUMO

BACKGROUND: Anxiety and depression (distress) over the first year following the initial adjuvant therapy for advanced breast cancer (ABC) remain poorly documented in non-Caucasian populations. This study describes trajectories of distress and their determinants in Chinese women with ABC. METHODS: Of the 228 Chinese women newly diagnosed with ABC recruited from six oncology units, 192 completed an interview before their first course of chemotherapy (baseline) and follow-up interviews at 1.5, 3, 6, and 12 months thereafter. At baseline, participants were assessed for supportive care needs, psychological distress, physical symptom distress, optimism, and cancer-related rumination. At follow-up, participants completed the measure of psychological distress. Latent growth mixture modeling was used to identify trajectory patterns of distress. Multinominal logistic regression was used to identify predictors of trajectory patterns adjusted for demographic and medical characteristics. RESULTS: Four distinct trajectories of anxiety and depression were identified. Most women showed low-stable levels of anxiety (68%) and depression (68%), but one in 11 women were chronically anxious (9%) and depressed (9%). Optimism, negative cancer-related rumination, and physical symptom distress predicted both anxiety and depression trajectories. Psychological needs predicted anxiety trajectories. Women in the low-stable distress group reported high optimism, low psychological supportive care needs, low physical symptom distress, and low negative cancer-related rumination. CONCLUSION: Most women with ABC did not experience psychological distress over 12 months following diagnosis of ABC. Preventive interventions should focus on women at risk of high persistent distress and reducing rumination, providing emotional support, and managing physical symptoms.


Assuntos
Transtornos de Ansiedade/psicologia , Ansiedade/psicologia , Povo Asiático/psicologia , Neoplasias da Mama/psicologia , Depressão/psicologia , Transtorno Depressivo/psicologia , Estresse Psicológico/psicologia , Adaptação Psicológica , Adulto , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Progressão da Doença , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Pessoa de Meia-Idade , Modelos Psicológicos , Análise Multivariada , Avaliação das Necessidades , Estadiamento de Neoplasias , Apoio Social
10.
Anaesthesia ; 67(11): 1242-50, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22827564

RESUMO

We conducted a study to assess pharmacokinetics of high-dose tranexamic acid for 24 h after administration of the drug in patients undergoing cardiac surgery with cardiopulmonary bypass. High-dose tranexamic acid involved a bolus of 30 mg.kg(-1) infused over 15 min followed by a 16 mg.kg(-1) .h(-1) infusion until chest closure with a 2 mg.kg(-1) load within the pump prime. Tranexamic acid followed first-order kinetics best described using a two-compartment model, with a total body clearance that approximated the glomerular filtration rate. Mean plasma tranexamic acid concentrations during the intra-operative period and in the first 6 postoperative hours were consistently higher than the suggested threshold to achieve 100% inhibition and 80% inhibition of tissue plasminogen activator. With recent studies implicating high-dose tranexamic acid as a possible aetiology of postoperative seizures following cardiac surgery, the minimum effective yet safe dose of tranexamic acid in high-risk cardiac surgery needs to be refined.


Assuntos
Antifibrinolíticos/farmacocinética , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar , Ácido Tranexâmico/farmacocinética , Idoso , Algoritmos , Anestesia , Antifibrinolíticos/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Distribuição Tecidual , Ácido Tranexâmico/administração & dosagem
11.
Braz J Biol ; 82: e256189, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36541981

RESUMO

Bacteria blight is one of the most serious bacterial diseases of rice worldwide. The identification of genetic potential against bacterial blight in the existing rice resources is a prerequisite to develop multigenic resistance to combat the threat of climate change. This investigation was conducted to evaluate alleles variation in 38 Malaysian cultivars using thirteen Simple Sequences Repeats markers and one Sequence Tagged Sites (STS) marker which were reported to be linked with the resistance to bacterial blight. Based on molecular data, a dendrogram was constructed which classified the rice cultivars into seven major clusters at 0.0, 0.28 and 0.3 of similarity coefficient. Cluster 5 was the largest group comprised of ten rice cultivars where multiple genes were identified. However, xa13 could not be detected in the current rice germplasm, whereas xa2 was detected in 25 cultivars. Molecular analysis revealed that Malaysian rice cultivars possess multigenic resistance.


Assuntos
Infecções Bacterianas , Oryza , Genes de Plantas , Oryza/genética , Infecções Bacterianas/genética , Doenças das Plantas/genética , Resistência à Doença/genética
12.
Br J Cancer ; 104(2): 369-75, 2011 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-21179028

RESUMO

BACKGROUND: Recent genome-wide association studies of colorectal cancer (CRC) have identified common single-nucleotide polymorphisms (SNPs) mapping to 10 independent loci that confer modest increased risk. These studies have been conducted in European populations and it is unclear whether these observations generalise to populations with different ethnicities and rates of CRC. METHODS: An association study was performed on 892 CRC cases and 890 controls recruited from the Hong Kong Chinese population, genotyping 32 SNPs, which were either associated with CRC in previous studies or are in close proximity to previously reported risk SNPs. RESULTS: Twelve of the SNPs showed evidence of an association. The strongest associations were provided by rs10795668 on 10p14, rs4779584 on 15q14 and rs12953717 on 18q21.2. There was significant linear association between CRC risk and the number of independent risk variants possessed by an individual (P=2.29 × 10(-5)). CONCLUSION: These results indicate that some previously reported SNP associations also impact on CRC risk in the Chinese population. Possible reasons for failure of replication for some loci include inadequate study power, differences in allele frequency, linkage disequilibrium structure or effect size between populations. Our results suggest that many associations for CRC are likely to generalise across populations.


Assuntos
Neoplasias Colorretais/genética , Polimorfismo de Nucleotídeo Único , Idoso , Estudos de Casos e Controles , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade
13.
Psychooncology ; 20(12): 1292-300, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22114044

RESUMO

BACKGROUND: There is no instrument available in Chinese for assessing psychosocial needs. This study aimed to assess the validity and reliability of the Chinese version of the Supportive Care Needs Survey short form (SCNS-SF34-C) in Chinese women with breast cancer (BC). METHODS: The Chinese version of the 34-item SCNS-SF34-C, a self-report measure for assessing psychosocial unmet needs, was administered to 348 Chinese women with BC at the outpatient oncology unit. Exploratory factor analysis (EFA) tested the factor structure. The internal consistency, convergent, divergent, and discriminant validity of the identified factor structure were assessed. RESULTS: In contrast to the five-factor structure identified in the original 34-item SCNS-SF34, our EFA produced a 33-item solution accounting for 54% of score variance comprising four-factors: (1) Health system, information, and patient support, (2) Psychological needs, (3) Physical and daily living, and (4) Sexuality needs. Separate dimensions for Health system and information, and the Patient care and support domains were not supported. Cronbach alphas ranged from 0.75 to 0.92. Correlations of psychological and physical symptom distress measures indicated acceptable convergent validity. No correlation with optimism and positive affect measures indicated divergent validity. Discriminant validity was demonstrated by effective differentiation between clinically distinct patient groups (no active treatment versus active treatment; advanced BC versus localized BC). DISCUSSION: The Chinese version of the Supportive Care Needs Survey has suitable factor structure and psychometric properties for use in assessing psychosocial needs among Chinese women with BC. Further validation is needed for other cancer types.


Assuntos
Neoplasias da Mama/psicologia , Inquéritos e Questionários/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/terapia , China , Análise Fatorial , Feminino , Humanos , Pessoa de Meia-Idade , Avaliação das Necessidades , Psicologia , Reprodutibilidade dos Testes , Tradução
14.
Postgrad Med J ; 92(1085): 123-4, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26917775
15.
Obes Res Clin Pract ; 15(6): 593-599, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34561173

RESUMO

OBJECTIVE: To compare the extent to which visceral adiposity, as measured by mesenteric fat thickness, contribute to cardiometabolic risk, especially insulin resistance, in women with PCOS and healthy control. METHODS: This is a cross-sectional study with a total of 190 women with PCOS fulfilling the Rotterdam diagnostic criteria. Women without PCOS were recruited from a previous study, which comprised 416 healthy women controls with normal glucose tolerance. All subjects underwent OGTT, biochemical assessment, and sonographic assessment with measurements of mesenteric, preperitoneal and subcutaneous fat thickness. RESULTS: Mesenteric fat thickness was strongly correlated to cardiometabolic traits including blood pressure, fasting and 2-h glucose, triglycerides, HOMA-IR; and was negatively correlated to HDL-C in both cohorts (all p < 0.01). In PCOS, positive correlation was observed between mesenteric fat thickness and free androgen index (p < 0.01). Compared with controls, the regression line between mesenteric fat and HOMA-IR is much steeper in PCOS (p < 0.01). CONCLUSION: Women with PCOS remain more insulin resistant compared to controls at any given degree of visceral adiposity.


Assuntos
Doenças Cardiovasculares , Resistência à Insulina , Síndrome do Ovário Policístico , Adiposidade , Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , China , Estudos Transversais , Feminino , Humanos , Síndrome do Ovário Policístico/complicações
16.
Br J Cancer ; 102(9): 1391-6, 2010 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-20424617

RESUMO

BACKGROUND: The metastatic propensity of invasive ductal carcinoma (IDC) of the breast correlates with axillary node involvement and with expression of the proliferation antigen Ki-67, whereas ductal carcinoma in situ (DCIS) is non-metastasising. To clarify whether concomitant DCIS affects IDC prognosis, we compared Ki-67 expression and node status of size-matched IDC subgroups either with DCIS (IDC-DCIS) or without DCIS (pure IDC). METHODS: We analysed data from 1355 breast cancer patients. End points were defined by the association of IDC (with or without DCIS) with grade, nodal status, Ki-67, and ER/HER2. RESULTS: Size-matched IDC-DCIS was more likely than pure IDC to be screen detected (P=0.03), to occur in pre-menopausal women (P=0.002), and to be either ER-positive (P=0.002) or HER2-positive (P<0.0005), but less likely to be treated with breast-conserving surgery (P=0.004). Grade and Ki-67 were lower in IDC-DCIS than in pure IDC (P=0.02), and declined as the DCIS enlarged (P<0.01). Node involvement and lymphovascular invasion in IDC-DCIS increased with the size ratio of IDC to DCIS (P<0.01). A 60-month cancer-specific survival favoured IDC-DCIS over size-matched pure IDC (97.4 vs 96.0%). CONCLUSION: IDC co-existing with DCIS is characterised by lower proliferation and metastatic potential than size-matched pure IDC, especially if the ratio of DCIS to IDC size is high. We submit that IDC-DCIS is biologically distinct from pure IDC, and propose an incremental molecular pathogenesis of IDC-DCIS evolution involving an intermediate DCIS precursor that remains dependent for replication on upstream mitogens.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal/patologia , Invasividade Neoplásica , Adulto , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Carcinoma in Situ/patologia , Carcinoma Ductal/mortalidade , Carcinoma Ductal/cirurgia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Antígeno Ki-67/genética , Metástase Linfática , Pessoa de Meia-Idade , Metástase Neoplásica , Pós-Menopausa , Pré-Menopausa , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Estrogênio/genética , Receptores de Progesterona/análise , Receptores de Progesterona/genética , Taxa de Sobrevida , Sobreviventes
17.
J Pathol ; 217(3): 353-61, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19090486

RESUMO

The NF-kappaB signalling pathway plays important roles in liver organogenesis and carcinogenesis. Mouse embryos deficient in IKKbeta die in mid-gestation, due to excessive apoptosis of hepatoblasts. Although activation of the NF-kappaB signalling pathway has been demonstrated in human hepatocellular carcinoma, the role of NF-kappaB is controversial. Here, we have generated transgenic mice in which a constitutively active form of IKKbeta was expressed in a hepatocyte-specific manner. Using electrophoretic mobility shift assay, we documented increased NF-kappaB activities and up-regulated levels of NF-kappaB downstream target genes, Bcl-xL and STAT5, in the transgenic mouse livers. These results confirmed that the NF-kappaB pathway was activated in the livers of the transgenic mice. However, there was no significant difference in tumour formation between transgenic and wild-type mice up to an age of 50 weeks. When we treated the transgenic mice with the chemical carcinogen diethylnitrosamine (DEN), we observed no significant differences in the incidence and size of liver tumours formed in these mice with and without DEN treatment at 35 weeks of age, suggesting that the activated NF-kappaB pathway in the livers of the transgenic mice did not enhance hepatocarcinogenesis. Interestingly, some of the transient transgenic embryos (E12.5) had abnormal excessive accumulation of nucleated red blood cells in their developing livers. In summary, NF-kappaB activation in hepatocytes did not significantly affect chemical hepatocarcinogenesis. In addition, the TTR/IKKCA transgenic mice may serve as a useful model for studying the role of NF-kappaB activation in hepatocarcinogenesis as well as inflammatory and metabolic diseases.


Assuntos
Carcinoma Hepatocelular/metabolismo , Hepatócitos/metabolismo , Quinase I-kappa B/genética , Neoplasias Hepáticas Experimentais/metabolismo , NF-kappa B/metabolismo , Animais , Western Blotting/métodos , Carcinoma Hepatocelular/induzido quimicamente , Linhagem Celular Tumoral , Dietilnitrosamina , Ensaio de Desvio de Mobilidade Eletroforética , Quinase I-kappa B/metabolismo , Imuno-Histoquímica , Fígado/embriologia , Neoplasias Hepáticas Experimentais/induzido quimicamente , Masculino , Camundongos , Camundongos Transgênicos , NF-kappa B/análise , Transfecção/métodos
18.
Hong Kong Med J ; 16(5): 373-7, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20890002

RESUMO

OBJECTIVE: Delayed presentation is an important obstacle to improving cancer treatment outcomes. We aimed to study the magnitude of this problem in Hong Kong and the factors associated with delayed presentation of patients with symptomatic breast cancers. DESIGN: Retrospective study using self-administered questionnaires. SETTING: Clinical Oncology Department in a regional public hospital in Hong Kong. PATIENTS: A total of 158 Chinese women with breast cancer referred to our hospital between October 2006 and December 2007 consented to participate in this study. Among these, 59 (37%) patients were referred after having surgery in private sector. RESULTS: The mean total delay (from first symptom to treatment) was 22 weeks. The mean patient delay (from first symptom to first consultation) was 13 weeks, constituting the largest component (60%) of the total delay. After symptom onset, the delay exceeded 12 weeks for consulting a doctor in 29%, and for receipt of treatment in 52% of them. Low family income (

Assuntos
Neoplasias da Mama/diagnóstico , Acessibilidade aos Serviços de Saúde , Hospitais Públicos/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/terapia , Feminino , Hong Kong , Humanos , Pessoa de Meia-Idade , Serviço Hospitalar de Oncologia/estatística & dados numéricos , Pobreza/estatística & dados numéricos , Encaminhamento e Consulta , Estudos Retrospectivos , Inquéritos e Questionários , Fatores de Tempo
19.
Hong Kong Med J ; 15(1): 69-72, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19197101

RESUMO

Large-cell neuroendocrine cervical carcinoma is a rare and aggressive cancer that tends to spread and recur early despite intensive multimodal treatment. The optimal mode of therapy is still controversial and management during pregnancy is challenging because foetal well-being must also be considered. We report a patient with clinically stage IIB large-cell neuroendocrine cervical carcinoma who presented with a cervical polyp and vaginal bleeding at 18 weeks of pregnancy. The patient received concurrent chemotherapy and radiation after termination of pregnancy and remained in complete remission 21 months after completion of treatment.


Assuntos
Carcinoma de Células Grandes , Carcinoma Neuroendócrino , Complicações Neoplásicas na Gravidez , Neoplasias do Colo do Útero , Aborto Induzido , Adulto , Antineoplásicos Fitogênicos/administração & dosagem , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/radioterapia , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/radioterapia , Colo do Útero/patologia , Etoposídeo/administração & dosagem , Feminino , Humanos , Pólipos/patologia , Gravidez , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Complicações Neoplásicas na Gravidez/patologia , Complicações Neoplásicas na Gravidez/radioterapia , Resultado do Tratamento , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/radioterapia
20.
Hong Kong Med J ; 15(2): 94-9, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19342734

RESUMO

OBJECTIVE: It has been proposed that young women should not be treated by breast conservation treatment because of a higher risk of local recurrences and worse survival. We therefore examined whether breast conservation treatment in young Chinese women yielded inferior clinical outcomes compared to modified radical mastectomy. DESIGN: Retrospective study. SETTING: Clinical oncology department in a public hospital in Hong Kong. PATIENTS: A total of 258 Chinese women with invasive breast cancer, aged below 40 years, and referred between January 1994 and July 2006. RESULTS: A total of 124 (48%) and 134 (52%) patients were treated by breast conservation treatment and modified radical mastectomy, respectively. Mastectomy patients tended to have larger primary tumours (P<0.001) and more nodal involvement (P<0.001). At a median follow-up of 6.5 years, there was no significant difference in the local failure-free survival rate (92% vs 93%, P=0.324) and loco-regional failure-free survival rate (89% vs 88%, P=0.721) in patients having breast conservation treatment and mastectomy. Probably due to their earlier presentation with disease, the former actually had better 6-year distant failure-free survival (88% vs 71%, P=0.002) and overall survival (92% vs 81%, P=0.173) rates. Multivariate analyses showed that both the resection margin status (hazard ratio=2.77, P=0.050) and the presence of peritumoural vascular invasion (hazard ratio=3.01, P=0.038) were independent predictors of local recurrence; the nodal status (hazard ratio=3.91, P<0.001) was the only predictive factor for overall survival. The choice of breast conservation treatment (vs modified radical mastectomy) had no apparent adverse impact on all the clinical outcome parameters analysed. CONCLUSION: Breast conservation treatment is a reasonable option for many suitably selected young Chinese women.


Assuntos
Neoplasias da Mama/cirurgia , Mastectomia Segmentar , Adulto , Fatores Etários , Povo Asiático , Neoplasias da Mama/mortalidade , Feminino , Seguimentos , Hong Kong , Humanos , Mastectomia Radical Modificada , Recidiva Local de Neoplasia , Estudos Retrospectivos , Taxa de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA