Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28
Filtrar
1.
Hong Kong Med J ; 30(3): 202-208, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38807255

RESUMO

INTRODUCTION: The Framingham risk model estimates a person's 10-year cardiovascular disease (CVD) risk. This study used this model to calculate the changes in sex- and age-specific CVD risks in the Hong Kong Population Health Survey (PHS) 2014/15 compared with two previous surveys conducted during 2003 and 2005, namely, PHS 2003/2004 and Heart Health Survey (HHS) 2004/2005. METHODS: This study included individuals aged 30 to 74 years from PHS 2014/15 (n=1662; n=4 445 868 after population weighting) and PHS 2003/2004 and HHS 2004/2005 (n=818; n=3 495 074 after population weighting) with complete data for calculating the risk of CVD predicted by the Framingham model. Sex-specific CVD risks were calculated based on age, total cholesterol and high-density lipoprotein cholesterol levels, mean systolic blood pressure, smoking habit, diabetic status, and hypertension treatment. Mean sex- and age-specific CVD risks were calculated; differences in CVD risk between the two surveys were compared by independent t tests. RESULTS: The difference in 10-year CVD risk from 2003-2005 to 2014-2015 was not statistically significant (10.2% vs 10.6%; P=0.29). After age standardisation according to World Health Organization world standard population data, a small decrease in CVD risk was observed, from 9.4% in 2003-2005 to 8.8% in 2014-2015. Analysis according to age-group showed that more participants aged 65 to 74 years were considered high risk in 2003 to 2005 (2003-2005: 66.8% vs 2014-2015: 53.1%; P=0.028). This difference may be due to the decrease in smokers among men (2003-2005: 30.5% vs 2014-2015: 24.0%; P<0.001). CONCLUSION: From 2003-2005 to 2014-2015, there was a small decrease in age-standardised 10-year CVD risk. A holistic public health approach simultaneously targeting multiple risk factors is needed to achieve greater decreases in CVD risk.


Assuntos
Doenças Cardiovasculares , Inquéritos Epidemiológicos , Humanos , Hong Kong/epidemiologia , Masculino , Pessoa de Meia-Idade , Feminino , Doenças Cardiovasculares/epidemiologia , Idoso , Adulto , Medição de Risco/métodos , Fatores de Risco de Doenças Cardíacas , Fatores de Risco , Fumar/epidemiologia , Fatores Etários , Hipertensão/epidemiologia , Fatores Sexuais , Pressão Sanguínea
4.
Eur Urol Focus ; 7(6): 1347-1354, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32771446

RESUMO

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) is associated with improved overall and cancer-specific survival. The post-NAC pathological stage has previously been reported to be a major determinant of outcome. OBJECTIVE: To develop a postoperative nomogram for survival based on pathological and clinical parameters from an international consortium. DESIGN, SETTING, AND PARTICIPANTS: Between 2000 and 2015, 1866 patients with MIBC were treated at 19 institutions in the USA, Canada, and Europe. Analysis was limited to 640 patients with adequate follow-up who had received three or more cycles of NAC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A nomogram for bladder cancer-specific mortality (BCSM) was developed by multivariable Cox regression analysis. Decision curve analysis was used to assess the model's clinical utility. RESULTS AND LIMITATIONS: A total of 640 patients were identified. Downstaging to non-MIBC (ypT1, ypTa, and ypTis) occurred in 271 patients (42 %), and 113 (17 %) achieved a complete response (ypT0N0). The 5-yr BCSM was 47.2 % (95 % confidence interval [CI]: 41.2-52.6 %). On multivariable analysis, covariates with a statistically significant association with BCSM were lymph node metastasis (hazard ratio [HR] 1.90 [95% CI: 1.4-2.6]; p < 0.001), positive surgical margins (HR 2.01 [95 % CI: 1.3-2.9]; p < 0.001), and pathological stage (with ypT0/Tis/Ta/T1 as reference: ypT2 [HR 2.77 {95 % CI: 1.7-4.6}; p < 0.001] and ypT3-4 [HR 5.9 {95 % CI: 3.8-9.3}; p < 0.001]). The area under the curve of the model predicting 5-yr BCSM after cross validation with 300 bootstraps was 75.4 % (95 % CI: 68.1-82.6 %). Decision curve analyses showed a modest net benefit for the use of the BCSM nomogram in the current cohort compared with the use of American Joint Committee on Cancer staging alone. Limitations include the retrospective study design and the lack of central pathology. CONCLUSIONS: We have developed and internally validated a nomogram predicting BCSM after NAC and radical cystectomy for MIBC. The nomogram will be useful for patient counseling and in the identification of patients at high risk for BCSM suitable for enrollment in clinical trials of adjuvant therapy. PATIENT SUMMARY: In this report, we looked at the outcomes of patients with muscle-invasive bladder cancer in a large multi-institutional population. We found that we can accurately predict death after radical surgical treatment in patients treated with chemotherapy before surgery. We conclude that the pathological report provides key factors for determining survival probability.


Assuntos
Cistectomia , Neoplasias da Bexiga Urinária , Cistectomia/métodos , Humanos , Músculos/patologia , Terapia Neoadjuvante/métodos , Nomogramas , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia
5.
Hong Kong Med J ; 26(5): 404-412, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33093243

RESUMO

INTRODUCTION: This study aimed to develop and validate a brief practitioner-friendly health literacy screening tool, called Rapid Estimate of Inadequate Health Literacy (REIHL), that estimates patients' health literacy inadequacy in demanding clinical settings. METHODS: This is a methodological study of 304 community-dwelling older adults recruited from one community health centre and five district elderly community centres. Logistic regression models were used to identify the coefficients of the REIHL score's significant factors. Receiver operating characteristic (ROC) curve analysis was then used to assess the REIHL's sensitivity and specificity. Path analysis was employed to examine the REIHL's criterion validity with the Chinese Health Literacy Scale for Chronic Care and concurrent validity with self-rated health scale and the Geriatric Depression Scale-15. RESULTS: The REIHL has scores ranging from 0 to 23. It had 76.9% agreement with the Chinese Health Literacy Scale for Chronic Care. The area under the ROC curve for predicting health literacy inadequacy was 0.82 (95% confidence interval=0.78-0.87, P<0.001). The ROC curve of the REIHL showed that scores ≥11 had a sensitivity of 77.8% and specificity of 75.6% for predicting health literacy inadequacy. The path analysis model showed excellent fit (Chi squared [2, 304] 0.16, P=0.92, comparative fit index 1.00, root mean square error of approximation <0.001, 90% confidence interval=0.00-0.04), indicating that the REIHL has good criterion and concurrent validity. CONCLUSION: The newly developed REIHL is a practical tool for estimating older adults' inadequate health literacy in clinical care settings.


Assuntos
Avaliação Geriátrica/métodos , Letramento em Saúde , Vida Independente/psicologia , Programas de Rastreamento/normas , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Hong Kong , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
6.
Hong Kong Med J ; 26(3): 176-183, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32475841

RESUMO

INTRODUCTION: This study evaluated the preparedness of family doctors during the early phase of the coronavirus disease 2019 (COVID-19) outbreak in Hong Kong. METHODS: All members of the Hong Kong College of Family Physicians were invited to participate in a cross-sectional online survey using a 20-item questionnaire to collect information on practice preparedness for the COVID-19 outbreak through an email followed by a reminder SMS message between 31 January 2020 and 3 February 2020. RESULTS: Of 1589 family doctors invited, 491 (31%) participated in the survey, including 242 (49%) from private sector. In all, 98% surveyed doctors continued to provide clinical services during the survey period, but reduced clinic service demands were observed in 45% private practices and 24% public clinics. Almost all wore masks during consultation and washed hands between or before patient contact. Significantly more private than public doctors (80% vs 26%, P<0.001) experienced difficulties in stocking personal protective equipment (PPE); more public doctors used guidelines to manage suspected patients. The main concern of the respondents was PPE shortage. Respondents appealed for effective public health interventions including border control, quarantine measures, designated clinic setup, and public education. CONCLUSION: Family doctors from public and private sectors demonstrated preparedness to serve the community from the early phase of the COVID-19 outbreak with heightened infection control measures and use of guidelines. However, there is a need for support from local health authorities to secure PPE supply and institute public health interventions.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Surtos de Doenças/prevenção & controle , Medicina de Família e Comunidade/organização & administração , Pesquisas sobre Atenção à Saúde/métodos , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Inquéritos e Questionários , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico/métodos , Técnicas de Laboratório Clínico/estatística & dados numéricos , Controle de Doenças Transmissíveis/métodos , Infecções por Coronavirus/diagnóstico , Surtos de Doenças/estatística & dados numéricos , Feminino , Hong Kong/epidemiologia , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Médicos de Família/estatística & dados numéricos
8.
Zhonghua Yi Xue Za Zhi ; 99(7): 532-536, 2019 Feb 19.
Artigo em Chinês | MEDLINE | ID: mdl-30786352

RESUMO

Objective: To compare the differences of cognitive function, daily living ability and neuropsychiatric symptoms in patients with sporadic type of Alzheimer's disease (AD) under different care modes, and find the most favorable care mode for delaying the progress of disease. Methods: One hundred and twenty cases of AD patients were divided into three groups: Spouse Care Group, Adult Child Care Group and Nursing Home Group. Medical history collection and scale evaluation were carried out by trained specialists on 3 groups of patients and caregivers. Assessment included socio-demographic data, including name, gender, age, course of the disease, the year of education and the way of care, Mini mental state examination (MMSE), Activity of Daily Living (ADL), Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-Cog), Neuropsychiatric Inventory (NPI), and the Relevant Outcome Scale for Alzheimer's disease (ROSA). All the evaluations were completed upon enrollment. The differences in cognitive function, daily living ability and neuropsychiatric symptoms were compared among the three groups. Results: There was no significant difference in age, gender, education duration and course of disease between the three groups (P>0.05). The MMSE average scores of Spouse Care Group, Adult Child Care Group and Nursing Home Group were 19±7, 15±6, 13±7 respectively. The ADAS-Cog median scores of Spouse Care Group, Adult Child Care Group and Nursing Home Group were 17.32(9.78, 26.50), 30.00(16.10, 38.55), 33.15 (16.28, 50.68). The NPI median total scores of Spouse Care Group, Adult Child Care Group and Nursing Home Group were 5.00(1.00, 13.00), 9.00(4.00, 20.00), 19.50(8.50, 28.50) respectively. The ADL average scores of Spouse Care Group, Adult Child Care Group and Nursing Home Group were 21±9, 25±9, 35±11. The difference of MMSE, ADAS-Cog, ADL and NPI was statistically significant among the three groups (P<0.05). No significant difference was found in care burden among the three groups (P>0.05). Conclusions: The AD patients with spouse care tend to suffer from mild diseases severitys, no matter in terms of cognitive function, daily living ability or neuropsychiatric symptoms. Close, familiar and comprehensive care plays an important role in delaying the progress of AD.


Assuntos
Doença de Alzheimer , Atividades Cotidianas , China , Cognição , Progressão da Doença , Humanos , Resultado do Tratamento
9.
World J Urol ; 37(1): 165-172, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29882105

RESUMO

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. PATIENTS AND METHODS: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. RESULTS: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the 'CIS' versus 'no-CIS' groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63-1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01-1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23-2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34-0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82-1.35; p = 0.70). CONCLUSION: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma in Situ/terapia , Cistectomia , Quimioterapia de Indução , Terapia Neoadjuvante , Neoplasias da Bexiga Urinária/terapia , Idoso , Carcinoma in Situ/mortalidade , Carcinoma in Situ/patologia , Cisplatino/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
10.
Diabetes Metab ; 44(5): 415-423, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29449147

RESUMO

AIM: The current trend on diabetes management advocates replacing the paradigm from a uniform to an individualized patient-centered haemoglobin A1c (HbA1c) target, but there is no consensus on the optimal HbA1c level. The study aimed at examining the association between HbA1c and the risk of cardiovascular diseases (CVD) for diabetic patients with different characteristics, in order to identify patient-centered treatment targets. METHODS: A retrospective cohort study was conducted on 115,782 Chinese adult primary care patients with type 2 diabetes mellitus (DM) but no known CVD history, who were prescribed antidiabetic medications in 2010-2011. The cumulative mean HbA1c over a median follow-up period of 5.8 years was used to evaluate the relationship between HbA1c and CVD incidence using Cox analysis. Subgroup analyses were conducted by stratifying different baseline characteristics including gender, age, smoking status, diabetes duration, body mass index, Charlson's comorbidity index and DM treatment modalities. RESULTS: For patients with a DM duration of<2years, an exponential relationship between HbA1c and risk of CVD was identified, suggesting that there was no threshold HbA1c level for CVD risk. For other diabetic patients, an HbA1c level of 6.8-7.2% was associated with a minimum risk for CVD and a J-shaped curvilinear association between HbA1c. The risk of CVD increased in patients with HbA1c<6.5% or ≥7.5%. CONCLUSION: Among Chinese primary care patients at the early (<2years) disease stage, lower HbA1c targets (<6.5%) may be warranted to prevent CVD events whilst for all others, excessively lower HbA1c levels may not necessarily better and can potentially be harmful.


Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Hemoglobinas Glicadas/metabolismo , Idoso , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hong Kong/epidemiologia , Humanos , Hipoglicemiantes/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Diabet Med ; 35(5): 576-582, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29438572

RESUMO

AIM: We aimed to determine the prospective association between baseline triglyceridaemic-waist phenotypes and diabetic mellitus incidence in individuals with impaired fasting glucose seen in primary care. METHODS: A cohort of 1101 participants (84.4% of the recruited individuals) with impaired fasting glucose were recruited from three primary care clinics during regular follow-ups to monitor their chronic conditions. Baseline triglyceridaemic-waist phenotypes were divided into four groups: (1) normal waistline and triglyceride level (n = 252); (2) isolated central obesity (n = 518); (3) isolated high triglyceride level (n = 80); and (4) central obesity with high triglyceride level (i.e. hypertriglyceridaemic-waist phenotype) (n = 251). The presence of diabetes at follow-up was determined by fasting plasma glucose (≥ 7.0 mmol/l) and/or 2-h 75-g oral glucose tolerance test (≥ 11.1 mmol/l) and/or HbA1c (47.5 mmol/mol; ≥ 6.5%) according to American Diabetes Association diagnostic criteria. Multivariable Cox proportional hazards regressions were established to assess the impact of different triglyceridaemic-waist phenotypes on time to diabetes onset. RESULTS: After a mean follow-up period of 6.5 months (sd 4.7 months), the number of diabetes cases was significantly higher in the group with hypertriglyceridaemic-waist phenotype (52.2%) compared with the other three phenotype groups (group 1: 28.2%; group 2: 34.6%; group 3: 30.0%). Only the hypertriglyceridaemic-waist phenotype showed an increased risk of developing diabetes (hazard ratio 1.581, 95% CI 1.172-2.134; P = 0.003) compared with the group with normal waistline and triglyceride level after controlling for confounders. CONCLUSIONS: The combination of central obesity and hypertriglyceridaemia is associated with > 50% risk of progression to diabetes within 6 months among individuals with impaired fasting glucose seen in primary care.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/epidemiologia , Hipertrigliceridemia/epidemiologia , Obesidade Abdominal/epidemiologia , Estado Pré-Diabético/epidemiologia , Atenção Primária à Saúde , Idoso , Estudos de Coortes , Diabetes Mellitus Tipo 2/metabolismo , Jejum/metabolismo , Feminino , Seguimentos , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Humanos , Hipertrigliceridemia/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Obesidade Abdominal/metabolismo , Fenótipo , Estado Pré-Diabético/metabolismo , Modelos de Riscos Proporcionais , Fatores de Risco
12.
Ann Oncol ; 29(2): 361-369, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29077785

RESUMO

Background: Cisplatin-based combination chemotherapy is the standard treatment of advanced urinary tract cancer (aUTC), but 50% of patients are ineligible for cisplatin according to recently published criteria. We used a multinational database to study patterns of chemotherapy utilization in patients with aUTC and determine their impact on survival. Patients and methods: This was a retrospective study of patients with: UTC (bladder, renal pelvis, ureter or urethra); advanced disease (stages T4b and/or N+ and/or M+); urothelial, squamous or adenocarcinoma histology. Primary objective was overall survival (OS). Eligibility-for-cisplatin was defined by Eastern Cooperative Oncology Group performance status ≤ 1, creatinine clearance ≥ 60 ml/min, no hearing loss, no neuropathy and no heart failure. Cox regression multivariate analyses were used to establish independent associations of cisplatin versus noncisplatin-based chemotherapy on OS. Results: 1794 patients treated between 2000 and 2013 at 29 centers were analyzed. Median follow-up was 29.1 months. About 1333 patients (74%) received first-line chemotherapy: the use of first-line chemotherapy was associated with longer OS: [hazard ratio (HR): 1.91, 95% confidence interval (CI): 1.67-2.20]. Type of first-line chemotherapy received was: cisplatin-based 669 (50%), carboplatin-based 399 (30%) and other 265 (20%). Cisplatin use was an independent favorable prognostic factor (HR: 1.54, 95% CI: 1.35-1.77). This benefit was independent of baseline characteristics or comorbidities but was associated with eligibility-for-cisplatin: eligible patients treated with cisplatin lived longer than those who were not (HR: 1.74, 95% CI: 1.36-2.21), while such benefit was not observed among ineligible patients. About 26% of patients who did not receive cisplatin were eligible for this agent. Median OS of ineligible patients was poor irrespective of the chemotherapy used. Conclusions: The importance of applying published criteria of eligibility-for-cisplatin was confirmed in a multinational, real-world setting in aUTC. The reasons for deviations from these criteria set targets to improve adherence. Effective therapies for cisplatin-ineligible patients are needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Urológicas/tratamento farmacológico , Cisplatino/administração & dosagem , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Urológicas/mortalidade
13.
Zhonghua Yi Xue Za Zhi ; 97(27): 2091-2094, 2017 Jul 18.
Artigo em Chinês | MEDLINE | ID: mdl-28763881

RESUMO

Objective: To explore the efficacy and tolerance of Memantine combined Reinhartdt And Sea Cucumber Capsule (R.S.C) on treating agitation in patients with moderate-severe Alzheimer disease (AD). Methods: One hundred and fifty-eight moderate-sever AD patients from Sep.2013 to Sep.2014 in Zhejiang Provincial People's Hospital were randomly divided into two groups: group of Memantine combined R. S.C and group of single Memantine. Then Mini-Mental Sate Examination (MMSE) and Neuropsychiatric Inventory (NPI) were used to evaluate cognition symptom, behavioral and psychological symptoms of dementia (BPSD) and agitation symptom at the baseline and the end of 24 weeks.The Treatment Emergent Symptom Scale (TESS) was used to assess adverse reaction and tolerance.At last, the data was analyzed by chi-square test, t-test and covariance test. Result: At the terminal of experience, the total NPI scores and agitation factor decreased markedly in both of the two groups (P<0.05). Among the patients who had agitation symptom at the baseline, the total NPI scores and agitation factor (18±5, 3.7±2.6) in group of Memantine combined R. S.C were notably lower than those in the group of single Memantine (21±6, 5.3±2.5) (P<0.05). The incidence of adverse reaction between the two groups had no significant difference (combined treatment group was 27.7%, single treatment group was 23.2%). One patient dropped out because of skin allergy, and most adverse reactions were tolerant. Conclusions: Both two groups are effective in agitation and BPSD, and Memantine combined R. S.C is better than single treatment.R.S.C dose not aggravate adverse reaction and can be well tolerated.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Memantina/uso terapêutico , Pepinos-do-Mar , Animais , Humanos , Testes Neuropsicológicos , Agitação Psicomotora , Índice de Gravidade de Doença
14.
Ann Oncol ; 27(6): 1116-1122, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27022067

RESUMO

BACKGROUND: Heat shock protein 27 (Hsp27) is a chaperone protein that regulates cell survival via androgen receptor and other signaling pathways, thereby mediating cancer progression. Apatorsen (OGX-427) is a 2'-methoxyethyl-modified antisense oligonucleotide that inhibits Hsp27 expression. This study evaluated the safety profile and recommended phase II dosing of apatorsen in patients with advanced cancer. PATIENTS AND METHODS: Patients with castration-resistant prostate (CRPC), breast, ovary, lung, or bladder cancer were enrolled to this phase I dose-escalation study. Apatorsen was administered i.v. weekly in 21-day cycles following 3 loading doses and over 5 dose levels (200-1000 mg). Apatorsen plasma concentrations, circulating tumor cells (CTCs) and CTC Hsp27 expression, and serum Hsp27 levels were evaluated. RESULTS: Forty-two patients were accrued, of which 52% had CRPC. Patients were heavily pretreated, with 57% having had ≥3 prior chemotherapy regimens. During the loading dose/cycle 1 and overall study period, 93% and 100% of patients (N = 42) experienced treatment-related adverse events, respectively; most were grade 1-2 and included chills, pruritus, flushing, prolonged aPTT, lymphopenia, and anemia. One patient experienced a dose-limiting toxicity at the 600 mg dose level (intracranial hemorrhage in a previously undiagnosed brain metastasis). A maximum tolerated dose was not defined. Apatorsen Cmax increased proportionally with dose. Decreases in tumor markers and declines in CTCs were observed, with a prostate-specific antigen decline >%50% occurring in 10% of patients with CRPC; 29/39 assessable patients (74%) had reductions from ≥5 CTC/7.5 ml at baseline to <5 CTC/7.5 ml post-treatment. Twelve patients had stable measurable disease as best response. CONCLUSIONS: Apatorsen was tolerated at the highest dose evaluated (1000 mg). Single-agent activity was suggested by changes in tumor markers, CTC, and stable measurable disease. Phase II studies evaluating apatorsen are underway. CLINICALTRIALSGOV ID: NCT00487786.


Assuntos
Diazepam/administração & dosagem , Proteínas de Choque Térmico HSP27/antagonistas & inibidores , Oligonucleotídeos Antissenso/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Diazepam/efeitos adversos , Diazepam/farmacocinética , Relação Dose-Resposta a Droga , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico , Humanos , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares , Células Neoplásicas Circulantes/efeitos dos fármacos , Células Neoplásicas Circulantes/patologia , Oligonucleotídeos Antissenso/efeitos adversos , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia
15.
Prostate Cancer Prostatic Dis ; 18(2): 122-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25600186

RESUMO

BACKGROUND: Enzalutamide and abiraterone are new androgen-axis disrupting treatments for metastatic castration-resistant prostate cancer (mCRPC). We examined the response and outcomes of enzalutamide-treated mCRPC patients in the real-world context of prior treatments of abiraterone and/or docetaxel. METHODS: We conducted a seven-institution retrospective study of mCRPC patients treated with enzalutamide between January 2009 and February 2014. We compared the baseline characteristics, PSA declines, PSA progression-free survival (PSA-PFS), duration on enzalutamide and overall survival (OS) across subgroups defined by prior abiraterone and/or docetaxel. RESULTS: Of 310 patients who received enzalutamide, 36 (12%) received neither prior abiraterone nor prior docetaxel, 79 (25%) received prior abiraterone, 30 (10%) received prior docetaxel and 165 (53%) received both prior abiraterone and prior docetaxel. Within these groups, respectively, ⩾30% PSA decline was achieved among 67, 28, 43 and 24% of patients; PSA-PFS was 5.5 (95% CI 4.2-9.1), 4.0 (3.2-4.8), 4.1 (2.9-5.4) and 2.8 (2.5-3.2) months; median duration of enzalutamide was 9.1 (7.3-not reached), 4.7 (3.7-7.7), 5.4 (3.8-8.4) and 3.9 (3.0-4.6) months. Median OS was reached only for the patients who received both prior abiraterone and docetaxel and was 12.2 months (95% CI 10.7-16.5). 12-month OS was 78% (59-100%), 64% (45-90%), 77% (61-97%) and 51% (41-62%). Of 70 patients who failed to achieve any PSA decline on prior abiraterone, 19 (27%) achieved ⩾30% PSA decline with subsequent enzalutamide. CONCLUSIONS: The activity of enzalutamide is blunted after abiraterone, after docetaxel, and still more after both, suggesting subsets of overlapping and distinct mechanisms of resistance.


Assuntos
Androstenos/administração & dosagem , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Benzamidas , Intervalo Livre de Doença , Docetaxel , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Nitrilas , Feniltioidantoína/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Resultado do Tratamento
16.
Br J Cancer ; 101(2): 263-8, 2009 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-19603032

RESUMO

BACKGROUND: Dasatinib is a small molecule kinase inhibitor that has recently been shown to inhibit Src family kinases (SFK) and also has activity against CaP. Of importance to metastatic CaP, which frequently metastasises to bone, SFK are also vital to the regulation of bone remodelling. We sought to determine the ability of dasatinib to inhibit growth of CaP in bone. METHODS: C4-2B CaP cells were injected into tibiae of SCID mice and treated with dasatinib, alone or in combination with docetaxel. Serum prostate-specific antigen levels, bone mineral density, radiographs and histology were analysed. RESULTS: Treatment with dasatinib alone significantly lowered sacrifice serum prostate-specific antigen levels compared to control, 2.3+/-0.4 vs 9.2+/-2.1 (P=0.004). Combination therapy improved efficacy over dasatinib alone (P=0.010). Dasatinib increased bone mineral density in tumoured tibiae by 25% over control tumoured tibiae (P<0.001). CONCLUSION: Dasatinib inhibits growth of C4-2B cells in bone with improved efficacy when combined with docetaxel. Additionally, dasatinib inhibits osteolysis associated with CaP. These data support further study of dasatinib in clinical trials for men with CaP bone metastases.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Osteólise/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Tiazóis/farmacologia , Animais , Densidade Óssea/efeitos dos fármacos , Neoplasias Ósseas/sangue , Linhagem Celular Tumoral , Dasatinibe , Docetaxel , Humanos , Masculino , Camundongos , Camundongos SCID , Osteólise/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Taxoides/administração & dosagem , Tiazóis/efeitos adversos , Ensaios Antitumorais Modelo de Xenoenxerto , Quinases da Família src/antagonistas & inibidores
18.
Biochim Biophys Acta ; 1527(3): 156-60, 2001 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-11479032

RESUMO

Sulfur K-edge X-ray absorption spectroscopy has been used to determine the chemical identity of the sulfur-containing species in horseradish (Armoracia lapthifolia) and wasabi (Wasabia japonica) in situ, before and after cell disruption. The major sulfur-containing species in the intact root is sinigrin (1-thio-beta-D-glucopyranose 1-N-(sulfoxy)-3-buteneimidate) and related congeners. Disrupting the cells by applying local pressure allowed the conversion of the sulfur moieties in sinigrin to isothiocyanates and sulfate in approximately equimolar amounts. In contrast to previous suggestions, no detectable thiocyanates were formed, but an unusual thio intermediate may have been identified for the first time.


Assuntos
Brassica/metabolismo , Glucosinolatos/metabolismo , Isotiocianatos/metabolismo , Microanálise por Sonda Eletrônica , Glucosinolatos/química , Glicosídeo Hidrolases/metabolismo , Isotiocianatos/química , Modelos Químicos
19.
Biochemistry ; 40(27): 8138-45, 2001 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-11434783

RESUMO

Many sulfide-oxidizing organisms, including the photosynthetic sulfur bacteria, store sulfur in "sulfur globules" that are readily detected microscopically. The chemical form of sulfur in these globules is currently the focus of a debate, because they have been described as "liquid" by some observers, although no known allotrope of sulfur is liquid at physiological temperatures. In the present work we have used sulfur K-edge X-ray absorption spectroscopy to identify and quantify the chemical forms of sulfur in a variety of bacterial cells, including photosynthetic sulfur bacteria. We have also taken advantage of X-ray fluorescence self-absorption to derive estimates of the size and density of the sulfur globules in photosynthetic bacteria. We find that the form of sulfur that most resembles the globule sulfur is simply solid S(8), rather than more exotic forms previously proposed.


Assuntos
Chlorobi/química , Chromatiaceae/química , Proteobactérias/química , Enxofre/química , Chlorobi/crescimento & desenvolvimento , Chromatiaceae/crescimento & desenvolvimento , Tamanho da Partícula , Proteobactérias/crescimento & desenvolvimento , Espectrometria de Fluorescência , Análise Espectral/métodos , Raios X
20.
J Cataract Refract Surg ; 27(1): 18, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11342070
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA