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Mar Drugs ; 17(12)2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31835449


To obtain chitinase-producing microorganisms with high chitinolytic activity at low temperature, samples collected from Fildes Peninsula in Antarctica were used as sources for bioprospecting of chitinolytic microorganisms. A cold-adapted strain, designated as GWSMS-1, was isolated from marine sediment and further characterized as Pseudomonas. To improve the chitinase production, one-factor-at-a-time and orthogonal test approaches were adopted to optimize the medium components and culture conditions. The results showed that the highest chitinolytic activity (6.36 times higher than that before optimization) was obtained with 95.41 U L-1 with 15 g L-1 of glucose, 1 g L-1 of peptone, 15 g L-1 of colloid chitin and 0.25 g L-1 of magnesium ions contained in the medium, cultivated under pH 7.0 and a temperature of 20 °C. To better understand the application potential of this strain, the enzymatic properties and the antifungal activity of the crude chitinase secreted by the strain were further investigated. The crude enzyme showed the maximum catalytic activity at 35 °C and pH 4.5, and it also exhibited excellent low-temperature activity, which still displayed more than 50% of its maximal activity at 0 °C. Furthermore, the crude chitinase showed significant inhibition of fungi Verticillium dahlia CICC 2534 and Fusarium oxysporum f. sp. cucumerinum CICC 2532, which can cause cotton wilt and cucumber blight, respectively, suggesting that strain GWSMS-1 could be a competitive candidate for biological control in agriculture, especially at low temperature.

BMC Cancer ; 19(1): 279, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30922248


BACKGROUND: With poor prognosis and limited treatment options for advanced hepatocellular carcinoma (HCC), development of novel therapeutic agents is urgently needed. This single-arm phase I study sought to assess the safety and preliminary efficacy of icaritin in human as a potential oral immunotherapy in addition to the immune-checkpoint inhibitors. METHODS: Eligible advanced HCC patients with Child-Pugh Class A or B were administered with a fixed oral dose of icaritin at either 600 or 800 mg b.i.d. The primary endpoint was safety, and the secondary endpoints included time-to-progression (TTP), overall survival (OS) and the clinical benefit rate (CBR). Icaritin treatment induced immune biomarkers and immune-modulating activities in myeloid cells were also explored. RESULTS: No drug-related adverse events ≥ Grade 3 were observed in all 20 enrolled HCC patients. Among the 15 evaluable patients, 7 (46.7%) achieved clinical benefit, representing one partial response (PR, 6.7%) and 6 stable disease (SD, 40%). The median TTP was 141 days (range: 20-343 days), and the median OS was 192 days (range: 33-1036 days). Durable survival was observed in PR/SD patients with a median OS of 488 days (range: 72-773). TTP was significantly associated with the dynamic changes of peripheral neutrophils (p = 0.0067) and lymphocytes (p = 0.0337). Icaritin treatment induced changes in immune biomarkers-and immune-suppressive myeloid cells were observed. CONCLUSIONS: Icaritin demonstrated safety profiles and preliminary durable survival benefits in advanced HCC patients, which were correlated with its immune-modulation activities and immune biomarkers. These results suggested the potential of icaritin as a novel oral immunotherapy for advanced HCC in addition to antibody-based PD-1/PD-L1 blockade therapies. TRIAL REGISTRATION: identifier. NCT02496949 (retrospectively registered, July 14, 2015).

Biomarcadores Tumorais/imunologia , Carcinoma Hepatocelular/tratamento farmacológico , Flavonoides/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Administração Oral , Adulto , Idoso , Carcinoma Hepatocelular/imunologia , Esquema de Medicação , Feminino , Flavonoides/efeitos adversos , Flavonoides/farmacologia , Humanos , Neoplasias Hepáticas/imunologia , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Análise de Sobrevida , Resultado do Tratamento
J Biopharm Stat ; 25(6): 1135-44, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25321600


Recently, a design was proposed for the Simultaneous Global Drug Development Program (SGDDP) to assess the impact of ethnic factors on the effect of a new treatment for a targeted ethnic (TE) population. It used weighted Z tests to combine the information collected from the TE and non-TE (NTE) subgroups in the SGDDP based on the fundamental assumption on their shared biological commonality. In this article, we mathematically formulated this assumption as the quantitative interaction between treatment effect and subgroup. We used it to more rigorously describe the hypotheses, and showed the unbiasedness of the weighted Z test. Moreover, to study the loss of efficiency from down weighting the NTE information in this SGDDP design, we compared the power of their test with that of the uniformly most powerful (UMP) test, which we showed was also a weighted Z test. We discussed that the choice of weight should balance the maximization of power when the assumption holds and the minimization of bias otherwise.

Grupos Étnicos/estatística & dados numéricos , Farmacologia Clínica/estatística & dados numéricos , Projetos de Pesquisa/estatística & dados numéricos , Algoritmos , Biometria , Interpretação Estatística de Dados , Desenho de Drogas , Interações de Medicamentos , Humanos , Tamanho da Amostra
Contemp Clin Trials ; 37(2): 225-33, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24462567


When analyzing the randomized controlled trial, we may employ various statistical methods to adjust for baseline measures. Depending on the method chosen to adjust for baseline measures, inferential results can vary. We investigate the Type 1 error and statistical power of tests comparing treatment outcomes based on parametric and nonparametic methods. We also explore the increasing levels of correlation between baseline and changes from the baseline, with or without underlying normality. These methods are illustrated and compared via simulations.

Viés , Modelos Estatísticos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa , Biometria , Humanos , Estatísticas não Paramétricas
Acad Radiol ; 20(7): 807-15, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23582776


RATIONALE AND OBJECTIVES: Based on imaging features, the optimal thresholds are typically determined as cutoff points to dichotomize the corresponding measurement scales. MATERIALS AND METHODS: Five metrics (ie, the Youden index, Euclidian distance, percent of correct diagnosis, kappa statistic, and mutual information) are individually maximized or minimized to derive the corresponding optimal threshold. These optimal thresholds are estimated under the parametric binormal assumption. Monte Carlo simulation studies are conducted to compare the performances of these different methods. A published radiological example on the choice of treatment outcomes following ureteral stones is used to illustrate and compare the estimated thresholds both empirically and parametrically. RESULTS: The optimal threshold can be a "moving target" because it would depend on modeling assumptions, metrics, and variability in the data. Even with large samples, disease prevalence has an impact on the robustness of the metrics. CONCLUSIONS: It is recommended that researchers compare different optimal cutoff points using several metrics and select one that is most clinically relevant. The ultimate goal is to maximize diagnostic performances that are clinically meaningful to achieve improved global health.

Modelos Estatísticos , Curva ROC , Tomografia Computadorizada Espiral/estatística & dados numéricos , Cálculos Ureterais/diagnóstico por imagem , Humanos , Sensibilidade e Especificidade , Tomografia Computadorizada Espiral/métodos , Ureter/diagnóstico por imagem