RESUMO
Two series of novel carbothioamide-substituted pyrazole and isoxazolidine derivatives were facilely prepared by functional interconversions in ring D of the tetracyclic diterpene isosteviol. The in vitro cytotoxic activities against four human tumor cell lines were evaluated. Our results indicated that carbothioamide-substituted pyrazole derivatives exhibited noteworthy cytotoxic activities. Specifically, compound 12p (IC(50)=6.51 µM) had the most potent cytotoxicity against Raji cell, which may be exploitable as a lead compound for the development of potent antitumor agents.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Azóis/síntese química , Azóis/farmacologia , Diterpenos do Tipo Caurano/química , Tioamidas/síntese química , Tioamidas/farmacologia , Linhagem Celular Tumoral , Cristalografia por Raios X , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Isoxazóis/síntese química , Isoxazóis/farmacologia , Pirazóis/síntese química , Pirazóis/farmacologia , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
A cluster-randomized controlled trial (RCT) was conducted to evaluate to the effectiveness of reducing mortality of upper gastrointestinal cancer (UGC) and feasibility of screening through a questionnaire combined with endoscopy in non-high-incidence urban areas in China. The trial design, recruitment performance, and preliminary results from baseline endoscopy are reported. Seventy-five communities in two urban cities with a non-high-incidence of UGC were randomized to a screening endoscopy arm (n = 38) or a control arm (n = 37). In the screening arm, individuals at high risk of UGC underwent endoscopic screening. The primary outcome was the UGC mortality, and secondary outcomes included the UGC detection rate, incidence rate, survival rate, and clinical stage at the time of diagnosis. A total of 10,416 and 9,565 individuals were recruited into the screening and control arms, respectively. The participation rate was 74.3%. In the screening arm, 5,242 individuals (50.3%) were estimated to be high-risk. Among them, 2,388 (45.6%) underwent endoscopic screening. Age and household income were associated with undergoing endoscopy. Three early esophageal cancer (0.13%), one gastric cancer (0.04%), 29 precancerous esophageal lesions (1.21%), and 53 precancerous gastric lesions (2.22%) were detected. Age, sex, a family history of cancer, intake of meat-egg-milk frequently, superficial gastritis, and clinical symptoms of gastric cancer were associated with the presence of precancerous lesions. The detection rate was low using endoscopic screening in non-high-incidence area given the relatively low compliance rate. These findings provide a reference for designing effective community-based UGC screening strategies in non-high-incidence urban areas.
Assuntos
Serviços de Saúde Comunitária/organização & administração , Detecção Precoce de Câncer/estatística & dados numéricos , Neoplasias Esofágicas/prevenção & controle , Lesões Pré-Cancerosas/epidemiologia , Neoplasias Gástricas/prevenção & controle , Adulto , Fatores Etários , Idoso , China/epidemiologia , Serviços de Saúde Comunitária/estatística & dados numéricos , Endoscopia Gastrointestinal/estatística & dados numéricos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/mortalidade , Estudos de Viabilidade , Feminino , Humanos , Incidência , Renda/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Participação do Paciente/estatística & dados numéricos , Lesões Pré-Cancerosas/diagnóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Inquéritos e Questionários/estatística & dados numéricos , Taxa de Sobrevida , Saúde da População Urbana/estatística & dados numéricosRESUMO
PURPOSE: This study aimed to construct two prognostic nomograms to predict survival in patients with non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) using a novel set of clinical parameters. PATIENTS AND METHODS: Two nomograms were developed, using a retrospective analysis of 5384 NSCLC and 647 SCLC patients seen during a 10-year period at Xiang Ya Affiliated Cancer Hospital (Changsha, China). The patients were randomly divided into training and validation cohorts. Univariate and multivariate analyses were used to identify the prognostic factors needed to establish nomograms for the training cohort. The model was internally validated via bootstrap resampling and externally certified using the validation cohort. Predictive accuracy and discriminatory capability were estimated using concordance index (C-index), calibration curves, and risk group stratification. RESULTS: The largest contributor to overall survival (OS) prognosis in the NSCLC nomogram was the therapeutic regimen and diagnostic method parameters, and in the SCLC nomogram was the therapeutic regimen and health insurance plan parameters. Calibration curves for the nomogram prediction and the actual observation were in optimal agreement for the 3-year OS and acceptable agreement for the 5-year OS in both training datasets. The C-index was higher for the NSCLC cohort nomogram than for the TNM staging system (0.67 vs. 0.64, P = 0.01) and higher for the SCLC nomogram than for the clinical staging system (limited vs. extensive) (0.60 vs. 0.53, P = 0.12). CONCLUSION: Treatment regimen parameter made the largest contribution to OS prognosis in both nomograms, and these nomograms might provide clinicians and patients a simple tool that improves their ability to accurately estimate survival based on individual patient parameters rather than using an averaged predefined treatment regimen.
RESUMO
Two series of novel isosteviol-fused pyrazoline and pyrazole derivatives were facilely synthesized via intramolecular 1,3-dipolar cycloaddition and condensation reaction, respectively. All compounds were characterized by NMR, IR and HRMS spectra. The stereochemistry of compounds 9b, 10, 11a and 11v were further confirmed by X-ray crystallographic analysis. The antiproliferative activities of the structurally related pyrazoline and pyrazole derivatives were tested in vitro on four human malignant cell lines (SGC 7901, A549, Raji and HeLa): Our results revealed that isosteviol-fused pyrazole derivatives exhibited noteworthy cytotoxic activities. Among them, 2,4-di-Cl-phenylpyrazole derivative 11t displayed better cytotoxities with IC50 values: 2.71, 3.18, 1.09 and 13.52 µM against SGC 7901, A549, Raji and HeLa, respectively, compared to cisplatin (IC50 values: 7.56, 17.78, 17.32 and 14.31 µM, respectively).
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Diterpenos do Tipo Caurano/química , Desenho de Fármacos , Pirazóis/síntese química , Pirazóis/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Ciclização , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Modelos Moleculares , Conformação Molecular , Pirazóis/química , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: To determine the incidence of non-fatal injuries and related influencing factors among children under 5 years old in China. METHODS: Data involving 10 819 children under 5 years old was from the Fourth National Health Service Survey of China. Injury-related indicators include: history of ever having had an injury, its frequency, cause, location and severity of the injury. A two-level Poisson regression was used to examine the significance of related socio-economic variables. RESULTS: The overall incidence rate of nonfatal injuries among children under 5 years old was 16.0 per 1000 population in the prior 12 months. The first three leading causes of non-fatal injuries were falls, animal bite, fire/burn among children under 1 year old, with the rates as 3.9, 1.8 and 1.8 per 1000 population, respectively. For children aged 1 to 4 years old, the first three leading causes were animal bite, fall, fire/burn with rates as 6.5, 6.0 and 2.9 per 1000 population, respectively. 83.0% and 69.0% of last injuries occurred at home for the above said two age groups. No disability was found among children younger than 1 year old who suffered from a nonfatal injury while for the 1 - 4 age group, the disability accounted for 1.0% of injury-induced outcomes. After adjusting other variables, boys had 1.57 times the risk of injury compared with girls in the 1 - 4 age group (P < 0.05). The differences on the effects regarding ethnicity, per capita household income, and place were insignificant (P > 0.05). None of the socio-economic variables was found that significantly related to the non-fatal injury risk among children under 1 year old (P > 0.05). CONCLUSION: The incidence of nonfatal injuries among children under 5 years old was 16.0 per 1000 population in the prior 12 months. The three leading causes of injuries were animal bite, falls, fire/burn respectively. Home was the most common place that non-fatal injuries occurred. Boys had a higher risk of injury compared with girls among children aged 1 to 4 years old and the difference was significant.
Assuntos
Acidentes/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Incidência , Lactente , Masculino , Fatores de RiscoRESUMO
A series of digoxin derivatives containing the gamma-alkylidene butenolide moiety were synthesised by way of stereoselective vinylogous aldol reaction of the unactivated butenolide in simple conditions. The structures of compounds synthesised were characterised by infrared (IR), nuclear magnetic resonance (NMR) and HR-MS. Preliminary bioassay shows that some of them have cardiac functions, especially compound 2g that induced a marked increase in myocardial contractility at 10ngml(-1) and 20ngml(-1) concentrations without digitalis toxicity.