RESUMEN
Polymorphism rs7214723 was reported to be associated with lung cancer risk in UK Caucasians and caused the E375G substitution of CAMKK1 which plays important role in the calcium/calmodulin-dependent kinase cascade. To analyze rs7214723 in CAMKK1 and lung cancer risk in a Chinese population, SNPscan(TM) was used to genotype polymorphism rs7214723 in 961 lung cancer cases and 999 control subjects. The frequencies of the TT, TC, and CC genotypes of CAMKK1 rs7214723 were 43.3, 42.6, and 14.0 % in controls, and 41.1, 48.0, and 10.9 % in cases, respectively (P = 0.025). Compared with the CC genotype, TC genotype was associated with increased risk of lung cancer (OR 1.500, 95 % CI 1.112-2.022) after adjustment for age, gender, smoking status, and family history. The T allele of rs7214723 is the risk allele for lung carcinogenesis in dominant model (OR 1.354, 95 % CI 1.020-1.797). In stratified analysis, the risk effect of the TC genotype of rs7214723 was more evident in subgroups of those who had never been smokers (OR 1.556, 95 % CI 1.074-2.254). For the population without a family history of cancer, both the TT (OR 1.488, 95 % CI 1.050-2.109) and TC (OR 1.668, 95 % CI 1.180-2.357) carrier had an increased lung cancer risk. E375 is located in the kinase domain of CAMKK1, and E375G may change the electrical charge at the surface and decrease the kinase activity. Polymorphism rs7214723 in CAMKK1 might contribute to the risk of lung cancer in Chinese populations. The T allele is a risk allele in lung carcinogenesis.
Asunto(s)
Adenocarcinoma/genética , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/genética , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido Simple , Adenocarcinoma/enzimología , Anciano , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/química , Carcinoma de Células Escamosas/enzimología , Estudios de Casos y Controles , Dominio Catalítico , China , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Neoplasias Pulmonares/enzimología , Masculino , Persona de Mediana Edad , Modelos Moleculares , Factores de Riesgo , Análisis de Secuencia de ADNRESUMEN
A novel and highly efficient dual-targeting PtII system was designed to improve the drug delivery capacity and selectivity in cancer treatment. The dual-targeting monofunctional PtII complexes (1-8) having glycosylated pendants as tridentated ligand were achieved by introducing glycosylation modification in the thioaminocarbazone compounds with potential lysosomal targeting ability. The structures and stability of 1-8 were further established by various techniques. Molecular docking studies showed that 2 was efficiently docked into glucose transporters protein 1 (GLUT1) and P-glycoprotein (Pgp) proteins with the optimal CDocker-interaction-energy of -64.84 and -48.85 kcal mol-1. Complex 2 with higher protein binding capacity demonstrated significant and broad-spectrum antitumor efficacy in vitro, even exhibiting a half maximal inhibitory concentration (IC50) value (â¼10 µM) than cisplatin (â¼17 µM) against human lung adenocarcinoma cells (A549). The inhibitor experiment revealed GLUT-mediated uptake of 2, and the subcellular localization experiment in A549 also proved that 2 could be localized in the lysosome, thereby causing cell apoptosis. Moreover, cellular thermal shift assay (CETSA) confirmed the binding of 2 with the target proteins of GLUT1 and Pgp. The above results indicated that 2 represents a potential anticancer candidate with dual-targeting functions.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Antineoplásicos , Compuestos de Platino , Humanos , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Transportador de Glucosa de Tipo 1 , Simulación del Acoplamiento Molecular , Compuestos de Platino/química , Compuestos de Platino/farmacología , Células A549RESUMEN
BACKGROUND: Lower extremity bursae are very vulnerable to injury during strenuous physical exercises. Understanding the imaging characteristics of normal bursae is essential for early diagnosis of morphological abnormalities. Therefore, we evaluated the normal range of lower extremity bursae in healthy young men using high-resolution ultrasound (HR-US) imaging. METHODS: Bursae in the lower extremities were examined by HR-US in 290 Chinese healthy young men with a median age of 18 years (range, 18-23 years). The bilateral suprapatellar bursa (SPB), deep infrapatellar bursa (DIPB), popliteal bursa (PB), and retrocalcaneal bursa (RCB) were imaged and measured for analysis. RESULTS: The HR-US identification rates of the SPB, DIPB, PB, and RCB were 89.0% (517/580), 55.0% (319/580), 29.4% (171/580), and 49.5% (287/580), respectively. With the assumption that the bursae were normal in 95% of the study participants, the length and width values at the maximal cross-section of the SPB, DIPB, PB, and RCB were ≤18.00 and 6.09 mm, 8.10 and 2.11 mm, 7.67 and 3.93 mm, and 7.82 and 2.04 mm, respectively. CONCLUSIONS: Using HR-US imaging, we were able to analyze lower extremity bursae with high detection rates in healthy young men. The normal ranges of lower extremity bursa dimensions in healthy young men measured by HR-US in this study could be used as reference values for evaluation of bursa abnormalities in the lower extremity.
Asunto(s)
Bolsa Sinovial/patología , Adolescente , Adulto , Estudios Transversales , Humanos , Extremidad Inferior/patología , Masculino , Adulto JovenRESUMEN
Pot experiments were performed to study the effectiveness of chelators (EDTA, citric acid) and peat in enhancing phyremediation of heavy metal Cd by ramie. The results showed that peat increased the ramie's biomass by improving soil's physical and chemical properties, and the relative yields of peat alone, chelators(EDTA, citric acid) combined with peat were 1.23, 1.13 and 1.41 respectively. So the combination of citric acid and peat was more useful for growth of the ramie. As far as improving Cd uptake was concerned, it seemed that the combination of chelators with peat significantly promoted Cd uptake by the plant, and the percent of changeable Cd in soil were 61.6% and 58.3% . In addition, it had better bioaccumulation effects to combine with chelators and peat, of which Cd bioaccumulation coefficients were 1.33 and 1.32, compared to 1.11, 1.11 and 1.05 in application of peat, EDTA and citric acid respectively. What's more, cadmium removal rates in soil were up to 1.13% and 1.22% respectively in applications of two kinds of chleators (EDTA, citric acid) combined with peat. Therefore, it had better effects of phytoremediation to accumulate more cadmium amounts by combining with citric acid and peat because of more biomass. In conclusion, the phytoremediation by ramie can be more effective when chelators and peat were combined and added to soils.