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1.
Chinese Medical Journal ; (24): 2665-2673, 2020.
Article in English | WPRIM | ID: wpr-877883

ABSTRACT

BACKGROUND@#Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis.@*METHODS@#This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12.@*RESULTS@#A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period.@*CONCLUSION@#Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , China , Double-Blind Method , Humans , Psoriasis/drug therapy , Severity of Illness Index , Treatment Outcome
2.
Acta Physiologica Sinica ; (6): 165-170, 2003.
Article in Chinese | WPRIM | ID: wpr-318923

ABSTRACT

We found previously that ACh can significantly inhibit the proliferation of cultured human pituitary adenoma cells. In order to make a further investigation of the mechanism of the inhibitory effect of ACh on the proliferation of pituitary adenoma cells, we observed the levels of protein kinase C (PKC), [Ca(2+)](i) and cAMP/cGMP in cultured pituitary adenoma cells after treatment with ACh. The results demonstrate that (1) compared with control, PMA, a PKC activator, increased the activity of cytoplasm, membrane and total PKC in human pituitary adenoma cells. However, after a 15-min treatment with ACh (10 micromol/L), a significant reduction of the activity of cytoplasm, membrane and total PKC in human pituitary adenoma cells was observed, and the reduction effect could be blocked by atropine. (2) The level of [Ca(2+)](i) of single adenoma cells was found to decrease immediately on the addition of ACh (10 micromol/L), which could also be blocked by atropine. (3) ACh increased the amount of cAMP in the cytoplasm of human pituitary adenoma cells, but had no effect on that of cGMP. These data provide an important clue to explore the molecular mechanisms of the inhibitory effect of ACh on the proliferation of pituitary adenoma cells, and suggest that the modulating effect of ACh on the proliferation of pituitary adenoma cells results from the interactions of several cellular signaling pathways.


Subject(s)
Acetylcholine , Physiology , Adenoma , Metabolism , Pathology , Calcium , Metabolism , Cyclic AMP , Metabolism , Cyclic GMP , Metabolism , Humans , Pituitary Neoplasms , Metabolism , Pathology , Protein Kinase C , Metabolism , Signal Transduction , Physiology , Tumor Cells, Cultured
3.
Acta Physiologica Sinica ; (6): 251-257, 2002.
Article in Chinese | WPRIM | ID: wpr-279302

ABSTRACT

In order to elucidate the effect of acetylcholine (ACh) on the occurrence and development of human pituitary adenoma, it was firstly observed whether there exists choline acetyl transferase (ChAT) which is necessary for the synthesis of acetylcholine in the cells of human pituitary adenoma, and then MTT method, (3)H TdR incorporation, cell cycle analysis and TUNEL were employed to estimate the influence of ACh on the proliferation, DNA synthesis and apoptosis of three kinds of human pituitary adenoma (human prolactinoma, somatotropinoma and non-functional tumor) cells cultured in vitro. The results showed that (1) the positive staining of ChAT was obviously observed in the cells of the three kinds of human pituitary adenoma, however, it was lower than that in normal human pituitary gland; (2) ACh had a similar effect on the proliferation of the three kinds of human pituitary adenoma cells. ACh at 0.1-10 micromol/L decreased the (3)H TdR incorporation and the MTT A value in a dose-dependent manner. At the same time, ACh decreased the ratio of S or G(2) phase pituitary adenoma cells significantly, but increased the ratio of G(1) phase pituitary tumour cells markedly; (3) the effect of acetylcholine on the proliferation of human pituitary adenoma cells was inhibited by atropine, but not by tubocurarine; (4) ACh had no effect on the apoptosis of human pituitary adenoma cells cultured in vitro. These data suggest that ACh may have a significant modulating effect on the proliferation of pituitary adenoma cells by means of paracrine or autocrine, and the effect is mediated by muscarinic receptor.


Subject(s)
Acetylcholine , Pharmacology , Physiology , Acetyltransferases , Physiology , Adenoma , Pathology , Bodily Secretions , Apoptosis , Cell Division , Dose-Response Relationship, Drug , Humans , Pituitary Neoplasms , Pathology , Bodily Secretions , Tumor Cells, Cultured
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