1.Literature case analysis of pulmonary hypertension induced by dasatinib
Yanjiao LI ; Ruixin XING ; Xinlu WANG ; Wenrui ZHANG ; Lirui SUN
Adverse Drug Reactions Journal 2022;24(2):74-79
Objective:To analyze the clinical characteristics of pulmonary hypertension (PH) induced by dasatinib.Methods:The relevant databases at home and abroad (as of December 31, 2020) were searched and the case reports on PH induced by dasatinib were collected. Clinical information including patient′s basic characteristics, dasatinib dose, occurrence time of PH, clinical manifestations, interventions, and outcomes were collected and analyzed by descriptive statistical method.Results:A total of 25 patients from 24 case reports were enrolled in the study, including 16 males and 9 females, aged from 23 to 73 years with an average age of 50 years. There were 22 patients with chronic myeloid leukemia (CML) and 3 with acute lymphoblastic leukemia (ALL); the dose of dasatinib was 140 mg daily in 14 patients, 100 mg daily in 7 patients, 70 mg daily in 2 patients, and unknown in 2 patients. Time from dasatinib application to PH occurrence was 10 days to 144 months, with a median time of 37 months. The clinical symptoms included varying degrees of dyspnea in 24 patients, edema in 8 patients, hepatomegaly in 5 patients, jugular vein dilatation in 5 patients, cough in 3 patients,and chest tightness in 3 patients, chest pain in 2 patients, and fatigue in 1 patient. Pleural effusion and/or pericardial effusion were found in 20 patients by chest CT, chest X-ray or echocardiography. Cardiac function was graded as Ⅳ in 8 patients, Ⅲ in 9 patients, and Ⅱ in 4 patients according to WHO classification method, and the grade was unknown in 4 patients. Right cardiac catheterization and/or echocardiography showed elevated mean pulmonary artery pressure and/or systolic pulmonary artery pressure in 25 patients. Twenty-four patients stopped dasatinib following the doctor′s advice after the diagnosis of PH, of which 22 patients were treated with phosphodiesterase 5 inhibitor, endothelin receptor antagonist, diuretic, and glucocorticoid, and the other 2 patients were not given special intervention; one patient took dasatinib intermittently by himself. Nineteen patients were switched to other tyrosine kinase inhibitors. After discontinuation of dasatinib and giving symptomatic treatments for 1 week to 36 months (mean 7 months), 17 patients were improved, 7 were partially improved, and 1 had unknown outcome.Conclusions:Dasatinib-related PH was more common in patients with CML, occurred more in male patients, and had a median occurrence time of 37 months after drug administration. The main clinical manifestation was dyspnea, often complicated with pleural effusion or pericardial effusion. After dasatinib withdrawal and specific treatments, most patients could be improved.
2.Literature case analysis of pulmonary hypertension induced by dasatinib
Yanjiao LI ; Ruixin XING ; Xinlu WANG ; Wenrui ZHANG ; Lirui SUN
Adverse Drug Reactions Journal 2022;24(2):74-79
Objective:To analyze the clinical characteristics of pulmonary hypertension (PH) induced by dasatinib.Methods:The relevant databases at home and abroad (as of December 31, 2020) were searched and the case reports on PH induced by dasatinib were collected. Clinical information including patient′s basic characteristics, dasatinib dose, occurrence time of PH, clinical manifestations, interventions, and outcomes were collected and analyzed by descriptive statistical method.Results:A total of 25 patients from 24 case reports were enrolled in the study, including 16 males and 9 females, aged from 23 to 73 years with an average age of 50 years. There were 22 patients with chronic myeloid leukemia (CML) and 3 with acute lymphoblastic leukemia (ALL); the dose of dasatinib was 140 mg daily in 14 patients, 100 mg daily in 7 patients, 70 mg daily in 2 patients, and unknown in 2 patients. Time from dasatinib application to PH occurrence was 10 days to 144 months, with a median time of 37 months. The clinical symptoms included varying degrees of dyspnea in 24 patients, edema in 8 patients, hepatomegaly in 5 patients, jugular vein dilatation in 5 patients, cough in 3 patients,and chest tightness in 3 patients, chest pain in 2 patients, and fatigue in 1 patient. Pleural effusion and/or pericardial effusion were found in 20 patients by chest CT, chest X-ray or echocardiography. Cardiac function was graded as Ⅳ in 8 patients, Ⅲ in 9 patients, and Ⅱ in 4 patients according to WHO classification method, and the grade was unknown in 4 patients. Right cardiac catheterization and/or echocardiography showed elevated mean pulmonary artery pressure and/or systolic pulmonary artery pressure in 25 patients. Twenty-four patients stopped dasatinib following the doctor′s advice after the diagnosis of PH, of which 22 patients were treated with phosphodiesterase 5 inhibitor, endothelin receptor antagonist, diuretic, and glucocorticoid, and the other 2 patients were not given special intervention; one patient took dasatinib intermittently by himself. Nineteen patients were switched to other tyrosine kinase inhibitors. After discontinuation of dasatinib and giving symptomatic treatments for 1 week to 36 months (mean 7 months), 17 patients were improved, 7 were partially improved, and 1 had unknown outcome.Conclusions:Dasatinib-related PH was more common in patients with CML, occurred more in male patients, and had a median occurrence time of 37 months after drug administration. The main clinical manifestation was dyspnea, often complicated with pleural effusion or pericardial effusion. After dasatinib withdrawal and specific treatments, most patients could be improved.
3.Sequence analysis of LEAFY homologous gene from Dendrobium moniliforme and application for identification of medicinal Dendrobium.
Wenrui XING ; Beiwei HOU ; Jingjiao GUAN ; Jing LUO ; Xiaoyu DING
Acta Pharmaceutica Sinica 2013;48(4):597-603
The LEAFY (LFY) homologous gene of Dendrobium moniliforme (L.) Sw. was cloned by new primers which were designed based on the conservative region of known sequences of orchid LEAFY gene. Partial LFY homologous gene was cloned by common PCR, then we got the complete LFY homologous gene Den LFY by Tail-PCR. The complete sequence of DenLFY gene was 3 575 bp which contained three exons and two introns. Using BLAST method, comparison analysis among the exon of LFY homologous gene indicted that the DenLFY gene had high identity with orchids LFY homologous, including the related fragment of PhalLFY (84%) in Phalaenopsis hybrid cultivar, LFY homologous gene in Oncidium (90%) and in other orchid (over 80%). Using MP analysis, Dendrobium is found to be the sister to Oncidium and Phalaenopsis. Homologous analysis demonstrated that the C-terminal amino acids were highly conserved. When the exons and introns were separately considered, exons and the sequence of amino acid were good markers for the function research of DenLFY gene. The second intron can be used in authentication research of Dendrobium based on the length polymorphism between Dendrobium moniliforme and Dendrobium officinale.

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