1.Lidamycin inhibits the proliferation of HERG K+ channel highly expressing cancer cells and shows synergy with anticancer drugs.
Boyang SHANG ; Yue SHANG ; Yongsu ZHEN ; Shuzhen CHEN
Acta Pharmaceutica Sinica 2011;46(11):1321-5
This study is to investigate inhibitory effects of lidamycin (LDM) on the proliferation of HERG K+ channel highly expressing cancer cells and its synergy with anticancer drugs. MTT assay was used to examine the inhibitory effects of lidamycin combined with various anticancer drugs on the proliferation of human lung cancer A549 cells, human colon cancer HT-29 cells and herg-stably-transfected A549 cells. Using the xenograft model of subcutaneously transplanted HT-29 in nude mice, inhibitory effect was appraised in vivo. The coefficient of drug interaction (CDI) was used to evaluate the synergistic effect of drug combination. LDM significantly inhibited the proliferation ofA549 cells and HT-29 cells with IC50 values of 2.14 and 4.64 ng mL(-1), respectively. The efficacy in HT-29 cells with high HERG potassium expression level is less potent than that in A549 cells with low expression level. In terms of IC50 values, LDM suppressed the growth of herg-stably-transfected A549 cells less potently than pCDNA3.1-stably-transfected A549 cells. There existed synergistic effects in the combinations of fluorouracil (5-FU) and LDM, doxorubicin (DOX) and LDM, or hydroxycamptothecine (HCPT) and LDM. CDI values of the combinations of 5-FU and LDM were more than 0.75. CDI values of LDM and DOX were more than 0.70, but some CDI values of LDM and HCPT were less than 0.70. As for the CDI values, synergistic effects of the combination of LDM and HCPT were the most potent of the three groups. There is no relationship between the inhibitory effect of the growth of cancer cells by 5-FU and HERG potassium expression level. HERG expression level negatively correlated with inhibitory effect on the proliferation of cancer cells by DOX. HERG expression levels and chemosensitivity were positively correlated for HCPT. In the model of subcutaneously xenograft transplanted HT-29 in vivo, LDM and/or HCPT effectively inhibited the growth of HT-29 in nude mice, and the optimum CDI of the combination of LDM and HCPT was less than 1. HERG expression level negatively correlates the chemosensitivity of cancer cells to LDM. There exist synergistic effects in vitro and in vivo in the combination of LDM and HCPT, which inhibitory effects of the proliferation of cancer cells positively modulated by HERG potassium expression level. HERG K+ channel may become a target of combined therapy for choosing anticancer drugs.
2.Effects of Fuzheng Xiaoai decoction joint tamoxifen on serum sex hormone and endometrial thickness with breast cancer
Fuming LI ; Danying XU ; Yan YUAN ; Yue LIU ; Shuzhen FANG
Chinese Journal of Biochemical Pharmaceutics 2017;37(3):122-124,127
Objective To analyze the effects of Fuzheng Xiaoai decoction joint tamoxifen on serum sex hormone and endometrial thickness with breast cancer.Methods 124 patients with breast cancer were divided into control group and research group by lot drawing method, all as 62 cases, treated with the same surgery, control group was treated with tamoxifen, research group was treated with Fuzheng Xiaoai decoction based on control group, the sex hormones, endometrial thickness, tumor markers, immune function and complications were compared between two groups.Results The prolactin (PRL), progesterone (P), estradiol (E2) of research group were all lower than control group, the difference were statistically significant (P<0.05).The endometrial thickness of research group [(8.61+1.07) mm]was lower than the control group [(9.74+1.21) mm](P<0.05).The tumor markers, immune function of research group were better than that of control group (P<0.05).The complications was no difference between two groups. Conclusion Fuzheng Xiaoai decoction joint tamoxifen can regulation the serum levels of sex hormone, relieve tamoxifen-induced endometrial thickening, can improve tumor markers and immune function .
3.Efficacy and safety of omalizumab in the treatment of chronic urticaria in children: a retrospective study
Shuzhen YUE ; Ye SHU ; Yangyang LUO ; Keyao LI ; Yuanyuan ZHANG ; Jianping TANG ; Zhu WEI
Chinese Journal of Dermatology 2024;57(4):354-358
Objective:To evaluate the efficacy and safety of omalizumab in the treatment of chronic urticaria in children.Methods:A retrospective study was conducted. Patients with chronic urticaria were collected from the Department of Dermatology, Hunan Children′s Hospital from January to December 2021, and divided into a control group and a combination group according to different medication regimens. The patients in the combination group received subcutaneous injections of omalizumab (150 mg, once every 4 weeks) combined with conventional-dosage antihistamines, while the patients in the control group were only treated with double-dosage or multiple types of antihistamines. The course of treatment was 3 to 6 months. The clinical efficacy and adverse reactions were evaluated at 3, 6, and 12 months after the start of treatment, and the recurrence was evaluated at 3 and 6 months after the end of treatment.Results:A total of 46 children with chronic urticaria were collected. There were 23 children (13 males and 10 females) in the combination group, aged from 6 to 17 years and including 16 aged from 6 to 12 years and 7 aged from 13 to 17 years; according to the total serum IgE levels before treatment, the patients in the combination group were divided into an increased IgE subgroup (11 cases) and a normal IgE subgroup (12 cases). In the control group, there were 13 males and 10 females, aged from 6.33 to 16 years and including 15 aged from 6 to 12 years and 8 aged from 13 to 17 years. At 3, 6, and 12 months after the start of treatment, the response rates in the combination group were all 86.96% (20/23), which were all significantly higher than those in the control group (52.17% [12/23], 56.52% [13/23], 56.52% [13/23], P = 0.010, 0.022, 0.022, respectively). In the combination group, the response rates at 3, 6, and 12 months after the start of treatment were all 14/16 in the children aged 6 to 12 years and 6/7 in those aged 13 to 17 years, and there were no significant differences between the two age groups (all χ2 = 0.01, P = 0.907) ; in the control group, the response rates were 5/15, 6/15 and 5/15 respectively in the children aged 6 to 12 years, which were all significantly lower than those in the combination group ( P = 0.002, 0.006, 0.006, respectively). In the combination group, the response rates at 3, 6, and 12 months after the start of treatment were all 9/11 in the increased IgE subgroup and 11/12 in the normal IgE subgroup, and there were no significant differences between the two subgroups (all P = 0.484). During the treatment, no serious adverse reactions were observed in the combination group or control group, and mild somnolence only occurred in 2 children in the control group. At 3 months after the end of treatment, no recurrence was observed in 16 patients in the combination group, 2 out of 6 patients experienced recurrence in the control group, and the recurrence rate was lower in the combination group than in the control group ( P = 0.030) ; at 6 months after the end of treatment, no recurrence was observed in 16 patients in the combination group, 3 out of 6 patients experienced recurrence in the control group, and the recurrence rate was lower in the combination group than in the control group ( P = 0.022) . Conclusion:Omalizumab combined with conventional-dosage antihistamines could improve the clinical efficacy and reduce the recurrence rate in the treatment of chronic urticaria in children, with few adverse reactions.
4.Treatment of Renal Injury in Wilson Disease Based on Pathogenesis of Latent Toxin in Kidney Collaterals
Ke DIAO ; Wenming YANG ; Xiang LI ; Yue YANG ; Yulong YANG ; Zhihong RAO ; Shuzhen FANG ; Yufeng DING
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):132-139
Hepatolenticular degeneration, also known as Wilson disease (WD), is a hereditary disease caused by mutations in the ATP7B gene, leading to copper metabolism disorders. Gene mutations result in impaired synthesis of copper-binding protein, and abnormal excretion of copper through bile leads to pathological deposition of copper in various organs, ultimately causing multi-organ damage. The insidious onset and low specificity of symptoms make it difficult to diagnose this disease. On the basis of existing studies and the theory of latent toxin, this paper proposes that latent toxin in kidney collaterals is the main pathogenesis of renal injury in WD. It is pointed out that health Qi deficiency and latent pathogen are the premises for the occurrence of this disease, and the transformation of latent pathogen into toxin is the ley pathological process. Toxin damaging kidney collaterals is the ultimate result. According to the pathogenesis, this paper proposes the treatment principle of reinforcing healthy Qi and resolving toxin and treatment based on syndrome differentiation. This review provides new ideas for the diagnosis and treatment of renal injury in WD with traditional Chinese medicine.
5.Clinical Efficacy of Gandouling Decoction Combined with Neuromuscular Electrical Stimulation on Dysphagia in Wilson Disease with Combined Phlegm and Stasis
Zhihong RAO ; Wenming YANG ; Yue YANG ; Xiang LI ; Peng HUANG ; Yulong YANG ; Ke DIAO ; Shuzhen FANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):155-162
ObjectiveTo observe the clinical efficacy of Gandouling decoction combined with neuromuscular electrical stimulation (NMES) in the treatment of dysphagia in Wilson disease (WD) with combined phlegm and stasis. MethodsA total of 80 WD patients with dysphagia due to combined phlegm and stasis treated in the Department of Encephalopathy, the First Affiliated Hospital of Anhui University of Chinese Medicine were randomized into a control group and an observation group, with 40 patients in each group. In addition, 40 healthy volunteers were recruited as the normal group. The control group was treated with basic copper drainage combined with NMES. The observation group was treated with Gandouling Decoction on the basis of the therapy in the control group. Each course of treatment lasted for 8 days, and the patients were treated for a total of 4 courses. All subjects underwent video fluoroscopic swallowing study (VFSS) before and after treatment. During the examination, contrast agents with 4 different characters were used for the swallowing action, and the passing time was recorded. The TCM syndrome score, water swallow test score, standard swallowing assessment (SSA) score, and 24-h urinary copper level before and after treatment were analyzed. ResultsWhen performing VFSS, the passing time of contrast agents of different characters in the oral stage was longer in the WD group than in the normal group (P<0.01), while it had no significant difference in the pharyngeal stage. After treatment, the passing time in the oral stage shortened in the control and observation groups (P<0.01), and the observation group outperformed the control group (P<0.01). After treatment, both the control and observation groups showed declines in TCM syndrome score and SSA score (P<0.01) and an increase in water swallow test score (P<0.01), and the changes were more obvious in the observation group than in the control group (P<0.01). In addition, the treatment in the control and observation groups elevated the 24-h urinary copper level (P<0.01), and the elevation in the observation group was more obvious than that in the control group (P<0.01). Neither group showed obvious adverse reaction. ConclusionGandouling decoction combined with NMES can significantly ameliorate dysphagia in WD patients with the syndrome of combined phlegm and stasis regarding the TCM syndrome score, water swallow test score, and SSA score, demonstrating definite clinical efficacy and high safety.