1.Effects of Erythropoietin on Activation of Cas pase-3 in Newborn Rat Hippocampal CA1 Region Pest Hypoxic-ischemic Brain Damage
Fengzhan CHEN ; Yingmei XU ; Xirong GUO
Chinese Journal of Perinatal Medicine 2003;0(06):-
ObjectiveTo investigate the effects of erythro po ietin on prevention hypoxic-ischemic brain damage (HIBD) and activation of Casp ase-3 in Hippocampal CA1 region in newborn rats. Methods7 d Sprague-Dawley rats were divided into hypoxic-ischemic (HI) group (n=11), recombinant human erythropoietin (rhEPO) treated group (n=11), and sham-op erated control group (n=9). HIBD was established in both HI group and rhEPO treated group. The number of rats animals with spontaneous left-turn in two gro ups was counted respectively at subsequent different time: 0, 6, 12 and 24 h. Th e expression and distribution of activated Caspase-3 was detected by immunohist ochemistry analysis. The positive cells were calculated in hippocampal CA1 regio n of every groups.ResultsTwo rats in HI group and one in rhE PO treated group died from continuous convulsion during hypoxia. all survival ra ts in up two groups had spontaneously left-turn Compared with HI group, the r ate of spontaneous left-turn was dramatically lower in rhEPO treated group (HI group vs rhEPO treated group, 1/10 vs 6/9, P=0.0198) at 24 h after hypox ia. The positive stained cells were distributed dispersively in the brain of con trol group, and more intensively in the hippocampus and cerebral cortex of the o ther two groups. In CA1 region, the number of positive cells in HI group, was si gnificant higher than that in control group ( 41.38 ?2.09 vs 10.52?2.70 , P
2.Breviscapine Ameliorates Fear Extinction and Anxiety in BALB/cJ Mice
Wei LIANG ; Jing HUANG ; Shuya YANG ; Peng HUANG ; Jun CHEN ; Chen CHEN ; Qun YANG ; Fengzhan LI
Psychiatry Investigation 2023;20(3):205-211
Objective:
In this research, the influence of breviscapine on anxiety, fear elimination, and aggression and the potential mechanism was investigated.
Methods:
Anxiety and locomotion were analyzed by elevated plus maze and open field test in mice. Bussey-Saksida Mouse Touch Screen Chambers were used to perform fear conditioning. Territorial aggression was assessed by resident intruder test. Protein levels were evaluated by Western blot. Breviscapine improved fear-extinction learning in BALB/cJ mice.
Results:
Breviscapine at 20–100 mg/kg increased center cross number, total distance traveled, and velocity in a dose-dependent manner. On the other hand, breviscapine at 20–100 mg/kg decreased the immobility time in open field test. In addition, breviscapine at 20–100 mg/kg increased the ratio of time on the open arm, time on the distal parts of the open arm, and total distance traveled in elevated plus maze. Breviscapine at 100 mg/kg increased the average attack latency and decreased the number of attacks over the last 3 days of resident intruder test. In hippocampus, protein levels of postsynaptic density protein-95 and synaptophysin were elevated by breviscapine at these three doses.
Conclusion
The administration of breviscapine alleviates fear extinction, anxiety, and aggression, while increases locomotor in a dose-dependent manner, which might be associated with its influence on synaptic function.
3.A multicenter randomized phase III trial of domestic product of rmhTNF in the treatment of non-small cell lung cancer.
Qinghua ZHOU ; Xi YAN ; Li REN ; Lu LI ; Meng QIU ; Yuqiong YANG ; Deyun LUO ; Wenxia HUANG ; Luming LIU ; Zhen CHEN ; Zhiqiang MENG ; Yajie WANG ; Qiang FU ; Yang XU ; Linjun YANG ; Mingzhong LI ; Enxiao LI ; Yi LI ; Yu YAO ; Xiangfu ZHANG ; Xing LIU ; Huishan LU ; Maohong ZHANG ; Xiuwen WANG ; Xuejun YU ; Fengzhan QIN ; Rongsheng ZHENG ; Yuqing CHEN ; Minghong BI
Chinese Journal of Lung Cancer 2003;6(4):264-267
BACKGROUNDTo evaluate and compare the effects and toxicity of the domestic product of recombinant mutant human tumor necrosis factor (rmhTNF) combined with chemotherapy and chemotherapy alone in the treatment of patients with non-small cell lung cancer (NSCLC).
METHODSTwo hundred patients with NSCLC in multicenter were randomly devided into trial group (150 cases) and control group (50 cases). Chemotherapy with CAP regimen was given to the patients. Meanwhile, rmhTNF injection of 4×10⁶U/m² was also given from the 1st to 7th days, the 11th to 17th days on the chemotherapy cycle in the trial group. The control patients received chemotherapy alone. Twenty-one days were as a cycle, 2 cycles were given to each patient. The chemotherapeutic effects and toxicity were observed and compared between the two groups after the therapy.
RESULTSof the 200 patients, 5 cases in the trial group and 3 cases in the control group were out of the trial because of economy. The other 192 cases (145 cases in the trial group and 47 cases in the control group) could be analyzed and evaluated the clinical effects and toxicity. The response rate of chemotherapy was 46.90% (68/145) in the trial group and 17.02% (8/47) in the control group respectively ( P =0.001). The KPS scores was 86.02±9.74 in the trial group, and 80.14±9.10 in the control group ( P =0.025). No significant difference of degree III+IV toxicity was observed between the two groups ( P > 0.05). The side effects related to rmhTNF included slight fever, cold-like symptoms, pain and red and swelling in the injection site. All of them were mild and didn't need any treatment and disappeared after the therapy. There were no severe abnormality of liver and kidney function and ECG in both groups.
CONCLUSIONSThe results demonstrate that the effects of domestic rmhTNF combined with chemotherapy are remarkably higher than that of chemotherapy alone in the treatment of NSCLC. rmhTNF can increase the sensitivity to chemotherapy and improve the quality of life of the patients with slight toxicity. Hence rmhTNF is worth expanding clinical use.
4.Results of randomized, multicenter, double-blind phase III trial of rh-endostatin (YH-16) in treatment of advanced non-small cell lung cancer patients.
Jinwan WANG ; Yan SUN ; Yongyu LIU ; Qitao YU ; Yiping ZHANG ; Kai LI ; Yunzhong ZHU ; Qinghua ZHOU ; Mei HOU ; Zhongzhen GUAN ; Weilian LI ; Wu ZHUANG ; Donglin WANG ; Houjie LIANG ; Fengzhan QIN ; Huishan LU ; Xiaoqing LIU ; Hong SUN ; Yanjun ZHANG ; Jiejun WANG ; Suxia LUO ; Ruihe YANG ; Yuanrong TU ; Xiuwen WANG ; Shuping SONG ; Jingmin ZHOU ; Lifen YOU ; Jing WANG ; Chen YAO
Chinese Journal of Lung Cancer 2005;8(4):283-290
BACKGROUNDEndostar™ (rh-endostatin, YH-16) is a new recombinant human endostatin developed by Medgenn Bioengineering Co. Ltd., Yantai, Shandong, P.R.China. Pre-clinical study indicated that YH-16 could inhibit tumor endothelial cell proliferation, angiogenesis and tumor growth. Phase I and phase II studies revealed that YH-16 was effective as single agent with good tolerance in clinical use.The current study was to compare the response rate , median ti me to progression (TTP) ,clinical benefit andsafety in patients with advanced non-small cell lung cancer ( NSCLC) , who were treated with YH-16 plus vi-norelbine and cisplatin (NP) or placebo plus NP.
METHODSFour hundred and ninety-three histologically or cy-tologically confirmed stage IIIB and IV NSCLC patients , withlife expectancy > 3 months and ECOG perform-ance status 0-2 , were enrolledin a randomized ,double-blind ,placebo-controlled , multicenter trial ,either trialgroup : NP plus YH-16 (vinorelbine 25 mg/m² on day 1 and day 5 ,cisplatin 30mg/m² on days 2 to 4 , YH-167.5mg/m² on days 1 to 14) or control group : NP plus placebo (vinorelbine 25 mg/m² on day 1 and day 5 ,cis-platin 30 mg/m² on days 2 to 4 ,0.9% sodium-chloride 3 .75 ml on days 1 to 14) every 3 weeks for 2-6 cycles .The trial endpoints included response rate ,clinical benefit rate ,time to progression,quality of life and safety .
RESULTSOf 486 assessable patients , overall response rate was 35.4% in trial group and 19.5% in controlgroup (P=0 .0003) . The median TTP was 6 .3 months and 3 .6 months for trial group and control group respectively (P < 0 .001) . The clinical benefit rate was 73 .3 %in trial group and 64.0% in control group (P=0 .035) .In untreated patients of trial group and control group ,the response rate was 40 .0% and 23.9%(P=0 .003) ,the clinical benefit rate was 76 .5 % and 65 .0 % (P=0 .023) ,the median TTP was 6 .6 and 3 .7months (P=0 .0000) ,respectively .In pretreated patients of trial group and control group ,the response ratewas 23.9% and 8.5%(P=0 .034) ,the clinical benefit rate was 65.2% and 61.7%(P=0 .68) ,the median TTP was 5 .7 and 3 .2 months (P=0 .0002) ,respectively . The relief rate of clinical symptoms in trial groupwas higher than that of those in control group ,but no significance existed (P > 0 .05) . The score of quality oflife in trial group was significantly higher than that in control group (P=0 .0155) after treatment . There were no significant differences in incidence of hematologic and non-hematologic toxicity , moderate and severe sideeffects betweentrial group and control group .
CONCLUSIONSThe addition of YH-16 to NP regimen results in significantly and clinically meaningful improvement in response rate , median time to tumor progression,and clinical benefit rate compared with NP alone in advanced NSCLC patients . YH-16 in combination with chemotherapy shows a synergic activity and a favorable toxic profile in advanced cancer patients .