1.THE EXPERIMENTAL STUDY ON THE CELL APOPTOSIS AND EXPRESSION OF BCL-2 PROTEIN IN INTRACEREBRAL HEMORRHAGE IN MODEL OF RATS
Gang BAO ; Ning GUO ; Zhonglin ZHANG ; Wei CHEN ; Dehu BAO
Journal of Pharmaceutical Analysis 2006;18(1):61-64
Otjective To study whether there is the apoptosis of neural cells and the expressionof Bcl-2 protein in intracerebral hemorrhage (ICH) in model of rats, for the further understanding the mechanism of the delayed damage of the neural cells around the hematoma after ICH. Methods Fifty SD rats were randomly divided into 5 groups, ten in each. With the Group A as the control, the rest 40 were used to set up intracerebral hemorrhage model. The brains were taken out at 12th, 24th, 48th and 72th hours, respectively. Apoptosis cells were detected with terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL), and the expression of Bcl-2 protein was detected with immunochemical stainging methed (SP). Results In the control group, no apoptosis cells and Bcl-2protein were detected. In rest groups, the apoptosis cells and Bcl-2 protein were expressed in different degree.Apoptosis rates verified and corresponded with the time after ICH, with the peak at 48th -72th hour after hemorrhage.The peak rate of apoptosis cells was (24. 50± 2.69)% and Bcl-2 protein expression was (20. 76 ± 1.97)% . There was significant difference between the experimental groups and control (P<0.05), and no linear relationship between the apoptosis rate and the expression of Bcl-2 protein. Conclusion Apoptosis may be an important factor in the secondary trauma of ICH. There is a time leg after hemorrhage. All this is instructive to clinical treatment in time. Bcl-2 protein keeps increasing in a certain time after hemorrhage, but not synchronize with the cell apoptosis. This indicates that bcl-2 has the effect to reduce the apoptosis of neural cells.
2.Recent advances in study of endothelium-dependent hyperpolarizing factor
Yifei FAN ; Dehu KONG ; Zhiwu CHEN ; Shan GAO
Chinese Journal of Clinical Pharmacology and Therapeutics 2004;0(10):-
Besides cyclooxygenase and nitric oxide synthase, another distinct endothelial pathway, endothelium-dependent hyperpolarization factor (EDHF), is involved in relaxation of the vascular smooth muscle cells. EDHF has been demonstrated unequivocally in various blood vessels from different species, including human, and is likely to play an important role in cardiovascular physiology and pharmacology.
3.Effects of total flavones of rhododendra (TFR) on bioelectricity of ventricular myocytes in guinea pig
Yifei FAN ; Dehu KONG ; Zhiwu CHEN ; Shan GAO
Chinese Pharmacological Bulletin 1986;0(06):-
Aim To study the effect of total flavones of Rhododendra(TFR)on bioelectricity changes of ventricular myocytes in guinea pigs. Methods Conventional microelectrode technique was used to record action potentials (AP) , resting potentials (RP) and effective refractory period (ERP). Results TFR 25,50 mg?L-1 decreased the action potential duration at 50%,90% repolarization (APD50,APD90) while TFR 100,200,400 mg?L-1 prolonged APD50 and APD90Significantlg. TFR 200,400 mg?L-1markedly decreased action potentials amplitude (APA) and velocity maximum of depolarization (Vmax). TFR 400 mg?L-1decreased resting potential. TFR 200 mg?L-1 prolonged ERP. Conclusion TFR may antagonize Ca2+ inward flow at lower concentration and block K+ inward flow at higher concentration.
4.Influence of CD133+expression on patients' survival and resistance of CD133+cells to anti-tumor reagents in gastric cancer
Dehu CHEN ; Ruiqi LU ; Xiaochun NI ; Jugang WU ; Shoulian WANG ; Bojian JIANG ; Jiwei YU
Asian Pacific Journal of Tropical Biomedicine 2015;(12):996-1004
Objective: To investigate the influence of CD133+expression on patients' survival and resistance of CD133+cells to anti-tumor agents in gastric cancer (GC).
Methods: Influence of CD133 expression on prognosis was analyzed employing sam-ples from patients with GC. GC cell lines were utilized to separate CD133+and CD133?subpopulations by immunomagnetic separation and to analyze the biological features of two subpopulations in vitro and in vivo, especially in resistant to anti-tumor reagents and its apoptotic mechanism.
Results: The lower CD133+group showed a significantly better survival compared with the higher CD133+group. The highest content of CD133+subpopulations for KATO-III cells had stronger proliferative ability than CD133?subpopulations. A single CD133+cell was capable of generating new cell colony and the tumorigenicity rate in nude mice was 100% for CD133+ clonal spheres or for CD133+ cells, but 0% for CD133? cells. Furthermore, the higher expression levels of Oct-4, Sox-2, Musashi-1 and ABCG2 in CD133+ clonal spheres were identified compared with CD133+ cells or CD133? cells. Under the treatment of anti-tumor reagents, CD133+ cells had lower suppression rates compared with CD133? cells while lower level of Bcl-2 and higher level of Bax were found in CD133+cells compared with CD133?cells.
Conclusions: The patients with lower CD133+expression had a better survival. Enriched CD133+ cells in clonal sphere shared the ability to be self-renewable, proliferative, tumorigenic and resistant to anti-tumor agents as probably regulated by Bcl-2 and Bax.
5.Experimental study of human bone marrow mesenchymal stem cells on regulating the biological characteristics of gastric cancer cells.
Jia WANG ; Jiwei YU ; Jugang WU ; Shoulian WANG ; Dehu CHEN ; Fan YANG ; Bao HUA ; Xiaolong XI ; Shuzheng SONG ; Linhai ZHENG ; Bojian JIANG
Chinese Journal of Gastrointestinal Surgery 2015;18(2):159-165
OBJECTIVETo investigate the regulatory mechanism of bone marrow mesenchymal stem cells(BMSC) on the biological profiles of KATO-III( cell lines of gastric cancer.
METHODSTranswell cubicle was applied to build the co-cultured model in non-contact style. The differences of cell proliferation and the resistance of anti-tumour drug (5-fluoropyrimidinedione, 5-FU and Cisplatin, CDDP) between co-cultured group and single cultured group were evaluated by Cell Counting Kit 8-assay(CCK-8). The invasion ability was detected by Transwell assay. The expressions of stem cell makers, apoptosis-related factors and epithelium-mesenchymal transition (EMT)-related factors were detected by RT-PCR.
RESULTSThe proliferation ability of KATO-III( cells in co-cultured group was significantly stronger than that in single cultured group. The growth rate of KATO-III( cells in co-cultured group was significantly higher than that in single cultured group after treatment of 5-FU and CDDP(P<0.05). The mRNA expression level of Bcl-2 was significantly higher in co-cultured group KATO-III( cells(P<0.05), while the mRNA expression level of Bax was significantly lower in co-cultured group KATO-III( cells(P<0.05) in comparison with those in single cultured group. As compared to KATO-III( cells in single cultured group, the number of infiltrating-membrane cells was significantly higher (37.33±5.22 vs 14.56±2.54, P<0.01) in co-cultured group, and the mRNA expression levels of Snail and N-cadherin were significantly higher in co-cultured group KATO-III( cells (P<0.05), while the mRNA expression level of E-cadherin was significantly lower in co-cultured group KATO-III( cells (P<0.05). The expressions of CD133, Nanog and Sox-2 mRNA in co-cultured group KATO-III( cells were significantly higher than those in single cultured group(P<0.05).
CONCLUSIONSIn co-cultured model sharing non-contact style, BMSC can enhance such properties of KATO-III( gastric cancer cells as the proliferation, the invasion and the chemoresistance. Furthermore, the regulatory mechanisms may be related to the increase of the expressions of some stem cell markers in gastric cancer cells.
Antineoplastic Agents ; Apoptosis ; Bone Marrow Cells ; Cadherins ; Cell Line, Tumor ; Cell Proliferation ; Cisplatin ; Coculture Techniques ; Epithelial-Mesenchymal Transition ; Fluorouracil ; Humans ; RNA, Messenger ; Stem Cells ; Stomach Neoplasms
6.Modified docetaxel regimen for prostate cancer patients who got poor tolerance to chemotherapy
Linjun HU ; Changling LI ; Jianzhong SHOU ; Jun TIAN ; Dong WANG ; Zhendong XIAO ; Zejun XIAO ; Xingang BI ; Kaopeng GUAN ; Hongsong BAI ; Chengming XIE ; Xingli SHAN ; Dehu LU ; Xiang AO ; Yonghai CHEN
Chinese Journal of Urology 2017;38(8):615-618
Objective To evaluate the efficacy and safety of the modified docetaxel plus prednisone scheme for the metastatic castration resistant prostate cancer patients who got poor tolerance to chemotherapy.Method The clinical data of 50 metastatic castration resistant prostate cancer who received docetaxel + prednisone chemotherapy from March 2010 to October 2015 were analyzed retrospectively.23 cases received the modified DP regimen (modified group),27 cases received the standard DP regimen (standard group).The median age of the modified group and the standard group were 69 years (47-80 years) and 63 years (52-77 years) (P =0.005).There were 19 and 24 cases with pain in modified group and standard group respectively;10 and 19 cases with lymph node metastasis respectively;3 and 4 cases of visceral metastasis respectively;all of the 50 patients were complicated with bone metastasis.For the pathological Gleason score,there were 7 cases scored ≤7 points,13 cases scored ≥ 8 points and 3 cases unscored in the modified group;7 cases scored ≤7 points,15 cases scored ≥8 points and 5 cases unscored in standard group.There was no significant difference of the pain,metastasis,and Gleason score between the two groups (P > 0.05).Progression free survival (PFS),overall survival (OS)and adverse events were analyzed using Kaplan-Meier curves,and the differences were assessed using the log-rank test.Results In the modified group and standard group,the median follow-up times were 11.0 months and 14.0 months respectively,the median chemotherapy cycles were 4.5 cycles and 5.0 cycles respectively;OS were 18.0 months and 27.5 months respectively (P =0.746).The PFS of the two groups were 6.0 months and 5.2 months,respectively (P =0.822).The PSA response were 13 cases and 17 cases in the modified group and standard group respectively (P =0.615),and the pain response were 8 cases and 7 cases (P =0.927),grade 3 to 4 adverse events were 3 cases and 14 cases (P =0.003).The main adverse events were blood toxicity,neutrophils,gastrointestinal reaction,edema,fatigue and oral mucositis etc.Conclusions Compared with the standard DP scheme,the modified DP scheme had no significant difference in OS,PFS,pain response rate and PSA response rate,while the incidence of grade 3 to 4 adverse events was significantly reduced.Modified DP scheme may be a better choice for patients with metastatic castration resistant prostate cancer who get poor tolerance to chemotherapy.
7.Docetaxel tolerance to metastatic castration-resistant prostate cancer and the correlation between dose and prognosis
Linjun HU ; Changling LI ; Jianzhong SHOU ; Jun TIAN ; Dong WANG ; Zhendong XIAO ; Zejun XIAO ; Xingang BI ; Kaopeng GUAN ; Hongsong BAI ; Chengming XIE ; Xingli SHAN ; Dehu LU ; Xiang AO ; Yonghai CHEN
Chinese Journal of Urology 2019;40(1):31-36
Objective To investigate the dose of docetaxel appropriate for patients with metastatic castration-resistant prostate cancer and its affects to the prognosis.Methods A retrospective analysis was performed on the clinical data of 75 patients with metastatic castration-resistant prostate cancer admitted from March 2010 to July 2016 who received docetaxel combined with prednisone chemotherapy.The patients were divided into the low-dose group (n =43,docetaxel < 65 mg/m2),the middle-dose group (n =21,docetaxel 65-70 mg/m2) and the high-dose group (n =11,docetaxel > 70 mg/m2).The median age in the low-dose group,middle-dose group and high-dose group was 67 (53-80),66 (56-78) and 61 (47-76) years old,respectively.Among 75 patients with bone metastasis,2 patients had no evidence of bone metastasis in the low-dose group.The lymph node metastasis was found in 26,13 and 6 cases in each group,respectively.And visceral and other metastasis were founded in 11,4 and 2 cases,respectively.The Gleason score in the low-dose group was≤7 points in 15 cases,≥8 points in 22 cases and no score in 6 cases.The Gleason score inthe middle-dose group was ≤7 points in 4 cases,≥8 points in 13 cases and no score in 4 cases.The Gleason score in the high-dose group was ≤7 points in 3 cases,≥8 points in 5 cases and no score in 3 cases.The number of patients with pain in the low-dose group,middle-dose group and high-dose group was 36,12 and 9,respectively,there were no significant differences in the above indicators (P > 0.05),except age,which showed relatively more aged patients in the low-dose group,(P =0.045).Kaplan-Meier method was used to compare the overall survival (OS),progression-free survival (PFS) and the incidence of ≥CTCAE-4 grade 3 adverse reactions between the two groups.The Cox regression model was adopted to analyzed the factors that might affect patient prognosis,including the effective time of first-line endocrine therapy,hemoglobin level,ECOG score,pain score,number of cycles of chemotherapy,age,dose of docetaxel and alkaline phosphatase (ALP).Kaplan-Meier method was used to analyze the effect of dose of docetaxel on the prognosis,and log-rank method was used to test the significance of the results.Results The median OS was respectively 24.1,18.5 and 23.5 months in the low-dose group,middle-dose group and high-dose group,respectively.The median PFS was 5.3 months in all three groups,which didn't show statistically significant differences.The incidence of grade 3/4 adverse reactions in the low-dose group,middle-dose group and high-dose group was 15 cases (34.9%),8 cases (38.1%) and 5 cases (45.5%) respectively.It showed an increasing trend,but no statistically significant difference.The single factors related to OS mainly include the effective time of first-line endocrine therapy,hemoglobin level,ECOG score,pain score,number of cycles of chemotherapy,there was no significant correlation with age,docetaxel dose,ALP and PSA value.Conclusions It is common to receive lower doses of docetaxel in clinical practice for patients with metastatic castration-resistant prostate cancer in China.The efficacy of low-dose docetaxel is similar to that of high doses (standard dosage).There was no significant correlation between the OS and the actual dose of docetaxel in the tolerable range.