2.Brain Irradiation Enhances Permeability of cis-Diamminedichloroplatinum into Blood-Brain Barrier
Li-Kun CHEN ; Guo-Zhen LIU ; Guang-Chuan XU
Chinese Journal of Cancer 2001;20(3):291-293
Objective:This study was designed to investigate the effect of brain irradiation on blood-brain barrier (BBB) quantitatively by measuring cis-diamminedichloroplatinum (DDP) concentration in cerebrospinal fluid (CSF). Methods:Twenty-two patients with brain metastases from non-small cell lung cancer (NSCLC) received brain irradiation (BI). During BI, DDP (20mg/m2) was given before radiotherapy and after cumulative doses of 10gray, 20gray, 30gray, and 40gray separately 3h prior to CSF collection and blood collection. Ten NSCLC patients without brain metastases were given the same dose DDP and the CSF and blood samples were collected. Samples were assayed for DDP levels by using flameless atomic absorption spectrophotometry. Results:There were 20 patients with and 10 without brain metastases assessable. The average DDP level in CSF was 1.02mg/L for patients with brain metastases before BI, which was significantly higher than the average level of 0.33mg/L for patients without brain metastases. The DDP level in CSF increased with the dose of BI and reached the highest level after 30gray irradiation(2.36mg/L). Conclusion:The BBB of patients with brain metastases is impaired in a certain degree and DDP could reach its therapeutic level in the CSF. The BBB would gradually open following BI, and DDP would reach the highest level after a dose of 30gray whole brain irradiation. In the CSF of patients with normal BBB, the DDP concentration is much lower than the therapeutic level.
4.Expression of growth factors in rats with focal cerebral ischemia after transplantation of bone marrow stromal cells and endothelial progenitor cells
Xu-Ying HE ; Ru-Xiang XU ; Chuan-Zhi DUAN ; Xin ZHANG ; Yin-Qian CAI ; Zhen-Zhou CHEN
Chinese Journal of Neuromedicine 2012;11(8):775-779
Objective To observe the expression of growth factors (vascular endothelial growth factor [VEGF],stromal cell-derived factor-1 [SDF-1 ],basic fibroblast growth factor [bFGF],insulin-like growth factor [IGF-1],transforming growth factor-β [TGF-β],platelet-derived growth factor [PDGF],brain derived neurotrophic factor [BDNF],glial cell line-derived neurotrophic factor [GDNF] and nerve growth factor [NGF]) in rat ischemic brain tissues after intravenous implantation of bone marrow stromal cells (BMSCs) and/or endothelial progenitor cells (EPCs). Methods Healthy adult Wistar rats were randomly divided into 4 groups:vehicle group,BMSCs transplantation group,EPCs transplantation group and BMSCs combined with EPCs transplantation group (n=20). The rats were subjected to middle cerebral artery occlusion (MCAO),and 24 h after that,they were intravenously transplanted with either 3×106 BMSCs,EPCs,BMSCs/EPCs or 1 mL physiological saline.Seven d after transplantation,real time-PCR and Western blotting were employed to detect the expressions of VEGF,SDF-1,bFGF,IGF-1,TGF-β,PDGF-BB,BDNF,GDNF and NGF. Results The mRNA expressions of bFGF,VEGF and BNDF in the BMSCs/EPCs transplantation group were significantly higher as compared with those in the other groups (P<0.05).BMSCs transplantation group enjoyed the highest mRNA levels of NGF,GDNF and TGF-β among all the groups, significantly higher as compared with those in the other groups (P<0.05),followed by BMSCs/EPCs transplantation group.EPCs transplantation group enjoyed the highest mRNA levels of PDGF,IGF-1 and SDF-1,significantly higher as compared with those in the other groups (P< 0.05), followed by BMSCs/EPCs transplantation group. Conclusion BMSCs combined with EPCs implantation can promote the functional rehabilitation in rats after focal cerebral ischemia, which provides new way for improving the transplantation success rate.
5.Suppression of invasion and angiogenesis in human prostate cancer PC-3 cells by adenovirus-mediated co-transfer of PTEN and P27.
Zhen QIU ; Fei-lun CUI ; Chuan-Liang XU ; Zheng-qin GU ; Ying-hao SUN
National Journal of Andrology 2007;13(3):201-205
OBJECTIVETo investigate the effects of adenovirus-mediated PTEN and P27 on the invasion of PC-3 in vitro and angiogenesis, along with their synergy in the treatment of prostate cancer.
METHODSRecombinant adenovirus vectors of the human tumor suppressor genes PTEN and P27 were constructed. The replication-incompetent recombinant adenovirus was packaged and propagated in HEK293 cells. The viral titer was examined by plaque assay and the mRNA and protein expressions of PTEN and P27 in human prostate cancer cell line PC-3 infected with Ad-PTEN and Ad-P27 were determined by RT-PCR and Western blot respectively. The invasion of PC-3 cells in vitro was examined by Boyden chamber assay. MTT assay was used to testify the effect of supernatant from PC-3 infected with Ad-PTEN and Ad-P27 on the proliferation of endothelial cells ECV-304 and the CAM test was used to testify the effect of PTEN and P27 on angiogenesis. The difference between the combined therapy group and the single gene therapy group was also examined.
RESULTSThe viral titers of Ad-PTEN and Ad-P27 were 1.8 x 10(7) pfu/ml and 1.2 x 10(9) pfu/ml respectively. Adenovirus infection verified that the mRNA and protein expression of PTEN and P27 were steady in human PC-3 cells. The invasion in vitro of PC-3 cells was significantly inhibited by infection with Ad-PTEN or/and Ad-P27. CAM and MTT assays of ECV-304 confirmed that the supernatant from PC-3 cells infected with Ad-PTEN or/and Ad-P27 could inhibit the angiogenesis effectively. There was a significant difference between the combined therapy group and the single gene therapy group.
CONCLUSIONThe combined gene therapy of Ad-PTEN and Ad-P27 plays a synergistic role in inhibiting the invasiveness of PC-3 cells and angiogenesis.
Adenoviridae ; genetics ; Cell Line, Tumor ; Cyclin-Dependent Kinase Inhibitor p27 ; genetics ; Humans ; Male ; Neoplasm Invasiveness ; PTEN Phosphohydrolase ; genetics ; Prostatic Neoplasms ; blood supply ; pathology ; Transfection
6.Study on the T lymphocytes early activation and soluble tumor necrosis factor receptor in patients with aplastic anemia.
Rong SHEN ; Cong-gao XU ; Li-zhen LI ; Ti ZHANG ; Xue-mei QIN ; Jie LI ; Chuan-li ZHAO
Chinese Journal of Hematology 2004;25(4):209-212
OBJECTIVETo investigate the expression of T cell early activation marker (CD(69)) on peripheral CD(4)(+) and CD(8)(+) lymphocytes and serum levels of soluble tumor necrosis factor receptor 1 and 2 (sTNF-R1 and sTNF-R2) in serum and bone marrow in patients with aplastic anemia (AA) and their pathophysiological significance.
METHODSIn vitro activation of T lymphocytes was carried out by whole blood cell culture containing PHA (20 micro g/ml). The CD(69) expressions on CD(4)(+) and CD(8)(+) lymphocytes at 0 h and 4 h after PHA exposure were analyzed by two-color flow cytometry. The levels of sTNF-R1 and sTNF-R2 in serum and bone marrow were measured by ELISA.
RESULTSThe CD(69) expression rates of CD(4)(+) and of CD(8)(+) cells in SAA patients were (8.96 +/- 7.23)% and (10.67 +/- 7.58)%, respectively, and that of CD(8)(+) cells in CAA patients was (7.36 +/- 5.49)% before PHA stimulation. The CD(69) expression rates of CD(4)(+) and of CD(8)(+) cells in SAA patients were (71.73 +/- 11.91)% and (61.74 +/- 13.44)% and in CAA (59.35 +/- 10.15)% and (48.78 +/- 8.25)% respectively, and were significantly elevated after PHA stimulation. CD(69) expression on CD(4)(+) cells was much higher than that on CD(8)(+) cells after stimulation. The levels of the two sTNF-R (sTNF-R1 and sTNF-R2) in peripheral blood and bone marrow of SAA patients were elevated and in the bone marrow of CAA patients were also increased. The serum levels of sTNF-R2 were positively related to the CD(69) expression rates of CD(8)(+) cells before PHA stimulation.
CONCLUSIONIncreased early activation and activated potentials of T lymphocytes, along with abnormally elevated immunologically active molecules might play a major role in the pathogenesis of AA.
Adolescent ; Adult ; Aged ; Anemia, Aplastic ; immunology ; Antigens, CD ; blood ; Antigens, Differentiation, T-Lymphocyte ; blood ; CD4-Positive T-Lymphocytes ; chemistry ; CD8-Positive T-Lymphocytes ; chemistry ; Child ; Female ; Humans ; Lectins, C-Type ; Male ; Middle Aged ; Receptors, Tumor Necrosis Factor ; blood ; Receptors, Tumor Necrosis Factor, Type I ; Receptors, Tumor Necrosis Factor, Type II
7.Nadaplatin or cisplatin combined with paclitaxol in treatment for non-small cell lung cancer: a randomized controlled study.
Li-Kun CHEN ; Guang-Chuan XU ; Zhong-Zhen GUAN ; Ying HANG ; Qun-Ying YANG
Chinese Journal of Oncology 2007;29(6):437-440
OBJECTIVETo investigate the therapeutic effect, long term survival and side effect on NSCLC patients treated with nadaplatin combined with paclitaxol and cisplatin combined with paclitaxol.
METHODSNSCLC patients with stage IIIB or IV were randomized into two groups in this prospective clinical study. TN group: nadaplatin 30 mg/m2 dl-3, paclitaxol 175 mg/m2 dl, repeated every 4 weeks. TP group: DDP 30 mg/m2 dl-3, paclitaxol 175 mg/m2 dl, repeated every 4 weeks.
RESULTSSixty patients were enrolled and 57 were evaluable with 30 in TN group and 27 in TP group. The overall response rate were 43.3% vs. 48.1% (P = 0.716), and the disease control rate were 86.7% vs. 88.8% in TN and TP group (P = 0.799), respectively. The median survival time was 14.3 vs. 13.0 months, and the 1- and 2-year survival rate was 62.5% vs. 59.1%, 0% vs. 5.8% in TN and TP group (P = 0.839), respectively. The rates of neutropenia and thrombocytopenia were similar in TN and TP groups whereas more patients in TP group than in TN group suffered from anemia (38.5% vs. 17.5%, P = 0.001), nausea and vomiting (82.6% vs. 35.6%, P = 0.000), fatigue (35.9% vs. 14.1%, P = 0.000) and peripheral neurotoxicity (50.0% vs. 21.9%, calculated by case, P = 0.023).
CONCLUSIONNadaplatin combined with paclitaxol is an effective treatment regimen for NSCLC patients. When compared with similar regimen with cisplatin, the response rate and survival were similar; however, nadaplatin regimen shows some superiority as regards some treatment side effect.
Adult ; Aged ; Anemia ; chemically induced ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Cisplatin ; administration & dosage ; adverse effects ; Female ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Neutropenia ; chemically induced ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; Paclitaxel ; administration & dosage ; adverse effects ; Prospective Studies ; Remission Induction ; Survival Analysis ; Thrombocytopenia ; chemically induced ; Treatment Outcome
8.PTEN and p27Kip1 have a cooperative role on inhibition proliferation, modulation of cell cycle and inducing apoptosis in prostate cancer PC-3 cell.
Zhen QIU ; Ying-hao SUN ; Chuan-liang XU ; Yuan-tian WANG ; Zheng-qin GU ; Yi LIU
Chinese Journal of Surgery 2004;42(10):600-603
OBJECTIVESTo investigate whether the human PC-3 cell infected with recombinant Ad-PTEN and Ad-p27Kip1 can steadily produce PTEN and p27Kip1 protein and change the biologic behaviors such as cell proliferation, cell cycle and apoptosis. The synergistic effect of PTEN and p27Kip1 on the therapy for prostate cancer has also been investigated.
METHODSWe constructed recombinant adenovirus vector of human tumor suppressor gene PTEN and p27Kip1. The viral titer was examined by plaque assay and the mRNA and protein expressions of PTEN and p27Kip1 in human prostate cancer cell line PC-3 infected with Ad-PTEN and Ad-p27Kip1 were determined by RT-PCR and Western blot respectively. MTT assay was used to determine the effect of PTEN and p27Kip1 on growth and proliferation of PC-3 cell; the change of cell cycle and apoptosis was examined by flow cytometry, and to compare between the combined therapy group and single gene therapy group.
RESULTSThe viral titers of Ad-PTEN and Ad-p27Kip1 were 1.8 x 10(7) pfu/ml and 1.2 x 10(9) pfu/ml respectively. After infected by adenovirus, it had been verified that the mRNA and protein expression of PTEN and p27Kip1 were steady in human PC-3 cell. Ad-PTEN and Ad-p27 Kip1 inhibited the growth and proliferation of PC-3 cells. The progression of cell cycle of PC-3 cell was arrested in G(0)-G(1) phase, meanwhile the apoptosis rate of PC-3 was also affected after Ad-PTEN or/and Ad-p27 Kip1 infected. There was significant difference between combined therapy group and single gene therapy group.
CONCLUSIONThe recombinant Ad-PTEN and Ad-p27Kip1 vector were constructed successfully and the expression of specific PTEN and p27Kip1 was high, steadily in PC-3 cell line. These results suggested that combination of PTEN with p27Kip1 has an application value in treatment of prostate cancer in future.
Adenoviridae ; genetics ; Apoptosis ; drug effects ; Cell Division ; drug effects ; Cell Line, Tumor ; Chromosomes, Human, Pair 10 ; genetics ; Cyclin-Dependent Kinase Inhibitor p27 ; Gene Deletion ; Genetic Therapy ; Genetic Vectors ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; pharmacology ; Male ; PTEN Phosphohydrolase ; genetics ; pharmacology ; Prostatic Neoplasms ; genetics ; physiopathology ; therapy ; Transfection
9.Application of computer assisted navigation in the treatment of unilateral zygomatic complex fractures.
Tao GAO ; Jian-ming FU ; Yong-zhen LOU ; Xiao-chuan XU ; Yong WANG
Chinese Journal of Stomatology 2012;47(4):238-240
OBJECTIVETo evaluate the effect of computer assisted navigation system in the treatment of unilateral zygomatic complex fractures.
METHODSFive patients with unilateral zygomatic complex fractures were included in this study.Preoperative design, intraoperative real-time navigation and postoperative evaluation with chromatogram were executed in the unaffected and affected side.
RESULTSUsing computer assisted navigation system, the position and direction of the affected side of the unilateral zygomatic complex fracture were confirmed and shown real-time on the screen. The global maximal deviation was less than 2 mm between the affected side and the mirror side of the healthy side with chromatogram.
CONCLUSIONSComputer assisted navigation system can instruct the treatment of unilateral zygomatic complex fractures effectively. The global comparison with chromatogram is more objective for the unilateral zygomatic complex fractures.
Adult ; Female ; Humans ; Male ; Surgery, Computer-Assisted ; methods ; Tomography, X-Ray Computed ; Young Adult ; Zygomatic Fractures ; diagnostic imaging ; surgery
10.Pharmacokinetics of patchouli alcohol and patchouli alcohol in patchouli oil after iv administrated to rats.
Fu-chuan YANG ; Li-zhen XU ; Zhong-mei ZOU ; Shi-lin YANG
Acta Pharmaceutica Sinica 2004;39(9):726-729
AIMTo develop a capillary gas chromatographic method for the determination and pharmacokinetic study of patchouli alcohol in rat plasma after iv administration.
METHODSThe drug was extracted with ethyl acetate. Eugenol was used as internal standard. The separation was carried out on a HP-5MS quartz capillary column, with high-purity nitrogen as carrier gas and flame ionization detector (FID) as detector. The column temperature was maintained at 80 degrees C for 1 min and then programmed to 200 degrees C at a rate of 15 degrees C x min(-1); it was held at 200 degrees C for 1 min, and then programmed to 290 degrees C at a rate of 60 degrees C x min(-1); the final temperature was held for 1 min. The temperature of both injector and detector was set at 290 degrees C.
RESULTSThe standard curve was linear from 25 to 5 000 microg x L(-1) in rat plasma. The recovery of this method was from 90.0% to 110.0% with satisfactory relative standard deviation (RSD) less than 10.0%. The pharmacokinetic parameters demonstrated patchouli alcohol were consistent with the two-compartment open model and showed linear pharmacokinetics. The T1/2beta, AUC and MRT of patchouli alcohol in patchouli oil were all higher than that of patchouli alcohol.
CONCLUSIONThis method is quick, precise and reliable. The pharmacokinetics of patchouli alcohol is different from that of patchouli alcohol in patchouli oil.
Animals ; Area Under Curve ; Injections, Intravenous ; Lamiaceae ; chemistry ; Male ; Oils, Volatile ; chemistry ; isolation & purification ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Sesquiterpenes ; blood ; isolation & purification ; pharmacokinetics