Table of Content

Volume 17 Issue 5
26 May 2012

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Problems in the recruitment and management of trial subjects for phase I clinical trials in China

ZHANG Zheng-fu, SHEN Yu-hong, LI Zheng-qi

2012, 17(5):  481-484. 

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Recruitment of trial subjects is an important part to affect the quality for phase I clinical trial. This paper reviews many problems in the recruitment and management of trial subjects for phase I clinical trial at present, and explores appropriate measures in order to protect the rights, benefits and safety of trial subjects, improve the level and quality of phase I clinical trials in China.

Effect and mechanism of acute and chronic vagus nerve stimulation on heroin relapse in rats

ZHU Hua-qiang, YU Jing, CHEN Wei-sheng, TANG Shuai-en, FU Dan, LIU Hui-feng, ZHOU Wen-hua

2012, 17(5):  485-490. 

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AIM: To investigate the therapeutic effect of vagus nerve stimulation(VNS)on heroin relapse in rats and its possible mechanism.METHODS: The SD rats were trained to self-administer heroin by nose-poking in a daily 4 hours session for consecutive 14 days,to establish an animal model of compulsive drug-seeking and drug-taking. The electrode was implanted into the left vagus nerve and followed by several days recovery,all rats were then trained to 10 daily extinction session and divided into 3 groups:sham control,acute VNS and chronic VNS. The rats in the chronic VNS group were given VNS 2 hours before all extinction and relapse test session,while the rats in the acute VNS group were given VNS 2 hours only before relapse test session. Cue-induced heroin relapse test were measured 24 hours after last extinction session.After relapse testing,c-Fos levels in brain regions of rats were measured by immunofluorescence.RESULTS:Compared with sham group,the active nose-poking of acute VNS and chronic VNS were all significantly decreased (P<0.01). The immunofluorescence results showed that the numbers of c-Fos immuno-positive neurons in central amygdala (Ce) were significantly decreased after acute VNS (P<0.05) or chronic VNS (P<0.01) compared with sham control. However,the numbers of c-Fos immuno-positive neurons in the infralimbic cortex (IL) were significantly increased in both acute VNS and chronic VNS group(P<0.05).CONCLUSION: Acute VNS or chronic VNS may inhibit cue-induced heroin relapse of rats,the possible mechanism might be associate with the alteration of neuron activity in Ce and IL.

In vivo tumor-inhibitory effects of Agkistrodon halys venom antitumor component I on tumor-bearing mice with human gastric cancer cell SGC-7901

LU Lin-ming, ZHOU Jue, ZHANG Gen-bao

2012, 17(5):  491-496. 

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AIM: To investigate the in vivo tumor-inhibitory effects of snake venom antitumor component I(AHVAC-I) from Agkistrodon halys living in south Anhui province on the tumor-bearing mice with human gastric cancer cell SGC-7901 and activities of the cell proliferation as well as its mechanisms.METHODS: Cell suspension of 0.1 mL was obtained from the well-grown cell SGC-7901 by cell count of 1×10⁷/mL and incubated subcutaneously into the nude mice via right axillary fossa. After tumor formation, the mice were randomized into groups of model controls, positive paclitaxiel controls, AHVAC-I of low, medium and low dosage in which the animals were managed with AHVAC-I every other day for 5 consecutive times. The tumor growth and its sizes were observed and measured for mapping the growth curve and calculating the inhibitory rate. HE staining was performed to examine the morphologic change of tumors, and streptavidin-peroxidase (SP) immunohistochemical technique was used to detect the proliferation index of Ki-67 and TUNEL method was for examination of the apoptotic index.RESULTS:AHVAC-I at dose of 1.0 mg/kg produced inhibitory effects on SGC-7901 with inhibition rate of 42.2%, and inhibitory effects were significant at dose of 3.0 mg/kg with a rate of 78.5%. Ki-67 protein was reduced in the positive cells of treatment groups, leading to increased apoptosis of tumor cells.CONCLUSION: AHVAC-I can effectively inhibit the in vivo growth of gastric cell SGC-7901 in nude mice, and the possible mechanisms may be associated with the induced apoptosis and suppressed proliferation of the gastric tumor cells.

Effect of oligomeric grape seed proanthocyanidins on prevention isoproterenol induced cardiomyocytes hypertrophy

GAO Shan, HUANG Chun-xia, HUANG Ling-ling, YU Ting-ting, WANG Xing-hui, ZHANG Ye

2012, 17(5):  497-501. 

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AIM: To investigate the effect of oligomeric grape seed proanthocyanidins (GSP) on neonatal cardiomyocytes hypertrophy induced by isoproterenol (Iso).METHODS: Hypertrophy in cultured neonatal rat cardiac myocytes was induced by Iso. Total protein content was measured by BCA method; reactive oxygen species (ROS) were detected by flow cytometry; colorimetric method was employed to measured MDA content and SOD antivity.RESULTS:1×10^-5 mol/L Iso can activate β-AR completely and induce cardiomyocytes hypertrophy markedly. GSP therapy potently inhibited the increase of protein content, ROS generation and MDA content, inhibited the decrease of SOD activity with a dose-dependent manner.CONCLUSION: GSP possess protective effect against Iso induced cardiomyocytes hypertrophy, this may be related to reducing the ROS generation and oxidative stress level, at least in part.

Renal protective effect of sesamin in spontaneously hypertensive rats

DU Shao-ling, YANG Jie-ren, ZHANG Jun-xiu, LI Wen-xing

2012, 17(5):  502-507. 

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AIM: To evaluate the protective effect of sesamin on kidney damage in spontaneously hypertensive rats (SHR).METHODS: Sesamin(160,80,40 mg/kg)was administrated to SHR intragastrically once a day for 16 weeks. The blood pressure (BP) before and after administration were measured. After the last BP measuring, rats were anesthetized. 5 mL of blood sample were collected from abdominal aorta for the detecting of blood urea nitrogen (BUN) and creatinine(Cr) concentration. The kidney was excised for HE and MASSON staining to observe the changes of pathology and collagen fibers. Glomerular ultrastructure was observed by transmission electron microscopy.RESULTS:After the administration of sesamin for 16 weeks, the BP,Cr and BUN were lowered significantly. Pathological changes such as glomerular distortion, atrophy, sclerosis and hyalinization were improved. There was no significant expansion in mesangial area, no thickening in basement membrane and no significant cell fusion of podocytes. Renal tubular cell injury and interstitial fibrosis was significantly reduced.CONCLUSION: Sesamin can improve the renal function of SHR kidneys and protect kidneys from damage.

Experimental study on the effects of amiodarone on thyroid function and morphology in SD rats

JIANG Li-qin, WANG Zhi-gang, JI Yu-zhen

2012, 17(5):  508-512. 

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AIM: To investigate the effects of amiodarone on thyroid hormone secretion, signaling protein expression and morphology.METHODS: SD rats were divided into low-dose group (50 mg·kg^-1·d^-1) and high-dose group (200 mg·kg^-1·d^-1), feeding amiodarone for 14 weeks respectively. Free triiodothyronine (FT3), free thyroxine (FT4), total protein (TP), glycerin three greases (TG) were measured from SD rats' blood. Analysis of the expression for Bcl-2 protein and the activity of Caspase-3 protein were observed from SD rats' thyroid gland, and pathology examination were performed.RESULTS:After amiodarone medication, SD rats' appearance were hair removal, sluggish, weight loss, serum total protein decreased, FT3 decreased with amiodarone's dose increasing, FT4 in the low-dose group slightly increased, while in the high-dose group decreased. The positive expression of Bcl-2 in low-dose group and high-dose group, while negative expression of Caspase-3 in all of them(P>0.05).CONCLUSION: Effects of amiodarone on SD rats' thyroid were manifested as thyroid hormone metabolism were inhibited with the dose increasing, and the expression of Bcl-2 protein were enhanced, while the apoptosis by Caspase-3 induced had not been initial.

Regulating effects of Ginseng Polysauharides on balance between Thromboxance B₂ and Prostacyclin F_1α during hepatic ischemia/reperfusion injury in rabbits

ZHENG Yan-rong , CHEN Liang, YAN Wang-xin, CHEN Hai-e, MA Ying-chun, CHEN Dan, WANG Wan-tie

2012, 17(5):  513-516. 

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AIM: To explore the influence of Ginseng Polysauharides on balance between Thromboxance B₂ and Prostacyclin F_1α during hepatic ischemia/reperfusion injury (HIRI) in rabbits.METHODS: Thirty rabbits were randomly divided into 3 groups:control group (Group C),ischemia/ reperfusion group (Group IR) and Ginseng Polysauharides group (Group GP). Thromboxance B₂(TXB₂), ProstacyclinF_1α(PGF_1α), TXB₂/PGF_1α and ALT of the three groups were measured in 10 minutes before ischemia, ischemia of 45 minutes and reperfusion after 45 minutes respectively, and the hepatocellular morphological changes were observed during HIRI in the electronic microscope.RESULTS: In Group IR, the content of TXB₂ in the plasma was obviously higher than that in Group C in the corresponding time point; the content of PGF_1α declined notably 45 minutes after reperfusion compared with 10 minutes before ischimia, TXB₂/PGF_1α increased significantly,the ultrastructure of hepatic cell was obviously abnormal. In Group GP, the content of TXB₂ declined a little and the PGF_1α increased compared with those in Group IR during reperfusion 45 minutes.TXB₂/PGF_1α were significantly higher than the ratio of Group IR, especially 45 minutes after reperfusion. The abnormal morphological changes of liver cells was ameliorated remarkably too during HIRI.CONCLUSION: Ginseng Polysauharides can regulate imbalance between TXB₂ and PGF_1α, and improve hepatic microcirculation, thus can prevent the hepatocell from the injury caused by hepatic ischemia reperfusion.

The impact of propofol pretreatment on hypoxia/reoxygenation in cultured hippocampal neurons metallothionein-3 protein expression

HE Jian-guo, HUANG Chang-shun, JIANG Juan, HU Ye, CAO Gang, LIU Zhen-wei

2012, 17(5):  517-520. 

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AIM: To observe the effects of propofol on caltured hippocampal neurons hypoxia and reoxygenation damage response and metallothionein protein-3(metllothionein-3,MT-3) in which the role.METHODS: Hippocampal neuron cells were cultured for 7-10 days for use. Hypoxic conditions were attained 4 h and reoxygenation was achieved with normoxia conditions for another 24 h. The expression level of metallothionein-3 (MT-3) was detected by Western blot; By using MT-3 specific siRNA, MT-3 was silenced and the effect of propofol on cell survival rate was evaluated by MTT method .RESULTS:In cultured hippocampal neuron cells, pretreatment with different concentrations of propofol (50, 150, 250 mol/L) for 24 h enhanced MT-3 expression level after hypoxia/reoxygenation. When MT-3 expression was silenced by specific siRNA, propofol failed to improve hippocampal neuron cell survival rate.CONCLUSION: MT-3 exerts hippocampal neuron protective effect, which may possibly be mediated by the upreguation of MT-3 expression.

Drug-drug interaction between irbesartan and hydrochlorothiazide in renal hypertensive rats: A case study of dose optimization

HUANG Xiao-hui, WANG Qin, WANG Kun, HUANG Ji-han, QIU Fu-rong, TANG Hai-qin, LI Jun

2012, 17(5):  521-528. 

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AIM: To quantitatively study the dose optimization of drug-drug interaction of irbesartan and hydrochlorothiazide in renal hypertensive rats using weighted modification model and nonlinear mixed effect model.METHODS: Renal hypertensive rats were randomly divided into six groups with different dose combination according to the experimental design of weighted modification method. The rates of change of systolic and diastolic blood pressures were measured as pharmacodynamic indices. Original and population weighted modification methods were comprehensively used to analyze the experimental data and evaluate the drug-drug interaction and dose optimization of irbesartan/hydrochlorothiazide in rats. The results and characteristics of original and population weighted modification methods were compared.RESULTS:The weighted modification models were built successfully. The optimal combination proportion between these two drugs was 10∶1 (irbesartan/hydrochlorothiazide) and the nature of interaction was synergism. The role of irbesartan is more important than that of hydrochlorothiazide when used combinedly. The basic research conclusions of original and population weighted modification methods were the same. However, population weighted modification method can provide more accurate parameters such as weighted index and useful information of inter- and intra-individual variabilities.CONCLUSION: The weighted modification methods can be used to quantitatively evaluate the drug-drug interaction and dose optimization of irbesartan/hydrochlorothiazide in rats.

Use of SAS iteration and Monte Carlo simulation to optimize use of Meropenem

SHEN Hui-feng, ZHANG Sui-yang, CHANG Yan, REN Juan

2012, 17(5):  529-535. 

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AIM: To choose optimized dosages and regimens of Meropenem based on different MICs of clinical organisms, meanwhile to evaluate pharmacodynamics of traditional(TIT),prolonged(PIT) and optimized two-step infusion therapy(OTIT) of Meropenem.METHODS: Firstly, use ofSAS iteration to choose optimized dosages and regimens of Meropenem based on different MICs of clinical organisms in the condition of two-step infusion therapy;secondly,use of Monte Carlo Simulation to calculate the %T>MIC and the probability of target attainments(PTAs) of TIT,PIT and OTIT, respectively.RESULTS:Based on the MICs of 1,2,4 μg/mL and means of CL and V_d, the dosing regimens of OTIT with 500 mg, 0.25 h/100 mg+2.75 h/400 mg; 500 mg, 0.25 h/250 mg+2.75 h/250 mg and 1000 mg, 0.25 h/400 mg+2.75 h/600 mg provided the highest %T>MIC with SAS iteration, respectively. Monte Carlo Simulation revealed that PIT and OTIT obtained higher %T>MIC and PTAs compared with TIT at different MICs,Meanwhile OTIT obtained shorter the time to maximum concentration(t_max) compared with PIT.CONCLUSION: SAS iteration may be performed to choose the best optimized dosages and regimens of antibiotics. Monte Carlo simulation may be performed to compare pharmacodynamic parameters of different dosing regimens.These results suggested that OTIT was better therapy against clinically serious infections.

A Meta-analysis of histamine-receptor antagonists use and risk of pneumonia

HU Ai-hong, LI Xiao-ming, MA Huan-jie

2012, 17(5):  536-542. 

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AIM: To evaluate whether the use of histamine-receptor antagonists will increase the risk of pneumonia.METHODS: By searching EMBSE , CENTRAL(the Cochrane central register of controlledtrials), CBM, Medline, CNKI and WANFANG et al , we collected published randomized controled trials(RCTs) about histamine use and risk of pneumonia.The effect size was incidence of pneumonia measured relative risk (RR) and its 95% confidence interval (95%CI).The cochran's chi-square test (Q test) was used to test the statistical heterogeneity.The Egger test was used to test the publication bias.RESULTS:18 trials that included a total of 2974 subjects were included in the meta-analysi.1508 subjects were in the histamine-receptor antagonists group and 1466 were in the placebo of sucralfate group.The pooled relative risk of pneumonia was higher in histamine-receptor antagonists group compared with placebo/sucralfate group(RR=1.22,95%CI=1.05-1.41,Z=2.61,P=0.009). Sub-group analysis ,the pneumonia risk was increase 21% in histamine-receptor antagonists group compared with placebo group(RR=1.21, 95%CI=1.02-1.45,Z=2.17,P=0.03).But statistical difference was observed between histamine-receptor antagonists group and sucralfate group RR=1.22, 95%CI=0.93-1.60,Z=1.45, P=0.148).CONCLUSION: The use of histamine-receptor antagonists may increase the risk of pneumonia.

Development of pyrosequencing method for detection of SLCO1B1 polymorphisms

WAN Zi-rui, XIE Hai-tang, GUO Dong, HU Dong-li, WANG Li-ping, WANG Guo

2012, 17(5):  543-548. 

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AIM: To establish a pyrosequencing based method for detection SLCO1B1 A388G and T521C polymorphisms and to determine the frequency of these polymorphisms in healthy Chinese.METHODS: After preparation of gDNA from blood of 300 subjects, the target fragments were amplified by PCR, polymorphisms were detected on PyroMark ID by pyrosequencing technology. The reliability of pyrosequencing methods were validated by repeat tests and Sanger sequencing.RESULTS:We established a new pyrosequencing method to detect the SLCO1B1 A388G and T521C polymorphisms polymorphisms in healthy Chinese. The detection rate and repetition rate were both 100%. The frequencies of 388A, 388G, 521T and 521C alleles were 28%,72%,89.5% and 10.5%, respectively. Genotype frequencies match the Hardy-Weinberg equilibrium.CONCLUSION: These pyrosequencing assays to detect SLCO1B1 polymorphisms are proved to be a rapid, accurate and high-throughput alternative to conventional methods, and it can be a preferred option in research and clinical application.

Quantification of Ranolazine in human plasma using HPLC-MS/MS for pharmacokinetic study of its sustained-release preparation

TAN Qin-you, ZHU Rong-hua, LI Huan-de, ZHANG Qi-zhi, FANG Ping-fei, YAN Miao, PENG Wen-xing

2012, 17(5):  549-553. 

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AIM: The LC-MS/MS method was developed and validated,and assessed the pharmacokinetic properties after a single dose of 500, 1000, or 1500 mg of ranolazine in healthy Chinese volunteers.METHODS: Twelve Chinese subjects (6 men, 6 women) were enrolled in the single-dose phase of the PK study. The study were assigned to open-label, randomized-sequence, 3×3 latin square design which consisted of three 1-day treatment periods and two 7-day washout periods.Volunteers were randomly allocated to receive a single dose of 500, 1000, or 1500 mg of ranolazine (sustained-release tablets), sequential blood samples (4 mL each) were collected into heparin tubes at 0 hour (before administration) and 0.5, 1.0, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36.0,and 48.0 hours after administration. The LC-MS/MS method was developed and validated.RESULTS:The main PK parameters for ranolazine after administration of a single oral dose of 500, 1000, and 1500 mg were as follows: C_max were (742±253), (1355±502), and (2329±890) ng/mL, respectively; AUC_0-48 were (9072±3400), (16574 ± 6806) , and (29324±10857) ng·mL^-1·h,AUC_0-∞ were (9827±3152),(16882±6791), and (29924±10706) ng·mL^-1·h; t_max were (5.3±1.4), (4.2±1.2), and (5.9±2.8) hours; t_1/2 were (6.4±3.3), (6.4±3.5), and (6.7±4.3) hours.CONCLUSION: In this group of healthy Chinese subjects, AUC and C_max increased proportionally with the dose, the PK properties of ranolazine were linear after administration of single oral doses of 500 to 1500 mg.These dosages were generally well tolerated by all the subjects.

Comparison of GL (Gemicitabine plus Lobaplatin) and GP(Gemicitabine plus Cisplatin) in the treatment of metastatic breast cancer patients with anthracycline and taxane resistance

HAO Ji-qing, MA Qiang, LIU Peng-kun

2012, 17(5):  554-558. 

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AIM: To evaluate the efficacy and adverse reactions of Gemicitabine / Lobaplatin (GL regimen) and Gemicitabine / Cisplatin ( GP regimen) in the treatment of metastatic breast cancer patients with anthracycline and taxane resistance.METHODS: A total of sixty-one patients with metastatic breast cancer were randomly assigned to receive the regimen of GL (n=30) or GP (n=31). GL regimen: Gemicitabine 1000 mg /m² by infusion on d1,d8,Lobaplatin 30 mg /m² on d1.GP regimen: Gemicitabine 1000 mg /m² by infusion on d1,d8,Cisplatin 25 mg /m² by infusion on d1-3.All the patients had failures and relapse after previous treatment with anthracycline and taxane.Twenty-one days was a cycle in the both two groups.Every patient was administered at least 2 cycles.RESULTS:The overall response rate(CR+PR) was 43.33% in GL regimen group and 38.71% in GP regimen group(P>0.05). The median time to progression (mTTP) in group GL and GP was 6.29 months and 5.59 months(P>0.05). There were more neutropenia and thrombocytopenia in the group GL, and more nausea and vomiting in the group GP. There were significant differences between the two groups(P<0.05).CONCLUSION: Both GL regimen and GP regimen are well effective for patients with anthracycline and taxane resistant metastatic breast cancer.And the response rate, median time to tumor progression were similar in both groups. The reaction of hematologic toxicity in the group GL was obviously higher than the group GP,but the gastrointestinal tract reaction was obviously higher in the group GP than the group GL. The two schemes may be suitable for different groups of people. And it is worthy of further clinical study.

Clinical observation on integrated traditional Chinese and western medicine stroke unit therapy in treatment of 156 patients with cerebral stroke

ZHU Jin-gang, XIE Dan-dan, CHENG Mao-liang

2012, 17(5):  559-561. 

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AIM: To explore the superiority of integrated traditional Chinese and western medicine stroke unit in treating cerebral stroke.METHODS: 298 patients with acute cerebral stroke onset were randomly divided in to two groups. 156 patients in the treatment group were treated with the integrated traditional Chinese and western medicine stroke unit and 142 patients were given the routine western therapy. The mortality rate, the cause of death, the infection rate, European stroke score ( ESS) in the day 21, the modified Bar index (MBI) of movement capability and daily activity in day 90 were observed.RESULTS:The mortality rate within 14 days in the treatment group was 3.85%, 16.7% of which was not of intracerebral causes and the infection rate was 22.4%. Compared with the control group, which were 6.34%, 33.3% and 26.76%, respectively, there were significant differences between the two groups (P<0.01). The nerve function score in the day 21 in the treatment group and the control group was (84.6±11.1) score and (68.1±10.4) score respectively (P<0.01). There was a significant difference of MBI in the day 90 between the two groups (P<0.01).CONCLUSION: Integrated traditional Chinese and western medicine stroke unit have advantage over the routine treatment model on acute cerebral stroke.

A clinical observation on the transarterial chemoembolization of advanced cardiac cancer

ZHANG Jun, XIE Ya-min, WU Cui-ling, WU Run-lin, WU Ke-wei

2012, 17(5):  562-565. 

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AIM: To investigate the clinical effects of the transarterial chemoembolization in the treatment of advanced cardiac cancer.METHODS: 60 patients with advanced cardiac cancer were randomly divided into 2 groups: the group combined arterial infusion chemotherapy with embolization (treatment group, n=30) and the intravenous chemotherapy group (control group, n=30).Patients in both groups were received same chemotherapy regimens. The recent effects of two treatment groups were evaluated according to the WHO criteria and the clinical symptom improvements were also observed.RESULTS:The response rate of treatment group was increased significantly (P<0.01) compared with the control group, and the clinical symptoms were improved significantly in treatment group.CONCLUSION: Combined arterial chemotherapy with embolization can improve the curative effects ,which can be used as an effective treatment in advanced cardiac cancer.

Clinical research of YANGXUE DANGGUI JIAONANG with functional dysmenorrhea

LIU Yong-mei, FANG Ling, JIN Zhu-ming, BAO Ying

2012, 17(5):  566-568. 

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AIM: To research the effects of YANGXUE DANGGUI JIAONANG with functional dysmenorrhea.METHODS: 112 cases of patients in trial group were treated with YANGXUE DANGGUI JIAONANG and 79 cases of patients in control group were given Ibuprofen capsules.RESULTS:The efficacy rate was 85.7% in trial group and 82.3% in control group, there was no significant difference between two groups (P>0.05). The cure rate was 13.4% in trial group and 1.3% in control group, there was significant difference between two groups (P<0.01) . The ADR rate was 0.89% in trial group and 12.6% in control group, there was significant difference between two groups (P<0.01).CONCLUSION: YANGXUE DANGGUI JIAONANG is effective and safe in treating functional dysmenorrhea.

Comparison of gefitinib and pemetrexed in treatment of advanced non-small cell lung cancer patients who have failed to first-line chemotherapy

GU Liang, ZHAO Tian, QIN Guang-yue

2012, 17(5):  569-572. 

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AIM: To evaluate the clinical difference between gefitinib and pemetrexed in treatment of advanced non-small cell lung cancer(NSCLC) patients who have failed to first-line chemotherapy.METHODS: From Feb 2009 to Oct 2011, 64 patients with NSCLC who received gefitinib or pemetrexed for second line chemotherapy were analysised retrospectively. The progression survival time and overall survival time were evaluated.RESULTS:There was no statistics difference between the gefitinib and pemetrexed group for progression free survival time( HR=1.21, 95%CI:0.68-2.16, χ²=0.41, P=0.52).But the overall survival time for patients received pemetrexed was much longer than that patients received gefinitib(HR=1.99 95%CI:1.04-3.85, χ²=4.30, P=0.04).No statistical difference between the two group in side effect(P＞0.05).CONCLUSION: For patients with advanced NSCLC who have failed to first-line chemotherapy, the overall survival time was longer for patients received pemetrexed but not for progression free time in the second line chemotherapy compared with treatment of pemetrexed. The side effect was acceptable and no statistical difference between the two groups was observed.

Recent status and progress of chemotherapy treatment for metastatic non-small-cell lung cancer

QI Quan, ZHAO Wen-ying

2012, 17(5):  573-581. 

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In recent years, smoking,pollution and lampblack lead to the morbidity and mortality of lung cancer rapid growth. Non-small-cell lung cancer onset occult, development is rapid, and the prognosis is poor. Most of the patients with newly diagnosed is transferred (IV stage) and lost the opportunity to surgery, chemotherapy is the main treatment method, which purpose is to prolonging the survival time and the quality of life. At present clinical application of chemotherapy is mainly platinum-based and the third generation cytotoxic drugs. The best treatment strategy which based on functional genomics and proteomics in individual therapy design for every patient with lung cancer is the direction of the clinical development and the ideal mode of treatment of the 2l century. This paper reviews the recent status and progress of chemotherapy treatment for metastatic non-small-cell lung cancer.

Effect of CYP2C9, CYP2C19, CYP3A4 polymorphism on metabolism of sulfonyluea antidiabetic drugs

LI Yun, HE Fang, ZENG Cai-wen, LIU Lin-lin, XIA Chun-hua

2012, 17(5):  582-587. 

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Sulfonylurea oral antidiabetic drugs were mainly metabolized by hepatic cytochrome P450 in human.Cytochrome P450 is one kind of important drug metabolizing enzymes in human and exhibits genetic polymorphism, which usually results in the difference of efficacy and adverse reaction among individuals.The purpose of this paper was to review the basic structure, genetic polymorphism and ethnic difference of CYP2C9, CYP2C19, CYP3A4 and the influence to sulfonylurea metabolism.

The educational strategies for pharmacogenomics Translational Medicine

LUO Zhi-ying, ZHANG Wei

2012, 17(5):  588-592. 

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The main purpose of pharmacogenomics translational medicine is that enable every patient receives the most appropriate medical treatment and the most suitable dosage and drug combination. After finding out the main problems of our medical education system and realizing the urgent situation of spreading the education of pharmacogenomics translational medicine, we summarize the education experience of domestic and foreign medical school in order to obtain more scientific education strategies.

Relation between bacterial efflux pump and antibiotic resistance

SUN Yuan, ZHA Wei-bin, ZHOU Fang, WU Xiao-lan, ZHANG Jing-wei, WANG Guang-ji

2012, 17(5):  593-600. 

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Drug resistance in bacteria has attracted much attention in clinical antibacterial therapy for years. In addition to the well known mechanisms, such as inactivation of drugs and alteration of targets, drug extruding pumps also play a major role in resistance to antibacterials. Efflux pumps are widespread in bacteria and have broad variety of substrates. Their presence contributes both intrinsic and acquired bacterial resistance. Efflux-mediated drug-resistance has been recognized as the major mechanism of resistance to antibacterial agents in Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. The impact of antibiotic efflux pumps on therapy must be taken fully into account for the selection of antimicrobials. The design of specific, potent inhibitors appears to be an important goal for the improved control of infectious diseases in the near future. An alternative approach is to develop antibacterials that would bypass the action of efflux pumps. This paper will review recent progress on the role of bacterial efflux transporters in antibiotic resistance from the aspects of classification, structure, regulation and the inhibitors, which will provide references for the further investigation.