Resistance is one of the most important reasons that restrict the clinical application of most chemotherapeutic medicines. Docetaxel is a very widely applicated antitumor medicine. Most of the researches on the mechanism of resistance against docetaxel focused on the drug transporters, changes in drug metabolism and pathway alteration of cell cycle and apoptnsis. The mechanism of docetaxel resistance and the predictive data based on clinical research to docetaxel therapy in cancer treatment were reviewed.

A number of medications have been proved to be able to either improve the antitumor effect of chemotherapeutics and molecular targeted drugs or reverse the resistance of tumors to chemotherapeutics and molecular targeted drugs,which are not traditionally used as anticancer drugs.Especially for late-stage tumors after multiple treatments,these agents are good alternatives when used independently or in combination with chemotherapeutics and molecular targeted drugs.These drugs include proton modulators,hypoglycemic agents and cardiovascular agents,etc.

Background and purpose:The growth,metastasis,relapse and the prognosis of tumor are correlated with tumor angiogenesis.Therefore,target to angiogenesis and antiangiogenic therapy has become one of the hot points in cancer research field.Some chemotherapeutic drugs can inhibit the growth of new vascular endothelial cell markedly in the way of low-dose and high time administration.This is metronomic chemotherapy or antiangiogenic chemotherapy.Traditional Chinese medicine has an effect on tumor control.In recent years,we discovered that some traditional Chinese medicine have an antiangiogenic effect.This experiment aimed to study the antiangiogenetic ability of oxaliplatin combined with composite radix sophora flavescentis injection(CRSFI) in vitro and in vivo. Methods :We used MTT method to observe the influence of oxaliplatin and composite radix sophora flavescentis injection on human umbilical vein endothelial cells(HUVEC) or LoVo proliferation.The influence of oxaliplatin and composite radix sophora flavescentis injection on HUVEC migration was evaluated by transwell.Chick embryo chorioallantoic membrane(CAM)model was used to check whether the neovascularization of CAM could be suppressed in vivo by them. Results :The survival rate of LoVo within the same doses of oxaliplatin and composite radix sophora flavescentis injection were higher than HUVEC.Oxaliplatin(2 ?g/ml) and composite radix sophora flavescentis Injection(25 ?l/ml) could inhibit the prolifetation of HUVEC;the rate of inhibition were 31.6%,32.1% respectively;the rate of the two drugs combination was 54.4%.So when combined,they had synergistic effect.There was coordinate repression to migration of HUVEC in vitro when we used oxaliplatin(0.5 ?g/ml) and composite radix sophora flavescentis injection(6.25 ?l/ml).They also suppressed angiogenesis of CAM in vivo. Conclusions :This experiment showed that low dose oxaliplatin combined with composite radix sophora flavescentis injection has anti-angiogenic synergetic ability in vivo and the ability of inhibiting the growth of the cells in vitro.

Objective:To get a rapid and stable method of induction of rapid cultivation and maturation of Dendritic Cells(DC) from human peripheral blood in vitro.Methods:Cultured plastic-adherent monocytes were isolated from tumor patient peripheral blood mononuclear cells and GM-CSF(1 000 u/ml),IL-4(500 u/ml) were added in the cells at 0 h,which were separated into four groups.Poly(I ∶ C)(Polyriboinosinic Polyribocytidylic Acid) were added in the first group cells at 24 h and the DC cells were collected at 48 h;TNF-? in the second group cells were added at 24 h and the cells were collected at 48 h;Poly(I ∶ C) were added in the third group cells at 36 h and the cells were collected at 72 h;TNF-? were added in the last group cells at 36 and the cells were collected at 72 h.Results:The results of flow cytometer showed that the third group got the most mature DC.The dendritic cells from the third group have significant stimulatory activity in allogeneic lymphocyte proliferation.Conclusion:The method of rapid cultivating and maturating of Dendritic Cells from human peripheral blood in vitro induced by Poly(I ∶ C) is rapid,stable,economical and simple.It may facilitate future studies of DC and its clinical application.

Objective To investigate whether the single nucleotide polymorphisms (SNP) in DNA repair gene XRCC1(X-ray repair cross-complementing 1) were associated with the survival of cisplatin based combination concurrent chemoradiotherapy in esophagus cancer. Methods Overall 286 esophagus cancer patients receiving cisplatinum based chemotherapy were investigated. 5' nuclease allelic discrimination assay (TaqMan) and real-time PCR were taken to assess XRCC1 genotypes. Efficacies and adverse-effects were analyzed individually according to their genotype. Results Short-time effects showed the RR rate in patients with Arg/Arg and Arg/GIn genotypes(A group) was 93.56 %, significantly higher than 69.81% (P<0.05) in patients with GIn/GIn genotype (B group). The 1-year and 3-year survival rates were 82.8 %, 41.2 % in A group, significantly (P<0.05) different from 58.5 %, 26.4 % in B group, respectively. No statistically differences were found on adverse effects. Conclusion Significant relationships are found between single nucleotide polymorphisms in XRCC1 and outcome in esophagus cancer receiving cisplatin based concurrent chemoradiotherapy.

Objective Based on the previous research that the ethanolic extract from traditional Chinese medicine fructus forsythiae (Lianqiao) can obviously inhibit cancer cells in vitro, the article aimed to investigate the anti-proliferation effects of dammar-24-ene-3β-acetate-20S-ol (DM) extracted from fructus forsythiae on gastric cancer cells and its mechanism.Methods MTT assay was used to assess the anti-proliferation effects of DM on gastric cancer cells including SGC-7901, BGC-823, and MKN-45 in vitro.There were MKN-45 control group and its low dose and high dose groups, BGC-823 control group and its low dose and high dose groups, SGC-7901 control group and its low dose and high dose groups in the experiment.Flow cytometry was used to analyze the cell apoptosis rate.Cellquest software was used to analyze the results and record the ratio of cells at different cycles.DCFH-DA probe was applied to detect the ROS levels of blank control group, docetaxol group and DM group.The reaction system of microtubule assembly test was set with 10?mol/L docetaxol, 50 or 100 μmol/L DM final density and no medicine in blank control group.The readings of UV spectrophotometer were recorded.Microtubule assembly assay and microtubule immunofluorescence staining were applied to investigate the effects of DM on microtubule system.Results The inhibition ratio of 50 μg/L DM on the proliferation three gastric cell lines were all above 80%, with IC50s of MKN-45 11.72±1.35 μg/mL, BGC-823 17.19±0.82 μg/mL, SGC-7901 7.55±0.79 μg/mL.8 days′ low density culturing at 48 hours after 2 μg/mL DM treatment, compared with control group, the number of cell clones significantly reduced without much change in clone size, while 48 hours after 10 μg/mL DM treatment, besides a few clones of BGC-823, there were just several megascopic clones of SGC-7901 and MKN-45.In comparison with apoptotic cell ratio in MKN-45 control group[(21.1±2.5)%], its low dose group and high dose group resulted in significant rise of apoptotic cell ratio[(25.1±1.3)% and (55.2±2.3)%] (P<0.01).Compared with apoptotic cell ratio in BGC-823 control group[(13.2±2.5)%], its low dose group and high dose group resulted in significant rise of apoptotic cell ratio[(18.2±2.1)% and (41.8±2.1)%] (P<0.01).Compared with apoptotic cell ratio in SGC-7901 control group[(10.5±1.8)%], significant rise was observed in its high dose group[(41.8±2.1)%] (P<0.05) while no statistical significance was found in its low dose group[(12.3±1.6)%] (P>0.05).In comparison with MKN-45 control group, the ratio of cells at S phase decreased in its low dose group[(14.5±2.7)% vs (12.3±3.3)%,P>0.05].In comparison with BGC-823 control group, the ratio of cells at S phase increased in its low dose group[(12.2±5.4)% vs (20.2±2.1)%,P<0.05].In comparison with SGC-7901 control group, the ratio of cells at S phase increased in its low dose group[(21.5±3.8)% vs (31.3±2.6)%,P<0.05].From the detection of intracellular active oxygen after DM treatment, dose-dependent ROS level increased in all three cell lines 48 hours after 10μg/mL and 50μg/mL DM treatment.From the results of microtubule immunofluorescence staining, 48 hours after the treatment of IC50 docetaxol and 10μg/mL DM, the fluorescence signals were in local concentration and disorder.Conclusion Dammar-24-ene-3β-acetate-20S-ol demonstrated anti-proliferation effects due to the apoptosis induced by cell cycle arrest at S phase.

Objective CA125 has been proved to be closely related to peritoneal metastasis of gastric cancer.This study aimed to screen and identify a novel ssDNA aptamer targeting the extracellular domain of Mucin16. Methods Using capillary elec-trophoresis, we screened the aptamers targeting the synthetic peptide of the extracellular domain of Mucin16 and quantitatively deter-mined the Kd value of each cycle and the affinity of the aptamers for the synthetic peptide by CE-SELEX.Then we evaluated the ability of the obtained aptamers to target cancer cells using confocal laser imaging. Results After five cycles of screening, sequencing, af-finity determination, we obtained an ssDNA aptamer targeting the extracellular domain of Mucin16, with a Kd value of 122.7 nm and visible green fluorescent signals on the cell membrane of the human ovarian cancer cell line expressing Mucin16, but not on that of the normal hepatocytes not expressing Mucin16.This confirmed the binding ability of the aptamer to the extracellular domain of Mucin16. Conclusion A novel aptamer targeting the synthetic peptide of the extracellular domain of Mucin16 was successfully obtained by capil-lary electrophoresis, which could be used as a new agent in the diagnosis and treatment of peritoneal metastasis of gastric cancer.

【Objective】 To compare three kinds of platelet antibody detection methods used to identify alloantibodies in patients with platelet transfusion refractory(PTR). 【Methods】 The 83 samples from PTR patients were analyzed base on three different methods, including solid phase ELISA, Luminex, and capture. The sensitivity, reproducibility, and consistency of different kits were evaluated. 【Results】 A total of 71 (62 positive and 9 negative) out of 83 samples showed consistent results by three methods. The consistency between Luminex and solid phase ELISA was 95.2% (Kapp value=0.829, P<0.05), between solid phase ELISA and capture method was 85.5% (Kapp value=0.512, P<0.05), and between Luminex and capture method was 90.3% (kappa value=0.636, P<0.05). Among the 12 samples with inconsistent results, 3 cases presented positive results by capture method alone and negative by other methods, which had incompatible cross-matching results with 6 random blood donors; 5 cases with HLA antibodies showed negative results by capture method alone and positive by both Luminex and solid phase ELISA; the other 4 cases were positive in both capture and Luminex, but negative in solid phase ELISA. 【Conclusion】 The consistency of three methods was 85.5%, and each has its limitations. The capture method is rapid, economic and registered domestically, which can be used for preliminary screening.Luminex has the optimal diagnostic performance, which can be used for high-throughput and HPA/HLA antibody analysis. The solid phase ELISA is convenient. The combination of them can detect platelet antibodies effectively.

Objective To evaluate the significance of COLD-PCR in detecting KRAS mutation of pancreatic cancer and colorectal cancer patients. Methods First, set up COLD-PCR and compared the sensitivities of COLD-PCR/Sanger sequencing with PCR/Sanger sequencing using mixed cell lines ( KRAS wild-type cell line SW116 and KRAS mutant cell line SW480).Then, detected KRAS mutation of 20 formalin-fixed paraffin-embedded samples of pancreatic cancer and 39 formalin-fixed paraffin-embedded samples of colorectal cancer using PCR/Sanger sequencing and COLD-PCR/Sanger sequencing, respectively and compared the coincidence rate and consistency. Results The low detection limits of PCR/Sanger respectively. KRAS frequency detected by COLD-PCR/Sanger sequencing [75% (15/20)] in 20 cases of pancreatic cancer was higher than that detected by regular PCR/Sanger sequencing [40% ( 8/20 ) ,x2 =5.013, P < 0.05]. KRAS frequency detected by COLD-PCR/Sanger sequencing [44% (17/39)] in 39 cases of colorectal cancer was higher than that detected by regular PCR/Sanger sequencing [31% (12/39) ,x2 =1. 372, P = 0. 174]. The coincidence rate of these two methods was 0. 730 and the difference had no statistical significance. The coincidence rate of detecting KRAS mutation was 65% in pancreatic cancer and the results showed a good correlation between two methods and the two methods had bad agreement in diagnosis (Kappa = 0. 364, P < 0. 05 ). COLD-PCR/Sanger sequencing could detect more cases of KRAS mutations from pancreatic caner than regular PCR/Sanger sequencing. This was because there were many non-tumor cells in pancreatic tumor tissue and COLD-PCR/Sanger sequencing was more sensitive than regular PCR/Sanger sequencing. The coincidence rate of detecting KRAS mutations was 87% in colorectal cancer and the results were showed a good correlation between two methods and the two methods had substantical agreement in diagonsis ( Kappa = 0. 730, P < 0. 05 ) . Conclusion COLD-PCR/Sanger sequencing is highly sensitive to screen KRAS mutation in pancreatic cancer and colorectal cancer patients.

Objective To investigate the efficacy and safety of balloon-assisted catheter directed thrombolysis (CDT) for acute lower extremity deep vein thrombosis (DVT).Methods From September 2008 to February 2011,94 patients with acute lower extremity DVT were admitted.The cases in early stage were treated by CDT (Group A,n =50),and the cases in late stage were treated by balloon-assisted CDT ( Group B,n =44).The clinical data of these patients were retrospectively analyzed.The circumference difference between normal and affected limbs,scores of venous patency,and rates of venous patency were recorded for judging the efficacy.The total dose of urokinase and retention time of infusion catheter was compared between the two groups.The incidence of pulmonary embolism and bleeding were used to judge the safety of treatment.The venous patency was followed up by ultrasound or/and venography.Measurement data with normal distribution was described by mean + standard,and was analyzed using T test.Measurement data with non-normal distribution was described by M ( QL,QU ),QL =P25,QU =P75,and was analyzed using Wilcoxon' s test.Categorical variable data was analyzed using Chi-Square test Results The prior treatment circunfference difference between normal and affectéd limbs were (5.37 ±1.97) cm (thigh) & (4.14 ± 1.57) cm (calf) in Group A and (5.41±2.22) cm (thigh) & (4.05 ±1.61) cm (calf) in Group B ; and the difference between the groups was insignificant ( thigh:t =- 0.113,P=0.910; calf:t =0.288,P =0.774).The post treatment correspondences were:(2.96 ± 1.10) cm (thigh) & ( 1.93 ± 0.84 ) cm (calf) in Group A and ( 1.78 ± 1.40) cm ( thigh ) & ( 1.41± 1.17 ) cm (calf) in Group B; the difference between the groups was significant (thigh:t =4.66,P ＜0.0001; calf:t =2.548,P =0.012 ).The prior treatment score of venous patency was 9 (8,10) in Group A and 8.3(7,10) in Group B without significant difference (Z =- 1.5172,P =0.1292).The post treatment score of venous patency was 3.5 ( 2,5 ) in Group A and 0 ( 0,1) in Group B with significant difference ( Z =-5.7702,P ＜0.01).The rate of venous patency after the treatment was 55.0％ (42.3％,72.4％ ) in Group A and 100％ (88.5％,100％ ) in Group B,with significant difference ( Z =4.9148,P ＜ 0.01).The total dose of urokinase used in the treatment was 5.950 ( 5.525,7.225 ) × 106U in Group A and 4.100 (3.600,5.050) × 106U in Group B with significant difference (Z =-6.0133,P ＜ 0.01).The retention time of perfusion catheter was 10 (9,12) d in Group A and 6 (5,7) d in Group B with significant difference ( Z =- 8.0358,P ＜ 0.01).No symptomatic pulmonary embolism occurred in both groups during the treatment and follow-up period.The rate of bleeding complication was 38.0％ (19/50) in Group A and 22.3％ (10/44) in Group B,without significant difference (x2 =2.5590,P =0.1097 ).The removal rate of optional filter was 88.37％ (38/43) in Group A and 100％ (39/39) in Group B,with significant difference ( x2 =4.829,P =0.028 ).The rate of venous patency at the last follow-up point was 50.0％ (44.4％,59.2％ ) in Group A,and 95.4％ (83.6％,100％ ) in Group B,with significant difference (Z =- 3.2721,P =0.0011).Conclusions Balloon-assisted CDT was a promising treatment for acute lower-extremity DVT.It improved the effect of thrombolysis and reduced the dosage of urokinase,and did not increase the risk of pulmonary embolism.