Tumor has long been a hard-nut problem in the world medical field. The effect of the conventional drugs is very limited because of the intervention of multiple micro-environmental factors during the occurrence and progression of tumors. With the characteristics of high efficiency, low toxicity and multi-targets synergistic effect, the long-circulating tumor targeted compound preparations show its unique advantages in improving tumor microenvironment and enhancing the therapeutic effect of treatment, thus it has gradually become a hotspot of studies both at home and abroad. Through consulting a great number of professional literatures at home and abroad in recent years, the authors summarized the current studies in vitro and in vive on long-circulating tumor targeted compound preparations in different carriers, in the expectation of providing new ideas and methods for the development of long-circulating tumor targeted compound preparations.
Animals ; Antineoplastic Agents ; blood ; chemistry ; therapeutic use ; Drug Compounding ; methods ; Humans ; Molecular Targeted Therapy ; methods ; Neoplasms ; blood ; drug therapy

Purpose To observe therapeutic effect of electroacupuncture Neixiyan (Ex-LE 4 ) and Dubi (ST 35) in treating osteoarthritis of knee joint. Method All the 120 cases were randomly divided into electroacupuncture and control groups, 60 cases in each group,and they were given electroacupuncture and Ritalin slowreleased tablet respectively, and pain, mobility and swelling degree of knee joint were observed before and after treatments. Results In treatment group, the average score increased by 18, while in control group, it increased by 12.33 ( P < 0. 05 ) after treatment. Conclusion Therapeutic effect of electroacupuncture Neixiyan (Ex-LE 4) and Dubi (ST 35) in treating osteoarthritis of knee joint was better than that of administration of Ritalin slow-released tablet.

Objective To study the relationship of three-dimensional power Doppler ultrasonographic parameters and endocrine profile in different symptoms of patients with polycystic ovary syndrome(PCOS).Methods One hundred and forty nine women with PCOS were divided into two groups,which included obese PCOS(OB-PCOS) group and non-obese PCOS (NOB-PCOS) group.The ultrasonic parameters such as follicle number,ovarian average diameter,ovarian volume,stromal volume,follicle volume,vascularization index(Ⅵ),flow index(FI),vascularization flow index(VFI) were measured and compared.Serum levels of luteinizing hormone (LH),follicle stimulating hormone (FSH),progesterone (P),estradiol (E2),testosterone(T),prolactin (PRL),sex hormone binding globulin (SHBG),free androgen index (FAI),fasting plasma glucose (FPG),fasting insulin (FINS),homeostasis model assessment-IR(HOMA-IR) were also measured and compared.The correlation of the ultrasonic parameters and hormonal factors were analyzed.Results The follicle number,ovarian average diameter,ovarian volume,stromal volume,follicle volume,FI and VFI,FINS,HOMA-IR,FAI of OB-PCOS were significantly higher than those of NOB-PCOS (P ＜0.01 or 0.05),the FSH,SHBG were significantly lower than those of NOB-PCOS (P ＜0.05 or 0.01).In OB-PCOS group,the follicle number was significantly associated with FSH(r =0.771,P ＜0.01).The ovarian volume,stromal volume,FI and VFI were significantly associated with HOMA-IR(r =0.412,0.842,0.389,0.415,P ＜0.05 or 0.01),FI was significantly associated with FAI (r =0.812,P ＜0.01).In NOB-PCOS group,the follicle number,ovarian volume were significantly associated with FAI(r =0.472,0.552,P ＜0.05)..Conclusions There are some different characters in ultrasonography and endocrine parameters between obese and non-obese PCOS patients.

The objective of the study was to prepare and evaluate the quality of curcumin-piperinedual drug loaded self-microemulsifying drug delivery system(Cur-PIP-SMEDDS). Simplex lattice design was constructed using optimal oil phase, surfactant and co-surfactant concentration as independent variables, and the curcumin and piperine were used as model drugs to optimize Cur-PIP-SMEDDS formulation. In the present study, the drug loadings of curcumin and piperine, mean particle size of Cur-PIP-SMEDDS were made as indicators, and the experiment design, model building and response surface analysis were established using Design Expert 8. 06 software to optimize and verify the composition of SMEDDS formulation. The quality of Cur-PIP-SMEDDS was evaluated by observing the appearance status, transmission electron microscope micrographs and determining particle diameter, electric potential, drug entrapment efficiency and drug loading of it. As a result, the optimal formulation of SMEDDS was CapryoL 90-Cremophor RH40-TranscutoL HP (10:60:30). The appearance of Cur-PIP-SMEDDS remained clarified and transparent, and the microemulsion droplets appeared spherical without aggregation with uniform particle size distribution. The mean size of microemulsion droplet formed from Cur-PIP-SMEDDS was 15.33 nm, the drug loading of SMEDDS for Cur and PIP were 40.90 mg · g(-1) and 0.97 mg · g(-1), respectively, the drug entrapment efficiency were 94.98% and 90.96%, respectively. The results show that Cur-PIP-SMEDDS can increase the solubility and stability of curcumin significantly, in the expectation of enhancing the bioavailability of it. Taken together, these findings can provide the reference to a preferable choice of the Cur formulation and contribute to therapeutic application in clinical research.
Alkaloids ; chemistry ; Benzodioxoles ; chemistry ; Chemistry, Pharmaceutical ; methods ; Curcumin ; chemistry ; Drug Carriers ; chemistry ; Drug Combinations ; Drug Delivery Systems ; Drugs, Chinese Herbal ; chemistry ; Emulsions ; chemistry ; Methylmethacrylates ; chemistry ; Particle Size ; Piperidines ; chemistry ; Polystyrenes ; chemistry ; Polyunsaturated Alkamides ; chemistry

Objective To detect the expression level of aquaporin 8 (AQP8) in patients with functional constipation(FC) or constipated irritable bowel syndrome (IBS-C),and the correlation between the expression of AQP8 and clinical features.Methods From March to December 2014,a total of 16 patients with IBS-C and 19 patients with FC met Rome Ⅲ criteria were collected,and nine healthy individuals were assigned to control group at the same period.The ascending and decending colonic tissues mucosa of FC,IBS-C and control group were taken under endoscope.The expression of AQP8 at mRNA and protein level was detected by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC).The differences in AQP8 mRNA expression and AQP8 relative area were analyzed by Kruskal-Wallis test among groups,and Pearson correlation coefficient was performed for correlation analysis between the expression and clinical features.Results The relative expressions of AQP8 mRNA of ascending colon and descending colon of FC patients (1.38,0.61 to 4.09;2.65,0.82 to 7.52) and IBS-C patients (2.23,0.82 to 4.67;1.35,0.51 to 2.03) were higher than those of control group (0.56,0.19 to 0.97;0.38,0.21 to 1.19),and the differences were statistically significant (ZFc =-2.435,-3.149,ZIBS-C =-2.690,-2.152;all P＜0.05).AQP8 mRNA expression of descending colon in patients with FC was higher than that of patients with IBS-C,and the difference was statistically significant (Z =-2.003,P =0.045).The expression of AQP8 in patients with FC and IBS-C was positively correlated with disease course (ascending colon r=0.57 and 0.53;descending colon r=0.49 and 0.54,all P＜0.05),and was negatively correlated with frequency of defecation (ascending colon r=-0.82 and-0.61;descending colon r=-0.49 and-0.53,all P＜0.05).There was no correlation between the expression of AQP8 and age,gender,onset age,presence of abdominal symptoms of the patients (all P＞ 0.05).Most of AQP8 of FC group was expressed in cytoplasm of colonic mucosa epithelial cells,while that of IBS-C group and control group was mostly expressed at apical membrane and basal membrane of epithelial cells.The results of semi-quantification demonstrated that AQP8 relative area of descending colon of FC and IBS-C group increased compared with that of control group (3.42％ (1.24％ to 5.61％),2.45％(1.72％ to 4.27％) vs 1.18％ (0.35％ to 2.81％);Z=-2.534,-2.151,both P＜0.05).Meanwhile,AQP8 relative area of ascending colon of FC group increased compared with that of control group (2.46％(1.48％ to 4.18％) vs 1.14％(1.29％ to 2.15％) Z=-2.041,P＜0.05).Conclusion There are differences in AQP8 expression quantity and location in cells of descending colon between patients with FC and patients with IBS-C,which is a way for differentiation these two diseases.

OBJECTIVETo evaluate the expression level of E-cadherin (E-CD) mRNA in gastric cancer and its relation to biological behavior.

METHODSThe expression level of E-CD mRNA was examined by RT-PCR in primary tumors, nearby tumor free tissues, metastatic lymph nodes and peritoneal lavage fluid from 35 cases with advanced gastric cancer.

RESULTSAll the specimens expressed E-CD mRNA. The expression level in primary tumors was significantly decreased compared with that in nearby tumor free tissues (P < 0.01). The decrease in E-CD expression was more marked in poorly differentiated, diffusely growing tumors invading through serosal membrane. E-CD expression in the primary tumor was more significantly decreased with the increase in the number of lymph nodes (LNS) metastasized and progression of the clinical stage. However, E-CD expression level was significantly increased in metastatic LNs. The difference in E-CD mRNA level between metastatic LN and the primary tumor was increasing with progression of the disease. The expression level of E-CD mRNA in peritoneal lavage fluid was increased in patients whose tumor had penetrated through serosa and larvage fluid was positive on exfoliative cytologic examination.

CONCLUSIONE-CD mRNA expression in primary tumors of gastric cancer is negatively correlated with the malignant behavior of the tumor. Nonetheless, that in the metastatic lymph nodes is increased with the progression of the disease.

Adult ; Aged ; Ascitic Fluid ; metabolism ; Cadherins ; biosynthesis ; genetics ; Female ; Humans ; Lymph Nodes ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; RNA, Messenger ; biosynthesis ; genetics ; Stomach Neoplasms ; metabolism ; pathology

OBJECTIVETo investigate the effects of 5-Aza-2'-deoxycytidine (5-Aza-dC) and trichostatin A (TSA) on DNA methylation and expression of P16, hMLH1 and MGMT genes in the human gastric cancer cell line MGC-803, and to explore the mechanism of P16, hMLH1 and MGMT gene silencing in human gastric cancer cells.

METHODSMGC-803 cells were cultured in RPMI-1640 medium and were treated with 5-Aza-dC or TSA. Methylation-specific polymerase chain reaction (MS-PCR) was used to detect the promoter methylation status of P16, hMLH1 and MGMT genes. RT-PCR was used to detect the mRNA expressions of P16, hMLH1 and MGMT.

RESULTSPromoter hypermethylation of P16, hMLH1 and MGMT genes were detected in MGC-803 cells, and mRNA expressions of P16, hMLH1 and MGMT were absent before treatment. After treatment with 5-Aza-dC, the promoter region of the P16, hMLH1 and MGMT gene exhibited a demethylation status, and their mRNA expressions were increased. The treatment with TSA had no effects on DNA demethylation or restoration of P16 or hMLH1 expression. P16, hMLH1 and MGMT mRNA relative expression levels after treatment with a combination of 5-Aza-dC and TSA were 0.412+/-0.030, 0.397+/-0.024 and 0.553+/-0.043 respectively, which were higher than those after 5-Aza-dC treatment alone (0.221+/-0.022, 0.214+/-0.018 and 0.156+/-0.017, all P<0.05).

CONCLUSIONSPromoter hypermethylation is a major mechanism of P16, hMLH1 and MGMT gene silencing in human gastric cancer cells. Treatment with 5-Aza-dC alone or the combination of 5-Aza-dC and TSA can reactivate the expressions of these genes.

Adaptor Proteins, Signal Transducing ; genetics ; Antimetabolites, Antineoplastic ; pharmacology ; Azacitidine ; analogs & derivatives ; pharmacology ; Cell Line, Tumor ; DNA Methylation ; drug effects ; DNA Modification Methylases ; genetics ; DNA Repair Enzymes ; genetics ; Genes, p16 ; Humans ; Hydroxamic Acids ; pharmacology ; MutL Protein Homolog 1 ; Nuclear Proteins ; genetics ; Promoter Regions, Genetic ; Stomach Neoplasms ; metabolism ; Tumor Suppressor Proteins ; genetics

This study was aimed to compare the proportion of endothelial cells (EC) in human bone marrow mesenchymal stem cell (BM-MSC) and human umbilical cord mesenchymal stem cells (UC-MSC), and to investigate the influence of vascular endothelial growth factor (VEGF) on proportion of EC in MSC. Flow cytometry was used to detect the proportion of CD34(+)CD133(+) and vWF(+)CD31(+) double positive cells in MSC. Wright's staining was employed to observe the influence of VEGF on morphology of MSC. The expressions of CD34, CD133, CD31, vWF were detected by immunofluorescence. qRT-PCR was performed to detect the influence of VEGF on EC marker genes' expression of MSC. The results showed that there were a small amount of EC and endothelial progenitor cells (EPC) in obtained BM-MSC and UC-MSC. After exposed to VEGF 10 ng/ml for 24 h, aspect ratio of MSC and the proportion of EC increased, while proportion of EPC decreased. Expression of EC related marker genes such as Tie-2 and ecNOS up-regulated, especially in UC-MSC. It is concluded that small amount of EC and EPC exists in cultured BM-MSC and UC-MSC, VEGF can enhance the proportion and function of EC in MSC.
Antigens, CD ; metabolism ; Bone Marrow Cells ; cytology ; Cell Separation ; Cells, Cultured ; Endothelial Cells ; cytology ; Humans ; Mesenchymal Stromal Cells ; cytology ; Umbilical Cord ; cytology ; Vascular Endothelial Growth Factor A ; pharmacology

OBJECTIVETo investigate the effect of lymphadenectomy adjacent to inferior mesenteric artery root on the prognosis of rectal cancer.

METHODSClinicopathological data of 260 cases with rectal cancer undergone radical operation were analyzed retrospectively. The patients were divided into two groups. Group D(2): the lymph nodes adjacent to mesenteric artery root were not excised (n=188). Group D(3): the lymph nodes adjacent to mesenteric artery root were excised (n=72). Prognosis of two groups was compared during the follow-up period.

RESULTSIn group D(2), the 1-, 3-, 5-year total survival rates (TS) were 97.3%, 87.2% and 77.1%, and tumor-free survival rates (TFS) were 93.1%, 83.0% and 76.8% respectively. In group D(3 ), the 1-, 3-, 5-year total survival rates (TS) were 94.4%, 79.2% and 73.6%, and tumor-free survival rates (TFS) were 86.1%, 76.4% and 71.0% respectively. The differences of TS and TFS between two groups were not significant according to Kaplan-Meier analysis (P>0.05). Multivariate analysis revealed that the excision of lymph nodes adjacent to mesenteric artery root was not statistically correlated with the recurrence, metastasis and survival time after radical operation of rectal cancer.

CONCLUSIONExcision of lymph nodes adjacent to inferior mesenteric artery root has no significant impact on prognosis and it is unnecessary in the radical operation of rectal cancer.

Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lymph Node Excision ; methods ; mortality ; Lymph Nodes ; surgery ; Lymphatic Metastasis ; Male ; Mesenteric Artery, Inferior ; surgery ; Middle Aged ; Prognosis ; Rectal Neoplasms ; mortality ; pathology ; surgery ; Survival Rate ; Treatment Outcome

OBJECTIVETo evaluate the clinical value of different regional lymph node staging system and to establish a predictive prognostic model for stage III( colon cancer.

METHODSA total of 256 Patients with stage III( colon cancer from January 1999 to December 2008 were identified from the China Medical University Cancer and underwent radical surgery. Based on information on regional lymph nodes, lymph nodes were staged LNR staging using pN stage in the 7th edition of the AJCC, the jN stage of the JGR, and LNR-stage on the basis of Log-rank statistics, respectively. Using the linear trend chi-square test, likelihood ratio Chi-square test, concordant index(c-index) to evaluate the homogeneity, monotonicity, and discrimination power of the staging system. Univariate and multivariate analyses were used to determine the clinical and pathological prognostic impact factors. After relevant diagnostic models were established, the Akaike Information Criterion (AIC) value was calculated to compare and identify the best diagnostic model.

RESULTSLog-rank statistics found that 0.11 and 0.39 were the optimal cut-off point. LNR staging system included LNR1 (LNR<0.11), LNR2 (0.11,0.39), and LNR3(0.39,1). The concordance indices were 0.624 for pN, 0.611 for jN, and 0.700 for LNR. The heterogeneity was the lowest for LNR. Cox regression model was used to establish prognostic models for pN, jN, and LNR, and the AIC was 99.937, 71.631, and 65.548, respectively. The prognostic value was the highest for LNR.

CONCLUSIONLNR staging is the ideal staging system for stage III( colon cancer patients, which is better than the latest version of the current AJCC pN stage and JGR jN staging.

China ; Colonic Neoplasms ; pathology ; Humans ; Lymph Nodes ; Lymphatic Metastasis ; Multivariate Analysis ; Neoplasm Staging ; Prognosis