OBJECTIVETo evaluate the effect of transcatheter arterial chemoembolization (TACE) with high-dose iodized oil on hepatic tumor growth and metastasis in rabbits.

METHODSForty-eight rabbits with implanted VX2 tumor were randomly divided into control group, routine dose iodized oil TACE group and high-dose iodized oil TACE group to receive perfusion through the hepatic artery with 0.9% saline, 5 mg adriamycin with routine-dose iodized oil, and 5 mg adriamycin with high-dose iodized oil, respectively. The tumor volume, tumor necrosis, intrahepatic and lung metastasis were examined 2 weeks after TACE.

RESULTSNo significant difference was found in the tumor volume between the 3 groups before TACE (P>0.05). The rabbits receiving TACE with iodized oil, especially at the high dose, showed significantly reduced tumor volume as compared with the control group (P<0.01). TACE with high-dose iodized oil resulted in significantly increased tumor necrosis rate in comparison with the control group and TACE with a routine dose of iodized oil (P<0.05); high-dose iodized oil TACE was also associated with reduced intrahepatic and lung metastasis as compared routine dose iodized oil TACE (P<0.05).

CONCLUSIONTACE with high-dose iodized oil can obviously inhibit the growth and intrahepatic and lung metastasis of transplanted VX2 liver tumor in rabbits .

Animals ; Catheterization, Peripheral ; Chemoembolization, Therapeutic ; methods ; Contrast Media ; administration & dosage ; Dose-Response Relationship, Drug ; Drug Carriers ; administration & dosage ; Female ; Hepatic Artery ; Iodized Oil ; administration & dosage ; Liver Neoplasms, Experimental ; therapy ; Male ; Rabbits

Comparative pharmacokinetic (PK) analysis is often carried out throughout the entire period of drug development, the common approach for the assessment of pharmacokinetics between different treatments requires that the individual PK parameters, which employs estimation of 90% confidence intervals for the ratio of average parameters, such as AUC and Cmax, these 90% confidence intervals then need to be compared with the pre-specified equivalent interval, and last we determine whether the two treatments are equivalent. Unfortunately in many clinical circumstances, some or even all of the individuals can only be sparsely sampled, making the individual evaluation difficult by the conventional non-compartmental analysis. In such cases, nonlinear mixed effect model (NONMEM) could be applied to analyze the sparse data. In this article, we simulated a sparsely sampling design trial based on the dense sampling data from a truly comparative PK study. The sparse data were analyzed with NONMEM method, and the original dense data were analyzed with non-compartment analysis. Although the trial design and analysis methods are different, the 90% confidence intervals for the ratio of PK parameters based on 1000 Bootstrap are very similar, indicated that the analysis based on NONMEM is a reliable method to treat with the sparse data in the comparative pharmacokinetic study.
Area Under Curve ; Confidence Intervals ; Humans ; Nonlinear Dynamics ; Pharmacokinetics ; Sampling Studies

OBJECTIVESTo investigate the relationship between the expression of transgelin-2 and the clinicopathological factors of colorectal carcinoma and evaluate the value of transgelin-2 in prognostic assessment of the colorectal cancer patients.

METHODSUsing tissue microarray and immunohistochemical methods, we examined transgelin-2 of 120 colorectal cancer patients received surgical treatment from September 2002 to April 2004, including 74 male and 46 female, age from 26 to 89 years. Analyzed the relationship between transgelin-2 and both the clinicopathological features and prognosis of the colorectal cancer by using χ² test and Kaplan-Meier survival analysis. Cox proportion hazard regression analysis was used to study the independent prognostic factors.

RESULTSThe positive rate of transgelin-2 expression was 69.2% in colorectal carcinoma. The transgelin-2 expression correlated with differentiation degree (χ² = 5.420), lymph nodes metastasis (χ² = 45.577), distant metastasis (χ² = 12.009), and TNM staging (χ² = 47.577). The survival time was (39 ± 5) months in patients with positive expression of the transgelin-2, while (59 ± 3) months in patients with negative expression. The patient's survival time was statistically correlated with the transgelin-2 expression (P = 0.003). Distant metastasis (RR = 8.318, 95%CI: 4.119 - 16.790), lymph nodes metastasis (RR = 2.794, 95%CI: 1.246 - 6.263) and transgelin-2 expression (RR = 1.834, 95%CI: 1.118- 2.973) were independent prognostic factors in patients with colorectal cancer (P < 0.05).

CONCLUSIONSThe expression of transgelin-2 is correlated with clinicopathological features and prognosis in colorectal cancer, may be the potential marker of metastasis and the prognosis of colorectal cancer patients.

Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Microfilament Proteins ; metabolism ; Middle Aged ; Muscle Proteins ; metabolism ; Prognosis ; Regression Analysis

OBJECTIVETo evaluate the association between the polymorphisms of excision repair cross complementation group 1 (ERCC1), X-ray repair cross complementing 1 (XRCC1), glutathione S-transferase Pi 1 (GSTP1) and the survival of advanced gastric cancer patients treated with oxaliplatin-based combination chemotherapy.

METHODSEighty five patients with advanced gastric cancer accepted oxaliplatin/5-FU-based chemotherapy as first-line chemotherapy were investigated. Peripheral venous blood was taken before chemotherapy. DNA was extracted from peripheral venous blood. The genetic polymorphisms were detected by real-time PCR assay. The association between time to progression, overall survival and the polymorphisms was analyzed.

RESULTSThe median time to progression of the 85 cases was 5.3 months, and the median overall survival was 8.0 months. ERCC1-118 C/C, XRCC1-399 G/G and GSTP1-105 A/G + G/G were favorable genotypes and the number of the favorable genotypes was associated with survival of the patients. The median overall survival was 12.5 months, 10.0 months, 6.5 months and 4.5 months for patients with 3 favorable genotypes, 2 favorable genotypes, 1 favorable genotype and none favorable genotype, respectively, with a significant difference (χ(2) = 35.54, P < 0.01).

CONCLUSIONGenetic polymorphisms of ERCC1-118, XRCC1-399 and GSTP1-105 are associated with TTP and OS of advanced gastric cancer patients treated with oxaliplatin/5-Fu-based combination chemotherapy as the first-line chemotherapy.

Adenocarcinoma ; drug therapy ; genetics ; pathology ; Adenocarcinoma, Mucinous ; drug therapy ; genetics ; pathology ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; DNA-Binding Proteins ; genetics ; Disease Progression ; Endonucleases ; genetics ; Female ; Fluorouracil ; administration & dosage ; Follow-Up Studies ; Glutathione S-Transferase pi ; genetics ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds ; administration & dosage ; Polymorphism, Genetic ; Stomach Neoplasms ; drug therapy ; genetics ; pathology ; Survival Rate ; X-ray Repair Cross Complementing Protein 1

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; metabolism ; pathology ; Carcinoma ; metabolism ; pathology ; Cyclin-Dependent Kinase Inhibitor p27 ; metabolism ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Phosphorylation ; Prognosis ; S-Phase Kinase-Associated Proteins ; metabolism ; Threonine ; metabolism

OBJECTIVETo investigate the role of antigen-processing machinery (APM) component defects in HLA class I antigen down-regulation in laryngeal squamous cell carcinoma (SCC) and to assess the clinical significance of these defects.

METHODSFifty-one formalin-fixed, paraffin-embedded SCC specimens were examined for the expressions of APM component transporter associated with antigen processing (TAP1) and low molecular weight polypeptide (LMP-7) and HLA class I antigen by immunohistochemistry.

RESULTSHLA class I antigens, TAP-1 and LMP-7 expressions were down-regulated in 56.9% (29/51), 39.2% (20/51) and 45.1% (23/51) of the tested specimens respectively, whereas HLA class I antigens, TAP-1 and LMP-7 expressions lost in 21.6% (11/51), 33.3% (17/51) and 27.5% (14/51) of the tested specimens respectively. TAP-1 and LMP-7 expressions were significantly correlated with HLA class I antigen expression (r=0.460, P<0.05 and r=0.685, P<0.05, respectively). HLA class I antigens down-regulation was significantly correlated with T stage (χ2=8.61, P<0.05). Both TAP-1 and LMP-7 down-regulations were significantly correlated with T stage (χ2 values were 9.72 and 8.97 respectively, P<0.05) and TNM stage (χ2 values were 9.18 and 7.70 respectively, P<0.05). TAP-1, LMP-7 and HLA class I antigen down-regulations were significantly associated with reduced patients' overall survival (P<0.05) and disease-free survival (P<0.05). Multivariate analysis showed lymph node metastasis, recurrence and HLA class I antigen down-regulation were unfavorable prognostic factors (P<0.05).

CONCLUSIONSDown-regulated expressions of HLA class I antigen and APM component TAP-1 and LMP-7 occur frequently in laryngeal squamous cell carcinoma, by which cancer cells could avoid immune surveillance, while HLA class I antigen down-regulation is a major contributing factor to tumour progression and mortality.

ATP-Binding Cassette Sub-Family B Member 2 ; ATP-Binding Cassette Transporters ; metabolism ; Adult ; Aged ; Aged, 80 and over ; Antigen Presentation ; Carcinoma, Squamous Cell ; immunology ; metabolism ; pathology ; Female ; Gene Expression Regulation, Neoplastic ; Histocompatibility Antigens Class I ; metabolism ; Humans ; Laryngeal Neoplasms ; immunology ; metabolism ; pathology ; Male ; Middle Aged ; Proteasome Endopeptidase Complex ; metabolism

OBJECTIVETo construct a recombinant adenovirus of survivin vector and provid valuable reference for gene therapy of laryngeal cancer.

METHODSThe survivin gene was cloned by PCR. After confirmation by enzyme restriction analysis and sequencing, the gene and the adenovirus vector were recombined together to construct the recombinant adenovirus vector. The recombinant adenovirus vector was confirmed via both sequencing and digestion restriction analysis, and then linearized and transfected into the HEK 293 cell line to generate recombinant adenovirus.

RESULTSThe sequence analysis demonstrated that the survivin gene sequence was the same as published in the literature, suggesting that a recombinant adenovirus vector has been successfully constructed.

CONCLUSIONSA survivin recombinant adenovirus has been successfully constructed.

Adenoviridae ; genetics ; Genetic Vectors ; HEK293 Cells ; Humans ; Inhibitor of Apoptosis Proteins ; genetics ; metabolism ; Plasmids ; Polymerase Chain Reaction ; Recombinant Fusion Proteins ; genetics ; metabolism ; Transfection

The paper aimed to find the optimal combination and evaluation of the interactions of antitumor effect of the curcumin (Cur) and adriamycin (ADM) in vitro. According to the factorial design and data characteristics, the parameter method combined with the response surface approach were used to analyze the pharmacodynamic interactions of in vitro antitumor effects of the combination of Cur and ADM at different dosages. The results showed that the dose-effect relationship of the combination with the ratio of ADM-Cur 1:3 showed significant differences in comparison with either used alone. The dose-effect curve was shift left in combination. The combination of adriamycin (ADM, 0.693-2.132 micromol L(-1)) and curcumin (Cur, 2.047-6.304 micromol L(-1)) with a fixed ratio (1:3) showed a synergism. With increasing doses of the combination, there is an additive effect. Computer simulation showed a trend of decreasing difference between the observed and expected effects with the dose increasing in Cur from 6.304 to 16.0 micromol L(-1) and ADM from 2.132 to 5.3 micromol L(-1). The response surface analysis showed the optimal combination to be Cur 18.50 micromol L(-1) and ADM 3.89 micromol L(-1) with a ratio of 5:1. This study suggests that the parameter method combined with the response surface analysis provides richer and more reasonable information, and is helpful for quantitative design of drug combination therapy and to describe the nature and degree of drug interaction.
Algorithms ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; Antineoplastic Agents ; administration & dosage ; pharmacology ; Cell Proliferation ; drug effects ; Computer Simulation ; Curcumin ; administration & dosage ; isolation & purification ; pharmacology ; Dose-Response Relationship, Drug ; Doxorubicin ; administration & dosage ; pharmacology ; Drug Synergism ; Humans ; K562 Cells

Objective To analyze the efficacy and safety of glimepiride treatment as initial monotherapy in newly diagnosed patients with type 2 diabetes mellitus (T2DM).Methods This was a subgroup analysis of the GREAT study,which investigated the efficacy and safety of glimepiride as initial monotherapy in Chinese patients with T2DM.This analysis was performed in 209 patients with disease duration less than 6 months and never received any anti-diabetic drugs.The change of HbA1C,fasting plasm glucose (FPG),2 h postprandial blood glucose (2hPPG),homeostasis model assessment for β-cell function index (HOMA-β),homeostasis model assessment for insulin-resistance index(HOMA-IR),the percentage of patients with HbA1C ＜ 7.0％ at endpoint and the incidence of hypoglycemia were evaluated after 16-weeks treatment.Results After 16-weeks glimepiride treatment,HbA1C value reduced significantly from baseline to endpoint,the reduction was statistically significant (9.21％ ± 1.65％ to 6.69％±0.83％,P＜0.001),69.7％ of the patients achieved HbA1C ＜7.0％ at study endpoint.Glimepiride-treated patients also achieved a significant improvement in FPG [from (10.15 ± 2.13) mmol/L to (7.23 ± 1.50) mmol/L,P＜0.001] and 2hPPG [from (17.21 ±4.14) mmol/L to (11.62 ± 3.34) mmol/L].HOMA-β was improved from 17.21± 15.19 [11.62 (2.90,115.8)] to 41.13 ± 44.12 [28.00 (5.1,360.00)],and HOMA-IR was reduced from 2.32± 1.90 [1.76 (0.60,12.80)] to 2.07 ± 1.74 [1.63 (0.4,12.3)].The incidence of all reported symptomatic hypoglycemia was 18.2％,and the incidence of confirmed hypoglycemia was 3.8％.Conclusion This analysis showed that glimepiride treatment as an initial mono-therapy could effectively improve blood glucose control in newly diagnosed patients with T2DM,and the treatment may improve islet β cell function,and the safety profile is reasonably good.

Objective To evaluate the impact of the flood disaster on schistosomiasis transmission along the Yangtze River basin in 2020, so as to provide insights into schistosomiasis prevention and control in flood-affected areas. Methods The data pertaining to the endemic situation of schistosomiasis were collected from 5 provinces of Hunan, Hubei, Jiangxi, Anhui and Jiangsu from 2013 to 2019, including Schistosoma japonicum infections in humans and livestock and snail distribution, and the warning water levels and actual water status were collected in water regions locating in these 5 provinces. The cumulative numbers of S. japonicum egg-positive individuals and bovines during the period from 2013 to 2019, the area of snail habitats in 2019 and the water level on July 12, 2020 were estimated at a county level and employed as parameters for classification of schistosomiasis transmission risk. Then, the cumulative value of each risk index was calculated to assess the risk of schistosomiasis transmission risk. Results After the flood disaster along the Yangtze River basin in 2020, there were 10, 5 and 9 counties (districts) at high risk of schistosomiasis transmission in 5 provinces of Hunan, Hubei, Jiangxi, Anhui and Jiangsu based on number of egg-positive individuals, number of egg-positive bovines and snail distribution, respectively. Based on comprehensive risk indices, there were 10 (8 in Dongting Lake regions of Hunan Province and 2 in Poyang Lake regions of Jiangxi Province) and 15 counties (districts) (4 in Hubei Province, 7 in Hunan Province and 4 in Jiangxi Province) identified at grades 5 and 4 risk of schistosomiasis transmission. Conclusions Dongting Lake regions and Poyang Lake regions are the most severely flood-affected schistosomiasis-endemic foci of China in 2020, and the flood disaster may facilitate the transmission of schistosomiasis in affected areas. Therefore, schistosomiasis control requires to be intensified after the flood disaster to prevent the rebound of the disease.