Adenocarcinoma ; pathology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Dose-Response Relationship, Drug ; Humans ; Nucleosides ; administration & dosage ; pharmacology ; Proto-Oncogene Proteins c-akt ; antagonists & inhibitors ; Pyridazines ; administration & dosage ; pharmacology ; Stomach Neoplasms ; pathology

Objective To identify the relationship between sorafenib's efficacy and its side effects in treatment of advanced renal cell carcinoma patients. Methods Fifty-one patients having measurable diseases were diagnosed with advanced renal cell carcinoma. Of whom, 26 patients were in stage T1Nx,0,1M1, 12 patients in stage T2Nx,0 M1, 8 patients in stage T3NxM1, 5 patients in stage T4NxM1. These 46 patients of T1 -T3 had their primary diseases removed, but the 5 T~ patients didn"t have their primary diseases removed. These 51 patients received oral sorafenib 400 mg Bid continual-ly and they had CT scan every two months to evaluate the progression. The dosage of sorafenib wasmodified according to efficacy and toxicity. Two patients changed the dosage to 200 mg Bid due to se-vere side effects. Sixteen patients increased the dosage to 600 mg Bid or 800 mg Bid. The response ofSorafenib and toxicities as well as their severity were recorded. The toxicity severity was graded ac-cording to National Cancer Institute Common Toxicity Criteria version 3.0. The efficacy was deter-mined by RECIST criteria. The efficacy and progression free survival (PFS) were recorded. The sta-tistics analysis was conducted between sorafenib's side effects and efficacy as well as their severity by multi-faetor Logistic regression. Results The rates of adverse events in the patients receiving oral sorafenib were hand-foot skin reaetion 68. 6% (35/51), diarrhea 39. 2% (20/51), rash 25. 5% (13/ 51), mucositis 23.5% (12/51), hypertension 17.6% (9/51), and myelosuppression 13. 7%(7/51). The response rate in the patients who had toxicity of grade 3-4 was 33.3%(12/36), and that in the patients who had slight toxicity was 12.0%(3/25). The rate of hand-foot skin reaction was higher than that of diarrhea, rash, mucositis, hypertension and bone marrow suppression (P<0.01). Sor-afenib's efficacy was eorrelated to rash and mueositis (P=0.048, 0.045 respectively). More grade 3 4 side effects occurred in the patients who would have better response to sorafenib (P=0.008). The median PFS was 15.0 months and PFS was not related to the toxicity and its severity. Conclusions It may help to predict the response for sorafenib's side effects and efficacy in the treatment of the patients with advaneed renal cell earcinoma.

Objective To analyze the effect and related factors of sorafenib in the treatment of metastatic renal cell carcinoma(MRCC), and identify the potential predictive factors of sorafenib re-sponse. Methods The data of 51 MRCC patients who received sorafenib therapy, with or without combination with interferon or chemotherapy were retrospectively reviewed. After two cycles of treat-ment, patients were evaluated for progression or response. Pearson Chi-square test and Logistic re-gression test were performed respectively as univariate and multivariate analyses of sorafenib response. Results The overall objective response rate was 29.4%(95% confidence interval 16.9% to 41.9%, with 1(2.0%) complete response and 14(27.4%) partial responses. Twenty-nine(56.9%) had stable disease, and 7 (13.7%) had progression disease (PD). Significant independent predictive factors asso-ciated with good response in multivariate analysis were lung metastasis only(P=0.021, HR=5.127). Conclusions Sorafenib is effective in MRCC patients. Lung metastasis only is predictive factor in mul-tivariate analysis for sorafenib response.

Objective To evaluate the efficacy and safety of sunitinib as first line treatment in patients with metastatic renal cell carcinoma (RCC). Methods This study included 46 Chinese patients who were diagnosed with metastatic RCC after radical nephrectomy. The patients received oral sunitinib (50 mg once daily on a 4 weeks on, 2 weeks off) on a 6 weeks cycle dose schedule until disease progression or intolerable toxicities occurred. Results The overall objective response rate was 32.6% (95% confidence interval [CI, 19.1% to 46. 1%]), and the disease control rate was 86.9%,with complete response (CR) 0 (0%), partial responses (PRs) 15 (32.6%), stable disease (SD) 25(54.3 %), and progression disease (PD) 6 ( 13. 1%). The median progression-free survival was 11 months, and the 1-year survival rate was 65.2%, while the median overall survival (mOS) has not been reached. The main adverse events included fatigue 33 (71.7%), skin discoloration 29 (63.0 %),anorexia 28 (60.9%), hand-foot syndrome 26 (56.5%), oral mucositis 25 (54.3%), hypertension 19 (41.3%), facial edema 18 (39.1%), diarrhea 17 (37.0%), hemorrhage 17 (37.0%), nausea 15 (32.6%), and hematological toxicity: leukopenia 32 (69.6%), neutropenia 30 (65.2%), thrombocytopenia 28 (60.9%), anemia 21 (45.7%). Most of grade 3/4 serious adverse events were thrombocytopenia in 15 (32. 6%) patients. Conclusions Sunitinib has a prominent effect in metastatic renal cell cancer in a Chinese population with mostly mild to moderate adverse reactions. More attention should be paid to grade 3/4 adverse reaction of thrombocytopenia.

Objective To investigate the prevalence of endemic fluorosis in Guide county of Qinghai province, in order to provide appropriate measures to monitor and control the disease. Methods Damo, Wenquan, Baoning villages(water source has been changed) and Taiping village(water source has not been changed) in Guide county were involved in the study in 2008. One tap water sample was collected in dry and rainy seasons, respectively. Water fluoride was tested in accordance with the "Standard Test Methods for Drinking Water" (GB/T 5750.5-2006); of all the children aged 8 to 12, dental fluorosis was diagnosed using Dean criteria; 6 copies of urine samples were collected in each age group, urinary fluoride was measured using fluoride ion-selective electrode (WS/T 89-1996). According to the "Clinical Diagnostic Criteria of Endemic Skeletal Fluorosis "(WS 192-2008), clinical skeletal fluorosis was determined in adults over the age of 16 by X-ray examination for 10 people in each selected village. Results The mean water fluoride was 0.58,0.38,2.28,0.37 mg/L in Damo, Wenquan, Taiping, and Baoning villages, respectively, and that of Taiping village exceeded the national standard(1.0 mg/L). One hundred and ninety-three children aged 8-12 were checked, the detection rate of dental fluorosis was 49.74% (96/193); urine samples of 116 children were tested, median urinary fluoride was 1.49 mg/L A total of 1503 adults over the age of 16 were examined, the clinical detection of skeletal fluorosis was 51.63%(776/1503); a total of 82 people were X-rayed, X-ray detection of skeletal fluorosis was 20.73%(17/82). The characteristic of X-rays were degeneration and ossification of interosseous membrane. Conclusions Prevalence of dental fluorosis of children and adult clinical skeletal fluorosis are higher. The endemic fluorosis is still comparatively serious. Prevention efforts need to be further strengthened.

Objective To observe the state of endemic flurosis, construction and running status of water improvement projects in order to provide a scientific basis for prevention and treatment fluorosis. Methods Water samples of the diseased and nondiseased villeges were collected from east, west, south, north and centre of each villege in 2005, and fluoride concentration was determined for each surveyed village with unimproved-water. At the same time, all the tap water and source water samples were collected to determine fluoride concentration in each water-improved village surveyed. In 2008, all the endemic fluorosis villages in Guied county were divided into slight, medium and heavy types according to the water fluoride content before water improved, and 1,1,3 survey villages were chosen from each type. In all of the village children aged 8 to 12 years were tested for dental fluorosis by Dean method. Six copies of the urinary fluoride were sampled in different age groups. The fluorine content in water and urine was determined by F-ion selective electrode. The situation of clinical skeletal fluorosis of adults over 16 years of age was investigated, 20 adults (evenly divided between men and women) in the villages of medium and heavy types were examined by X-ray for skeletal fluorosis. Results In 3 village fluoride content of drinking water exceeded the national drinking water standards ( <1.0 mg/L) of 85 surveyed villages with improved-water. Among the 16 projects, 8 were intermittently running and 3 were retired, leaving only 31.25% of the projects active. Theprevalence of enamel fluorosis was 41.13%( 116/282), that of skeletal flurosis was 47.95%(969/2021) and that of X-ray checked was 20.73% (17/82). The median of urine fluoride was 1.06 mg/L and the scope was 0.20 - 9.44 mg/L.Conclusions Most of the improved-water projects do not normally supply water in the disease ward of Guide county. Therefore, there is an increasing trend of the disease, so further control measures are needed.

According to the super-position principle of the reinforcement of biological activities, a series of novel E-substituted 2, 3-diaryl propenoic acyloxy phosphonate derivatives were designed and synthesized. And the structures of the target compounds were confirmed by IR, 1H NMR, 13C NMR and elemental analysis. Furthermore, the cytotoxicities of all compounds on A-549, SGC-7901 and EC-109 in vitro were evaluated by MTT assay, and some of them showed good antitumor activity. Among the active compounds, especially, the IC50 value of compound 3e was (12.7 ± 1.9) μmol x L(-1) against A-549 cells, similar to cisplatin [IC50 = (8.0 ± 1.5) μmol x L(-1)], compounds 3g and 3k had better inhibition effect on EC-109 cells growth, with the IC50 values of (9.5 ± 1.8) μmol x L(-1) and (11.5 ± 0.9) μmol x L(-1) respectively, and compounds 3i and 3k exhibited good cytotoxic property on A-549, SGC-7901 and EC-109, which were worth further investigation.
Antineoplastic Agents ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; Drug Design ; Humans ; Organophosphonates ; chemical synthesis ; pharmacology

BACKGROUNDTo develop HPV16 L1/E6 and L1/E7 prophylactic and therapeutic DNA vaccines.

METHODSThe nucleotides within HPV 16 E6 and E7 genes, which are responsible for viral transforming activity, were mutated by mega primer site-directed mutagenesis method. The correctly mutated E6 and E7 fragments were separately cloned into an eukaryotic expression vector pVAX1, together with HPV 16 L1 gene, generating chimeric recombinants plasmids 1MpVAX1-L1E6, 2MpVAX1-L1E6, 1MpVAX1-L1E7, 2MpVAX1-L1E7 and 3MpVAX1-L1E7. CHO cells were transiently transfected with the individual DNA vaccines by calcium phosphate method. Target protein expressions in the extracts of the transfected cell lines were measured by ELISA and immunohistochemistry, with HPV 16 L1 and E6 specific monoclonal antibodies.

RESULTSELISA showed the P/N ratios in the cell extracts transfected with L1E6 and L1E7 plasmids were greater than 2.1. Immunohistochemistry revealed brownish precipitant signal in cytoplasm and nuclei of the transfected cells.

CONCLUSIONSSuccessful constructions of prophylactic and therapeutic DNA vaccine plasmids may be useful for future animal experiment and clinical trial.

Animals ; CHO Cells ; Capsid Proteins ; Cricetinae ; Cricetulus ; Enzyme-Linked Immunosorbent Assay ; Humans ; Mutagenesis, Site-Directed ; Oncogene Proteins, Fusion ; biosynthesis ; immunology ; Oncogene Proteins, Viral ; biosynthesis ; genetics ; immunology ; Papillomaviridae ; genetics ; Papillomavirus E7 Proteins ; Plasmids ; genetics ; Point Mutation ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; Repressor Proteins ; Transfection ; Vaccines, DNA ; biosynthesis ; genetics ; Viral Vaccines ; biosynthesis ; genetics

OBJECTIVETo compare the influence of propofol and isoflurane on pro-inflammatory and anti-inflammatory cytokine response to perioperative period of tongue cancer surgery.

METHODSTwenty-four adult patients undergone the operation of tongue cancer were assigned to two groups randomly, propofol group (Group P) and isoflurane group (Group I). In group P, anesthesia was induced with fentanyl 2-3 microg/kg, propofol 2 mg/kg, atracurium 0.6 mg/kg and maintained with propofol 5-8 mg x kg(-1) x h(-1) and inhalation of 50% nirous oxide (N2O:O2=50%:50%). In group I, anesthesia was induced with 3%-4% isoflurane, fentanyl 2-3 microg/kg, diazepam 0.06-0.1 mg/kg, atracurium 0.6 mg/kg and maintained with inhalation of 50% N2O and isoflurane (ended-tidal isoflurane was maintained at 0.6%), in two groups atracurium was given intermittently. Blood samples were taken from peripheral vein before anesthesia (TO), at the end of operation (T1), 24 h (T2) and 48 h (T3) after operation for determination of serum IL-6 and IL-10 concentrations. The mean arterial pressure (MAP) and body temperature in two groups were recorded.

RESULTSIL-6 and IL-10 levels increased significantly in two groups at T1, T2 and T3 compared with T0 (P < 0.01). The increasing trend of IL-6 and IL-10 levels were similar in both groups, whereas the level of IL-6 at T1 in propofol group was lower than that of isoflurane group significantly (P < 0.01), however the level of IL-10 was much higher in propofol group than that of isoflurane group at T1 and T2 (P < 0.05).

CONCLUSIONThe influence of total intravenous anesthesia of propofol on post-operation inflammatory response is much gentler than isoflurane.

Adult ; Anesthesia, Intravenous ; Cytokines ; Female ; Humans ; Interleukin-10 ; Interleukin-6 ; Isoflurane ; Male ; Middle Aged ; Neoplasms ; Perioperative Period ; Postoperative Period ; Propofol

OBJECTIVETo construct full-length hepatitis B core particles presenting preS1 aa 21-47 epitope and truncated core particles presenting preS1 aa 37-45 epitope on their surface and compare their antigenicity.

METHODSPreS1 aa21-47 epitope and aa 37-45 epitope were inserted respectively into full-length hepatitis B core (aa 1-183) and truncated HBcAg (aa 1-144), between the 78th (Asp) and 79th (Pro). The genes synthesized after the codon optimization were ligated to the pET43. 1a vector with the same cohesive terminal (NdeI and XhoI) and expressed in the E. coli expression system. The morphology of the proteins of interest were observed by electron microscope and characterized by ELISA and Western Blotting.

RESULTSThe morphology of the virus-like particles were confirmed by electron microscope. H2 were solid particles with a diameter of (31.61 +/- 1.27) nm, while H3 were hollow particles with a diameter of (28.46 +/- 1.16) nm. Statistical analysis showed that H2 is larger than H3 in the diameter (P < 0.01). The antigenicity of the inserted epitopes and carrier protein were identified by ELISA and Western Blotting.

CONCLUSIONChimeric hepatitis B core particles presenting the preS1 neutralizing epitopes on their surface have been expressed, purified and identified, which lays the foundation for its application in vaccine research.

Epitopes ; chemistry ; genetics ; immunology ; Hepatitis B ; immunology ; virology ; Hepatitis B Core Antigens ; chemistry ; genetics ; immunology ; Hepatitis B Surface Antigens ; chemistry ; genetics ; immunology ; Hepatitis B virus ; chemistry ; genetics ; immunology ; Humans ; Neutralization Tests ; Protein Precursors ; chemistry ; genetics ; immunology ; Recombinant Fusion Proteins ; chemistry ; genetics ; immunology