OBJECTIVETo throw a light on the possible factors which might induce resistance of vascular targeting treatment in tumors by reviewing the recent publications in the field of tumor angiogenesis and vascular targeting treatment. Data sources The data used in this review were mainly from Medline and PubMed for relevant English language articles published from 1971 to January 2008. The search terms were "angiogenesis", "vascular targeting treatment" and "endothelial progenitor cells". Study selection Articles involved in the possible influence factors during angiogenesis and vascular targeting treatment were selected, including angiogenic or anti-angiogenic mechanism, tumor vasculature, tumor cells, cancer stem cells and endothelial progenitor cells.

RESULTSAs a promising strategy vascular targeting treatment still has experimental and clinical setbacks which may term tumor vasculature's resistance to anti-angiogenesis agents. There are several possible explanations for such a resistance that might account for clinical and preclinical failures of anti-angiogenic treatment against tumor. Proangiogenic effect of hypoxia, normal tumor vasculature, escape of tumor cells and tumor vasculogenesis are included. This review reveals some clues which might be helpful to direct future research in order to remove obstacles to vascular targeting treatment.

CONCLUSIONSGenerally and undoubtedly vascular targeting treatment remains a promising strategy. But we still have to realize the existence of a challenging future. Further research is required to enhance our knowledge of vascular targeting treatment strategy before it could make a more substantial success.

Antineoplastic Agents ; pharmacology ; Blood Vessels ; drug effects ; Cell Hypoxia ; Endothelial Cells ; cytology ; Humans ; Neoplasms ; blood supply ; drug therapy ; Neoplastic Stem Cells ; drug effects ; Neovascularization, Physiologic ; drug effects ; Phenotype ; Stem Cells ; cytology

13C metabolic flux analysis(13CMFA)have been the research hotspots of metabolic engineering internationally due to its accuracy and applicability.It is vital that the measurement of 13C labelling pattern of proteinogenic amino acids for 13C metabolic flux analysis.To acquire 13C-labelling proteinogenic amino acids,Pseudomonas denitrifican which products Vitamin B12 was firstly fed with mimimal culture medium contained 20% U-13C and 80% natural glucose,after the culture reached a steady state,then about 20 mg biomass was hydrolyzed by 1 ml of 6 mol/L hydrochloric acid for 24h at 110℃.Then amino acids was separated,concentrated,evaporated in a vacuum,and derivatized with MBDSTFA,TBDMS-derivatized amino acids can be observed by GC-MS last we get 13C labelling pattern of fifteen aminio acids through mass spectrum.The experimental methods and sample preparation offers referential value for the development of 13C metabolic flux analysis in our courtry.

Animals ; Calcium Channel Blockers ; therapeutic use ; Dogs ; Hypothermia ; complications ; Male ; Nimodipine ; therapeutic use ; Ventricular Fibrillation ; etiology ; prevention & control

The purpose of the present study was to investigate the effect of sodium nitrite (SN) on alcohol-induced acute liver injury in mice. Forty male C57bL/6 mice were randomly divided into 4 groups. Acute alcohol-induced liver injury group were injected intraperitoneal (ip) with alcohol (4.5 g/kg); SN preconditioning group were pretreated with SN (16 mg/kg, ip) for 12 h, and received alcohol (4.5 g/kg, ip) injection; Control and SN groups were treated with saline and SN, respectively. After the treatments, liver index (liver/body weight ratio) was determined. Colorimetric technique was performed to measure the serum alanine transaminase (ALT), aspartate transaminase (AST), liver superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activities, as well as malondialdehyde (MDA) content. The pathological index of liver tissue was assayed by HE and TUNEL fluorometric staining. Using Western blot and immunohistochemistry staining, the expression of hypoxia-inducible factor-1α (HIF-1α) protein was detected. The results showed that, compared with acute alcohol-induced liver injury group, pretreatment with low doses of SN decreased liver index and serum levels of ALT and AST, weakened acute alcohol-induced hepatocyte necrosis, improved pathological changes in liver tissue, increased live tissue SOD, GSH-Px and CAT activities, reduced MDA content and apoptosis index of hepatocytes, and up-regulated HIF-1α protein level in liver tissue. These results suggest that the pretreatment of SN can protect hepatocytes against alcohol-induced acute injury, and the protective mechanism involves inhibition of oxidative stress and up-regulation of HIF-1α protein level.
Alanine Transaminase ; metabolism ; Alcohols ; adverse effects ; Animals ; Apoptosis ; Aspartate Aminotransferases ; metabolism ; Chemical and Drug Induced Liver Injury ; drug therapy ; Glutathione Peroxidase ; metabolism ; Hepatocytes ; drug effects ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Male ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Protective Agents ; pharmacology ; Sodium Nitrite ; pharmacology ; Superoxide Dismutase ; metabolism ; Up-Regulation

AIMTo study the chemical composition of Tripterygirm wilfordii Hook. f.

METHODSColunm chromatography was used to separate the chemical constituents. UV, IR, MS, HRMS, 1HNMR, 13CNMR (COM and OFR), 1H-1H COSY, 1H-13C COSY, NOESY and COLOC spectra were used to determine the structures of the isolated constituents.

RESULTSTwo sesquiterpene alkaloids were isolated and their structures were elucidated as wilforgine and wilfordlongine on the basis of spectral evidence.

CONCLUSIONWilfordclonine is a new sesquiterpene alkaloid.

Lactones ; chemistry ; isolation & purification ; Molecular Structure ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Pyridines ; chemistry ; isolation & purification ; Tripterygium ; chemistry

OBJECTIVETo investigate the risk factorsthat predict pain during colonoscopy for decision of sedation or analgesia before the examination.

METHODSA total of 283 consecutive patients undergoing colonoscopicexamination at Nanfang Hospital between July, 2016 and September, 2016were retrospectively analyzed. The clinical data and visual analogue scale after the examination were analyzed to identify the risk factors for pain during colonoscopy using univariate analysis and multivariate logistic regression. A risk stratification model for predicting pain in colonoscopy was established.

RESULTSThe completion rate of the procedure was significantly lower in patients with a visual analogue scale ≥5 (P<0.000). Univariate analysis showed that female patients, previous abdominal surgery, no previous experience with colonoscopy, complaint of abdominal pain before colonoscopy, insufficient experience of the endoscopists, patient's anticipation of high painlevelbefore examination, and a low body mass index (BMI) were all associated with the experience of pain in colonoscopy (P<0.05). Multivariate logistic regressionanalysis identified BMI index (X), level of experience of the endoscopist (A, A, A) and the patient's anticipation of painlevel (X) as the risk factors of pain in colonoscopy(P<0.05), and the establishedmodel with the 3 variables was: P=e/(1+e),Y=0.049-0.124×X-0.97×X+1.713×A+0.781×A+0.147×A, which showed a sensitivity of 70.3% and a specificity of 67.5%for predicting pain in colonoscopy.

CONCLUSIONThe patient's anticipation of a high pain level in colonoscopy, insufficient experience of the endoscopist, and a low BMI are the independent risk factors for pain in colonoscopy, and evaluation of these factors can help in the decision-making concerning the use of sedation or analgesia before colonoscopy.

Abdominal Pain ; etiology ; Analgesia ; Colonoscopy ; adverse effects ; Conscious Sedation ; Female ; Humans ; Male ; Pain Management ; Pain Measurement ; Retrospective Studies ; Risk Factors

OBJECTIVETo investigate the aberrant promoter methylation of hMLH1 gene promoter and its clinical significance in papillary thyroid cancer (PTC).

METHODSmethylation of hMLH1 gene promoter in the cancer tissue and matched tumor-adjacent normal tissue of 152 PTC patients were detected by real-time methylation specific PCR (qMSP). The relationship between the methylation of hMLH1 gene promoter and clinicopathological features was analyzed.

RESULTSThe methylation rate of hMLH1 gene promoter in cancer tissues was 37.5% (57/152), of which 33 cases were totally methylated and 24 cases were partially methylated. The methylation rate of adjacent normal tissues was 5.3% (8/152)(all were partially methylated). The methylation rate of PTC tissues was significantly higher than that in the tumor-adjacent normal tissue (P < 0.01). The promoter methylation of hMLH1 gene in PTC was significantly correlated with age, size and number of the primary lesion, local invasion, T stage and lymph node metastasis (P < 0.05) , but not correlated with gender and clinical stage (P > 0.05).

CONCLUSIONPromoter methylation of hMLH1 gene is a common molecular event in PTC tissue, and it is significantly correlated with the progression of PTC.

Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; Adolescent ; Adult ; Age Factors ; Aged ; Carcinoma ; genetics ; metabolism ; pathology ; Carcinoma, Papillary ; DNA Methylation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; MutL Protein Homolog 1 ; Neoplasm Invasiveness ; Neoplasm Staging ; Nuclear Proteins ; genetics ; metabolism ; Promoter Regions, Genetic ; genetics ; Thyroid Neoplasms ; genetics ; metabolism ; pathology ; Tumor Burden ; Young Adult

OBJECTIVETo investigate the value of urgent colonoscopy in the diagnosis of severe acute lower gastrointestinal bleeding and the optimal bowel preparation before examination.

METHODSThe clinical data were collected from 188 patients undergoing wither urgent or elective colonoscopy for severe acute lower gastrointestinal bleeding in Nanfang Hospital. Univariate analysis was used to assess the effect of the timing of colonoscopy on the diagnostic rate of hemorrhage, and a multivariate model which stratified bowel cleanliness was used to analyze the impact of bowel cleanliness on the diagnostic rate of urgent colonoscopy.

RESULTSOf the 188 patients, 118 underwent urgent colonoscopy and 70 underwent elective colonoscopy examinations. The diagnostic rates were comparable between the two groups (44.1% vs 41.4%, P=0.724), but urgent colonoscopy resulted in a significantly higher diagnostic rate for identifying the bleeding source (32.2% vs 18.6%, P=0.041). The proportion of the patients taking oral laxatives was significantly lower in urgent colonoscopy group (P<0.001). Oral laxatives versus enema resulted in good, moderate, and poor bowel cleanliness in 63.6% vs 13.5%, 28.6% vs 24.3%, and 7.8% vs 62.2% of the patients (P<0.001). Univariate analysis indicated that good bowel cleanliness was associated with a significantly higher diagnostic rate of colonoscopy than poor bowel cleanliness (P=0.012). Multivariate analysis showed that with good bowel cleanliness, urgent colonoscopy yielded a significantly higher diagnostic rate than elective colonoscopy (P=0.030); subgroup analyses suggested that good bowel cleanliness improved the diagnostic rate of urgent colonoscopy as compared with poor bowel cleanliness (P=0.015).

CONCLUSIONIn patients with good bowel cleanliness, urgent colonoscopy yields a higher diagnostic rate than elective colonoscopy for severe acute lower gastrointestinal bleeding. Poor bowel cleanliness resulting from bowel preparation by enema significantly lowers the diagnostic performance of urgent colonoscopy. Oral laxatives are recommended over enemas for bowel preparation before urgent colonoscopy when the patients have stable hemodynamics.

Acute Disease ; Cathartics ; administration & dosage ; classification ; Colonoscopy ; standards ; Gastrointestinal Hemorrhage ; diagnosis ; Humans ; Time Factors

This study is to report the determination of the effect of sodium nitrite induced oxygen species (ROS) on the epithelial-mesenchymal transition in hepatoma cells in mice bearing H22 and investigation of its role in hypoxia-inducible factor 1alpha (HIF-1alpha) in this process. Mice hepatocarcinoma cell line H22 was inoculated subcutaneously into right axillary of sixty male Kunming mice and then randomly divided into four groups: control group; low-dose sodium nitrite group (10 mg x kg(-1)), medium-dose sodium nitrite group (20 mg x kg(-1)) and high-dose sodium nitrite group (30 mg x kg(-1)). Sodium nitrite group was given (ig) sodium nitrite with 10-30 mg x kg(-1) x d(-1) for 21 days. Compared with control group, there was no obvious difference between the two groups in the volume or weight of xenografts, but in sodium nitrite treatment group, the activity of SOD and CAT decreased and contents of MDA or nitrite increased in tumor tissue of mice bearing H22; epithelial-mesenchymal transition (EMT) of hepatoma cells was induced, the EMT-phenotype tumors displayed a greater degree of local aggressiveness, with dissection through adjacent fascia and skeletal muscle. The increased expression of HIF-la and vimentin and declination of E-cadherin were confirmed by immunohistochemistry and Western blotting. These data indicate sodium nitrite treatment could improve the epithelial-mesenchymal transition of xenografts in mice bearing H22, which might relate to the fact that ROS mediated signal pathway increased the expression of HIF-1alpha.
Animals ; Cadherins ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Catalase ; metabolism ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Epithelial-Mesenchymal Transition ; drug effects ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Liver Neoplasms ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Mice ; Neoplasm Transplantation ; Random Allocation ; Reactive Oxygen Species ; metabolism ; Signal Transduction ; drug effects ; Sodium Nitrite ; administration & dosage ; pharmacology ; Superoxide Dismutase ; metabolism ; Tumor Burden ; drug effects ; Vimentin ; metabolism

Aged ; Femur ; Head and Neck Neoplasms ; surgery ; Humans ; Male ; Reconstructive Surgical Procedures ; methods ; Skin Transplantation ; Surgical Flaps