Calcium-Calmodulin-Dependent Protein Kinases ; antagonists & inhibitors ; Carcinoma ; pathology ; Cell Cycle ; drug effects ; Cell Line ; Cell Line, Tumor ; Enzyme Inhibitors ; pharmacology ; Female ; Flavonoids ; pharmacology ; Gene Expression Regulation ; drug effects ; Humans ; Ovarian Neoplasms ; pathology ; Proto-Oncogene Proteins c-fos ; genetics ; metabolism

OBJECTIVETo investigate the expression of HER2/neu, Ki-67 and TK1 protein in meningiomas in correlation with tumor grades and recurrence.

METHODSTwenty cases of each of the following types of meningiomas were selected for the study, namely: the benign non-recurrent, recurrent benign, atypical and malignant, according to the World Health Organization (WHO) histological classification of nervous system, 2007. Immunohistochemistry study for HER2/neu, Ki-67 and TK1 protein was performed. HER2/neu gene amplification was detected using FISH. Cases with HER2 protein overexpression were studied by immunohistochemistry staining. The results of the biomarker assays were also used to study the correlationship with the tumor grades and tumor recurrency.

RESULTSImmunohistochemistry showed that the positive rates of HER2 expression in non-recurrence benign group, recurrence benign group, atypical group and malignant group were 3 cases (15%), 6 cases (30%), 7 cases (35%), and 10 cases (50%), respectively (P < 0.05). A higher tumor grade was correlated with a higher rate of HER2/neu expression. The Ki-67 and TK1 labeling index (LI) in non-recurrence group were lower than those in the atypical or malignant group (P < 0.05), whereas the atypical group had lower LI than that of the malignant group (P < 0.05). Higher levels of LI of Ki-67 and TK1 were correlated with higher tumor grades and recurrence of the benign meningiomas (P < 0.05). Expression of HER2 was positively correlated with Ki-67 and TK1 (r = 0.445, P < 0.01; r = 0.501, P < 0.01, respectively), and there was a positive correlation between Ki-67 and TK1 (r = 0.450, P < 0.01) as well. HER2/neu gene copy amplification in 7 of 26 cases (26.9%) of HER2 immunopositive meningiomas. The rates of HER2/neu gene amplification were 0 in tumors with 1+ immunopositivity, 4/6 in tumor with 2+ immunopositivity and 3/4 in tumor with 3+ immunopositivity. HER2/neu gene amplification in 3+ and 2+ immunopositive cases had no statistical significance (P > 0.05). Aneuploidy of chromosome 17 existed in 9 of 26 of HER2 immunopositive meningiomas (34.6%). However, the rates of chromosome 17 aneuploidy had no significant difference among tumors with variable HER2/neu imumopositivity (P > 0.05).

CONCLUSIONSHigh levels of HER2 and Ki-67 or TK1 expression correlate with the increase of tumor grades and tumor recurrence. HER2/neu gene amplification is seen in a subset of meningiomas with the protein expression (26.9%). A combination of biomarker study including HER2/neu, Ki-67 and TK1 may be useful in predicting the biological behavior of meningiomas.

Aneuploidy ; Chromosomes, Human, Pair 17 ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen ; metabolism ; Male ; Meningeal Neoplasms ; genetics ; metabolism ; pathology ; Meningioma ; genetics ; metabolism ; pathology ; Middle Aged ; Neoplasm Recurrence, Local ; Receptor, ErbB-2 ; genetics ; metabolism ; Thymidine Kinase ; metabolism

Organic anion transporting polypeptide 1B1 (OATP1B1) is an important liver-specific uptake transporter, which mediates transport of numerous endogenous substances and drugs from blood into hepatocytes. To identify and investigate potential modulators of OATP1B1 from natural products, the effect of 21 frequently used natural compounds and extracts on OATP1B1-mediated fluorescein methotrexate transport was studied by using Chinese hamster ovary cells stably expressing OATP1B1 (CHO-OATP1B1) in 96-well plates. This method could be used for the screening of large compound libraries. Our studies showed that some flavonoids (e.g., quercetin, quercitrin, rutin, chrysanthemum flavonoids and mulberrin) and triterpenoids (e.g., glycyrrhetinic acid and glycyrrhizic acid) were inhibitors of OATP1B1 with IC50 values less than 16 µmol · L(-1). The IC50 value of glycyrrhetinic acid on OATP1B1 was comparable to its blood concentration in clinics, indicating an OATPlB1-mediated drug-drug interaction could occur. Structure-activity relationship analysis showed that flavonoids had much higher inhibitory activity than their glycosides. Furthermore, the type and length of saccharides had a significant effect on their activity. In addition, we used OATP1B1 substrates fluvastatin and rosuvastatin as probe drugs to investigate the substrate-dependent effect of several natural compounds on the function of OATP1B1 in vitro. Our results demonstrated that the effect of these natural products on the function of OATPlB1 was substrate-dependent. In summary, this study would be conducive to predicting and avoiding potential OATP1B1-mediated drug-drug and drug-food interactions and thus provide the experimental basis and guidance for rational drug use.
Animals ; Biological Products ; CHO Cells ; Cricetulus ; Drug Interactions ; Fatty Acids, Monounsaturated ; pharmacology ; Flavonoids ; pharmacology ; Indoles ; pharmacology ; Inhibitory Concentration 50 ; Organic Anion Transporters ; genetics ; metabolism ; Rosuvastatin Calcium ; pharmacology ; Structure-Activity Relationship

Aged ; Antigens, CD34 ; analysis ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Solitary Fibrous Tumors ; metabolism ; pathology

Objective to investigate the value of diffusion-weighted echo-planar MR imaging in the diagnosis of head and neck lesions.Methods Fifty-seven patients with 85 head and neck lesions were enrolled in the study,including 22 patients with 22 malignant tumors,13 patients with 13 benign tumors, 13 patients with 17 cystic and liquefactive lesions(including 8 patients with 12 cystic lesions,4 patients with 4 tumor necrosis,1 patients with 1 abcess)and 33 lymph nodes.The lesions were all confirmed by operation and clinical follow up.Echo-planar difffusion-weighted imaging (DWI)was performed with different b values (0,500,and 1,000s?mm~(-2)),and the apparent diffusion coefficients (ADCs)were measured.Results Malignant and benign tumors had different characteristics in DWI with different b values.With the increase of b value,the signal intensity of tumor/spinal cord ratio decreased quickly in DWI in benign tumors,while the signal intensity of tumor/spinal cord ratio remained similar in DWI in malignant tumors.The mean ADC value of'malignant tumors[(0.78?0.24)?10~(-3)mm~2? s~(-1)] was significantly lower than that of benign tumors [(1.48?+0.20)?10~(-3)mm~2?s~(-1)] (t = 8.9,P

Objective To explore the changes of serum gastrin(GAS),plasma motilin(MTL) and somatostatin(SST) in critically ill children with gastrointestinal dysfunction(GID).Methods According to pediatric critical illness score,75 cases were divided into greatly critical group(score90).Fifty cases of greatly critical and critical group were divided into GID group and non-GID group.The levels of serum GAS,plasma MTL and SST were detected on an empty stomach at acute stage and convalescence stage,comparing with those of normal control group,and then,the relationship between the levels of serum GAS,plasma MTL,SST and GID,the severity of disease were analyzed.Results At acute stage,the levels of serum GAS and plasma MTL of greatly critical group and critical group were higher than those of normal control group,the levels of plasma SST of greatly critical group and critical group were lower than that of normal control group,the more severe condition of critical children,the higher level of serum GAS and plasma MTL,the lower level of plasma SST.At convalescence stage,the level of serum GAS and plasma MTL of the greatly critical group and critical group decreased and the level of plasma SST increased.The levels of serum GAS and plasma MTL of GID group were higher than those of non-GID group,but the level of plasma SST of GID group was lower than that of non-GID group.Conclusion The level of serum GAS,plasma MTL and SST can be used to assess the severity of illness and prognosis,judge the change of disease and determine the efficacy of treatment programs,and detect gastrointestinal functional lesion.

AIMTo determine the protective effect and influence on NOS expression of Montelukast sodium--a leukotriene antagonist on myocardial necrosis in rats.

METHODSMyocardial ischemia and necrosis were induced in rats by isoproterenol (2 mg.kg-1, s.c., qd for 2 d). Serum activity of LDH, CK, MDA, NO content in myocardium and scope of myocardial necrosis were measured. nNOS, iNOS and eNOS were investigated by immunohistochemical evaluation.

RESULTSDecreased serum level of LDH, CK, MDA and attenuated myocardial necrosis area were found in rats pretreated with Montelukast sodium 10 and 30 mg.kg-1. Montelukast sodium 30 mg.kg-1 also enhanced NO content in myocardium. Montelukast sodium activated the eNOS expression and reduced the iNOS expression.

CONCLUSIONMontelukast sodium is cardioprotective during myocardial injury in rats by halting the leukotrienes-induced inflammatory response and upregulating the eNOS expression as well as downregulating the iNOS expression. This may represent an approach to the treatment of myocardial ischemia with leukotriene antagonists.

Acetates ; pharmacology ; Animals ; Cardiotonic Agents ; pharmacology ; Female ; Isoproterenol ; Leukotriene Antagonists ; pharmacology ; Male ; Myocardial Ischemia ; chemically induced ; enzymology ; pathology ; Myocardium ; metabolism ; pathology ; Necrosis ; Nitric Oxide Synthase ; metabolism ; Nitric Oxide Synthase Type II ; Nitric Oxide Synthase Type III ; Quinolines ; pharmacology ; Rats ; Rats, Sprague-Dawley

In this study, daphnetin and its major metabolites in the intestinal wall of rats were identified by liquid chromatography and quatrupole-time of flight mass spectrometry. Perfusion fluid of duodenum, jejunum, ileum and colon were collected separately for 2 hours from the rat intestine following perfusion with daphnetin. The metabolites of daphnetin in the perfusion fluid of different intestine segments were analyzed by the liquid chromatography and quatrupole-time of flight mass spectrometry. It is shown that the parent drug daphnetin and four metabolites were found in the perfusion fluid of duodenum, jejunum and ileum. However, no metabolites were found in the colon. Among the four metabolites, two daphnetin sulfates (m/z 257) were first discovered as the phase II metabolites of daphnetin in rats, which revealed a new way of daphnetin metabolism in rats.
Animals ; Chromatography, High Pressure Liquid ; Colon ; metabolism ; Duodenum ; metabolism ; Ileum ; metabolism ; Intestines ; metabolism ; Jejunum ; metabolism ; Male ; Perfusion ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Electrospray Ionization ; Umbelliferones ; metabolism ; pharmacokinetics

OBJECTIVETo observe effects of acupuncture at Neiguan (PC 6) on function of sinoatrial node, so as to provide experimental basis for clinical application of Neiguan (PC 6) to treatment of heart diseases.

METHODSFifty cases of heart diseases were randomly divided into 2 groups, a no-blocking group (n = 35) and a blocking group (n = 15). In the no-blocking group, sinoatrial node recovery time (SNRT), sinoatrial conduction time (SACT), sinoatrial node effective refractory period (SNERP) and heart rate (HR) were determined by using esophagus-left cardiac atrium regulating pulsation technique before and after acupuncture at Neiguan (PC 6); and in the blocking group, the vegetative nerve was blocked by intravenous injection of Propanolol and Atropine, and then SNRT, SACT, SNERP and intrinsic heart rate (IHR) were detected before and after acupuncture.

RESULTSIn the no-blocking group there were significant differences in SACT, SNERP and HR (all P < 0.05) and no significant difference in SNRT (P > 0.05) before and after treatment. In the blocking group, there were no significant differences in SNRT, SACT and SNERP and a significant difference in IHR before and after acupuncture (P < 0.05).

CONCLUSIONAcupuncture at Neiguan (PC 6) has a significant effect on function of sinoatrial node, and the mechanism is possibly related with the bidirectional regulative action of acupuncture at Neiguan (PC 6) on the autonomic nerve in the sinoatrial node.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Female ; Heart Rate ; Humans ; Male ; Middle Aged ; Refractory Period, Electrophysiological ; Sinoatrial Node ; physiology

Animals ; COS Cells ; Female ; Hepatitis B Core Antigens ; genetics ; Hepatitis B Surface Antigens ; genetics ; Hepatitis B Vaccines ; immunology ; Interleukin-12 ; genetics ; Mice ; Mice, Inbred BALB C ; Vaccines, DNA ; immunology