17-allylamino-17-demethoxygeldanamycin (17-AAG) is a heat shock protein 90 ( HSP90) inhibitor. It is capable of target-inhibiting tumor-derived HSP90, leading to the depletion of on-cogenic client proteins which play key roles in several signal transduction pathways. Then cell growth and differetiation are inhibited. 17-AAG results in cytostasis and apoptosis. A lot of trials have indicated that 17-AAG is a selective target drug for cancer therapy. It can efficiently inhibit multiple signal transduction pathways involved in tumor cell proliferation and survival. Clinical phaseⅠand phaseⅡtrials have shown that 17-AAG has good pharmacokinetic-pharmacodynamic profile. Moreover, it can combine with radiation and the traditional chemotherapeutics and increase the therapeutic efficacy.

The evaluation of quality of life after stroke primarily includes body,psychology, society,and the ability of activities of daily living,and they can be mainly obtained from self rating quality of life by the patients,The commonly used evaluation methods include six generic measurement scales and four updated Stroke Specific Quality of Life Scales.The latter includes the Stroke Adapted Sickness Impact Profile,the Stroke Impact Scale,Stroke Specific Quality of Life Scales,and Stroke and Aphasia Quality of Life Scale.This article reviews the generic meas- urement scales,Stroke Specific Quality of Life Scales and the various factors that influencing quality of life after stroke.

Objective To investigate the effect of intravenous fluid infusion combined with water throuth gastrointestinal tract in treating the patients with hyperosmolar hyperglycemic state(HHS).Methods 30 HHS pa- tients were recruited.All the patients were given water throuth gastrointestinal infusion while they were administrat- ed continuously intravenous infusion.Laboratory parameters such as serum natrium,serum potasium,serum glucose and serum osmolarity ect were monitored at the admission and after treatment.Results Serum glucose and serum osmolarity of HHS patients were decreased smoothly at the speed of less than 3 mmol?L~(-1).h~(-1)during the first 12 hours after treatment.After 48 hour-treatment,serum natrium,serum potassium and serum osmolarity recovered to normal levels except 2 deaths,serum glucose decreased to(10.8?5.2)mmol/L.Conclusion Intravenous fluid infu- sion combined with water throuth gastrointestinal tract for the patients could lower smoothly serum glucose and serum osmolarity and decrease the mortality of the HHS patients.

To investigate the secondary metabolites of endophytic fungi Pericinia sp. F-31. Column chromatography on silica gel, Sephadex LH-20 and semi-preparative HPLC were used to separate and purify the compounds. Two compounds were isolated from the fermentation broth of Periconia sp. Their structures were identified as 5-(1-hydroxyhexyl) -6-methyl-2H-pyran-2-one (1) and 2-(3-hydroxy-4-methylphenyl) -propanoic acid (2). Compound 1 was a new lactone compound, compound 2 was new natural product, and the NMR data of compound 2 was reported for the first time.
Annona ; microbiology ; Ascomycota ; chemistry ; genetics ; isolation & purification ; metabolism ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; metabolism ; Endophytes ; chemistry ; genetics ; isolation & purification ; metabolism ; Lactones ; chemistry ; isolation & purification ; metabolism ; Mass Spectrometry ; Molecular Structure

In the research and development of new drugs, it is very important to investigate the in vitro metabolism of candidate drugs. Traditional models such as liver microsomes have many limitations, while the in vitro model of recombinant human drug metabolizing enzymes is considered as an important and useful approach because of its convenient access, stable activity and low cost. In this study, six major human UDP-glucuronosyltransferases (UGTs) genes (UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) were cloned from human liver cDNA and heterologously expressed in Saccharomyces cerevisiae and baculovirus-infected insect cell. UGT1A1, 1A3, 1A6 and 1A9 were successfully expressed in yeast and showed glucuronidation activity against a variety of different structural types of substrates, but their activities were low. All six UGTs were successfully expressed and exhibited significantly improved glucuronidation activity when Trichopolusia ni cells BTI-TN5B1-4 (High Five) were used as the host. The recombinant human UGTs expressed in insect cells can catalyze the glucuronidation of their specific substrates, and the glucuronidation products were synthesized at milligram-scale with yields of 13%-66% for the first time, of which the structures were identified via MS, ¹H NMR, and ¹³C NMR spectroscopic analysis. Above all, the recombinant human UGTs yeast and insect cell expression systems constructed in this study can be used for in vitro metabolism evaluation in the early stage of new drugs research and development, and also provide a new tool for the synthesis of glucuronide metabolites.

BACKGROUNDRNA interference (RNAi) technology is emerging as a very potent tool to generate a cellular knockdown of a desired gene. The aim of this study was to explore whether RNAi targeting vascular endothelial growth factor-C (VEGF-C) could inhibit colorectal tumor lymphangiogenesis and tumor growth.

METHODSWe used vector-based RNAi to inhibit VEGF-C expression in colon cancer in vitro and in vivo. VEGF-C expression was quantified by real-time polymerase chain reaction and Westen blotting. To establish LoVo cell tumor xenografts in mice, we subcutaneously inoculated 1.0 x 10(6) LoVo cells in nude mice; after injection, tumors were allowed to grow for 4 weeks until the volume reached (75.8+/-55.8) mm(3). The mice were then randomly divided into two groups: (1) the VEGF-C-siRNA group (n=10) received direct injection of "therapeutic" plasmid 50 microg of LoVo-VEGF-C-siRNA into the tumor mass; (2) the control group (n=10) were injected with LoVo-control in 20 microl of sterile 0.9% NaCl solution into the tumor mass. Tumor growth, microlymphatics and microvessels were compared for mice administered either systemic VEGF-C-siRNA or control over 4 weeks.

RESULTSThe mRNA and protein expression of VEGF-C in the colon tumor cell line, LoVo, stably transfected with a VEGF-C-siRNA vector, were significantly downregulated 45.3% and 35.3% respectively. In vivo, four weeks after injection, the tumor volume were significantly smaller in VEGF-C-siRNA group than in LoVo-control group ((314.8+/-54.8) mm(3) vs (553.9+/-90.1) mm(3)); the incidences of lymph node metastasis (30%) in VEGF-C-siRNA were significantly inhibited compared with LoVo-control group (70%); in VEGF-C-siRNA group, the number of microlymphatics per microscopic field was (5.3+/-0.7) and the number of microvessels per microscopic field was (24.2+/-6.5) decreased compared with LoVo-control group (12.5+/-6.9) and (42.1+/-7.4) (all P<0.001).

CONCLUSIONInhibition of VEGF-C expression using siRNA-mediated gene silencing vectors reduced lymphangiogenesis and lymph node metastasis and enhanced survival.

Animals ; Cell Line, Tumor ; Colorectal Neoplasms ; blood supply ; pathology ; therapy ; Genetic Vectors ; Humans ; Lymphangiogenesis ; Lymphatic Metastasis ; Mice ; Neovascularization, Pathologic ; prevention & control ; RNA Interference ; RNA, Small Interfering ; genetics ; Vascular Endothelial Growth Factor C ; antagonists & inhibitors ; genetics

AIM: To study the chemical constituents of Siegesbeckia pubescens. METHODS: The chemical constituents were isolated by extraction, crystallization and various chromatographic methods, and the chemical structures were elucidated on the basis of spectral analysis. In addition, the cytotoxic activity of compound 1 was evaluated using human lung cancer cell A 549. RESULTS: Four compounds were obtained, and their structures were identified as (E)-3-(3-oxobut-1-enyl)phenyl dimethylcarbamate (1), ent-2-oxo-15, 16, 19-trihydroxypimar-8(14)-ene (2), 16-acetylkirenol (3), 3, 7-dimethylquercetin (4). CONCLUSION Compound 1 is a new carbamate, and the IC(50) in MTT method of compound 1 was 58 μg·mL(-1).
Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; therapeutic use ; Asteraceae ; chemistry ; Carbamates ; isolation & purification ; pharmacology ; therapeutic use ; Cell Line, Tumor ; Humans ; Inhibitory Concentration 50 ; Lung Neoplasms ; drug therapy ; Molecular Structure ; Phytotherapy ; Plant Components, Aerial ; chemistry ; Plant Extracts ; chemistry ; pharmacology ; therapeutic use ; Quercetin ; analogs & derivatives ; isolation & purification

OBJECTIVETo evaluate the alterations in coagulation in patients during conditioning with modified busulfan plus cyclophosphamide (BU/CY) +/- antithymocyte globulin (ATG) regimen before allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to assess the effect of ATG on coagulation system.

METHODSThirty-five patients with various hematological malignancies undergoing allo-HSCT were assessed. Of them, 19 patients with HLA-matched sibling donors (group A) were conditioned with modified BU/CY regimen, 16 with HLA-mismatched family members or HLA-matched unrelated donors (group B) were conditioned with modified BU/CY + ATG regimen. Blood samples were collected before the beginning of conditioning till d + 1 after allo-HSCT. The following parameters were measured: prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fg), antithrombin (AT), D-Dimer, fibrin degradation product (FDP), platelet (BPC), liver enzymes and bilirubin. FVIII: C, FIX: C, FXI: C and FXII: C in prolonged APTT blood samples were also determined. Clinical hemorrhagic symptoms were monitored.

RESULTSDuring conditioning, temporary lengthening of APTT, persistent rising in Fg and declining of BPC were observed in the two groups. Alterations of Fg and BPC were more significant in group B than in group A. Transient D-Dimer increase occurred only in group B on administration of ATG. Among intrinsic pathway coagulation factors, FXII: C and FXI: C were commonly decreased while APTT prolonged. No difference between the two groups was found with regard to PT, FDP, AT and liver parameters which remained in normal ranges. Most of patients in the two groups did not have overt bleeding manifestations.

CONCLUSIONSModified BU/CY +/- ATG conditioning regimen can induce subclinical alterations in coagulation. The regimen containing ATG has more significant effect on coagulation parameters.

Adolescent ; Adult ; Antilymphocyte Serum ; therapeutic use ; Blood Coagulation ; drug effects ; Child ; Cyclophosphamide ; therapeutic use ; Female ; Hematologic Neoplasms ; physiopathology ; surgery ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Partial Thromboplastin Time ; Prothrombin Time ; Transplantation Conditioning ; Young Adult

Adolescent ; Adult ; Blood Donors ; Cord Blood Stem Cell Transplantation ; adverse effects ; Female ; Graft vs Host Disease ; etiology ; Hematopoiesis ; Histocompatibility Testing ; Humans ; Leukemia ; blood ; mortality ; therapy ; Male ; Recurrence

"Shengdeng" is its Tibetan transliteration referring to many medicines. Tibetan doctors and pharmacists in different areas use different drugs in formulation and clinical application, which are easily confused. In order to grasp the formula and clinical application accurately, we conduct a literature survey on history and current state of botanical origin and clinical application of "Shengdeng", making clear the application of various herbs named "Shengdeng" and providing reference to all Tibetan researchers and clinical workers in formulation and clinical application.
Drug Therapy ; history ; Drugs, Chinese Herbal ; analysis ; history ; therapeutic use ; History, Ancient ; Humans ; Medicine, Tibetan Traditional ; history ; Plants, Medicinal ; chemistry