Adult ; Aged ; Colectomy ; Colonic Neoplasms ; pathology ; surgery ; Female ; Gastrectomy ; Humans ; Male ; Middle Aged ; Rectal Neoplasms ; pathology ; surgery ; Rectum ; surgery ; Stomach Neoplasms ; pathology ; surgery ; T-Lymphocyte Subsets ; pathology ; T-Lymphocytes, Cytotoxic ; pathology ; Th1 Cells ; pathology ; Th2 Cells ; pathology

Background and purpose:Chemotherapy plays an important role in the treatment of breast carcinoma by inhibiting the tumor growth and inducing the apoptosis.MAPK transduction pathway is closely related to proliferation and apoptosis of varieties of tumor cells,inhibition of MAPK pathway may increase the efficiency and decrease the toxicity of chemotherapy.Our study was to investigate the effect of MEK inhibitor PD98059 in response of breast cancer cell lines to Epirubicin.Methods:Human breast cancer cell lines MCF-7 and MCF-7/ADR were used as cell models.Epirubicin(EADM),PD98059(inhibitor of MAPK Kinase-MEK),or EADM+PD98059 was added into the culture medium,the expression of MEK2 and p-ERK were measured by Western blot,the growth of the two cell lines were measured by MTT.Results:ERK activity was elevated in MCF-7 after the treatment of EADM,the cells were more sensitive to EADM if combined with PD98059,while in MCF-7/ADR,ERK activity kept unchanged after EADM treatment,and PD98059 has no effect on the sensitivity of cells to EADM.Conclusion:MAPK signal transduction may be activated in some cells treated by EADM,adding inhibitor of MAPK signal transduction could improve the sensitivity of the cells to EADM.

The purpose of this study is to investigate the enantioselectivity of norgestrel (NG) transdermal permeation and the potential influence of linalool and lipids on the enantioselectivity. In vitro skin permeation studies of NG across the excised rat skins were performed with Valia-Chien diffusion cells, and the permeation samples were analyzed by enantioselective HPLC. The possible enantioselective permeation of NG across intact rat back skin and lipids extracted rat back skin and the influence of linalool were evaluated. The skin permeation rate of dl-NG was two times higher than that of l-NG when donor solutions (EtOH/H2O 2 : 8, v/v) containing l-NG or dl-NG. It may be mainly attributed to the solubility discrepancy between enantiomer and racemate. The enantioselective permeation of dl-NG across intact rat skin was observed when the donor solutions containing dl-linalool. The permeation flux of l-NG was 22% higher than that of d-NG. But interestingly, the enantioselective permeation of dl-NG disappeared under the same experimental condition except that the lipid extracted rat skin was used. Attenuated total reflection-fourier transform infrared spectroscopy analysis of stratum corneum showed that the wave number for asymmetric CH2 stretching vibrations of lipids treated with dl-linalool was greater than that of the control. The results indicated that the enantioselective permeation of NG may be contributed by the interaction between dl-linalool and lipids. More than half of lipids were composed of ceramides. The stereospecific interaction maybe existed among chiral enhancer (linalool), lipids (ceramides) and/or chiral drugs (NG).
Administration, Cutaneous ; Animals ; Lipids ; pharmacology ; Monoterpenes ; pharmacology ; Norgestrel ; pharmacokinetics ; Rats ; Skin Absorption ; drug effects ; Spectroscopy, Fourier Transform Infrared ; Stereoisomerism

OBJECTIVETo investigate the Bmi1 protein level in human colorectal cancer specimen and associated clinicopathological parameters, and to determine the influence of Bmi1 on the proliferation and apoptosis of colorectal cancer cells.

METHODSBmi1 protein level was assessed in 85 patients with colorectal cancer and adjacent normal tissue by immunohistochemistry. SW480 cells were transfected with Bmi siRNA plasmid. MTT assay and flow cytometry were used to measure the proliferation and apoptosis of SW480 cells. The expression of Bmi1 and Bcl-2 were measured by Western blot.

RESULTSThe positive rate of Bmi1 expression in colorectal cancer tissues was 56.5%(48/85), significantly higher than that in the adjacent noncancerous tissues[17.6%(15/85), P<0.05)]. It was found that the overexpression of Bmi1 was associated with degree of differentiation, status of lymph nodes metastasis, and TNM staging in colorectal cancer(P<0.05). After transfection of SW480 with Bmi1 siRNA, the cell proliferation was inhibited and the apoptosis was significant. The cell proliferation inhibitory rates were 13.1%, 16.5%, and 18.3% at 24 h, 48 h and 72 h after transfection. The apoptotic rates were 15.7%, 45.6%, 40.2%, respectively. Expression of Bmi1 was downregulated after 48 h, as was that of Bcl-2.

CONCLUSIONSBmi1 expression is associated with the clinicopathological characteristics of colorectal cancer. Blockade of Bmi1 can inhibit the proliferation and accelerate the apoptosis of colorectal cancer cells.

Aged ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Colorectal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Polycomb Repressive Complex 1 ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism

The clinical decision support system can provide medical staff with targeted patient diagnosis, treatment and care plan according to the recommendations of the guidelines, and assist medical staff to make clinical decisions. However, the adherence to clinical decision support system which based on guidelines was poor in clinical practice. Therefore, this article reviewed the influence factors of adherence to clinical decision support system which based on guideline from four aspects: system factors, individual factors, organizational factors and environmental factors, so as to improve the hindering factors and promote the application of clinical decision support system which based on guideline in future research and clinical practice.

BACKGROUNDSolamargine (SM), a steroidal glycoalkaloid isolated from the Chinese herb Solanum incanum, has been shown to inhibit the growth of some cancer cell lines and induce significant apoptosis. However, the effects of SM on multidrug-resistant (MDR) cells and the molecular mechanisms involved are poorly understood. The purpose of this study was to evaluate the anti-MDR effects of SM and the associated mechanisms in MDR K562/A02 cells.

METHODSThe cytotoxicity of SM was measured by 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay. The 14',6-diamidino-2-phenylindole (DAPI) nuclear staining and flow cytometry were used to detect SM-induced apoptosis. The mRNA expression of P-glycoprotein (P-gp) was investigated by real-time PCR (RT-PCR). Western blotting was used to determine the expression of Bcl-2, Bax, and actin. The changes in the morphology of actin were examined with immunofluorescence staining.

RESULTSMTT results showed that SM effectively killed the MDR sublines K562/A02, KB/VCR, and H460/paclitaxel (Taxol), and their parental cell lines K562, KB, and H460 to an equivalent or more sensitive degree. Based on the results by flow cytometry and immunostaining, the pro-apoptotic effects of SM were observed in MDR K562/A02 cells. Furthermore, the RT-PCR results showed that SM induced the downregulation of MDR1 mRNA. In addition, the expression of P-gp and actin was decreased in the SM-treated cells, as measured by western blotting and immunostaining.

CONCLUSIONSThese results demonstrate that SM effectively triggers apoptosis in MDR tumor cells, which is associated with actin disruption and downregulation of MDR1 expression. This compound may merit further investigation as a potential therapeutic agent that bypasses the MDR mechanism for the treatment of MDR tumors.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Actins ; metabolism ; Cell Line, Tumor ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; K562 Cells ; Solanaceous Alkaloids ; pharmacology

In order to research into the cytology mechanism of anti-virus action of total flavone of Scutellaria barbata (TFSB), the effects of TFSB on host cells membrane potential, Na(+)-K(+)-ATPase activity and membrane fluidity after parainfluenza virus type1 (PIV-1) infection were studied. The changes of membrane potential which was fluorescent labeled with DiBAC4(3) and its changes were measured by flow cytometer. Phosphorus determination method and spectrophotometry were used to measure the Na(+)-K(+)-ATPase activity of Hep-2 cells membrane after PIV-1 infection. Hep-2 cells membrane phospholipids were fluorescent labeled with NBD-C6-HPC and membrane fluidity was measured by confocal scanning laser microscope. The result demonstrated that post PIV-1 infection membrane potential decreased significantly and the membrane was in a state of hyperpolarization, Na(+)-K(+)-ATPase activity increased significantly and membrane fluidity decreased significantly. There was no apparent interfere effect of TFSB on the changes of membrane potential and Na(+)-K(+)-ATPase activity after PIV-1 infection, while membrane fluidity improved significantly. It was indicated that the cytology mechanism of PIV-1 infection might be related to membrane hyperpolarization, Na(+)-K(+)-ATPase activity increase and membrane fluidity decrease. TFSB can improve membrane fluidity and prevent the infection by protecting the cell membrane. But it is possible that the anti-PIV-1 mechanisms of TFSB had nothing to do with membrane potential and Na(+)-K(+)-ATPase activity.
Antiviral Agents ; isolation & purification ; pharmacology ; Cell Line, Tumor ; Cell Membrane ; drug effects ; Flavones ; isolation & purification ; pharmacology ; Humans ; Laryngeal Neoplasms ; pathology ; virology ; Membrane Fluidity ; drug effects ; Membrane Potentials ; drug effects ; Parainfluenza Virus 1, Human ; drug effects ; Phospholipids ; metabolism ; Plants, Medicinal ; chemistry ; Respirovirus Infections ; drug therapy ; Scutellaria ; chemistry ; Sodium-Potassium-Exchanging ATPase ; metabolism

In order to study the anti-viral mechanism of extracted ZG from Gardenia, the effect of extracted ZG on Hep-2 cell membrane potential, Na -K+-ATPase activity and membrane fluidity post infected with parainfluenza virus type 1 (PIV-1) was observed. Acetylcholine which was fluorescent labeled with DiBAC4 (3) was taken as positive control to observe the changes of membrane potential and was measured by flow cytometer. The phosphorus determination method and spectrophotometer were used to measure the Na+-K+-ATPase activity of Hep-2 cell membrane post PIV-1 infection. Hep-2 cell membrane phospholipids was labeled with fluorescent NBD-C6-HPC and membrane fluidity was measured by confocal laser scanning microscope. The results demonstated that after PIV-1 infection the Hep-2 cell membrane potential decreased significantly and the membrane was in the state of hyperpolarization, Na+-K+-ATPase activity increased and membrane fluidity decreased significantly. There was no apparent interferring effect of extracted ZG on the changes of membrane potential and Na+-K+-ATPase activity post PIV-1 infection, while membrane fluidity was improved significantly. Acetylcholine improved the state of hyperpolarization. The changes of membrane potential, Na -K+-ATPase activity and membrane fluidity might be the biomechanism of PIV-1 infectoin. The extracted ZG improved membrane fluidity to prevent from PIV-1 infection by protecting the cell membrane, which was probably the mechanism of anti-PIV-1 activity of the extracted ZG, but ZG probably had nothing to do with membrane potential and Na+-K+-ATPase activity.
Acetylcholine ; pharmacology ; Antiviral Agents ; pharmacology ; Cell Line, Tumor ; Cell Membrane ; drug effects ; Gardenia ; chemistry ; Humans ; Membrane Fluidity ; drug effects ; Membrane Potentials ; drug effects ; Parainfluenza Virus 1, Human ; drug effects ; Plant Extracts ; pharmacology ; Sodium-Potassium-Exchanging ATPase ; metabolism

This study is to investigate the treatment of YinQiaojiedu soft capsule for influenza virus A/PR8/34 (H1N1) infection. The model of pneumonia was established by dropping influenza virus into the nose of normal mice, and the lung index and death rate were observed. Real time RT-PCR and Western blotting technique were used to detect the virus load and the relative expression of M1 protein in lungs of mice on the 1st, 3rd, 5th and 7th day after infection. The results showed that YinQiaojiedu soft capsule in 1 g x kg(-1) and 0.5 g x kg(-1) dose groups can decrease the lung index significantly on the 3rd, 5th and 7th day after being infected (P < 0.05, P < 0.01), and the number of death in the two groups of animals decreased significantly. YinQiaojiedu soft capsule in 1 g x kg(-1) dose group can decreased virus load at each time point, and lower it in 0.5 g x kg(-1) dose group at the 3rd, 5th and 7th day (P < 0.05, P < 0.01). YinQiaojiedu soft capsule can decrease the relative expression of M1 protein in lungs of mice, 1 g x kg(-1) and 0.5 g x kg(-1) dose groups are significantly lower in expression of M1 protein compared with model group at the 3rd and 7th day (P < 0.05, P < 0.01). It can be concluded that YinQiaojiedu soft capsule exerts antiviral effects against influenza virus by downregulating expression of virus load and M1 protein.
Animals ; Antiviral Agents ; administration & dosage ; pharmacology ; Capsules ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Female ; Influenza A Virus, H1N1 Subtype ; Lung ; metabolism ; virology ; Male ; Mice ; Mice, Inbred ICR ; Orthomyxoviridae Infections ; drug therapy ; metabolism ; virology ; Pneumonia ; metabolism ; virology ; Viral Load ; drug effects ; Viral Matrix Proteins ; metabolism