Four-Dimensional Computed Tomography ; Humans ; Liver Neoplasms ; diagnostic imaging ; radiotherapy ; Lung Neoplasms ; diagnostic imaging ; radiotherapy ; Male ; Prostatic Neoplasms ; diagnostic imaging ; radiotherapy ; Radiotherapy Planning, Computer-Assisted ; methods ; Radiotherapy, Intensity-Modulated ; methods

AIMTo investigate the effect of resveratrol on EMMPRIN expression of macrophages.

METHODSHuman monocytic cell line THP-1 cells were co-cultured with EMMPRIN-highly-expressed MCF-7 cells; MMP-9 production was assayed by zymography. THP-1 cells were induced by PMA, expression of EMMPRIN was assayed by Western blotting. Cells were treated with resveratrol or PPARgamma agonist--pioglitazone during differentiation, EMMPRIN expression and MMP-9 activity were assayed. U937 cells were co-transfected with PPARy expression and luciferase-coding reporter vector, then cultured with pioglitazone or resveratrol, the activating capability of resveratrol on PPARgamma was evaluated by measuring the luciferase activity. THP-1 cells were pretreated with PPARgamma antagonist--GW9662 before pioglitazone or resveratrol treatment, then assayed for EMMPRIN expression and MMP-9 production.

RESULTSEMMPRIN expression was greatly increased during the differentiation from monocytes to macrophages; co-culturing with MCF-7 cells significantly increased MMP-9 production by monocytes. Both resveratrol and pioglitazone markedly inhibited EMMPRIN expression during monocytes differentiation. Resveratrol significantly activated PPARgamma and GW9662 greatly decreased the effect of resveratrol on EMMPRIN and MMP-9.

CONCLUSIONEMMPRIN expression is greatly up-regulated from monocytes to macrophages, which may play a role in inducing MMPs production by monocytes/macrophages. Resveratrol can significantly inhibit EMMPRIN expression via activating PPARgamma, which may be the underlying mechanism of its inhibitory effect on MMPs production by monocytes/macrophages.

Anilides ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Basigin ; biosynthesis ; genetics ; Blotting, Western ; Breast Neoplasms ; metabolism ; pathology ; Cell Differentiation ; drug effects ; Cell Line ; Cell Line, Tumor ; Coculture Techniques ; Dose-Response Relationship, Drug ; Female ; Humans ; Luciferases ; genetics ; metabolism ; Macrophages ; cytology ; drug effects ; metabolism ; Matrix Metalloproteinase 9 ; biosynthesis ; Monocytes ; cytology ; drug effects ; metabolism ; PPAR gamma ; genetics ; metabolism ; Recombinant Fusion Proteins ; genetics ; metabolism ; Stilbenes ; pharmacology ; Thiazolidinediones ; pharmacology ; U937 Cells

Objective:To explore the role ofDNA methyltransferase 1 (DNMT1) in mouse skin aging.Methods:Epidermal conditional K14 Cre-mediated DNA methyltransferase 1 (DNMT1) knockout mice (Mut group,n=4) and the littermate normal mice with the same age (WT group) n=4) were used in this study.HE staining was used to detect the pathological changes of skin;the changes of number in the dermal elastic fibers were detected by Gomori aldehyde fuchsin staining,the number of 5-bromo-2-deoxyuridine (BrdU)-labeled transit amplifying cells (TAC) in epidermis were detected by immunohistochemical staining;the number of chlorodeoxyuridine (CldU)-labelretaining cells (LRC) in epidermis were detected by immunofluorescent staining.Results:Compared with the WT group,the skin showed premature aging symptoms in the Mut group concomitant with the decreased epidermal thickness as well as the number of dermal collagen fibers,while the increased dermal elastic fiber fracture.Compared with the WT group,the number of TAC in the epidermis was significantly increased (P＜0.05),and the number of LRC was significantly decreased (P＜0.05) in the Mut group.Conclusion:The phenotype of skin premature aging in epidermal stem cell conditional DNMT1-knockout mice suggests an important role of DNMT 1 in skin aging.

OBJECTIVETo investigate the correlation of expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (Ki67) with sensitivity to neoadjuvant chemoradiation in rectal adenocarcinoma.

METHODSSamples of pretreatment biopsies and the resected specimens after neoadjuvant therapy in 32 patients with rectal adenocarcinoma were collected, and the expression of Ki67 and VEGF were detected by immunohistochemistry using specific antibodies. The correlation of Ki67 and VEGF expression with clinicopathological factors were analyzed.

RESULTSThe level of VEGF expression was significantly correlated with lymph node metastasis (P = 0.033), depth of tumor invasion (P = 0.007) and TNM stage (P = 0.016), but not with histological type, tumor size, age and gender of the patients (P > 0.05). However, VEGF expression was found to be negatively and significantly correlated with the sensitivity to neoadjuvant chemoradiation (P = 0.016), and a transient increase of VEGF expression was detected in the resected specimens after neoadjuvant therapy (P = 0.035). Ki67 labeling index (Ki67-LI) was found to be significantly correlated with lymph node metastasis (P = 0.028), but not with tumor size, age and gender of the patients (P > 0.05). It was also found that tumors with lower Ki67-LI expression were more sensitive to neoadjuvant therapy than that with higher expression of Ki67-LI (P = 0.032). In contrast with VEGF, the Ki67 expression level decreased after neoadjuvant therapy, but no statistical significance was found between pretreatment and posttreatment specimens (P > 0.05).

CONCLUSIONThe preliminary results of this study demonstrate that the expression of VEGF and Ki67 in pretreatment biopsy of rectal adenocarcinoma may be used as a biomarker to predict tumor response to neoadjuvant chemoradiation.

Adenocarcinoma ; metabolism ; pathology ; surgery ; therapy ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; metabolism ; Female ; Humans ; Ki-67 Antigen ; metabolism ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Invasiveness ; Neoplasm Staging ; Radiotherapy, Conformal ; Rectal Neoplasms ; metabolism ; pathology ; surgery ; therapy ; Vascular Endothelial Growth Factor A ; metabolism ; Young Adult

The effects of testosterone on norepinephrine release were investigated in the isolated rat hearts.Sprague-Dawley male rats (n=120) were randomized to testosterone and control groups.The rats in testosterone group were perfused with modified Krebs-Henseleit buffer containing different concentrations of testosterone (0.1,1.0,10.0,and 100.0 nmol/L,respectively).Myocardial ischemia was induced by globally stopping the perfusion flow.Exocytotic norepinephrine release was induced by electrical field stimulation at 5 V (effective voltage) and 6 Hz (pulse width of 2 ms) for 1 min.The overflow of norepinephrine was determined by high pressure liquid chromatography and electrochemical detection (HPLC-EC).Following acute ischemia,testosterone (1.0,10.0 and 100.0 nmol/L) significantly reduced norepinephrine release (P＜0.01),and the norepinepherine overflow was similar between the control and 0.1 nmol/L testosterone group (P＞0.05).Electrical stimulation of the ventricle evoked norepinepherine release,and this was diminished by the perfusion with testosterone at the concentrations of 1.0,10.0 and 100.0 nmol/L (P＜0.01).It is suggested that testosterone suppresses ischemia- and electrical stimulation-induced norepinepherine release in the isolated rat hearts.

OBJECTIVETo investigate the effect and related mechanism of retinoid X receptor (RXR) activation on oxidized low-density lipoprotein (ox-LDL) induced differentiation of macrophage into dendritic cell.

METHODSRAW264.7 murine macrophage cell line was cultured with ox-LDL for 48 h in the absence and presence of RXR activator 9-cisRA or SR11237. Cell morphology was observed by phase contrast microscope and cell surface markers involved in dendritic cell immune maturation and activation was analyzed by FACS. Cellular reactive oxygen species production was detected by CM-H2DCFDA fluorescent probe.

RESULTSox-LDL-treated RAW264.7 murine macrophage cell line differentiated into dendritic like cells after 48 h and cell surface markers CD40, CD86, CD83, MHC Class II and CD1d were upregulated. These changes could be attenuated by cotreatment with 9-cisRA or SR11237. Upregulated cell surface markers CD40, CD86, CD83, MHC Class II and CD1d by ox-LDL were decreased about 47%, 43%, 48%, 32% and 17% respectively by 9-cisRA and 38%, 38%, 46%, 36% and 32% respectively by SR11237. The effect of 9-cisRA and SR11237 was dose dependent. Cellular reactive oxygen species were significantly increased in ox-LDL-treated RAW264.7 cells (MFI 38.24 +/- 4.20 vs. 4.46 +/- 0.39, P < 0.05) and which was significantly reduced by 9-cisRA (10(-7) mol/L) and SR11237 (10(-6) mol/L) to 12.60 +/- 1.52 and 17.89 +/- 1.91 respectively (all P < 0.05).

CONCLUSIONRXR activation partly inhibits the differentiation of ox-LDL induced macrophage into dendritic cell by reducing oxidative stress injury.

Animals ; Benzoates ; pharmacology ; Cell Differentiation ; drug effects ; Cell Line ; Dendritic Cells ; cytology ; drug effects ; Lipoproteins, LDL ; metabolism ; Macrophages ; cytology ; drug effects ; Mice ; Retinoid X Receptors ; metabolism ; Retinoids ; pharmacology ; Tretinoin ; pharmacology

OBJECTIVESTo study the effects of c9,t11-conjugated linoleic acid (c9,t11-CLA) on invasive ability of human gastric carcinoma cell line (SGC-7901) and to explore its possible mechanism.

METHODSReconstituted basement membrane invasion assay was used to evaluate invasive ability of cancer cells. Expression of TIMP-1, TIMP-2 and nm23-H(1) mRNA was measured by reverse transcription polymerase chain reaction (RT-PCR) in SGC-7901 cells.

RESULTSAt the concentrations of 200 micromol/L, 100 micromol/L and 50 micromol/L, c9,t11-CLA suppressed their reconstituted basement membrane invasion of SGC-7901 by 53.7%, 40.9% and 29.3%, respectively. c9,t11-CLA could induce the expression of TIMP-1, TIMP-2 and nm23-H(1) mRNA in SGC-7901 cells.

CONCLUSIONSThe invasion of SGC-7901 cells could be inhibited by c9,t11-CLA through reconstituted basement membrane. Anti-invasion action of c9,t11-CLA might be associated with induction of expression of TIMP-1, TIMP-2 and nm23-H(1) mRNA in tumor cells.

Adenocarcinoma ; pathology ; Gene Expression ; drug effects ; Humans ; Linoleic Acid ; pharmacology ; therapeutic use ; Monomeric GTP-Binding Proteins ; biosynthesis ; genetics ; NM23 Nucleoside Diphosphate Kinases ; Neoplasm Invasiveness ; prevention & control ; Nucleoside-Diphosphate Kinase ; RNA, Messenger ; biosynthesis ; drug effects ; Stomach Neoplasms ; pathology ; Tissue Inhibitor of Metalloproteinase-1 ; biosynthesis ; genetics ; Tissue Inhibitor of Metalloproteinase-2 ; biosynthesis ; genetics ; Transcription Factors ; biosynthesis ; genetics ; Tumor Cells, Cultured

AIM:To study the effect of Aurora protein kinase inhibitor VX-680 on homogeneous adhesion and migration ability in human hepatocellular carcinoma cell line HepG 2.METHODS:The HepG2 cell were divided into ex-perimental group and control group, respectively.VX-680 was used in experimental groups at 3 concentrations(3.125 μmol/L group,6.25 μmol/L group and 12.5 μmol/L group).DMSO was used in the control group.The effects of VX-680 at different concentrations on the adhesion ability of human hepatocellular carcinoma HepG 2 cells were observed by cell slow aggregation test and separation experiment.The effects of VX-680 at different concentrations on the migration ability of HepG2 cells was detected by wound healing assay.The expression of E-cadherin in HepG2 cells was detected by Western blot.RESULTS:The results of the slow aggregation test showed that compared with the control group,the number of cell clumps formed in experimental groups was significantly decreased(P<0.01).The results of separation experiment showed that the ratio of NTC/NTEgradually decreased with the increased concentration of VX-680.The results of wound healing as-say showed that as the concentration of VX-680 increased, the cell scratch healing ability gradually weakened compared with control group.The results of Western blot showed that the protein expression of E-cadherin in the HepG2 cells in-creased with the increased concentration of VX-680(P<0.05).CONCLUSION:VX-680 increases the homogeneous ad-hesion and inhibits the migration of HepG 2 cells.

OBJECTIVETo ascertain a clinically meaningful thermal dose unit-temperature equivalent minute (TEM) 42.5 degrees C and the relationship between TEM 42.5 degrees C and tumor response rate.

METHODSFrom August 1998 to December 2002, 49 patients with recurrent or metastatic malignancies in the pelvis were treated with hyperthermia combined with conventional radiotherapy. Direct thermometry with high resistance lead needle was used whenever possible to measure the temperature by inserting Teflon catheter into the tumor. TEM 42.5 degrees C was used as the thermal dose unit and the relationship between TEM 42.5 degrees C and tumor response rate was monitored.

RESULTSThere was a positive correlation between response rate TEM 42.5 degrees C and the radiation dose. The tumor volume and number of heat treatment showed no influence on response.

CONCLUSIONBoth univariate analysis and multivariate logistic regression analysis indicate that there is a positive correlation between the response rate, TEM 42.5 degrees C and the radiation dose. TEM 42.5 degrees C may act as a useful thermal dose unit in the combination of hyperthermia and radiotherapy. To lower the incidence of complications in thermometry, direct thermometry with high resistance lead needle can be used to measure the temperature by inserting Teflon catheter into the deep-seated malignancies.

Adenocarcinoma ; pathology ; radiotherapy ; therapy ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; pathology ; radiotherapy ; therapy ; Combined Modality Therapy ; Female ; Humans ; Hyperthermia, Induced ; methods ; Male ; Middle Aged ; Pelvic Neoplasms ; pathology ; radiotherapy ; therapy ; Radiation Dosage ; Radiotherapy, High-Energy ; Rectal Neoplasms ; pathology ; radiotherapy ; therapy ; Remission Induction ; Temperature ; Uterine Cervical Neoplasms ; pathology ; radiotherapy ; therapy

Adult ; Aged ; Carcinoma, Hepatocellular ; radiotherapy ; Female ; Humans ; Liver Neoplasms ; radiotherapy ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplastic Cells, Circulating ; pathology ; Portal Vein ; pathology ; Radiotherapy Planning, Computer-Assisted ; methods