OBJECTIVETo investigate the effect of botulinum toxin type A on the expression of substance P (SP), calcitonin gene-related peptide (CGRP), transforming growth factor beta-1 (TGF-beta1) and alpha smooth muscle actin A (alpha-SMA) in wound healing.

METHODS60 rats were randomly divided into group C (control) group L (low-dose) and group H (high-dose), with 20 rats in each group. The wound-healing model was established by excision of four full-thickness skin (1 cm x 1 cm, around the injection site) on the back of all SD rats on the 7th day after BTA injection. The wound size was measured and the expression of SP, CGRP, TGF-beta1 and alpha-SMA in wound granulation tissue was assayed by immunohistochemical staining and computerized image analysis before operation, and 3 days, 7 days and 14 days after operation.

RESULTSAll the wounds healed 14 days after operation. The wound size in L and H group was not significantly different with that in C group on the 3rd day and 7th day after operation. The positive immuno-staining of SP, CGRP, TGF-beta1 and alpha-SMA in group L and H was significantly weaker than those in C group. Meanwhile, the positive immuno-staining of all above substances in H group was weaker than those in L group significantly.

CONCLUSIONSBotulinum toxin type A can decrease the expression of SP, CGRP, TGF-beta1, and alpha-SMA in wound healing in a dose-dependent manner with no effect on the healing time.

Actins ; metabolism ; Animals ; Botulinum Toxins, Type A ; pharmacology ; Calcitonin Gene-Related Peptide ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects ; metabolism ; Substance P ; metabolism ; Transforming Growth Factor beta1 ; metabolism ; Wound Healing ; drug effects

Adult ; Humans ; Lateral Ventricles ; pathology ; Male ; Neurocytoma ; pathology

Adult ; Brain ; pathology ; Brain Neoplasms ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Female ; Ganglioglioma ; metabolism ; pathology ; surgery ; Humans ; Neoplasms, Neuroepithelial ; pathology ; S100 Proteins ; metabolism ; Synaptophysin ; metabolism

OBJECTIVETo investigate the effect of curcumin (Cur) on radiosensitivity of nasopharyngeal carcinoma cell CNE-2 and its mechanism.

METHODThe effect of curcumin on radiosensitivity was determined by the clone formation assay. The cell survival curve was fitted by Graph prism 6. 0. The changes in cell cycle were analyzed by flow cytometry (FCM). The differential expression of long non-coding RNA was detected by gene chip technology. Part of differentially expressed genes was verified by Real-time PCR.

RESULTAfter 10 micro mol L-1 Cur had worked for 24 h, its sensitization enhancement ratio was 1. 03, indicating that low concentration of curcumin could increase the radiosensitivity of nasopharyngeal carcinoma cells; FCM displayed a significant increase of G2 phase cells and significant decrease of S phase cells in the Cur combined radiation group. In the Cur group, the GUCY2GP, H2BFXP, LINC00623 IncRNA were significantly up-regulated and ZRANB2-AS2 LOC100506835, FLJ36000 IncRNA were significantly down-regulated.

CONCLUSIONCur has radiosensitizing effect on human nasopharyngeal carcinoma CNE-2 cells. Its mechanism may be related to the changes in the cell cycle distribution and the expression of long non-coding IncRNA.

Cell Cycle ; drug effects ; radiation effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; radiation effects ; Curcumin ; pharmacology ; Gene Expression Regulation, Neoplastic ; drug effects ; radiation effects ; Humans ; RNA, Long Noncoding ; genetics ; Radiation Tolerance ; drug effects

OBJECTIVETo evaluate the impact of luteinizing hormone-releasing hormone (LHRH) on the protection of thymic function after allogenic hematopoietic stem cell transplantation (allo-HSCT).

METHODSMurine model of MHC mismatched allogeneic HSCT (C57BL/6-->BALB/c) was established. The severity of acute graft-versus-host-disease (GVHD) was assessed according to a clinical scoring system. The intra-cellular levels of IFN gamma, TNFalpha and IL-1 beta in thymocyte were analyzed by protein array and thymic function by quantification of signal-joint TCR rearrangement excision circles (sjTRECs).

RESULTSAll recipients in group A (allogeneic mice), B (allogeneic LHRH castrated-mice) and C (syngenic mice) achieved hematopoietic reconstitution. White blood cell (WBC) over 1.0 x 10(9)/L in groups A, B and C were on day (11.2 +/- 1.4), day (9.8 +/- 0.6) and day (9.7 +/- 0.7), respectively (P = 0.003, 0.002). The onset of acute GVHD in group B was (14.1 +/- 0.7) d and in group A was (11.4 +/- 1.2) d (P = 0.000). All mice in groups A and B developed acute GVHD. No mice occurred aGVHD in group C. The average scores of acute GVHD in groups A and B were (9.1 +/- 0.7) and (5.1 +/- 1.0), respectively (P = 0.000). The levels of IFN gamma, TNFalpha and IL-1 beta in control group were (2.3 +/- 2.5) ng/ml, (1.7 +/- 1.1) pg/ml and (1.8 +/- 1.2) pg/ml, respectively. The IFN gamma levels in groups A, B and C were (10.5 +/- 2.1) ng/ml, (6.7 +/- 2.1) ng/ml and (5.2 +/- 3.3) ng/ml, TNFalpha levels were (7.0 +/- 2.6) pg/ml, (4.3 +/- 0.8) pg/ml and (3.0 +/- 1.8) pg/ml, and IL-1 beta levels were (24.9 +/- 9.0) pg/ml, (17.4 +/- 3.9) pg/ml and (10.8 +/- 3.1) pg/ml, respectively. There were significant differences in the levels of cytokines between group A and the control group (P = 0.000, 0.000, 0.000). The levels of cytokines in group B were significantly higher than those in control group (P = 0.000, 0.003, 0.000). The levels of IFN gamma and IL-beta in group C were significantly higher than those of in control group (P = 0.015, 0.013), and so did in group A than in group B (P = 0.002, 0.002, 0.004), and in group A than in group C (P = 0.000, 0.000, 0.000). The analysis of linear regression showed that the average levels of IFN gamma and TNFalpha paralleled with aGVHD scores (r(2) = 0.359, P = 0.045; r(2) = 0.228, P = 0.019). The average sjTRECs copies/1000 PBMNCs were (39.4 +/- 44.7) in the control group and (12.3 +/- 13.0), (58.0 +/- 71.8) and (19.6 +/- 14.6) in groups A, B and C, respectively. There was no significant difference in the multiple comparisons of peripheral blood levels of sjTRECs among these four groups (P = 0.468).

CONCLUSIONIFN gamma, TNFalpha and IL-1 beta might be involved in the damage to the thymus by acute GVHD. Sex steroid inhibitor can not only reduce the severity of thymic damage after allo-HSCT, but also reduce the severity of aGVHD and the mechanism might be associated with the reduction of intra-cellular levels of IFN gamma in thymocyte.

Animals ; Castration ; methods ; Female ; Gonadotropin-Releasing Hormone ; therapeutic use ; Graft vs Host Disease ; pathology ; prevention & control ; Hematopoietic Stem Cell Transplantation ; Interferon-gamma ; metabolism ; Interleukin-1beta ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Thymus Gland ; immunology ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo summarize the resectable rate of advanced gastric cancer characterized by abdominal lymph node metastases with the arteriovenous neoadjuvant FLEOX chemotherapy plus appropriate nutritional support.

METHODSArteriovenous neoadjuvant FLEOX chemotherapy was administered to 50 patients of gastric cancer with advanced abdominal lymph node metastases. Of the 50 patients, 42 had never received any previous therapy and preoperative CT scanning revealed unresectable tumors because of advanced lymph node (station No.3, 7, 9, 12) or distant lymph node (No.14,16) metastases. The other 8 were characterized with relapse of severe lymph node metastases or with unresectable lymph node metastases demonstrated by exploratory laparotomy. Arteriovenous neoadjuvant FLEOX chemotherapy was conducted as follows: from day 1 to day 5, 5-FU 370 mg/m(2) and leukovorin 30 mg/kg intravenously, at day 6 and day 20, CDDP 70 mg/m(2) and epotoside 70 mg/m(2) intraarterially. This FLEOX regimen was repeated every five weeks for two or three courses. Out of the 50 patients,12 malnutritional cases received parenteral and/or enteral nutritional support according to the nutritional condition. Arteriovenous neoadjuvant FLEOX chemotherapy was then administered after the improvement of nutritional state. Their nutritional support methods were adapted to their chemotherapy as well.

RESULTSAll the patients' general conditions and symptoms were improved significantly. For the 50 cases, the imageological and histological response rate (CR+PR) was 84.0%, and curative resection rate was 78.0%. Thus, 39 patients underwent subtotal or total gastrectomy, even combined organ resection, with D(2)+alpha or D(3) lymphadenectomy. Despite neoadjuvant chemotherapy, all malnutritional cases had significant weight gain after nutritional support, and other nutritional indexes,such as serum albumin, also resumed to normal.

CONCLUSIONArteriovenous neoadjuvant FLEOX chemotherapy proves favorable therapeutic effect for gastric cancer with advanced abdominal lymph node metastases, and downstages inoperable metastatic lymph nodes for radical operation. This combined modality regimen and nutritional support may play an important role in the treatment of advanced gastric cancer.

Adult ; Aged ; Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; methods ; Nutritional Support ; Stomach Neoplasms ; surgery ; therapy

OBJECTIVETo investigate the effect of botulinum toxin type A (Botox A) injection on hypertrophic scar in rabbit ear model.

METHODSThe hypertrophic scar model was established in 16 Japanese rabbits' ears. These wounds were divided into two groups as group T (treated with Botox A, n = 48) and group S (not treated, n = 48). The wounds healing times and scar hypertrophy were observed with 8 specimen of normal skin at the rabbit ears as sham group B. HE stain was used to assess the hypertrophic index (HI). The expression of collagen I and III was tested by western-blot. The cell cycle of fibroblasts was studied by flow cytometry.

RESULTSThe HI was significantly lower in group T than in group S (P < 0.01). The expression of collagen I and III, as well as the ratio of I to III, was markedly stronger in group S than in group T (P < 0.01). Compared with group T, more fibroblasts were in G2-M in group S and fewer in G0-G1 (P < 0.05).

CONCLUSIONSLocal injection of Botox A can inhibit the formation of hypertrophic scar and the activity of fibroblasts in rabbit ear model. It can significantly decrease the expression of collagen I and III in hypertrophic scar, as well as the ratio of collagen I to III. It serves as the basis for the treatment of hypertrophic scar with Botox A.

Animals ; Botulinum Toxins, Type A ; pharmacology ; Cells, Cultured ; Cicatrix, Hypertrophic ; metabolism ; pathology ; Ear ; pathology ; Female ; Fibroblasts ; drug effects ; Injections, Subcutaneous ; Rabbits ; Wound Healing ; drug effects

OBJECTIVETo construct a dendritic cell vaccine transduced by murine alpha-fetoprotein (mAFP) gene, and evaluate its immunoprotective effect on C57BL/6J mice during the induction of hepatocellular carcinoma by diethylnitrosamines, carbon tetrachloride and ethanol.

METHODSDendritic cells (DCs) were induced and augmented by murine IL-4 and GM-CSF, and transfected by recombinant adenovirus engineered with mAFP gene. Major MHC class I and II, B7.1 (CD80), B7.2 (CD86), CD18a, and CD54 molecules on DC were analyzed by FACS. 80 C57BL/6J male mice were randomly divided into 4 groups (20 mice per group): Simple DC inoculated group, pAdBM5-mAFP-DC inoculated group, pAdBM5-mAFP plasmid inoculated group, and PBS control group. They were immunized once with 5 x 10(5) DCs (0.1 ml)/mouse administered s. c. in the left flank or 100 mg pAdBMS-mAFP plasmid/mouse administered i. m. in the left tibialis anterior muscle. Inoculation was conducted once a week for 4 weeks after 3 times consecutive immunization initially. At the same time of immunization, DEN/CCl4/ethanol were given to induce hepatocellular carcinoma. Tumor incidence was assessed after 20 weeks.

RESULTSA transgenic DC vaccine was successfully constructed and the mAFP transgenic DCs expressed high level molecules of major MHC class I and II , B7.1, B7.2, CD18a, and CD54. After the 20-week induction, the incidence of primary hepatocellular carcinoma (PLC) was 70.0% in simple DC inoculated group, 25.0% in pAdBMS-mAFP-DC inoculated group, 65.0% in pAdBM5-mAFP plasmid inoculated group, and 75.0% in PBS control group. There was a significant difference between group B and other groups (P < 0.05).

CONCLUSIONmAFP transgenic DC tumor vaccine inoculation may induce strong immunoprotection against liver carcinogenesis and tumor development and reduce PLC incidence induced by DEN/CCl4/ethanol.

Adenoviridae ; genetics ; Animals ; B7-1 Antigen ; metabolism ; Cancer Vaccines ; Carbon Tetrachloride ; Cells, Cultured ; Dendritic Cells ; cytology ; immunology ; metabolism ; Diethylnitrosamine ; Ethanol ; Genetic Vectors ; Histocompatibility Antigens Class I ; metabolism ; Histocompatibility Antigens Class II ; metabolism ; Intercellular Adhesion Molecule-1 ; metabolism ; Liver Neoplasms, Experimental ; chemically induced ; immunology ; prevention & control ; Male ; Mice ; Mice, Inbred C57BL ; Random Allocation ; Recombinant Proteins ; genetics ; metabolism ; Transfection ; alpha-Fetoproteins ; genetics ; metabolism

OBJECTIVETo investigate the incidence of HBV reactivation and its clinical characteristics in the non-active HBsAg carriers receiving chemotherapy or immunosuppressant treatment, and to evaluate the role of nucleos(t)ide analogues against HBV reactivation.

METHODSNon-active HBsAg carriers suffering from cancer, autoimmune diseases recieving immunosuppression therapy or cytotoxic chemotherapy were enrolled in the study. The in-patients from June 2002 to April 2007 in the Second Affiliated Hospital of Chongqing Medical University were assigned in the control group. The outpatients or in-patients with the similar disease condition from April 2007 to July 2008 were enrolled in the preventive group. The characteristics of HBV replication, liver damage, clinical symptoms and effectiveness of nucleos(t)ide analogues as prophylaxis for HBV reactivation were observed. The nucleos(t)ide analogues were used before chemotheraphy or immunosuppressive agents. The characheristics and clinical manifestations about HBV reactivation were investigated.

RESULTSOf the 32 patients in preventive group, the amount of HBV DNA was detected in the 1rst, 3rd, 6th and 12th month after nucleos(t)ide analogues treatment. After chemotherapy or immunosuppressant treatment, only 9.4% (3/32) of them suffered from HBV reactivation, as indicated by positive HBV DNA in the serum and abnormal liver function. Ot the 77 patients in control group without nucleos(t)ide analogues treatment before chemotherapy or immunosuppression therapy, 58.4% (45/77) shown HBV reactivation, 4 patients in the control group died of liver failure, and one liver failure patient recieved liver transplantation.

CONCLUSIONHBV can be activated in immunosuppressed patients, nucleos(t)ide analogues should be used in early phase to prevent HBV reactivation.

Adult ; Antineoplastic Agents ; adverse effects ; Antiviral Agents ; therapeutic use ; Carrier State ; DNA, Viral ; blood ; Female ; Hepatitis B ; drug therapy ; prevention & control ; virology ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; drug effects ; Humans ; Immunosuppressive Agents ; adverse effects ; Lamivudine ; adverse effects ; therapeutic use ; Liver Function Tests ; Male ; Middle Aged ; Nucleosides ; therapeutic use ; Retrospective Studies ; Virus Activation ; drug effects

The fusion protein (F) gene of Newcastle disease virus was amplified by polymerase chain reaction (PCR) from the recombinant plasmid pVAX1-F, and subcloned into eukaryotic expression vector pmcDNA3. 1+. The F gene was identified by sequencing. The recombinant plasmid was transformed into attenuated Salmonella typhimurium SL7207, and the recombinant was designated as SL7207 (pmcDNA3. 1-F). In vitro and in vivo experiments showed that the plasmid stability of pmcDNA3. 1-F was apparently higher than that of pcDNA3. 1-F in SL7207. In order to compare the immune response induced by these two re combinant bacteria, BALB/c mice were immunized orally with them at the dosage of 2 x 10(9) CFU respectively. Both SL7207(pcDNA3. 1-F) and SL7207(pmcDNA3. 1-F) initiated F-specific serum and mucosal antibodies in immunized mice. Furthermore, 4-day-old SPF chickens were immunized with SL7207(pcDNA3. 1-F) and SL7207(pmcDNA3. 1-F) at the dosage of 5 x 10(9) CFU and boosted two weeks later with the same dosage. Humoral and intestinal mucosal immune responses were observed and their levels were significantly higher than that of negative and positive controls. The result of protective efficacy showed that the chickens immunized with SL7207(pmcDNA3. 1-F) had the protective rate of 70.0%, higher than that of the SL7207 (pcDNA3. 1-F) with 50.0%. In summary, the DNA vaccine delivered by attenuated Salmonella typhimurium has good immunogenicity. A novel mucosal DNA vaccine has been developed and could be useful for controlling the infection and epidemic of Newcastle disease in the poultry.
Animals ; Chickens ; Female ; Immunization ; Mice ; Mice, Inbred BALB C ; Newcastle disease virus ; immunology ; Plasmids ; Salmonella typhimurium ; genetics ; Vaccines, Attenuated ; immunology ; Vaccines, DNA ; immunology ; Viral Vaccines ; immunology