BACKGROUNDCD44v6 plays an important role in invasion and metastasis of tumor, Livin has anti-apoptotic effects. The present study aimed to explore the expression and clinical significance of CD44v6 and Livin in gastric cancer tissue.

METHODSStreptavidin-peroxidase linked immunohistochemical method was used to determine the expression of CD44v6 and Livin in gastric cancer tissue and adjacent normal gastric tissues from 59 patients with histopathologically confirmed gastric cancer, and in gastric tissue specimens of 15 patients with gastric polyps, and 15 patients with chronic non-atrophic gastritis. The chi-square test was used for comparison of the relevant factors, Spearman's rank correlation test was applied for relationship among positive expression of the proteins.

RESULTSThe expresion of CD44v6 was positive in 64.4% of the gastric cancer patients; 5.1%, 0 and 13.3% in specimens of normal tissues adjacent to the cancer tissues, in gastric tissue specimens of patients with gastric polyps, and patients with chronic non-atrophic gastritis, respectively. The expression of Livin was positive in 52.5% of the gastric cancer tissues, 6.8%, 0 and 6.7% in the adjacent normal gastric tissue, specimens of patients with gastric polyps and chronic non-atrophic gastritis, respectively. The expression of CD44v6 was significantly correlated with the depth of invasion, the degree of differentiation, and lymphnode metastasis of gastric cancer (P < 0.05). The positive expression rate of Livin protein was also significantly correlated with degree of differentiation of gastric cancer cells and metastasis to lymphnodes (P < 0.05), but not correlated with the depth of invasion and pathological types (P > 0.05). The expression of CD44v6 and Livin in the gastric cancer tissue was positively correlated (r(s) = 0.286, P = 0.028).

CONCLUSIONSThe increased expression of CD44v6 and Livin in gastric cancer tissue may be closely related with development and progression of gastric cancer. CD44v6 and Livin may be new biological markers of gastric cancer.

Adaptor Proteins, Signal Transducing ; analysis ; physiology ; Aged ; Female ; Humans ; Hyaluronan Receptors ; analysis ; physiology ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins ; analysis ; physiology ; Male ; Middle Aged ; Neoplasm Proteins ; analysis ; physiology ; Stomach Neoplasms ; chemistry ; metabolism ; pathology

Objective:To investigate the analgesic effect of neurotropin (NTP) on bone cancer pain (BCP) and its preliminary mechanisms in rats.Methods:(1) According to the random number table method, 72 Sprague-Dawley (SD) female rats were randomly and equally divided into 6 groups: normal control group, sham-operated group, BCP model group, BCP+low-dose NTP group, BCP+medium-dose NTP group, and BCP+high-dose NTP group ( n=12). The SHZ-88 breast cancer cells were inoculated into the tibias of rats in the latter 4 groups to establish BCP models. After 15-21 d of modeling, the rats of the latter 3 groups were intraperitoneally administered with 1.2, 2.4 and 3.6 unit NTP, respectively, once per d for 7 consecutive d. The mechanical withdrawal threshold (MWT) changes were measured in each group before BCP and 5, 7, 10, 14, 17, and 21 d after BCP. The number of 5-hydroxytryptamine 7 (5-HT7) positive cells and 5-HT7 protein expression in the ventrolateral periaqueductal gray (vlPAG) were detected by immunohistochemistry and Western blotting, respectively. (2) Twenty-four rats 21 d after BCP modeling were randomly divided into BCP group, BCP+high-dose NTP group (BCP rats with intraperitoneal injection of 3.6 unit NTP), BCP+NTP+SB-269970 group (BCP rats with pretreatment of specific 5-HT7 receptor antagonist SB-269970 in the vlPAG for 30 min, and then, with intraperitoneal injection of 3.6 unit NTP, n=8). The MWT changes were measured in each group before NTP and 15, 30, 45, 60 min after NTP. Results:(1) Seventeen and 21 d after modeling, the MWT values of the modeled hind limb of rats in BCP+low-dose NTP group, BCP+medium-dose NTP group, and BCP+high-dose NTP group were significantly higher than those in BCP group; those in the BCP+high-dose NTP group were significantly higher than those in BCP+low-dose NTP group and BCP+medium-dose NTP group; those in BCP+medium-dose NTP group were statistically higher than those in the BCP+low-dose NTP group ( P<0.05). Twenty-one d after modeling, the number of 5-HT7 receptor positive cells and protein expression in the vlPAG of rats in the BCP+low-dose NTP group, BCP+medium-dose NTP group, and BCP+high-dose NTP group were significantly larger/higher than those in BCP group; those in the BCP+high-dose NTP group were significantly larger/higher than those in BCP+low-dose NTP group and BCP+medium-dose NTP group; those in BCP+medium-dose NTP group were statistically larger/higher than those in the BCP+low-dose NTP group ( P<0.05). (2) At 15, 30, 45 and 60 min after injection of NTP, the MWT values of the modeled hind limb of rats in the BCP+high-dose NTP group and BCP+NTP+SB-269970 group increased gradually, enjoying statistical significance as compared with those in the BCP group at the same time point ( P<0.05); however, the MWT values of the BCP+NTP+SB-269970 group were significantly lower as compared with those in the BCP+high-dose NTP group at the same time point ( P<0.05). Conclusion:The activation of 5-HT7 receptor in the vlPAG is involved in the analgesic effect of NTP on BCP in rats.

BACKGROUND: Chinese medicine is effective for preventing and treating glucocorticoid-induced osteoporosis, however, the underlying mechanism remains unclear. DKK1, an inhibitor of Wnt/β-catenin signaling pathway, can be up-regulated by glucocorticoid. Thereafter, DKK1 is an important target in the prevention and treatment of osteoporosis. OBJECTIVE: To explore the regulatory effect of Zuogui pill on DKK1 in the prevention and treatment of glucocorticoid-induced osteoporosis. METHODS: Eighteen three-month-old female Sprague-Dawley rats were randomly divided into three groups: control group, model group and Zuogui pill group. Rats in the model and Zuogui pill groups received the subcutaneous injection of dexamethasone to establish the model of glucocorticoid-induced osteoporosis. The Zuogui pill group rats were administrated Zuogui pill extracts, and the control rats were given the same volume of normal saline. At 1 month after modeling, the lumbar vertebrae were removed to test the bone mass and microstructures by micro-CT scanning. The biomechanical properties were detected by compression test. The mRNA expression levels of DKK1, Runx2 and CTSK were determined by Qpcr. The serum alkaline phosphatase activity was tested. RESULTS AND CONCLUSION: Compared with the control group, in the model group, the volumetric bone mineral density, trabecular bone volume fraction, trabecular number, and trabecular thickness were significantly decreased (P ＜ 0.05), the trabecular separation and structure model index were significantly increased (P ＜ 0.05). The serum alkaline phosphatase activity was on a decline. The mRNA expression level of DKK1 showed a significant up-regulation (P ＜ 0.05). The mRNA expression level of Runx2 showed a down-regulated trend while mRNA expression level of CTSK showed an up-regulated trend. Compared with the model group, the Zuogui pill group showed significantly enhanced volumetric bone mineral density, trabecular bone volume fraction, and trabecular number (P ＜ 0.05); the structure model index was significantly decreased (P ＜ 0.05); the trabecular separation was reduced; the serum alkaline phosphatase activity was enhanced; the mRNA expression level of DKK1 showed a significant down-regulation (P ＜ 0.05); the mRNA expression level of Runx2 showed an up-regulated trend while mRNA expression level of CTSK showed a down-regulated trend. The vertebral compressive strength in the Zuogui pill group was significantly higher than that in the model group (P＜0.05). In summary, Zuogui pill prevents and treats glucocorticoid-induced osteoporosis possibly through the down-regulation of mRNA expression of DKK1.

BACKGROUNDAttention-deficit hyperactivity disorder (ADHD) is the most common mental and behavioral disorder in school-aged children. This study evaluated the effect of osmotic-release oral system (OROS) methylphenidate (MPH) on cognitive function and academic performance of Chinese school-aged children with ADHD.

METHODSThis 12-week, prospective, multicenter, open-label, self-controlled study enrolled 153 Chinese school-aged children with ADHD and 41 non-ADHD children. Children with ADHD were treated with once-daily OROS-MPH (18 mg, 36 mg, or 54 mg). The primary endpoints were Inattention/Overactivity (I/O) with Aggression Conners Behavior Rating Scale (IOWA) and Digit Span Test at week 12 compared with baseline. Secondary endpoints included opposition/defiant (O/D) subscale of IOWA, Clinical Global Impression (CGI), Coding Test, Stroop Color-word Test, Wisconsin Card Sorting Test (WCST), academic performance on teacher-rated school examinations, and safety at week 12 compared with baseline. Both non-ADHD and ADHD children received the same frequency of cognitive operational test to avoid the possible bias caused by training.

RESULTSA total of 128 patients were evaluated with cognitive assessments. The OROS-MPH treatment significantly improved IOWA Conners I/O subscale scores at week 12 (3.8 ± 2.3) versus baseline (10.0 ± 2.4; P < 0.0001). Digit Span Test scores improved significantly (P < 0.0001) with a high remission rate (81.1%) at week 12 versus baseline. A significant (P < 0.0001) improvement was observed in O/D subscale of IOWA, CGI, Coding Test, Stroop Color-word Test, WCST, and academic performance at week 12 versus baseline. Very few practice-related improvements were noticed in the non-ADHD group at week 12 compared with baseline. No serious adverse events and deaths were reported during the study.

CONCLUSIONSThe OROS-MPH treatment effectively controlled symptoms of ADHD and significantly improved academic performance and cognitive function of Chinese school-aged children with ADHD. The treatment was found to be safe and generally well-tolerated over 12 weeks.

TRIAL REGISTRATIONClinicalTrials.gov, NCT01933880; http://clinicaltrials.gov/ct2/show/NCT01933880?term=CONCERTAATT4099&rank=1.

Administration, Oral ; Attention Deficit Disorder with Hyperactivity ; drug therapy ; physiopathology ; Child ; Cognition ; drug effects ; Female ; Humans ; Male ; Methylphenidate ; administration & dosage ; adverse effects ; therapeutic use ; Neuropsychological Tests ; Prospective Studies ; Treatment Outcome

This study was aimed to investigate the expression levels of CXCR4 and VEGF in serum of patients with DLBCL and their clinical significances. The peripheral blood of 44 patients with newly diagnosed DLBCL and 20 healthy adults as a control group were chosen for study. And the expression levels of CXCR4 and VEGF in serum were detected by ELISA. The results showed that the expressions of VEGF and CXCR4 in DLBCL patients were higher than those in the control group (P < 0.05). The expression of VEGF was positively correlated with the expression of CXCR4 in DLBCL patients, and the correlation coefficient was 0.743 (P < 0.05). The VEGF expression in DLBCL patients was correlated with LDH, immunotyping, the number of extranodal involvements, Ann Arbor staging and ECOG performance score; while the expression of CXCR4 was correlated with LDH, immunotyping, the number of extranodal involvements and Ann Arbor staging. Univariate analysis showed that LDH, extranodal involvements, immunotyping, Ann Arbor staging, CXCR4 and VEGF were associated with OS. Multivariate analysis showed that the immunotyping and CXCR4 expression independently associated with OS. It is concluded that both expression levels of VEGF and CXCR4 are significant higher than those in the control group. CXCR4 expression positively correlates with VEGF expression and displays a prognostic significance for OS. This study suggests that combined targeting VEGF and CXCR4 may become a novel therapeutic strategy for diffuse large B cell lymphoma.
Adolescent ; Adult ; Aged ; Case-Control Studies ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse ; metabolism ; pathology ; Male ; Middle Aged ; Prognosis ; Receptors, CXCR4 ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism ; Young Adult

OBJECTIVETo study the influence of the mutants of hepatitis B surface antigen on the cell immunity.

METHODSThe recombinant plasmids of NS2Swt, NS2S126, NS2S133, NS2S141 and NS2S145 were transfected into Chinese hamster ovary (CHO) cells and the expressed proteins were detected by means of ELISA. Following PHA-activated lymphoblasts proliferation assay and IFN-gamma, IL-2, IL-10 induction assay were done with these proteins.

RESULTSIt was identified that these proteins of HBsAg could stimulate human lymphoblasts proliferation. Besides, there were no significant difference between the mutants and the wild. It was deserved to point out that the HBsAg with T126S mutation could increase the expression of IFN-gamma in the culture medium while the HBsAg with M133T mutation induced more expression of IL-10.

CONCLUSIONThe results suggested that the cellular immune response to mutants of HBV might not be strengthened or weakened. But it should not be ignored that HBV T126S or M133T mutation may assert a potential impact on the cell immunity.

Animals ; CHO Cells ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cricetinae ; Cricetulus ; Enzyme-Linked Immunosorbent Assay ; Hepatitis B Surface Antigens ; genetics ; Humans ; Interferon-gamma ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-2 ; metabolism ; Lymphocytes ; cytology ; drug effects ; metabolism ; Mutant Proteins ; genetics ; Mutation ; Plasmids ; genetics ; Recombinant Proteins ; pharmacology ; Transfection

BACKGROUND AND OBJECTIVEPatients with clinical stage I seminoma accounts for 70%-80% of patients with this disease. This study was to analyze the relationship between different therapeutic methods and the prognosis of this disease.

METHODSThe data of all patients with clinical Stage I seminoma treated by multi-disciplinary approach from 1999 to 2008 in Sun Yat-sen University Cancer Center were analyzed. The patients were divided into 3 groups based on the treatment they received after orchiectomy: 30 patients treated with chemotherapy, 8 with radiotherapy, and 20 under surveillance. The prognosis of different treatment groups was evaluated.

RESULTSAmong the 58 patients with stage I seminoma, 57 were followed up successfully. The median follow-up time was 50 months (range, 8-115 months). No relapse or metastasis was seen in the chemotherapy group. One patient relapsed in the radiotherapy group. Four patients had metastasis of retroperitoneal lymph node in the surveillance group. The disease-free survival was higher in the chemotherapy group than that in the surveillance group (P=0.005). There was no significant difference in the relapse-free survival between the surveillance group and the radiotherapy group (P=0.364).

CONCLUSIONSChemotherapy is a safe and effective treatment for patients with Stage-1 seminoma after radical orchidectomy.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bleomycin ; therapeutic use ; Cisplatin ; therapeutic use ; Combined Modality Therapy ; Disease-Free Survival ; Etoposide ; therapeutic use ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Orchiectomy ; methods ; Retrospective Studies ; Seminoma ; drug therapy ; pathology ; radiotherapy ; surgery ; Testicular Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Treatment Outcome ; Young Adult

BACKGROUND AND OBJECTIVEThe most effective therapy against renal cell carcinoma (RCC) is surgical treatment; however, there have been few large-scale studies that focused on the oncological outcome of this disease in China. The aim of the current study was to report the clinicopathological results and cancer-specific survival (CSS) rate in RCC patients after surgical treatment in our center.

METHODSWe retrospectively analyzed the clinicopathological data of 336 RCC patients who underwent radical or partial nephrectomy between 1999 and 2006. Of the 336 patients, 226 were male and 110 were female; the median age was 51 years. Univariate and multivariate analyses were conducted to identify the independent prognostic predictors for this cohort of RCC patients.

RESULTSDuring follow-up, the overall 5-year CSS rate was 81.4%. The 5-year CSS rates for patients with stage-I, -II, -III, and -IV RCC were 94.7%, 88.9%, 68.8%, and 19.3%, respectively. The patients with T1N0M0 (T1) and T2N0M0 (T2) tumors had similar survival curves. For patients with T1 category tumor, the survival rate did not differ significantly between the radical nephrectomy and nephron-sparing surgery groups. For the 21 patients with metastasis confined to the local lymph nodes, the 5-year survival rate was 31.6% after radical nephrectomy and lymph node dissection. For the 15 patients with vena caval tumor thrombus, the 5-year survival rate was 52.5% after radical nephrectomy and tumor thrombus extirpation. Multivariate Cox regression showed that stage was an independent predictor for CSS (hazard ratio, 3.359; P < 0.001).

CONCLUSIONSFor localized RCC, the oncological outcome of this cohort is comparable to that reported in the Western literature. For some patients with locally advanced RCC, aggressive surgical treatment can lead to better long-term survival. However, the prognosis of the patients with metastasis still needs to be improved.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Renal Cell ; pathology ; surgery ; Child ; Child, Preschool ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neoplastic Cells, Circulating ; Nephrectomy ; methods ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Young Adult

OBJECTIVETo study the immunomodulatory effects and mechanisms of mesenchymal stem cells (MSC) derived from the bone marrow in acute leukemia patients in vitro.

METHODSBone marrow mononuclear cells from acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) were obtained and cultured in low serum medium. The immunophenotypes were assessed by FACS and immunol histochemistry. The levels of cytokines were evaluated by enzyme linked immunosorbant assay (ELISA). T-cell suppression ability was evaluated by Transwell chamber assay. Moreover, the immunoregulatory ability of AML- and ALL-derived MSC was detected by mixed lymphocyte culture assay.

RESULTSALL-derived MSC showed a typical fibroblast-like morphology. They were positive for CD29, CD44 and CD105, the positive rate were 98.81%, 99.25% and 90.52%, respectively, while negative for CD31, CD45 and CD34. Moreover, ALL- and AML-derived MSC didn't express HLA-DR and co-stirnulatory molecules (CD40, CD80 and CD86). ALL and AML derived MSC could secret several cytokines, such as TGF-β1 (567.58 ± 52.64 and 357.15 ± 33.52), HGF (647.27 ± 102.54 and 219.67 ± 62.37), IL-6 (59.67 ± 15.69 and 54.35 ± 12.31) and IL-11 (102.58 ± 23.54 and 78.21 ± 9.67), the level of secretion of TGF-β1 and HGF were higher in ALL bone marrow derived MSC than that of in AML bone marrow derived MSC. ALL and AML derived MSC significantly suppressed T lymphocyte proliferation in a dose-dependent manner, the counts per minute (CPM) were (3.58 ± 0.54) × 10(4), (2.87 ± 0.33) × 10(4), (1.78 ± 0.51) × 10(4) and (1.15 ± 0.15) × 10(4) for AML derived MSC, and CPM were (1.96 ± 0.31) × 10(4), (1.57 ± 0.28) × 10(4), (0.91 ± 0.41) × 10(4) and (0.22 ± 0.11) × 10(4) for ALL derived MSC when MSC were 0.5 × 10(4), 1 × 10(4), 2 × 10(4) and 5 × 10(4). In addition, the CPM was (4.01 ± 0.72) × 10(4) in control group. The immunosuppressive ability was different between MSCs derived from AML and ALL. The immunosuppressive effect of ALL derived MSC could be reversed by anti-TGF-β1 and anti-HGF antibody.

CONCLUSIONALL-derived MSC show immunoregulatory effect in vitro and this effect is achieved through cytokines. But MSCs derived from AML display abnormal changes in T-cell suppression ability.

Bone Marrow ; immunology ; Bone Marrow Cells ; cytology ; Cell Proliferation ; drug effects ; Cytokines ; pharmacology ; Humans ; Immunophenotyping ; Interleukin-11 ; metabolism ; Interleukin-6 ; metabolism ; Leukemia, Myeloid, Acute ; immunology ; Mesenchymal Stromal Cells ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; immunology ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo observe the treating effect of collage-heparin sulfate after the 10 mm rat sciatic nerve defect was bridged by it.

METHODSA new kind of nervous tissue engineering scaffold was produced by freeze-drying technique from collagen-heparin sulfate. Thirty-two SD rats were randomly divided into A, B, C and D groups. Sciatic nerve defect in group A was bridged by collagen-heparin sulfate. In group B, sciatic nerve was bridged by auto-nerve transplantation. Group C was the blank control group. Animals in group D were normal. And 10 mm sciatic nerve defect was bridged in the experiment. Thirty-six weeks after the operation, the experimental animals were detected by HRP labeled retrograde trace, HE staining, toluidine staining, silvering staining, S100, GAP-43 and NF immunohistological staining, MBP immunofluorescence staining and transmission electron microscope to observe the nerve regeneration inducing effect of this new scaffold.

RESULTSNine months after operation, the collage-heparin sulfate scaffold was replaced by newly regenerated nerve. The number of HRP labeled spinal cord anterior horn cells and the area of sensation nerve fiber at the posterior horn were similar with that was repaired by auto-nerve. GAP-43, NF and S100 labeled regenerated nerve fiber had passed the total scaffold and entered the distal terminal. The regenerated nerve fibers were paralleled, lineage arranged, coincide with the prearranged regenerating "channel" in the collagen-heparin sulfate scaffold. MBP immunofluorescence staining also proved that the newly regenerated nerve fiber could be ensheathed. In the experimental group, the area of myelinated nerve fiber and the thickness of the myelin sheath had no obvious difference with that of the group repaired by auto-nerve, except that the density of the regenerated myelinated sheath fiber was lower than that of the control group.

CONCLUSIONNervous tissue engineering scaffold produced by collagen-heparin sulfate can guide the regeneration of nerve fibers. The nerve function recovers fine. This kind of material has great application potential.

Animals ; Biocompatible Materials ; Heparitin Sulfate ; Male ; Prosthesis Implantation ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; injuries ; pathology ; surgery ; Sulfuric Acid Esters ; Tissue Engineering ; methods