Animals ; Cardiomyopathy, Dilated ; metabolism ; Connexin 43 ; metabolism ; Disease Models, Animal ; Hypericum ; Male ; Plant Extracts ; pharmacology ; Rats ; Rats, Wistar

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ; analogs & derivatives ; pharmacology ; Animals ; Cardiomyopathy, Hypertrophic ; drug therapy ; metabolism ; Connexin 43 ; metabolism ; Disease Models, Animal ; Male ; Myocardium ; metabolism ; Rats ; Rats, Wistar

OBJECTIVETo study the effect of angiogenesis inhibitor SU6668 on the growth and metastasis of gastric cancer in SCID mice.

METHODSMetastatic model was established by orthotopic implantation of histologically intact human tumor tissue into the gastric wall of SCID mice. Forty-eight mice were randomly divided into four groups, and saline, 5-FU, SU6668, and 5-FU plus SU6668 were administered by i.p. every day for 6 weeks after tumor implantation. The mice were killed and tumor weight, tumor inhibition rate, intratumoral microvessel density(MVD), apoptotic index(AI) and metastasis inhibition were evaluated.

RESULTSCompared with the control, tumor growth was significantly inhibited in mice treated respectively with 5-FU, SU6668 and 5-FU plus SU6668 with inhibition rates of 47.5%, 64.1% and 69.2% respectively. Decreased MVD and increased AI were noted in the mice treated with SU6668 and 5-FU plus SU6668. The incidences of liver and peritoneal metastases was significantly inhibited and decreased to 62.5%, 69.9% in SU6668 group, and 74.9%, 90% in 5-FU plus SU6668 group. The growth and metastasis of human gastric cancer implanted in SCID mice were significantly inhibited in SU6668 group and combined group, especially in combined group.

CONCLUSIONAngiogenesis inhibitor SU6668 has a strong inhibitory effect on tumor growth and metastasis of human gastric cancer transplanted in SCID mice, and has synergistic effect combined with cytotoxic agents.

Angiogenesis Inhibitors ; pharmacology ; therapeutic use ; Animals ; Apoptosis ; drug effects ; Cell Line, Tumor ; Drug Synergism ; Fluorouracil ; pharmacology ; therapeutic use ; Humans ; Indoles ; pharmacology ; therapeutic use ; Liver Neoplasms ; prevention & control ; secondary ; Male ; Mice ; Mice, SCID ; Neoplasm Transplantation ; Neoplasms, Experimental ; Neovascularization, Pathologic ; drug therapy ; Pyrroles ; pharmacology ; therapeutic use ; Stomach Neoplasms ; drug therapy ; pathology

OBJECTIVETo investigate the association of SOX9 expression and clinicopathologic factors and prognosis of gastric cancer.

METHODSA retrospective cohort study including 112 gastric cancer patients admitted to the Zhejiang Provincial People's Hospital from 2004 to 2006 was performed. Immunohistochemical analysis was used to evaluate the expression of SOX9 in the 112 specimens of gastric cancer tissues and 70 non-cancerous tissues adjacent to the tumor.

RESULTSLow expression of SOX9 was seen in 5(7.1%) tissues out of 70 non-cancerous tissues adjacent to the tumor. A total of 94(83.9%) patients had varying expression of SOX9, of whom 51(45.4%) had overexpression. Univariate analysis demonstrated that the expression of SOX9 was significantly associated with Lauren classification (P<0.05), tumor invasion(P<0.01), lymph node metastasis(P<0.05), distant metastasis(P<0.05) and tumor stage(P<0.05), however there was no significant association between SOX9 expression and sex, age, histological type, histology differentiation or tumor size. Kaplan-Meier analysis showed that the 5-year survival rate of patients with SOX9 over-expression was significantly lower than that of patients with low expression(29.4% vs. 49.2%, P=0.031). Multivariate Cox regression analysis showed that histology differentiation(P=0.046), tumor invasion(P=0.001), and distant metastasis(P<0.01) were independent prognostic factors for gastric cancer, however the over-expression of SOX9 was not significant(P=0.948).

CONCLUSIONSThe expression SOX9 is associated with the growth, invasion, and metastasis of gastric cancer, as well as the prognosis. However, SOX9 expression is not an independent factor for the prognosis in patients with gastric cancer.

Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; SOX9 Transcription Factor ; metabolism ; Stomach Neoplasms ; metabolism ; pathology

OBJECTIVETo investigate the growth inhibition and apoptosis of gastric cancer cell MKN45 induced by oridonin and its mechanism.

METHODSThe MTT method was used to investigate the inhibitory effect of oridonin on MKN45 cells. The AO/EB and Hoechst 33258 staining were used to observe the cell morphologic changes of apoptosis induced by oridonin. Prophase apoptotic ratio and cell cycle change were evaluated by GuavaEasycyte PCA-96 system. The expressions of Bcl-2, Bax and caspase 3 proteins were determined by Western blot.

RESULTSOridonin significantly inhibited the proliferation of MKN45 cells in dose- and time-dependent manner. Typical apoptotic features of the cells treated with oridonin were found by AO/EB and Hoechest33258 staining. When MKN45 cells were treated with different doses of oridonin for 12 h, the prophase apoptotic ratio was stepped up from 3.3% (untreated group) to 8.7%-17.9%; after 24 h, from 4.8% (untreated group) to 13.9%-29.3%. There was significant difference between treated and untreated groups (P <0.01). After treatment with oridonin for 24 h, MKN45 cells were arrested at G(2)/M phase. Western blot analysis showed up-regulated expression of Bax and caspase-3, and no significant change of Bcl-2, but Bcl-2/Bax ratio decreased significantly.

CONCLUSIONSOridonin significantly inhibits the proliferation of MKN45 cell. Apoptosis of MKN45 induced by oridonin may be associated with the up-regulated expression of Bax and the change of Bcl-2/Bax ratio, thus to activate the caspase pathway.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Diterpenes, Kaurane ; pharmacology ; Humans ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Stomach Neoplasms ; metabolism ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo investigate the relationship between the expression of vascular endothelial growth factor (VEGF) and fms-like tyrosine kinase (Flt-1) mRNA and tumor progression, microvessel density and survival time in gastric carcinoma.

METHODSIn situ hybridization and immunohistochemical techniques were used to detect the gene expression of VEGF, Flt-1 and CD34 in 118 gastric carcinoma specimens.

RESULTSIn situ hybridization revealed that positive expression rates of VEGF and Flt-1 mRNA in gastric carcinoma were 54.24% and 55.9% respectively. There was a significant correlation between the expression of VEGF and Flt-1 mRNA and growth pattern, the depth of tumor invasion, vessel invasion, lymph node and distant metastasis (P < 0.01). The mean tumor microvessel densities (MVD) in patients of stage T3-T4 or those with vessel invasion, lymph node and distant metastases were significantly higher than those of stage T1-T2 and without metastases (P < 0.01). MVD value was correlated with the expression levels of VEGF and Flt-1 mRNA (P < 0.01). The mean survival time and survival rate of patients with positive mRNA expression and mean MVD value >or=54.9/mm2 were significantly lower than those of patients with negative mRNA expression and mean MVD value < 54.9/mm2.

CONCLUSIONSThe expression of VEGF and Flt-1 can promote tumor angiogenesis and contribute to tumor invasion and metastasis in gastric carcinoma. VEGF and Flt-1 may serve as valuable indicators of biological behaviour, prognosis and target of gene therapy in gastric carcinoma.

Adult ; Aged ; Female ; Humans ; In Situ Hybridization ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; RNA, Messenger ; genetics ; Stomach Neoplasms ; metabolism ; pathology ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism

The rapidly evolving aging society in China is associated with increased incidences of osteoporosis and fractures, which have become common health problems that threaten the quality of life of the elderly. Gut microbiota colonizing in the human intestinal tract form a mutual symbiotic relationship with the host and play an important role in the metabolism and immune regulation of the host. In recent years increasing studies have demonstrated that gut microbiota not only affect the digestive system but also contribute to the disease conditions involving the immune system, and have a close relationship with the occurrence and progression of osteoporosis. This review summarizes the progress and hotspots in recent researches of the associations among gut microbiota, the immune system, osteoporosis.
Aged ; Aging ; China ; Gastrointestinal Microbiome ; Gastrointestinal Tract ; microbiology ; Humans ; Microbiota ; Osteoporosis ; microbiology ; Quality of Life

OBJECTIVETo investigate the association of AKR1B10 expression in gastric cancer tissues with clinicopathologic features and prognosis of gastric cancer patients.

METHODSReal-time polymerase chain reaction (RT-PCR) was conducted to detect AKR1B10 mRNA expression in gastric cancer and adjacent gastric mucosa tissues (n=36). AKR1B10 protein expression was measured by immunohistochemistry in primary gastric cancer tissues (n=100) and non-tumorous gastric mucosa tissues (n=70).

RESULTSRT-PCR results confirmed that AKR1B10 was significantly down-regulated in gastric cancer tissues compared with that in paired adjacent mucosa [8.3% (3/36) vs. 91.7% (33/36), P=0.000]. Immunohistochemistry revealed that the percentage of AKR1B10 positive specimens in gastric carcinoma was lower than that in normal specimens [33.0% (33/100) vs. 92.9% (65/70), P=0.000]. The frequencies of positive AKR1B10 in patients was significantly correlated with tumor size (P=0.000), invasive depth (P=0.004), lymph node metastasis (P=0.028), distant metastasis (P=0.031) and TNM stages (P=0.000). The 5-year survival rate of positive AKR1B10 group was significantly higher as compared to negative group (60.6% vs. 32.8%, P<0.01).

CONCLUSIONThe down-regulation of AKR1B10 expression in gastric cancer may be associated with the progress of gastric cancer is suggestive of poor prognosis.

Adult ; Aged ; Aged, 80 and over ; Aldehyde Reductase ; genetics ; metabolism ; Female ; Gastric Mucosa ; enzymology ; pathology ; Humans ; Male ; Middle Aged ; Prognosis ; RNA, Messenger ; genetics ; Stomach Neoplasms ; diagnosis ; enzymology ; pathology

OBJECTIVETo compare the surgical outcomes between laparoscopic and open wedge resection for gastrointestinal stromal tumors of the stomach.

METHODSClinical data of 18 cases undergoing laparoscopic wedge resection from June 2000 to August 2009 at the Zhejiang Provincial People's Hospital were compared with 30 patients treated by open surgery. The perioperative parameters and prognosis data of the two groups were compared.

RESULTSCompared to the open group, laparoscopic group was found with longer operative time, less blood loss, less requirement of postoperative analgesia, earlier resumption of oral intake, earlier return of first flatus, and shorter postoperative hospital stay(all P<0.05). There were no postoperative deaths in both groups. Postoperative complication rate was significantly lower in the laparoscopic group(5.5% vs. 33.3%, P<0.05). The postoperative recurrence rates were 11.8%(2/17) and 10.7%(3/28); the 5-year survival rates were 78% and 63%, respectively, and the difference was not statistically significant(P>0.05).

CONCLUSIONLaparoscopic wedge resection is a feasible treatment option for GISTs of the stomach.

Adult ; Female ; Gastrectomy ; methods ; Gastrointestinal Stromal Tumors ; diagnosis ; pathology ; surgery ; Humans ; Laparoscopy ; Male ; Middle Aged ; Prognosis ; Retrospective Studies

OBJECTIVETo investigate the effects of the self-developed anti-heparanase polypeptide antibodies on growth and invasion of human hepatocellular carcinoma HCCLM6 cells.

METHODSUsing MTT, flow cytometry, plate clone formation, transwell invasion and heparan degrading enzyme assay, the growth and invasion changes of human hepatocellular carcinoma HCCLM6 cells by co-culture with each of three self-developed rabbit anti-heparanase polyclonal antibodies were detected.

RESULTSCompared with normal rabbit IgG, in the presence of each anti-heparanase polypeptide antibody, the growth, cell cycle and clone formation remained unchanged, and under the P1 or P2 anti-heparanase polypeptide antibody (with final concentration 100 microg/ml), the cell invasiveness was inhibited by 52.5% and 36.6%, respectively, and the heparanase activity was inhibited by 42.9% and 39.1%, respectively.

CONCLUSIONThe P1 and P2 anti-heparanase polypeptide antibodies can effectively inhibit the invasion ability and heparanase activity of liver cancer HCCLM6 cells. However, All the three antibodies have no effects on its growth, cell cycle and clone formation.

Antibodies ; pharmacology ; Carcinoma, Hepatocellular ; enzymology ; pathology ; Cell Adhesion ; Cell Differentiation ; Cell Line, Tumor ; Cell Movement ; Coculture Techniques ; Enzyme Activation ; Glucuronidase ; immunology ; metabolism ; Humans ; Liver Neoplasms ; enzymology ; pathology ; Neoplasm Invasiveness