A novel PI3K inhibitor XH30 suppresses orthotopic glioblastoma and brain metastasis in mice models

Glioblastoma is carcinogenesis of glial cells in central nervous system and has the highest incidence among primary brain tumors. Brain metastasis, such as breast cancer and lung cancer, also leads to high mortality. The available medicines are limited due to blood-brain barrier. Abnormal activation of phosphatidylinositol 3-kinases (PI3K) signaling pathway is prevalent in glioblastoma and metastatic tumors. Here, we characterized a 2-amino-4-methylquinazoline derivative XH30 as a potent PI3K inhibitor with excellent anti-tumor activity against human glioblastoma. XH30 significantly repressed the proliferation of various brain cancer cells and decreased the phosphorylation of key proteins of PI3K signaling pathway, induced cell cycle arrest in G1 phase as well. Additionally, XH30 inhibited the migration of glioma cells and blocked the activation of PI3K pathway by interleukin-17A (IL-17A), which increased the migration of U87MG. Oral administration of XH30 significantly suppressed the tumor growth in both subcutaneous and orthotopic tumor models. XH30 also repressed tumor growth in brain metastasis models of lung cancers. Moreover, XH30 reduced IL-17A and its receptor IL-17RA in vivo. These results indicate that XH30 might be a potential therapeutic drug candidate for glioblastoma migration and brain metastasis.

The roles of NOD1 and NOD2 in tumorigenesis and development / 中国生化药物杂志

Theinnate immunity system of human body has more and more attention for its antibacterial, antiviral, maintainingimmunehemostasis and promoting tissue damage and repair and other physiological functions.As members of NOD-like receptors(NLRs), NOD1 and NOD2 receptors are identified as intracellular pattern recognition receptors(PRRs), can be identified with molecular damage endogenous(damage-associated molecular patterns, DAMPs)and exogenous injury-molecular pathogen associated molecular(pathogen-associated molecular patterns, PAMPs), and initiation of innate and specific immune response, maintain the steady balance of body.Recently, a bunch of evidence have demonstrated that the importance of NOD1 receptor and NOD2 receptor is not limited in field of anti-infection, and the insulin resistance, kidney and liver damage recovery, cardiovascular disease and tumorigenesis are also closely related with these two receptors.So the aim of this article is to interpret the NOD1 and NOD2 general structure and function, and summarize the link between these two PRRs and tumorigenesis and finally make a clue for cancer immunotherapy.

Effect of different stimulants on the LAG3 expression and function of spleen lymphocytes in mice / 中国生化药物杂志

Objective To investigate the effect of different stimulants on the LAG3 expression and function of spleen lymphocytes in mice. Methods The spleen lymphocytes from mice were isolated by density centrifugation.The LAG3 expressions in T cell subsets after exposure to conA, PMA, PHA or anti-CD3/28 antibodies for 24 h or 72 h were analyzed by Flow cytometry.The IFN-γsecretions of conditional medium were detected by ELISA kit.The proliferation of lymphocytes was examined by MTT analysis.Results Treatment with conA for 24 h or 72 h dose-dependently increased LAG3 +CD3 +and LAG3 +CD4 +CD3 +T cell percentages.Similarly, an exposure of anti-CD3/28 antibodies for 72 h significantly increased LAG3 +CD3 +and LAG3 +CD4 +CD3 + T cell percentages.Meanwhile, conA and anti-CD3/28 antibodies increased the IFN-γsecretion of lymphocytes in a time-dependent manner.Furthermore, Treatment with conA, PMA, PHA or anti-CD3/28 antibodies for 72 h could enhance the proliferation of lymphocyte. Conclusion conA and anti-CD3/28 antibodies are effective activators of T cells, and both of them could promote the expression of LAG3 and IFN-γsecretion of lymphocytes.

Association of vascular endothelial growth factor gene polymorphisms with ectopic pregnancy among Chinese women / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of vascular endothelial growth factor (VEGF) gene polymorphisms with ectopic pregnancy (EP) among Chinese women.</p><p><b>METHODS</b>A case-control study was carried out, which compared 192 women with a history of EP with 210 post-menopausal controls who had two pregnancies but no history of EP for the genotypes of the VEGF gene. Polymorphisms of the VEGF gene including -460C/T, -1154G/A, -2578C/A and +936C/T were determined with a polymerase chain reaction-restriction fragment length polymorphism method.</p><p><b>RESULTS</b>No significant difference was found in the genotypic and allelic distribution of the -460C/T and +936C/T polymorphisms between the two groups. Compared with the GG genotype, the VEGF -1154 AA+GA genotype could significantly decrease the risk of EP (OR=0.61, 95%CI: 0.42-0.87). Compared with the CC genotype, VEGF -2578 AA+CA genotype could significantly reduce the risk of EP (OR=0.66, 95%CI:0.44-0.99). Haplotype analysis suggested that the T-A-A (VEGF -460/-1154/-2578) and C-A-A haplotypes could significantly decrease the risk of EP compared with the T-G-C haplotype (P=0.020, OR=0.41, 95%CI:0.19-0.89, P=0.014, OR=0.29, 95%CI:0.11-0.82).</p><p><b>CONCLUSION</b>The -1154A or -2578A alleles of the VEGF gene can significantly decrease the risk of EP among Chinese women. The VEGF -460C/T, -1154G/A and -2578C/A polymorphisms showed a linkage disequilibrium. Both T-A-A and C-A-A haplotypes can significantly decrease the risk of EP.</p>

Vascular endothelial growth factor andβ-human chorionic gonadotropin are associated with trophoblastic invasion into the tubal wall in ectopic pregnancy / 天津医药

Objective To assess the association between the depth of trophoblastic penetration into the tubal wall with serum concentrations of vascular endothelial growth factor (VEGF) and β-human chorionic gonadotropin (β-HCG). Meth-ods Eighty patients with a diagnosis of tubal pregnancy in the ampullary region underwent radical surgical treatment (sal-pingectomy), were included in this study. The serum levels of VEGF andβ-HCG were detected on the day of surgery. The se-rum level of VEGF was measured by ELISA. The serum level ofβ-HCG was quantified with a two-site immunofluorimetric assay based on the direct sandwichtechnique. Histological material was stained with Masson's trichrome to identify muscular fibers. Immunohistochemical staining was used for human placental lactogen (hPL) to identify intermediate trophoblast and determine the depth of trophoblastic invasion into the tubal wall. The ampullary pregnancies were classified histologically ac-cording to the depth of trophoblastic infiltration into the tubal wall. Results The mean serum values of VEGF andβ-HCG were significantly lower in patients with stage I tubal infiltration than those of stageⅡ, and which were significantly lower in patients with stageⅡthan those in stageⅢ(P<0.05). The threshold serum value of VEGF was 308.6 ng/L, the sensitivity was 100.0%and the specificity was 92.6%for stageⅠand stageⅡ. The threshold serum value of VEGF was 431.9 ng/L, the sensitivity was 79.3%and specificity was 79.2%for stageⅡandⅢ. The threshold serum value ofβ-hCG was 2 509.6 IU/L, the sensitivity was 91.7%and specificity was 81.5%for stageⅠand stageⅡ, and levels of 13 142.6 IU/L, 72.4%and 95.8%for stageⅡand stageⅢ. Conclusion The depth of trophoblastic penetration into the tubal wall is associated with maternal serum concentrations of VEGF andβ-HCG, which can be used as the evaluation index for histological staging of trophoblas-tic tissue infiltration.

study on relation of dietary fiber from different sources, acceptable daily intake of calcium and colorectal cancer of 30 to 45 years old

This paper selects Jiashan, Zhejiang, the high incidence area of colorectal cancer in China, as research site and adopts case control as research method to study relative hazards of colorectal cancer, especially the relation between dietary factor and colorectal cancer. It makes a further understanding of the possible cause of high incidence of colorectal cancer in Jiashan in order to provide a scientific basis for the prevention of colorectal cancer

Significance of the mutation of c-kit gene in the clinical prognosis of gastrointestinal stromal tumor / 中国普通外科杂志

Objective To investigate the significance of the mutation of c-kit gene in the development,(clinical) pathology and prognosis of gastrointestinal stromal tumors(GISTs).Methods The technique of(PCR-SSCP) was used to detect ckit gene mutation in 106 cases of GIST,and 57 of the cases were(followed-up).Results The c-kit gene mutation rate in the whole group was 45.3%(48/106),and(3.4)%(2/41) in benign GIST,and 70.8%(46/65) in malignant GIST.The 1-,3 and 5-year survival rates and median survival time of the mutation positive group were all markedlly lower than those of the(mutation) negative group.A comparison of the parameters that can differentiate the benign GISTs from malignant ones such as size,histological necrosis,aggressive grade,nucleus mitotic count and nuclear discrepancy,showed significant difference between the of postive and negative gene mutation(P