OBJECTIVETo study the mechanism of interleukin 7/interleukin 7 receptor (IL-7/IL-7R) in promoting cell proliferation and inducing lymphangiogenesis of non-small cell lung cancer (NSCLC) in vivo and in vitro.

METHODSImmunohistochemical study for IL-7, IL-7R, cyclin D1 and vascular endothelial growth factor-D (VEGF-D) was carried out in NSCLC tissues from 95 patients. The relationship between IL-7/IL-7R expression and various parameters was analyzed. The mechanism of IL-7/IL-7R in promoting cell proliferation and inducing lymphangiogenesis was studied by methylthiazolyldiphenyl-tetrazolium bromide, fluorescence-activated cell sorting, reverse transcriptase-PCR, Western blot, co-immunoprecipitation, chromatin immunoprecipitation and nude mice experiments with xenograft tumors.

RESULTSIL-7 (63.2%, 60/95), IL-7R (61.1%, 58/95), cyclin D1 (52.6%, 50/95) and VEGF-D (58.9%, 56/95) showed that high level of expression in NSCLC. IL-7/IL-7R over-expression correlated with cyclin D1 expression (P < 0.01, P < 0.01), VEGF-D expression (P < 0.01, P < 0.01), increased lymphovascular density (P = 0.005, P = 0.013), advanced clinical stage (P = 0.008, P = 0.005) and presence of lymph node metastasis (P < 0.01, P < 0.01). IL-7/IL-7R could promote proliferation of A549 cell, increase cyclin D1 and VEGF-D expression, and enhance c-Fos/c-Jun expression and phosphorylation, resulting in formation of heterodimer. Furthermore, IL-7/IL-7R could induce binding of c-Fos/c-Jun to cyclin D1/VEGF-D promoters and regulate their transcription. IL-7/IL-7R could also promote proliferation and lymphangiogenesis of lung cancer xenograft tumors.

CONCLUSIONSIL-7/IL-7R promotes c-Fos/c-Jun expression and activity in NSCLC. This further facilitates cyclin D1 expression and accelerates proliferation of cells and VEGF-D-induced lymphovascular formation.

Animals ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Cyclin D1 ; metabolism ; Female ; Humans ; Interleukin-7 ; metabolism ; physiology ; Lung Neoplasms ; metabolism ; pathology ; Lymphangiogenesis ; Lymphatic Metastasis ; Male ; Mice ; Mice, Nude ; Middle Aged ; Neoplasm Staging ; Neoplasm Transplantation ; Proto-Oncogene Proteins c-fos ; metabolism ; Proto-Oncogene Proteins c-jun ; metabolism ; Receptors, Interleukin-7 ; metabolism ; physiology ; Vascular Endothelial Growth Factor D ; metabolism

OBJECTIVETo study the chemical constituents of the leaves of Isatis indigotica.

METHODThe leaves of I. indigotica were extracted with 80% ethanol. The EtOH extract was dispersed in H20 and extracted with petroleum, EtOAc and BuOH successively. The EtOAc fraction was isolated and purified by column chromatography on silica gel, Sephadex LH -20 and Rp-8, Rp-18. All the compounds were identified on the basis of spectral analyses (including MS, 1H-NMR, 13 C-NMR) , RESULT: Eleven compounds were isolated from the leaves of I. indigotica, and structures were characterized as 10H-indolo [3, 2-b] quinoline (1), indirubin (2), 4 (3H)-quinazo-linone (3), (E)-3-(3', 5'-dimethoxy-4'-hydroxybenzylidene) -2-indolinone (4), 2, 3-dihydropyrrolo [2, 1-b] quinazolin-9(1H) -one (5) , benzoic acid (6) , o-droxy-benzoic acid (7), ( - ) -lariciresinol (8) , ( + ) -isolariciresinol (9), isovitexin (10), 6-f-D-glucopyranosyldiosmetin (11).

CONCLUSION1, 4, 5, 8, 9, 11 were obtained from the leaves of I. indigotica for the first time.

Furans ; chemistry ; isolation & purification ; Indole Alkaloids ; chemistry ; isolation & purification ; Isatis ; chemistry ; Lignans ; chemistry ; isolation & purification ; Lignin ; chemistry ; isolation & purification ; Naphthols ; chemistry ; isolation & purification ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; Quinolines ; chemistry ; isolation & purification

OBJECTIVETo detect the expression of VEGF receptors in papillary renal cell carcinoma and to explore the correlation between their expression and clinical prognosis.

METHODSExpression of VEGF receptors and PCNA (proliferating cell nuclear antigen) were evaluated in 82 patients with papillary renal cell carcinoma using tissue microarray and SP immunohistochemical staining.

RESULTSThe expression of VEGFR-1 in papillary renal cell carcinoma was 82.93%, VEGFR-2 63.41%, VEGFR-3 34.15% and PCNA 67.07%, respectively. Increased VEGFR-2 expression was significantly correlated with tumor size (P = 0.016), histological grade (P = 0.034) and distant metastasis (P = 0.002). VEGFR-3 expression was correlated with histological grade (P = 0.028), lymph node status (P = 0.010) and distant metastasis (P = 0.018), but not correlated with gender, age, location, tumor size and TNM staging. VEGFR-1 expression had no correlation with any clinic and pathologic factors. PCNA expression was correlated with histological grade (P = 0.011), but not correlated with other factors. The expression of VEGFR-2 and VEGFR-3 in death cases were higher than that in surviving patients.

CONCLUSIONBoth VEGFR-2 and VEGFR-3 can serve as markers for prognosis of papillary renal cell carcinoma. Differently, VEGFR-3 is a predictor of lymph node metastasis, increased VEGFR-2 expression could be used to predict a potential blood dissemination.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Papillary ; metabolism ; pathology ; Carcinoma, Renal Cell ; metabolism ; pathology ; Female ; Humans ; Kidney Neoplasms ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Proliferating Cell Nuclear Antigen ; metabolism ; Proportional Hazards Models ; Survival Rate ; Tumor Burden ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism ; Vascular Endothelial Growth Factor Receptor-3 ; metabolism