title: Hypoxia, tumour-associated macrophages, microvessel density, VEGF and matrix metalloproteinases in human gastric cancer: interaction and impact on survival.
abstract: BACKGROUND
  Hypoxia is a key feature of the microenvironment of cancer cells actively participating in tumour progression. Our study was aimed to evaluate the impact of hypoxia and hypoxia-associated factors on tumour progression and survival of patients with gastric cancer.
  
  
  METHODS
  One hundred and five resected specimens were used. The level of tumour hypoxia was evaluated using (31)P NMR spectroscopy, CD68 (tumour-associated macrophages), CD34 (microvessel density, MVD) and VEGF expression, immunohistochemistry, MMP-2 and MMP-9 activity, zymography. Statistical analysis was conducted using Pearson's test, Kaplan-Meier survival analysis, log-rank test and Cox proportional hazards model.
  
  
  RESULTS
  Intratumoral hypoxia level has been significantly correlated with VEGF expression, TAM number and total protease activity. The overall survival rate of patients with strong tumour hypoxia, high level of MVD, VEGF expression, TAM and MMP activity was significantly lower than that of the patients without the mentioned tumour characteristics.
  
  
  CONCLUSIONS
  The hypoxia-associated signalling that is activated in tumours promotes tumour progression through the recruitment of macrophages, remodelling of extracellular matrix and neoangiogenesis.
authors.affiliation: Department of Microenvironment of Tumor Cells, R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kiev, Ukraine. osion@onconet.kiev.ua
authors.forename: Sergej
authors.initials: S
authors.lastname: Osinsky
authors.forename: Larissa
authors.initials: L
authors.lastname: Bubnovskaya
authors.forename: Irina
authors.initials: I
authors.lastname: Ganusevich
authors.forename: Antonina
authors.initials: A
authors.lastname: Kovelskaya
authors.forename: Lilya
authors.initials: L
authors.lastname: Gumenyuk
authors.forename: Gennadij
authors.initials: G
authors.lastname: Olijnichenko
authors.forename: Sergej
authors.initials: S
authors.lastname: Merentsev
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D000328:Adult; D000368:Aged; D002452:Cell Count; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D013274:Stomach Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020782:Matrix Metalloproteinases