[Matrix metalloproteinases, their inhibitors and angiogenesis in different morphological types of lung precancer in persons who have long lived in the radioactive substance-polluted area of the Semipalatinsk Region, Kazakhstan].
The aim of the present investigation was to study a role of matrix metalloproteinases and their inhibitors in the pathogenesis of fibrosis and angiogenesis in lung precancer processes, which could be used to develop new pathogenetically substantiated lines in therapy. The investigation was conducted using intraoperative and biopsy specimens of the removed lungs and their parts from 113 patients with lung precancer changes with the diagnoses of lung cancer, chronic abscess, bronchoectatic disease, idiopathic fibrosing alveolitis, tuberculosis, of whom 41 patients had lived from childhood to 2002 in vicinity of a polygon and long exposed to radiation (annual radiation dose was greater than 0.1 Rem) (Group 1). The intraoperative and biopsy specimens from 72 patients who lived in the unchanged radiation areas of Kazakhstan (n = 32) and Moscow (n = 40) (Group 2) were used as a comparison group. The specimens were stained with hematoxylin and eosin, alcian blue, picrofuchsin as descried by van Gieson. The paraffin sections were immunohistochemically studied by the immunoperoxidase technique, by applying mono- and polyclonal antibodies to MMP-1, MMP-2, MMP-9, TIMP-1, VEGF, CD34, chromogranin, CD68, and Ki-67. Thus, lung precancer resulting from increased radiation is of high risk for invasive growth due to the imbalance between the expression of metalloproteinases and their inhibitors and the activation of antiblastomic defense mechanisms. Angionesis in the stroma of the adjacent tissues also creates favorable conditions for invasive epithelial growth. The relatively high level of metalloproteinases in radiation-induced precancer may be indirect evidence for the occurrence of precancer in the presence radiation-associated fibrosis and evidence for its high malignant potential.
G E
GE
Sagindikova
E A
EA
Kogan
E B
EB
Satbaeva
N B
NB
Paramonova
D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D007623:Kazakhstan; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism* / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology*; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology*; D011480:Protease Inhibitors / Q000378:metabolism*; D011848:Radioactive Pollutants / Q000009:adverse effects*; D012189:Retrospective Studies
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D011480:Protease Inhibitors; D011848:Radioactive Pollutants; D020782:Matrix Metalloproteinases