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Proteinase administration reduces growth of human breast and pancreatic cancer in nude mice and diminishes expression of some tumorigenesis biomarkers

Wald M.,1 Šebková V.,2 Österreicher J.,3 Zadinová M.,4 Pou?ková P.4

1 Department of Surgery, Second Medical School, Charles University, Prague, Czech Republic
2 Department of Immunology, St. Elisabeth Hospital, Na Slupi 6, Prague, Czech Republic
3 Purkyn? Military Medical Academy, Hradec Králové, Czech Republic
4 Department of Biophysics, First Medical Schoo, Charles University, Prague, Czech Republic

Int. J. Immunotherapy 2001, Vol. XVII, No. 2/3/4, pp. 65-73  - ISSN 0255-9625


The aim of this investigation was to study the effect of proteinases on the growth of human breast and pancreatic cancer transplanted to nude mice. Animals were divided into active groups receiving a specific mixture of serine and cysteine proteinases, and control groups receiving saline. Enzyme treatment significantly reduced tumor growth (up to 50 %) irrespective of the transplanted cell line. To study the effect of proteolytic enzymes on several molecular biomarkers that may play a role in breast cancer tumorigenesis, expression of Ki-67, c-erbB-2, bcl-2, and CD-34 was investigated using immunohistochemical examination. Expression of Ki-67 and c-erbB-2 was significantly reduced in the enzyme-treated animals compared with control animals. Evaluation of necroses revealed that the extent of necrotic tissue in the enzyme-treated mice was approximately  30% lower than in the control group. In the enzyme group, reduced density of CD44 adhesion molecule was measured on the surface of tumor cells.

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