CLINICAL PROSPECTS OF TUMOR-ASSOCIATED PROTEASES AND THEIR TISSUE INHIBITORS INVESTIGATION IN ONCOLOGIC PATIENTS

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Abstract

Review of authors’ results and the most representative literature data on the role of tumor-associated proteolitic systems involved in invasion, metastasizing and angiogenic processes in diagnostics and prognosis in various oncologic diseases is presented in this paper. The main attention is paid to the key matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) as well as to the plasminogen activation system components (uPA, PAI-1) study in tumor tissues and peripheral blood. Personal results demonstrated an increase of most MMPs, uPA and PAI-1 expression in the tumors of 70–90% patients with various neoplasms as compared to histologically unchanged adjacent tissues. MMP-7 was shown to be a promising serologic marker of ovarian and colorectal cancer (CRC): its sensitivity at 70% specificity level comprised about 70% in both diseases. The greatest clinical interest should be paid to the implication of tumor-associated proteases as prognostic factors. Thus, results of 5-years monitoring have demonstrated that high preoperative serum MMP-7 and TIMP-1 levels were independent unfavorable prognostic factors for CRC and univariate analysis revealed unfavorable prognostic role of high tumor MMP-7 in patients with disseminated process. Tumor PAI-1 level was shown to be a valuable prognostic factor for stage III CRC. In the final part of the review possibilities and prospects of tumor-associated proteases usage as targets for specific molecular directed therapy are discussed.

 

About the authors

E. S. Gershtein

N.N. Blokhin Russian Cancer Research Center of RAMS, Moscow, Russian Federation

Author for correspondence.
Email: esgershtein@gmail.com
PhD, Professor, Leading Research Worker, the Clinical Biochemistry Laboratory, N. N. Blokhin Russian Cancer Research Center of RAMS Address: 115478, Moscow, Kashirskoye Highway 24; tel.: (499) 324-11-59 Russian Federation

N. E. Kushlinskii

N.N. Blokhin Russian Cancer Research Center of RAMS, Moscow, Russian Federation

Email: biochimia@mtu-net.ru
PhD, Professor, RAMS cor. member, Head of the Clinical Biochemistry Laboratory, N. N. Blokhin Russian Cancer Research Center of RAMS Address: 115478, Moscow, Kashirskoye Highway 24; tel.: (499) 324-11-59 Russian Federation

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