PROGNOSTIC SIGNIFICANCE OF EXPRESSION OF TRANSCRIPTION FACTORS, VEGF GROWTH FACTOR AND ITS RECEPTOR, m-TOR PROTEIN KINASE AND THE ACTIVITY OF INTRACELLULAR PROTEINASES IN PATIENTS WITH DISSEMINATED RENAL CELL CARCINOMA
Abstract
Background. Search for more informative prognostic parameters in patients with renal cell carcinoma is an actual problem of modern oncology. Purpose: to study the prognostic significance of expression of transcription factors, VEGF growth factors, its receptors, m-TOR protein kinase and the activity of intracellular proteinases in patients with disseminated renal cell carcinoma. Material and methods. Forty patients with metastatic renal cell carcinoma (T3–4N0–1M1) were included into the study. In accordance with the MSKCC scale, all patients were divided into 3 groups: with good prognosis (n=13), intermediate (n=26) and unfavorable prognosis (n=1). Further, the analysis included patients with good and intermediate prognosis (n=39). All patients received targeted therapy with pazopanib or everolimus. Palliative nephrectomy was performed after completion of preoperative treatment. The level of transcription and growth factors was studied using IFA method. The proteasome and calpain activities were assayed fluorometrically. Results. Initially high levels of the expression of HIF-1 transcription factor and VEGF growth factor in renal cell carcinoma were associated with good disease prognosis evaluated according to the MSKCC scale. The targeted therapy with pazopanib/ everolimus resulted in decrease in the expression of HIF-1, NF-κB р65, NF-κB and р50 transcription factors, VEGF growth factor and the proteasome activity. The increased calpain activity in patients with intermediate prognosis was associated with disease progression. Conclusion. Additional molecular parameters that increase the informative value of the MSKCC scale were identified, allowing for more precise prediction of the disease outcome in patients with metastatic renal cell carcinoma.
About the Authors
Z. A. Yurmazov
Tomsk Cancer Research Institute
Russian Federation
Russian Federation
Yurmazov Zakhar Alexandrovich, oncologist, General Oncology Department,.
Phone: +7 (3822) 41-80-56. E-mail: pzahar@sibmail.com
Е. A. Usynin
Tomsk Cancer Research Institute
Russian Federation
Russian Federation
Usynin Evgeny Anatolyevich, MD, PhD, Researcher, General Oncology Department.
Phone: +7 (3822) 41-80-92. E-mail: gusi70@list.ru. SPIN-code: 1804-0292
L. V. Spirina
Tomsk Cancer Research Institute;
Siberian State Medical University, Tomsk
Russian Federation
Russian Federation
Spirina Lyudmila Viktorovna, MD, DSc, Senior Researcher, Laboratory of Tumor Biochemistry, Tomsk Cancer Research Center.
Phone: +7 (3822) 51-45-98. E-mail: spirinalv@oncology.tomsk.ru. SPIN-code: 1336-8363
I. V. Kondakova
Tomsk Cancer Research Institute
Russian Federation
Russian Federation
Kondakova Irina Viktorovna, Tumor Biochemistry.
Phone: +7 (3822) 5125-29. E-mail: kondakova@oncology.tomsk.ru. SPIN-code: 9338-4149
Е. M. Slonimskaya
Tomsk Cancer Research Institute;
Siberian State Medical University, Tomsk
Russian Federation
Russian Federation
Slonimskaya Elena Mikhailovna, MD, DSC, Professor, Head of General Oncology Department, Tomsk Cancer Research Institute.
Phone: +7 (3822) 41-80-92. E-mail: slonimskaya@rambler.ru. SPIN-code: 7763-6417
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Review
For citations:
Yurmazov Z.A., Usynin Е.A., Spirina L.V., Kondakova I.V., Slonimskaya Е.M. PROGNOSTIC SIGNIFICANCE OF EXPRESSION OF TRANSCRIPTION FACTORS, VEGF GROWTH FACTOR AND ITS RECEPTOR, m-TOR PROTEIN KINASE AND THE ACTIVITY OF INTRACELLULAR PROTEINASES IN PATIENTS WITH DISSEMINATED RENAL CELL CARCINOMA. Siberian journal of oncology. 2015;1(5):44-50. (In Russ.)
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