Saratov JOURNAL of Medical and Scientific Research

Ponukalin A.N.

Saratov State Medical University, Department of Urology, Assistant Professor, Candidate of Medical Science

The value of tumor markers in prognos-ing the outcomes of treatment of patients with bladder cancer

Year: 2018, volume 14 Issue: №4 Pages: 661-666
Heading: Urology Article type: Review
Authors: Ponukalin A.N., Zakharova N.B., Skriptsova S.A., Fomkin R.N., Chekhonatskaya M.L.
Organization: Saratov State Medical University n.a. V I. Razumovsky, Scientific Research Institute of Fundamental and Clinical Uronephrology, Saratov State Medical University
Summary:

The review analyzes the recent publications of the results of the use of molecular genetic markers of bladder cancer (RMP) in clinical practice. The prospects of application of a series of molecules determined in tumor tissue, serum, urine in the diagnosis of RMP are presented. One ofthe most promising areas of finding a marker forthe diagnosis and control of treatment of RMP in recent years are the study ofthe proteomic composition of urine.

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Biomarkers of renal damage and immunohistochemical detection of oncogenesis in the surgical treatment of renal cell carcinoma

Year: 2018, volume 14 Issue: №3 Pages: 420-426
Heading: Urology Article type: Original article
Authors: Tarasenko A.l., Rossolovsky A.N., Berezinets O.L., Ponukalin A.N., Medvedeva A.M., Zakharova N.B., Popkov V.M., Maslyakova G.N.
Organization: Saratov State Medical University, I.M. Sechenov First Moscow State Medical University
Summary:

Objective: to assess the possibility of using markers of renal injury and carcinogenesis as additional criteria for the choice of the method of surgical treatment of RCC and to minimize the risk of development and progression of kidney injury. Material and Methods. 60 patients with morphologically confirmed RCC T1-3M0N0 operated on in the volume of open nephrectomy or laparoscopic nephrectomy or laparoscopic resection and the kidney were examined. Patients were divided into 3 groups: group 1: patients after nephrectomy performed for kidney cancer using traditional surgical technique, group 2: patients after laparoscopic nephrectomy and group 3: after laparoscopic resection of kidney tumor. Before surgical operation, on the 5-7 day and after 1 month, all patients were examined by concentrations of urinary excreted lipocalin 2 (NGAL), and serum concentrations of IL-18, MMP-9 and IGF-1. Renal function was estimated using the calculated GFR equation (CKD-EPI 2009) based on serum creatinine level. Immunohistochemical study of histological preparations of distant tumors on proliferation antibodies (Ki-67, PCNA), apoptosis (BAX, Bcl-2) was performed. Differences in clinical data and clinical variables were compared using Spearman rank correlations and t-test. Results. The studied indices of renal damage of IL-18, NGAL, MMP-9 and IGF-1 both in the early (5-7 days) and later (1 month) postoperative period showed a correlation between the surgical intervention method and the degree of tumor cell differentiation. Conclusion. The levels of biomolecular markers of renal damage (IL-18, NGAL, MMP-9 and IGF-1) correlate with the degree of differentiation in thetumoral cells and functional activity of the remaining renal parenchyma in the postoperative period, but also depend on the individual characteristics of the patient's body. A certain level of expression of MMP-9 and IL-18 with a small tumor size can be a guide to determine the indications for the choice of organ-preserving surgery in patients.

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The prospects for application of biomarker "vascular endothelial growth factor" in predicting the treatment outcomes of bladder cancer

Year: 2018, volume 14 Issue: №2 Pages: 268-272
Heading: Urology Article type: Original article
Authors: Zakharova N.B., Ponukalin A.N., Skriptsova S.A.
Organization: Saratov State Medical University
Summary:

Purpose: assessment of the diagnostic value of Vascular Endothelial Growth Factor (VEGF) in predicting the outcome treatment of patients with muscle-invasive bladder cancer. Material and Methods. The study involved 264 people: 204 patients with RMP; 60 people aged 21 to 60 years were the comparison group. Patients with RMP are divided into stages of the disease. With non-muscle-invasive ВС (NIRMP) under TA-1NxMo there were 75 patients. Out of 129 patients with muscle-invasive ВС (MIRE) within the body (pT2aN0M0-T2bN0M0) was diagnosed in 69 of people. In 60 patients, the tumor sprouted paravesical tissue and surrounding organs (rt3a-bn0m0-41; pT36N1M0-11; pT4N1M0-5; T4N1M1-3); 19 patients had metastases to the iliac lymph nodes are installed only after the operation. Metastases were found in three patients out of 19 in addition to the lymphonoduses in the lungs. Tumors had the following gradations: G1-97; G2-37; G3-58. All patients NMIN (n=75) completed a TUR of the bladder wall with the tumor. MERE patients underwent radical cystectomy (n=117), open resection of the bladder (n=12), palliative surgery (n=3). The period of follow-up after surgical treatment was 3.5±0.5years. Quantitative determination of VEGF in blood serum was performed by solid-phase ELISA. Results. Despite the fact that the increase in VEGF level of blood serum in groups of patients with NIMRE and MIRE has significant differences both before and in the postoperative period, it is associated with the aggressiveness of tumor growth, development of metastases and recurrences of the disease. Conclusion. The increase in the content of VEGF serum suitable for use as an indicator: the risk of relapse within the first year after TUR in patients NMIN; development of relapses and metastases in pre and postoperative periods in MERE patients.

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Dynamics of angiogenesis and inflammation biomarkers in patients with urolithic disease with obstructive uropathy

Year: 2017, volume 13 Issue: №3 Pages:
Heading: Urology Article type: Original article
Authors: Popkov V.M., Zakharova N.B., Ponukalin A.N., Polozov A.B., Khotko D.N., Khotko A.l., Spirin P.V.
Organization: Scientific Research Institute of Traumatology Orthopedics and Neurosurgery of Saratov State Medical University n.a. V.I. Razumovsky
Summary:

Purpose: to establish the nature of changes in markers of angiogenesis and inflammation in the blood serum and urine in patients with obstruction of the ureteropelvic segment or upper third of the ureter by ureteral stones in different terms of the kidney drainage. Material and Methods. 53 patients with urolithiasis have been examined. The main group consisted of 33 patients with concrements of the upper third of the ureter or renal pelvis-ureteral segment with pres- ent obstructive uropathy. The comparison group consisted of 20 patients with calculi of the kidney without symptoms of obstruction. In the main group patients underwent drainage of the kidney by percutaneous-nephrostomy puncture. Results. Patients of the main group revealed a significant increase in the levels of markers of angiogenesis and inflammation before the kidney drainage. The level of MCP-1 correlated with the level of serum creatinine. In the process of drainage the levels of these markers were decreased as a result of increased GFR. Determination of the concentration of urinary VEGF, IL-8 and MCP-1 in patients may have clinical value in personalized management of patients with obstructive uropathy to determine the optimal terms of the second stage of the surgical intervention. Conclusion. Determination of markers of inflammation and angiogenesis in the urine of patients in conjunction with assessment of renal function by creatinine level is important for determining the term of kidney drainage.

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The diagnostic importance of biomarkers of angio-genesis and inflammation at patients with prostate diseases

Year: 2016, volume 12 Issue: №4 Pages: 593-598
Heading: Urology Article type: Original article
Authors: Popkov V.M., Zakharova N.B., Ponukalin A.N., Tonkoschkur A.N.
Organization: Saratov State Medical University
Summary:

Purpose: to establish the nature of change of the maintenance of PSA and markers of angiogenesis and inflammation in blood serum at patients with prostate diseases. Material and Methods. 72 patients with the level of the general PSA more than 4 ju/ml were examined. The first group of patients with benign prostatic hyperplasia with histology conclusion and with benign prostatic hyperplasia and prostatic intraepithelial neoplasia of low degree included 29 patients, the second group consisted of 9 patients with prostatic intraepithelial neoplasia of high degree, the third group included 5 patients with the localized prostate cancer, the fourth group consisted of 25 patients with locally advanced prostate cancer, and the fifth group with 6 metastatic prostate cancer patients. Results. At patients with prostate diseases the rise of VEGF level in blood serum occurs with increase of the maintenance of PSA and develops at the precancer stage (the prostatic intraepithelial neoplasia of high degree) and against high concentration of biomarkers of inflammation. Determination of VEGF concentration in blood serum at patients with "a gray zone" of PSA may have clinical value at the personified maintaining of patients with prostate cancer at the stage of pre-biopsy diagnostics. Conclusion. The simultaneous increase of the VEGF content in blood serum and the general PSA at prostate cancer patients is one of characteristics of a progression of tumoral growth.

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Diagnosis and combined treatment of patients with locally advanced prostate cancer

Year: 2015, volume 11 Issue: №3 Pages: 317-322
Heading: Urology Article type: Review
Authors: Popkov V.M., Kim T.D., Ponukalin A.N.
Organization: Saratov State Medical University
Summary:

Prostate cancer is one of the most urgent problems of modern oncology. The article provides an overview of the methods of treatment of locally advanced prostate cancer, comparative characteristics, the advantages of both independent and combined methods. The results of multicenter studies have been stated.

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Пиелонефрит и метаболические нарушения после уретеросигмостомии Mainz pouch II у больных раком мочевого пузыря

Year: 2015, volume 11 Issue: №2 Pages: 193-197
Heading: Urology Article type: Review
Authors: Попков В.М., Понукалин А.Н., Гордеева В.А.
Organization: Saratov State Medical University
Summary:

В обзоре литературы представлены сведения об отдаленных осложнениях уретеросигмостомии Mainz pouch II, таких, как пиелонефрит и метаболические нарушения. Анализируются механизмы их развития, обсуждаются перспективы прогноза, ранней диагностики и способов борьбы с ними.

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Efficacy evaluation of various immunohistochemical markers in stage definition and prognosis of muscle invasive urinary bladder cancer

Year: 2014, volume 10 Issue: №1 Pages: 124-128
Heading: Urology Article type: Original article
Authors: Ponukalin A.N., Maslyakova G.N., Tsmokalyuk E.N.
Organization: Saratov State Medical University
Summary:

Objective: to carry out the comparative efficacy evaluation of various immunohistochemical markers in stage definition and prognosis of muscle-invasive urinary bladder cancer. Material and methods. Surgical material has included 80 patients with urinary bladder neoplasms. Clinical, histological, immunohistochemical and statistical methods of research has been used. Results. The immunohistochemical investigation has showed that only 4 markers from the 12 (Ki-67, рбЗ, p53 и EGFR) make possible to determine the stage of urinary bladder cancer and the disease prognosis. Conclusion. The proliferative activity of marker Ki-67 can be used as an auxiliary marker in the choice of volume of surgical treatment, which could predict an unfavorable outcome of disease in 81,2% of cases.

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Assessment of range of uric and serum biomarkers in determination of bladder cancer severity

Year: 2013, volume 9 Issue: №4 Pages: 735-740
Heading: Urology Article type: Original article
Authors: Popkov V.M., Ponukalin A.N. Zakharova N.B.
Organization: Saratov State Medical University
Summary:

Purpose: to establish efficiency of a range of uric and serum biomarkers of bladder cancer for diagnostics and the prognosis of risk of development of disease recurrence. Material and methods: TPA and TPS, VEGF level research in blood serum, UBC in urine in 176 people, among which 135 patients with bladder cancer (RMP) have been conducted. Group of comparison has included16 patients (patients with cystitis). The control group has been made of 25 almost healthy men. 75 patients had non-muscle invasive RMP (Ta-1N0M0). Results. It has been statistically determined that reliable growth of of TPA, TPS in blood serum and UBC in urine in patients with non-muscle invasive RMP in comparison with patients in groups of control and comparison has been established. The increase of UBC in urine of patients of this group with recurrence of tumoral growth within a year has been noted. In comparison with cytological research of urine sedimentation, molecular markers of RMP (the uric UBC and serum TPA, TPS) possess diagnostic sensitivity, allow to confirm the presence of disease, to carry out diagnostics of stages of organ and extra invasion. RMP is possible to consider as an additional prognostic serum marker increase in the VEGF level in blood serum. Conclusion. Inclusion in diagnostic process in the clinical research of biomarkers showed that identification of NMIRMP increased from 18,1% in 2006 to 55,6% in 2011. The chosen volume of complex treatment allowed to reduce recurrence and lethality in the first two years from 32 to 15,5%.

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Morphological changes in the organs of laboratory animals during the prolonged oral administration of gold nanoparticles

Year: 2013, volume 9 Issue: №2 Pages: 208-213
Heading: Macro- and Micromorphology Article type: Original article
Authors: Maslyakova G.N., Pakhomiy S. S., Bucharskaya А.В., Zlobina O.V., Navolokin N.A., Ponukalin A.N., Khlebtsov N.B., Khlebtsov B.N., Bogatyrev V.A.
Organization: Saratov State Medical University, Институт биохимии и физиологии растений и микроорганизмов РАН
Summary:

The purpose of the article is to assess the severity of the morphological changes in the internal organs of laboratory animals with prolonged oral administration of gold nanoparticles of different sizes. Material and methods: The experiment was carried out on 40 albino rats which were divided into 4 groups. Animals of the experimental group received oral gold nanoparticles by the appropriate scheme. Results: At comparing the morphological changes in the internal organs of laboratory animals it was established that the introduction of gold nanoparticles of different sizes leads to the same type of disturbances of morphological structure, the gold nanoparticles of 1-3 and 50 nm cause the most expressive changes. Conclusion: The most significant morphological modifications in the internal organs were caused by gold nanoparticles of 1-3 and 50 nm. It points out to the size-dependence of the effect of gold nanoparticles.

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