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Документ 6-gene promoter methylation assay is potentially applicable for prostate cancer clinical staging based on urine collection following prostatic massage(Spandidos Publications, Великобританія, 2019-10-29) Nekrasov, K. A.; Vikarchuk, M. V.; Rudenko, E. E.; Ivanitskiy, I. V.; Grygorenko, V. M.; Danylets, R. O.; Kondratov, A. G.; Stoliar, L. A.; Sharopov, B. R.; Kashuba, V. I.The detection of prostate cancer (PCa) biomarkers in bodily fluids, a process known as liquid biopsy, is a promising approach and particularly beneficial when performed in urine samples due to their maximal non‑invasiveness requirement of collection. A number of gene panels proposed for this purpose have allowed discrimination between disease‑free prostate and PCa; however, they bear no significant prognostic value. With the purpose to develop a gene panel for PCa diagnosis and prognosis, the methylation status of 17 cancer-associated genes were analyzed in urine cell‑free DNA obtained from 31 patients with PCa and 33 control individuals using methylation‑specific polymerase chain reaction (MSP). Among these, 13 genes indicated the increase in methylation frequency in patients with PCa compared with controls. No prior association has been reported between adenomatosis polyposis coli 2 (APC2), homeobox A9, Wnt family member 7A (WNT7A) and N‑Myc downstream‑regulated gene 4 protein genes with PCa. The 6‑gene panel consisting of APC2, cadherin 1, forkhead box P1, leucine rich repeat containing 3B, WNT7A and zinc family protein of the cerebellum 4 was subsequently developed providing PCa detection with 78% sensitivity and 100% specificity. The number of genes methylated (NGM) value introduced for this panel was indicated to rise monotonically from 0.27 in control individuals to 4.6 and 4.25 in patients with highly developed and metastatic T2/T3 stage cancer, respectively. Therefore, the approach of defining the NGM value may not only allow for the detection of PCa, but also provide a rough evaluation of tumor malignancy and metastatic potential by non‑invasive MSP analysis of urine samples.Документ Аналіз прогностичних властивостей [-2]проПСА для диференційної діагностики доброякісних та злоякісних пухлин передміхурової залози(Українська медична стоматологічна академія, 2017) Данилець, Ростислав Олегович; Горбань, Л. В.; Гавриш, І. Т.; Григоренко, В'ячеслав Миколайович; Клепко, А. В.; Данилец, Ростислав Олегович; Гавриш, И. Т.; Григоренко, Вячеслав Николаевич; Danylets, R. О.; Gorban, L. V.; Gavrysh, I. T.; Grygorenko, V. M.; Klepko, А. V.Проведено вивчення вмісту загального простатоспецифічного антигену (зПСА) та [-2]проПСА в крові 246 чоловіків різного віку (від 49 до 79 років), з котрих 68 не мали будь-яких ознак патології передміхурової залози і тому були віднесені до групи умовно здорових (УЗ) пацієнтів, тоді як до групи хворих на доброякісну гіперплазію передміхурової залози (ДГПЗ) входило 71 чоловік, а до групи хворих на рак передміхурової залози (РПЗ) – 107 чоловік, причому з них 45 мали злоякісні пухлини агресивного типу з рахунком Глісона ≥7, а 62 – неагресивні індолентні пухлини з рахунком Глісона ≤6. В результаті проведеного дослідження встановлено більш виражені прогностичні властивості [-2]проПСА порівняно із зПСА щодо диференційної діагностики патологічних станів передміхурової залози (ДГПЗ та РПЗ), а також визначення злоякісних пухлин агресивного типу; Изучено содержание общего простатоспецифического антигена (оПСА) и [-2]проПСА в крови 246 мужчин разного возраста (от 49 до 79 лет), из которых 68 не имели каких-либо признаков патологии предстательной железы (ПЖ) и поэтому были отнесены к группе условно здоровых пациентов. В группу пациентов с доброкачественной гиперплазией ПЖ было включено 71 пациента, а в группу больных аденокарциномой, или раком предстательной железы (РПЖ), – 107 пациентов, причем 45 из них имели злокачественные опухоли агрессивного типа со счетом Глисона равным или больше 7, а остальные 62 – злокачественные опухоли неагрессивного типа со счетом Глисона равным 6 и меньше. В результате проведенных исследований установлено наличие более выраженных прогностических свойств у [-2]проПСА по сравнению с общим ПСА, показано возможность использовать [-2]проПСА в дифференцированной диагностике патологических состояний ПЖ для выявления ДГПЖ и РПЖ, а также определения злокачественных опухолей агрессивного типа; Prostate specific antigen (PSA) is a serum marker that is widely used as an aid in the detection of prostate cancer. However, since many prostate cancers progress slowly, there is also an urgent need for better markers to identify prostate cancers with a higher malignant potential. Poorly differentiated prostate cancers and those that have the potential to spread beyond the prostatic capsule are of particular concern. [-2]proPSA is a constituent of the free PSA which is secreted mainly by prostatic epithelial tissue after malignant transformation. In view of this its specificity for cancer emerging is anticipated. A research was devoted to studying prognostic patterns of [-2]proPSA for the discrimination of benign and malignant tumors of prostate in human males in the age interval of 49-79 years. [-2]proPSA was identified in the blood sera of 246 patients by the aid of immunochemical analyzer Chem Well (USA) using ELISA kits of DL Develop with double antibodies against the analyte. Tumor aggressiveness was classified by Gleason grading of biopsies. Statisical evaluation of raw data was done by the nonparametric methods of Mann-Whitney and Kruskal-Wallis. The determination of [-2]proPSA blood contents in three groups of patients with malignant tumors of prostate (PCa) (107 patients), with benign hyperplasia of prostate (BPH) (71 patients) and without any evidence of prostate pathology (EPP) – 68 persons was executed. The statistically meaningful differences in [-2]proPSA contents were elucidated between all three groups of patients for the wide range of total prostate specific antigen (tPSA) concentrations (0-20 ng/ml). Incidentally mean value of [-2]proPSA was shown to be dependent of tPSA concentration and prostate pathology. Thus, in EPP group blood contents of [-2]proPSA equaled 5 pg/ml, BPH – 9 pg/ml and PCa – 10,5 pg/ml in 0-2 ng/ml tPSA range whereas the elevation of tPSA in the blood simultaneously increased [-2]proPSA mean values for all three groups of patients. In this connection, for tPSA range 4-10 ng/ml [-2] proPSA mean achieved 14 pg/ml, 21 pg/ml and 23,5 pg/ml in EPP, BPH and PCa patients, respectively. In the last diapason of tPSA (10,1-20,0 ng/ml) [-2]proPSA mean was 28 pg/ml for BPH and 43 pg/ml for PCa. Furthermore, analysis of discriminative qualities of [-2]proPSA as to the differential diagnostics between malignant and nonmalignant states revealed a high prognostic potential of the substance under investigation in prostate tumor risk assessment. Apart from this, [-2]proPSA contents in the blood of PCa patients was shown to correlate highly with Gleason score. In PCA patients having malignancies with Gleason score ≥7 [-2]proPSA mean values significantly surpassed this index in PCa patients with indolent tumors (Gleason score 6 or less). Moreover, in the Gleason score span 5-9 [-2]proPSA exponentially increased from 10 pg/ml at Gleason score 5 to 72 pg/ml at Gleason score 9. Thus, [-2]proPSA may be proposed for further application in medical practice as independent biomarker or in conjunction with PSA test for strengthening its specificity, the latter being warranted by the peculiarities of [-2] proPSA, a stable component of free PSA (fPSA), which is directly related to malignant transformation of prostate. Further investigations will be dealt with the evaluation of prognostic qualities of [-2]proPSA derivatives, namely % [-2]proPSA and prostate health index, the former being the percentage ratio of [-2]proPSA to fPSA and the latter – the product of ratio [-2]proPSA to fPSA and √tPSA. The prognostic characteristics of aforementioned indices will be compared and assessed.Документ Застосування % вПСА та % [-2]проПСА як можливих біомаркерів при диференційній діагностиці пухлин передміхурової залози(Українська медична стоматологічна академія, 2017) Данилець, Ростислав Олегович; Гавриш, І. Т.; Григоренко, В'ячеслав Миколайович; Трофіменко, О. В.; Клепко, А. В.; Данилец, Ростислав Олегович; Гавриш, И. Т.; Григоренко, Вячеслав Николаевич; Трофименко, Е. В.; Клепко, А. В.; Danylets, R. О.; Gavrysh, I. T.; Grygorenko, V. M.; Trofimenko, O. V.; Klepko, А. V.Проведено вивчення прогностичних властивостей % вільного простатоспецифічного антигену (% вПСА) та % [-2]проПСА для використання їх при проведенні диференційної діагностики раку передміхурової залози (РПЗ) серед 246 пацієнтів різного віку (49-79 років) без будь-яких ознак урогенітальних інфекцій. Проведені дослідження встановили наявність більш високого прогностичного потенціалу у % [-2] проПСА порівняно з % вПСА в діапазоні загального ПСА (зПСА) в крові пацієнтів в межах 2,1 – 20,0 нг/мл. Крім того, % [-2]проПСА, на відміну від % вПСА, був придатним не тільки для визначення РПЗ, а також виявив ефективність для дискримінації агресивних злоякісних пухлин від індолентних пухлин, оскільки абсолютна величина % [-2]проПСА прямим чином залежала від величини рахунку Глісона; Изучено прогностические свойства % свободного ПСА (% сПСА) и % [-2]проПСА для использования в дифференциальной диагностике различных патологических состояний предстательной железы (ПЖ), а именно рак ПЖ (РПЖ) агрессивного и неагрессивного генеза, а также доброкачественной гиперплазии ПЖ. Исследования были проведены среди 246 пациентов в возрасте 49-79 лет, которые характеризовались отсутствием каких-либо признаков урогенитальных инфекций. Проведенные исследования установили наличие более высокого прогностического потенциала у % [-2]проПСА в сравнении с % сПСА в диапазоне концентраций общего ПСА (оПСА) в крови пациентов в пределах 2,1 – 20 нг/мл. Кроме этого, % [-2]проПСА, в отличии от % сПСА, оказался эффективным не только при определении РПЖ, а также обладал дискриминационными возможностями для выявления агрессивных злокачественных опухолей ПЖ, поскольку абсолютная величина % [-2]проПСА прямым образом зависела от значения счета Глисона; Prostate specific antigen (PSA) is a serum marker that is widely used as an aid in the detection of prostate cancer. However, since many prostate cancers progress slowly, there is also an urgent need for better markers to identify prostatic tumors of high malignancy. Poorly differentiated prostate cancers and those that have the potential to spread beyond the prostatic capsule are of particular concern. [-2]proPSA is a constituent of the free PSA (fPSA) which is secreted mainly by prostatic epithelial tissue after malignant transformation. In view of this its specificity for cancer emerging is anticipated. Admittedly, fPSA exists in uncomplexed state without protease inhibitors. It is secreted by epithelial prostate cells of both peripheral and central zone. A research was devoted to studying prognostic patterns of % [-2]proPSA for the discrimination of benign and malignant tumors of prostate in human males in the age interval of 49-79 years. [-2]proPSA was identified in the blood sera of 246 patients by the aid of immunochemical analyzer Chem Well (USA) using ELISA kits of DL Develop with double antibodies against the analyte. Tumor aggressiveness was classified by Gleason grading of biopsies. Then % [-2]proPSA was calculated according to the formula: % [-2]proPSA = [-2]proPSA / fPSA × 100%. fPSA and tPSA were also identified immunochemically. % fPSA was estimated as following: % fPSA = fPSA / tPSA × 100%. Statistical evaluation of raw data was done by the non-parametric methods of Mann-Whitney and Kruskal-Wallis. The determination of % [-2]proPSA and % fPSA in three groups of patients with malignant tumors of prostate (PCa) (107 patients), with benign hyperplasia of prostate (BPH) (71 patients) and without any evidence of prostate pathology (EPP) – 68 persons was executed. The statistically meaningful differences in % [-2]proPSA contents were elucidated between all three groups of patients for the wide range of total prostate specific antigen (tPSA) concentrations (0-20 ng/ml). Incidentally mean value of % [-2]proPSA was shown to be dependent of tPSA concentration and prostate pathology. Thus, in EPP group blood contents of [-2]proPSA equaled 5 pg/ml, BPH – 9 pg/ml and PCa – 10,5 pg/ml in 0–2 ng/ml tPSA range whereas the elevation of tPSA in the blood simultaneously increased [-2]proPSA mean values for all three groups of patients. In this connection, for tPSA range 4–10 ng/ml [-2]proPSA mean achieved 14 pg/ml, 21 pg/ml and 23,5 pg/ml in EPP, BPH and PCa patients, respectively. In the last diapason of tPSA (10,1–20,0 ng/ml) [-2]proPSA mean was 28 pg/ml for BPH and 43 pg/ml for PCa. Furthermore, analysis of discriminative qualities of % [-2]proPSA as to the differential diagnostics between malignant and nonmalignant states revealed a high prognostic potential for prostate tumor risk assessment. Apart from this, % [-2] proPSA of PCa patients was shown to correlate highly with Gleason score. In PCA patients having malignancies with Gleason score ≥7 [-2]proPSA mean values significantly surpassed this index in PCa patients with indolent tumors (Gleason score 6 or less). Moreover, in the Gleason score span 5-7% [-2]proPSA linearly increased and then reached its maximum at Gleason score 9. Thus, % [-2]proPSA may be proposed for further application in medical practice as independent biomarker or in conjunction with PSA test for strengthening its specificity, the latter being warranted by the peculiarities of [-2]proPSA, a stable component of free PSA (fPSA), which is directly related to malignant transformation of prostate. Further investigations will be dealt with the evaluation of prognostic qualities of other [-2]proPSA derivative, namely prostate health index, which is a product of ratio [-2]proPSA to fPSA and √tPSA. The prognostic characteristics of aforementioned indices will be compared and assessed.