Background. Tumors of stroma of the sex cord include a family of tumors that are diverse in structure and biological characteristics, including hormone-active ovarian tumors, such as granulosa cell tumor (GCT) of the ovary and a tumor from Sertoli–Leydig cells. For these types of tumors, of particular importance is the analysis of biochemical markers, among which the most promising is inhibin B.The objective of the study. Comparative analysis of inhibin B levels in the blood serum of patients with stromal cell tumors and other types malignancies.Materials and methods. 64 patients with primary ovarian tumors were examined: 31 – GCT of the ovary, 16 – tumors from Sertoli–Leydig cells, 17 – adenocarcinomas. Comparison group – 20 patients with malignant tumors of other localizations, control – 74 healthy women and 37 patients with benign ovarian tumors. Inhibin B was determined in blood serum using the standardized Inhibin B Gen II ELISA (Beckman Coulter, USA) immunoassay.Results. The analysis of inhibin B levels in last days of the luteal phase, show an increase of marker level in patients with GCT and tumors from Sertoli–Leydig cells, while in ovarian adenocarcinomas and malignant tumors of other locations inhibin B secretion doesn’t differ from the control. The sensitivity of inhibin B in diagnostics of GCT was 93.5 %, in tumor from Sertoli–Leydig cells – 81.3 % with specificity – 100 %.Conclusion. Inhibin B is an effective biomarker of GCT and ovarian tumors from Sertoli–Leydig cells, which results must be interpreted according the functional state of the ovaries.
We present the comparative study of plasma chromogranin A (CgA) levels measured in 232 patients with different types of neuroendocrine tumors (NETs) and 66 healthy individuals using enzyme immunoassay Chromogranin A ELISA kit (Dako). CgA levels were significantly higher in patients with all types of NETs than in healthy subjects. CgA secretion were highly variable. The study demonstrate high diagnostic sensitivity of CgA, which was 80.6 % in overall group of NETs with specificity 98.5 %. We confirmed the prognostic significance of CgA, in this case the high basal levels of CgA (above 100 U/l) were significantly associated with less favorable prognosis of progression free survival after different types of treatment. The data confirms high efficiency of CgA as biomarker, which measurement enhances the accuracy of diagnosis and prognosis of NETs.
Background: The utility of biochemical markers in the monitoring of treatment efficacy in patients with neuroendocrine tumors (NETs) goes beyond any doubt. However, there are still no clear criteria for the assessment of clinically significant abnormalities of the main NET biomarkers chromogranin A (CgA) and serotonin. Aim: To evaluate the value of serial measurement of serum CgA and serotonin in the monitoring of the treatment effect in NET patients. Materials and methods: Serum CgA and serotonin levels were measured in 107 patients with NETs at baseline and at 3–4 weeks after the end of treatment (chemotherapy, biotherapy), as well as in 60 healthy controls. We used enzyme immunoassay based on Chromogranin A NEOLISA (Euro Diagnostica) and Serotonin ELISA (IBL International GmbH) test systems. Results: There was an association between CgA levels and the efficacy of chemotherapy in NET patients. With progression of the disease, median CgA increased significantly from 412 to 2679 ng/mL (p = 0.012), whereas in the patients with partial response it decreased from 811 to 254 ng/mL (p = 0.023). The ROC analysis showed the 33% cut-off for significant CgA changes for progression, with sensitivity of 80.0% and specificity of 95.6%. A decrease (of more than 33% compared to baseline levels) or absence of significant CgA changes was associated with stabilization of the disease or with partial response to treatment. Significantly decreased CgA levels were found in 75.0% cases of partial response and 43.48% of stabilized patients, whereas the absence of any significant changes in 25 and 66.7%, respectively. There was no association between serotonin levels and the disease behavior under treatment.Conclusion: CgA could be used as a sensitive marker of NET progression on chemotherapy.
Цель исследования. Разработка протокола проведения нормобарического гипоксического теста и критериев оценки устойчивости -чувствительности к нормобарической гипоксии детей и подростков. Характеристика детей и методы исследования. Гипоксический тест проводили у 56 здоровых детей в возрасте от 8 до 12 лет посредством создания гипоксемии (SpO 2 80%) при масочном дыхании ребенком газовой смесью с 11% О 2 . В исследовании использовали сертифицированную в Российской Федерации нормобарическую установку для получения гипоксических и гипероксических газовых смесей ReOxy Cardio («S.A. Aimediq», Люксембург) со встроенным пульсоксиметрическим датчиком («Mаsimo Rad-5», США). На протяжении гипоксического теста мониторировали величину насыщения артериальной крови кислородом (SpO 2 ) и ЧСС (уд/мин), и автоматически фиксировали индивидуальные значения минимального уровня SpO 2 (SpO 2 min) и максимальной частоты сердечных сокращений -ЧСС (ЧСС maх). Критерием прекращения «гипоксической фазы» гипоксического теста служили SpO 2 до 80% и ниже либо истечение 9 мин дыхания гипоксической газовой смесью. Дополнительным критерием было повышение ЧСС на 30% и более от исходного уровня. При достижении одного из описанных критериев подросток начинал дышать атмосферным воздухом, с определением времени восстановления SpO 2 до 97%. Кроме того, рассчитывали гипоксический индекс -отношение времени десатурации к времени реоксигенации. Результаты. В результате проведенного исследования разработан протокол проведения и оценки гипоксической устойчивости детей и подростков. Выявлены типы (фенотипы) реакции подростков на дозированную нормобарическую гипоксию: с низкой устойчивостью к гипоксии, средним и высоким уровнем устойчивости к дозированной аппаратной гипоксии. Заключение. Предложенный вариант проведения гипоксического теста отражает индивидуальную толерантность к гипоксии и может применяться для индивидуализации курсов гипокситерапии, а также в качестве дополнительного диагностического инструмента в оценке адаптационных возможностей и неспецифической реактивности детского организма.
Therapy with immune checkpoints inhibitors (anti-PD-1 therapy) has become the standard of care for metastatic renal cell carcinoma (mRCC) patients with resistance to tyrosine kinase inhibitors (TKI). Identification of reliable predictive markers for anti-PD-1 therapy would help to select patients who are most likely to respond to checkpoints inhibitors. This article represents the results of treatment of 23 mRCC patients who received nivolumab as part of the expanded access program in Russia. All patients demonstrated resistance to previous lines of TKI therapy. Overall response rate for nivolumab was 21.7 % with median progression-free survival of 4 months (95%CI=1.37–10.04). The median overall survival was not reached with the median follow-up of 10 months (3–14 months). The grade 3–4 toxicity was observed in 3 (13 %) pts. Favorable MSKCC prognosis before treatment, the initial level of sPD-1 exceeding the estimated threshold value and the development of any grade hypothyroidism after treatment initiation were associated with greater progression free survival. The number of preceding lines of TKI therapy, the level of PD-L1 and FOXP3 expression on tumor-infiltrating leukocytes (TILs) did not significantly affect progression-free survival in this group of mRCC patients. The ef ficacy and toxicity profile of nivolumab corresponded to the results of phase 2–3 trials.
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