Функционализация кальцийфосфатных материалов биологически активными соединениями белковой природы

Recent approaches to the calcium phosphate (CaP) materials functionalization with drugs and biomolecules have been actively developed for bone defect reconstruction. However, the current techniques are low efficient in context of drug incorporation and non-controlled release from the materials. Eventually, continuous therapeutic effect in bone defect area couldn’t be achieved. The aim of this work was to develop an effective method for biologically active molecules incorporation onto the surface of CаP materials, and to study the dynamics of its release. Octacalcium phosphate (OCP), β-tricalcium phosphate (β-TCP) and β-tricalcium phosphate with biomimetic calcium phosphate layer (β-TCPmod.) were used as ceramic bioactive carriers. Bovine serum albumin (BSA) was used as a model compounds. BSA incorporation on the ceramics surface was performed by biomimetic co-precipitation from several buffer solutions containing the incorporated compound. The efficiency of biomolecules incorporation was evaluated by measuring BSA concentrations in solutions before and after materials incubation. The release of the incorporated molecules from the materials was investigated for 6 days. The structure and composition of the obtained materials were studied by application of XRD, FTIR, SEM, BET methods. It was shown that the OCP specific surface (surface area, (SBET)) was almost in 12 times higher than SBET of β-TCP. By using biomimetic approach the increase of β-TCP surface area in 1.6 times was achieved; this enhanced protein incorporation more than 3 times. The BSA biomimetic co-precipitation together with CaP on the OCP surface proved to be more effective than its adsorption from salt free solutions. The study of BSA release revealed that only 45% of loaded albumin released during 6 days of observation. Therefore, the effective method of CaP functionalization was developed. Based on biomolecules incorporation by biomimetic co-precipitation from CaP solutions, it provided a low rate of its release.В последнее время активно разрабатываются подходы к функционализации кальцийфосфатных (КФ) материалов лекарственными препаратами и биологически активными соединениями с целью использования их в качестве платформы для адресной доставки в зону костного дефекта. Однако существующие технологии характеризуются низкой эффективностью инкорпорации и неудовлетворительной скоростью высвобождения препаратов из материалов, не обеспечивающей постоянный и длительный терапевтический эффект в области дефекта. Целью данной работы стала разработка эффективного способа функционализации КФ материалов биологически активными соединениями и изучение динамики их высвобождения. В работе использовали гранулированные КФ материалы октакальциевый фосфат (ОКФ), β-трикальциевый фосфат (β-ТКФ) и β-ТКФ с дополнительным КФ слоем на поверхности (β-ТКФмод.), а в качестве модельного соединения - бычий сывороточный альбумин (BSA). Инкорпорацию BSA на поверхность керамики производили совместно с биомиметическим осаждением из различных КФ буферных растворов, содержащих инкорпорируемое соединение. Эффективность инкорпорации BSA оценивали, измеряя его концентрации в растворах до и после инкубации с материалами. Динамику выхода BSA из материалов исследовали в течение 6 суток. Поверхность и структуру КФ материалов исследовали с помощью комплекса методов: сканирующей электронной микроскопии, рентгенофазового анализа, ИК-Фурье спектрального анализа, низкотемпературной адсорбции азота. В работе показано, что удельная площадь поверхности (Sуд.) ОКФ составила 5.9 м2/г, β-ТКФ – 0.5 м2/г. Модификация поверхности β-ТКФ привела к увеличению Sуд. в 1.6 раз и увеличению количества встроенного BSA на его поверхность в 3 раза. Совместная преципитация BSA и фосфатов кальция в процессе биомиметического осаждения была значительно эффективнее адсорбции BSA без использования КФ растворов. Исследование динамики высвобождения BSA из функционализированного ОКФ выявило, что в течение 6 суток наблюдения высвобождается 45% встроенного в материал белка. Таким образом, был разработан эффективный метод функционализации КФ материалов, основанный на инкорпорации биологически активных соединений совместно с биомиметическим осаждением из кальций- фосфатного раствора и обеспечивающий низкую скорость их высвобождения

Клинико-эпидемиологические особенности проявлений папилломавирусной инфекции на примере рака шейки матки и аногенитальных (венерических) бородавок

Background: Cervical cancer and genital warts (GWs) are some of the most common manifestations of human papillomavirus infection (HPV). These lesions cause significant damage to the reproductive health of the population, which leads to increased attention to the prevention of HPV infection among various population groups. Aims: To determine the clinical and epidemiological features of the HPV manifestations by the example of cervical cancer and genital warts. Methods: A retrospective analysis of anamnestic information of 115 women with an established diagnosis of cervical cancer and 177 patients with an established diagnosis of GWs was performed. The clinical and epidemiological characteristics of patients with diagnoses of GWs and cervical cancer were based on the development of outpatient admission cards and inpatient histories, as well as test data for HPV. Results: HPV 16 was the most common HPV type among patients with GWs and cervical cancer ― it was detected in 37.6% of cases. Also the most frequently encountered: HPV 6/18/11/31/51/52. In 43.2% cases of HPV detection, two or more types were detected at once, the most common combinations: HPV16 and HPV18, HPV6 and HPV16, HPV6 and HPV11. Analysis of the frequency of screening for cervical cancer and visits to the gynecologist for 5 years before establishing the diagnosis showed that among those who did not screen for cervical cancer, the risk of diagnosing stage IIIV was 5.2 times higher than among individuals who underwent cervical screening 2 years ago, or once a year for the last five years. Among patients with GWs who had 2 or more sexual partners for 1 year, 13.5% of patients regularly used barrier contraception methods (condoms) during sexual contact, not regularly ― 61.5%, did not use them at all ― 25.0%. Conclusions: Identifying the clinical and epidemiological features of HPV infection should contribute to the development of new and optimize existing prevention programs for a wide range of HPV-associated diseases.Обоснование. Рак шейки матки (РШМ) и аногенитальные (венерические) бородавки являются наиболее распространенными проявлениями папилломавирусной инфекции. Данные поражения наносят существенный ущерб репродуктивному здоровью населения, что обусловливает повышенное внимание к вопросам профилактики папилломавирусной инфекции среди различных групп населения. Цель исследования ― определение отдельных клинико-эпидемиологических особенностей папилломавирусной инфекции на примере рака шейки матки и аногенитальных (венерических) бородавок. Методы. Выполнено ретроспективное исследование; объектом исследования были пациенты с диагнозами РШМ и аногенитальных (венерических) бородавок, обратившиеся за медицинской помощью в период с 2015 по 2018 г. Данные получены с помощью сбора информации из медицинских карт стационарного больного (форма 003/у) и медицинских карт пациента, получающего медицинскую помощь в амбулаторных условиях (форма 025/у). Методы анализа и обработки материала ― аналитический и статистический. Результаты. В рамках исследования были проанализированы 292 карты пациентов, обратившихся за медицинской помощью. Наиболее часто ― в 37,6% случаев ― у пациентов с аногенитальными бородавками и РШМ при лабораторном обследовании выявлялся вирус папилломы человека (ВПЧ) 16-го типа. Также часто встречались ВПЧ 6/18/11/31/51/52. В 43,2% случаев определялись одновременно два и более типов ВПЧ, при этом наиболее частыми сочетаниями были ВПЧ16 и ВПЧ18, ВПЧ6 и ВПЧ16, ВПЧ6 и ВПЧ11. Проведенный анализ частоты скрининга на РШМ и посещения врача-гинеколога в течение 5 лет до установления диагноза показал, что среди лиц, не проходивших скрининг на РШМ, или прошедших его при обнаружении заболевания, риск выявления диагноза на IIIV стадии был в 5,2 раза выше, чем среди лиц, которые проходили цервикальный скрининг 2 года назад или 1 раз в год в течение последних 5 лет. Среди всех пациентов с аногенитальными бородавками, имевших по два и более половых партнера в течение 1 года, о регулярном использовании методов барьерной контрацепции (презервативов) при половом контакте сообщили 13,5%, о нерегулярном использовании ― 61,5%; 25,0% пациентов вообще не задумывались о методах предохранения. Заключение. Выявление клинико-эпидемиологических особенностей папилломавирусной инфекции должно способствовать разработке новых и оптимизации существующих профилактических программ в отношении широкого спектра ВПЧ-ассоциированных заболеваний

Impact of the covid-19 pandemic on the oncological practice

Detailed, systematic review of the world literature data, including all aspects that reflect the impact of the COVID-19 pandemic on the oncological practice was conducted. The information sources were taken from Pubmed, MedLine, Scopus, Web of Science, and RSCI systems. The data from retrospective and prospective clinical trials have been analyzed. This review presents current data on the impact of COVID-19 on cancer patients, mortality and prognosis of cancer patients infected with COVID-19, treatment options for COVID-19, as well as the case report of the cancer patient with rare atypical COVID-19 course of disease. To date, the groups of increased risk of being infected with a new coronavirus have been identified. These groups include cancer patients. Despite the pandemic, treatment of cancer patients must be continued, since the presence of a tumor process does not allow the therapy to be delayed. The world cancer community is actively continuing to develop recommendations for optimal management of cancer patients in the context of the pandemic. The most relevant of them are described in this article. © 2020, Tomsk National Research Medical Center of the Russian Academy of Sciences. All rights reserved

Breast cancer associated with CHEK2 mutation carriage

The paper presents clinical cases in which the patients were diagnosed with breast cancer (BC) associated with mutations in the CHEK2 gene. Objective. To investigate the characteristics of treatment and prevention in patients with BC associated with CHEK2 mutation carriage. Subjects and methods. In 2016-2017, the P.A. Herzen Moscow Oncology Research Institute treated three patients diagnosed with BC associated with CHEK2 mutation carriage. Two cases underwent preventive surgery: prophylactic subcutaneous mastectomy with single-stage reconstruction in one case and prophylactic bilateral tubo-ovariectomy in the other. A further follow-up of these patients and their relatives will be able to draw conclusions about the correctness of preventive surgery policy. Results. In all the three clinical cases, the patients were diagnosed with germline missense I157T mutation (p.I1e157Thr) in exon 3 of the CHEK 2 gene, which results in amino acid substitution (isoleucine to threonine at codon 470 – c.470T>C) in a heterozygous state. The volume of surgical interventions for BC, preventive surgery on the breast and ovaries in our patients was decided individually based on their clinical data. Genetic examination of their relatives is needed for primary prevention of BC. Conclusion. There is a need for further investigations in patients with BRCA1, 2, CHEK 2 mutations, as there will be a growing number of patients with mutations in these genes due to a larger number of genetic laboratories. Knowing the characteristics of inheritance and development of hereditary BC, it is necessary to elaborate surgical treatment policy for these patients, algorithms for follow-up of the patients, and an algorithm for examination and prevention of BC among their relatives. © Bionika Media Ltd

Breast cancer associated with CHEK2 mutation carriage

The paper presents clinical cases in which the patients were diagnosed with breast cancer (BC) associated with mutations in the CHEK2 gene. Objective. To investigate the characteristics of treatment and prevention in patients with BC associated with CHEK2 mutation carriage. Subjects and methods. In 2016-2017, the P.A. Herzen Moscow Oncology Research Institute treated three patients diagnosed with BC associated with CHEK2 mutation carriage. Two cases underwent preventive surgery: prophylactic subcutaneous mastectomy with single-stage reconstruction in one case and prophylactic bilateral tubo-ovariectomy in the other. A further follow-up of these patients and their relatives will be able to draw conclusions about the correctness of preventive surgery policy. Results. In all the three clinical cases, the patients were diagnosed with germline missense I157T mutation (p.I1e157Thr) in exon 3 of the CHEK 2 gene, which results in amino acid substitution (isoleucine to threonine at codon 470 – c.470T>C) in a heterozygous state. The volume of surgical interventions for BC, preventive surgery on the breast and ovaries in our patients was decided individually based on their clinical data. Genetic examination of their relatives is needed for primary prevention of BC. Conclusion. There is a need for further investigations in patients with BRCA1, 2, CHEK 2 mutations, as there will be a growing number of patients with mutations in these genes due to a larger number of genetic laboratories. Knowing the characteristics of inheritance and development of hereditary BC, it is necessary to elaborate surgical treatment policy for these patients, algorithms for follow-up of the patients, and an algorithm for examination and prevention of BC among their relatives. © Bionika Media Ltd

Терапия препаратом радий-223 больных с костными метастазами кастрационно-резистентного рака предстательной железы

The development of resistance to endocrine therapy and the tumor progression in patients with prostate cancer are associated with an unfavourable prognosis. The article presents a review of clinical trials of efficacy and safety, as well as the experience in using radioisotope radium-223 chloride in clinical practice in patients with castration-resistant prostate cancer with bone metastases without visceral metastases. It was shown that radium-223 chloride therapy in this category of patients leads to an increase in overall survival and time to the development of bone complications, and is characterized by good tolerability.Развитие резистентности к гормональной терапии и прогрессирование опухолевого процесса у больных раком предстательной железы ассоциируются с неблагоприятным прогнозом. В статье представлен обзор результатов клинических исследований эффективности и безопасности, а также опыта применения в клинической практике радиоизотопного препарата радия-223 хлорида у больных с костными метастазами при кастрационно-резистентном раке предстательной железы без висцеральных метастазов. Показано, что терапия радия-223 хлоридом у данной категории больных приводит к увеличению общей выживаемости и времени до развития костных осложнений, а также характеризуется хорошей переносимостью

Modern trends in the breast cancer conserving surgery and oncoplastic breast surgery

Introduction: The highest priority for modern clinical oncology is functionally-sparing and organ-conserving treatment. In Russia, breast cancer (BC), among all malignant tumors, accounted for 21.1 % of women in 2017. Oncoplastic radical resections (OPS-BCS = oncoplastic surgery – breast conserving surgery) have been widely used. This term means resection of the breast for cancer using plastic surgery to restore the shape of the breast, in most cases with one-stage correction of the contralateral breast. Purpose: It was the creation of various techniques of oncoplastic breast surgery, applicable for the appropriate localization of breast cancer and the evaluation of surgical, oncological and aesthetic results. Methods: From 2013 to 2017, in the P.A. Hertsen Moscow Oncology Research Center, organ-conserving surgery were performed in 570 patients with BC with an average age of 54.2. Stage 0 was diagnosed in 4.6 %, I – 5.9 %, IIA – 28.7 %, IIB – 6 %, IIIA – 5.1 %, IIIC – 3.3 %, IIIB – 0.2 %, IV – 0.2 %. Radical resection in the standard version was performed in 290 patients with breast cancer, oncoplastic breast surgery in various modifications – in 280. All patients after the organ-conserving surgical treatment received radiation therapy. Patients received chemotherapy, targeted therapy and hormone therapy according to the indications in depending the disease stage and the immunohistochemical type of the tumor. Results: After an urgent and planned morphological study positive margins of resection were revealed in 10 patients, which required reresection of the edges to a negative state of them in case of an urgent intraoperative response and mastectomy – in case of a planned response. Within 4 years, local recurrences were detected in 4 patients (0.7 %), which required a mastectomy with a one-stage reconstruction. In 1 patient (0.2 %), the disease progressed as metastases to the lung – in this case lobectomy and a necessary chemotherapy were conducted. Cosmetic results were defined as excellent in 70 % cases, good – 25 %, satisfactory – 5 %. Conclusion: If there are indications for organ-conserving treatment of breast cancer and the patient’s decision concerning this surgery, the patient should be offered methods of oncoplastic surgery for the prevention of psychological and emotional stress, effective rehabilitation, and a quick return to active social life. © 2018 Medical Radiology and Radiation Safety. All rights reserved