рак

Анемия при хронических заболеваниях: ключевые механизмы патогенеза у пациентов со злокачественными новообразованиями и возможные подходы к классификации

АНЕМИИ , , , , , , ,

В.Т. Сахин1, Е.Р. Маджанова1, Е.В. Крюков3, А.В. Сотников2, А.В. Гордиенко2, О.А. Рукавицын3

1 ФГКУ «1586 Военный клинический госпиталь» Минобороны России, ул. Маштакова, д. 4, Московская область, Подольск, Российская Федерация, 142110

2 ФГБВОУ ВО «Военно-медицинская академия им. С.М. Кирова» Минобороны России, ул. Академика Лебедева, д. 6, Санкт-Петербург, Российская Федерация, 194044

3 ФГБУ «Главный военный клинический госпиталь им. акад. Н.Н. Бурденко» Минобороны России, Госпитальная пл., д. 3, Москва, Российская Федерация, 105229

Для переписки: Валерий Тимофеевич Сахин, канд. мед. наук, ул. Маштакова, д. 4, Московская область, Подольск, Российская Федерация, 142110; тел.: +7(916)314-31-11; e-mail: SahinVT@yandex.ru

Для цитирования: Сахин В.Т., Маджанова Е.Р., Крюков Е.В. и др. Анемия при хронических заболеваниях: ключевые механизмы патогенеза у пациентов со злокачественными новообразованиями и возможные подходы к классификации. Клиническая онкогематология. 2019;12(3):344-9

doi: 10.21320/2500-2139-2019-12-3-344-349

РЕФЕРАТ

Цель. Изучить влияние гепцидина, растворимого рецептора трансферрина (sTfR), цитокинов на обмен железа и развитие анемии у пациентов со злокачественными новообразованиями; на основании полученных данных предложить рабочий вариант классификации анемии при хронических заболеваниях (АХЗ) по ведущему патогенетическому фактору.

Материалы и методы. В исследование включено 63 пациента со II–IV стадией злокачественных новообразований. Больных с анемией было 41 (34 мужчины, 7 женщин, средний возраст 67,1 ± 9,9 года), без анемии — 22 (17 мужчин, 5 женщин, средний возраст 60,2 ± 14,9 года). Выполнен сравнительный анализ показателей обмена железа, С-реактивного белка (СРБ), гепцидина, sTfR, а также провоспалительных (интерлейкин-6 [ИЛ-6], фактор некроза опухолей α [ФНО-α]) и противовоспалительных (ИЛ-10) цитокинов у больных со злокачественными (солидными) новообразованиями с анемией и без нее. Проведен корреляционный анализ между ИЛ-6, ИЛ-10, ФНО-α, гепцидином, sTfR и показателями гемограммы.

Результаты. У больных с анемией в сравнении с контрольной группой выявлены более низкие концентрации железа, общей железосвязывающей способности (ОЖСС), коэффициента насыщения трансферрина железом (КНТ) и более высокие концентрации СРБ, гепцидина, sTfR, ИЛ-6, ИЛ-10, ФНО-α (p < 0,05). Показано негативное влияние на уровень эритроцитов ИЛ-6 (r = –0,58), ФНО-α (r = –0,32), гепцидина (r = –0,57). Установлена отрицательная взаимосвязь между концентрацией гемоглобина и ИЛ-6 (r = –0,57), ИЛ-10 (r = –0,64), ФНО-α (r = –0,65), гепцидина (r = –0,3), sTfR (r = –0,57). Выявлена корреляция между концентрациями гепцидина и ИЛ-6 (r = 0,58), ИЛ-10 (r = 0,33), ФНО-α (r = –0,4), а также между концентрациями sTfR и ИЛ-10 (r = 0,58), ФНО-α (r = –0,53). Установлена взаимосвязь между концентрацией ИЛ-6 и уровнями железа (r = –0,38), ОЖСС (r = –0,56), КНТ (r = –0,31), ферритина (r = 0,56), трансферрина (r = –0,72), СРБ (r = 0,86); между концентрациями ИЛ-10 и железа (r = –0,63), КНТ (r = –0,67), трансферрина (r = –0,7), ферритина (r = 0,55), СРБ (r = 0,65), ОЖСС (r = –0,71). Показано наличие корреляции между уровнями ФНО-α и ОЖСС (r = –0,36), трансферрина (r = –0,5).

Заключение. Описан многокомпонентный патогенез анемии у больных со злокачественными новообразованиями. Важное значение имеют дефицит железа и нарушение эритропоэза. Предложен рабочий вариант классификации АХЗ на основании ведущего патогенетического фактора развития анемии (АХЗ с преимущественным дефицитом железа, АХЗ с нарушениями регуляторных механизмов эритропоэза, АХЗ с недостаточной продукцией эритропоэтина).

Ключевые слова: рак, анемия, обмен железа, интерлейкин-6, интерлейкин-10, фактор некроза опухолей α, гепцидин, растворимый рецептор трансферрина.

Получено: 21 января 2019 г.

Принято в печать: 18 июня 2019 г.

Читать статью в PDF 

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Патогенетические особенности анемии у больных с солидными опухолями

АНЕМИИ , , , ,

В.Т. Сахин1, Е.Р. Маджанова1, Е.В. Крюков3, А.В. Сотников2, А.В. Гордиенко2, О.А. Рукавицын3

1ФГКУ «1586 Военный клинический госпиталь» Минобороны России, ул. Маштакова д. 4, Московская область, Подольск, Российская Федерация, 142110

2ФГБВОУ ВПО «Военно-медицинская академия им. С.М. Кирова» Минобороны России, ул. Академика Лебедева, д. 6, Санкт-Петербург, Российская Федерация, 194044

3ФГКУ «Главный военный клинический госпиталь им. Н.Н. Бурденко» Минобороны России, Госпитальная пл., д. 3, Москва, Российская Федерация, 105229

Для переписки: Валерий Тимофеевич Сахин, канд. мед. наук, ул. Маштакова, д. 4, Московская область, Подольск, Российская Федерация, 142110; Тел.:+7(916)314-31-11; e-mail: SahinVT@yandex.ru

Для цитирования: Сахин В.Т., Маджанова Е.Р., Крюков Е.В. и др. Патогенетические особенности анемии у больных с солидными опухолями. Клиническая онкогематология. 2017;10(4):514–8.

DOI: 10.21320/2500-2139-2017-10-4-514-518

РЕФЕРАТ

Цель. Изучить значение нарушений обмена железа и влияние некоторых цитокинов на развитие анемии у пациентов с солидными опухолями.

Материалы и методы. В исследование включено 42 пациента со злокачественными новообразованиями. Среди них пациентов с анемией было 24 (19 мужчин, 5 женщин; средний возраст 67,7 ± 10 лет), без анемии — 18 (15 мужчин, 3 женщины; средний возраст 65,7 ± 14 лет). Диагноз анемии установлен в соответствии с критериями ВОЗ (у мужчин: число эритроцитов менее 4 × 1012/л, гемоглобин менее 130 г/л, гематокрит менее 39 %; у женщин: число эритроцитов менее 3,8 × 1012/л, гемоглобин менее 120 г/л, гематокрит менее 36 %).

Результаты. Выполнен сравнительный анализ показателей обмена железа у пациентов с анемией и без таковой. Установлены более низкие значения сывороточного железа и коэффициента насыщения трансферрина железом у пациентов с анемией (p < 0,05). Пациенты с анемией в сравнении с пациентами без таковой имели более низкий уровень железа и коэффициент насыщения трансферрина железом (p < 0,05). Общая железосвязывающая способность сыворотки, уровень ферритина, трансферрина, С-реактивного белка, непрямого билирубина в исследуемых группах не имели статистически значимых различий (p > 0,05). У пациентов с анемией отмечалось более высокое содержание интерлейкинов (ИЛ-6 и ИЛ-10) (p < 0,05). Для ИЛ-6 показана отрицательная корреляция умеренной силы с уровнем эритроцитов (r = –0,58), гемоглобина (r = –0,57), гематокрита (r = –0,52) и прямая корреляция с уровнем лейкоцитов (r = 0,42). Между ИЛ-10 и уровнем эритроцитов, лейкоцитов, тромбоцитов, MCV, MCH также установлены слабые связи (r < 0,3). Для ИЛ-10 выявлена сильная отрицательная корреляция с MCHC (r = –0,71) и отрицательная корреляция умеренной силы с уровнем гемоглобина (r = –0,64) и гематокрита (r = –0,32). Наличие взаимосвязей между уровнями ИЛ-6, ИЛ-10 и уровнями гемоглобина, эритроцитов и некоторых цветовых индексов может свидетельствовать об их влиянии на развитие анемии у данной категории пациентов.

Заключение. Установлено наличие функционального дефицита железа у пациентов с анемией; показаны несколько причин развития анемии и значимая роль интерлейкинов в ее патогенезе.

Ключевые слова: рак, анемия, обмен железа, интерлейкин-6, интерлейкин-10.

Получено: 21 марта 2017 г.

Принято в печать: 22 июля 2017 г.

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ЛИТЕРАТУРА

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Нарушенный метаболизм метионина в злокачественных клетках — потенциальная мишень для противоопухолевой терапии

ОБЗОРЫ , , , , , ,

В.С. Покровский1, Д.Ж. Давыдов1, Н.В. Ануфриева2, Д.Д. Жданов3, Е.М. Трещалина1, Т.В. Демидкина2, Е.А. Морозова2

1 ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России, лаборатория комбинированной терапии опухолей, Каширское ш., д. 24, Москва, Российская Федерация, 154478

2 ФГБУН «Институт молекулярной биологии им. В.А. Энгельгардта» РАН, ул. Вавилова, д. 32, Москва, Российская Федерация, 119991

3 ФГБУ «НИИ биомедицинской химии им. В.Н. Ореховича», Погодинская ул., д. 10, стр. 8, Москва, Российская Федерация, 119121

Для переписки: Вадим Сергеевич Покровский, д-р мед. наук, Каширское ш., д. 24, Москва, Российская Федерация, 154478; тел.: 8(499)324-14-09; e-mail: vadimpokrovsky@yandex.ru

Для цитирования: Покровский В.С., Давыдов Д.Ж., Ануфриева Н.В. и др. Нарушенный метаболизм метионина в злокачественных клетках — потенциальная мишень для противоопухолевой терапии. Клиническая онкогематология. 2017;10(3):324–32.

DOI: 10.21320/2500-2139-2017-10-3-324-332

РЕФЕРАТ

В обзоре представлены особенности клеточного метаболизма метионина, а также известные данные о механизмах развития метиониновой зависимости в злокачественных клетках. Рассмотрены возможности использования безметиониновой диеты для контроля опухолевого роста у больных с различными формами рака. Сгруппированы и обобщены новейшие сведения о метионин-γ-лиазе — ферменте, обеспечивающем элиминацию метионина из плазмы. Раскрыта его роль в качестве потенциального противоопухолевого фермента. Обобщены сведения о продуцентах метионин-γ-лиазы, активности данного фермента, полученного из различных источников, и сведения о моделях опухолей и клеточных культурах, проявляющих метиониновую зависимость.

Ключевые слова: метионин-γ-лиаза, метионин, метиониновая зависимость, злокачественные клетки, рак, противоопухолевые ферменты, противоопухолевая терапия.

Получено: 16 декабря 2016 г.

Принято в печать: 6 марта 2017 г.

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Хромотрипсис в онкологии: обзор литературы и собственное наблюдение

МИЕЛОИДНЫЕ ОПУХОЛИ ,

Н.Н. Мамаев1, Т.Л. Гиндина1, Э.Г. Бойченко2

1 НИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой, ГБОУ ВПО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова», ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022

2 Детская городская больница № 1, ул. Авангардная, д. 14, Санкт-Петербург, Российская Федерация, 198205

Для переписки: Татьяна Леонидовна Гиндина, канд. мед. наук, ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022; тел.: + 7(812)233-12-43; e-mail: cytogenetics.bmt.lab@gmail.com

Для цитирования: Мамаев Н.Н., Гиндина Т.Л., Бойченко Э.Г. Хромотрипсис в онкологии: обзор литературы и собственное наблюдение. Клиническая онкогематология. 2017;10(2):191–205.

DOI: 10.21320/2500-2139-2017-10-2-191-205

РЕФЕРАТ

Представлено собственное наблюдение и обзор литературы, посвященный недавно открытому феномену хромотрипсиса в онкологии. Хромотрипсис — тип комплексных геномных изменений, при которых хромосома сначала разрывается на десятки и даже тысячи частей, а потом эти фрагменты соединяются в случайном порядке. Иногда в перестройке участвует несколько хромосом. В результате формируются мутантные зоны генома, провоцирующие развитие онкологических и врожденных заболеваний. Иными словами, использование определенных методических подходов (многоцветной флюоресцентной гибридизации in situ, метода SKY и некоторых других) позволяет увидеть под микроскопом распад на фрагменты двух или более хромосом и воссоединение этих фрагментов в новые необычные двух- или многоцветные структуры — хромосомные маркеры. Хромотрипсис — редкий феномен со своеобразной картиной, наблюдаемой в клонах клеток самых разнообразных опухолей, включая новообразования кроветворной и лимфоидной тканей. В литературе имеются указания о большей частоте этого феномена у больных с миелодиспластическим синдромом и опухолями костей. Важную роль в формировании хромотрипсиса играют мутации гена TP53. Использование секвенирования концевой спаренной ДНК или метода SNP в онкологии представляется перспективным как в теоретическом, так и клиническом плане. В первую когорту исследуемых должны включаться пациенты с мутациями генов TP53 и MLL, со сложными хромосомными нарушениями, гиперэкспрессией гена EVI1 и некоторые другие. В статье представлен феномен хромотрипсиса у девочки 8 мес. с М7-вариантом острого миелоидного лейкоза.

Ключевые слова: хромотрипсис, онкогематология, рак, мутации гена TР53.

Получено: 2 октября 2016 г.

Принято в печать: 6 января 2017 г.

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Анемии в онкологии: современные возможности поддерживающей терапии

ПОДДЕРЖИВАЮЩАЯ ТЕРАПИЯ , , , ,

А.В. Снеговой, В.Б. Ларионова, Л.В. Манзюк, И.Б. Кононенко

ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Москва, Российская Федерация, 115478

Для переписки: Антон Владимирович Снеговой, канд. мед. наук, Каширское ш., д. 24, Москва, Российская Федерация, 115478; тел.: +7(499)324-41-09; e-mail: anvs2012@gmail.com

Для цитирования: Снеговой А.В., Ларионова В.Б., Манзюк Л.В., Кононенко И.Б. Анемии в онкологии: современные возможности поддерживающей терапии. Клиническая онкогематология. 2016;9(3):326-35.

DOI: 10.21320/2500-2139-2016-9-3-326-35

РЕФЕРАТ

Развитие анемии в период химио- или химиолучевой терапии злокачественных опухолей является серьезным нежелательным явлением, отрицательно влияющим на качество жизни и эффективность проводимого лечения. В связи с этим ведущие консенсусные комиссии NCCN, ESMO, ASCO, RUSSCO разработали и постоянно обновляют рекомендации по диагностике и лечению анемии у онкологических больных. В статье представлены современные данные о патогенезе и методах лечения анемии у онкологических больных, в т. ч. использование стимуляторов эритропоэза: рекомбинантных эритропоэтинов и внутривенных препаратов железа, витаминов, трансфузий эритроцитной массы.

Ключевые слова: рак, анемия, эритропоэтины, препараты железа для внутривенного введения, трансфузия эритроцитной массы.

Получено: 29 февраля 2016 г.

Принято в печать: 31 марта 2016 г.

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Влияние противоопухолевого лечения на репродуктивную систему женщин: методы защиты и сохранения функции яичников

ОБЗОРЫ , , , , ,

М.В. Волочаева1, Р.Г. Шмаков1, Е.А. Демина2

1 ФГБУ «Научный центр акушерства, гинекологии и перинатологии им. В.И. Кулакова» МЗ РФ, Москва, Российская Федерация

2 ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» РАМН, Москва, Российская Федерация

РЕФЕРАТ

Последние исследования показали особую важность обсуждения вопроса защиты и сохранения функции яичников у женщин с онкологическими заболеваниями. В настоящее время, когда созданы во многом эффективные схемы лечения злокачественных опухолей, для ряда больных становится актуальным продолжение полноценной жизни после успешной противоопухолевой терапии. В обзоре рассматриваются методики защиты и сохранения функции яичников: фармакологическая, c применением вспомогательных репродуктивных технологий, в т. ч. криоконсервации и трансплантация ткани яичников, криоконсервации ооцитов и эмбрионов.

Ключевые слова: защита яичников, cохранение функции яичников, рак, криоконсервация ткани, криоконсервация ооцитов, криоконсервация эмбрионов.

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 ЛИТЕРАТУРА

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Анемии и дефицит железа у онкологических больных

АНЕМИИ , , , , , ,

В.В. Птушкин

ФГБУ «ФНКЦ Детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздравсоцразвития, Москва, Российская Федерация

РЕФЕРАТ

Многочисленные исследования последних лет показали, что анемии являются частым осложнением онкологических заболеваний, и особенно при проведении химиотерапии. Снижение содержания гемоглобина в крови сопровождается слабостью, уменьшением толерантности к физической и умственной нагрузкам с закономерным ухудшением качества жизни. Кроме того, анемия ассоциируется с ухудшением показателей выживаемости онкологических больных. Опухолевая анемия помимо прочих механизмов может быть обусловлена продукцией провоспалительных цитокинов, обладающих негативным влиянием на различные этапы продукции эритроцитов в костном мозге, длительность их жизни и обмен железа. Применение эритропоэтинов у онкологических больных с анемией вызывает повышение уровня гемоглобина и сокращение потребности в заместительных гемотрансфузиях, однако повышает риск тромбозов. Повышение продукции провоспалительных цитокинов у онкологических пациентов снижает доступность железа для эффективного эритропоэза. В настоящем обзоре обобщены клинические последствия дефицита железа и анемии у онкологических больных, обсуждаются механизмы нарушения гомеостаза железа, а также диагностика этого состояния и его лечение. Представлены данные клинических исследований, в которых оценивается эффективность различных препаратов железа с или без сопутствующей терапии эритропоэтинами.

Ключевые слова: Анемия, рак, эритропоэтины, препараты железа, карбоксимальтозат железа, ферритин, трансферрин

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Таксономическая структура и резистентность к антибиотикам возбудителей инфекций кровотока у онкогематологических больных

ИНФЕКЦИИ В ОНКОГЕМАТОЛОГИИ , , , , , ,

Багирова Н.С. 

ФГБНУ «Российский онкологический научный центр им. Н.Н. Блохина», Каширское ш., д. 24, Москва, Российская Федерация, 115478

Для переписки: Наталья Сергеевна Багирова, д-р мед. наук, Каширское ш., д. 24, Москва, Российская Федерация, 115478; тел.: +7(499)324-18-60; e-mail: nbagirova@mail.ru

Для цитирования: Багирова Н.С. Таксономическая структура и резистентность к антибиотикам возбудителей инфекций кровотока у онкогематологических больных. Клиническая онкогематология. 2015;8(2):191–200.

РЕФЕРАТ

Актуальность и цели. В онкогематологии инфекции являются одной из основных причин летальности у больных. Меняющиеся эпидемиологические закономерности отражают не только появление новых возбудителей инфекций кровотока, но и рост резистентности патогенов к противомикробным препаратам. Очень важно проводить постоянный мониторинг таксономической структуры возбудителей инфекций кровотока и их резистентности к антимикробным препаратам в целях адекватной и своевременной терапии тяжелых инфекций. Цель — анализ таксономической структуры возбудителей, выделенных при диагностике бактериемии у взрослых онкогематологических больных с использованием современных приборов, и эффективности терапии тяжелых инфекций.

Методы. Проведено микробиологическое исследование образцов крови онкогематологических больных при подозрении на сепсис и другие тяжелые инфекции за период с 2005 по 2013 г. Диагностику бактериемии проводили с использованием геманализаторов-инкубаторов Bactec FX400 (Becton Dickinson, США) и Bact/Alert (BioMerieux, Франция), идентификацию штаммов — с использованием масс-спектрометра MALDI-TOF Microflex LT (Biotyper, Bruker Daltonics, Германия). Чувствительность к антимикробным препаратам определяли на автоматическом анализаторе Microscan Walk Away 40/96+ (Siemens, Германия) и Vitek 2 (BioMerieux, Франция). Представлены сравнительные данные зарубежных исследователей.

Результаты. Было получено 3794 гемокультуры, из которых в 600 (15,8 %) случаях отмечен рост. Только 210 (53,6 %) из 392 штаммов были расценены как возбудители истинной бактериемии. Статистически значимых различий в частоте выделения грамположительных кокков (47,6 %) и грамотрицательных палочек (39,5 %) не выявлено. Грибы регистрировались статистически значимо реже грамположительных кокков и грамотрицательных палочек (9 %; p < 0,0001). Прочие микроорганизмы составили 3,8 %.

Заключение. Терапия и профилактика инфекционных осложнений у онкогематологических больных сопровождаются развитием нарастающей резистентности возбудителей к антибиотикам. Изменения в таксономической структуре возбудителей инфекций кровотока необходимо учитывать при назначении эмпирической и этиотропной терапии.

Ключевые слова: инфекции, рак, инфекции кровотока, бактериемия, антимикробная резистентность, онкогематологические заболевания, антимикробная терапия.

Получено: 12 января 2015 г.

Принято в печать: 30 января 2015 г.

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