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Non-Hematologic Toxicity of Bortezomib in Multiple Myeloma: The Neuromuscular and Cardiovascular Adverse Effects.

The overall approach to the treatment of multiple myeloma (MM) has undergone several changes during the past decade. and proteasome inhibitors (PIs) including bortezomib, carfilzomib, and ixazomib have considerably improved the outcomes in affected patients. The first-in-class selective PI bortezomib has been initially approved for the refractory forms of the disease but has now become, in combination with other drugs, the backbone of the frontline therapy for newly diagnosed MM patients, as well as in the maintenance therapy and relapsed/refractory setting. Despite being among the most widely

Cyclic Peptides in Modern Drug Discovery: Trends and Therapeutic Directions.

Peptide therapeutics are an important drug modality due to their high specificity, favorable safety, and expanding design potential. Among them, cyclic peptides occupy a space between small molecules and biologics, offering improved rigidity, stability, and target engagement. This report analyzes trends in cyclic peptide research using data from the CAS Content Collection over the past two decades. Results show a steady rise in academic publications and patents, reflecting growing interest across discovery and development. Notably, oral administration is gaining attention, indicating progress

Опыт и экспертный консенсус в отношении промежуточной терапии до клеточной терапии против BCMA CAR-T в множестве миеломы.

Расширяется применение антиклеточной терапии против созревания (BCMA) химерика антигенного рецептора Т-клетки (CAR-T) для лечения повторной/охлажденной множественной миеломы. Исследования показывают, что эффективная переходная терапия (БТ) до антиБМА CAR-T терапия может повысить эффективность и безопасность. На основе качественных опросов и проведения рабочего совещания на основе консенсуса, 10 Европейские эксперты поделились своим клиническим опытом в отношении оптимального выбора, эффективности, безопасности и результатов после CAR-T, сосредотачивая внимание на пациентах, прошедших интенсивн

Integrating Artificial Intelligence, Circulating Tumor DNA, and Real-World Evidence to Optimize Hematologic Clinical Trials: Toward Adaptive and Learning Trial Designs.

The integration of emerging technologies and real-world data is transforming the landscape of hematologic clinical trials. Artificial intelligence (AI) offers remarkable capabilities for predictive modeling, patient stratification, and adaptive trial design, while circulating tumor DNA (ctDNA) provides a minimally invasive biomarker for disease monitoring, the early detection of relapse, and treatment response assessment. Concurrently, real-world evidence (RWE) complements traditional clinical trial data by capturing treatment effectiveness, safety, and patient outcomes in broader, heterogeneo

Clinical Practice Guidelines for Menopause: An Executive Summary and Recommendations: Indian Menopause Society 2026.

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Molecular Mechanisms of Symptom Fluctuations in Malignant Tumor Patients: Stable by Day and Severe at Night.

Patients with malignant tumors often experience fluctuations in the severity of their symptoms depending on the time of day. In traditional Chinese medicine, symptoms are said to follow a pattern of "mild in the morning, stable by day, worsening in the evening, and severe at night." This article investigates the circadian chronobiology of symptoms and examines their molecular pathophysiology. Evidence suggests that disruptions in core circadian clock genes, such as BMAL1 and PER, along with the dysregulation of cellular metabolic pathways, immune responses, and endocrine functions, synergistic

Resistance to Antiangiogenic Therapy in Hepatocellular Carcinoma: From Molecular Mechanisms to Clinical Impact.

Antiangiogenic drugs were the only mainstay of advanced hepatocellular carcinoma (HCC) treatment from 2007 to 2017. However, primary or secondary resistance hampered their efficacy. Primary resistance could be due to different molecular and/or genetic characteristics of HCC and their knowledge would clarify the optimal treatment approach in each patient. Several molecular mechanisms responsible for secondary resistance have been discovered over the last few years; they represent potential targets for new specific drugs. In this light, the advent of checkpoint inhibitors (ICIs) has been a new o

Cell-Selective Altered Cargo Properties of Extracellular Vesicles Following In Vitro Exposures to Intermittent Hypoxia.

Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), is associated with cardiovascular and metabolic dysfunction. However, the mechanisms underlying these morbidities remain poorly delineated. Extracellular vesicles (EVs) mediate intercellular communications, play pivotal roles in a multitude of physiological and pathological processes, and could mediate IH-induced cellular effects. Here, the effects of IH on human primary cells and the release of EVs were examined. Microvascular endothelial cells (HMVEC-d), THP1 monocytes, THP1 macrophages M0, THP1 macrophages M1, THP1 macr

Совпадение в полном тексте источника
… Exosomes and Metabolic Function in Mice Exposed to Alternating Dark-Light Cycles Mimicking Night Shift Work Schedules Front. Physiol. 2017 8 882 10.3389/fphys.2017.00882 29163218 PMC5673652 86. Tan J. Xing H. Sha S. Li J. Miao Y. Zhang Q. …

Immunotherapy of Multiple Myeloma: Promise and Challenges.

Whereas the treatment of MM was dependent solely on alkylating agents and corticosteroids during the prior three decades, the landscape of therapeutic measures to treat the disease began to expand enormously early in the current century. The introduction of new classes of small-molecule drugs, such as proteasome blockers (bortezomib and carfilzomib), immunomodulators (lenalidomide and pomalidomide), nuclear export inhibitors (selinexor), and histone deacetylase blockers (panobinostat), as well as the application of autologous stem cell transplantation (ASCT), resulted in a seismic shift in how

Качество жизни, связанное со здоровьем, и скорректированное на качество свободное выживание для карфилзомиба и дексаметазона после спасательной аутологической трансплантации стволовых клеток у пациентов с множественной миеломой: случайная трансплантация фазы 2 :: судебное разбирательство, проведенное Исследовательской группой Северной Европы по миеломе.

ЗАКРЫТИЕ: Решения, касающиеся лечения пациентов с множественной миеломой, должны приниматься с учетом как эффективности лечения, так и связанных со здоровьем последствий для качества жизни. В ходе испытания CARFI пациенты с первым рецидивом множественной миэломы прошли спасательную аутологическую трансплантацию стволовых клеток (Salvage ASCT) до случайного введения в карфилзомиб-дексамасона для лечения (Kd) или наблюдения. Первостепенной клинической точкой было время для продвижения, которое было продлено 8 Месяцами Кд. Цель настоящего документа состоит в том, чтобы представить все параметры п

How can Cytokine-induced killer cells overcome CAR-T cell limits.

The successful treatment of patients affected by B-cell malignancies with Chimeric Antigen Receptor (CAR)-T cells represented a breakthrough in the field of adoptive cell therapy (ACT). However, CAR-T therapy is not an option for every patient, and several needs remain unmet. In particular, the production of CAR-T cells is expensive, labor-intensive and logistically challenging; additionally, the toxicities deriving from CAR-T cells infusion, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), have been documented extensively. Alternative

Myeloma bone disease: pathogenesis and management in the era of new anti-myeloma agents.

IntroductionMultiple myeloma (MM) is a malignancy of plasma cells with characteristic bone disease. Despite recent great strides achieved in MM treatment owing to the implementation of new anti-MM agents, MM is still incurable and bone destruction remains a serious unmet issue in patients with MM.ApproachIn this review, we will summarize and discuss the mechanisms of the formation of bone disease in MM and the available preclinical and clinical evidence on the treatment for MM bone disease.ConclusionsMM cells produce a variety of cytokines to stimulate receptor activator of nuclear factor-κB l

Immunosenescence and cancer predisposition in pediatric transplant recipients: An emerging paradigm.

Pediatric solid organ and hematopoietic stem cell transplant recipients paradoxically experience accelerated immune aging despite chronological youth, establishing a paradigm with profound implications for cancer risk and long-term outcomes. This comprehensive review synthesizes current evidence demonstrating how transplantation-related factors, anti-thymocyte globulin-mediated T cell depletion, cytomegalovirus reactivation, chronic immunosuppression, and thymic dysfunction, induce premature immunosenescent phenotypes. These processes converge to generate T cell populations exhibiting CD28 los

Advances in antisense oligonucleotide treatment for cancer.

RNA therapeutics, including antisense oligonucleotides (ASOs), have emerged as a promising class of drugs, with several already approved for clinical use. To date, most approved ASO-based RNA therapies target non-malignant disorders such as neurodegenerative diseases, and only a single therapy in this class has been approved for cancer. Notably, nearly half of existing RNA therapeutics act by modulating RNA splicing. Given the growing evidence implicating aberrant RNA splicing in cancer pathogenesis, the development of ASO-based therapeutics for oncologic indications is expected to accelerate.

ESMO/ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2023.

The European Society for Medical Oncology (ESMO) and ASCO are publishing a new edition of the ESMO/ASCO Global Curriculum (GC) with contributions from more than 150 authors. The purpose of the GC is to provide recommendations for the training of physicians in medical oncology and to establish a set of educational standards for trainees to qualify as medical oncologists. This edition builds on prior ones in 2004, 2010, and 2016 and incorporates scientific advances and input from an ESMO/ASCO survey on GC adoption conducted in 2019, which revealed that GC has been adopted or adapted in as many a

Прогнозирующее значение динамического мониторинга состояния минимальных остаточных заболеваний у пациентов с множественной миеломой: исследование реального мира.

Фон: Минимальное остаточное заболевание (МВД) является установленным прогнозным фактором в миеломе (ММ), однако значение динамических изменений MRD до и после аутологической трансплантации стволовых клеток (ASCT) остается неясным. Методы: Ретроспективный анализ 335 Недавно диагностировали пациентов MM, прошедших первичную ACCT. Общий показатель выживаемости (ОС) и выживаемости без прогрессирования (ПФС) оценивался с использованием метода Kapan-Meier и сопоставлялся с использованием теста log-rk. Для оценки коэффициентов опасности (HR) и 95% Интервал доверия (CI), коррекция с учетом клинических

Gaucher disease: the hematologist's perspective of a multisystemic disorder.

Gaucher disease (GD) exemplifies how a single genetic mutation can give rise to a complex multisystem disorder with profound hematological implications. Central to its pathophysiology is the lysosomal accumulation of glucosylceramide due to deficient glucocerebrosidase activity, together with abnormal folding and trafficking of the enzyme that induce endoplasmic reticulum stress and cellular dysfunction. These processes disrupt reticuloendothelial homeostasis and interfere with hematopoiesis. As a consequence, macrophage activation and chronic inflammation contribute to the cytopenias, splenom

The State of Obesity in Kansas: A Community Based Approach to Chronic Care Management.

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Прогнозирование релапирования и индивидуализированная модель лечения-воздействия при повторном склерозе: систематический обзор.

ВВЕДЕНИЕ: Индивидуальное прогнозирование результатов, связанных с рецидивом, может способствовать отбору и мониторингу лечения при повторном склерозе. Однако существующие исследования существенно отличаются друг от друга по клиническим целям, целевым результатам, подходам к моделированию и стратегиям проверки. МЕТОДЫ: Мы провели систематический обзор в соответствии с ПРИСМА 2020. Пубмед, Web of Science, IEEE Xplore и Scopus были найдены записи на английском языке, опубликованные на английском языке. 1 Январь 2010 в адрес 14 Январь 2026. Были включены исследования по разработке или оценке модел

Систематический обзор моноклональной антителной терапии при повторном многоразовом склерозе: компаратор-сортифицированный анализ результатов релапса и инвалидности.

UNLABELLED: " Фон: моноколональная антителная терапия " представляет собой высокоэффективные методы лечения для повторного применения различных форм склероза (MS). Вместе с тем отсутствие непосредственных выборочных испытаний по принципу < < от головы до головы > > и использование разнородных компараторов во всех важнейших исследованиях осложняют сравнительные оценки эффективности. Хотя сетевой метаанализ (НМА) обеспечивает основу для интеграции фактических данных, раздробленная структура имеющейся фактологической базы исключает использование традиционной НМА с глобальным