Результаты поиска

Предотвращение событий, связанных со скелетом, в новой диагностированной миеломе.

Несмотря на увеличение числа новых методов лечения недавно диагностированной множественной миеломы (НДММ), предотвращение событий, связанных со скелетом (СРП), по-прежнему является сложной задачей. В настоящем обзоре резюмируются механистические причины болезни костей миэломы, данные, подтверждающие использование бисфофонатов и ингибиторов РАНКЛ, а также оптимальное управление предотвращением НОС у пациентов НДММ. Как золедронная кислота (ZA), так и деносумаб являются приемлемыми вариантами обработки с сопоставимыми характеристиками безопасности и эффективности. Однако у пациентов, которые явл

The TNF-α/TNFR2 Pathway: Targeting a Brake to Release the Anti-tumor Immune Response.

Newly discovered anti-cancer immunotherapies, such as immune checkpoint inhibitors and chimeric antigen receptor T cells, focus on spurring the anti-tumor effector T cell (Teff) response. Although such strategies have already demonstrated a sustained beneficial effect in certain malignancies, a substantial proportion of treated patients does not respond. CD4+FOXP3+ regulatory T cells (Tregs), a suppressive subset of T cells, can impair anti-tumor responses and reduce the efficacy of currently available immunotherapies. An alternative view that has emerged over the last decade proposes to tackl

Цель METTL3/m6A/SOCS3 перепрограммирует макрофажную поляризацию, связанную с опухолью, с тем чтобы повысить эффективность анти-PD-1-терапии в множестве миеломы.

ИССЛЕДОВАНИЯ: В ходе этого исследования были изучены функции иммуномодулятора подавителя цитокина, сигнализирующего 3 (SOCS3) в макрофаге поляризации и активации цитотоксичных Т-клеток в микроопухоли (TME) множественной миэломы (MM). МЕТОДЫ: Выражение SOCS3 оценивалось в клинических образцах MM и здоровом контроле. Для разъяснения воздействия SOCS3 на злокачественное развитие клеток MM и поляризацию макрофага были разработаны анализы эффективности и потери функций, а также система кокультуры MM-камер. В рамках механистических исследований основное внимание было уделено модуляции SOCS3 при помо

Pathogenesis and Treatment of Myeloma-Related Bone Disease.

Multiple myeloma is a hematologic malignancy of plasma cells that causes bone-destructive lesions and associated skeletal-related events (SREs). The pathogenesis of myeloma-related bone disease (MBD) is the imbalance of the bone-remodeling process, which results from osteoclast activation, osteoblast suppression, and the immunosuppressed bone marrow microenvironment. Many important signaling cascades, including the RANKL/RANK/OPG axis, Notch signaling, the Wnt/β-Catenin signaling pathways, and signaling molecules, such as DKK-1, sclerostin, osteopontin, activin A, chemokines, and interleukins

Role of Toll-Like Receptors in Myeloid Neoplasms: Focuses on the Molecular Mechanisms and Clinical Impact on Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myeloid Leukemia.

Toll-like receptors (TLRs) are essential components of the innate immune system, functioning as pattern recognition receptors (PRRs) to detect pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). In hematological malignancies, particularly myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML), TLRs influence inflammation, disease progression, and therapeutic response. This review highlights the prognostic relevance of TLR expression, the role of the MyD88 signaling pathway in clonal evolution, and the dual

DNA-hydrolysing activity of IgG antibodies from the sera of patients with schizophrenia.

It is believed that damage to the membranes of brain cells of schizophrenia (SCZ) patients induces the formation of autoantigens and autoantibodies. Nevertheless, the importance of immunological changes leading to the loss of tolerance to self-antigens in the genesis of SCZ has not been established. The MALDI mass spectra of the IgG light chains of 20 healthy donors were relatively homogeneous and characterized by one peak with only one maximum. In contrast to the healthy donors, the MALDI mass spectra of IgG light chains corresponding to 20 SCZ patients demonstrated, similarly to 20 autoimmun

NF-κB in biology and targeted therapy: new insights and translational implications.

NF-κB signaling has been discovered for nearly 40 years. Initially, NF-κB signaling was identified as a pivotal pathway in mediating inflammatory responses. However, with extensive and in-depth investigations, researchers have discovered that its role can be expanded to a variety of signaling mechanisms, biological processes, human diseases, and treatment options. In this review, we first scrutinize the research process of NF-κB signaling, and summarize the composition, activation, and regulatory mechanism of NF-κB signaling. We investigate the interaction of NF-κB signaling with other importa

BH3 Mimetics in Hematologic Malignancies.

Hematologic malignancies (HM) comprise diverse cancers of lymphoid and myeloid origin, including lymphomas (approx. 40%), chronic lymphocytic leukemia (CLL, approx. 15%), multiple myeloma (MM, approx. 15%), acute myeloid leukemia (AML, approx. 10%), and many other diseases. Despite considerable improvement in treatment options and survival parameters in the new millennium, many patients with HM still develop chemotherapy‑refractory diseases and require re-treatment. Because frontline therapies for the majority of HM (except for CLL) are still largely based on classical cytostatics, the relapse

The Molecular Basis and Clinical Consequences of Chronic Inflammation in Prostatic Diseases: Prostatitis, Benign Prostatic Hyperplasia, and Prostate Cancer.

Chronic inflammation is now recognized as one of the major risk factors and molecular hallmarks of chronic prostatitis, benign prostatic hyperplasia (BPH), and prostate tumorigenesis. However, the molecular mechanisms by which chronic inflammation signaling contributes to the pathogenesis of these prostate diseases are poorly understood. Previous efforts to therapeutically target the upstream (e.g., TLRs and IL1-Rs) and downstream (e.g., NF-κB subunits and cytokines) inflammatory signaling molecules in people with these conditions have been clinically ambiguous and unsatisfactory, hence foster

EP300 as a Molecular Integrator of Fibrotic Transcriptional Programs.

Fibrosis is a condition characterized by the excessive accumulation of extracellular matrix proteins in tissues, leading to organ dysfunction and failure. Recent studies have identified EP300, a histone acetyltransferase, as a crucial regulator of the epigenetic changes that contribute to fibrosis. In fact, EP300-mediated acetylation of histones alters global chromatin structure and gene expression, promoting the development and progression of fibrosis. Here, we review the role of EP300-mediated epigenetic regulation in multi-organ fibrosis and its potential as a therapeutic target. We discuss

The roles of osteoprotegerin in cancer, far beyond a bone player.

Osteoprotegerin (OPG), also known as tumor necrosis factor receptor superfamily member 11B (TNFRSF11B), is a member of the tumor necrosis factor (TNF) receptor superfamily. Characterized by its ability to bind to receptor activator of nuclear factor kappa B ligand (RANKL), OPG is critically involved in bone remodeling. Emerging evidence implies that OPG is far beyond a bone-specific modulator, and is involved in multiple physiological and pathological processes, such as immunoregulation, vascular function, and fibrosis. Notably, numerous preclinical and clinical studies have been conducted to

The Multiple Roles of Microrna-223 in Regulating Bone Metabolism.

Bone metabolism is a lifelong process for maintaining skeletal system homeostasis, which is regulated by bone-resorbing osteoclasts and bone-forming osteoblasts. Aberrant differentiation of osteoclasts and osteoblasts leads to imbalanced bone metabolism, resulting in ossification and osteolysis diseases. MicroRNAs (miRNAs) are pivotal factors in regulating bone metabolism via post-transcriptional inhibition of target genes. Recent studies have revealed that miR-223 exerts multiple effects on bone metabolism, especially in the processes of osteoclast and osteoblasts differentiation. In this rev

Компендиум одноклеточных человеческих цереброспинных жидкостей идентифицирует популяции иммунных клеток, связанные с болезнями.

Одноклеточная транскриптомика, применяемая к цереброспинной жидкости (CSF) для разъяснения патофизиологии неврологических заболеваний, позволила получить лишь предварительную характеристику иммунных клеток CSF. CSF образуется из ткани центральной нервной системы (CNS) и граничит с ней, что позволяет проводить полный учет типов клеток наряду с их относительным изобилием и иммунологическими характеристиками, имеющими отношение к заболеваниям CNS. Используя методы интеграции, применяемые к общедоступным наборам данных в сочетании с нашими собственными исследованиями, мы подготовили компендиум, со

Совпадение в полном тексте источника
… Computational advancements including canonical correlation analysis and linear correlation methods only recently have enabled integration of large datasets that reside in public repositories ( 19 , 20 ), although these compilations have not yet included CSF immune cells. … First, we relied on Seurat with canonical correlation analysis ( 68 ) and Harmony ( 69 ) for integration of scRNA-Seq datasets obtained using different technologies and platforms because they are efficient and scalable and improve the accuracy of integration with biological meaning and disease context …

Революция онкологии: роль искусственного интеллекта (AI) в качестве антителного дизайна и средств оптимизации.

Антитела играют решающую роль в защите человеческого тела от болезней, включая такие опасные для жизни заболевания, как рак. Они оказывают посреднические услуги в связи с иммунной реакцией на иностранные антигены и, в некоторых случаях, на самоантигены. С течением времени антителные технологии эволюционировали от моноклонных антител (mAbs) до химерика антигенных рецепторов Т (клеток CAR-T), оказывая значительное влияние на биотехнологию, диагностику и лечение. Хотя эти достижения способствовали активизации терапевтического вмешательства, интеграция искусственного интеллекта (АИ) революционизир

Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectives.

Multiple myeloma (MM) is a hematological malignancy that leads to significant bone destruction, resulting in debilitating pain and skeletal-related events. The pathophysiology of osteolytic bone destruction in MM involves complex interactions between malignant plasma cells (PCs) and the bone marrow (BM) microenvironment. This review aims to provide a comprehensive synthesis of the cellular and molecular pathways underlying MM-associated bone disease. We discuss the role of osteoclast (OC), osteoblast (OB), osteocytes, along with the complex interactions between immune cells and the BM microenv

Macrophage Activation Markers, CD163 and CD206, in Acute-on-Chronic Liver Failure.

Macrophages facilitate essential homeostatic functions e.g., endocytosis, phagocytosis, and signaling during inflammation, and express a variety of scavenger receptors including CD163 and CD206, which are upregulated in response to inflammation. In healthy individuals, soluble forms of CD163 and CD206 are constitutively shed from macrophages, however, during inflammation pathogen- and damage-associated stimuli induce this shedding. Activation of resident liver macrophages viz. Kupffer cells is part of the inflammatory cascade occurring in acute and chronic liver diseases. We here review the ex

Pathogenesis and treatment of multiple myeloma bone disease.

Multiple myeloma (Plasma cell myeloma), a malignancy of the plasma cells, exhibits tumor expansion preferentially in the bone marrow and the development of bone-destructive lesions. Multiple myeloma is still an incurable disease with changes in the bone marrow microenvironment in favor of the survival and proliferation of multiple myeloma cells and bone destruction. In this review, we described the recent findings on the regulators involved in the development of myeloma bone diseases, and succinctly summarize currently available therapeutic options and the development of novel bone modifying a

Cancer Cells Exploit Notch Signaling to Redefine a Supportive Cytokine Milieu.

Notch signaling is a well-known key player in the communication between adjacent cells during organ development, when it controls several processes involved in cell differentiation. Notch-mediated communication may occur through the interaction of Notch receptors with ligands on adjacent cells or by a paracrine/endocrine fashion, through soluble molecules that can mediate the communication between cells at distant sites. Dysregulation of Notch pathway causes a number of disorders, including cancer. Notch hyperactivation may be caused by mutations of Notch-related genes, dysregulated upstream p

Ферроптоз в множестве миеломы: молекулярные механизмы и терапевтические возможности.

Множественная миелома (ММ) — гематологическая порча, вызванная распространением клональных плазменных клеток, и остается в значительной степени неизлечимой из-за рецидива заболеваний и приобретенной лекарственной устойчивости. Ферроптоз, основанная на железной зависимости форма регулируемой клеточной смертности, характеризующейся чрезмерным липидным пероксидацией, стала потенциальной терапевтической целью в раке и все чаще причастна к биологии MM. В отличие от апоптоза и других классических путей смерти клеток, ферроптоз тесно связан с дисрегулируемым метаболизмом железа, окислительным стрессо

PI3K/AKT сигнализирующий путь: молекулярный перекресток в опухоли и терапевтические инновации.

PI3K/AKT сигнализирующий путь служит центральным регулирующим узлом, регулирующим основные клеточные процессы, включая рост, распространение, метаболизм, выживание и миграцию. В контексте развития опухоли и рака аберральная активация этого пути приводит к злокачественным преобразованиям, усиливает инвазивный и метастатический потенциал и оказывает сопротивление терапевтическому вмешательству, что в конечном счете приводит к прогрессированию опухоли и более низким клиническим результатам. В этом исследовании всесторонне изучается ИП3К/АКТ, сигнализирующий о его причастности к различным человече