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The Landscape of lncRNAs in Multiple Myeloma: Implications in the "Hallmarks of Cancer", Clinical Perspectives and Therapeutic Opportunities.

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides that are not translated into proteins. Nowadays, lncRNAs are gaining importance as key regulators of gene expression and, consequently, of several biological functions in physiological and pathological conditions, including cancer. Here, we point out the role of lncRNAs in the pathogenesis of multiple myeloma (MM). We focus on their ability to regulate the biological processes identified as "hallmarks of cancer" that enable malignant cell transformation, early tumor onset and progression. The aberrant expression of lncR

Polyphyllin I Inhibits the Metastasis of Cervical Cancer Through the Regulation of the β-Catenin Signaling Pathway.

Cervical cancer ranks as the fourth most prevalent cancer and cause of cancer-related mortality among women globally. It exhibits a recurrence/metastasis rate of approximately 30% and a dismal 5-year survival of only 17% in metastatic cases. Despite significant advancements in surgical techniques, chemoradiotherapy, and targeted therapies, effective treatment options for metastatic cervical cancer remain limited. This study explored Polyphyllin I (PPI), which is a monomeric compound derived from the Rhizoma of Paris Polyphyllin, as a potential inhibitor of cervical cancer metastasis. Mechanist

A novel role of lysophosphatidic acid (LPA) in human myeloma resistance to proteasome inhibitors.

Lysophosphatidic acid (LPA) is a naturally occurring phospholipid that regulates cell proliferation, survival, and migration. However, its role on human multiple myeloma (MM) cells is largely unknown. In this study, we show that LPA, which is highly elevated in MM patients, plays an important role in protecting human MM cells against proteasome inhibitor (PI)-induced apoptosis. LPA bound to its receptor LPAR2 activated its downstream MEK1/2-ERK1/2 signaling pathway and enhanced oxidative phosphorylation (OXPHOS) in mitochondria in MM cells. Increased OXPHOS activity produced more NAD+ and ATP,

Histone H3K18 Lactylation Promotes the Malignant Progression of Wilms Tumor via a PSRC1/AKT/HIF-1α Positive Feedback Loop.

Nephroblastoma, also known as Wilms tumor (WT), is the most common pediatric renal malignancy. Current treatment regimens exhibit limited efficacy in high-risk patients and are associated with long-term adverse effects. Through gene set enrichment analysis (GSEA) and validation using clinical specimens, we identified aberrant glycolytic activity in WT, which drives lactate accumulation. Lactate is not merely a metabolic byproduct but also a critical epigenetic regulator that mediates histone lactylation; however, its functional role in WT remains uncharacterized. In this study, we found that t

Interleukin-1 Beta-A Friend or Foe in Malignancies?

Interleukin-1 beta (IL-1β) is induced by inflammatory signals in a broad number of immune cell types. IL-1β (and IL-18) are the only cytokines which are processed by caspase-1 after inflammasome-mediated activation. This review aims to summarize current knowledge about parameters of regulation of IL-1β expression and its multi-facetted role in pathophysiological conditions. IL-1 signaling activates innate immune cells including antigen presenting cells, and drives polarization of CD4+ T cells towards T helper type (Th) 1 and Th17 cells. Therefore, IL-1β has been attributed a largely beneficial

Ремонт тканей в центральной нервной системе: эпигенетическое программирование регуляторных Т клеток.

Регулирующие Т клетки хорошо известны своей иммуномодуляционной ролью, но также их регенеративная функция все чаще признается в различных типах тканей, включая скелетные мышцы, легкие и центральную нервную систему (ЦНС). В CNS Tregs, как было показано, поощряют дифференциацию олигодендроцитов в прекурсорных клетках, и их взаимодействие с микроглией поддерживает стимулирующую регенеративную микроокружную среду в мозгу. Подавляющая функция Tregs в значительной степени зависит от эпигенетической сигнатуры, в частности метилации ДНК, определенной сети связанных с Treg генов, включая FOXP3, CTLA4,

Dasatinib as a bone-modifying agent: anabolic and anti-resorptive effects.

BACKGROUND: Bone loss, in malignant or non-malignant diseases, is caused by increased osteoclast resorption and/or reduced osteoblast bone formation, and is commonly associated with skeletal complications. Thus, there is a need to identify new agents capable of influencing bone remodeling. We aimed to further pre-clinically evaluate the effects of dasatinib (BMS-354825), a multitargeted tyrosine kinase inhibitor, on osteoblast and osteoclast differentiation and function. METHODS: For studies on osteoblasts, primary human bone marrow mensenchymal stem cells (hMSCs) together with the hMSC-TERT

The Role of Cullin-RING Ligases in Striated Muscle Development, Function, and Disease.

The well-orchestrated turnover of proteins in cross-striated muscles is one of the fundamental processes required for muscle cell function and survival. Dysfunction of the intricate protein degradation machinery is often associated with development of cardiac and skeletal muscle myopathies. Most muscle proteins are degraded by the ubiquitin-proteasome system (UPS). The UPS involves a number of enzymes, including E3-ligases, which tightly control which protein substrates are marked for degradation by the proteasome. Recent data reveal that E3-ligases of the cullin family play more diverse and c

Switching Homes: How Cancer Moves to Bone.

Bone metastases (BM) are a very common complication of the most prevalent human cancers. BM are extremely painful and may be life-threatening when associated with hypercalcaemia. BM can lead to kidney failure and cardiac arrhythmias and arrest, but why and how do cancer cells decide to "switch homes" and move to bone? In this review, we will present what answers science has provided so far, with focus on the molecular mechanisms and cellular aspects of well-established findings, such as the concept of "vicious cycle" and "osteolytic" vs. "osteosclerotic" bone metastases; as well as on novel co

Сетевая биоинформатика Reveal Microenvironment-Driven Cell-Cell Communication in the Progress of Multieloma.

Секвенирование РНК в одной клетке (scRNAseq) фиксирует уникальные профили отдельных клеток и обнаруживает связь между клетками (CCC) посредством взаимодействия лиганда-рецептора (LR). Кроме того, он показывает механизмы сигнализации, лежащие в основе клеточной неоднородности и сложности реакции вниз по течению в здоровых и болезнетворных состояниях. В ходе этой работы мы разработали композитный вычислительный трубопровод для отслеживания структуры КХЦ в опухолей микроокружающей среды (TME) в процессе развития Multieloma (MM) в качестве тематического исследования. Three Обнародованные наборы да

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… Anchor-based canonical correlation analysis (CCA) was selected for the integration of PCA analyses. This approach identifies shared correlation structures among datasets. The RNA layers of all the samples were then merged and, like the unintegrated analysis, neighbours and clusters were found. … Abbreviations The following abbreviations are used in this manuscript: CCA | Canonical correlation analysis CCC | Cell-to-cell communication CCL5 | C-C motif chemokine ligand 5 DCs | Dendritic cells EGA | European Genome–Phenome Archive GEO | Gene Expression Omnibus HSCs | Hematopoietic stem cells …

Маккулярные внутренние слои сетчатки в множестве склерозов.

AIM: Оценить структурные изменения отдельных внутренних слоев сетчатки в макулярной области и определить наиболее затронутый слой в подгруппах пациентов с множественным склерозом (MS) по сравнению со здоровым контролем (HC). МЕТОДЫ: В целом ретроспективно были экспортированы данные о оптической согласованности томографии (OCT) от 507 пациентов с НР и 183 HC. Пациенты MS были сгруппированы по подтипам MS, первичным прогрессивным (PP), релапсирующим-излучающим (RR) и вторичным прогрессивным (SP). Толщина четырех внутренних слоев сетчатки, макульского слоя нервно-паралитического волокна (NFL), га

Prospects of Chimeric Antigen Receptor T-Cell Therapy in Myelofibrosis: From Immunopathogenesis to Therapeutic Strategies.

Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by clonal hematopoietic dysregulation, amplification of chronic inflammation, and progressive remodeling of the bone marrow fibrotic niche, clinically manifesting as bone marrow failure, splenomegaly, and systemic inflammatory symptoms. Although Janus kinase (JAK) inhibitors can alleviate symptom burden and reduce spleen size, they have limited capacity to eradicate malignant clones or reverse fibrosis. Allogeneic hematopoietic stem cell transplantation remains the only potentially curative option; however, its application is co

ENPP1/CD203a-targeting heavy-chain antibody reveals cell-specific expression on human immune cells.

ENPP1/CD203a is a membrane-bound ectonucleotidase capable of hydrolyzing ATP, cGAMP and other substrates. Its enzymatic activity plays an important role in the balance of extracellular adenine nucleotides and the modulation of purinergic signaling, in soft tissue calcification, and in the regulation of the cGAS/STING pathway. However, a detailed analysis of ENPP1 surface expression on human immune cells has not been performed. Here, we selected VHH domains from human ENPP1-immunized alpacas to generate heavy-chain antibodies targeting ENPP1, and analyzed cell surface expression on all circulat

Myeloid-Derived Suppressor Cells in Sepsis: Pathophysiology, Duality, and Therapeutic Frontiers.

Sepsis-induced immunosuppression, one of the factors contributing to mortality, is closely mediated by myeloid-derived suppressor cells (MDSCs). This review first outlines MDSC biology, describing their origin from pathological emergency myelopoiesis and classification into polymorphonuclear and monocytic subsets. We then discuss their dual role: an early, protective modulation of cytokine storm that later evolves into harmful immunosuppression associated with secondary infections and death. The underlying mechanisms involve L-arginine depletion ( via arginase 1/inducible nitric oxide synthase

Highlighting recent achievements to advance more effective cancer immunotherapy.

From 17 to 19th October 2024, the XXI Italian Network for Bio-Immunotherapy of Tumors Meeting (NIBIT) took place in Palermo, in the marvelous historical location of Teatro Politeama, under the auspices of the Italian Association of Medical Oncology (AIOM), Italian Association of Cancer Research (AIRC), Fondazione Pezcoller, Italian Alliance against Cancer (ACC), Italian Lymphoma Foundation (FIL), Grazia Focacci Foundation and Melagioco Foundation. The conference covered a spectrum of topics ranging from target discovery to therapeutic advances in immuno-oncology, bringing world-renowned expert

Реституция CXCR3+CCR6+T17.1-Like Клетки в ответ на офатумумабскую терапию у пациентов с множественным склерозом.

СПРАВОЧНАЯ ИНФОРМАЦИЯ И ЦЕЛИ: Офатумумаб, полностью человек anti-CD20 Моноклональная антитела эффективна в сокращении рецидивов и развития инвалидности у пациентов с множественным склерозом. Цель этого исследования состояла в изучении изменений иммунных характеристик, связанных с атумумабами, у будущей группы китайских пациентов с повторно излучающимся множественным склерозом (RRMS). МЕТОДЫ: Seventeen Пациенты РУМС были зачислены в это неконтролируемое, перспективное когортное исследование наблюдений (ОМНИСКЕННОЕ исследование) и получали регулярное подкожное лечение от атумумаба. Подмножества

B-cell lymphoma 2 family members and sarcomas: a promising target in a heterogeneous disease.

Targeting the B-cell lymphoma 2 (Bcl-2) family proteins has been the backbone for hematological malignancies with overall survival improvements. The Bcl-2 family is a major player in apoptosis regulation and, has captured the researcher's interest in the treatment of solid tumors. Sarcomas are a heterogeneous group of diseases, comprising several entities, with high morbidity and mortality and with few specific therapies available. The treatment for sarcomas is based on platinum regimens, with variable results and poor outcomes, especially in advanced lesions. The high number of different sarc

Targeting the nuclear export receptor exportin-1 in acute myeloid leukaemia: From biology to clinical translation.

BACKGROUND: Exportin-1 (XPO1), a key regulator of nucleocytoplasmic transport, is frequently dysregulated in acute myeloid leukemia (AML) and contributes to leukemogenesis, disease progression and therapeutic resistance. Selective inhibitors of nuclear export (SINEs), especially selinexor and eltanexor, have shown promising antileukemic potential. However, their clinical value, optimal therapeutic positioning and rational use in AML remain to be fully clarified. METHODS: We collected and reviewed relevant literature to summarize the biological roles of XPO1 in AML and the therapeutic potentia

The roles of inflammasomes in cancer.

Inflammation is a key characteristic of all stages of tumor development, including tumor initiation, progression, malignant transformation, invasion, and metastasis. Inflammasomes are an important component of the inflammatory response and an indispensable part of the innate immune system. Inflammasomes regulate the nature of infiltrating immune cells by signaling the secretion of different cytokines and chemokines, thus regulating the anti-tumor immunity of the body. Inflammasome expression patterns vary across different tumor types and stages, playing different roles during tumor progression

Bridging the gap: ferroptosis of immune cells in the tumor microenvironment.

Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, is increasingly recognized as a pivotal immunomodulatory mechanism within the tumor microenvironment (TME). Beyond its well-established role in tumor cell elimination, emerging evidence reveals that immune cell subsets exhibit distinct susceptibility to ferroptosis, with profound consequences for antitumor immunity. This review systematically delineates the dual and cell-type-specific roles of ferroptosis across innate and adaptive immune populations: while ferroptosis-mediated depletion of immunosuppress