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Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential.

Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes of proliferation, differentiation, migration, and stem cell self-renewal, is associated with multiple aspects of disease. Bone homeostasis is severely disturbed by Wnt antagonists that are secreted by the malignant plasma cells in the bone marrow. In the vast majority of patients, this results in osteolytic

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… Incorporation of Wnt ligands in membrane-enclosed vesicles, including exosomes, ensures adequate transport over larger distances of extracellular space [ 31 ]. The canonical Wnt signaling pathway all revolves around the transcriptional co-activator β-catenin. …

Neurology

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The trinity of T cell engagement: navigating the molecular and clinical landscape of CAR-T, TILs, and TCEs in the war against cancer.

The advent of cancer immunotherapy has fundamentally restructured the oncological paradigm, moving away from agents that directly target tumor cell kinetics toward strategies that empower the host immune system to recognize and eliminate malignancy. Central to this revolution is the cytotoxic T lymphocyte (CTL), now harnessed as a potent "living drug" through engineered and naturally selected modalities. This review provides a critical, in-depth examination of the three dominant pillars of T cell-driven therapies: Chimeric Antigen Receptor T-cell (CAR-T) therapy, Tumor-Infiltrating Lymphocyte

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… Simultaneously, the massive glycolytic flux of the tumor generates copious amounts of lactic acid, which is actively exported into the extracellular space via monocarboxylate transporters. …

Leptomeningeal carcinomatosis in gastric cancer: A Review.

Gastric cancer is the fifth most common cancer worldwide and leptomeningeal carcinomatosis (LM) occurs in 0.06% of gastric cancers. As such, trials are difficult to power and quantitative analyses difficult to standardize. We composed a review and analysis of 47 recent cases to be used as a comprehensive resource for an oncologist faced with managing this highly morbid, rapidly fatal disease. Gold-standard of diagnosis of LM is through cerebral spinal fluid (CSF) cytology; MRI is the preferred imaging modality to identify LM. However, repeated lumbar punctures and imaging studies are often req

Monoclonal antibody and protein therapeutic formulations for subcutaneous delivery: high-concentration, low-volume vs. low-concentration, high-volume.

Biologic drugs are used to treat a variety of cancers and chronic diseases. While most of these treatments are administered intravenously by trained healthcare professionals, a noticeable trend has emerged favoring subcutaneous (SC) administration. SC administration of biologics poses several challenges. Biologic drugs often require higher doses for optimal efficacy, surpassing the low volume capacity of traditional SC delivery methods like autoinjectors. Consequently, high concentrations of active ingredients are needed, creating time-consuming formulation obstacles. Alternatives to tradition

The Role of the CREB Protein Family Members and the Related Transcription Factors in Radioresistance Mechanisms.

In the framework of space flight, the risk of radiation carcinogenesis is considered a "red" risk due to the high likelihood of occurrence as well as the high potential impact on the quality of life in terms of disease-free survival after space missions. The cyclic AMP response element-binding protein (CREB) is overexpressed both in haematological malignancies and solid tumours and its expression and function are modulated following irradiation. The CREB protein is a transcription factor and member of the CREB/activating transcription factor (ATF) family. As such, it has an essential role in a

Bone targeted nano-drug and nano-delivery.

There are currently no targeted delivery systems to satisfactorily treat bone-related disorders. Many clinical drugs consisting of small organic molecules have a short circulation half-life and do not effectively reach the diseased tissue site. This coupled with repeatedly high dose usage that leads to severe side effects. With the advance in nanotechnology, drugs contained within a nano-delivery device or drugs aggregated into nanoparticles (nano-drugs) have shown promises in targeted drug delivery. The ability to design nanoparticles to target bone has attracted many researchers to develop n

MSC-EV therapy for bone/cartilage diseases.

Mesenchymal stromal cells (MSCs) have been utilized in cell therapy for various diseases. Recent studies have demonstrated that extracellular vesicles (EVs) released by MSCs play an important role in their therapeutic activities. EVs contain a variety of bioactive molecules such as proteins, messenger RNAs (mRNAs), and micro RNAs (miRNAs) and modify the function of the recipient cells by transferring these molecules. Despite the promising potential of EV therapy as a substitute for MSC therapy, there are challenges that need to be addressed for the clinical success of EV therapy. EV quality ha

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… These intraluminal vesicles are extruded into the extracellular space as exosomes by fusing MVEs with the plasma membrane. Microvesicles range in size from 100 nm to 1000 nm in diameter. … They are generated by the outward budding and fission of the plasma membrane and subsequently secreted out to the extracellular space ( Mathieu et al., 2019 ; Théry et al., 2009 ; Théry et al., 2018 ). Apoptotic bodies are cellular debris that is produced when cells undergo apoptosis. …

Подстегнутая стрессом связь с нанотрубкой в глиальных клетках CNS: последствия провокационного демиэлирования и отказа в ремонте.

Множественные склерозы и связанные с ними воспалительные расстройства центральной нервной системы, включая расстройство спектра нейромиелита, расстройство спектра и болезнь миэлина олигодендроцита гликопротеина, связанные с антителами, характеризуются повреждениями имунной ткани, глиальной дисфункцией, метаболическим стрессом и неполным ремонтом. Хотя периферическая иммунная инфильтрация и антителные механизмы объясняют многие аспекты образования острых повреждений, они не в полной мере учитывают стойкую активность повреждения, метаболическую нестабильность или отказ от ремиэлирования в местно

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… Extracellular vesicles are released into the extracellular space and can reach multiple recipient cells, whereas TNTs maintain direct connections between defined cell pairs and support more spatially restricted transfer, including movement of intact intracellular structures. …

Hypertrophic Cardiomyopathy Phenocopies: Classification, Key Features, and Differential Diagnosis.

Among cardiomyopathies, the hypertrophic phenotype is the most common, and hypertrophic cardiomyopathy (HCM) phenocopies represent a heterogeneous group of conditions. They are defined by a left ventricular wall thickness ≥15 mm in the absence of other causes such as loading conditions, ischemia, or valvular disease. Although they mimic similar clinical and morphological features, their etiologies are distinct and include genetic, metabolic, and infiltrative mechanisms. Therefore, accurate classification and differential diagnosis are crucial for effective management and treatment. Sarcomeric

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… Gadolinium is a contrast agent with extracellular distribution; thus, LGE can explore extracellular space, differentiating between HCM due to storage (as Fabry disease) or extracellular infiltrates (as amyloidosis). … Furthermore, extracellular space itself can be derived as a percentage through native T1 and post-contrast T1 comparison. The latter is higher than normal in infiltrative diseases and lower in storage diseases. …

Molecular events in the jaw vascular unit: A traditional review of the mechanisms involved in inflammatory jaw bone diseases.

Inflammatory jaw bone diseases are common in stomatology, including periodontitis, peri-implantitis, medication-related osteonecrosis of the jaw, radiation osteomyelitis of the jaw, age-related osteoporosis, and other specific infections. These diseases may lead to tooth loss and maxillofacial deformities, severely affecting patients' quality of life. Over the years, the reconstruction of jaw bone deficiency caused by inflammatory diseases has emerged as a medical and socioeconomic challenge. Therefore, exploring the pathogenesis of inflammatory diseases associated with jaw bones is crucial fo

Emergency Care

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The Power of Extracellular Vesicles in Myeloproliferative Neoplasms: "Crafting" a Microenvironment That Matters.

Myeloproliferative Neoplasms (MPN) are acquired clonal disorders of the hematopoietic stem cells and include Essential Thrombocythemia, Polycythemia Vera and Myelofibrosis. MPN are characterized by mutations in three driver genes (JAK2, CALR and MPL) and by a state of chronic inflammation. Notably, MPN patients experience increased risk of thrombosis, disease progression, second neoplasia and evolution to acute leukemia. Extracellular vesicles (EVs) are a heterogeneous population of microparticles with a role in cell-cell communication. The EV-mediated cross-talk occurs via the trafficking of

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… The multivesicular bodies in turn can fuse with lysosomes or, alternatively, with the cell membrane releasing the intraluminal vesicles into the extracellular space. …

The science of tumor-infiltrating lymphocytes (TIL): perspectives from the SITC Surgery Committee.

Immunity to solid tumors is associated with the hallmarks of cancer-associated inflammation and the ability of immune mechanisms to limit tumor progression. Application of expanded tumor-infiltrating lymphocyte adoptive T cell therapy (TIL ACT) in clinical trials is now practiced at many sites around the world. Prior to immune checkpoint blockade (ICB), an approximate 50% objective response rate was consistently observed across multiple institutions for patients with melanoma. This now-approved strategy approaches 35% in recent studies from the USA and 49% with more highly selected patients in

Role of Nanomedicine-Based Therapeutics in the Treatment of CNS Disorders.

Central nervous system disorders, especially neurodegenerative diseases, are a public health priority and demand a strong scientific response. Various therapy procedures have been used in the past, but their therapeutic value has been insufficient. The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier is two of the barriers that protect the central nervous system (CNS), but are the main barriers to medicine delivery into the CNS for treating CNS disorders, such as brain tumors, Parkinson's disease, Alzheimer's disease, and Huntington's disease. Nanotechnology-based medicinal

Targeting Tumor Microenvironment for Cancer Therapy.

Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in tumor cells result in hyperplasia, uncontrolled growth, resistance to apoptosis, and metabolic shift towards anaerobic glycolysis (Warburg effect). These events create hypoxia, oxidative stress and acidosis within the TME triggering an adjustment of the extracellular matrix (ECM), a response

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… Once released to the extracellular space, exosomes enable the transfer of proteins, lipids and RNA between different cells, and modulate the recipient cells’ phenotype [ 133 , 134 ]. As exosomes can be found in body fluids, attention has been made to use them as biomarkers of cancer. …

ISEV2025 Резюме книги.

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… When the external membrane of these MV‐lEVs ruptures spontaneously, ILVs are released into the extracellular space through a ‘torn bag’ mechanism, a process distinct from multivesicular body (MVB) exocytosis and plasma membrane shedding of small ectosomes. …

Оценка полезности гибридного ПЕТ/МР нейроимации во воспламенительной демиэлизации и энцефалите.

В связи с увеличением в последние годы количества гибридных ПЕТ/МСД этот метод все шире используется для нейроимации в клинической практике. Она сочетает преимущества МРТ (включая высокоразрешенную съемку внутрицеребральных повреждений и данных, полученных в результате специализированных последовательности МРТ) с преимуществами ПЕТ, которая визуализирует функциональные изменения в мозге, а также оценивает изменения в количестве миелинов и остроту воспаления. Использование ПЕТ/МОИ может помочь устранить ограничения МРТ, указанные в виде обезображивающих подстрекательских заболеваний (таких, как

Двойная роль микроглии в множественном склерозе и его последствия для диагностики и ремонта.

Микроглия играет ключевую роль в развитии, иммунной слежке и восстановлении центральной нервной системы. Эти клетки играют многогранную роль в множестве склероза (MS), при этом есть основания полагать, что микроглия может способствовать как активному воспалению, так и воспалению. Например, было продемонстрировано, что микроглия может поддерживать разработку олигодендроцитов и фигоцитоза миелиновых обломков, способствуя тем самым надлежащему восстановлению. Однако чрезмерная активация микроглии в повреждениях MS усугубляет нейроинфламму, высвобождая подстрекательские цитокины и облегчая активац

Exploring the applicability, combined strategies, and challenges of ablation in hematology based on its characteristics and immunomodulatory mechanisms.

Malignant hematological diseases, such as lymphoma, leukemia, and multiple myeloma, are frequently accompanied by clinical challenges including local progressive lesions, relapsed/refractory conditions, and poor tolerance to standard treatments in special populations. Systemic therapies represented by chemotherapy and targeted therapy have inherent limitations in addressing local tumor burden, relieving organ compression, and being suitable for frail patients. As a minimally invasive local treatment technology, ablation has been widely used in solid tumor therapy due to its advantages of preci