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Митохондриальная пригодность как функциональная контрольная точка в раке: метаболическая пластичность, эволюция опухолей и иммунотерапия.

Митохондрия все чаще признается в качестве динамичных регуляторов адаптации к раковым клеткам, иммунной функции и терапевтической реакции. Помимо их канонической роли в производстве энергии, митохондриальный метаболизм, динамика, контроль качества и сигнализация стресса влияют на выживание клеток опухоли и способность клеток иммунного эффекта поддерживать антитумберную активность в микроопухоли. В этом обзоре мы рассматриваем митохондриальную пригодность как многоаспектное функциональное достояние, включающее биоэнергетику, метаболическую гибкость, повторное гомеостаз, контроль качества митохо

Role of Non-Coding RNAs in the Development of Targeted Therapy and Immunotherapy Approaches for Chronic Lymphocytic Leukemia.

In the past decade, novel targeted therapy approaches, such as BTK inhibitors and Bcl2 blockers, and innovative treatments that regulate the immune response against cancer cells, such as monoclonal antibodies, CAR-T cell therapy, and immunomodulatory molecules, have been established to provide support for the treatment of patients. However, drug resistance development and relapse are still major challenges in CLL treatment. Several studies revealed that non-coding RNAs have a main role in the development and progression of CLL. Specifically, microRNAs (miRs) and tRNA-derived small-RNAs (tsRNAs

Therapeutic Modulation of Autophagy in Leukaemia and Lymphoma.

Haematopoiesis is a tightly orchestrated process where a pool of hematopoietic stem and progenitor cells (HSPCs) with high self-renewal potential can give rise to both lymphoid and myeloid lineages. The HSPCs pool is reduced with ageing resulting in few HSPC clones maintaining haematopoiesis thereby reducing blood cell diversity, a phenomenon called clonal haematopoiesis. Clonal expansion of HSPCs carrying specific genetic mutations leads to increased risk for haematological malignancies. Therefore, it comes as no surprise that hematopoietic tumours develop in higher frequency in elderly peopl

Pediatric Drug Development: Reviewing Challenges and Opportunities by Tracking Innovative Therapies.

The paradigm of pediatric drug development has been evolving in a "carrot-and-stick"-based tactic to address population-specific issues. However, the off-label prescription of adult medicines to pediatric patients remains a feature of clinical practice, which may compromise the age-appropriate evaluation of treatments. Therefore, the United States and the European Pediatric Formulation Initiative have recommended applying nanotechnology-based delivery systems to tackle some of these challenges, particularly applying inorganic, polymeric, and lipid-based nanoparticles. Connected with these, adv

Nanoparticles Based Therapeutic Approaches in Oncogenic Viral Infections: A Review.

Nanotechnology has revolutionized biomedical research by providing novel strategies for the prevention, diagnosis, and treatment of oncogenic viral infections. Nanoparticles, possessing tunable physicochemical properties, enable targeted drug delivery, enhance vaccine efficacy, and facilitate advanced viral diagnostics, addressing key limitations of conventional therapies. Oncogenic viruses contribute substantially to the global burden of cancer through persistent infections and are influenced by environmental and lifestyle factors. The objective of this review is to synthesize and critically

Novel Therapeutic Approaches in Pediatric Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, characterized by the clonal proliferation of immature lymphoid precursors. The distinction between B-cell ALL (B-ALL) and T-cell ALL (T-ALL) is fundamental, as each subtype exhibits distinct cytomorphological, genetic, and clinical features influencing prognosis and therapeutic strategies. Conventional multi-phase chemotherapy has significantly improved survival rates, yet its efficacy is limited by severe short- and long-term toxicities, highlighting the need for more selective therapeutic approaches. Advances in mole

MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment.

Among childhood cancers, neuroblastoma is the most diffuse solid tumor and the deadliest in children. While to date, the pathology has become progressively manageable with a significant increase in 5-year survival for its less aggressive form, high-risk neuroblastoma (HR-NB) remains a major issue with poor outcome and little survivability of patients. The staging system has also been improved to better fit patient needs and to administer therapies in a more focused manner in consideration of pathology features. New and improved therapies have been developed; nevertheless, low efficacy and high

Crosstalk of thioredoxin system and programmed cell death: from pathophysiology to novel therapy.

The thioredoxin (Trx) system, an integral component of cellular redox regulation, preserves protein dithiol-disulfide equilibrium through its conserved Cys-Gly-Pro-Cys active site and is involved in key cellular functions, including cell proliferation, apoptosis, and signal transduction. In cancer biology, the thioredoxin system plays dual roles: overexpression can suppress oxidative stress and promote tumor growth, whereas dysfunction can trigger programmed cell death (PCD). However, a critical area for future research is to delineate how Trx modulates the intricate networks of PCD, and to id

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… T-cell lymphoproliferative disorders such as T-ALL (T cell acute lymphoblastic leukemia) and CTCL (cutaneous T-cell lymphoma) are characterized by constitutive NF-κB activation, which is essential for their survival. …

The synergistic immunotherapeutic impact of engineered CAR-T cells with PD-1 blockade in lymphomas and solid tumors: a systematic review.

Currently, therapies such as chimeric antigen receptor-T Cell (CAR-T) and immune checkpoint inhibitors like programmed cell death protein-1 (PD-1) blockers are showing promising results for numerous cancer patients. However, significant advancements are required before CAR-T therapies become readily available as off-the-shelf treatments, particularly for solid tumors and lymphomas. In this review, we have systematically analyzed the combination therapy involving engineered CAR-T cells and anti PD-1 agents. This approach aims at overcoming the limitations of current treatments and offers potent

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… These diverse expressions of CD30 highlight its significance as a diagnostic and therapeutic target across various lymphoproliferative disorders and certain non-hematological malignancies ( 32 , 165 – 167 ). …

Targeting Cellular Senescence in Aging and Age-Related Diseases: Challenges, Considerations, and the Emerging Role of Senolytic and Senomorphic Therapies.

Cellular senescence is characterized by the permanent arrest of cell proliferation and is a response to endogenous and exogenous stress. The continuous accumulation of senescent cells (SnCs) in the body leads to the development of aging and age-related diseases (such as neurodegenerative diseases, cancer, metabolic diseases, cardiovascular diseases, and osteoarthritis). In the face of the growing challenge of aging and age-related diseases, several compounds have received widespread attention for their potential to target SnCs. As a result, senolytics (compounds that selectively eliminate SnCs

" Nucleolus in Human Beasons: Ribosome Biogenesis " , " Nucleolar Survey " и " Terrapeutic Opportunities " .

Nucleolus превратился в динамичную и многофункциональную субядерную органилию, интегрирующую рибосомный биогенез с клеточным ростом и сигнализацией стресса. Регулирование нуклеолярной функции все чаще признается в качестве главного движителя человеческих заболеваний, связывающего изменённое рибосомное производство и нуклеолярное наблюдение с раком, рибосомопатиями, синдромами преждевременного старения, нейродегенерацией и иммунными расстройствами. В этом обзоре мы интегрируем структурные, молекулярные и болезнетворные перспективы нуклеолярной биологии для определения того, как рипосомный биоге

The convergent evolution of influenza A virus: Implications, therapeutic strategies and what we need to know.

Influenza virus infection, more commonly known as the 'cold flu', is an etiological agent that gives rise to recurrent annual flu and many pandemics. Dated back to the 1918- Spanish Flu, the influenza infection has caused the loss of many human lives and significantly impacted the economy and daily lives. Influenza virus can be classified into four different genera: influenza A-D, with the former two, influenza A and B, relevant to humans. The capacity of antigenic drift and shift in Influenza A has given rise to many novel variants, rendering vaccines and antiviral therapies useless. In light

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… Compromised immunity Immunocompromised individuals, such as individuals with human immunodeficiency virus (HIV) infection, cancers (chronic lymphoproliferative disorders, multiple myeloma), and those receiving antineoplastic therapy are vulnerable to severe influenza outcomes and death ( Safdar and …

Role of Bruton's tyrosine kinase in B cells and malignancies.

Bruton's tyrosine kinase (BTK) is a non-receptor kinase that plays a crucial role in oncogenic signaling that is critical for proliferation and survival of leukemic cells in many B cell malignancies. BTK was initially shown to be defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) and is essential both for B cell development and function of mature B cells. Shortly after its discovery, BTK was placed in the signal transduction pathway downstream of the B cell antigen receptor (BCR). More recently, small-molecule inhibitors of this kinase have shown excellent anti-tumor a

Предварительная обработка сигнатуры эндокринного недоедания прогнозируют клиническую пользу от PD-1/PD-L1 Блокирование гематологовых магнатов.

Гематологические заболевания создают значительное бремя для здоровья людей во всем мире, а запрограммированная клеточная смертность protein-1 (В тыс.PD-1)/запрограммированный смертельный лиганж клеток 1 (В тыс.PD-L1) ингибиторы, революционизирующие лечение в подтипах, таких, как классическая лимфома Ходжкина (cHL) и первичная медистинальная лимфома В-клеток (PMBCL), достигающая высоких объективных показателей ответов (ORR). Однако эффективность варьируется в широких пределах, при этом успех в множестве миеломы ограничен.< 10% ORR) и лейкемии, подчеркивая необходимость лучшего прогнозирования,

Total Body Irradiation in Haematopoietic Stem Cell Transplantation for Paediatric Acute Lymphoblastic Leukaemia: Review of the Literature and Future Directions.

Total body irradiation (TBI) has been a pivotal component of the conditioning regimen for allogeneic myeloablative haematopoietic stem cell transplantation (HSCT) in very-high-risk acute lymphoblastic leukaemia (ALL) for decades, especially in children and young adults. The myeloablative conditioning regimen has two aims: (1) to eradicate leukaemic cells, and (2) to prevent rejection of the graft through suppression of the recipient's immune system. Radiotherapy has the advantage of achieving an adequate dose effect in sanctuary sites and in areas with poor blood supply. However, radiotherapy

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… . | ( 261 ) Specific articles | In a cohort of 3,182 childhood acute leukaemia survivors who underwent HSCT, 25 solid tumours and 20 post-transplant lymphoproliferative disorders were observed after a median of 6 years (range 0.4–14.3 years). …

Артериальный тромбоэмболизм

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Natural Killer Cells in the Malignant Niche of Multiple Myeloma.

Natural killer (NK) cells represent a subset of CD3- CD7+ CD56+/dim lymphocytes with cytotoxic and suppressor activity against virus-infected cells and cancer cells. The overall potential of NK cells has brought them to the spotlight of targeted immunotherapy in solid and hematological malignancies, including multiple myeloma (MM). Nonetheless, NK cells are subjected to a variety of cancer defense mechanisms, leading to impaired maturation, chemotaxis, target recognition, and killing. This review aims to summarize the available and most current knowledge about cancer-related impairment of NK c

Targeting Oncoproteins for Molecular Cancer Therapy

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34th Европейский конгресс патологии - резюме.

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The 45th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians - Oral Session.

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