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Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia.

The advent of tyrosine kinase inhibitors (TKI) targeting BCR-ABL has drastically changed the treatment approach of chronic myeloid leukemia (CML), greatly prolonged the life of CML patients, and improved their prognosis. However, TKI resistance is still a major problem with CML patients, reducing the efficacy of treatment and their quality of life. TKI resistance is mainly divided into BCR-ABL-dependent and BCR-ABL-independent resistance. Now, the main clinical strategy addressing TKI resistance is to switch to newly developed TKIs. However, data have shown that these new drugs may cause serio

Mutations with epigenetic effects in myeloproliferative neoplasms and recent progress in treatment: Proceedings from the 5th International Post-ASH Symposium.

Immediately following the 2010 annual American Society of Hematology (ASH) meeting, the 5th International Post-ASH Symposium on Chronic Myelogenous Leukemia and BCR-ABL1-Negative Myeloproliferative Neoplasms (MPNs) took place on 7-8 December 2010 in Orlando, Florida, USA. During this meeting, the most recent advances in laboratory research and clinical practice, including those that were presented at the 2010 ASH meeting, were discussed among recognized authorities in the field. The current paper summarizes the proceedings of this meeting in BCR-ABL1-negative MPN. We provide a detailed overvie

Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy.

A paradigm shift has recently occurred in the field of cancer therapeutics. Traditional anticancer agents, such as chemotherapy, radiotherapy and small-molecule drugs targeting specific signalling pathways, have been joined by cellular immunotherapies based on T cell engineering. The rapid adoption of novel, patient-specific cellular therapies builds on scientific developments in tumour immunology, genetic engineering and cell manufacturing, best illustrated by the curative potential of chimeric antigen receptor (CAR) T cell therapy targeting CD19-expressing malignancies. However, the clinical

Manic and hypomanic states in cancer patients: A systematic review.

OBJECTIVES: While there have been reports on the relationship between cancer and depression, reports on the association between cancer and manic states, a reciprocal state of depression, have been relatively few. Therefore, we conducted a systematic review on the relationships between cancer and manic states, focusing on their etiology, clinical course, and impact on cancer treatments. METHODS: A systematic review was conducted using four electronic databases, following the PRISMA guidelines. The scope of the study included research on manic or hypomanic states associated with cancer in patie

16th International Congress on Antiphospholipid Antibodies Task Force Report on Antiphospholipid Syndrome Treatment Trends.

Antiphospholipid syndrome (APS), an acquired autoimmune thrombophilia, is characterised by thrombosis and/or pregnancy morbidity in association with persistent antiphospholipid antibodies. The 16th International Congress on Antiphospholipid Antibodies Task Force on APS Treatment Trends reviewed the current status with regard to existing and novel treatment trends for APS, which is the focus of this Task Force report. The report addresses current treatments and developments since the last report, on the use of direct oral anticoagulants in patients with APS, antiplatelet agents, adjunctive ther

Recent Advances in Cancer Vaccines: Challenges, Achievements, and Futuristic Prospects.

Cancer is a chronic disease, and it can be lethal due to limited therapeutic options. The conventional treatment options for cancer have numerous challenges, such as a low blood circulation time as well as poor solubility of anticancer drugs. Therapeutic cancer vaccines emerged to try to improve anticancer drugs' efficiency and to deliver them to the target site. Cancer vaccines are considered a viable therapeutic technique for most solid tumors. Vaccines boost antitumor immunity by delivering tumor antigens, nucleic acids, entire cells, and peptides. Cancer vaccines are designed to induce lon

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… CpG-Oligodeoxynucleotides Enhance T-Cell Receptor-Triggered Interferon-Gamma Production and Up-Regulation of CD69 via Induction of Antigen-Presenting Cell-Derived Interferon Type I and Interleukin-12. Immunology. 2000;99:170–178. doi: 10.1046/j.1365-2567.2000.00964.x. 87. Cai H., Sun Z. …

33rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2018) : Washington, D.C., USA. 7-11 November 2018.

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Inflammation and Cancer: Molecular Mechanisms and Therapeutic Targets.

Inflammation is a core pathological factor regulating tumor initiation, progression, and therapeutic resistance, and elucidating its molecular crosstalk with tumors is crucial for developing effective clinical therapies. Internal drivers of inflammation-tumor transformation include genomic disorder, epigenetic memory, mitochondrial stress, and metabolic reprogramming, which synergistically initiate carcinogenesis. External factors amplifying tumor progression cover immune dysfunction, stromal fibrosis, microbial dysbiosis, vascular neoplasia, and neurotoxicity, collectively accelerating tumor

Review and Updates on Systemic Mastocytosis and Related Entities.

Mast cell disorders range from benign proliferations to systemic diseases that cause anaphylaxis and other diverse symptoms to mast cell neoplasms with varied clinical outcomes. Mastocytosis is the pathologic process of the accumulation of abnormal mast cells in different organs, mostly driven by KIT mutations, and can present as cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma. The WHO 5th edition classification divides systemic mastocytosis into bone marrow mastocytosis, indolent systemic mastocytosis, smoldering systemic mastocytosis, aggressive systemic mastocytosi

Overcoming immunosuppression in cancer: how ketogenic diets boost immune checkpoint blockade.

Immune checkpoint blockade (ICB) is now part of the standard of care in the treatment of many forms of cancer, yet it lacks efficacy in some patients, necessitating adjunct therapies to support the anti-tumor immune response. Ketogenic diets (KDs), i.e., high-fat low-carbohydrate diets, have been shown to have antiproliferative and immunomodulatory effects in various preclinical cancer studies. Here, we review current knowledge of the complex interplay of KDs and the anti-tumor immune response in the context of ICB therapy, to update our understanding of diet-induced immunometabolic reprogramm

Identification of alemtuzumab-suitable multiple sclerosis patients in Slovakia and sequencing of post-alemtuzumab immunomodulatory treatment.

BackgroundAlemtuzumab (ALEM) is a humanised monoclonal antibody that depletes circulating lymphocytes by selectively targeting CD52, which is expressed in high levels on T- and B-lymphocytes. This depletion is followed by lymphocyte repopulation and a cytokine expression shift towards a lesser inflammatory profile, both of which may contribute to prolonged efficacy. National recommendations for enrolling and treating multiple sclerosis (MS) patients with ALEM have been established. However, there are no recommendations in place for the treatment of MS reactivation after the ALEM treatment.Obje

Относительный риск инфицирования у лиц с множественным склерозом с использованием методов лечения, позволяющих регулировать заболевания: систематический обзор результатов наблюдений.

ЦЕНТРАЛЬНАЯ ИНФОРМАЦИЯ: Некоторые методы лечения различных видов склероза (MS) с целью видоизменения заболеваний повышают риск инфицирования, однако по-прежнему неизвестно, каким образом этот риск сравнивается между испытаниями и наблюдениями. ЦЕЛЬ: Оценить нынешнее состояние наблюдений за риском инфицирования людей с MS и с использованием DMT. МЕТОДЫ: PubMed и Embase искали результаты исследований наблюдений, опубликованных 4 апреля 2023 года или ранее и описывающих инфекцию у людей с MS, с сопоставлением по меньшей мере 1 DMT с отсутствием DMT или другой DMT. Мы изучили, какие контрасты ДМТ

Ginsenoside-Mediated Ferroptosis Regulation: Bidirectional Effects and Therapeutic Potential in Diseases.

Notably, certain ginsenoside components exhibit distinct bidirectional and context-dependent regulatory effects on ferroptosis depending on the disease setting. In aberrantly proliferating or activated cells, ginsenosides function as ferroptosis inducers, whereas in damaged quiescent cells of normal tissues, they act as ferroptosis inhibitors. The pro-ferroptotic effect is predominantly observed in cells characterized by abnormal proliferation or activation, such as cancer cells and activated hepatic stellate cells in liver fibrosis. In this context, ginsenosides modulate key iron metabolism p

Targeting CD38 Across Autoimmune and Plasma Cell-Driven Immune-Mediated Diseases: Rationale, Clinical Evidence, and Emerging Therapeutic Landscape.

Autoimmune diseases remain a major cause of chronic morbidity despite substantial advances in targeted immunomodulatory therapies. In many autoantibody-mediated conditions, disease refractoriness and relapse are driven by long-lived plasma cells, which are largely resistant to conventional immunosuppression and upstream B cell-directed strategies. CD38, a surface molecule highly expressed on plasmablasts and plasma cells and functionally involved in immunometabolic regulation, has emerged as a promising therapeutic target to overcome this limitation. Clinical interest in anti-CD38 therapy has

Synthetic Flozins in Cancer Prevention and Combination Strategies: Structural Insights and Therapeutic Potential.

The growing number of cancer cases highlights the urgent need to develop new therapies based on effective molecules. Although anticancer activity remains a key element of oncological pharmacology, the importance of agents that support physiological functions and improve the quality of life of cancer patients is also recognised. Compounds that combine these two functions could represent a significant trend in oncology. Moreover, repurposing approved drugs for conditions beyond their original indications could be a promising strategy. An interesting example of this is synthetic flozins (SGLT2 in

Viruses

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Краткосрочные факторы риска потери костей при множественном склерозе: перспективное исследование и анализ литературы.

У людей с множественным склерозом (pwMS) часто наблюдается уменьшение массы костей и повышенный риск остеопороза. Цель этого исследования заключалась в определении факторов риска краткосрочной потери костей в НР. МЕТОДЫ: Это перспективное исследование включало 139 ПМС (возрасты) 18-65). Базовые данные включают демографические данные, индекс массы тела, физическую активность, курение, состояние менопаузы, 25- Гидроксичные уровни витамина D и история применения глюкокортикоида. Плотность костных минералов (BMD) измерялась в исходных условиях и после 2 - годы с использованием рентгеновской рентге

Cancer Immunotherapy with Immune Checkpoint Inhibitors-Biomarkers of Response and Toxicity; Current Limitations and Future Promise.

Immune checkpoint inhibitors are monoclonal antibodies that are used to treat over one in three cancer patients. While they have changed the natural history of disease, prolonging life and preserving quality of life, they are highly active in less than 40% of patients, even in the most responsive malignancies such as melanoma, and cause significant autoimmune side effects. Licenced biomarkers include tumour Programmed Death Ligand 1 expression by immunohistochemistry, microsatellite instability, and tumour mutational burden, none of which are particularly sensitive or specific. Emerging tumour

Oncolytic virotherapy as emerging immunotherapeutic modality: potential of parvovirus h-1.

Human tumors develop multiple strategies to evade recognition and efficient suppression by the immune system. Therefore, a variety of immunotherapeutic strategies have been developed to reactivate and reorganize the human immune system. The recent development of new antibodies against immune check points may help to overcome the immune silencing induced by human tumors. Some of these antibodies have already been approved for treatment of various solid tumor entities. Interestingly, targeting antibodies may be combined with standard chemotherapy or radiation protocols. Furthermore, recent evide

Investigating the functions and molecular mechanisms of DTX3L in cancer progression.

In the field of tumor research, the process by which E3 ubiquitin ligases specifically ubiquitinate substrate proteins and promote their degradation has garnered significant attention. DTX3L, an emerging E3 ubiquitin ligase of the Deltex family, is closely associated with the development and progression of various malignant tumors. Through multiple mechanisms such as epigenetic modifications, signal pathway activation, and protein interaction networks, DTX3L precisely regulates key biological processes, including cell proliferation, cycle progression, migration, invasion, and apoptosis. This r