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Targeting hedgehog signaling in myelofibrosis and other hematologic malignancies.

Treatment of myelofibrosis (MF), a BCR-ABL-negative myeloproliferative neoplasm, is challenging. The only current potentially curative option, allogeneic hematopoietic stem cell transplant, is recommended for few patients. The remaining patients are treated with palliative therapies to manage MF-related anemia and splenomegaly. Identification of a mutation in the Janus kinase 2 (JAK2) gene (JAK2 V617F) in more than half of all patients with MF has prompted the discovery and clinical development of inhibitors that target JAK2. Although treatment with JAK2 inhibitors has been shown to improve sy

Иммуномодулирующий и противовоспалительный потенциал S-нитросглутатиона (GSNO) при множественной склерозе: обзор механизмов и терапевтических перспектив.

Многофакторная демиелинизация (МС) — это хроническое аутоиммунное заболевание центральной нервной системы (СНС), характеризующееся длительной нейроинфляминацией, окислительным стрессом, демиелинизацией и прогрессирующей нейродегенерацией. Несмотря на то, что МС остается неизлечимым, современные терапевтические средства (ТМС) помогают снизить частоту обострений и задерживать прогрессирование заболевания. Недавно разработанные инъекционные и инфузийные биологические ТМС обеспечивают целенаправленную иммуномодуляцию, но их клиническая полезность ограничена родственными методами введения и возможн

Поощрение использования продольных электронных медицинских записей: обучение по изучению реальных мировых данных о последствиях хронических заболеваний.

Для борьбы с хроническими заболеваниями требуется постоянный мониторинг деятельности по борьбе с заболеваниями и терапевтическое реагирование в целях оптимизации планов лечения. С учетом растущей доступности методов лечения, позволяющих сглаживать заболевания, крайне важно изучить вопрос о сравнительной эффективности и долгосрочных результатах, помимо тех, которые могут быть получены в ходе выборочных клинических испытаний. Мы внедряем всеобъемлющий трубопровод для получения воспроизводимых и обобщенных реальных данных о результатах болезней за счет использования электронных данных о состоянии

Совпадение в полном тексте источника
… Improving the generalizability of data imputation and causal analysis: First, data projection and harmonization techniques—such as canonical correlation analysis, manifold alignment, or autoencoder-based representation learning—can be used to project datasets from multiple sources into a shared latent …

Mesenchymal Stromal Cells in Neuroblastoma: Exploring Crosstalk and Therapeutic Implications.

Neuroblastoma (NB) is the second most common solid cancer in childhood, accounting for 15% of cancer-related deaths in children. In high-risk NB patients, the majority suffers from metastasis. Despite intensive multimodal treatment, long-term survival remains <40%. The bone marrow (BM) is among the most common sites of distant metastasis in patients with high-risk NB. In this environment, small populations of tumor cells can persist after treatment (minimal residual disease) and induce relapse. Therapy resistance of these residual tumor cells in BM remains a major obstacle for the cure of NB.

Human-Induced Pluripotent Stem Cell Models for Amyloid Cardiomyopathy: From Mechanistic Insights to Therapeutic Discovery.

Amyloid cardiomyopathy (ACM), driven by transthyretin (TTR) and immunoglobulin light chain (LC) amyloid fibrils, remains a major clinical challenge due to limited mechanistic understanding and insufficient preclinical models. Human-induced pluripotent stem cells (iPSCs) have emerged as a transformative platform to model ACM, offering patient-specific and genetically controlled systems. In this review, we summarize recent advances in the use of iPSC-derived cardiomyocytes (iPSC-CMs) in both two-dimensional (2D) monolayer cultures and three-dimensional (3D) constructs-including spheroids, organo

Targeting pancreatic cancer immune evasion by inhibiting histone deacetylases.

The immune system plays a vital role in maintaining the delicate balance between immune recognition and tumor development. Regardless, it is not uncommon that cancerous cells can intelligently acquire abilities to bypass the antitumor immune responses, thus allowing continuous tumor growth and development. Immune evasion has emerged as a significant factor contributing to the progression and immune resistance of pancreatic cancer. Compared with other cancers, pancreatic cancer has a tumor microenvironment that can resist most treatment modalities, including emerging immunotherapy. Sadly, the u

Chemokine-Directed Tumor Microenvironment Modulation in Cancer Immunotherapy.

Chemokines are a large family of small chemotactic cytokines that coordinates immune cell trafficking. In cancer, they have a pivotal role in the migration pattern of immune cells into the tumor, thereby shaping the tumor microenvironment immune profile, often towards a pro-tumorigenic state. Furthermore, chemokines can directly target non-immune cells in the tumor microenvironment, including cancer, stromal and vascular endothelial cells. As such, chemokines participate in several cancer development processes such as angiogenesis, metastasis, cancer cell proliferation, stemness and invasivene

Anti-cancer effects of nitrogen-containing bisphosphonates on human cancer cells.

Zoledronic acid, a potent nitrogen-containing bisphosphonate (NBP), has been extensively used to limit bone turnover in a various diseases including tumors. Recent clinical studies have demonstrated direct anti-cancer effects of zoledronic acid, in addition to its clinical benefits for skeletal-related events. Here we investigated the effects of 4 clinically available NBPs on human tumor cell proliferation. Our data demonstrate a potent anti-proliferative effect of zoledronic acid against glioblastoma (GBM) cell lines, breast cancer cells and GBM patient-derived lines. Zoledronic acid also eff

Development and characterization of chimeric antigen receptor macrophages for amyloid clearance.

Systemic amyloidosis is a protein folding disorder characterized by the extracellular deposition of protein fibrils in tissues and vital organs, leading to dysfunction and mortality. While there are monoclonal antibody-based therapies that promote cell-mediated amyloid clearance in various stages of clinical development, there are currently no treatment options which focus on reducing the tissue amyloid burden. Therefore, the urgent need for a transformative approach to facilitate amyloid clearance and restore organ function remains paramount. We demonstrate that a short, polybasic peptide (p5

Genetic Regulation of Tryptase Production and Clinical Impact: Hereditary Alpha Tryptasemia, Mastocytosis and Beyond.

Tryptase is a serine protease that is predominantly produced by tissue mast cells (MCs) and stored in secretory granules together with other pre-formed mediators. MC activation, degranulation and mediator release contribute to various immunological processes, but also to several specific diseases, such as IgE-dependent allergies and clonal MC disorders. Biologically active tryptase tetramers primarily derive from the two genes TPSB2 (encoding β-tryptase) and TPSAB1 (encoding either α- or β-tryptase). Based on the most common gene copy numbers, three genotypes, 0α:4β, 1α:3β and 2α:2β, were defi

Targeting myeloid villains in the treatment with immune checkpoint inhibitors in gastrointestinal cancer.

Despite the clinical outcomes being extremely limited, blocking immune inhibitory checkpoint pathways has been in the spotlight as a promising strategy for treating gastrointestinal cancer. However, a distinct strategy for the successful treatment is obviously needed in the clinical settings. Myeloid cells, such as neutrophils, macrophages, dendritic cells, and mast cells, are the majority of cellular components in the human immune system, but have received relatively less attention for the practical implementation than T cells and NK cells in cancer therapy because of concentration of the int

Serum Onconeural Antibodies in Dogs and Cats for Early Diagnosis of Cancer.

Cancer is one of the leading causes of death in dogs and cats worldwide, and effective early detection techniques and reliable therapies are still lacking. Given the high demand for early cancer detection and differentiation in veterinary diagnostics, we developed and validated a new diagnostic approach to assess onconeural antibodies, also known as high-risk antibodies, in dog and cat blood serum samples. We determined the presence of systemic onconeural/high-risk (ONHR) antibodies, their suitability for early cancer diagnostics, and the feasibility of differentiating various malignancies. Ou

Миэлоидно-подавительские клетки в карциноме ларингеальных клеток: недостаточно изученная иммунодепрессивная ось и стратегическая цель преодоления ингибиторного сопротивления на контрольно-пропускных пунктах.

Углубленные клеточные карциномы (LSCC) указывают на неизменно низкий коэффициент объективной реакции на ингибиторы на контрольно-пропускных пунктах (ИКИ) в отношении запрограммированных death-1 (В тыс.PD-1Путь. Его иммуновосприимчивая опухоль (TME), обогащенная макрофагами, связанными с опухолью, иммунодепрессивными опухолью, связанными с нейтрофилами (TANs), и регуляционными Т клетками, является основным фактором отказа ICI. Пока что one Миелоидное население, имеющее центральное значение для сопротивления ИКИ во многих случаях, не получает особого внимания в связи с этим заболеванием. Миелиои

Synthetic lethality and DNA damage response targeting in cancer stem cells: a comprehensive review.

This comprehensive review explores the critical intersection of Synthetic Lethality (SL) and DNA Damage Response (DDR) targeting within Cancer Stem Cells (CSCs), a subpopulation central to tumor initiation, metastasis, and therapeutic resistance. CSCs exhibit unique biological properties, including enhanced DNA repair mechanisms and metabolic plasticity, rendering them intrinsically resistant to conventional therapies. The fundamental mechanisms of DDR pathways and their dysregulation in cancer are delineated, highlighting how these vulnerabilities can be exploited through SL. The review synth

Role of TRP Channels in Cancer-Induced Bone Pain.

The burden of cancer is growing in almost every country. Bone metastases significantly affect the prognosis and lead to an increase in mortality and morbidity. The management of cancer-induced bone pain (CIBP) still shows various unmet needs. Opioid use is burdened by a number of possible side effects. Moreover, recent progresses in cancer treatment significantly increased the life expectancy of cancer patients, even those with metastatic disease. In this narrative review, we reported the main findings regarding TRP channel function in cancer pain models. TRP cation channels play a key role in

Anti-Cancer Stem-like Cell Compounds in Clinical Development - An Overview and Critical Appraisal.

Cancer stem-like cells (CSC) represent a subpopulation of tumor cells with elevated tumor-initiating potential. Upon differentiation, they replenish the bulk of the tumor cell population. Enhanced tumor-forming capacity, resistance to antitumor drugs, and metastasis-forming potential are the hallmark traits of CSCs. Given these properties, it is not surprising that CSCs have become a therapeutic target of prime interest in drug discovery. In fact, over the last few years, an enormous number of articles describing compounds endowed with anti-CSC activities have been published. In the meanwhile,

Премии победителей и резюме 32nd Ежегодный симпозиум Общества протеинов; Бостон, ОЭТ, июль 9-12, 2018.

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The role of LGR4 in bone metabolism and tumor bone metastasis.

The Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) is a member of the G protein-coupled receptor family and plays an important role in bone metabolism and tumor bone metastasis. LGR4 affects bone metabolism by regulating the differentiation and activity of osteoblasts and osteoclasts, and is involved in the balance between bone resorption and bone formation. Deficiency of LGR4 leads to osteoporosis, whereas the up-regulation of LGR4 may help to alleviate the development of traumatic osteoarthritis. Furthermore, in breast cancer and multiple myeloma, LGR4 promotes tumor cell

Центральная ингибиция TYK2 идентифицирует TYK2 как ключевой нейроиммунный модулятор.

GWAS выявила тирозиновую киназу 2 (TYK2) в многочисленных провокационных расстройствах, в частности защитную гипоморфическую аллею TYK2 (P1104A) в множественных склерозах (MS). Поврежденный TYK2 сигнал в центральной нервной системе (CNS) может вызывать защитное воздействие аллеля TYK2 P1104A в MS. Мы использовали ингибиторы TYK2 (cTYK2i) в дополнение к периферически ограниченному ингибитору TYK2 (pTYK2i; BMS-986165) для того, чтобы рассеять влияние центрального ингибитора TYK2 в различных моделях нейроинфламмации. В то время как PTYK2i не оказывал существенного воздействия, cTYK2i уменьшили кл

A dual-mechanism model of Selinexor in DLBCL: p53 reactivation and metabolic reprogramming.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy with limited therapeutic options in the relapsed or refractory setting. Selinexor, a selective inhibitor of nuclear export targeting XPO1, has demonstrated clinical activity in DLBCL. However, the molecular mechanisms underlying its antitumor effects remain incompletely defined. METHODS: We evaluated the clinical efficacy of Selinexor in a real-world cohort of lymphoma patients and performed integrative transcriptomic and proteomic analyses in DLBCL cell models representing germinal center B-cell–like (GCB) and non-G