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RNA modifications in cancer.

RNA modifications are emerging as critical cancer regulators that influence tumorigenesis and progression. Key modifications, such as N6-methyladenosine (m6A) and 5-methylcytosine (m5C), are implicated in various cellular processes. These modifications are regulated by proteins that write, erase, and read RNA and modulate RNA stability, splicing, translation, and degradation. Recent studies have highlighted their roles in metabolic reprogramming, signaling pathways, and cell cycle control, which are essential for tumor proliferation and survival. Despite these scientific advances, the precise

Является ли DEXI множественным склерозом удобочитаемым геном?

Генетический ландшафт множественного склероза (MS) был тщательно просчитан, что позволило глубже понять молекулярные механизмы расстройства. В ходе первых исследований были выявлены ключевые гены, связанные с иммунной системой, в частности с Т клетками, которые имеют решающее значение для MS-чувствительности. В ходе последующих широкомасштабных исследований, проведенных в рамках всей ассоциации генома (GWAS), было выявлено более 200 генетических вариантов, связанных с MS, что выявило сложную взаимосвязь между риском, связанным с MS, и генами, вовлеченными в различные процессы в рамках адаптивн

Проверка основанных на правилах методов обнаружения рецидивов при множественном склерозе.

СПРАВОЧНАЯ ИНФОРМАЦИЯ: Выявление рецидивов в электронных медицинских записях (ЭПЧ) сопряжено с трудностями у пациентов с множественным склерозом (МС). Цель этого исследования заключалась в проверке основанных на установленных правилах методов обнаружения рецидивов с использованием структурированных в Саудовской Аравии данных ЭПЧ. МЕТОДЫ: Two Были разработаны методы обнаружения, основанные на установленных нормах, с использованием данных о пациентах НР, полученных от крупного многорегионального медицинского учреждения Саудовской Аравии. Метод обнаружения I требовал применения высокодозированных

Respiratory and Thoracic Medicine

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Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer.

PurposeAdoptively transferred, ex vivo expanded multi-antigen-targeted T cells (multiTAA-T) represent a new, potentially effective, and nontoxic therapeutic approach for patients with breast cancer (BC). In this first-in-human trial, we investigated the safety and clinical effects of administering multiTAA T cells targeting the tumor-expressed antigens, Survivin, NY-ESO-1, MAGE-A4, SSX2, and PRAME, to patients with relapsed/refractory/metastatic BC.Materials and methodsMultiTAA T-cell products were generated from the peripheral blood of heavily pre-treated patients with metastatic or locally r

Dying of Stress: Chemotherapy, Radiotherapy, and Small-Molecule Inhibitors in Immunogenic Cell Death and Immunogenic Modulation.

Innovative strategies to re-establish the immune-mediated destruction of malignant cells is paramount to the success of anti-cancer therapy. Accumulating evidence suggests that radiotherapy and select chemotherapeutic drugs and small molecule inhibitors induce immunogenic cell stress on tumors that results in improved immune recognition and targeting of the malignant cells. Through immunogenic cell death, which entails the release of antigens and danger signals, and immunogenic modulation, wherein the phenotype of stressed cells is altered to become more susceptible to immune attack, radiother

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… Chemotherapeutics and radiation stimulate MHC class I expression through elevated interferon-beta signaling in breast cancer cells. PLoS ONE. 2012;7:e32542. doi: 10.1371/journal.pone.0032542. 85. Hargadon K.M., Johnson C.E., Williams C.J. …

[Generalisability of Phase III Clinical Trials Using the Example of Two German Multiple Sclerosis Registries].

Newly approved therapies usually have unknown adverse events, although the clinical trials that led to approval had already tested them for safety and efficacy. One reason for this is that the inclusion and exclusion criteria of the trials often do not fully reflect the usually heterogeneous patient population in routine clinical care.The aim of the study was to analyse the extent to which patients with multiple sclerosis (MS) in routine clinical care fulfil the inclusion and exclusion criteria for the corresponding clinical phase III trial of the respective drug.Sociodemographic and clinical

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… In dieser Analyse wurde die Einteilung der betrachteten DMDs wie folgt durchgeführt: Wirksamkeitskategorie 1 (Dimethylfumarat, Glatirameracetat, Interferon-beta, Teriflunomid); Wirksamkeitskategorie 2 (Cladribin, Fingolimod); Wirksamkeitskategorie 3 (Alemtuzumab, Natalizumab, Ocrelizumab); ohne Kategorie …

Cancer Immunotherapy in Combination with Radiotherapy and/or Chemotherapy: Mechanisms and Clinical Therapy.

Since the United States Food and Drug Administration approved the first immune checkpoint inhibitor ipilimumab for metastatic melanoma in 2011, ICIs have been approved for a range of cancers and significantly improving treatment outcomes. However, the objective response rate of ICI monotherapy remains modest (10-40%), with clinical benefit observed in only 15-20% of patients. The limited efficacy of ICIs in many patients is often attributed to poorly immunogenic ("cold") tumors. Radiotherapy and chemotherapy exhibit immunomodulatory properties that can enhance tumor immunogenicity. These effec

Fetal hemoglobin induction during decitabine treatment of elderly patients with high-risk myelodysplastic syndrome or acute myeloid leukemia: a potential dynamic biomarker of outcome.

Hematologic responses to hypomethylating agents are often delayed in patients with myelodysplastic syndrome or acute myeloid leukemia. Fetal hemoglobin is a potential novel bio-marker of response: recently, we demonstrated that a high fetal hemoglobin level prior to decitabine treatment was associated with superior outcome. Here we investigated whether early fetal hemoglobin induction during decitabine treatment also had prognostic value, and studied the potential of decitabine to induce erythroid differentiation and fetal hemoglobin expression in vitro Fetal hemoglobin levels were measured by

Immune mediated support of metastasis: Implication for bone invasion.

Bone is a common organ affected by metastasis in various advanced cancers, including lung, breast, prostate, colorectal, and melanoma. Once a patient is diagnosed with bone metastasis, the patient's quality of life and overall survival are significantly reduced owing to a wide range of morbidities and the increasing difficulty of treatment. Many studies have shown that bone metastasis is closely related to bone microenvironment, especially bone immune microenvironment. However, the effects of various immune cells in the bone microenvironment on bone metastasis remain unclear. Here, we describe

Computational proteomics to enhance personalized treatment of COVID-19 and Long COVID.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to significant global health burden, including both acute infections and persistent post-acute sequelae, also known as Long COVID (LC) in survivors. While clinical management has reduced case-fatality rates, a substantial proportion of patients develop LC, a heterogeneous syndrome with long-term symptoms. This complex continuum requires therapeutic strategies for both the acute and chronic phases. Plasma proteomics has emerged as a powerful tool in precision medicin

Epigenetic modification in diabetic kidney disease.

Diabetic kidney disease (DKD) is a common microangiopathy in diabetic patients and the main cause of death in diabetic patients. The main manifestations of DKD are proteinuria and decreased renal filtration capacity. The glomerular filtration rate and urinary albumin level are two of the most important hallmarks of the progression of DKD. The classical treatment of DKD is controlling blood glucose and blood pressure. However, the commonly used clinical therapeutic strategies and the existing biomarkers only partially slow the progression of DKD and roughly predict disease progression. Therefor

Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges.

Uncontrolled inflammation is a salient factor in multiple chronic inflammatory diseases and cancers. In this review, we provided an in-depth analysis of the relationships and distinctions between uncontrolled inflammation, fibrosis and cancers, while emphasizing the challenges and opportunities of developing novel therapies for the treatment and/or management of these diseases. We described how drug delivery systems, combination therapy and the integration of tissue-targeted and/or pathways selective strategies could overcome the challenges of current agents for managing and/or treating chroni

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

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… inhibitors DDR1 discoidin domain receptor 1 ERK extracellular signal-regulated kinase GSH glutathione GLUT glucose transporters γ-GT gamma-glutamyl transferase HCC hepatocellular carcinoma HFrEF heart failure with reduced ejection fraction HF heart failure HIF-1α hypoxia-inducible factor 1-alpha IFN-β interferon-beta … beta; WNT/β-catenin—Wingless-integrated/β-catenin; ROS—reactive oxygen species; CD4 + and CD8 + T cells—cluster of differentiation 4 and 8 positive T cells. …

The Ubiquitin-Proteasome System (UPS) as a Cancer Drug Target: Emerging Mechanisms and Therapeutics

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Immune evasion in cancer: mechanisms and cutting-edge therapeutic approaches.

Immune evasion represents a significant challenge in oncology. It allows tumors to evade immune surveillance and destruction, thereby complicating therapeutic interventions and contributing to suboptimal patient outcomes. This review addresses the critical need to understand how cancers evade immune surveillance. It aims to provide a comprehensive overview of strategies of tumors to escape immune detection by examining tumor-induced immune suppression, immune checkpoint regulation, and genetic and epigenetic influences. Moreover, it explores the dynamic role of the tumor microenvironment (TME)

Antitumor, Anti-Inflammatory and Antiallergic Effects of Agaricus blazei Mushroom Extract and the Related Medicinal Basidiomycetes Mushrooms, Hericium erinaceus and Grifola frondosa: A Review of Preclinical and Clinical Studies.

Since the 1980s, medicinal effects have been documented in scientific studies with the related Basidiomycota mushrooms Agaricus blazei Murill (AbM), Hericium erinaceus (HE) and Grifola frondosa (GF) from Brazilian and Eastern traditional medicine. Special focus has been on their antitumor effects, but the mushrooms' anti-inflammatory and antiallergic properties have also been investigated. The antitumor mechanisms were either direct tumor attack, e.g., apoptosis and metastatic suppression, or indirect defense, e.g., inhibited tumor neovascularization and T helper cell (Th) 1 immune response. T

Характеристики рациона питания и факторы питания при множественном склерозе: обзор скрипта.

Множественный склероз (MS) — хроническое иммунное расстройство центральной нервной системы, характеризующееся воспалением, обезвоживанием и прогрессивной неврологической дисфункцией. Все большее внимание уделяется потенциальной роли рациона питания в качестве предписательной стратегии для улучшения симптомов, модуляции воспаления и повышения качества жизни людей с НР. В настоящем докладе рассматриваются текущие данные, полученные в ходе клинических испытаний, наблюдений и соответствующих обзоров воздействия рациона питания и отдельных компонентов питания на клинические результаты в MS с уделен

Исследование взаимосвязи между элементами сериальной трассы и уровнями MSFC в области множественного склероза: перекрестное тематическое исследование.

Воздействие микроэлементов в течение многих лет изучалось в многократной склерозовой (МС) этиологии. Однако общие результаты еще не получены в ходе предыдущих исследований. Поэтому в качестве межсекторального исследования по вопросам контроля за конкретными случаями мы стремились изучить взаимосвязь между микроэлементами и MS в провинции Конья, где загрязнение воздуха является интенсивным. Участники исследования с МЗ были исследованы в отношении расширенных показателей инвалидности (ЭДСС) и множественных функциональных склерозовых композиционных шкал (МСФК). Кроме того, была проведена оценка в

Тела эндогенных кетонов связаны с метаболической уязвимостью и инвалидностью при множественном склерозе.

Цель: Тела кетона могут быть полезными биомаркерами в множестве склероза (МС), поскольку патофизиологические процессы, лежащие в основе развития заболеваний MS, вызывают метаболический стресс. Цель заключалась в оценке связей кетоновых тел с биомаркерами метаболического, подстрекательского и окислительного стресса в MS. Методы: Образцы крови и неврологические оценки были получены от 153 здоровых контрольных приборов (HC), 187 релапсирующих излучающих веществ (RRMS) и 91 пациента с прогрессивным MS (PMS). AcAc, BHB и ацетон измерялись с помощью спектроскопии протонного ядерного магнитного резон