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No patient left behind: The promise of immune priming with epigenetic agents.

Checkpoint inhibitors, monoclonal antibodies that inhibit PD-1 or CTLA-4, have revolutionized the treatment of multiple cancers. Despite the enthusiasm for the clinical successes of checkpoint inhibitors, and immunotherapy, in general, only a minority of patients with specific tumor types actually benefit from treatment. Emerging evidence implicates epigenetic alterations as a mechanism of clinical resistance to immunotherapy. This review presents evidence for that association, summarizes the epi-based mechanisms by which tumors evade immunogenic cell death, discusses epigenetic modulation as

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… Tumour suppression by p53: The importance of apoptosis and cellular senescence. J Pathol 2009; 219:3-15; PMID:19562738; https://doi.org/ 10.1002/path.2584 128. Suda T, Takahashi T, Golstein P, Nagata S. …

Neutrophil diversity and function in health and disease.

Neutrophils, the most abundant type of granulocyte, are widely recognized as one of the pivotal contributors to the acute inflammatory response. Initially, neutrophils were considered the mobile infantry of the innate immune system, tasked with the immediate response to invading pathogens. However, recent studies have demonstrated that neutrophils are versatile cells, capable of regulating various biological processes and impacting both human health and disease. Cytokines and other active mediators regulate the functional activity of neutrophils by activating multiple receptors on these cells,

Targeting Abnormal Hematopoietic Stem Cells in Chronic Myeloid Leukemia and Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms.

Myeloproliferative neoplasms (MPNs) are unique hematopoietic stem cell disorders sharing mutations that constitutively activate the signal-transduction pathways involved in haematopoiesis. They are characterized by stem cell-derived clonal myeloproliferation. The key MPNs comprise chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). CML is defined by the presence of the Philadelphia (Ph) chromosome and BCR-ABL1 fusion gene. Despite effective cytoreductive agents and targeted therapy, complete CML/MPN stem cell eradication is r

Лечение связанного с лекарствами остеонекроза челюсти с помощью клеточной терапии.

Введение: Остеонекроз челюсти (MRONJ), связанный с лекарственными препаратами, представляет собой серьезную проблему с учетом отсутствия «золотого стандартного» лечения. Клеточная терапия и тканевая инженерия предлагают перспективные терапевтические альтернативы. Цель этого исследования заключалась в использовании регенеративных свойств стромальной сосудистой фракции (AT-SVF) и лейкоцитного фибрина с высоким содержанием лейкоцита (L-PRF) для обработки MRONJ. AT-SVF содержит мезенхимальные стромальные клетки (MSC) и эндотелиальные клетки потомства (EPC), которые способствуют образованию костей,

Mesenchymal-Stem-Cell-Based Therapy against Gliomas.

Glioblastoma is the most aggressive, malignant, and lethal brain tumor of the central nervous system. Its poor prognosis lies in its inefficient response to currently available treatments that consist of surgical resection, radiotherapy, and chemotherapy. Recently, the use of mesenchymal stem cells (MSCs) as a possible kind of cell therapy against glioblastoma is gaining great interest due to their immunomodulatory properties, tumor tropism, and differentiation into other cell types. However, MSCs seem to present both antitumor and pro-tumor properties depending on the tissue from which they c

The DNA damage response network in the treatment of head and neck squamous cell carcinoma.

BACKGROUND: We sought to determine whether DNA damage response (DDR)-related aberrations predict therapeutic benefit in cisplatin-treated head and neck squamous cell carcinoma (HNSCC) patients and how DDR pathways are modulated after treatment with olaparib alone or in combination with cisplatin or durvalumab. PATIENTS AND METHODS: Oxidative stress, abasic sites and DDR-related parameters, including endogenous DNA damage, DNA repair mechanisms and apoptosis rates, were evaluated in HNSCC cell lines and peripheral blood mononuclear cells from 46 healthy controls (HC) and 70 HNSCC patients at b

Декодирование GPCR, сигнализирующее перепрограммирование рака: молекулярные механизмы и терапевтические последствия.

G белковые рецепторы (GPCR) представляют собой крупнейшую мембранную группу рецепторов в геноме человека и служат ключевыми регуляторами клеточного сигнала, гомеостаза и фармакологической реакции. Помимо их классической роли в посредничестве внеклеточной стимуляции по зависящим от G-протеина и независимым путям, которые играют ключевую роль при помощи GPCR сигнальных путей, включая CAMP-PKA/EPAC, IP3/PLC, PI3K/Akt/mTOR и ERK/MAPK cascades, в вождении онкогенного распространения, апоптоза и метастаза. Кроме того, ГПХР замешаны в опухоли с помощью различных молекулярных механизмов, в рамках кото

Quantitative systems pharmacology modeling sheds light into the dose response relationship of a trispecific T cell engager in multiple myeloma.

In relapsed and refractory multiple myeloma (RRMM), there are few treatment options once patients progress from the established standard of care. Several bispecific T-cell engagers (TCE) are in clinical development for multiple myeloma (MM), designed to promote T-cell activation and tumor killing by binding a T-cell receptor and a myeloma target. In this study we employ both computational and experimental tools to investigate how a novel trispecific TCE improves activation, proliferation, and cytolytic activity of T-cells against MM cells. In addition to binding CD3 on T-cells and CD38 on tumo

Colorectal Cancer Immunotherapy: Options and Strategies.

Colorectal cancer is the third most common cancer in the world with increasing incidence and mortality rates globally. Standard treatments for colorectal cancer have always been surgery, chemotherapy and radiotherapy which may be used in combination to treat patients. However, these treatments have many side effects due to their non-specificity and cytotoxicity toward any cells including normal cells that are growing and dividing. Furthermore, many patients succumb to relapse even after a series of treatments. Thus, it is crucial to have more alternative and effective treatments to treat CRC p

Эпигенетическая ось Лактата-H4K12la-HDAC1 регулирует переход к микроглиальному состоянию во время экспериментального аутоиммунного энцефаломиелита у женских мышей.

Микроглиальная функциональная пластичность формируется метаболическим и эпигенетическим перепрограммированием, но то, как эти процессы регулируют автоиммунитет центральной нервной системы, остается неясным. Мы находим, что уровень цереброспинарной жидкости лактат коррелирует с множественным склерозом. Используя женские модели мыши экспериментального аутоиммунного энцефаломиэлита, аккумуляция спинного лакта приводит к стойкой микроглиальной гистоне лактилации, связывающей с гликолитической активацией. Микроглиавое исключение лактата дегидрогеназы А уменьшает эту лактиляцию и усугубляет остроту

Antimitotic drugs in the treatment of cancer.

Cancer is a complex disease since it is adaptive in such a way that it can promote proliferation and invasion by means of an overactive cell cycle and in turn cellular division which is targeted by antimitotic drugs that are highly validated chemotherapy agents. However, antimitotic drug cytotoxicity to non-tumorigenic cells and multiple cancer resistance developed in response to drugs such as taxanes and vinca alkaloids are obstacles faced in both the clinical and basic research field to date. In this review, the classes of antimitotic compounds, their mechanisms of action and cancer cell res

Hallmarks of ribosomopathies.

Ribosomopathies are diseases caused by defects in ribosomal constituents or in factors with a role in ribosome assembly. Intriguingly, congenital ribosomopathies display a paradoxical transition from early symptoms due to cellular hypo-proliferation to an elevated cancer risk later in life. Another association between ribosome defects and cancer came into view after the recent discovery of somatic mutations in ribosomal proteins and rDNA copy number changes in a variety of tumor types, giving rise to somatic ribosomopathies. Despite these clear connections between ribosome defects and cancer,

Development of CAR T Cell Therapy in Children-A Comprehensive Overview.

CAR T cell therapy has revolutionized immunotherapy in the last decade with the successful establishment of chimeric antigen receptor (CAR)-expressing cellular therapies as an alternative treatment in relapsed and refractory CD19-positive leukemias and lymphomas. There are fundamental reasons why CAR T cell therapy has been approved by the Food and Drug administration and the European Medicines Agency for pediatric and young adult patients first. Commonly, novel therapies are developed for adult patients and then adapted for pediatric use, due to regulatory and commercial reasons. Both strateg

2020 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference.

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Освещение нанотерапевтики с точными глазами: от оптического к радионаностантике.

Рак по-прежнему относится к числу самых смертоносных заболеваний во всем мире, унося много жизней из-за высоких показателей смертности. Химиотерапия, являющаяся одной из основных форм лечения рака, приносит значительные выгоды, однако ей мешают недостатки, которые ставят под угрозу качество жизни пациентов. Таким образом, разработка альтернатив минимально инвазивному лечению по-прежнему представляет собой серьезную проблему. Среди них наноматериалы, легкая фототерапия, включая фотодинамическую терапию, фототермальную терапию и радиотерапию, являются перспективными вариантами, обеспечивающими т

Causal relationships between immune cells, inflammatory factors, serum metabolites, and hepatic cancer: A two-sample Mendelian randomization study.

BackgroundObservational studies and clinical trials suggest associations between immune cells, inflammatory factors, serum metabolites, and hepatic cancer. However, the causal relationships between these factors and hepatic cancer remain to be established.ObjectiveTo explore the causal relationships between immune cells, inflammatory factors, serum metabolites, and hepatic cancer.MethodsThis study employed comprehensive two-sample Mendelian randomization (MR) utilizing publicly available genetic data (GWAS) to analyze causal relationships between 731 immune cell traits, 91 inflammatory factors

Тонаберсат усиливает цитотоксичность в глиобластоме с помощью темозоломида путем нарушения межклеточной связи через коннексин 43 ингибирование.

Клетки глиобластомы зависят от коннексина 43 (Cx43) на основе данных о разрыве (GJs) для межклеточной связи, позволяющей им интегрироваться в широко разветвленную злокачественную сеть. Несмотря на многообещающие перспективы новой целевой терапии, отсутствие клинически осуществимых ингибиторов GJ препятствует их внедрению в клинической практике. В настоящем исследовании мы изучили тонаберсат (ТО) — лекарство, вызывающее кровоизлияние в мозг и имеющее свойства GJ-ингиберия, с точки зрения его способности разобрать межклеточную связь в сетях глиобластомы. Для изучения функциональной межклеточной

An updated overview of the search for biomarkers of osteoporosis based on human proteomics.

Osteoporosis is a chronic metabolic disease that increases bone fragility and, leads to severe osteoporotic fractures. In recent years, the use of high-throughput omics to explore physiological and pathological biomarkers related to bone metabolism has gained popularity. In this review, we first briefly review the technical approaches of proteomics. Additionally, we summarize the relevant literature in the last decade to provide a comprehensive overview of advances in human proteomics related to osteoporosis. We describe the specific roles of various proteins related to human bone metabolism,

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… Of these proteins, five (CD14, CHL1, CO7, FCGBP and PZP) were linked to hip fracture events, whereas the remaining proteins were involved in cellular senescence, complement activation, and innate immunity. …

Extracellular Vesicles in Multiple Myeloma-Cracking the Code to a Better Understanding of the Disease.

Multiple myeloma (MM) is a plasma cell-derived malignancy that stands for around 1.5% of newly discovered cancer cases. Despite constantly improving treatment methods, the disease is incurable with over 13,000 deaths in the US and over 30,000 in Europe. Recent studies suggest that extracellular vesicles (EVs) might play a significant role in the pathogenesis and evolution of MM. Further investigation of their role could prove to be beneficial in establishing new therapies and hence, improve the prognosis of MM patients. What is more, EVs might serve as novel markers in diagnosing and monitorin

A role for curcumin in preventing liver fibrosis in animals: a systematic review and meta-analysis.

ObjectiveThis meta-analysis aimed to determine the efficacy of curcumin in preventing liver fibrosis in animal models.MethodsA systematic search was conducted on studies published from establishment to November 2023 in PubMed, Web of Science, Embase, Cochrane Library, and other databases. The methodological quality was assessed using Sycle's RoB tool. An analysis of sensitivity and subgroups were performed when high heterogeneity was observed. A funnel plot was used to assess publication bias.ResultsThis meta-analysis included 24 studies involving 440 animals with methodological quality scores