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Терапия клеток CAR-T и модуляция микробиоты в мультислерозе: новые терапевтические стратегии и текущие ограничения.

Множественный склероз (MS) — хроническое аутоиммунное воспалительное заболевание центральной нервной системы (CNS), характеризующееся разрушением миелиновой оболочки вокруг нервных клеток. Широкое распространение и серьезные последствия НР свидетельствуют о недостатках существующих методов лечения и о важности разработки новаторских терапевтических подходов. На основе успешных экспериментальных исследований среди пациентов и экспериментальной модели мышью аутоиммунного энцефаломиелита (EAE) клетки CAR-T предлагают новый терапевтический механизм путем непосредственной адресации и ликвидации кле

IL1B Полиморфизм (rs1143634) и IL-1β Концентрация плазмы в качестве предсказателей расстройств питания и прогнозирующих факторов у многих пациентов с миеломой.

Множественная миелома (ММ) — гематологическая опухоль раннего прекурсора клеток В. Наиболее характерные симптомы, наблюдаемые во время MM, включают гипокалкемию, анемию, бактериальные инфекции и почечные повреждения. Отмечаются расстройства питания, особенно недоедание 35-71% Пациентов MM. Interleukin 1 бета (IL-1β) — цитокин, производящий мускулистую атрофию и липолиз во время недоедания и качексии. Цель этого исследования заключалась в оценке полезности полиморфизма однонуклеотида IL1B (SNP) (rs1143634) и плазменной концентрации IL-.1β при оценке риска нарушения питания и прогнозирования у п

Interleukin-1 Beta-A Friend or Foe in Malignancies?

Interleukin-1 beta (IL-1β) is induced by inflammatory signals in a broad number of immune cell types. IL-1β (and IL-18) are the only cytokines which are processed by caspase-1 after inflammasome-mediated activation. This review aims to summarize current knowledge about parameters of regulation of IL-1β expression and its multi-facetted role in pathophysiological conditions. IL-1 signaling activates innate immune cells including antigen presenting cells, and drives polarization of CD4+ T cells towards T helper type (Th) 1 and Th17 cells. Therefore, IL-1β has been attributed a largely beneficial

Расследовать внеклеточные везы Т в качестве биомаркеров активности заболеваний, аксоновых травм и инвалидности при множественном склерозе.

ВВЕДЕНИЕ: Множественный склероз (MS) представляет собой хроническое иммунопосредованное демиелионирующее заболевание центральной нервной системы, при котором активность клинических заболеваний контролируется главным образом с помощью магнитного резонансного изображения. МЕТОДЫ: С учетом ограничений, связанных с внедрением и приобретением новых и новейших биомаркеров изображений в обычной клинической практике, открытие биомаркеров с биофильтром может стать более простой и эффективной с точки зрения затрат мерой, которая позволит улучшить доступность, стандартизацию и уход за пациентами. Внешнек

Mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer.

Bone metastatic prostate cancer (PCa) promotes mesenchymal stem cell (MSC) recruitment and their differentiation into osteoblasts. However, the effects of bone-marrow derived MSCs on PCa cells are less explored. Here, we report MSC-derived interleukin-28 (IL-28) triggers prostate cancer cell apoptosis via IL-28 receptor alpha (IL-28Rα)-STAT1 signaling. However, chronic exposure to MSCs drives the selection of prostate cancer cells that are resistant to IL-28-induced apoptosis and therapeutics such as docetaxel. Further, MSC-selected/IL-28-resistant prostate cancer cells grow at accelerated rat

Различия между мужчинами и женщинами-неврофилами, в отношении которых в полиомиках присутствуют РНК.

КОЛИЧЕСТВО: Мужчины и женщины демонстрируют различия в распространенности связанных с нейтрофильом заболеваний, таких, как системная волчанка, эритематос, ревматоидный артрит и множественный склероз, а также различия в нейтрофильных физиологических реакциях, таких, как реакция на инфекцию, повреждение тканей и химотактические факторы. Однако мало что известно об основах различий по признаку пола среди нейтрофилов. МЕТОДЫ: Начиная с людей, нейтрофилов от здоровых доноров, мы использовали RNA-seq для изучения общих профилей RNA, RNA, не связанных с рибосом и, следовательно, не переведенных, RNA

Cardiovascular disease and chimeric antigen receptor cellular therapy.

Chimeric antigen receptor T-cell (CAR T) therapy is a revolutionary personalized therapy that has significantly impacted the treatment of patients with hematologic malignancies refractory to other therapies. Cytokine release syndrome (CRS) is a major side effect of CAR T therapy that can occur in 70-90% of patients, with roughly 40% of patients at grade 2 or higher. CRS can cause an intense inflammatory state leading to cardiovascular complications, including troponin elevation, arrhythmias, hemodynamic instability, and depressed left ventricular systolic function. There are currently no stand

Clinical characteristics, laboratory parameters and outcomes of COVID-19 in cancer and non-cancer patients from a tertiary Cancer Centre in India.

BackgroundThere is paucity of data regarding clinical characteristics, laboratory parameters and outcomes of coronavirus disease (COVID-19) in cancer versus non-cancer patients, particularly from India.Materials and methodsThis was an observational, single-centre, retrospective analysis of patients with laboratory-confirmed COVID-19 hospitalised in our institution between 22 May 2020 and 1 December 2020. We compared baseline clinical characteristics, laboratory parameters and outcomes of COVID-19 (overall mortality, time to discharge) between cancer and non-cancer patients.ResultsA total of 20

Biomarkers in Multiple Sclerosis: An Up-to-Date Overview

During the last decades, the effort of establishing satisfactory biomarkers for multiple sclerosis has been proven to be very difficult, due to the clinical and pathophysiological complexities of the disease. Recent knowledge acquired in the domains of genomics-immunogenetics and neuroimmunology, as well as the evolution in neuroimaging, has provided a whole new list of biomarkers. This variety, though, leads inevitably to confusion in the effort of decision making concerning strategic and individualized therapeutics. In this paper, our primary goal is to provide the reader with a list of the

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… Soluble vascular cell adhesion molecule (VCAM) is associated with treatment effects of Interferon beta-1b in patients with Secondary Progressive Multiple Sclerosis. Journal of Neurology. 2005;252(5):526–533. doi: 10.1007/s00415-005-0681-7. 133. Axtell RC, Raman C, Steinman L. …

Growth inhibition of head and neck squamous cell carcinoma cells by sgRNA targeting the cyclin D1 mRNA based on TRUE gene silencing.

Head and neck squamous cell carcinoma (HNSCC) exhibits increased expression of cyclin D1 (CCND1). Previous studies have shown a correlation between poor prognosis of HNSCC and cyclin D1 overexpression. tRNase ZL-utilizing efficacious gene silencing (TRUE gene silencing) is one of the RNA-mediated gene expression control technologies that have therapeutic potential. This technology is based on a unique enzymatic property of mammalian tRNase ZL, which is that it can cleave any target RNA at any desired site by recognizing a pre-tRNA-like complex formed between the target RNA and an artificial sm

Влияние уровня образования на задержки в диагностике и лечении при множественном склерозе: общенациональное когортное исследование в Дании.

В случае множественного склероза (MS) редко изучается градиент образования при задержках с диагностикой и корректировкой заболеваний (DMT), и результаты неоднозначны. ЦЕЛИ: Среди пациентов с повторной эмиссией MS (RRMS) мы стремились изучить градиент образования при диагностических задержках и задержках с началом первого DMT. DESIGN: Национальное когортное исследование. МЕТОДЫ: Мы увязали Датский реестр множественных склерозов с другими национальными реестрами. Диагностическая задержка была оценена в 4344 пациенты ⩾20 годы на клиническом этапе с клиническим наступлением с января 1, 2012, начин

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… DMTs in this study included ofatumumab, teriflunomide, interferon beta-1a, glatiramer acetate, interferon beta-1b, fingolimod, stem cells transplantation, alemtuzumab, rituximab, cladribine, mitoxantrone, ocrelizumab, peginterferon, human immunoglobulin, dimethyl fumarate, treosulfan, natalizumab, daclizumab …

The Clinical Application of Ozonetherapy

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Aging modulation of the immune system and immunotherapy efficacy in cancer.

Immunosenescence is characterized by immune decline and chronic inflammation. With advancing age, the incidence of tumors increases significantly. Understanding how immunosenescence influences the initiation and progression of tumors, as well as its implications for tumor immunotherapy, has become a matter of urgent importance. This review begins with an analysis of the phenotypic changes and underlying mechanisms associated with immune system and immune cell aging, and further explores the interplay between immunosenescence and tumorigenesis. Evidence indicates that cytokines, cell interactio

Future perspectives in melanoma research : Meeting report from the "Melanoma Bridge". Napoli, December 1st-4th 2015.

The sixth "Melanoma Bridge Meeting" took place in Naples, Italy, December 1st-4th, 2015. The four sessions at this meeting were focused on: (1) molecular and immune advances; (2) combination therapies; (3) news in immunotherapy; and 4) tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS) of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including

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

Potential Immunotherapy Targets for Liver-Directed Therapies, and the Current Scope of Immunotherapeutics for Liver-Related Malignancies.

Liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, is increasing in incidence and mortality across the globe. An improved understanding of the complex tumor microenvironment has opened many therapeutic doors and led to the development of novel pharmaceuticals targeting cellular signaling pathways or immune checkpoints. These interventions have significantly improved tumor control rates and patient outcomes, both in clinical trials and in real-world practice. Interventional radiologists play an important role in the multidisciplinary team given their expertise

Daratumumab in systemic lupus erythematosus: a single-arm phase 2 trial.

Antibody-secreting cells (ASCs) play a central role in the pathophysiology of systemic lupus erythematosus (SLE). This single-arm, open-label, phase 2 clinical trial aims to evaluate the safety and efficacy of the ASC-depleting anti-CD38 monoclonal antibody daratumumab in patients with SLE (NCT04810754). The primary endpoint is the reduction in serum anti-double-stranded DNA (anti-dsDNA) antibody levels at week 12. Key secondary end points include safety, clinical efficacy, and immunologic changes. Ten female patients with active disease and inadequate responses to at least two immunosuppressi

Immune Therapies for Myelodysplastic Syndromes and Acute Myeloid Leukemia.

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies arising from the bone marrow. Despite recent advances in treating these diseases, patients with higher-risk MDS and AML continue to have a poor prognosis with limited survival. It has long been recognized that there is an immune component to the pathogenesis of MDS and AML, but until recently, immune therapies have played a limited role in treating these diseases. Immune suppressive therapy exhibits durable clinical responses in selected patients with MDS, but the question of which patients are most s

Novel drug targets for personalized precision medicine in relapsed/refractory diffuse large B-cell lymphoma: a comprehensive review.

Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous lymphoid malignancy and the most common subtype of non-Hodgkin's lymphoma in adults, with one of the highest mortality rates in most developed areas of the world. More than half of DLBLC patients can be cured with standard R-CHOP regimens, however approximately 30 to 40 % of patients will develop relapsed/refractory disease that remains a major cause of morbidity and mortality due to the limited therapeutic options.Recent advances in gene expression profiling have led to the identification of at least three distinct molecular

Recent advances in the management of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease presenting highly heterogeneous clinical manifestations and multi-systemic involvement. Patients are susceptible to relapse- and remission, thus making management challenging. Moreover, a considerable number of side effects may occur with conventional therapies; therefore, there is clearly a need for new therapeutic strategies. Since the pathogenesis of SLE is highly complex, it is far from being fully understood. However, greater understanding of the pathways and of the cellular and molecular mediators involved in SLE is being