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Combinatorial Approaches for Cancer Treatment Using Oncolytic Viruses: Projecting the Perspectives through Clinical Trials Outcomes.

Recent cancer immunotherapy breakthroughs have fundamentally changed oncology and revived the fading hope for a cancer cure. The immune checkpoint inhibitors (ICI) became an indispensable tool for the treatment of many malignant tumors. Alongside ICI, the application of oncolytic viruses in clinical trials is demonstrating encouraging outcomes. Dozens of combinations of oncolytic viruses with conventional radiotherapy and chemotherapy are widely used or studied, but it seems quite complicated to highlight the most effective combinations. Our review summarizes the results of clinical trials eva

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… Other payloads include interferon-beta (INF-b) to improve oncoselectivity and stimulate the antitumor response, p53 to induce apoptosis, and MAGE-3 as one of the well-studied conservative tumor antigens—they were used in eight, six and three studies, respectively [ 42 , 171 , 230 ]. …

Drug repurposing approach to fight COVID-19.

Currently, there are no treatment options available for the deadly contagious disease, coronavirus disease 2019 (COVID-19). Drug repurposing is a process of identifying new uses for approved or investigational drugs and it is considered as a very effective strategy for drug discovery as it involves less time and cost to find a therapeutic agent in comparison to the de novo drug discovery process. The present review will focus on the repurposing efficacy of the currently used drugs against COVID-19 and their mechanisms of action, pharmacokinetics, dosing, safety, and their future perspective. R

The JAK/STAT signaling pathway: from bench to clinic.

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway was discovered more than a quarter-century ago. As a fulcrum of many vital cellular processes, the JAK/STAT pathway constitutes a rapid membrane-to-nucleus signaling module and induces the expression of various critical mediators of cancer and inflammation. Growing evidence suggests that dysregulation of the JAK/STAT pathway is associated with various cancers and autoimmune diseases. In this review, we discuss the current knowledge about the composition, activation, and regulation of the JAK/STAT pat

Can type 1 diabetes be an unexpected complication of obesity?

Type 1 diabetes (T1D) is one of the most common chronic autoimmune diseases, characterized by absolute insulin deficiency caused via inflammatory destruction of the pancreatic β-cell. Genetic, epigenetic, and environmental factors play a role in the development of diseases. Almost ⅕ of cases involve people under the age of 20. In recent years, the incidence of both T1D and obesity has been increasing, especially among children, adolescents, and young people. In addition, according to the latest study, the prevalence of overweight or obesity in people with T1D has increased significantly. The r

Лептин и Лептин Сигналинг в множестве склерозов: обзор скрипта.

Ожирение - проблема, связанная с пандемией здоровья, - в настоящее время рассматривается как хроническое провокационное состояние, связанное со многими аутоиммунными заболеваниями, такими, как множественный склероз. Таким образом, адипокины, подстрекательские посредники, скрытые жировой тканью, играют важную роль в стимулировании иммунной реакции. В этом контексте ожирение, особенно в подростковом возрасте, как представляется, является одним из ключевых факторов развития множественного склероза. Лептин, главный провоспалительный адипокин, скрытый жировой тканью, был обнаружен у пациентов с мно

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… However, it has been observed that overweight or obese individuals respond less favorably to interferon-beta treatment. … Moreover, leptin levels may be a marker of activity in treated with interferon-beta (Batocchi et al., 2003 ). Without considering obesity, no relationship with body mass index (BMI) was found. …

The trinity of T cell engagement: navigating the molecular and clinical landscape of CAR-T, TILs, and TCEs in the war against cancer.

The advent of cancer immunotherapy has fundamentally restructured the oncological paradigm, moving away from agents that directly target tumor cell kinetics toward strategies that empower the host immune system to recognize and eliminate malignancy. Central to this revolution is the cytotoxic T lymphocyte (CTL), now harnessed as a potent "living drug" through engineered and naturally selected modalities. This review provides a critical, in-depth examination of the three dominant pillars of T cell-driven therapies: Chimeric Antigen Receptor T-cell (CAR-T) therapy, Tumor-Infiltrating Lymphocyte

A systematic review of the incidence and prevalence of comorbidity in multiple sclerosis: overview.

BackgroundComorbidity is an area of increasing interest in multiple sclerosis (MS).ObjectiveThe objective of this review is to estimate the incidence and prevalence of comorbidity in people with MS and assess the quality of included studies.MethodsWe searched the PubMed, SCOPUS, EMBASE and Web of Knowledge databases, conference proceedings, and reference lists of retrieved articles. Two reviewers independently screened abstracts. One reviewer abstracted data using a standardized form and the abstraction was verified by a second reviewer. We assessed study quality using a standardized approach.

Сверхурочные проблемы с диагностикой и лечением у двух педиатрических пациентов с обширным церебральным церебральным церебральным стечением, иллюстрирующие множественный склероз типа Baló.

Концентрический склероз Бало выделяется как редкая форма множественного склероза, в котором имеются большие повреждения, подобные опухоли, которые напоминают опухоли мозга и создают значительные диагностические и терапевтические препятствия для педиатрических пациентов. КИСЛОТЫ: Мы представляем два тематических исследования педиатрических пациентов в возрасте 11 и 15 лет, у которых диагностирован обширный церебральный тюпфективный провокационный поражение, указывающий на множественный склероз (MS) типа Balo. В обоих случаях подчеркиваются уникальные проблемы, с которыми приходится сталкиваться

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… The medical team recommended interferon-beta as a long-term treatment approach, but the family wished for a new therapy that was not approved for children, and initiation was delayed with spontaneous favorable evolution. The EDSS score was systematically assessed after each relapse. … After the third episode, the family opted for a B-cell-depleting therapy instead of interferon-beta (which was the standard immunomodulatory option available in our country for pediatric MS at that time). The patient received rituximab infusions abroad. …

Supportive Treatment with Tocilizumab for COVID-19: A Systematic Review.

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Раннее переключение на атумумаб позволяет избежать эффекта возврата после прекращения родовспоможения у многих пациентов склероза.

СПРАВОЧНАЯ ИНФОРМАЦИЯ: В случае пациентов с множественным склерозом (МС) после прекращения беременности был четко выявлен риск возобновления болезни. Ряд исследований продемонстрировали низкий риск возобновления или восстановления пациентов, переходящих на антиCD20, однако имеются ограниченные данные об атумумабах. ЦЕЛЬ: В ходе настоящего исследования мы провели оценку группы из 61 пациента с НР, которые перешли от родовспоможения к atalizumab. РЕЗУЛЬТАТЫ: После среднего периода, составляющего 2,4 года (диапазон: от 6 месяцев до 4 лет), ни один из пациентов не испытывал какого-либо клиническог

Fighting the Host Reaction to SARS-COv-2 in Critically Ill Patients: The Possible Contribution of Off-Label Drugs.

The severe acute respiratory syndrome coronavirus 2 (SARS-COv-2) is the etiologic agent of the 2019 coronavirus disease (COVID19). The majority of infected people presents flu like symptoms and among them 15-20% develops a severe interstitial pneumonitis (IP) that may eventually evolve in acute respiratory distress syndrome (ARDS). IP is caused by the viral glycoprotein spike (S) binding to the angiotensin converting enzyme 2 (ACE2) expressed on the surface of alveolar pneumocytes. The virus is recognized by the "pattern recognition receptors" (PRR) of the immune cells that release cytokines a

An overview of cancer health disparities: new approaches and insights and why they matter.

Cancer health disparities remain stubbornly entrenched in the US health care system. The Affordable Care Act was legislation to target these disparities in health outcomes. Expanded access to health care, reduction in tobacco use, uptake of other preventive measures and cancer screening, and improved cancer therapies greatly reduced cancer mortality among women and men and underserved communities in this country. Yet, disparities in cancer outcomes remain. Underserved populations continue to experience an excessive cancer burden. This burden is largely explained by health care disparities, lif

Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice.

Over the past few decades, there has been growing interest in understanding the molecular mechanisms of cancer pathogenesis and progression, as it is still associated with high morbidity and mortality. Current management of large bone sarcomas typically includes the complex therapeutic approach of limb salvage or sacrifice combined with pre- and postoperative multidrug chemotherapy and/or radiotherapy, and is still associated with high recurrence rates. The development of cellular strategies against specific characteristics of tumour cells appears to be promising, as they can target cancer cel

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… Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors Cancer Res 62 2002 3603 3608 http://www.ncbi.nlm.nih.gov/pubmed/12097260 12097260 103 Horwitz E.M. Andreef M. Frassoni F. Mesenchymal Stromal Cells Biol. … Synergistic effect of therapeutic stem cells expressing cytosine deaminase and interferon-beta via apoptotic pathway in the metastatic mouse model of breast cancer Oncotarget 7 2015 www.impactjournals.com/oncotarget 10.18632/oncotarget.6719 PMC4868735 26716512 107 Matsuzuka T. Rachakatla R.S. …

Периодическая запоздалая нейтрализация после лечения атумумаба в случае множественного склероза.

ЦЕЛЬ: варианты лечения иммуномодулями при множественном склерозе свидетельствуют об обратном риске - коэффициенте выгод от побочных эффектов и эффективности лечения. Несмотря на редкие случаи, антиклеточная терапия может вызвать острую или поздние нейтропенсии. Мы сообщали о случае сильной периодически повторяющейся нейтропенсии после лечения атумумаба. Результаты: Мы наблюдали four Повторяются даже после задержки с лечением atumumumab и повторной гранулоцитовой стимуляцией (G-CSF). В общей сложности произошла нейтропенсия five Временами и были связаны с повторяющимися легочными, мочевыми трак

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

The multiple roles of interferon regulatory factor family in health and disease.

Interferon Regulatory Factors (IRFs), a family of transcription factors, profoundly influence the immune system, impacting both physiological and pathological processes. This review explores the diverse functions of nine mammalian IRF members, each featuring conserved domains essential for interactions with other transcription factors and cofactors. These interactions allow IRFs to modulate a broad spectrum of physiological processes, encompassing host defense, immune response, and cell development. Conversely, their pivotal role in immune regulation implicates them in the pathophysiology of v

Качество жизни снижается у лиц с повторно излучающимся множественным склерозом, которые развиваются независимо от рецидивной активности.

ВВЕДЕНИЕ: Снижение качества жизни (QoL) является одной из первых черт множественного склероза (MS). Воздействие прогресса, независимого от активности рецидива (ИПРА), на QoL мало изучено. ЦЕЛЬ: ОЦЕНКА ВОЗДЕЙСТВИЯ ПИРА на QOL с использованием мер конечных результатов, сообщаемых пациентами (ПРОМ). МЕТОДЫ: В перспективном исследовании 125 Число лиц, которым был поставлен диагноз " повторное образование " MS (PwRRMS) " . 5 годы с: EuroQoL-5-Dimension-3-level (В тыс.EQ-5D-3L), EQ-визуально-аналоговый масштаб (EQ-VAS) и 29-item-MS-Impact-Scale (В тыс.MSIS-29). PwRRMS был дихотомизиро

Evaluating natalizumab first-line and later-line use in multiple sclerosis: a US claims database analysis.

BACKGROUND: Limited information exists on the healthcare resource utilization (HCRU) associated with real-world natalizumab used as a first-line (1L) versus later-line (2L+) treatment in multiple sclerosis (MS). OBJECTIVES: To describe natalizumab use in newly diagnosed MS patients treated as 1L or 2L+ and evaluate unadjusted annualized relapse rates (ARR) and MS-related HCRU before and after treatment initiation. DESIGN: This retrospective observational study utilized Komodo Health Sentinel claims data from October 2015 to August 2022. The study included adults diagnosed with incident MS wh

Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells.

Hematopoietic stem cells (HSCs) are a rare subset of bone marrow cells that usually exist in a quiescent state, only entering the cell cycle to replenish the blood compartment, thereby limiting the potential for errors in replication. Inflammatory signals that are released in response to environmental stressors, such as infection, trigger active cycling of HSCs. These inflammatory signals can also directly induce HSCs to release cytokines into the bone marrow environment, promoting myeloid differentiation. After stress myelopoiesis is triggered, HSCs require intracellular signaling programs to

Alteration of SHP-1/p-STAT3 Signaling: A Potential Target for Anticancer Therapy.

The Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 1 (SHP-1), a non-receptor protein tyrosine phosphatase, has been reported as a negative regulator of phosphorylated signal transducer and activator of transcription 3 (STAT3) and linked to tumor development. In this present review, we will discuss the importance and function of SHP-1/p-STAT3 signaling in nonmalignant conditions as well as malignancies, its cross-talk with other pathways, the current clinical development and the potential role of inhibitors of this pathway in anticancer therapy and clinical relevance of SHP