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CKD-5, a novel pan-histone deacetylase inhibitor, synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma.

BackgroundHistone deacetylase inhibitors (HDACIs) have distinctive epigenetic targets involved in hepatocarcinogenesis and chemoresistance. A recent phase I/II study reported the possibility of HDACI as a chemosensitizer in sorafenib-resistant patients. In this study, we evaluated whether CKD-5, a novel pan-HDACI, can potentiate the efficacy of sorafenib.MethodsThe anticancer effect of CKD-5 with and without sorafenib was evaluated in vitro using an MTS assay with human HCC cells (SNU-3058 and SNU-761) under both normoxic and hypoxic conditions. Microarray analysis was performed to investigate

The use of RNA-based treatments in the field of cancer immunotherapy.

Over the past several decades, mRNA vaccines have evolved from a theoretical concept to a clinical reality. These vaccines offer several advantages over traditional vaccine techniques, including their high potency, rapid development, low-cost manufacturing, and safe administration. However, until recently, concerns over the instability and inefficient distribution of mRNA in vivo have limited their utility. Fortunately, recent technological advancements have mostly resolved these concerns, resulting in the development of numerous mRNA vaccination platforms for infectious diseases and various t

Hepatocellular carcinoma: Understanding molecular mechanisms for defining potential clinical modalities.

Liver cancer is the sixth most commonly occurring cancer and costs millions of lives per year. The diagnosis of hepatocellular carcinoma (HCC) has relied on scanning techniques and serum-based markers such as α-fetoprotein. These measures have limitations due to their detection limits and asymptomatic conditions during the early stages, resulting in late-stage cancer diagnosis where targeted chemotherapy or systemic treatment with sorafenib is offered. However, the aid of conventional therapy for patients in the advanced stage of HCC has limited outcomes. Thus, it is essential to seek a new tr

[XVIII Митинг после ECTRIMS: Обзор новых разработок, представленных на Конгресс ECTRIMS 2025 (Часть I)]

18-е издание совещания Европейского комитета по лечению и исследованию множественной скlerоза (ECTRIMS) прошло 17-18 октября 2025 года в Мадриде, объединив испанских нейрологов, специализирующихся на множественной склерозе (МС), которые представили наиболее значимые достижения, обсуждённые на конгрессе ECTRIMS несколько дней ранее в Барселоне. Целью собрания было обобщить последние достижения в патогенезе, новые критерии диагностики и биомаркеры МС. Эта статья является первой частью двухчастной серии (I и II), которая обзором последних данных о транспортировке клеток в центральную нервную сист

Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network.

During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved the treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drug classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events.

Острая поздняя нейтропения у беременной пациентки с множественным склерозом после Оклелизумаба.

ВВЕДЕНИЕ: &lt; &lt; Окрелизумаб &gt; &gt; является рекомбинантом, очеловеченным anti-CD20 Моноклональная антитела лечила множественный склероз. Запоздалая нейтроплания, абсолютное число нейтрофильов <1.5 × 109/L, развивающийся >4 Неделю спустя после последней наркодирекции известное неблагоприятное событие, связанное с anti-CD20 моноклонные антитела, включая ritoximab и ocrelizumab. ПРЕДСТАВЛЕНИЕ СЛЕДУЮЩЕЙ СЛЕДУЮЩЕЙ ГРУППЫ: 27-year-old Женщина, разработавшая серьёзную нейтрализацию в течение третьего триместра беременности после лечения острелизумомb 6 Несколько месяцев назад.ЗАКЛЮЧЕНИЕ: Невро

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… Due to positive JC virus seroconversion in November 2019, natalizumab was discontinued and ocrelizumab started. When her first pregnancy was confirmed, therapy with ocrelizumab was paused and subsequently resumed postpartum. …

Immunosuppression in Glomerular Diseases: Implications for SARS-CoV-2 Vaccines and COVID-19.

BackgroundGlomerular diseases (GD) are chronic conditions that often involve immune dysfunction and require immunosuppressive therapy (IST) to control underlying pathogenesis. Unfortunately, such diseases appear to heighten risks of severe outcomes in COVID-19 and predispose to other infections that may be life-threatening. Thus, averting preventable infections is imperative in GD patients.SummaryThe advent of vaccines demonstrated to be safe and efficacious against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has favorably impacted the COVID-19 pandemic epidemiology. However,

Imiglucerase in the treatment of Gaucher disease: a history and perspective.

The scientific and therapeutic development of imiglucerase (Cerezyme(®)) by the Genzyme Corporation is a paradigm case for a critical examination of current trends in biotechnology. In this article the authors argue that contemporary interest in treatments for rare diseases by major pharmaceutical companies stems in large part from an exception among rarities: the astonishing commercial success of Cerezyme. The fortunes of the Genzyme Corporation, latterly acquired by global giant Sanofi SA, were founded on the evolution of a blockbuster therapy for a single but, as it turns out, propitious ul

Carcinoembryonic antigen-expressing oncolytic measles virus derivative in recurrent glioblastoma: a phase 1 trial.

Measles virus (MV) vaccine strains have shown significant preclinical antitumor activity against glioblastoma (GBM), the most lethal glioma histology. In this first in human trial (NCT00390299), a carcinoembryonic antigen-expressing oncolytic measles virus derivative (MV-CEA), was administered in recurrent GBM patients either at the resection cavity (Group A), or, intratumorally on day 1, followed by a second dose administered in the resection cavity after tumor resection on day 5 (Group B). A total of 22 patients received study treatment, 9 in Group A and 13 in Group B. Primary endpoint was s

Lipid nanoparticles for targeted siRNA delivery - going from bench to bedside.

This review covers the basic aspects of small interfering RNA delivery by lipid nano-particles (LNPs) and elaborates on the current status of clinical trials for these systems. We briefly describe the roles of all LNP components and possible strategies for their improvement. We also focus on the current clinical trials using LNP-formulated RNA and the possible outcomes for therapy in the near future. Also, we present a critical analysis of selected clinical trials that reveals the common logic behind target selection. We address this review to a wide audience, especially to medical doctors who

Тенденции заболеваемости астмой, аптечным дерматитом и множественным склерозом до, во время и после COVID-19 Пандемия в базе данных о претензиях США.

Имеются лишь ограниченные данные о том, каким образом сокращение использования ресурсов здравоохранения в период COVID-19 Пандемия повлияла на выявление подстрекательских и иммунологических заболеваний. Мы стремились описать наблюдаемые показатели заболеваемости (ИР) астмой, атомным дерматитом (АД) и множественным склерозом (МС) до, во время и после пандемии. Лица пожилого возраста ≥6 Годы были определены в базе данных Optum, в которой не были указаны данные по клинформатике. 2018 в адрес 2022 для изготовления 20 сезонные когорты. Была проведена оценка ИП астмы, AD и MS с разбивкой по возрасту

Treatment of Psoriasis with Secukinumab in Challenging Patient Scenarios: A Review of the Available Evidence.

Psoriasis (PsO) is a common, systemic, chronic, inflammatory disease characterized by key clinical symptoms, including itching, pain, and scaling. PsO is associated with a high prevalence of comorbidities, including other autoimmune diseases and malignancies. Furthermore, special populations, such as pregnant, pediatric, and elderly patients, and those with erythrodermic PsO, are challenging to treat and require tightly monitored disease and treatment management. Because certain populations have demographic or clinical characteristics that can affect the presentation of PsO and complicate trea

Nucleo-cytoplasmic transport as a therapeutic target of cancer.

Shuttling of specific proteins out of the nucleus is essential for the regulation of the cell cycle and proliferation of both normal and malignant tissues. Dysregulation of this fundamental process may affect many other important cellular processes such as tumor growth, inflammatory response, cell cycle, and apoptosis. It is known that XPO1 (Exportin-1/Chromosome Region Maintenance 1/CRM1) is the main mediator of nuclear export in many cell types. Nuclear proteins exported to the cytoplasm by XPO1 include the drug targets topoisomerase IIα (topo IIα) and BCR-ABL and tumor suppressor proteins s

Toxicities of Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma: An Overview of Experience From Clinical Trials, Pathophysiology, and Management Strategies.

In the last few years, monoclonal antibodies (mAbs) such as elotuzumab and daratutumab have brought the treatment of multiple myeloma (MM) into the new era of immunotherapy. More recently, chimeric antigen receptor (CAR) modified T cell, a novel cellular immunotherapy, has been developed for treatment of relapsed/refractory (RR) MM, and early phase clinical trials have shown promising efficacy of CAR T cell therapy. Many patients with end stage RRMM regard CAR T cell therapy as their "last chance" and a "hope of cure". However, severe adverse events (AEs) and even toxic death related to CAR T

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… Indeed, progressive multifocal leukoencephalopathy (PML) caused by JC virus and fatal cerebral hemorrhage have already been observed in patients treated with CAR T cells ( 70 , 131 ). …

One Giant Step for Giant Cell Arteritis: Updates in Diagnosis and Treatment.

Purpose of reviewGiant cell arteritis (GCA), a medium and large vessel vasculitis occurring in the aged, remains a formidable disease, capable of taking both vision and life, through a multitude of vascular complications. Our understanding of the spectrum of its manifestations has grown over the years, to include limb claudication, aortitis, and cardiac disease, in addition to the more classic visual complications resulting from of ischemia to branches of the external and internal carotid arteries. While a clinical presentation of headache, jaw claudication, scalp tenderness, fever and other s

Acute Kidney Injury Associated with Anticancer Therapies: Small Molecules and Targeted Therapies.

Molecular targeted therapy has revolutionized cancer treatment by significantly improving patient survival compared with standard conventional chemotherapies. The use of these drugs targets specific molecules or targets, which block growth and spread of cancer cells. Many of these therapies have been approved for use with remarkable success in breast, blood, colorectal, lung, and ovarian cancers. The advantage over conventional chemotherapy is its ability to deliver drugs effectively with high specificity while being less toxic. Although known as "targeted," many of these agents lack specifici

Биоинформатический анализ взаимодействия миелинов и микробов говорит о том, что в патогенезе множественных склерозов присутствуют различные виды молекулярной имитации.

Множественный склероз (MS) — разрушительная аутоиммунная болезнь, приводящая к разрушению милиновой оболочки в центральной нервной системе человека (КНС). Было установлено, что инфекция вирусов и бактерий тесно связана с наступлением мороза или его остротой. Мы предположили, что атака иммунной системы на милиновую оболочку может быть спровоцирована вирусами и бактериальными антигенами, которые напоминают компоненты миелиновой оболочки. Для выявления вирусных и бактериальных антигенов, похожих на миелин олигодендроцит гликпротеин (МОГ) и миелинский основной протеин (МБП), был применен подход, о

TNFα inhibitors as targets for protective therapies in MSA: a viewpoint.

Multiple system atrophy (MSA) is a unique and fatal α-synucleinopathy associated with oligodendroglial inclusions and secondary neurodegeneration affecting striatum, substantia nigra, pons, and cerebellum. The pathogenesis remains elusive; however, there is emerging evidence suggesting a prominent role of neuroinflammation. Here, we critically review the relationship between αS and microglial activation depending on its aggregation state and its role in neuroinflammation to explore the potential of TNFα inhibitors as a treatment strategy for MSA and other neurodegenerative diseases.

Central pain processing in chronic chemotherapy-induced peripheral neuropathy: a functional magnetic resonance imaging study.

Life expectancy in multiple myeloma has significantly increased. However, a high incidence of chemotherapy induced peripheral neuropathy (CIPN) can negatively influence quality of life during this period. This study applied functional magnetic resonance imaging (fMRI) to compare areas associated with central pain processing in patients with multiple myeloma who had chemotherapy induced peripheral neuropathy (MM-CIPN) with those from healthy volunteers (HV). Twenty-four participants (n = 12 MM-CIPN, n = 12 HV) underwent Blood Oxygen Level-Dependent (BOLD) fMRI at 3T whilst noxious heat-pain sti

Recommendations on the follow-up of patients with Gaucher disease in Spain: Results from a Delphi survey.

Management of Gaucher disease (GD) is challenging due to its wide genotypic and phenotypic variability and changing clinical manifestations due to effective treatment. Sixteen face-to-face meetings with experts were held in order to discuss daily clinical practice and identify controversies regarding the management of GD. With this information, a questionnaire with 93 recommendations for different clinical scenarios was designed, and a Delphi survey among 86 physicians with experience in GD was conducted. Consensus was reached on 73 out of the 93 items. Recommendations on follow-up of adult an