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Pathogenesis of Oral Toxicities Associated with Targeted Therapy and Immunotherapy.

Targeted therapy and immunotherapy have redefined cancer treatment. While they have enhanced tumor response and improved survival rates in many cancer types, toxicities continue to occur, and these often involve the oral cavity. Broadly reported as "mucositis" or "stomatitis," oral toxicities induced by targeted therapies differ clinically and mechanistically from those associated with conventional chemotherapy. Manifesting primarily as mucosal lesions, salivary gland hypofunction, or orofacial neuropathies, these oral toxicities may nonetheless lead to significant morbidity and impact patient

CRISPR-Cas9-Mediated Gene Editing in Hematological Disorders: Advancing Translational and Clinical Applications.

Clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9)-mediated gene editing has emerged as a pivotal advancement in hematological medicine, addressing genetic and regulatory abnormalities underlying inherited and acquired blood disorders. Conventional therapeutic strategies offer symptomatic control or partial disease modification, leaving substantial unmet clinical need for durable, mechanism-driven interventions. This narrative review aims to synthesize the translational and clinical progress of CRISPR-Cas9 applications in hematological disorders, with

Перспективы Талкетамаба и его полезности в лечении множественной миеломы: безопасность, эффективность и место в терапии.

Несмотря на недавние достижения, большинство пациентов с множественной миэломой в конечном итоге развивают сопротивление имеющимся методам лечения, подчеркивая необходимость новых терапевтических стратегий. G Класс рецептора с протеиновыми соединениями C 5 Член D (GPRC5D) стал жизнеспособной новой терапевтической целью для клеток миэломы, которая привела к клиническому развитию талькетамаба, первого GPRC5D-directed bi специфичный Т-активист (TCE). В августе Талкетамаб получил ускоренное утверждение 2023 Управление по контролю за продуктами питания и лекарствами. Помимо ожидаемой краткосрочной

Indoleamine 2,3-dioxygenase 1 (IDO1) activity in leukemia blasts correlates with poor outcome in childhood acute myeloid leukemia.

Microenvironmental factors contribute to the immune dysfunction characterizing acute myeloid leukemia (AML). Indoleamine 2,3-dioxygenase 1 (IDO1) is an interferon (IFN)-γ-inducible enzyme that degrades tryptophan into kynurenine, which, in turn, inhibits effector T cells and promotes regulatory T-cell (Treg) differentiation. It is presently unknown whether childhood AML cells express IDO1 and whether IDO1 activity correlates with patient outcome. We investigated IDO1 expression and function in 37 children with newly diagnosed AML other than acute promyelocytic leukemia. Blast cells were cultur

The Relevance of Mass Spectrometry Analysis for Personalized Medicine through Its Successful Application in Cancer "Omics".

Mass spectrometry (MS) is an essential analytical technology on which the emerging omics domains; such as genomics; transcriptomics; proteomics and metabolomics; are based. This quantifiable technique allows for the identification of thousands of proteins from cell culture; bodily fluids or tissue using either global or targeted strategies; or detection of biologically active metabolites in ultra amounts. The routine performance of MS technology in the oncological field provides a better understanding of human diseases in terms of pathophysiology; prevention; diagnosis and treatment; as well a

DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome-Relevance as Complementary Prognostic Biomarkers.

Oxidative stress and abnormal DNA methylation have been implicated in cancer, including myelodysplastic syndromes (MDSs). This fact leads us to investigate whether oxidative stress is correlated with localized and global DNA methylations in the peripheral blood of MDS patients. Sixty-six MDS patients and 26 healthy individuals were analyzed. Several oxidative stress and macromolecule damage parameters were analyzed. Localized (gene promotor) and global DNA methylations (5-mC and 5-hmC levels; LINE-1 methylation) were assessed. MDS patients had lower levels of reduced glutathione and total anti

RNF25 serves as a novel diagnostic and prognostic biomarker in multiple myeloma: a multi-cohort integrative analysis.

BackgroundUbiquitination-related genes (UbRGs) play critical roles in tumor biology. However, their functions in multiple myeloma (MM) remain insufficiently explored.MethodsTranscriptomic data from public databases were integrated to identify UbRGs in MM through WGCNA, differential expression, and protein-protein interaction (PPI) analyses. Functional roles were examined by GO, KEGG, and GSEA, while immune infiltration and drug sensitivity were evaluated using CIBERSORT, ESTIMATE, and OncoPredict. UbRG expression was validated in clinical samples and cell lines by qRT-PCR and western blot, and

How I treat unique and difficult-to-manage cases of CAR T-cell therapy-associated neurotoxicity.

With growing indications for chimeric antigen receptor (CAR) T-cell therapy, toxicity profiles are evolving. There is an urgent and unmet need of approaches to optimally manage emerging adverse events that extend beyond the standard paradigm of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS). Although management guidelines exist for ICANS, there is little guidance on how to approach patients with neurologic comorbidities, and how to manage rare neurotoxicity presentations, such as CAR T-cell therapy-related cerebral edema, severe motor complications

Molecular mechanisms underlying methotrexate-induced intestinal injury and protective strategies.

Methotrexate (MTX) is a folic acid reductase inhibitor that manages various malignancies as well as immune-mediated inflammatory chronic diseases. Despite being frequently prescribed, MTX's severe multiple toxicities can occasionally limit its therapeutic potential. Intestinal toxicity is a severe adverse effect associated with the administration of MTX, and patients are significantly burdened by MTX-provoked intestinal mucositis. However, the mechanism of such intestinal toxicity is not entirely understood, mechanistic studies demonstrated oxidative stress and inflammatory reactions as key fa

Linoleate-pazopanib conjugation as active pharmacological ingredient to abolish hepatocellular carcinoma growth.

Small molecule compounds targeting multiple kinases involved in neoangiogenesis have shown survival benefits in patients with unresectable hepatocellular carcinoma (HCC). Nonetheless, despite the beneficial effects of multikinase inhibitors (MKIs), a lack of boosting adjuvant limits their objective response rate. Lipid conjugates have been used to improve delivery efficacy or pharmaceutical benefits for decades. However, the feasibility of utilizing lipid-drug conjugates (LDCs) in HCC regimens remains untested. In this study, oral feeding of linoleate-fluorescein isothiocyanate conjugates show

Modelling Gaucher disease progression: long-term enzyme replacement therapy reduces the incidence of splenectomy and bone complications.

Long-term complications and associated conditions of type 1 Gaucher Disease (GD) can include splenectomy, bone complications, pulmonary hypertension, Parkinson disease and malignancies. Enzyme replacement therapy (ERT) reverses cytopenia and reduces organomegaly. To study the effects of ERT on long-term complications and associated conditions, the course of Gaucher disease was modelled.

Совпадение в полном тексте источника
… The course of GD including the age of onset of signs and/or symptoms may be influenced by precipitating factors i.e. Epstein-Barr virus infections or pregnancy [ 1 ],[ 2 ]. …

Carfilzomib enhances cisplatin-induced apoptosis in SK-N-BE(2)-M17 human neuroblastoma cells.

Neuroblastoma is a solid malignant tumor of the sympathetic nervous system, which accounts for 8-10% of childhood cancers. Considering the overall high risk and poor prognosis associated with neuroblastoma, effective therapeutics should be developed to improve patient survival and quality of life. A recent study showed that a proteasome inhibitor, carfilzomib (CFZ), reduced cell viability of SK-N-BE(2)-M17 neuroblastoma cells. Therefore, we investigated the molecular mechanisms by which CFZ lower the cell viability of neuroblastoma cells. CFZ reduced cell viability via cell cycle arrest at G2/

Acute kidney injury: pathogenesis and therapeutic interventions.

Acute kidney injury (AKI) is a prevalent clinical condition that is associated with unacceptably high morbidity and mortality, as well as the development of chronic kidney disease (CKD). The pathogenesis of AKI is highly complex and heterogeneous, primarily attributed to metabolic disturbances arising from the disease itself and the administration of medications related to treatment. In recent years, AKI in cancer patients is highly concerned. The emergence of AKI caused injuries and dysfunction of remote organs but also enhanced the health-care costs. It's essential for early recognition of A

Efficacy and safety of antibody-drug conjugates in HER2-positive and HER2-low advanced gastric cancer: a systematic review and update.

PURPOSE: Gastric cancer is a highly prevalent malignancy of the digestive tract in China. Conventional chemotherapeutic drugs and human epidermal growth factor receptor 2 (HER2)‑targeted agents such as trastuzumab remain limited by significant challenges in the treatment of GC, including high rates of drug resistance, significant toxicity and adverse effects, and suboptimal tolerability. The advent of antibody-drug conjugates (ADCs) has marked a paradigm shift in the therapeutic landscape. This review systematically summarises the structural design, mechanisms of action, and current clinical a

Neurology

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Critically Ill Immunosuppressed Host

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Нейрогенная желудочно-кишечная, мочевая и сексуальная дисфункция при множественном склерозе: многодисциплинарная основа для клинической практики.

Нейрогенные желудочно-кишечные, мочевые и сексуальные симптомы широко распространены у людей с множественным склерозом и существенно ухудшают качество жизни, повседневное функционирование и психосоциальное благополучие. Несмотря на их частотность и клиническую актуальность, управление по-прежнему носит разрозненный характер по различным специальностям, тесная взаимосвязь между этими симптомами зачастую игнорируется, а у клинических работников отсутствует прагматическая основа, адаптированная к различным условиям здравоохранения. Этот обзор преобразует нынешние данные в прагматичную модель уход

Оптимизация доставки каннабидиол: повышение растворимости и проницаемости воды посредством фосфолипидной комплексации.

Каннабидиол (КБР) продемонстрировал терапевтический потенциал в лечении эпилепсии, множественного склероза, болезни Альцгеймера, Паркинсона и Крона. Несмотря на ее многообещающие последствия и анальгетические, антивоспалительные и аксиолитические свойства, полный потенциал КБР сдерживается низкой растворимостью воды (0,7-10 мкг/мл), низкой проницаемостью и химической нестабильностью. Цель этого исследования состояла в том, чтобы повысить проницаемость кишечника (GI) в результате распада, стабильности и проницаемости кишечника КБР путем создания комплекса КБР-фосфолипид (CBD-PLC). Мы предположи

Cardiotoxicity of Biological Therapies in Cancer Patients: An In-depth Review.

Cardiotoxicity from chemotherapy regimens has been long reported. However, the understanding of cardiac side effects of biological therapies is rapidly evolving. With cancer patients achieving higher life expectancy due to the use of personalized medicine and novel targeted anticancer agents, the occurrence of cardiotoxicity is becoming more significant. Novel biological therapies include anti-HER2 antibodies, tyrosine kinase inhibitors, bruton kinase inhibitors, antivascular endothelial growth factors, proteasome inhibitors, immunomodulator drugs, and immune checkpoint inhibitors. Potential c

What Are the Peripheral Blood Determinants for Increased Osteoclast Formation in the Various Inflammatory Diseases Associated With Bone Loss?

Local priming of osteoclast precursors (OCp) has long been considered the main and obvious pathway that takes place in the human body, where local bone lining cells and RANKL-expressing osteocytes may facilitate the differentiation of OCp. However, priming of OCp away from bone, such as in inflammatory tissues, as revealed in peripheral blood, may represent a second pathway, particularly relevant in individuals who suffer from systemic bone loss such as prevalent in inflammatory diseases. In this review, we used a systematic approach to review the literature on osteoclast formation in peripher