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Defining neuroblastoma: From origin to precision medicine.

Neuroblastoma (NB), a heterogenous pediatric tumor of the sympathetic nervous system, is the most common and deadly extracranial solid malignancy diagnosed in infants. Numerous efforts have been invested in understanding its origin and in development of novel curative targeted therapies. Here, we summarize the recent advances in the identification of the cell of origin and the genetic alterations occurring during development that contribute to NB. We discuss current treatment regimens, present and future directions for the identification of novel therapeutic metabolic targets, differentiation

Project EVOLVE: an international analysis of postimmunotherapy lineage switch, an emergent form of relapse in leukemia.

AbstractLineage switch (LS), defined as the immunophenotypic transformation of acute leukemia, has emerged as a mechanism of relapse after antigen-targeted immunotherapy, which is associated with dismal outcomes. Through an international collaborative effort, we identified cases of LS after a host of antigen-targeted therapies (eg, CD19, CD22, CD38, and CD7), described how LS was diagnosed, reviewed treatment approaches, and analyzed overall outcomes for this form of postimmunotherapy relapse. Collectively, 75 cases of LS were evaluated, including 53 (70.7%) cases of B-cell acute lymphoblastic

Combating Methotrexate Resistance in Cancer Treatment: A Review on Navigating Pathways and Enhancing Its Efficacy With Fat-Soluble Vitamins.

Methotrexate (MTX), a potent analogue and antagonist of folic acid, is a first-line treatment for rheumatoid arthritis, IBD and cancer. The development of MTX resistance contributes to the reduced efficacy and development of adverse reactions, forcing clinicians to withdraw treatment early. This drawback requires combinational approaches to combat the resistance and enhance the efficacy and safety of MTX. To provide a brief overview of MTX resistance and strategies to mitigate its aftereffects in cancer therapy, a literature-based search was conducted using keywords such as cancer pathology, M

State of the Art of Pharmacological Activators of p53 in Ocular Malignancies.

The pivotal role of p53 in the regulation of a vast array of cellular functions has been the subject of extensive research. The biological activity of p53 is not strictly limited to cell cycle arrest but also includes the regulation of homeostasis, DNA repair, apoptosis, and senescence. Thus, mutations in the p53 gene with loss of function represent one of the major mechanisms for cancer development. As expected, due to its key role, p53 is expressed throughout the human body including the eye. Specifically, altered p53 signaling pathways have been implicated in the development of conjunctival

Многомерное профилирование и модели риска, основанные на клиническом развертывании АИ, в МГУС и миеломе.

Моноклональная гаммопатия неопределённого значения (MGUS), храпающая миелома (SMM) и множественная миелома (MM) образуют континуум расстройств плазменных клеток, причем прогрессировать от MGUS до MM трудно предсказать. Нынешние модели стратификации риска, в значительной степени основанные на клинических, лабораторных и цитогенетических маркерах, не отражают молекулярную сложность, лежащую в основе развития заболеваний, что ограничивает их прогнозную точность. Последние достижения в области мультиомики, включая геномику, транскриптомику, протеомику и метаболомику, позволили глубже понять молеку

Cancer-Induced Cardiac Dysfunction: Mechanisms, Diagnostics, and Emerging Therapeutics in the Era of Onco-Cardiology.

Cancer-induced cardiac dysfunction has become a major clinical challenge as advances in cancer therapies continue to extend patient survival. Once regarded as a secondary concern, cardiotoxicity is now recognized as a leading contributor to morbidity and mortality among cancer patients and survivors. Its pathophysiology is multifactorial, involving systemic inflammation (e.g., TNF-α, IL-6), oxidative stress driven by reactive oxygen species (ROS), neurohormonal imbalances (e.g., angiotensin II, endothelin-1), and metabolic disturbances. These mechanisms collectively promote cardiomyocyte apopt

Vitamin D: A Bridge between Kidney and Heart.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factors, such as hypertension, diabetes, obesity, and smoking, among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CV

Совпадение в полном тексте источника
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PET Molecular Imaging: A Holistic Review of Current Practice and Emerging Perspectives for Diagnosis, Therapeutic Evaluation and Prognosis in Clinical Oncology.

PET/CT molecular imaging has been imposed in clinical oncological practice over the past 20 years, driven by its two well-grounded foundations: quantification and radiolabeled molecular probe vectorization. From basic visual interpretation to more sophisticated full kinetic modeling, PET technology provides a unique opportunity to characterize various biological processes with different levels of analysis. In clinical practice, many efforts have been made during the last two decades to standardize image analyses at the international level, but advanced metrics are still under use in practice.

От статического риска до динамического мониторинга заболеваний: роль MRD и иммунного профилирования в множестве миелом.

Терапевтический ландшафт множественной миеломы (ММ) претерпел глубокие изменения, при этом высокоэффективные комбинированные режимы и иммунная терапия позволили обеспечить беспрецедентные темпы глубоких и устойчивых ответных мер. В результате этого одной традиционной стратификации базовых рисков становится все более недостаточно для объяснения неоднородности клинических результатов или для направления лечения на протяжении всего курса лечения. Эта эволюционирующая парадигма сместила внимание на динамическое, адаптированное к реакциям наблюдение за заболеваниями, сосредоточенное на поддающихся

Emerging Role of Epigenetic Modifiers in Breast Cancer Pathogenesis and Therapeutic Response.

Breast cancer pathogenesis, treatment, and patient outcomes are shaped by tumor-intrinsic genomic alterations that divide breast tumors into molecular subtypes. These molecular subtypes often dictate viable therapeutic interventions and, ultimately, patient outcomes. However, heterogeneity in therapeutic response may be a result of underlying epigenetic features that may further stratify breast cancer patient outcomes. In this review, we examine non-genetic mechanisms that drive functional changes to chromatin in breast cancer to contribute to cell and tumor fitness and highlight how epigeneti

Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.

Temozolomide (TMZ) remains the cornerstone chemotherapy for glioma, yet intrinsic and acquired resistance mechanisms significantly limit its clinical effectiveness. This review summarizes the multifaceted molecular pathways contributing to TMZ resistance, including enhanced DNA repair mechanisms such as O6-methylguanine-DNA methyltransferase (MGMT), mismatch repair (MMR), and base excision repair (BER). Additional resistance factors include genetic mutations that affect the drug response, dysregulated non-coding RNAs (miRNAs, lncRNAs, and circRNAs), glioma stem cells (GSCs), cytoprotective aut

Immunotherapy for pediatric solid tumors: overcoming biological barriers through rational multimodal combinations.

Pediatric solid tumors remain among the most treatment-refractory childhood malignancies, defined by biological features that have largely resisted the immunotherapeutic advances transforming adult oncology. Exceptionally low tumor mutational burden, sparse neoantigen landscapes, and profoundly immunosuppressive tumor microenvironments collectively undermine the T cell-dependent mechanisms on which most current immunotherapies depend. Yet the field is undergoing a meaningful shift. Anti-GD2 monoclonal antibodies have established a survival benchmark in high-risk neuroblastoma, and next-generat

Reprogramming of nitrogen metabolism in tumors: mechanisms and therapeutic implications.

Nitrogen metabolism plays a key role in maintaining normal physiological functions of the organism and cell proliferation and differentiation. Nitrogen metabolism in normal human body maintains a dynamic balance to meet the body's demand for synthesis of biological macromolecules such as proteins and nucleic acids. However, in the process of tumor development, the nitrogen metabolism of tumor cells is reprogrammed to meet the demand of rapid proliferation, showing significantly different metabolic characteristics from normal cells. Key enzymes in the tumor microenvironment affect nitrogen meta

Hallmarks of Cancer Affected by the MIF Cytokine Family.

New diagnostic methods and treatments have significantly decreased the mortality rates of cancer patients, but further improvements are warranted based on the identification of novel tumor-promoting molecules that can serve as therapeutic targets. The macrophage migration inhibitory factor (MIF) family of cytokines, comprising MIF and DDT (also known as MIF2), are overexpressed in almost all cancer types, and their high expressions are related to a worse prognosis for the patients. MIF is involved in 9 of the 10 hallmarks of cancer, and its inhibition by antibodies, nanobodies, or small synthe

Одноклеточная транскриптомика для иммунного профилирования цереброспинной жидкости в неврологических заболеваниях.

В ходе этого всеобъемлющего обзора мы прорабатываем значительный объем исследований по одноклеточной транскриптомике в цереброспайнальной жидкости (CSF) для понимания неврологических заболеваний с аутоиммунным, нейродегенеративным, инфекционным или онкогенным происхождением. Мы тщательно изучаем все опубликованные исследования в этих областях с особым акцентом на множественный склероз, болезнь Альцгеймера и болезнь Паркинсона. Что касается этих заболеваний, то мы анализируем результаты, связанные с иммунными клетками, проникающими в мозг, на основе вскрытого анализа тканей мозга и с использова

Acute myeloid leukemia: from NGS, through scRNA-seq, to CAR-T. dissect cancer heterogeneity and tailor the treatment.

Acute myeloid leukemia (AML) is a malignant blood cancer with marked cellular heterogeneity due to altered maturation and differentiation of myeloid blasts, the possible causes of which are transcriptional or epigenetic alterations, impaired apoptosis, and excessive cell proliferation. This neoplasm has a high rate of resistance to anticancer therapies and thus a high risk of relapse and mortality because of both the biological diversity of the patient and intratumoral heterogeneity due to the acquisition of new somatic changes. For more than 40 years, the old gold standard "one size fits all"

Cellular Senescence and the Kidney: Potential Therapeutic Targets and Tools.

Chronic kidney disease (CKD) is an increasing health burden (affecting approximately 13.4% of the population). Currently, no curative treatment options are available and treatment is focused on limiting the disease progression. The accumulation of senescent cells has been implicated in the development of kidney fibrosis by limiting tissue rejuvenation and through the secretion of pro-fibrotic and pro-inflammatory mediators termed as the senescence-associated secretory phenotype. The clearance of senescent cells in aging models results in improved kidney function, which shows promise for the op

Reframing small cell lung cancer: therapeutic lessons from hematologic malignancies.

Small cell lung cancer (SCLC) remains one of the most aggressive malignancies, characterized by rapid proliferation, early metastatic dissemination, and poor long-term survival despite initial sensitivity to therapy. SCLC shares several biologic and therapeutic principles with hematologic malignancies, including lineage state dependence, adaptive resistance through non-genetic plasticity, and emerging susceptibility to antigen-directed immune therapies. Reframing SCLC through this lens provides a conceptual framework for understanding treatment failure and identifying new therapeutic strategie

Пространственные омики нейроинфламмации: осмысления заболеваний мозга.

Нейроинфламмация является общей патологической особенностью различных заболеваний мозга, однако подстрекательская активность редко распределяется равномерно по заболевшим тканям. Вместо этого микроглии, астроциты, проникающие в иммунные клетки и подстрекательские посредники, часто организуются вокруг конкретных патологических структур, включая амилоидные таблетки, демиелинированные поражающие ободья, ишемические границы, некротические области опухоли и белые отсеки периваскулярной материи. Хотя в рамках одноклеточных подходов, основанных на оптовых и диссоциационных подходах, было определено м

Lithium: A Promising Anticancer Agent.

Lithium is a therapeutic cation used to treat bipolar disorders but also has some important features as an anti-cancer agent. In this review, we provide a general overview of lithium, from its transport into cells, to its innovative administration forms, and based on genomic, transcriptomic, and proteomic data. Lithium formulations such as lithium acetoacetate (LiAcAc), lithium chloride (LiCl), lithium citrate (Li3C6H5O7), and lithium carbonate (Li2CO3) induce apoptosis, autophagy, and inhibition of tumor growth and also participate in the regulation of tumor proliferation, tumor invasion, and