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The evolving global landscape of first-in-class oncology drug innovation.

First-in-class (FIC) oncology drugs-defined by their novel mechanisms of action or targeting of previously unaddressed molecular targets-have emerged as a leading force in cancer therapeutic innovation. In this Review, we delineate the global landscape of FIC oncology drug approvals between 2009 and 2024 and analyze the evolving characteristics of both approved FIC therapies and potential FIC (PFIC) candidates in clinical development. To clarify the underlying dynamics of this evolution, we construct an analytic framework encompassing four distinct archetypes of FIC development: new targets, n

Роль микроглии в множественном склерозе: последствия для лечения ингибиторами тиросина Брютона.

Множественный склероз (MS) — хроническое аутоиммунное заболевание, затрагивающее центральную нервную систему (CNS), характеризующееся воспалением и нейродегенерацией. Патофизиология MS, особенно его прогрессивные формы, включает различные клеточные компоненты, включая микроглию, являющиеся основными постоянными иммунными клетками CNS. В настоящем обзоре рассматривается роль микроглии в нейроинфламмации, ремонте тканей и нейронном гомеостазе, а также их участие в MS и изучаются потенциальные терапевтические стратегии, ориентированные на микроглиальную функцию.МЕТОДЫ: Поиск литературы, проведенн

Clinical Insights Into Novel Immune Checkpoint Inhibitors.

The success of immune checkpoint inhibitors (ICIs), notably anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) as well as inhibitors of CTLA-4, programmed death 1 (PD-1), and programmed death ligand-1 (PD-L1), has revolutionized treatment options for solid tumors. However, the lack of response to treatment, in terms of de novo or acquired resistance, and immune related adverse events (IRAE) remain as hurdles. One mechanisms to overcome the limitations of ICIs is to target other immune checkpoints associated with tumor microenvironment. Immune checkpoints such as lymphocyte activation ge

The dual balance of the cytokine network: key messengers of immune activation and triggers of cytokine storm.

The cytokine network is the central regulatory system for intercellular communication within the immune system. Its proper function depends on the dynamic balance between pro-inflammatory and anti-inflammatory cytokines. Through complex positive and negative feedback loops, this balance precisely regulates the intensity and duration of immune responses, thereby playing a critical role in both physiological and pathological states. This review systematically summarizes the compositional features and classification framework of the cytokine network, as well as the mechanisms by which it maintain

Galectin Targeted Therapy in Oncology: Current Knowledge and Perspectives.

The incidence and mortality of cancer have increased over the past decades. Significant progress has been made in understanding the underpinnings of this disease and developing therapies. Despite this, cancer still remains a major therapeutic challenge. Current therapeutic research has targeted several aspects of the disease such as cancer development, growth, angiogenesis and metastases. Many molecular and cellular mechanisms remain unknown and current therapies have so far failed to meet their intended potential. Recent studies show that glycans, especially oligosaccharide chains, may play a

Комплексный метаанализ транскриптомов астроцитов человека показывает, что в ответ на подстрекательские и иммунные стимулы потенциальные признаки повторяются.

Астроциты являются ключевыми регуляторами подстрекательской и иммунной реакции в центральной нервной системе, особенно в патологических условиях. Мы проводили систематический поиск баз данных НКОИ по ГЭП и ЭНА в целях выявления транскриптивных исследований стимулируемых астроцитов. Этот метаанализ объединяет 11 наборов данных RNA-Seq, охватывающих в общей сложности 153 пробы (91 стимулируемый и 62 средства контроля), подвергающиеся воздействию провоспалительных стимулов, таких, как цитокины (TNF-α, IL-6 и IL-1β), пальмовая кислота и патогены, такие, как SARS-COV-2 и Borrelia burborferi. Благод

Advances in Leukemia detection and classification: A Systematic review of AI and image processing techniques.

BACKGROUND: Leukemia, a heterogeneous group of blood cancers, poses significant challenges to global health due to its complexity, diverse risk factors, and variable outcomes. Accurate and early diagnosis is critical but remains a significant hurdle, particularly in low-resource settings. Recent advancements in artificial intelligence (AI) and image processing offer transformative solutions to improve leukemia detection and classification, addressing limitations in traditional diagnostic methods. METHODS: This study systematically reviewed over 25,000 scientific articles sourced from Scopus,

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… The extracted features are then fused using Canonical Correlation Analysis (CCA) to improve the discriminative power of the features. … Correlation Analysis (CCA), Bagging Ensemble classifier | Dataset of 4150 images | 97.04% accuracy (Bagging Ensemble) | 33 Shafique and Tehsin (2018) | ALL Detection and Classification Using AlexNet | Transfer learning with AlexNet (five convolutional layers, three fully connected layers), data augmentation …

Corneal Findings in Patients Treated with Belantamab Mafodotin: A Prospective Case Series Focusing on Corneal Nerves.

IntroductionThis prospective case series investigated corneal epithelial and subbasal nerve plexus changes associated with belantamab mafodotin (Belamaf) therapy in patients with refractory/relapsed multiple myeloma using a multimodal imaging approach.MethodsWe included eight patients (mean age 66 ± 10) scheduled for Belamaf who were monitored for at least three treatment cycles. Standard clinical eye exams with Snellen best corrected visual acuity (BCVA) measurements were complemented by epithelial thickness mapping, slit lamp photography, corneal sensitivity testing, and corneal confocal mic

Ubiquitylomics: An Emerging Approach for Profiling Protein Ubiquitylation in Skeletal Muscle.

Skeletal muscle is a highly adaptable tissue, finely tuned by various physiological and pathological factors. Whilst the pivotal role of skeletal muscle in overall health is widely acknowledged, unravelling the underlying molecular mechanisms poses ongoing challenges. Protein ubiquitylation, a crucial post-translational modification, is involved in regulating most biological processes. This widespread impact is achieved through a diverse set of enzymes capable of generating structurally and functionally distinct ubiquitin modifications on proteins. The complexity of protein ubiquitylation has

Tumor microenvironment signaling and therapeutics in cancer progression.

Tumor development and metastasis are facilitated by the complex interactions between cancer cells and their microenvironment, which comprises stromal cells and extracellular matrix (ECM) components, among other factors. Stromal cells can adopt new phenotypes to promote tumor cell invasion. A deep understanding of the signaling pathways involved in cell-to-cell and cell-to-ECM interactions is needed to design effective intervention strategies that might interrupt these interactions. In this review, we describe the tumor microenvironment (TME) components and associated therapeutics. We discuss t

The Adiponectin-AdipoR1 Axis Mediates Tumor Progression and Tyrosine Kinase Inhibitor Resistance in Metastatic Renal Cell Carcinoma.

The survival of patients diagnosed with metastatic renal cell carcinoma (RCC) is still limited and the current targeted therapies are only partially effective. Herein, we investigated the clinical value and functions of adiponectin receptors (AdipoR1 and AdipoR2) in metastatic renal cell carcinoma (RCC) patients treated with tyrosine kinase inhibitors (TKIs). A total of 127 mRCC patients treated with first-line TKIs between 2008 and 2017 at a single institution were collected. AdipoR1 and AdipoR2 expression was assessed by immunohistochemistry. AdipoR1 was positively expressed in 87.4% (111/12

VP3.15, двойной ингибитор GSK-3β/PDE7, уменьшает рост опухоли глиобластомы, изменяя микроопухоль в контексте PTEN дикой природы.

Глиобластома (ГБ) — неизлечимый рак мозга, и необходимо срочно определить эффективные методы лечения. Это может быть достигнуто либо путем идентификации новых молекул, либо путем переочистки наркотиков. Для определения терапевтического потенциала известных ингибиторов GSK-3β и/или PDE7 в GB был проведен анализ наркотиков с использованием модели глиомы Дрософила меланогастера. VP3.15, двойной ингибитор с противовоспалительными и нейрозащитными функциями при множественном склерозе, был выбран для дальнейшего изучения. VP3.15 продемонстрировал высокую антиопухоль против панели клеток человека и м

The complex regulation of TGF-β in cardiovascular disease.

Transforming growth factor β (TGF-β1) is a pleiotropic cytokine with many and complex effects in cell and tissue physiology. This is made possible by a very complex and interwoven signaling system, whose regulation continues to be the focus of a growing line of research. This complex regulation translates to a key role in cardiovascular physiology, hemostasis, and the blood-vessel interface. In accordance with this, the TGF-β1 pathway appears to be deregulated in related disorders, such as atherosclerotic vascular disease and myeloproliferative syndromes. It is expected that the growing amount

Targeting strategies for bone diseases: signaling pathways and clinical studies.

Since the proposal of Paul Ehrlich's magic bullet concept over 100 years ago, tremendous advances have occurred in targeted therapy. From the initial selective antibody, antitoxin to targeted drug delivery that emerged in the past decades, more precise therapeutic efficacy is realized in specific pathological sites of clinical diseases. As a highly pyknotic mineralized tissue with lessened blood flow, bone is characterized by a complex remodeling and homeostatic regulation mechanism, which makes drug therapy for skeletal diseases more challenging than other tissues. Bone-targeted therapy has b

Molecular classification of gastric cancer: Towards a pathway-driven targeted therapy.

Gastric cancer (GC) is the third leading cause of cancer mortality worldwide. Although surgical resection is a potentially curative approach for localized cases of GC, most cases of GC are diagnosed in an advanced, non-curable stage and the response to traditional chemotherapy is limited. Fortunately, recent advances in our understanding of the molecular mechanisms that mediate GC hold great promise for the development of more effective treatment strategies. In this review, an overview of the morphological classification, current treatment approaches, and molecular alterations that have been c

Cataract Induced by Glucocorticoids.

Glucocorticoids (GCs) remain a cornerstone therapy for noninfectious uveitis and autoimmune disorders; however, chronic administration is strongly associated with sight-threatening complications, particularly glucocorticoid-induced cataracts (GIC). This comprehensive review synthesizes current evidence on the molecular pathogenesis, epidemiological patterns, and clinical management of GIC. Epidemiological analyses indicate that over 50% of patients receiving systemic corticosteroids for >60 days develop ocular complications, with cataract formation (36%) and glaucoma (16%) representing the pre

Cutting edge developments in bone oncology - Highlights from the Cancer and Bone Society 2024 annual meeting.

The 2024 Annual Conference of the Cancer and Bone Society (CABS), held jointly with the Bone Research Society at the University of Sheffield, highlighted the Society's enduring mission to advance understanding of cancer-bone interactions through collaboration, mentorship, and scientific excellence. Established from the early Cancer Induced Bone Disease meetings and re-emerging as an independent body in 2016, CABS continues to serve as a global community bridging basic, translational, and clinical research. This year's meeting featured a comprehensive scientific program spanning tumor-bone biol

Exploratory Analysis of Circulating miRNA Signatures in Atrial Fibrillation Patients Determining Potential Biomarkers to Support Decision-Making in Anticoagulation and Catheter Ablation.

Novel biomarkers are desired to improve risk management for patients with atrial fibrillation (AF). We measured 179 plasma miRNAs in 83 AF patients using multiplex qRT-PCR. Plasma levels of eight (i.e., hsa-miR-22-3p, hsa-miR-128-3p, hsa-miR-130a-3p, hsa-miR-140-5p, hsa-miR-143-3p, hsa-miR-148b-3p, hsa-miR-497-5p, hsa-miR-652-3p) and three (i.e., hsa-miR-144-5p, hsa-miR-192-5p, hsa-miR-194-5p) miRNAs showed positive and negative correlations with CHA2DS2-VASc scores, respectively, which also showed negative and positive correlations with catheter ablation (CA) procedure, respectively, within t

A thirteen-gene expression signature predicts survival of patients with pancreatic cancer and identifies new genes of interest.

BackgroundCurrently, prognostication for pancreatic ductal adenocarcinoma (PDAC) is based upon a coarse clinical staging system. Thus, more accurate prognostic tests are needed for PDAC patients to aid treatment decisions.Methods and findingsAffymetrix gene expression profiling was carried out on 15 human PDAC tumors and from the data we identified a 13-gene expression signature (risk score) that correlated with patient survival. The gene expression risk score was then independently validated using published gene expression data and survival data for an additional 101 patients with pancreatic

" Nucleolus in Human Beasons: Ribosome Biogenesis " , " Nucleolar Survey " и " Terrapeutic Opportunities " .

Nucleolus превратился в динамичную и многофункциональную субядерную органилию, интегрирующую рибосомный биогенез с клеточным ростом и сигнализацией стресса. Регулирование нуклеолярной функции все чаще признается в качестве главного движителя человеческих заболеваний, связывающего изменённое рибосомное производство и нуклеолярное наблюдение с раком, рибосомопатиями, синдромами преждевременного старения, нейродегенерацией и иммунными расстройствами. В этом обзоре мы интегрируем структурные, молекулярные и болезнетворные перспективы нуклеолярной биологии для определения того, как рипосомный биоге