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Challenges and innovations in CAR-T cell therapy: a comprehensive analysis.

Recent years have seen a marked increase in research on chimeric antigen receptor T (CAR-T) cells, with specific relevance to the treatment of hematological malignancies. Here, the structural principles, iterative processes, and target selection of CAR-T cells for therapeutic applications are described in detail, as well as the challenges faced in the treatment of solid tumors and hematological malignancies. These challenges include insufficient infiltration of cells, off-target effects, cytokine release syndrome, and tumor lysis syndrome. In addition, directions in the iterative development o

Biological and clinical basis for molecular studies of interferons.

The cytokine family of interferons (IFNs) has multiple functions, including antiviral, anti-tumor, and immunomodulatory effects and regulation of cell differentiation. The multiple functions of the IFN system are thought to be an innate defense against microbes and foreign substances. The IFN system consists first of cells that produce IFNs in response to viral infection or other foreign stimuli and second of cells that establish the antiviral state in response to IFNs. This process of innate immunity involves multiple signaling mechanisms and activation of various host genes. Viruses have evo

Paraneoplastic scleroderma: a patient with a history of breast cancer presenting with sclerodactyly and Raynaud's phenomenon.

A woman in her 70s with a past history of breast cancer in remission presented with several months of dyspnoea, skin tightness and Raynaud's phenomenon. Physical examination was significant for hypertension, hypoxaemia, sclerodactyly, diffuse crackles on auscultation and mild respiratory distress. Work-up revealed elevated serum creatinine, elevated right ventricular systolic pressure on echocardiography and nuclear bone scan findings of osseous metastatic disease. Captopril was initiated with concern for scleroderma renal crisis. The scleroderma panel was positive for RNA polymerase 11 and 15

Mechanisms of cancer-associated thrombosis.

A State-of-the-Art lecture titled "Mechanisms of cancer-associated thrombosis" was presented at the ISTH Congress in 2022. Patients with cancer have a 4-fold to 9-fold increased risk of venous thromboembolism (VTE) compared with the general population, so-called cancer-associated thrombosis (CAT). Different rates of VTE are observed in different types of cancer, suggesting that there are cancer-type specific mechanisms of CAT. We will discuss 4 pathways of CAT: tissue factor, podoplanin, neutrophil extracellular traps, and plasminogen activator inhibitor-1. In addition, specific gene mutations

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

Enhancing the Safety of Nanoparticles in Medicine: Highlights of Progress and Critical Objectives.

Nanoparticles have transformed drug delivery, imaging, vaccination, and precision therapeutics, but their clinical translation remains constrained by safety profiles that are inseparable from material design, biological identity, host factors, and manufacturing. This review critically evaluates recent progress, persistent limitations, and priority objectives for safer nanomedicine. Unlike reviews organized primarily by material class or isolated toxicology endpoints, we integrate physicochemical determinants, protein corona formation, immune recognition, organ disposition, preclinical models,

Futibatinib, an Irreversible FGFR1-4 Inhibitor for the Treatment of FGFR-Aberrant Tumors.

Fibroblast growth factor receptors (FGFR) are emerging as an important therapeutic target for patients with advanced, refractory cancers. Most selective FGFR inhibitors under investigation show reversible binding, and their activity is limited by acquired drug resistance. This review summarizes the preclinical and clinical development of futibatinib, an irreversible FGFR1-4 inhibitor. Futibatinib stands out among FGFR inhibitors because of its covalent binding mechanism and low susceptibility to acquired resistance. Preclinical data indicated robust activity of futibatinib against acquired res

Immune checkpoint and inflammation as therapeutic targets in pancreatic carcinoma.

Pancreatic adenocarcinoma (PAC) is one of the most deadly malignant neoplasms, and the efficacy of conventional cytotoxic chemotherapy is far from satisfactory. Recent research studies have revealed that immunosuppression and inflammation are associated with oncogenesis, as well as tumor development, invasion, and metastasis in PAC. Thus, immunosuppression-related signaling, especially that involving immune checkpoint and inflammation, has emerged as novel treatment targets for PAC. However, PAC is an immune-resistant tumor, and it is still unclear whether immune checkpoint or anti-inflammatio

Targeting autoimmune mechanisms by precision medicine in Myasthenia Gravis.

Myasthenia Gravis (MG) is a chronic disabling autoimmune disease caused by autoantibodies to the neuromuscular junction (NMJ), characterized clinically by fluctuating weakness and early fatigability of ocular, skeletal and bulbar muscles. Despite being commonly considered a prototypic autoimmune disorder, MG is a complex and heterogeneous condition, presenting with variable clinical phenotypes, likely due to distinct pathophysiological settings related with different immunoreactivities, symptoms' distribution, disease severity, age at onset, thymic histopathology and response to therapies. Cur

Oxidative Stress: Signaling Pathways, Biological Functions, and Disease.

The dysregulated accumulation of reactive oxygen species (ROS) and reactive nitrogen species disrupts redox homeostasis, triggering oxidative stress (OS) and driving pathophysiological changes across multiple organ systems. OS modulates critical signaling pathways, induces inflammation, impairs mitochondrial function, alters metabolic homeostasis, and dysregulates autophagy, contributing to disease progression. While prior research has largely focused on OS within single-organ diseases (e.g., neurodegenerative, cardiovascular, and oncological disorders), the systemic role of OS in pan-organ di

Совокупное и интерактивное воздействие тяжелых металлов на нейродегенеративные заболевания: сравнительный обзор болезни Альцгеймера, Паркинсона, амиотропического бокового склероза и множественного склероза.

Тяжелые металлы и металллоиды являются стойкими загрязнителями окружающей среды, которые накапливаются в центральной нервной системе и взаимодействуют с местными основными металлами, однако в большинстве нейротоксических исследований металлы по-прежнему рассматриваются как независимые агенты, а не как смешанные смеси. В настоящем обзоре систематически сопоставляются данные о совокупном и интерактивном воздействии смесей тяжелых металлов на четыре основных нейродегенеративных заболевания: болезнь Альцгеймера (AD), болезнь Паркинсона (PD), амиотропический боковой склероз (ALS) и множественный ск

Spotlight on ixazomib: potential in the treatment of multiple myeloma.

Despite the significant therapeutic advances achieved with proteasome inhibitors (PIs) such as bortezomib and carfilzomib in prolonging the survival of patients with multiple myeloma, the development of drug resistance, peripheral neuropathy, and pharmacokinetic limitations continue to pose major challenges when using these compounds. Ixazomib is a second-generation PI with improved activity over other PIs. Unlike bortezomib and carfilzomib, which are administered by injection, ixazomib is the first oral PI approved by US Food and Drug Administration. This review discusses the biochemical prop

A Narrative Review on the Antitumoral Effects of Selected Mediterranean Plant Products from Southern Italy.

Natural products are a valuable source of bioactive compounds with established roles in oncology. Their structural diversity and ability to target multiple cancer-related pathways make them promising candidates for anticancer drug development. Increasing preclinical and clinical data highlight their potential not only to exert direct antitumor effects but also to enhance patient tolerance to conventional therapies by reducing side effects and improving treatment adherence. The Mediterranean region, known for its biodiversity and traditional dietary habits, provides a rich array of natural comp

Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis.

BACKGROUND: The assessment and characterization of the gut microbiome has become a focus of research in the area of human autoimmune diseases. Ankylosing spondylitis is an inflammatory autoimmune disease and evidence showed that ankylosing spondylitis may be a microbiome-driven disease. RESULTS: To investigate the relationship between the gut microbiome and ankylosing spondylitis, a quantitative metagenomics study based on deep shotgun sequencing was performed, using gut microbial DNA from 211 Chinese individuals. A total of 23,709 genes and 12 metagenomic species were shown to be differentia

The pleiotropic effects of erythropoietin in infection and inflammation.

Erythropoietin (EPO) is a multi-functional cytokine, which exerts erythropoietic effects but also carries anti-apoptotic and immune-modulatory activities upon binding to two distinct receptors which are expressed on erythroid, parenchymal and immune cells, respectively. Whereas EPO ameliorates hemolytic anemia in malaria or trypanosomiasis and improves the course of autoimmune diseases such as inflammatory bowel disease or autoimmune encephalomyelitis, it deleteriously inhibits macrophage functions in Salmonella infection in animal models. Thus, the specific modulation of extra-erythropoietic

Update on cutaneous calciphylaxis.

Calciphylaxis is a devastating disorder with a mortality rate of 80% due to sepsis and organ failure. Hallmarks of this rare disease are arteriolar media calcification, thrombotic cutaneous ischemia, and necrotic ulcerations. Different mechanisms of vascular calcification can lead to calciphylaxis. Early diagnosis by deep cutaneous ulcer biopsy is most important for prognosis. Here, dermatologists play a significant role although treatment usually needs an interdisciplinary approach. Surgical procedures had been the cornerstone of treatment in the past including parathyroidectomy, but recently

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Targeting the ROCK2/UBA52/DRP1 axis enhances ferroptosis and overcomes pemigatinib resistance in Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a highly aggressive cancer that arises from the bile duct and has an extremely poor prognosis. Pemigatinib is the only Food and Drug Administration (FDA)-approved CCA-targeted drug. The CCA treatment options are insufficient considering its poor prognosis and increasing morbidity. Recently, Rho-associated coiled-coil containing protein kinase 2 (ROCK2) has been reported to promote resistance to chemotherapy. In this study, we investigated the role that ROCK2 plays in the development of resistance of CCA cells to Pemigatinib. Here, we developed Pemigatinib-resistant

Osteoimmuno-Oncology: Therapeutic Opportunities for Targeting Immune Cells in Bone Metastasis.

Immunotherapies provide a potential treatment option for currently incurable bone metastases. Bone marrow is an important secondary lymphoid organ with a unique immune contexture. Even at non-disease state immune cells and bone cells interact with each other, bone cells supporting the development of immune cells and immune cells regulating bone turnover. In cancer, tumor cells interfere with this homeostatic process starting from formation of pre-metastatic niche and later supporting growth of bone metastases. In this review, we introduce a novel concept osteoimmuno-oncology (OIO), which refer

Bone Turnover Markers in Chronic Periodontitis: A Literature Review.

Chronic periodontitis (CP) is a multifactorial oral inflammatory disease characterized by progressive destruction of bone and ultimate tooth loss. The alarming rise in the prevalence of periodontitis has led to the development of innovative diagnostic techniques. Several quantifiable biomarkers in the gingival crevicular fluid (GCF) and saliva of chronic periodontitis patients have been detected in the field of oral fluid diagnostics. Bone turnover biomarkers hold a valuable diagnostic potential in determining the extent of alveolar bone destruction and the risk of future bone loss. This revie

Current Status of 68Ga-Pentixafor in Solid Tumours.

Chemokine receptor CXCR4 is overexpressed in neoplasms and its expression is related to tumour invasion, metastasis and aggressiveness. 68Ga-Pentixafor is used to non-invasively image the expression of CXCR4 in tumours and has been widely used in haematological malignancies. Recent evidence shows that therapies targeting CXCR4 can increase the chemosensitivity of the tumour as well as inhibit tumour metastasis and aggressiveness. 68Ga-Pentixafor has shown promise as an elegant radiotracer to aid in the selection of patients whose tumours demonstrate CXCR4 overexpression and who therefore may b