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Smart Targeting To Improve Cancer Therapeutics.

Cancer is the second largest cause of death worldwide with the number of new cancer cases predicted to grow significantly in the next decades. Biotechnology and medicine can and should work hand-in-hand to improve cancer diagnosis and treatment efficacy. However, success has been frequently limited, in particular when treating late-stage solid tumors. There still is the need to develop smart and synergistic therapeutic approaches to achieve the synthesis of strong and effective drugs and delivery systems. Much interest has been paid to the development of smart drug delivery systems (drug-loade

Pathophysiological Roles of the CX3CL1-CX3CR1 Axis in Renal Disease, Cardiovascular Disease, and Cancer.

CX3CL1 and its unique receptor, CX3CR1, are leukocyte migration factors and are involved in the pathogenesis and progression of many inflammatory diseases and malignancies. The CX3CL1-CX3CR1 axis induces a variety of responses, including cell proliferation, migration, invasion, and apoptosis resistance. CX3CL1 is a transmembrane protein, and proteolysis generates a soluble form. The membrane and soluble forms of CX3CL1 exhibit different functions, but both bind to the chemokine receptor CX3CR1. The CX3CL1-CX3CR1 axis is a chemokine system that has attracted attention not only as a therapeutic

CAR T Cell Therapy of Non-hematopoietic Malignancies: Detours on the Road to Clinical Success.

Chimeric antigen receptor (CAR)-engineered T cells represent a breakthrough in personalized medicine. In this strategy, a patient's own T lymphocytes are genetically reprogrammed to encode a synthetic receptor that binds a tumor antigen, allowing T cells to recognize and kill antigen-expressing cancer cells. As a result of complete and durable responses in individuals who are refractory to standard of care therapy, CAR T cells directed against the CD19 protein have been granted United States Food and Drug Administration (FDA) approval as a therapy for treatment of pediatric and young adult acu

Chest and Mediastinum

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Advances in Molecularly Imprinted Polymers for Bone Biomarker Detection and Therapeutic Applications.

This review explores the application of molecularly imprinted polymers (MIPs) in detecting bone turnover biomarkers and advancing osteogenic treatment strategies. MIPs, designed to mimic biological recognition sites, offer innovative solutions for precise molecular recognition in bone health management. Chemical methodologies for MIPs synthesis and their integration into diagnostic systems for detecting bone resorption markers are highlighted. Furthermore, MIP-driven therapeutic advancements, including controlled drug release, cell imprinting for osteogenic differentiation, and functional scaf

Angiogenesis and Anti-Angiogenic Treatment in Prostate Cancer: Mechanisms of Action and Molecular Targets.

Prostate cancer (PC) is the most common cancer in men and the second leading cause of cancer-related death worldwide. Many therapeutic advances over the last two decades have led to an improvement in the survival of patients with metastatic PC, yet the majority of these patients still succumb to their disease. Antiagiogenic therapies have shown substantial benefits for many types of cancer but only a marginal benefit for PC. Ongoing clinical trials investigate antiangiogenic monotherapies or combination therapies. Despite the important role of angiogenesis in PC, clinical trials in refractory

Non-Exosomal and Exosomal Circulatory MicroRNAs: Which Are More Valid as Biomarkers?

MicroRNAs (miRNAs) are a group of small non-coding RNAs with approximately 19-25 nucleotides that are involved in regulating a range of developmental and physiological processes. Non-exosomal circulating and exosomal miRNAs have also been proposed to be useful in diagnostics as biomarkers for diseases and different types of cancer. In this review, the quantity of miRNAs and of reliable experimental data analyses of miRNAs that come from exosomal and non-exosomal sources are discussed from the perspective of their use as biomarkers for cancer and other diseases, including viral infections, nerv

ADMET-Guided Design and In Silico Planning of Boron Delivery Systems for BNCT: From Transport and Biodistribution to PBPK-Informed Irradiation Windows.

BNCT (Boron Neutron Capture Therapy) is a binary radiotherapeutic modality in which high LET (Linear Energy Transfer) particles are generated from 10B(n,α)7Li reaction, ideally within boron-loaded tumour cells, so the therapeutic outcome depends critically on the pharmacokinetics and biodistribution of boron carriers. In this review, boron-containing agents for BNCT, with a focus on ADMET (absorption, distribution, metabolism, excretion and toxicity) and model-informed design, were examined. Low-MW (low-molecular-weight) compounds, peptide conjugates, polymeric and nanostructured platforms and

When Cancer Clots: An Extensive Radiologic Analysis of Cancer-Associated Thromboembolism.

Cancer-associated thrombosis (CAT) is a leading cause of morbidity and mortality in patients with malignancy, yet its imaging manifestations extend far beyond the conventional diagnosis of deep vein thrombosis and pulmonary embolism. This comprehensive review examines the full spectrum of CAT as encountered by radiologists, from routine venous thromboembolism to unusual-site thromboses, arterial thromboembolic events, catheter-related complications, and endovascular management strategies. Patients with cancer face a four- to seven-fold increased risk of venous thromboembolism compared with the

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… Cancer also causes activation of platelets and leukocytes, formation of neutrophil extracellular traps, endothelial dysfunction, and direct vascular invasion. … Active vasculitis increases VTE risk through endothelial injury, inflammatory activation of coagulation pathways, and neutrophil extracellular trap formation expressing tissue factor [ 55 , 56 , 57 ]. …

Recent clinical trials with stem cells to slow or reverse normal aging processes.

Aging is associated with a decline in the regenerative potential of stem cells. In recent years, several clinical trials have been launched in order to evaluate the efficacy of mesenchymal stem cell interventions to slow or reverse normal aging processes (aging conditions). Information concerning those clinical trials was extracted from national and international databases (United States, EU, China, Japan, and World Health Organization). Mesenchymal stem cell preparations were in development for two main aging conditions: physical frailty and facial skin aging. With regard to physical frailty,

The science of tumor-infiltrating lymphocytes (TIL): perspectives from the SITC Surgery Committee.

Immunity to solid tumors is associated with the hallmarks of cancer-associated inflammation and the ability of immune mechanisms to limit tumor progression. Application of expanded tumor-infiltrating lymphocyte adoptive T cell therapy (TIL ACT) in clinical trials is now practiced at many sites around the world. Prior to immune checkpoint blockade (ICB), an approximate 50% objective response rate was consistently observed across multiple institutions for patients with melanoma. This now-approved strategy approaches 35% in recent studies from the USA and 49% with more highly selected patients in

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… DC, dendritic cell; IL-2, interleukin 2; IL2Rg, interleukin 2 receptor gamma chain; IT, intratumoral; NETs, neutrophil extracellular traps; PD-1, programmed death 1; PGE2, prostaglandin E2; TIL, tumor-infiltrating lymphocyte. …

Targeting the P-selectin/PSGL-1 pathway: discovery of disease-modifying therapeutics for disorders of thromboinflammation.

P-selectin is a membrane glycoprotein and a member of the selectin family of cell adhesion molecules. It is prestored in α-granules of platelets and Weibel-Palade bodies of endothelial cells and is rapidly expressed on their surfaces upon activation during the course of an inflammatory response. Although a critical component of the innate immune system, the interaction of P-selectin with its cognate ligand, P-selectin glycoprotein ligand 1 (PSGL-1) may mediate maladaptive events central to the pathophysiology of venous thromboembolism, cardiovascular disease, stroke, metabolic syndrome, and si

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… In immunothrombosis, P-selectin mediated interactions help localize leukocytes at sites of infection with the release of neutrophil extracellular traps and formation of microvascular thrombi that trap and clear pathogens. …

Targeting the CD47-TSP1 Axis in Abdominal Aortic Aneurysm: A Novel Immunotherapeutic Approach.

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disorder characterized by progressive dilation and weakening of the abdominal aortic wall. Despite advances in surgical repair, rupture remains associated with mortality rates exceeding 65%, and no effective pharmacological therapy exists to prevent disease progression. Increasing evidence highlights chronic inflammation, extracellular matrix degradation, and immune dysregulation as central drivers of AAA pathogenesis. Among these mechanisms, the thrombospondin-1 (TSP1)-CD47 signaling axis has emerged as a critical upstream regulat

Engineered cell therapies for autoimmune diseases: evaluating CAR-T and CAR-M progress and prospects.

Autoimmune diseases (AID) comprise a diverse group of disorders driven by aberrant B-cell and T-cell reactivity against self-tissues. In recent years, cell-based therapies utilizing engineered T cells have emerged as a promising therapeutic strategy for AIDs. Notably, chimeric antigen receptor (CAR)-T cells have demonstrated the ability to selectively target and eliminate autoreactive immune populations, including pathogenic B cells and antibody-producing plasma cells. Beyond T-cell modulation, macrophages (MΦs) exhibit remarkable plasticity, differentiating into pro-inflammatory (M1) or anti-

Bioengineered Mesenchymal Stem/Stromal Cells in Anti-Cancer Therapy: Current Trends and Future Prospects.

Mesenchymal stem/stromal cells (MSCs) are one of the most widely used cell types in advanced therapies due to their therapeutic potential in the regulation of tissue repair and homeostasis, and immune modulation. However, their use in cancer therapy is controversial: they can inhibit cancer cell proliferation, but also potentially promote tumour growth by supporting angiogenesis, modulation of the immune milieu and increasing cancer stem cell invasiveness. This opposite behaviour highlights the need for careful and nuanced use of MSCs in cancer treatment. To optimize their anti-cancer effects,

Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectives.

Multiple myeloma (MM) is a hematological malignancy that leads to significant bone destruction, resulting in debilitating pain and skeletal-related events. The pathophysiology of osteolytic bone destruction in MM involves complex interactions between malignant plasma cells (PCs) and the bone marrow (BM) microenvironment. This review aims to provide a comprehensive synthesis of the cellular and molecular pathways underlying MM-associated bone disease. We discuss the role of osteoclast (OC), osteoblast (OB), osteocytes, along with the complex interactions between immune cells and the BM microenv

Последние достижения в области мезенхимической стволовой клеточной терапии для множественных склерозов: клинические виды применения и проблемы.

Множественный склероз (MS), хроническое аутоиммунное расстройство центральной нервной системы (CNS), характеризуется воспалением, обезвоживанием и нейродегенерацией, что приводит к различным клиническим проявлениям, таким, как усталость, сенсорное расстройство и когнитивная дисфункция. Текущее фармакологическое лечение направлено прежде всего на иммунную модуляцию, но не позволяет остановить прогрессию заболеваний или полностью обратить на нет повреждения CNS. Лечение стволовыми клетками (MSC) является многообещающей альтернативой, используя иммуномудуляторы, нейрозащиту и регенеративные спосо

Blood Coagulation and Beyond: Position Paper from the Fourth Maastricht Consensus Conference on Thrombosis.

The Fourth Maastricht Consensus Conference on Thrombosis included the following themes. Theme 1: The "coagulome" as a critical driver of cardiovascular disease. Blood coagulation proteins also play divergent roles in biology and pathophysiology, related to specific organs, including brain, heart, bone marrow, and kidney. Four investigators shared their views on these organ-specific topics. Theme 2: Novel mechanisms of thrombosis. Mechanisms linking factor XII to fibrin, including their structural and physical properties, contribute to thrombosis, which is also affected by variation in microbio

Primary Osteoporosis Induced by Androgen and Estrogen Deficiency: The Molecular and Cellular Perspective on Pathophysiological Mechanisms and Treatments.

Primary osteoporosis is closely linked to hormone deficiency, which disrupts the balance of bone remodeling. It affects postmenopausal women but also significantly impacts older men. Estrogen can promote the production of osteoprotegerin, a decoy receptor for RANKL, thereby preventing RANKL from activating osteoclasts. Furthermore, estrogen promotes osteoblast survival and function via activation of the Wnt signaling pathway. Likewise, androgens play a critical role in bone metabolism, primarily through their conversion to estrogen in men. Estrogen deficiency accelerates bone resorption throug

Current and Emerging Therapies for Targeting the ERK1/2 & PI3K Pathways in Cancer.

The ERK1/2 and PI3K signaling pathways play important roles in cellular proliferation, survival, differentiation, and metabolism. In cancer, these pathways are frequently dysregulated and overactivated, resulting in poor patient prognosis and resistance to treatment. These pathways are activated by receptor tyrosine kinases and send downstream signals to effectors such as RAS, RAF, MEK, AKT, and mTOR. In this review, we highlight the key components of the ERK1/2 and PI3K pathways, the roles they play in tumor progression, and the development of inhibitors and combination therapies designed to