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Tumor buster - where will the CAR-T cell therapy 'missile' go?

Chimeric antigen receptor (CAR) T cell (CAR-T cell) therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal. Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME

Resveratrol and Cardiovascular Diseases.

The increased incidence of cardiovascular diseases (CVDs) has stimulated research for substances that could improve cardiovascular health. Among them, resveratrol (RES), a polyphenolic compound notably present in grapes and red wine, has been involved in the "French paradox". RES is known for its antioxidant and anti-inflammatory properties and for its ability to upregulate endothelial NO synthase (eNOS). RES was able to scavenge (•)OH/O₂(•-) and peroxyl radicals, which can limit the lipid peroxidation processes. Moreover, in bovine aortic endothelial cells (BAEC) under glucose-induced oxidati

The Role of Injectables in the Treatment and Prevention of Cancer-Associated Thrombosis.

Cancer-associated thrombosis (CAT) is a leading cause of death among patients with cancer. CAT can manifest itself as venous thromboembolism (VTE), in the form of deep vein thrombosis or pulmonary embolism, or arterial thromboembolism. The pathophysiology of CAT is complex and depends on cancer-, patient-, treatment- and biomarkers-related factors. Treatment of VTE in patients with cancer is complex and includes three major classes of anticoagulant agents: heparin and its derivatives, e.g., low molecular weight heparins, direct oral anticoagulants (DOACs), and vitamin K inhibitors. Given the t

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

Guidelines on deep vein thrombosis of the Brazilian Society of Angiology and Vascular Surgery.

Deep vein thrombosis is one of the main causes of inpatient and outpatient morbidity, both in medical and surgical patients, significantly impacting mortality statistics and requiring prompt diagnosis so that treatment can be initiated immediately. This document was prepared and reviewed by 11 specialists certified by the Brazilian Society of Angiology and Vascular Surgery, who searched the main databases for the best evidence on the diagnostic (physical examination, imaging) and therapeutic approaches (heparin, coumarins, direct oral anticoagulants, fibrinolytics) to the disease.

Extracellular matrix dysregulation in aging, calcification, and cancer diseases: insights into cellular senescence, inflammation, and novel therapeutic strategies.

This review underscores the dynamic role of the extracellular matrix (ECM) in regulating cellular behavior and maintaining tissue homeostasis, highlighting its pivotal involvement in aging, calcification, and cancer diseases. In healthy tissues, controlled ECM remodeling provides essential biochemical and mechanical cues, but dysregulation (driven by chronic inflammation, cellular senescence, and altered intercellular communication) leads to fibrosis, calcification, and the creation of a pro-tumorigenic microenvironment. Senescent cells contribute to these changes through senescence-associated

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… On the one hand, serine proteases such as plasmin (activated by urokinase and tissue plasminogen activators) degrade fibrin, fibronectin, and laminin 95 . …

Senescent T cells: Beneficial and detrimental roles.

As the thymus involutes during aging, the T-cell pool has to be maintained by the periodic expansion of preexisting T cells during adulthood. A conundrum is that repeated episodes of activation and proliferation drive the differentiation of T cells toward replicative senescence, due to telomere erosion. This review discusses mechanisms that regulate the end-stage differentiation (senescence) of T cells. Although these cells, within both CD4 and CD8 compartments, lose proliferative activity after antigen-specific challenge, they acquire innate-like immune function. While this may confer broad i

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

The Mediterranean Diet, a Rich Source of Angiopreventive Compounds in Cancer.

Diet-based chemoprevention of cancer has emerged as an interesting approach to evade the disease or even target its early phases, reducing its incidence or slowing down tumor progression. In its basis in the essential role of angiogenesis for tumor growth and metastasis, angioprevention proposes the use of inhibitors of angiogenesis in cancer prevention. The anti-angiogenic potential exhibited by many natural compounds contained in many Mediterranean diet constituents makes this dietary pattern especially interesting as a source of chemopreventive agents, defined within the angioprevention str

Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: children and adolescents.

The Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Children and Adolescents was developed by dietitians, physicians, and pediatric hematologists from 10 Brazilian reference centers in hematopoietic stem cell transplantation. The aim was to emphasize the importance of nutritional status and body composition during treatment, as well as the main characteristics related to patient´s nutritional assessment. This consensus is intended to improve and standardize nutrition therapy during hematopoietic stem cell transplantation. The consensus was approved by the Brazilian

Anti-Inflammatory Drugs as Anticancer Agents.

Inflammation is strictly associated with cancer and plays a key role in tumor development and progression. Several epidemiological studies have demonstrated that inflammation can predispose to tumors, therefore targeting inflammation and the molecules involved in the inflammatory process could represent a good strategy for cancer prevention and therapy. In the past, several clinical studies have demonstrated that many anti-inflammatory agents, including non-steroidal anti-inflammatory drugs (NSAIDs), are able to interfere with the tumor microenvironment by reducing cell migration and increasin

Nano-formulations in disease therapy: designs, advances, challenges, and future directions.

Nano-formulations, as an innovative drug delivery system, offer distinct advantages in enhancing drug administration methods, improving bioavailability, promoting biodegradability, and enabling targeted delivery. By exploiting the unique size advantages of nano-formulations, therapeutic agents, including drugs, genes, and proteins, can be precisely reorganized at the microscale level. This modification not only facilitates the precise release of these agents but also significantly enhances their efficacy while minimizing adverse effects, thereby creating novel opportunities for treatment of a

Cyanobacterial Peptides in Anticancer Therapy: A Comprehensive Review of Mechanisms, Clinical Advances, and Biotechnological Innovation.

Cyanobacteria-derived peptides represent a promising class of anticancer agents due to their structural diversity and potent bioactivity. They exert cytotoxic effects through mechanisms including microtubule disruption, histone deacetylase inhibition, and apoptosis induction. Several peptides-most notably the dolastatin-derived auristatins-have achieved clinical success as cytotoxic payloads in antibody-drug conjugates (ADCs). However, challenges such as limited tumor selectivity, systemic toxicity, and production scalability remain barriers to broader application. Recent advances in targeted

Advances in α-Lipoic Acid for Disease Prevention: Mechanisms and Therapeutic Insights.

α-Lipoic acid (ALA) is a naturally occurring compound with diverse biological functions, widely distributed in animal and plant tissues. It has attracted considerable attention due to its versatile therapeutic potential. However, despite these promising prospects, the clinical application of ALA remains limited by its low bioavailability and chemical instability and an incomplete understanding of its multifaceted mechanisms across various diseases. This review provides a comprehensive overview of the biochemical properties of ALA, including its direct free-radical-scavenging activity, regenera

Epithelial-Mesenchymal Transition in Cancer: Insights Into Therapeutic Targets and Clinical Implications.

Radiation therapy is a fundamental component of cancer treatment, benefiting 50%-70% of patients by selectively targeting malignant tissues. However, radioresistance remains a significant challenge, often driven by epithelial-mesenchymal transition (EMT). EMT increases cancer invasiveness and metastasis by upregulating mesenchymal markers, including vimentin and N-cadherin, and downregulating epithelial markers, such as E-cadherin. EMT under radiation involves principal signaling pathways, including TGF-β, Wnt/β-catenin, Notch, and ERK, which regulate EMT through transcription factors such as

The Inclusion of Dietary and Medicinal Mushrooms into Translational Oncology: Pros and Cons at the Molecular Level.

Mushrooms are valued for their nutritional qualities and have been used in traditional medicine since the Neolithic era. They exhibit various bioactivities, including antioxidant, hypocholesterolemic, immunomodulatory, and anticancer effects. The anticancer effects arise via direct action on tumor cells and indirect modulation of the immune system; the latter is the predominant mechanism. Numerous studies indicate that various mushroom species are potent immunostimulants because their cell wall polysaccharides and proteoglycans are recognized by intestinal immune cells. This enhances antitumor

Exosomes for angiogenesis induction in ischemic disorders.

Ischaemic disorders are leading causes of morbidity and mortality worldwide. While the current therapeutic approaches have improved life expectancy and quality of life, they are unable to "cure" ischemic diseases and instate regeneration of damaged tissues. Exosomes are a class of extracellular vesicles with an average size of 100-150 nm, secreted by many cell types and considered a potent factor of cells for paracrine effects. Since exosomes contain multiple bioactive components such as growth factors, molecular intermediates of different intracellular pathways, microRNAs and nucleic acids, t

Hypoxia-driven angiogenesis and metabolic reprogramming in vascular tumors.

Hypoxia is a hallmark of the tumor microenvironment (TME), and it plays a crucial role in the occurrence and progression in vascular tumors. Under hypoxic conditions, hypoxia-inducible factor 1-alpha (HIF-1α) is stabilized, inducing changes in the expression of various target genes involved in angiogenesis, metabolism, and cell survival. This includes the upregulation of pro-angiogenic factors like VEGF, which promotes the formation of dysfunctional blood vessels, contributing to the worsening of the hypoxic microenvironment. At the same time, hypoxia induces a metabolic shift toward glycolysi

Efficacy of oncolytic virus in the treatment of intermediate-to-advanced solid tumors: a systematic review and meta-analysis.

This meta-analysis assessed oncolytic virus therapy's efficacy for intermediate-to-advanced solid tumors. We systematically searched PubMed, Cochrane Library, and Embase databases until March 6, 2025. Our review included 87 studies, involving 5,385 individuals, encompassing 75 clinical trials and 12 retrospective studies. Patient response rates were as follows: complete response (CR) 11%, partial response (PR) 18%, stable disease (SD) 32%, and progressive disease (PD) 32%. The overall response rate (ORR) was 29%, and the durable response rate (DRR) was 39%. Comparing oncolytic virus therapy to

Immune mediated support of metastasis: Implication for bone invasion.

Bone is a common organ affected by metastasis in various advanced cancers, including lung, breast, prostate, colorectal, and melanoma. Once a patient is diagnosed with bone metastasis, the patient's quality of life and overall survival are significantly reduced owing to a wide range of morbidities and the increasing difficulty of treatment. Many studies have shown that bone metastasis is closely related to bone microenvironment, especially bone immune microenvironment. However, the effects of various immune cells in the bone microenvironment on bone metastasis remain unclear. Here, we describe