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High-Dose Vitamin C in Advanced-Stage Cancer Patients.

High-dose intravenously administered vitamin C (IVC) is widely used in cancer patients by complementary and alternative medicine practitioners. The most frequent indications for IVC therapy result from the belief in its effectiveness as a potent anti-cancer agent which additionally enhances chemosensitivity of cancer cells and reduces chemotherapy-related toxicities and fatigue intensity. In this narrative review, we decided to deal with this issue, trying to answer the question whether there is any scientific evidence supporting the rationale for application of high-dose IVC therapy in advanc

HDACs and Their Inhibitors on Post-Translational Modifications: The Regulation of Cardiovascular Disease.

Cardiovascular diseases (CVD), such as myocardial hypertrophy, heart failure, atherosclerosis, and myocardial ischemia/reperfusion (I/R) injury, are among the major threats to human health worldwide. Post-translational modifications alter the function of proteins through dynamic chemical modification after synthesis. This mechanism not only plays an important role in maintaining homeostasis and plays a crucial role in maintaining normal cardiovascular function, but is also closely related to the pathological state of various diseases. Histone deacetylases (HDACs) play an important role in the

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2023.

With 54 new drugs and seven cellular and gene therapy products, the approvals by the US Food and Drug Administration (FDA) recovered 2023 from the 2022 dent back to the levels of 2020-2021. As in previous years of this annual review, we assign these new drugs to one of three levels of innovation: first drug against a condition ("first-in-indication"), first drug using a novel molecular mechanism ("first-in-class"), and "next-in-class," i.e., a drug using an already exploited molecular mechanism. We identify four (7%) "first-in-indication," 22 (36%) "first-in-class," and 35 (57%) "next-in-class

Anti-Infective-Associated AKI: A Narrative Review of the Epidemiology, Mechanisms, Risk Factors, Biomarkers, Clinical Course, Monitoring, Prevention, and Therapeutic Strategies.

Acute kidney injury (AKI) occurs commonly in hospitalized patients, especially patients in intensive care units (ICUs). Medications are among the major causative factors of AKI. This narrative review addressed and updated different aspects of anti-infective-associated AKI, including amphotericin B, cidofovir, foscarnet, polymyxins, vancomycin, and aminoglycosides. There is no standard definition or operational criteria to describe anti-infective-associated AKI. Characteristically, it usually occurs during the first two weeks of treatment and is typically dose dependent. Functional resolution o

Semaglutide: a key medication for managing cardiovascular-kidney-metabolic syndrome.

Recent trials underscore the cardiovascular (CV), renal, and metabolic benefits of semaglutide in individuals with and without type 2 diabetes (T2D). In T2D, semaglutide enhances glycemic control, reduces major adverse CV events (MACE), and slows chronic kidney disease (CKD) progression. The SUSTAIN-6 trial demonstrated a 26% MACE reduction (HR 0.74; 95% CI: 0.58-0.95; p = 0.02) in high CV-risk patients with T2D using semaglutide (0.5 or 1.0 mg weekly). Similarly, the FLOW trial showed a 24% reduction in major kidney disease events (HR 0.76; 95% CI: 0.66-0.88; p = 0.002) with weekly 1.0 mg sem

Interpreting clinical assays for histone deacetylase inhibitors.

As opposed to genetics, dealing with gene expressions by direct DNA sequence modifications, the term epigenetics applies to all the external influences that target the chromatin structure of cells with impact on gene expression unrelated to the sequence coding of DNA itself. In normal cells, epigenetics modulates gene expression through all development steps. When "imprinted" early by the environment, epigenetic changes influence the organism at an early stage and can be transmitted to the progeny. Together with DNA sequence alterations, DNA aberrant cytosine methylation and microRNA deregulat

Recent Insights into the Creation of Histone Deacetylase Inhibitors for the Treatment of Human Diseases.

This review examines publications over the past two years devoted to histone deacetylase inhibitors for the treatment of cancer, diseases of the nervous, cardiovascular, digestive, and respiratory systems, and autoimmune diseases. The review covers various classes of histone deacetylase inhibitors depending on the zinc-binding group, in particular hydroxamic acids, benzamides, hydrazides, carboxylic acids, and cyclic peptides. The review pays special attention to the mechanisms of development of pathologies involving various isoforms of histone deacetylases. The review shows that, for the trea

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… IPF is characterized by damage to the alveolar epithelium, initiating the production of cytokines and growth factors TGF-β and ET-1 (endothelin-1) [ 119 ]. …

Personal Medicine and Bone Metastases: Biomarkers, Micro-RNAs and Bone Metastases.

Bone metastasis is a major cause of morbidity within solid tumours of the breast, prostate, lung and kidney. Metastasis to the skeleton is associated with a wide range of complications including bone fractures, spinal cord compression, hypercalcaemia and increased bone pain. Improved treatments for bone metastasis, such as the use of anti-bone resorptive bisphosphonate agents, within post-menopausal women have improved disease-free survival; however, these treatments are not without side effects. There is thus a need for biomarkers, which will predict the risk of developing the spread to bone

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… PTHrP is not the only growth factor released by metastatic breast cancer cells, which cause this alteration in RANKL: OPG, Wnt-family members, transforming growth-factor-β (TGFβ), endothelin-1 (ET-1) and bone morphogenetic proteins (BMPs) also play a key role. …

Cancer Therapy and Exercise Intolerance: The Heart Is But a Part: JACC: CardioOncology State-of-the-Art Review.

The landscape of cancer therapeutics is continually evolving, with successes in improved survivorship and reduced disease progression for many patients with cancer. Improved cancer outcomes expose competing comorbidities, some of which may be exacerbated by cancer therapies. The leading cause of disability and death for many early-stage cancers is cardiovascular disease (CVD), which is often attributed to direct or indirect cardiac injury from cancer therapy. In this review, the authors propose that toxicities related to conventional and novel cancer therapeutics should be considered beyond th

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… Endothelial dysfunction, characterized by reduced vasodilator bioavailability (ie, nitric oxide and prostacyclin) and increased endothelium-derived vasoconstrictor activity (ie, endothelin-1, prostaglandin, and thromboxane), might impair oxygen delivery by increasing peripheral resistance and blunting …

The Arrhythmic Burden of Cardiac Amyloidosis: A Comprehensive Review.

Cardiac amyloidosis (CA) represents a growing etiology of heart failure (HF) and arrhythmogenesis, driven by the intramyocardial deposition of aberrantly folded proteins, notably immunoglobulin light chains (AL) and transthyretin (ATTR). This infiltrative process compromises myocardial compliance and disrupts the cardiac conduction system, leading to a diverse spectrum of dysrhythmias. The escalating prevalence of CA, particularly within geriatric demographics and individuals with plasma cell dyscrasias, underscores the imperative for refined diagnostic and therapeutic paradigms. The considera

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… The specific array of released factors, including ANP, angiotensin II, endothelin-1, transforming growth factor-β, and inflammatory cytokines, engages intricate signaling cascades that collectively augment susceptibility to AF.[ 21 , 22 , 23 ] Furthermore, AF compromises both atrial contractile function …

Sending the Signal to Bone: How Tumor-Derived EVs Orchestrate Pre-Metastatic Niche Formation and Skeletal Colonization.

Bone is a preferred site for disseminated tumor cells, yet the molecular mechanisms that prepare the skeletal microenvironment for metastatic colonization are only beginning to be understood. At the heart of this process are extracellular vesicles (EVs), nano-sized, lipid-encapsulated particles secreted by cancer cells and stromal components. This review consolidates current findings that position EVs as key architects of the bone-metastatic niche. We detail the biogenesis of EVs and their organotropic distribution, focusing on how integrin patterns and bone-specific ligands guide vesicle homi

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… A Causal Role for Endothelin-1 in the Pathogenesis of Osteoblastic Bone Metastases Proc. Natl. Acad. Sci. USA 2003 100 10954 10959 10.1073/pnas.1830978100 12941866 PMC196909 13. Tamura T. Yoshioka Y. Sakamoto S. Ichikawa T. Ochiya T. …

Targeting Sphingosine 1-Phosphate Metabolism as a Therapeutic Avenue for Prostate Cancer.

Prostate cancer (PC) is the second most common cancer in men worldwide. More than 65% of men diagnosed with PC are above 65. Patients with localized PC show high long-term survival, however with the disease progression into a metastatic form, it becomes incurable, even after strong radio- and/or chemotherapy. Sphingosine 1-phosphate (S1P) is a bioactive lipid that participates in all the steps of oncogenesis including tumor cell proliferation, survival, migration, invasion, and metastatic spread. The S1P-producing enzymes sphingosine kinases 1 and 2 (SK1 and SK2), and the S1P degrading enzyme

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… To sum up, PC cancer cells that have migrated to the bone adapt to and modify, the surrounding microenvironment by secreting active molecules that promote osteoblast differentiation and proliferation, including TGF-β and endothelin-1. …

Interactions between kidney disease and diabetes: dangerous liaisons.

BackgroundType 2 diabetes mellitus (DM) globally affects 18-20 % of adults over the age of 65 years. Diabetic kidney disease (DKD) is one of the most frequent and dangerous complications of DM2, affecting about one-third of the patients with DM2. In addition to the pancreas, adipocytes, liver, and intestines, the kidneys also play an important role in glycemic control, particularly due to renal contribution to gluconeogenesis and tubular reabsorption of glucose.MethodsIn this review article, based on a report of discussions from an interdisciplinary group of experts in the areas of endocrinolo

Muscle and Bone Defects in Metastatic Disease.

PURPOSE OF REVIEW: The present review addresses most recently identified mechanisms implicated in metastasis-induced bone resorption and muscle-wasting syndrome, known as cachexia. RECENT FINDINGS: Metastatic disease in bone and soft tissues is often associated with skeletal muscle defects. Recent studies have identified a number of secreted molecules and extracellular vesicles that contribute to cancer cell growth and metastasis leading to bone destruction and muscle atrophy. In addition, alterations in muscle microenvironment including dysfunctions in hepatic and mitochondrial metabolism ha

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… Conversely, osteoblastic metastasis in prostate cancer results from excessive bone formation activated by many factors such as endothelin-1 (ET-1), BMPs, PDGF, and TGF-β [ 83 ]. Cancer cells preferentially colonize the trabecular region of bone enriched with osteoblasts and micro-vessels [ 106 ]. …

Tumour Immunotherapy and Applications of Immunological Products: A Review of Literature.

Malignant tumors, characterized by uncontrolled cell proliferation, are a leading global health challenge, responsible for over 9.7 million deaths in 2022, with new cases expected to rise to 35 million annually by 2050. Immunotherapy is preferred to other cancer therapies, offering precise targeting of malignant cells while simultaneously strengthening the immune system's complex responses. Advances in this novel field of science have been closely linked to a deeper knowledge of tumor biology, particularly the intricate interplay between tumor cells, the immune system, and the tumor microenvir

Epigenetic mechanisms in cardiovascular complications of diabetes: towards future therapies.

The pathophysiological mechanisms of cardiovascular disease and microvascular complications in diabetes have been extensively studied, but effective methods of prevention and treatment are still lacking. In recent years, DNA methylation, histone modifications, and non-coding RNAs have arisen as possible mechanisms involved in the development, maintenance, and progression of micro- and macro-vascular complications of diabetes. Epigenetic changes have the characteristic of being heritable or deletable. For this reason, they are now being studied as a therapeutic target for the treatment of diabe

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… The hyperactivation of PKC induced by hyperglycaemia is responsible for numerous deleterious effects at the level of different tissues such as reduced expression of the endothelial nitric oxide (NO) synthase (eNOS) and increased expression of vasoconstrictor endothelin-1 in endothelium, or increased …

Mitochondrial Determinants of Anti-Cancer Drug-Induced Cardiotoxicity.

Mitochondria are key organelles for the maintenance of myocardial tissue homeostasis, playing a pivotal role in adenosine triphosphate (ATP) production, calcium signaling, redox homeostasis, and thermogenesis, as well as in the regulation of crucial pathways involved in cell survival. On this basis, it is not surprising that structural and functional impairments of mitochondria can lead to contractile dysfunction, and have been widely implicated in the onset of diverse cardiovascular diseases, including ischemic cardiomyopathy, heart failure, and stroke. Several studies support mitochondrial t

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… Commonly, the most strongly observed effect in response to anti-VEGF therapies is hypertension, which is due to unbalanced production in blood pressure regulators (i.e., increased endothelin-1 and decreased nitric oxide production, respectively), as well as reduced capillary density [ 157 ]. …

Critical considerations for targeting colorectal liver metastases with nanotechnology.

Colorectal cancer remains a significant cause of morbidity and mortality worldwide. Half of all patients develop liver metastases, presenting unique challenges for their treatment. The shortcomings of conventional chemotherapy has encouraged the use of nanomedicines; the application of nanotechnology in the diagnosis and treatment of disease. In spite of technological improvements in nanotechnology, the complexity of biological systems hinders the prospect of nanomedicines being applied in cancer therapy at the present time. This review highlights current biological barriers and discusses aspe

Bone health in patients with cancer: a SEOM-SEIOMM consensus review of risk factors, assessment strategies, and management approaches.

Anticancer therapies frequently compromise skeletal health and increase fracture risk. This narrative review synthesizes information and provides guidance on assessment, prevention, and management of therapy-related bone loss in adults with cancer. Major contributors to bone loss in this population include aromatase inhibitors, androgen deprivation therapy, systemic glucocorticoids, chemotherapy, and selected targeted or immune agents. Recommended assessments include clinical evaluation, laboratory tests (calcium, vitamin D, and renal function), and bone mineral density by dual-energy X-ray ab

Endothelial dysfunction in congenital adrenal hyperplasia due to 21-hydroxylase deficiency: current knowledge and novel biomarkers.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is a complex endocrine disorder characterized by impaired cortisol synthesis and androgen excess. Beyond its hormonal and metabolic implications, CAH has been increasingly associated with an elevated risk of cardiovascular complications, including endothelial dysfunction, a critical precursor to atherosclerosis and a risk factor for cardiovascular and metabolic diseases. This review explores the current knowledge on endothelial function in patients with CAH, focusing on the interplay between chronic hormonal imbalanc

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… In endothelial cells, it upregulates cell adhesion molecules, MCP-1, endothelin-1, and PAI-1, while decreasing prostacyclin release and tPA activity ( 265 ). Additionally, CRP has been shown to reduce eNOS activity and lower NO levels ( 165 ). …