Innovative Therapies against Human Glioblastoma Multiforme

Glioblastoma multiforme is the most invasive and aggressive brain tumor in humans, and despite the latest chemical and radiative therapeutic approaches, it is still scarcely sensitive to these treatments and is generally considered an incurable disease. This paper will focus on the latest approaches to the treatment of this cancer, including the new chemicals such as proautophagic drugs and kinases inhibitors, and differentiating agents. In this field, there have been opening new perspectives as the discovery of possible specific targets such as the EGFRvIII, a truncated form of the EGF receptor. Antibodies against these targets can be used as proapoptotic agents and as possible carriers for chemicals, drugs, radioisotopes, and toxins. In this paper, we review the possible mechanism of action of these therapies, with particular attention to the combined use of toxic substances (for example, immunotoxins) and antiproliferative/differentiating compounds (i.e., ATRA, PPARγ agonists). All these aspects will be discussed in the view of progress clinical trials and of possible new approaches for directed drug formulations

Nanoparticles of Cerium Oxide Targeted to an Amyloid-Beta Antigen of Alzheimer\u27s Disease and Associated Methods

Disclosed is a composition immunologically targeted to Alzheimer’s disease (AD), the composition containing amine functionalized nanoparticles of Cerium oxide coated with polyethylene glycol and bearing an antibody specific for an amyloid-beta antigen associated with AD. The invention also includes a medication manufactured with the targeted nanoceria particles and methods of treatment by administering the targeted nanoceria particles to patients in need thereof

PPARs in Human Neuroepithelial Tumors: PPAR Ligands as Anticancer Therapies for the Most Common Human Neuroepithelial Tumors

Neuroepithelial tumors represent a heterogeneous class of human tumors including benignant and malignant tumors. The incidence of central nervous system neoplasms ranges from 3.8 to 5.1 cases per 100,000 in the population. Among malignant neuroepithelial tumors, with regard to PPAR ligands, the most extensively studied were tumors of astrocytic origin and neuroblastoma. PPARs are expressed in developing and adult neuroepithelial cells, even if with different localization and relative abundance. The majority of malignant neuroepithelial tumors have poor prognosis and do not respond to conventional therapeutic protocols, therefore, new therapeutic approaches are needed. Natural and synthetic PPAR ligands may represent a starting point for the formulation of new therapeutic approaches to be used as coadjuvants to the standard therapeutic protocols. This review will focus on the major studies dealing with PPAR expression in gliomas and neuroblastoma and the therapeutic implications of using PPAR agonists for the treatment of these neoplasms

The Emerging Role of Cyclin-Dependent Kinase Inhibitors in Treating Diet-Induced Obesity: New Opportunities for Breast and Ovarian Cancers?

Simple Summary This review aims to provide an outline of the potential use of plant-based foods, nutraceuticals, and derived micronutrients-particularly those typically found in the Mediterranean diet-as anticancer agents, with a focus on their mechanism of action as cyclin-dependent kinase inhibitors (CDKIs) by inactivating the CDK 4/6 pathway and the regulation of the cell-cycle cascade. We discuss the preclinical and pharmacological significance of some already approved CDK blockers as a promising therapeutic approach against breast and ovarian cancers. Overweight and obesity constitute the most impactful lifestyle-dependent risk factors for cancer and have been tightly linked to a higher number of tumor-related deaths nowadays. The excessive accumulation of energy can lead to an imbalance in the level of essential cellular biomolecules that may result in inflammation and cell-cycle dysregulation. Nutritional strategies and phytochemicals are gaining interest in the management of obesity-related cancers, with several ongoing and completed clinical studies that support their effectiveness. At the same time, cyclin-dependent kinases (CDKs) are becoming an important target in breast and ovarian cancer treatment, with various FDA-approved CDK4/6 inhibitors that have recently received more attention for their potential role in diet-induced obesity (DIO). Here we provide an overview of the most recent studies involving nutraceuticals and other dietary strategies affecting cell-cycle pathways, which might impact the management of breast and ovarian cancers, as well as the repurposing of already commercialized chemotherapeutic options to treat DIO

Neuronal Cells Rearrangement During Aging and Neurodegenerative Disease: Metabolism, Oxidative Stress and Organelles Dynamic

Brain cells normally respond adaptively to oxidative stress or bioenergetic challenges, resulting from ongoing activity in neuronal circuits. During aging and in neurodegenerative disorders, these mechanisms are compromised. In fact, neurons show unique age-related changes in functions and metabolism, resulting in greater susceptibility to insults and disease. Aging affects the nervous system as well as other organs. More precisely, as the nervous system ages, neuron metabolism may change, inducing glucose hypometabolism, impaired transport of critical substrates underlying metabolism, alterations in calcium signaling, and mitochondrial dysfunction. Moreover, in neuronal aging, an accumulation of impaired and aggregated proteins in the cytoplasm and in mitochondria is observed, as the result of oxidative stress: reduced antioxidant defenses and/or increase of reactive oxygen species (ROS). These changes lead to greater vulnerability of neurons in various regions of the brain and increased susceptibility to several diseases. Specifically, the first part of the review article will focus on the major neuronal cells’ rearrangements during aging in response to changes in metabolism and oxidative stress, while the second part will cover the neurodegenerative disease areas in detail

Physiology and Pathophysiology of PPARs in the Eye

Peroxisome proliferator-activated receptor (PPARs) are ligand-activated transcription factors that exert significant roles in the control of multiple physiological processes. The last decade has shown an increasing interest in the role played by the agonists of PPARs in anti-inflammatory, anti-angiogenic, anti-fibrotic effects and in modulating oxidative stress response in different organs. Since the pathologic mechanisms of the majority of the blinding diseases, such as diabetic retinopathy (DR), age-related macular degeneration (AMD), glaucoma and optic neuropathy (ON), often involve neo-angiogenesis, inflammation and oxidative stress-mediated cell death, evidences are accumulating on the potential benefits of PPAR modulation to prevent or ameliorate eye pathologies. In this review, we focused on the description of what is known about the role of PPARs in the ocular pathophysiological processes and on PPARs agonists as innovative adjuvants in the treatment of ocular diseases

Effects of Chronic Oral Probiotic Treatment in Paclitaxel-Induced Neuropathic Pain

Chemotherapy-induced peripheral neuropathy (CIPN) represents one of the most prevalent and potentially disabling side effects due to the use of anticancer drugs, one of the primary neuropathies detected is peripheral neuropathy induced by administration of taxanes, including paclitaxel. It has been demonstrated that gut microbiota is crucial for the therapeutic effect of chemotherapeutic drugs for inhibiting tumor growth and contributed to the pathogenesis of the CIPN. The use of nutraceuticals has receiving growing attention from the research community due to their phytochemical, biological, and pharmacological properties. It has been demonstrated that probiotic formulations may both reduce inflammation and modulate the expression of pain receptors. Our studies tested the efficacy of a probiotic formulation, SLAB51, in preventing paclitaxel-induced neuropathy. Interestingly, our probiotic formulation was able to keep the gut integrity, preserving its functionality, in CIPN-mice, moreover, it prevented the mechanical and cold hypersensitivity induced in paclitaxel-mice. Additionally, ex-vivo analysis showed that in CIPN-mice the pro-biotic treatment increased the expression of opioid and cannabinoid receptors in spinal cord, it prevented in the reduction in nerve fiber damage in the paws and modulated the serum proinflammatory cytokines concentration. On basis of these data, the use of this specific probiotic formulation may represent a valid adjuvant agent to paclitaxel, useful and not toxic for long-lasting therapies

Inhibition of de novo ceramide biosynthesis affects aging phenotype in an in vitro model of neuronal senescence.

Although aging is considered to be an unavoidable event, recent experimental evidence suggests that the process can be counteracted. Intracellular calcium (Ca2+i) dyshomeostasis, mitochondrial dysfunction, oxidative stress, and lipid dysregulation are critical factors that contribute to senescence-related processes. Ceramides, a pleiotropic class of sphingolipids, are important mediators of cellular senescence, but their role in neuronal aging is still largely unexplored. In this study, we investigated the effects of L-cycloserine (L-CS), an inhibitor of thede novoceramide biosynthesis, on the aging phenotype of cortical neurons cultured for 22 days, a setting employed as anin vitromodel of senescence. Our findings indicate that, compared to control cultures, 'aged' neurons display dysregulation of [Ca2+]ilevels, mitochondrial dysfunction, increased generation of reactive oxygen species (ROS), altered synaptic activity as well as the activation of neuronal death-related molecules. Treatment with L-CS positively affected the senescent phenotype, a result associated with recovery of neuronal [Ca2+]isignaling and reduction of mitochondrial dysfunction and ROS generation. The results suggest that thede novoceramide biosynthesis represents a critical intermediate in the molecular and functional cascade leading to neuronal senescence and identify ceramide biosynthesis inhibitors as promising pharmacological tools to decrease age-related neuronal dysfunctions