Prooxidant state in anticancer drugs and prospect use of mitochondrial cofactors and anti-inflammatory agents in cancer prevention.

An extensive body of literature has associated cancer with redox imbalance and inflammatory conditions. Thus, several studies and current clinical practice have relied on the use of anticancer drugs known to be associated with prooxidant state. On the other hand, a number of studies have reported on the effects of several antioxidants, anti-inflammatory agents and of mitochondrial cofactors (also termed mitochondrial nutrients, MNs) in counteracting or slowing carcinogenesis, or in controlling cancer growth.

Transdermal delivery of PeptiCRAd cancer vaccine using microneedle patches.

Microneedles (MNs) are a prospective system in cancer immunotherapy to overcome barriers regarding proper antigen delivery and presentation. This study aims at identifying the potential of MNs for the delivery of Peptide-coated Conditionally Replicating Adenoviruses (PeptiCRAd), whereby peptides enhance the immunogenic properties of adenoviruses presenting tumor associated antigens. The combination of PeptiCRAd with MNs containing polyvinylpyrrolidone and sucrose was tested for the preservation of structure, induction of immune response, and tumor eradication.

Low-dose decitabine enhances the efficacy of viral cancer vaccines for immunotherapy.

Cancer immunotherapy requires a specific antitumor CD8 T cell-driven immune response; however, upon genetic and epigenetic alterations of the antigen processing and presenting components, cancer cells escape the CD8 T cell recognition. As a result, poorly immunogenic tumors are refractory to conventional immunotherapy. In this context, the use of viral cancer vaccines in combination with hypomethylating agents represents a promising strategy to prevent cancer from escaping immune system recognition.

Mitochondrial dysfunction in Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome: prospect use of antioxidants and mitochondrial nutrients.

Fragile X syndrome (FXS) is a genetic disorder characterized by mutation in the FMR1 gene, leading to the absence or reduced levels of fragile X Messenger Ribonucleoprotein 1 (FMRP). This results in neurodevelopmental deficits, including autistic spectrum conditions. On the other hand, Fragile X-associated tremor/ataxia syndrome (FXTAS) is a distinct disorder caused by the premutation in the FMR1 gene.

Novel peptide-based oncolytic vaccine for enhancement of adaptive antitumor immune response via co-engagement of innate Fcγ and Fcα receptors.

Background: Cancer immunotherapy relies on using the immune system to recognize and eradicate cancer cells. Adaptive immunity, which consists of mainly antigen-specific cytotoxic T cells, plays a pivotal role in controlling cancer progression. However, innate immunity is a necessary component of the cancer immune response to support an immunomodulatory state, enabling T-cell immunosurveillance.

Novel combinatorial therapy of oncolytic adenovirus AdV5/3-D24-ICOSL-CD40L with anti PD-1 exhibits enhanced anti-cancer efficacy through promotion of intratumoral T-cell infiltration and modulation of tumour microenvironment in mesothelioma mouse model.

Introduction: Malignant mesothelioma is a rare and aggressive form of cancer. Despite improvements in cancer treatment, there are still no curative treatment modalities for advanced stage of the malignancy. The aim of this study was to evaluate the anti-tumor efficacy of a novel combinatorial therapy combining AdV5/3-D24-ICOSL-CD40L, an oncolytic vector, with an anti-PD-1 monoclonal antibody.

Development of mesothelioma-specific oncolytic immunotherapy enabled by immunopeptidomics of murine and human mesothelioma tumors.

Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. As the available therapeutic options show a lack of efficacy, novel therapeutic strategies are urgently needed. Given its T-cell infiltration, we hypothesized that MPM is a suitable target for therapeutic cancer vaccination.

Integrating immunopeptidome analysis for the design and development of cancer vaccines.

The repertoire of naturally presented peptides within the MHC (major histocompatibility complex) or HLA (human leukocyte antigens) system on the cellular surface of every mammalian cell is referred to as ligandome or immunopeptidome. This later gained momentum upon the discovery of CD8 + T cells able to recognize and kill cancer cells in an MHC-I antigen-restricted manner. Indeed, cancer immune surveillance relies on T cell recognition of MHC-I-restricted peptides, making the identification of those peptides the core for designing T cell-based cancer vaccines.

Hormetic Effects of Cerium, Lanthanum and Their Combination at Sub-micromolar Concentrations in Sea Urchin Sperm.

Rare earth elements (REEs) cerium (Ce) and lanthanum (La) and their combination were tested across a concentration range, from toxic (10 to 10 M) to lower concentrations (10 to 10 M) for their effects on sea urchin (Sphaerechinus granularis) sperm. A significantly decreased fertilization rate (FR) was found for sperm exposed to 10 M Ce, La and their combination, opposed to a significant increase of FR following 10 and 10 M REE sperm exposure. The offspring of REE-exposed sperm showed significantly increased developmental defects following sperm exposure to 10 M REEs vs.

Controlled release of enhanced cross-hybrid IgGA Fc PD-L1 inhibitors using oncolytic adenoviruses.

Immune checkpoint inhibitors have clinical success in prolonging the life of many cancer patients. However, only a minority of patients benefit from such therapy, calling for further improvements. Currently, most PD-L1 checkpoint inhibitors in the clinic do not elicit Fc effector mechanisms that would substantially increase their efficacy.

Cancer immunotherapies: A hope for the uncurable?

The use of cancer immunotherapies is not novel but has been used over the decades in the clinic. Only recently have we found the true potential of stimulating an anti-tumor response after the breakthrough of checkpoint inhibitors. Cancer immunotherapies have become the first line treatment for many malignancies at various stages.

Cytogenetic and developmental toxicity of bisphenol A and bisphenol S in Arbacia lixula sea urchin embryos.

Bisphenol S (BP-S) is one of the most important substitutes of bisphenol A (BP-A), and its environmental occurrence is predicted to intensify in the future. Both BP-A and BP-S were tested for adverse effects on early life stages of Arbacia lixula sea urchins at 0.1 up to 100 µM test concentrations, by evaluating cytogenetic and developmental toxicity endpoints.

Evaluation of Rare Earth Element-Associated Hormetic Effects in Candidate Fertilizers and Livestock Feed Additives.

Rare earth elements (REEs) are recognized as emerging contaminants with implications in human and environmental health. Apart from their adverse effects, REEs have been reported as having positive effects when amended to fertilizers and livestock feed additives, thus suggesting a hormetic trend, implying a concentration-related shift from stimulation to inhibition and toxicity, with analogous trends that have been assessed for a number of xenobiotics. In view of optimizing the success of REE mixtures in stimulating crop yield and/or livestock growth or egg production, one should foresee the comparative concentration-related effects of individual REEs (e.

Lutein levels in arterial cord blood correlate with neurotrophic calcium binding S100B protein in healthy preterm and term newborns.

Background: S100B is an established biomarker of brain development and damage. Lutein (LT) is a naturally occurring xanthophyll carotenoid mainly concentrated in the central nervous system (CNS), but its neurotrophic role is still debated. We investigated whether LT cord blood concentrations correlate with S100B in a cohort of preterm and term healthy newborns.

A novel cancer vaccine for melanoma based on an approved vaccine against measles, mumps, and rubella.

Common vaccines for infectious diseases have been repurposed as cancer immunotherapies. The intratumoral administration of these repurposed vaccines can induce immune cell infiltration into the treated tumor. Here, we have used an approved trivalent live attenuated measles, mumps, and rubella (MMR) vaccine in our previously developed PeptiENV cancer vaccine platform.

Peptides-Coated Oncolytic Vaccines for Cancer Personalized Medicine.

Oncolytic Viruses (OVs) work through two main mechanisms of action: the direct lysis of the virus-infected cancer cells and the release of tumor antigens as a result of the viral burst. In this sc.enario, the OVs act as cancer vaccines, since the immunogenicity of the virus is combined with tumor antigens, that direct the specificity of the anti-tumor adaptive immune response.

A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines.

Besides the isolation and identification of major histocompatibility complex I-restricted peptides from the surface of cancer cells, one of the challenges is eliciting an effective antitumor CD8+ T-cell-mediated response as part of therapeutic cancer vaccine. Therefore, the establishment of a solid pipeline for the downstream selection of clinically relevant peptides and the subsequent creation of therapeutic cancer vaccines are of utmost importance. Indeed, the use of peptides for eliciting specific antitumor adaptive immunity is hindered by two main limitations: the efficient selection of the most optimal candidate peptides and the use of a highly immunogenic platform to combine with the peptides to induce effective tumor-specific adaptive immune responses.

Oncolytic ImmunoViroTherapy: A long history of crosstalk between viruses and immune system for cancer treatment.

Cancer Immunotherapy relies on harnessing a patient's immune system to fine-tune specific anti-tumor responses and ultimately eradicate cancer. Among diverse therapeutic approaches, oncolytic viruses (OVs) have emerged as a novel form of cancer immunotherapy. OVs are a naturally occurring or genetically modified class of viruses able to selectively kill cancer cells, leaving healthy cells unharmed; in the last two decades, the role of OVs has been redefined to act beyond their oncolytic activity.

Mitigating the pro-oxidant state and melanogenesis of Retinitis pigmentosa: by counteracting mitochondrial dysfunction.

Retinitis pigmentosa (RP) is a group of mitochondrial diseases characterized by progressive degeneration of rods and cones leading to retinal loss of light sensitivity and, consequently, to blindness. To date, no cure is available according to the clinical literature. As a disease associated with pigmentation-related, pro-oxidant state, and mitochondrial dysfunction, RP may be viewed at the crossroads of different pathogenetic pathways involved in adverse health outcomes, where mitochondria play a preeminent role.

Ankle dorsiflexion after isolated medial versus complete proximal gastrocnemius recession: A cadaveric study.

Purpose: Gastrocnemius recession has been described in the treatment of gastrocnemius contracture. The aims of this study were: (1) to assess the change in ankle dorsiflexion after isolated medial gastrocnemius recession performed according to L.S.

PeptiCHIP: A Microfluidic Platform for Tumor Antigen Landscape Identification.

Identification of HLA class I ligands from the tumor surface (ligandome or immunopeptidome) is essential for designing T-cell mediated cancer therapeutic approaches. However, the sensitivity of the process for isolating MHC-I restricted tumor-specific peptides has been the major limiting factor for reliable tumor antigen characterization, making clear the need for technical improvement. Here, we describe our work from the fabrication and development of a microfluidic-based chip (PeptiCHIP) and its use to identify and characterize tumor-specific ligands on clinically relevant human samples.