Radiotherapy is still a long way from personalizing cancer treatment plans, and its effectiveness depends on the radiosensitivity of tumor cells. Indeed, therapies that are efficient and successful ...for some patients may be relatively ineffective for others. Based on this, radiobiological research is focusing on the ability of some reagents to make cancer cells more responsive to ionizing radiation, as well as to protect the surrounding healthy tissues from possible side effects. In this scenario, zebrafish emerged as an effective model system to test for radiation modifiers that can potentially be used for radiotherapeutic purposes in humans. The adoption of this experimental organism is fully justified and supported by the high similarity between fish and humans in both their genome sequences and the effects provoked in them by ionizing radiation. This review aims to provide the literature state of the art of zebrafish in vivo model for radiobiological studies, particularly focusing on the epigenetic and radiomodifying effects produced during fish embryos’ and larvae’s exposure to radiotherapy treatments.
Conditioned media harvested from stem cell culturing have the potential to be innovative therapeutic tools against various diseases, due to their high content of growth, trophic and protective ...factors. The evaluation in vivo of the effects and biosafety of these products is essential, and zebrafish provides an ideal platform for high-throughput toxicological analysis, concurrently allowing the minimization of the use of mammalian models without losing reliability. In this study, we assessed the biological effects elicited by the exposure of zebrafish embryos to a conditioned medium derived from Wharton’s jelly mesenchymal stem cells. By a multiparametric investigation combining molecular, embryological, behavioural and in vivo imaging techniques, we found that exposure to a conditioned medium at a non-toxic/non-lethal dosage triggers antioxidant, anti-apoptotic and pro-regenerative effects, by upregulation of a set of genes involved in antioxidant defence (nrf2, brg1, sirt1, sirt6, foxO3a, sod2 and cat), glycolysis (ldha) and cell survival (bcl2l1, mcl1a and bim), coupled to downregulation of pro-apoptotic markers (baxa, caspase-3a and caspase-8). To our knowledge, this is the first study comprehensively addressing the effects of a conditioned medium on a whole organism from a developmental, molecular and behavioural perspective, and we are fairly confident that it will pave the way for future therapeutic application.
The hypoxic pattern of glioblastoma (GBM) is known to be a primary cause of radioresistance. Our study explored the possibility of using gene knockdown of key factors involved in the molecular ...response to hypoxia, to overcome GBM radioresistance. We used the U87 cell line subjected to chemical hypoxia generated by CoCl2 and exposed to 2 Gy of X-rays, as single or combined treatments, and evaluated gene expression changes of biomarkers involved in the Warburg effect, cell cycle control, and survival to identify the best molecular targets to be knocked-down, among those directly activated by the HIF-1α transcription factor. By this approach,
and
genes were chosen, and the effects of their morpholino-induced gene silencing were evaluated by exploring the proliferative rates and the molecular modifications of the above-mentioned biomarkers. We found that, after combined treatments,
gene knockdown induced a greater decrease in cell proliferation, compared to
gene knockdown and strong upregulation of
and
, as a sign of cell response to restore the anaerobic glycolysis pathway. Overall,
gene knockdown offered a better chance of controlling the anaerobic use of pyruvate and a better proliferation rate reduction, suggesting it is a suitable silencing target to overcome radioresistance.
The improvement of diagnostic techniques and the efficacy of new therapies in clinical practice have allowed cancer patients to reach a higher chance to be cured together with a better quality of ...life. However, tumors still represent the second leading cause of death worldwide. On the contrary, chemotherapy and radiotherapy (RT) still lack treatment plans which take into account the biological features of tumors and depend on this for their response to treatment. Tumor cells' response to RT is strictly-connected to their radiosensitivity, namely, their ability to resist and to overcome cell damage induced by ionizing radiation (IR). For this reason, radiobiological research is focusing on the ability of chemical compounds to radiosensitize cancer cells so to make them more responsive to IR. In recent years, the interests of researchers have been focused on natural compounds that show antitumoral effects with limited collateral issues. Moreover, nutraceuticals are easy to recover and are thus less expensive. On these bases, several scientific projects have aimed to test also their ability to induce tumor radiosensitization both in vitro and in vivo. The goal of this review is to describe what is known about the role of nutraceuticals in radiotherapy, their use and their potential application.
Protontherapy is a rapidly expanding radiotherapy modality where accelerated proton beams are used to precisely deliver the dose to the tumor target but is generally considered ineffective against ...radioresistant tumors. Proton-Boron Capture Therapy (PBCT) is a novel approach aimed at enhancing proton biological effectiveness. PBCT exploits a nuclear fusion reaction between low-energy protons and
11
B atoms, i.e. p+
11
B→ 3α (p-B), which is supposed to produce highly-DNA damaging α-particles exclusively across the tumor-conformed Spread-Out Bragg Peak (SOBP), without harming healthy tissues in the beam entrance channel. To confirm previous work on PBCT, here we report new in-vitro data obtained at the 62-MeV ocular melanoma-dedicated proton beamline of the INFN-Laboratori Nazionali del Sud (LNS), Catania, Italy. For the first time, we also tested PBCT at the 250-MeV proton beamline used for deep-seated cancers at the Centro Nazionale di Adroterapia Oncologica (CNAO), Pavia, Italy. We used Sodium Mercaptododecaborate (BSH) as
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B carrier, DU145 prostate cancer cells to assess cell killing and non-cancer epithelial breast MCF-10A cells for quantifying chromosome aberrations (CAs) by FISH painting and DNA repair pathway protein expression by western blotting. Cells were exposed at various depths along the two clinical SOBPs. Compared to exposure in the absence of boron, proton irradiation in the presence of BSH significantly reduced DU145 clonogenic survival and increased both frequency and complexity of CAs in MCF-10A cells at the mid- and distal SOBP positions, but not at the beam entrance. BSH-mediated enhancement of DNA damage response was also found at mid-SOBP. These results corroborate PBCT as a strategy to render protontherapy amenable towards radiotherapy-resilient tumor. If coupled with emerging proton FLASH radiotherapy modalities, PBCT could thus widen the protontherapy therapeutic index.
The rapid improvement of space technologies is leading to the continuous increase of space missions that will soon bring humans back to the Moon and, in the coming future, toward longer ...interplanetary missions such as the one to Mars. The idea of living in space is charming and fascinating; however, the space environment is a harsh place to host human life and exposes the crew to many physical challenges. The absence of gravity experienced in space affects many aspects of human biology and can be reproduced in vitro with the help of microgravity simulators. Simulated microgravity (s-μg) is applied in many fields of research, ranging from cell biology to physics, including cancer biology. In our study, we aimed to characterize, at the biological and mechanical level, a Random Positioning Machine in order to simulate microgravity in an in vitro model of Triple-Negative Breast Cancer (TNBC). We investigated the effects played by s-μg by analyzing the change of expression of some genes that drive proliferation, survival, cell death, cancer stemness, and metastasis in the human MDA-MB-231 cell line. Besides the mechanical verification of the RPM used in our studies, our biological findings highlighted the impact of s-μg and its putative involvement in cancer progression.
Radiation therapy (RT) represents a therapeutic option in breast cancer (BC). Even if a great number of BC patients receive RT, not all of them report benefits, due to radioresistance that gets ...activated through several factors, such as the hormone receptor status. Herein, we analyzed the gene expression profiles (GEP) induced by RT in triple-negative BC (TNBC) MDA-MB-231, to study signalling networks involved in radioresistance.
GEP of MDA-MB-231 BC cells treated with a high dose of radiation, went through cDNA microarray analysis. In addition, to examine the cellular effects induced by RT, analyses of morphology and clonogenic evaluation were also conducted.
A descriptive report of GEP and pathways induced by IR is reported from our microarray data. Moreover, the MDA-MB-231 Radioresistent Cell Fraction (RCF) selected, included specific molecules able to drive radioresistance.
In summary, our data highlight, the RT response of TNBC MDA-MB-231 cell line at a transcriptional level, in terms of activating radioresistance in these cells, as a model of late-stage BC.
Oxidative stress occurs when physiological antioxidant systems do not manage to counteract the excessive intracellular production of reactive oxygen species (ROS), which accumulate leading to ...irreversible oxidation of DNA and other biomacromolecules, and thus to the onset of pathological conditions. Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disease characterized by autosomal recessive mutations in the sacsin gene (
). It has been demonstrated that cells of ARSACS patients show bioenergetic and mitochondrial impairment, denoted by reduced respiratory chain activities and ATP synthesis. In order to design a suitable therapy for ARSACS, it is essential to consider that treatments need to cross the blood-brain barrier (BBB), a specialized structure that separates the subtle environment of the brain from blood circulation. Nanostructured lipid carriers (NLCs), constituted by a solid lipid shell and a liquid lipid phase in the core, have been fabricated for loading hydrophobic molecules, improving their bioavailability. Idebenone (IDE), a synthetic analogue of coenzyme Q
, is able to inhibit lipid peroxidation and detoxify several free radicals. However, because of its poor solubility, it requires
drug-delivery systems for enhancing its pharmacokinetic properties, preventing undesired cytotoxicity. In this work, NLCs loaded with idebenone (IDE-NLCs) have been prepared. The nanovectors have been physicochemically characterized, and their biological activity has been evaluated on different central nervous system cell lines. IDE-NLCs demonstrated to be stable in water and in cell culture media, and showed a sustained drug release profile. Interestingly, preliminary data demonstrated their ability to permeate an
BBB model. Their protective antioxidant activity in human healthy primary skin fibroblasts and their therapeutic efficacy in ARSACS-derived primary skin fibroblasts have been also investigated, showing their potential for future development as therapeutic agents.
In the last decade, some wine producers have re‐evaluated the role of micro‐oxygenation guaranteed by the porosity of the earthenware in the fermentation and refinement phases and, thus, the ...potential and limitations of this technique on the flavour and aromatic profile of wine need further investigations. The wine volatile profile was analysed by headspace solid phase microextraction coupled with gas chromatography—mass spectrometry, and the volatile compound percentages in Sangiovese and Cabernet Franc vinified in Stainless Steel Containers and in amphorae over time were compared. Results showed that the in‐amphorae vinification enhances the aromatic components of the Cabernet Franc wine, while there is no substantial difference for Sangiovese wine. A metabolomic approach was also attempted for the first time, and the NMR analysis highlighted a difference between the spectra of the samples vinified in‐amphorae with respect to those vinified in steel suggesting a potential new approach to obtain a significant traceability.
The influence of in‐amphorae winemaking on the volatile profile of two different type of wines was evaluated. The volatile profile highlighted a different effect based on the type of grape used; a metabolomic approach was applied for the traceability of wines in amphora.
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