1,720,972 research outputs found
Evaluation of the activity of photoactivatable compounds under different irradiation conditions on human cancer cell lines for photochemotherapeutic applications
Full text linkABSTRACT
During these 3 years of PhD course, my research activity has focused on the evaluation of the antiproliferative activity of known photosensitizing compounds, using activation under different selected wavelengths.
Evaluation of 8-Methoxypsoralen (8-MOP) and 4,6,6’-Trimethylangelicin (TMA) antiproliferative activity in combination with Blue Light irradiation
Psoralens and angelicins are known photosensitizing agents, used in combination with UVA light (PUVA) for the treatment of a variety of diseases (i.e. psoriasis, vitiligo, mycosis fungoides, Graft-versus-Host disease, cutaneous T-cell lymphoma). Although this therapeutic approach proved to be highly effective, side effects may occur with PUVA therapy, including skin cancer (squamous cell carcinoma and basal cell carcinoma). The use of UVA irradiation also limits the light penetration into tissues, restricting the application of this therapeutic approach to superficial areas and it is known to cause DNA damages.
Previous studies indicated that psoralens can be activated with longer wavelengths (417 nm), with a reduced formation of mutagenic lesions, such as DNA crosslinks. These evidences gave us the idea to use blue light (BL) for the activation of psoralens, in order to reduce the toxicity of the treatment and to extend the application of this therapeutic approach to solid tumors as BL is also more penetrating than UVA.
Thus, the antiproliferative activity of 8-MOP and TMA was evaluated in combination with blue light on DU145 human prostate cancer cell line, along with the detection of DNA damages, ROS generation inside the cells and western blot analysis of proapoptotic, prosurvival and proliferative molecular pathways. Flow cytometry was used for the determination of cell death mechanism and to analyse the expression of CD44 receptors, which are markers for stem cell features.
Potential anticancer activity of Fluphenazine activated with UVA light
Fluphenazine (FPZ) is an antipsychotic agent from the phenothiazine family. It exerts its activity by blocking postsynaptic D2 dopamine receptors in the limbic, cortical system and basal ganglia areas of the brain. Blocking the action of dopamine, it reduces the hallucinations and delusions that are associated with schizophrenia. FPZ has a wide adverse effect profile, including extrapyramidal symptoms (akathisia, tremors, dyskinesia). In particular, fluphenazine induces photosensitization in patients exposed to sunlight as adverse effect.
Exploiting this last side effect of FPZ under light exposure, its cytotoxic activity in combination with UVA light was investigated on three different cell line
Overview of Nanoparticle-Based Approaches for the Combination of Photodynamic Therapy (PDT) and Chemotherapy at the Preclinical Stage
Full text linkThe widespread diffusion of photodynamic therapy (PDT) as a clinical treatment for solid tumors is mainly limited by the patient’s adverse reaction (skin photosensivity), insufficient light penetration in deeply seated neoplastic lesions, unfavorable photosensitizers (PSs) biodistribution, and photokilling efficiency due to PS aggregation in biological environments. Despite this, recent preclinical studies reported on successful combinatorial regimes of PSs with chemotherapeutics obtained through the drugs encapsulation in multifunctional nanometric delivery systems. The aim of the present review deals with the punctual description of several nanosystems designed not only with the objective of co-transporting a PS and a chemodrug for combination therapy, but also with the goal of improving the therapeutic efficacy by facing the main critical issues of both therapies (side effects, scarce tumor oxygenation and light penetration, premature drug clearance, unspecific biodistribution, etc.). Therefore, particular attention is paid to the description of bio-responsive drugs and nanoparticles (NPs), targeted nanosystems, biomimetic approaches, and upconverting NPs, including analyzing the therapeutic efficacy of the proposed photo-chemotherapeutic regimens in in vitro and in vivo cancer models
Analysis of Radiation Toxicity in Mammalian Cells Stably Transduced with Mitochondrial Stat3.
Full text linkSynthesis, Conformational Analysis and Antitumor Activity of the Naturally Occurring Antimicrobial Medium-Length Peptaibol Pentadecaibin and Spin-Labeled Analogs Thereof
Full text linkPeptaibols are proteolysis-resistant, membrane-active peptides. Their remarkably stable helical 3D-structures are key for their bioactivity. They can insert themselves into the lipid bilayer as barrel staves, or lay on its surface like carpets, depending on both their length and the thickness of the lipid bilayer. Medium-length peptaibols are of particular interest for studying the peptide–membrane interaction because their length allows them to adopt either orientation as a function of the membrane thickness, which, in turn, might even result in an enhanced selectivity. Electron paramagnetic resonance (EPR) is the election technique used to this aim, but it requires the synthesis of spin-labeled medium-length peptaibols, which, in turn, is hampered by the poor reactivity of the Cα-tetrasubstituted residues featured in their sequences. After several years of trial and error, we are now able to give state-of-the-art advice for a successful synthesis of nitroxide-containing peptaibols, avoiding deleted sequences, side reactions and difficult purification steps. Herein, we describe our strategy and itsapplication to the synthesis of spin-labeled analogs of the recently discovered, natural, medium-length peptaibol pentadecaibin. We studied the antitumor activity of pentadecaibin and its analogs, finding potent cytotoxicity against human triple-negative breast cancer and ovarian cancer. Finally, our analysis of the peptide conformational preferences and membrane interaction proved that pentadecaibinspin-labeling does not alter the biological features of the native sequence and is suitable for further EPR studies. The nitroxide-containing pentadecaibins, and their synthetic strategy described herein, will help to shed light on the mechanism of the peptide–membrane interaction of medium-length peptaibols
Towards a better understanding of light-glucose induced modifications on the structure and biological activity of formulated Nivolumab
Full text linkIn the last years, monoclonal antibodies (mAbs) have rapidly escalated as biopharmaceuticals into cancer
treatments, mainly for their target specificity accompanied by less side effects than the traditional chemotherapy,
and stimulation of reliable long-term anti-tumoral responses. They are potentially unstable macromolecules
under shaking, temperature fluctuations, humidity, and indoor and outdoor light exposure, all stressors occurring
throughout their production, transport, storage, handling, and administration steps. The chemical and physical
modifications of mAbs can lead not only to the loss of their bioactivity, but also to the enhancement of their
immunogenicity with increasing risk of severe hypersensitivity reactions in treated patients because of aggregation. The photostability of Nivolumab, the active principle of Opdivo, has been here studied. The chemical
modifications detected by LC-MS/MS after the light stressor showed Trp and Met mono and double oxidations as
primary damage induced by light on this mAb. The oxidations were stronger when the mAb was diluted in sterile
glucose solution where 5-HMF, a major heat glucose degradation product, acted as singlet oxygen producer
under irradiation. However, no significant changes in the mAb conformation were found. On the contrary,
formation of a significant extent of aggregates has been detected after shining high simulated sunlight doses. This
again took place particularly when Nivolumab was diluted in sterile glucose, thus raising a direct correlation
between the aggregation and the oxidative processes. Finally, the biological activity under light stress assessed by
a blockade assay test demonstrated the maintenance of the PD-1 target recognition even under high light doses
and in glucose solution, in line with the preservation of the secondary and tertiary structures of the mAb. Based
on our results, as sterile glucose is mostly used for children’s therapies, special warnings, and precautions for
healthcare professionals should be included for their use to the pediatric population
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Studi di citotossicità di flufenazina su cellule tumorali umane in seguito ad attivazione con luce UVA
No full textVariations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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