949 research outputs found
Lab-on-a-chip and integrated strategies in tumor immunotheraphy
No full textBackground
While conventional chemotherapy and radiation therapy have improved the survival of many cancer patients, there are still major disadvantages associated with these treatments such as high toxicity and drug-resistance. The possibility to manipulate the immune system to recognize and kill tumor cells is very attractive despite numerous obstacles remaining to be overcome. In particular, the ability of the immune system to destroy disseminated metastases in a specific way makes immunotherapy an attractive alternative to conventional therapies. Nevertheless, other unconventional technologies emerged in recent years seem to be very promising; in particular the analysis and monitoring of single cell-to-cell interactions and the capability to individually control single cells by Lab-on-a-chip devices have become of great interest in different areas of life sciences. These new technologies, in combination with progresses reached in anti-tumor vaccines, could be useful to improve immune T cell responses against tumor antigen for a more efficient immunotherapy.
Aims
This thesis focuses on two tumor immunotherapy issues: 1) design, realization and validation of innovative Lab-on-a-chip devices for immune system study, that allows single tumor cell and effector cell interaction, detection and isolation; 2) identification of molecular mechanisms that prevent EBV-associated tumors (e.g. Burkitt’s lymphoma) recognition by T cells and study of their potential correction by specific treatments. The main goal of this study remains indeed the evaluation of an integrated strategy for immunotherapy development enhancing for malignancies treatment.
Methods
Biocompatibility test, generation of memory CTL cultures, 51Cr release assay, IFN-Elispot, proteasomes purification, western blot assay, enzymatic assay, immunofluorescence, RT-PCR.
Main Results
As concerns the first part of the thesis, a main achievement was the design of Lab-on-a-chip platform that combined microfluidics and electronics together, consisting in a matrix of
up to thousand microwells where living cells can be deposited. Subsequently, different materials have been evaluated to identify the most biocompatible ones for biosensor manufacturing. Once developed Lab-on-a-chip prototype, it has been tested from a functional point of view. In particular, it has been demonstrated that the biosensor is able to isolate and trap single cells inside microwells by dielectrophoresis, that recovered cells are still alive and that their biological functions and gene expression remain unaltered. Furthermore, tumor cell lysis by immune effector cells could be successfully monitored inside device microwells, showing that biosensor could be used for cell to cell interaction studies.
Regarding the second aim of this thesis, it has been identified a new epitope-specific T cell response against EBV nuclear antigen 1 (EBNA1). It has also been demonstrated that CTLs specific for another EBNA1-derived epitope (referred as HPV) are detectable in the majority of HLA-B35 individuals, and recognize EBV-transformed B lymphocytes (LCL) but not Burkitt’s lymphoma (BL). Afterwards LCL and BL have been compared for their antigen processing machinery, demonstrating that one of the major differences was at the proteasome level; indeed, proteasomes from BL cells have displayed a far lower chymotryptic and tryptic-like activities. Interestingly, it has also been shown that treatment with proteasome inhibitors partially restored the capacity of BL cells to present the HPV epitope.
Conclusions
The results achieved in single cell manipulation and cell to cell analysis interaction by Lab-on-a-chip technology, and the findings reached to improve BL immune recognition, represent an implementation of innovative tools that could allow important progresses in cancer diagnosis and immunotherapy
Post-stroke depression: research methodology of a large multicentre observational study (DESTRO)
No full textThe heterogeneity of published data regarding post-stroke depression (PSD) prompted an Italian multicenter observational study (DESTRO), which took place in 2000-2003. The investigation involved 53 Italian neurology centers: of these, 50 treat acute patients and 3 provide rehabilitation care; 21 centres are in Northern Italy, 20 are in Central Italy, and 12 are in Southern Italy. The time schedule was articulated into three phases: registration of 6289 stroke patients; selection of 1817 cases and enrollment of 1074 patients; and follow-up for two years (1064 patients). Mood assessment was performed by evaluating depressive symptoms according to DSM IV and the Beck depression inventory (visual analog mood scale for aphasic patients). Depressed patients were also administered the Montgomery-Asberg depression rating scale. Scores were related to function (Barthel index, modified Rankin scale), cognition (MMSE), quality of life (SF-36), and clinical data. Data analysis will provide information on PSD prevalence, onset and evolution, correlation with ischemic clinical syndrome, impact on activities of daily living, cognitive level and quality of life. The few data available at the present time concern PSD prevalence in the first six months after stroke (33.6%). DESTRO is a longitudinal investigation of a large patient sample and is expected to provide insights into the relationship of PDS with the functional and clinical consequences of stroke
Competing C═O···C═O, C–H···O, Cl···O, and Cl···Cl Interactions Governing the Structural Phase Transition of 2,6-Dichloro-p-benzoquinone at Tc=122.6 K
No full text2,6-Dichloro-p-benzoquinone (DCBQ) has been investigated by single-crystal X-ray diffraction experiments in the T range of 300−21 K and quantum-mechanical simulations. A reversible monoclinic (high-T) to triclinic
(low-T) phase transition has been detected at Tc = 122.6(5) K. The various
noncovalent interactions (NCIs) that determine the solid-state self recognition of DCBQ have been characterized as a function of T through
the quantum theory of atoms in molecules. On lowering T, carbonyl−carbonyl interactions progressively strengthen, inducing a change in the crystal structure, while the dipolar C−Cl···O=C NCIs and the relatively strong Cl···Cl halogen bonds (XBs) and CH···O hydrogen bonds play an essential, but ancillary, role. Dispersive forces cooperate with other closed-shell dipolar NCIs, and particularly with XBs, in determining their overall attractive character, even when bulky and positively charged chlorine atoms are drawn closer and closer at low temperatures. The intermolecular interaction energies have been evaluated above and below Tc as sums of electrostatic, repulsion, and dispersion contributions
Processi evolutivi ed elaborazioni finali della persona
No full textTITOLO: Processi evolutivi ed elaborazioni finali della persona.
La persona è da intendersi come un continuo processo di produzione ed evoluzione dell' "essere al mondo" all'interno di specifici ambienti morali locali e all'interno
delle strategie, non ultime quelle di ordine religioso (Destro e Pesce 1997).
PARTE 1. Costruzioni e limitazioni della persona. Inizio e fine della vita fisica e attribuzioni fatte post-mortem.
a. La produzione della persona va ben al di là da un processo di determinazione degli individui: nel plasmare gli individui è un mondo morale e ideale in sintesi che
viene messo in scena, che viene prodotto e materializzato.
b. Le nuove tecnologie biomediche hanno contributo a ridefinire radicalmente ambiti della persona culturalmente pensati come dati e inviolabili, facendo registrare il
loro impatto al cuore della costruzione sociale dei confini fra vita e morte.
c. Il rapporto fra persona e realtà sociale viene a configurarsi nei termini di una complicità ontologica.
Un'ulteriore tematica, sempre della prima parte, è quella relativa alla permanenza del significato della persona dopo la sua scomparsa fisica:
a. Il corpo morto nella sua unità è, attraverso pratiche e azioni, uno strumento da de-costruire e da segnare nelle sue singole parti.
b. La persona, dopo la morte, può essere reinserita nel suo gruppo di appartenenza attraverso il suo corpo.
c. In questo processo di recupero della persona il corpo morto va analizzato da un punto di vista rappresentazionale (intellettualistico o medico-biologico).
PARTE 2. "Contenimento" normativo della persona: i divieti-limiti nelle costruzioni simbolico-religiose.
a. La costruzione della persona poggia su una rete di norme che indicano all'individuo - dalla nascita alla morte - le modalità da seguire.
b. In ambito simbolico-religioso l'essere umano è sovente considerato l'interfaccia della divinità. Nella condotta religiosa, la tendenza al contenimento sembra essere
in primo piano. All'interno del sistema religioso, dunque, ciò che rende nettamente individuabile la persona è, seppure non in modo assoluto, il rapporto tra ciò che
gli permesso fare, ciò che fa (o che intende fare).Appare dunque essenziale indagare con quali modalità il meccanismo dei divieti si estenda a vari testi o si presenti
con vigore in vari mondi religiosi (mediorientali, islamici, africani, europei).
c. Alcuni divieti sono inequivocabilmente connessi al flusso della vita reale. Questo nodo tematico diventa il polo attorno al quale si sviluppano molte dinamiche
personali, si garantiscono confini e percorsi "esemplari" della persona
“I fear the secrets of time”. Excerpts from Sogar Papageien überleben uns
No full textPresented here, in the Italian translation by Elisa Destro, are several excerpts from the novel Sogar Papageien überleben uns (2010) by German-Russian author Olga Martynova.Si presentano qui, nella traduzione italiana di Elisa Destro, alcuni estratti dal romanzo Sogar Papageien überleben uns (2010) dell\u27autrice russo-tedesca Olga Martynova
Journal of Anthropological Sciences
No full textGiovanni Destro Bisol e' Editor e Direttore Responsabile della rivista sopra indicata
A Simple Homemade Apparatus for Real-Time Visualization of Nucleic Acid Electrophoresis That Saves Time, Optimizes Separation, and Reduces Chemical Risk
No full text[No abstract available
Journal of Anthropological Sciences
No full textGiovanni Destro Bisol e' Editor della rivista sopra indicat
Inhibition of FasL sustains phagocytic cells and delays myogenesis in regenerating muscles fibers
No full textJ Leukoc Biol. 2001 Mar;69(3):482-9.
Inhibition of fasL sustains phagocytic cells and delays myogenesis in regenerating muscle fibers.
Sandri M, Sandri C, Brun B, Giurisato E, Cantini M, Rossini K, Destro C, Arslan P, Carraro U.
Source
Department of Biomedical Sciences, University of Padova, Italy. [email protected]
Abstract
Macrophage-muscle cell interactions are complex, and the majority is unknown. The persistence of inflammatory cells in skeletal muscle could be critical for myofiber viability. In the present paper, we show that FasL plays a role in the resolution of muscle inflammation. We analyzed inflamed muscles of normal mice treated from day 3 to day 8 with a FasL inhibitor (Fas-Ig) or with control Ig. Treated muscles were collected at 3, 5, and 10 days. The treatment with recombinant Fas-Ig protein induced a severe persistence of inflammatory cells at 5 days (115,000+/-27,838 vs. 41,661+/-6848, p<0.01) and 10 days from injury (145,500+/-40,850 vs. 5000+/-1000, p<0.001). Myofiber regeneration was highly impaired (37+/-14 vs. 252+/-28, p<0.01). Apoptosis of phagocytic cells was absent during Fas-Ig treatment (0.9+/-0.6 vs. 1300+/-150, p<0.0001), but apoptotic, mononucleated cells appeared at day 10, 2 days after the suspension of Fas-Ig administration. The time course of FasL expression during muscle inflammation, at mRNA and protein level, reveals a peak during myoblast proliferation. The peak of FasL expression coincides with the peak of apoptosis of phagocytic cells. In situ hybridization shows the co-expression of FasL and MyoD mRNA in mononucleated cells, i.e., myoblasts. Experiments on the myoblast cell culture confirmed the expression of FasL in myoblasts. The findings shown here indicate one of the pathways to control myoblast-macrophage interaction and might be relevant for the control of inflammatory cells in muscle tissue. Perhaps altering FasL expression with recombinant proteins could ameliorate inflammation in degenerative myopathies and up-regulate muscle regeneration.
PMID:
11261797
[PubMed - indexed for MEDLINE
Legami intergenerazionali e identificazioni inconsce nel romanzo L'ottava vita (per Brilka) di Nino Haratischwili
No full textThe article aims to investigate the representation of the transgenerational transmission of traumatic experiences in the novel Das achte Leben (für Brilka) (2014) by the Georgian-born author Nino Haratischwili, by drawing on psychoanalytic and epigenetic studies on the subject, as well as cultural studies on memory and post-memory. The article highlights psychic processes such as phantasmatic projections and telescopic identifications of the unconscious, which denote a disturbance in genealogy – ascribable to unprocessed grief and trauma – and transmitted from one generation to another on an unconscious level as a void. At the same time, the essay also examines the therapeutic journey that needs to be undertaken by the descendants of the family at the centre of the work in order to re-engage with their past history. If, on the one hand, the narrative is full of gaps and circular structures (a symptom of an unspeakable trauma that cannot be expressed and always returns to itself), on the other hand, the blank pages at the end, as well as the circular structure of the frame, have a positive meaning – that of (post-)memory, which attempts to return to its origins in order to create a new, meaningful narrative and, with it, a new life
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