+publisher:"Università degli Studi di Milano" +contributor:("FORNASARI, DIEGO MARIA MICHELE")

1. C. Bossio. TRANSDIFFERENZIAMENTO DI CELLULE STAMINALI MESENCHIMALI DI RODITORE IN CELLULE DEL SISTEMA NERVOSO CENTRALE.

Degree: 2012, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/171967

► One of the most important challenges in modern medicine is the identification of cell therapy protocols, enabling identification of personalized treatment strategies. WIthin this context,… (more)

▼ One of the most important challenges in modern medicine is the identification of cell therapy protocols, enabling identification of personalized treatment strategies. WIthin this context, adult stem cells (ASC) have a large applicative potential. Contrary to ESCs (embryonic stem cells) and IPSCs (induced pluripotent stem cells), ASCs can be easily extracted from different tissues (bone marrow, skin, adipose tissue, muscle) without raising ethical issues . Moreover, they can be used for autologous transplantation, eliminating the complications associated with autoimmune reactions. Mesenchymal stem cells (MSC,), are an ASC population present in the bone marrow, adipose tissue and other tissues. MSCs are readily available and are able to self-replicate and differentiate, supported by the presence of appropriate stimuli, into cell lines derived from mesodermal lineage (osteoblasts, chondrocytes, adipocytes, and muscle cells). In the last decade it has also been observed that MSCs are able to trans-differentiate into cell types of ectodermal and endodermal origin (transdifferentiation).. The purpose of my work was to develop and define the conditions which can induce trans-differentiation of MSCs extracted from rat adipose tissue toward the neuronal phenotype. The study is part of a major project of regenerative medicine focused on identifying new strategies aimed at restoring functionality in degenerated brain tissue. Initially, MSCs have been characterized by the induction of osteoblastic differentiation, one of their physiological differentiations, and their interaction with biocompatible materials ( titanium dioxide) was analyzed, in order to assess their possible application in medicine for the creation, for example, of prothesic solutions. Subsequently, we sought to devise a GMP compliant cell culturing medium for MSC proliferation, crucial in order to obtain a clinically relevant cell number to differentiate following isolation from adipose tissue. For that reason we tried to induce the differentiation of MSCs into a neural phenotype; a first approach has been to apply protocols already known in literature for the differentiation of different types of stem cells toward the neuronal phenotype.. We considered both the direct differentiation protocols, as well as those that encompassed intermediate stages (sphere-forming). The protocols of differentiation by sphere formation resulted in differentiated MSC expressing glial markers (GFAP), but the protocol was too long(30 days) and a number of differentiated cells very low.. A second approach has been to develop a proprietary differentiation medium (NZ4) using the knowledge and expertise gained from the literature and from the negative results previously obtained The cells maintained in NZ4 differentiation medium , showed a clear morphological change and a high vitality; moreover they expressed both markers of specific neurons in the early stages of development (nestin, doublecortin) as well as markers expressed by mature neurons (βIIItubulin,… Advisors/Committee Members: relatore: D.M.M. Fornasari, tutor: F. Bianco, FORNASARI, DIEGO MARIA MICHELE.

Subjects/Keywords: Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bossio, C. (2012). TRANSDIFFERENZIAMENTO DI CELLULE STAMINALI MESENCHIMALI DI RODITORE IN CELLULE DEL SISTEMA NERVOSO CENTRALE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/171967

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bossio, C.. “TRANSDIFFERENZIAMENTO DI CELLULE STAMINALI MESENCHIMALI DI RODITORE IN CELLULE DEL SISTEMA NERVOSO CENTRALE.” 2012. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/171967.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bossio, C.. “TRANSDIFFERENZIAMENTO DI CELLULE STAMINALI MESENCHIMALI DI RODITORE IN CELLULE DEL SISTEMA NERVOSO CENTRALE.” 2012. Web. 19 Jan 2021.

Vancouver:

Bossio C. TRANSDIFFERENZIAMENTO DI CELLULE STAMINALI MESENCHIMALI DI RODITORE IN CELLULE DEL SISTEMA NERVOSO CENTRALE. [Internet] [Thesis]. Università degli Studi di Milano; 2012. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/171967.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bossio C. TRANSDIFFERENZIAMENTO DI CELLULE STAMINALI MESENCHIMALI DI RODITORE IN CELLULE DEL SISTEMA NERVOSO CENTRALE. [Thesis]. Università degli Studi di Milano; 2012. Available from: http://hdl.handle.net/2434/171967

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

2. V. Alari. CARATTERIZZAZIONE MOLECOLARE E FUNZIONALE DEL GENE CHRFAM7A, FORMA DUPLICATA DELLA SUBUNITÀ ALPHA7 DEL RECETTORE NICOTINICO.

Degree: 2013, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/215883

► The α7 nicotinic acetylcholine receptor (α7 nAChR) has a key role in the innate immune system’s inflammatory response, as part of “cholinergic anti-inflammatory pathway”: a… (more)

▼ The α7 nicotinic acetylcholine receptor (α7 nAChR) has a key role in the innate immune system’s inflammatory response, as part of “cholinergic anti-inflammatory pathway”: a process by which acetylcholine from the vagus nerve reduces the release of the pro-inflammatory cytokine TNFα, thus allowing for a controlled response to infection. The CHRNA7 gene, in humans, is partially duplicated from exon 5-10 and forms an hybrid with four exons (D-A) of a novel gene, FAM7A. This new gene, CHRFAM7A, which is located in the opposite orientation, at 1.6 Mb, from CHRNA7, is not present on every chromosome 15 and a polymorphic variant, in linkage disequilibrium with a 2bp deletion in exon 6, in the same orientation to the CHRNA7 gene, has been described in a cohort of patients with bipolar disorders and schizophrenia. THP-1 monocytic-like cell line expresses only CHRFAM7A, which was down-regulated on treatment with LPS, by a direct transcriptional mechanism reliant on NF-kB. This effect has been confirmed in primary monocytes and macrophages cell cultures, where CHRFAM7A is expressed 200-1000 times more than CHRNA7. Here, the conventional α7 subunit was up-regulated by LPS treatment, thus suggesting the involvement of CHRFAM7A in the regulation of cell surface α7 receptors’ level (a mechanism unique to humans) and the ability of immune cells to respond to acetylcholine, released from the vagus nerve, during infection. This hypothesis seems to be supported by recent works showing that the duplicated form may have a dominant negative effect on the activity of α7 nAChR. Infact, co-expression of CHRFAM7A with α7 results in a significant reduction of the Ach-evoked currents, suggesting the presence of heteromeric non functional receptors at the plasma membrane. The promoter region that regulates the expression of CHRFAM7A is still unknown. To try to identify and characterize this region, 5'-RACE experiments were carried out to map the CHRFAM7A mRNA 5’UTR. RNA was extracted from three different cell lines: THP-1 cells, primary human macrophages and SHSY5Y neuroblastoma cell line. Multiple transcription start sites were identified, depending on the cell line used, suggesting the existence of alternative promoters. A series of constructs that recapitulate the mapping of the CHRFAM7A regulatory region, according to the transcription start sites identified, was also generated. They were cloned into a reporter vector and their functionality was tested by transient transfection both in THP-1 and SHSY5Y cell models. Through these experiments, an intronic region (-702/-208 bp from ATG codon, in exon B) and an Alu sequence (-1155/-821 bp) were identified as negative regulators of reporter gene transcription. Future experiments will allow us to identify other regulatory sites, important for proper CHRFAM7A gene expression in different tissues. Furthermore, two variants exist for CHRFAM7A gene, due to alternative splicing, that gives rise to two protein products of predicted 36 and 47 KDa, whose function is currently unknown. The N-terminally… Advisors/Committee Members: tutor:D. Fornasari, coordinatore: A. Gianni, FORNASARI, DIEGO MARIA MICHELE, GIANNI, ALESSANDRO.

Subjects/Keywords: CHRFAM7A; cholinergic anti-inflammatory pathway; CHRNA7; alpha7; Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Alari, V. (2013). CARATTERIZZAZIONE MOLECOLARE E FUNZIONALE DEL GENE CHRFAM7A, FORMA DUPLICATA DELLA SUBUNITÀ ALPHA7 DEL RECETTORE NICOTINICO. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/215883

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Alari, V.. “CARATTERIZZAZIONE MOLECOLARE E FUNZIONALE DEL GENE CHRFAM7A, FORMA DUPLICATA DELLA SUBUNITÀ ALPHA7 DEL RECETTORE NICOTINICO.” 2013. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/215883.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Alari, V.. “CARATTERIZZAZIONE MOLECOLARE E FUNZIONALE DEL GENE CHRFAM7A, FORMA DUPLICATA DELLA SUBUNITÀ ALPHA7 DEL RECETTORE NICOTINICO.” 2013. Web. 19 Jan 2021.

Vancouver:

Alari V. CARATTERIZZAZIONE MOLECOLARE E FUNZIONALE DEL GENE CHRFAM7A, FORMA DUPLICATA DELLA SUBUNITÀ ALPHA7 DEL RECETTORE NICOTINICO. [Internet] [Thesis]. Università degli Studi di Milano; 2013. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/215883.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Alari V. CARATTERIZZAZIONE MOLECOLARE E FUNZIONALE DEL GENE CHRFAM7A, FORMA DUPLICATA DELLA SUBUNITÀ ALPHA7 DEL RECETTORE NICOTINICO. [Thesis]. Università degli Studi di Milano; 2013. Available from: http://hdl.handle.net/2434/215883

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

3. E. Moretto. TSPAN5 IS A KEY PLAYER IN DENDRITIC SPINES FORMATION AND AMPA RECEPTORS RECYCLING.

Degree: 2016, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/359419

► TSPAN5 is a brain enriched protein member of the tetraspanin superfamily, a group of transmembrane proteins some of which have been shown to fundamentally regulate… (more)

▼ TSPAN5 is a brain enriched protein member of the tetraspanin superfamily, a group of transmembrane proteins some of which have been shown to fundamentally regulate the development of mammalian nervous system. This class of proteins presents the peculiar ability to clusterize forming specialized membrane region called Tetraspanin Enriched Microdomains (TEMs) where they can accumulate other proteins. We found that in developing neurons TSPAN5 was mainly present at the surface membrane while it was concentrated in an intracellular compartment in the postsynapse of mature neurons. We hypothesized that these different localisations could be due to different functions. To deepen the first function of the protein, we knocked down the expression of the protein and found that this led to a dramatic reduction in the number of dendritic spines. We, thus, hypothesized that TSPAN5, through the formation of TEMs, could be responsible of dendritic spines formation. We observed in differential lysis of developing rat hippocampal neurons that two proteins, fundamental for dendritic spines formation, Neuroligin-1 and GluA2 AMPA receptor subunit, were associated with TSPAN5 TEMs. We found that the knockdown of TSPAN5 led to increased mobility of Neuroligin-1 and GluA2 AMPA receptors suggesting the loss of clusterization typical of the first moments of spines formation. To understand the second function of TSPAN5 we identified AP-4 complex as an interactor of the C-terminal intracellular tail of TSPAN5. This complex is known to act on AMPARs trafficking through direct binding of Stargazin, an AMPARs auxiliary subunit. We observed that the knockdown of TSPAN5, carried out after the majority of the synaptogenesis was occurred, caused a strong decrease in surface and total level of GluA2. Different evidences suggested an involvement of TSPAN5 in vesicular transport of GluA2 and we demonstrated that TSPAN5 was necessary for the correct recycling of this receptor. These results highlight multiple roles of TSPAN5 in the regulation of both synapse formation and synaptic functioning in mammalian brain through two distinct mechanisms of action. Advisors/Committee Members: relatore: D. Fornasari, correlatore: M. Passafaro, FORNASARI, DIEGO MARIA MICHELE.

Subjects/Keywords: Settore BIO/10 - Biochimica; Settore BIO/13 - Biologia Applicata

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Moretto, E. (2016). TSPAN5 IS A KEY PLAYER IN DENDRITIC SPINES FORMATION AND AMPA RECEPTORS RECYCLING. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/359419

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Moretto, E.. “TSPAN5 IS A KEY PLAYER IN DENDRITIC SPINES FORMATION AND AMPA RECEPTORS RECYCLING.” 2016. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/359419.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Moretto, E.. “TSPAN5 IS A KEY PLAYER IN DENDRITIC SPINES FORMATION AND AMPA RECEPTORS RECYCLING.” 2016. Web. 19 Jan 2021.

Vancouver:

Moretto E. TSPAN5 IS A KEY PLAYER IN DENDRITIC SPINES FORMATION AND AMPA RECEPTORS RECYCLING. [Internet] [Thesis]. Università degli Studi di Milano; 2016. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/359419.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Moretto E. TSPAN5 IS A KEY PLAYER IN DENDRITIC SPINES FORMATION AND AMPA RECEPTORS RECYCLING. [Thesis]. Università degli Studi di Milano; 2016. Available from: http://hdl.handle.net/2434/359419

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

4. A.C. Folci. HNRNP K: A NEW PROTEIN IN NEURON DEVELOPMENT AND FUNCTION.

Degree: 2012, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/171964

► Regulation of actin polymerization is crucial for neuronal morphogenesis, in particular in neurite elongation and branching, in synaptogenesis and in synaptic plasticity. The heterogeneous nuclear… (more)

▼ Regulation of actin polymerization is crucial for neuronal morphogenesis, in particular in neurite elongation and branching, in synaptogenesis and in synaptic plasticity. The heterogeneous nuclear ribonucleoprotein (hnRNP) K protein is an RNA-binding protein characterized by three K homology domains that mediate RNA-binding. hnRNP K is involved in a host of processes that comprise gene expression, such as chromatin remodeling, transcription, pre-mRNA splicing, mRNA export and translation. Moreover in heterologous cells hnRNP K regulates negatively N-WASP, a protein that interacts with Arp2/3 complex . The main aim of this project was the characterization of hnRNP K function in neurons, we analyzed its role on neuron morphology, subsequently on synaptic function. We found that hippocampal neurons overexpressing hnRNP K siRNA show normal spine morphology, but reduced spine density than control neurons, moreover the knockdown of hnRNP K increases the spine turnover. Furthermore we observed a significant decrease in PSD95 and GluA2 in silenced neurons while no effect was detected on VGAT and VGLUT expression; moreover the hnRNP K knockdown impairs the postsynaptic compartment in excitatory synapse, while the presynaptic compartment was not affected. Since the involvement of GluA2 subunit, we performed electrophysiological recordings in order to investigate functional changes in AMPARs physiology. Preliminary results show a dramatic decrease in excitatory, AMPARs mediated, miniature postsynaptic currents (mEPSCs) frequency in hnRNP K-silenced neurons. The importance of hnRNP K in synaptic activity was confirmed by its increase after chemical LTP induction; moreover the role of hnRNP K in LTP was also demonstrated by the impairment of this phenomena in silenced neurons. Now we are investigating the molecular mechanism underling these alterations studying the interaction with N-WASP. We demonstrated the directly interaction between hnRNP K and N-WASP in neurons by coimmunoprecipitation. The alterations observed in hnRNP K silenced neurons were described from a morphological and a functional perspective, evidencing a strong impairment of excitatory synaptic structures. Besides, our data suggest a strong link between this protein and actin dynamics, suggesting that these effects could eventually be consequent to the actin cytoskeleton rearrangements caused by hnRNP K loss. Advisors/Committee Members: coordinatore: E. Ginelli, correlatore: D. Fornasari, tutor M. Passafaro, FORNASARI, DIEGO MARIA MICHELE, GINELLI, ENRICO.

Subjects/Keywords: RNA binding protein; hnRNP K; excitatory synapse; long-term potentiation; Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Folci, A. (2012). HNRNP K: A NEW PROTEIN IN NEURON DEVELOPMENT AND FUNCTION. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/171964

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Folci, A.C.. “HNRNP K: A NEW PROTEIN IN NEURON DEVELOPMENT AND FUNCTION.” 2012. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/171964.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Folci, A.C.. “HNRNP K: A NEW PROTEIN IN NEURON DEVELOPMENT AND FUNCTION.” 2012. Web. 19 Jan 2021.

Vancouver:

Folci A. HNRNP K: A NEW PROTEIN IN NEURON DEVELOPMENT AND FUNCTION. [Internet] [Thesis]. Università degli Studi di Milano; 2012. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/171964.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Folci A. HNRNP K: A NEW PROTEIN IN NEURON DEVELOPMENT AND FUNCTION. [Thesis]. Università degli Studi di Milano; 2012. Available from: http://hdl.handle.net/2434/171964

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

5. S. Lopa. BASIC AND TRANSLATIONAL ASPECTS OF CELL-BASED APPROACHES FOR EARLY AND LATE STAGE OSTEOARTHRITIS.

Degree: 2014, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/232420

► Osteoarthritis (OA) is a highly disabling pathology which is worldwide investigated by the scientific community due to its increasing diffusion. The incidence of this age-related… (more)

▼ Osteoarthritis (OA) is a highly disabling pathology which is worldwide investigated by the scientific community due to its increasing diffusion. The incidence of this age-related disease is increasing with population ageing and worldwide estimates indicate that 9.6% of men and 18% of women with more than 60 years present OA-related symptoms. Osteoarthritis induces the progressive damage of articular cartilage and subchondral bone and can eventually lead to the complete loss of joint functionality. Nowadays, the management of OA includes non-pharmacological, pharmacological, and surgical treatments. Non pharmacological approaches include exercise, weight loss, and physiotherapy and are used in conjunction with pharmacological treatments. The pharmacological management of OA patients is mainly based on the use of anti-inflammatory drugs for pain control. Hence, the pharmacological approach to OA patients is synptomatic, but not resolutive, since it is not able to alter the progression of the disease. These therapeutical options are not suitable for late stage OA patients, whereby the severe pain and the functional limitations caused by advanced OA degeneration are currently resolved by joint replacement. Due to the low self-repair ability of articular cartilage, untreated cartilage lesions can easily degenerate into OA. Different strategies have been developed to treat promptly chondral lesions, comprising cell-based therapies, such as autologous chondrocyte implantation (ACI). These cell-based therapies have been recently proposed also for the treatment of early OA patients in order to overcome or at least delay the need for a more invasive intervention such as joint replacement. However, major issues associated to the clinical use of autologous articular chondrocytes (ACs) are the limited number of cell harvestable from a small cartilage biopsy and the de-differentiation process occurring during the expansion phase required to achieve a clinically relevant number of cells. Furthermore, advanced age and pathological state of joints negatively affect the chondrogenic potential of ACs, representing important factors to be considered when applying chondrocyte-based therapies in particular categories of patients. In view of a possible use of autologous cell-based therapies for OA patients, we analyzed specific features of ACs as cellular yield, cell doubling rates and the dependence between these parameters and patient-related data in a set of 211 OA patients undergoing total joint replacement (Chapter 3). The patient age was not statistically correlated to the cellular yield, but was negatively correlated with the proliferation rate. No significant correlation was observed between the level of cartilage degeneration (ICRS score) and cellular yield and proliferation rates. However, in samples with the highest degree of cartilage degeneration (ICRS score 4) the cellular yield was lower compared to the other three groups (ICRS scores 1-3). In conclusion, we found that age and degenerative state of cartilage affect some… Advisors/Committee Members: tutor: M. Moretti, D. Fornasari, coordinatore: A. Gianni, FORNASARI, DIEGO MARIA MICHELE, GIANNI, ALESSANDRO.

Subjects/Keywords: osteoarthritis; cell-based therapy; cartilage; tissue engineering; prosthesis; bioreactor; chondrocytes; mesenchymal stem cells; Settore BIO/13 - Biologia Applicata; Settore BIO/14 - Farmacologia; Settore MED/33 - Malattie Apparato Locomotore

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lopa, S. (2014). BASIC AND TRANSLATIONAL ASPECTS OF CELL-BASED APPROACHES FOR EARLY AND LATE STAGE OSTEOARTHRITIS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/232420

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lopa, S.. “BASIC AND TRANSLATIONAL ASPECTS OF CELL-BASED APPROACHES FOR EARLY AND LATE STAGE OSTEOARTHRITIS.” 2014. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/232420.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lopa, S.. “BASIC AND TRANSLATIONAL ASPECTS OF CELL-BASED APPROACHES FOR EARLY AND LATE STAGE OSTEOARTHRITIS.” 2014. Web. 19 Jan 2021.

Vancouver:

Lopa S. BASIC AND TRANSLATIONAL ASPECTS OF CELL-BASED APPROACHES FOR EARLY AND LATE STAGE OSTEOARTHRITIS. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/232420.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lopa S. BASIC AND TRANSLATIONAL ASPECTS OF CELL-BASED APPROACHES FOR EARLY AND LATE STAGE OSTEOARTHRITIS. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/232420

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

6. A. Barbieri. PROGRESSI NELLA TECNOLOGIA DEL VETTORE POXVIRALE MVA: 1. PRODUZIONE DI RICOMBINANTI ESPRIMENTI DUE TRANSGENI 2. TRANSATTIVAZIONE DI GENI CELLULARI.

Degree: 2015, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/251560

► Il virus Modified Vaccinia Ankara (MVA) è un ceppo fortemente attenuato di Vaccinia Virus ed è da tempo utilizzato in qualità di vettore vaccinale nell’uomo.… (more)

Subjects/Keywords: Poxvirus; Modified Vaccinia Ankara; MVA; recombinant; rMVA; multiple; mrMVA; HA; NP; HLAC; ENV; CIITA; C2TA; MHC2TA; MHC; Class-II; transactivator; transactivation; immunotherapy; Settore BIO/11 - Biologia Molecolare; Settore BIO/13 - Biologia Applicata; Settore BIO/19 - Microbiologia Generale

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Barbieri, A. (2015). PROGRESSI NELLA TECNOLOGIA DEL VETTORE POXVIRALE MVA: 1. PRODUZIONE DI RICOMBINANTI ESPRIMENTI DUE TRANSGENI 2. TRANSATTIVAZIONE DI GENI CELLULARI. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/251560

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Barbieri, A.. “PROGRESSI NELLA TECNOLOGIA DEL VETTORE POXVIRALE MVA: 1. PRODUZIONE DI RICOMBINANTI ESPRIMENTI DUE TRANSGENI 2. TRANSATTIVAZIONE DI GENI CELLULARI.” 2015. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/251560.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Barbieri, A.. “PROGRESSI NELLA TECNOLOGIA DEL VETTORE POXVIRALE MVA: 1. PRODUZIONE DI RICOMBINANTI ESPRIMENTI DUE TRANSGENI 2. TRANSATTIVAZIONE DI GENI CELLULARI.” 2015. Web. 19 Jan 2021.

Vancouver:

Barbieri A. PROGRESSI NELLA TECNOLOGIA DEL VETTORE POXVIRALE MVA: 1. PRODUZIONE DI RICOMBINANTI ESPRIMENTI DUE TRANSGENI 2. TRANSATTIVAZIONE DI GENI CELLULARI. [Internet] [Thesis]. Università degli Studi di Milano; 2015. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/251560.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Barbieri A. PROGRESSI NELLA TECNOLOGIA DEL VETTORE POXVIRALE MVA: 1. PRODUZIONE DI RICOMBINANTI ESPRIMENTI DUE TRANSGENI 2. TRANSATTIVAZIONE DI GENI CELLULARI. [Thesis]. Università degli Studi di Milano; 2015. Available from: http://hdl.handle.net/2434/251560

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

7. D. Belperio. EFFECTS OF 3-KETODESOGESTREL AND ALL-TRANS RETINOIC ACID ON PHOX2A AND PHOX2B EXPRESSION: A COMMON STRATEGY AS NEW THERAPEUTIC PERSPECTIVE IN CONGENITAL CENTRAL HYPOVENTILATION SYNDROME (CCHS) AND NEUROBLASTOMA (NB) TREATMENT.

Degree: 2017, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/488326

► PHOX2B (Paired-like homeobox2B) and PHOX2A (Paired-like homeobox2A), are two paired like homeodomain proteins required for the correct autonomic nervous system development and for the specification… (more)

▼ PHOX2B (Paired-like homeobox2B) and PHOX2A (Paired-like homeobox2A), are two paired like homeodomain proteins required for the correct autonomic nervous system development and for the specification of the noradrenergic phenotype. The neuronal development and specification driven by PHOX2 proteins is the result of a fine temporal and spatial control of the two-paralogue proteins. In particular, PHOX2B is considered a “master regulatory gene” in the network leading to the cathecolaminergic phenotype specification, and regulate PHOX2A expression (Coppola et al., 2005). As PHOX2 proteins play crucial role in embryonic neuronal differentiation, their mutations or altered regulation are linked to congenital pathologies, such as Congenital Central Hypoventilation Syndrome (CCHS), a neurodevelopmental disorder characterized by a failure in the autonomic control of breathing, and neuroblastic tumours. The aim of this project was to disclose still unknown mechanisms involved in the pathogenetic mechanisms of PHOX2B-driven disease development, to improve the recognition of new sensitive therapeutic intracellular targets The results obtained during the three years of my PhD thesis are organized in three parts. Part 1) In the first part of the project, we better characterized PHOX2B homeodomain-mediated functions, as hetero-/homo-dimerization and nuclear import, also in the perspective of better analysing the possible effect of polyalanine expansion on these functions, as the expansion of the polyalanine tract in PHOX2B results in a protein with altered DNA-binding, reduced transcriptional activity and defect in nuclear localisation (Trochet et al., 2005; Bachetti et al., 2005; Di Lascio et al., 2013). Interestingly our data clearly underlined a strong interaction between PHOX2A and PHOX2B wild type/ mutants proteins, indicating a possible involvement of PHOX2A in the pathogenesis of CCHS. Part 2) Consistently with PHOX2B role as transcriptional regulator, it is reasonable to suppose that transcriptional dysregulation might be an important mechanism of CCHS pathogenesis and/or tumour development. Recently, studies conducted on NB cell lines have highlighted a correlation between drugs, used in NB treatment or clinical trials (e.g. GA, 17-AAG), and the modulation of PHOX2B gene expression. Moreover, NBs are very sensitive to retinoids, and they were introduced in NB treatment as “additional drugs” in order to induce differentiation in residual cancer cells after NB surgical elimination. In the second part of the project, we showed that “all trans retinoic acid” (ATRA), a retinoid drug that is known to suppress growth in cancer, differently regulates both PHOX2A and PHOX2B expression in SK-N-BE(2)C neuroblastoma cell line, thus suggesting that the molecular mechanism for retinoic-induced cellular differentiation, in NB treatment, is due to a direct regulation of PHOX2 protein expression. Part 3) An interesting strategy into treatments of CCHS, that is currently under investigation, regards the use of progestinic drugs… Advisors/Committee Members: coordinatore: M. Locati, tutor: D. Fornasari, FORNASARI, DIEGO MARIA MICHELE, Benfante, Roberta, LOCATI, MASSIMO.

Subjects/Keywords: PHOX2B; PHOX2A; Congenital Central Hypoventilation Syndrom; Neuroblastoma; 3-keto-desogestrel; All-trans retinoic acid; Settore BIO/11 - Biologia Molecolare; Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Belperio, D. (2017). EFFECTS OF 3-KETODESOGESTREL AND ALL-TRANS RETINOIC ACID ON PHOX2A AND PHOX2B EXPRESSION: A COMMON STRATEGY AS NEW THERAPEUTIC PERSPECTIVE IN CONGENITAL CENTRAL HYPOVENTILATION SYNDROME (CCHS) AND NEUROBLASTOMA (NB) TREATMENT. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/488326

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Belperio, D.. “EFFECTS OF 3-KETODESOGESTREL AND ALL-TRANS RETINOIC ACID ON PHOX2A AND PHOX2B EXPRESSION: A COMMON STRATEGY AS NEW THERAPEUTIC PERSPECTIVE IN CONGENITAL CENTRAL HYPOVENTILATION SYNDROME (CCHS) AND NEUROBLASTOMA (NB) TREATMENT.” 2017. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/488326.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Belperio, D.. “EFFECTS OF 3-KETODESOGESTREL AND ALL-TRANS RETINOIC ACID ON PHOX2A AND PHOX2B EXPRESSION: A COMMON STRATEGY AS NEW THERAPEUTIC PERSPECTIVE IN CONGENITAL CENTRAL HYPOVENTILATION SYNDROME (CCHS) AND NEUROBLASTOMA (NB) TREATMENT.” 2017. Web. 19 Jan 2021.

Vancouver:

Belperio D. EFFECTS OF 3-KETODESOGESTREL AND ALL-TRANS RETINOIC ACID ON PHOX2A AND PHOX2B EXPRESSION: A COMMON STRATEGY AS NEW THERAPEUTIC PERSPECTIVE IN CONGENITAL CENTRAL HYPOVENTILATION SYNDROME (CCHS) AND NEUROBLASTOMA (NB) TREATMENT. [Internet] [Thesis]. Università degli Studi di Milano; 2017. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/488326.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Belperio D. EFFECTS OF 3-KETODESOGESTREL AND ALL-TRANS RETINOIC ACID ON PHOX2A AND PHOX2B EXPRESSION: A COMMON STRATEGY AS NEW THERAPEUTIC PERSPECTIVE IN CONGENITAL CENTRAL HYPOVENTILATION SYNDROME (CCHS) AND NEUROBLASTOMA (NB) TREATMENT. [Thesis]. Università degli Studi di Milano; 2017. Available from: http://hdl.handle.net/2434/488326

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

8. M. Recagni. SELF-AMPLIFYING RNA VECTORS ENCODING FOR SURVIVIN AS ANTI-TUMORAL VACCINE CANDIDATES.

Degree: 2016, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/365945

► Tumor associated antigens (TAAs) can be the target for cancer therapies. In particular, vaccination represents an attractive strategy to elicit specific immune responses against TAAs,… (more)

▼ Tumor associated antigens (TAAs) can be the target for cancer therapies. In particular, vaccination represents an attractive strategy to elicit specific immune responses against TAAs, harnessing the immune system to fight against tumor. Adenovirus and poxvirus derived-viral vectors have been widely used in infectious diseases and as cancer treatment in pre-clinical and clinical trials showing encouraging results in prolonging survival and tumor protection. Nevertheless, viral vectors present various limitations such as a possible pre-existing immunity against the vector, and the induction of neutralizing antibody responses against the vector itself, therefore multiple vaccinations with the same vector become inefficient. The aim of this thesis is to investigate an alternative strategy to overcome viral vector limitations; we focus our attention on alphavirus derived self-amplifying (SA) RNA vectors, when carry non-structural genes to encode the RNA replication machinery, while the structural genes are replaced with the transgene of interest. In the final configuration (Novartis patent) SA-RNA will be delivered by specially designed totally non immunogenic liposomes. SA-RNA presents different advantages: it derives from a totally chemical procedure (no cell cultures involved), it induces high gene expression, it is transiently expressed only in the cytoplasm, it does not induce an immune response against vector itself and it is fast (and cheap) to manufacture. To validate this new technology, Survivin has been chosen as a suitable benchmark TAA because it is over-expressed in virtually every human cancer, and it presents multiple functions involved in tumor maintenance and progression. SA-RNA encoding Survivin has been tested in vitro in terms of ability to replicate inside the cells and to produce Survivin protein. To test SA-RNA in in vivo experiments viral replicon particles (VRPs) have been used as delivery strategy, because the liposomes are not available as yet. VRPs do not present pre-existing immunity against the vector and they are poorly immunogenic, allowing repetitive vaccinations. VRPs encoding Survivin have been tested in vivo in wild-type mice, to evaluate a possible Survivin-specific immune response. The results show that there is a weak immune response against Survivin, in line with what described in the literature, and the experiments suggest that the best immunization schedule is 3 doses 2 weeks apart. In the last part of the project, the efficacy of VRPs encoding Survivin has been tested in two mouse cancer models: pancreatic cancer and malignant mesothelioma. In pancreatic cancer model, a trend in survival increase is observed in treated mice. In malignant mesothelioma model, only an initial difference in survival has been shown, nevertheless, VRPs encoding Survivin induce a biological effect in term of reduced tumor dissemination and increased intra-tumoral cell death in treated mice. From these results and similar results obtained with other vectors, it is clear that Survivin vaccination has a… Advisors/Committee Members: supervisor: Antonio Siccardi, relatore: Diego Fornasari, coordinatore: Massimo Locati, FORNASARI, DIEGO MARIA MICHELE, LOCATI, MASSIMO.

Subjects/Keywords: Settore BIO/13 - Biologia Applicata; Settore BIO/11 - Biologia Molecolare; Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Recagni, M. (2016). SELF-AMPLIFYING RNA VECTORS ENCODING FOR SURVIVIN AS ANTI-TUMORAL VACCINE CANDIDATES. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/365945

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Recagni, M.. “SELF-AMPLIFYING RNA VECTORS ENCODING FOR SURVIVIN AS ANTI-TUMORAL VACCINE CANDIDATES.” 2016. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/365945.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Recagni, M.. “SELF-AMPLIFYING RNA VECTORS ENCODING FOR SURVIVIN AS ANTI-TUMORAL VACCINE CANDIDATES.” 2016. Web. 19 Jan 2021.

Vancouver:

Recagni M. SELF-AMPLIFYING RNA VECTORS ENCODING FOR SURVIVIN AS ANTI-TUMORAL VACCINE CANDIDATES. [Internet] [Thesis]. Università degli Studi di Milano; 2016. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/365945.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Recagni M. SELF-AMPLIFYING RNA VECTORS ENCODING FOR SURVIVIN AS ANTI-TUMORAL VACCINE CANDIDATES. [Thesis]. Università degli Studi di Milano; 2016. Available from: http://hdl.handle.net/2434/365945

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

9. S. Cardani. NEWLY IDENTIFIED PHOX2B-REGULATED GENES AS POSSIBLE DRUG TARGETS FOR THE PHARMACOLOGICAL INTERVENTION IN CONGENITAL CENTRAL HYPOVENTILATION SYNDROME (CCHS).

Degree: 2019, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/610106

► Congenital Central Hypoventilation Syndrome (CCHS, OMIM209880) is a very rare neonatal neurological disorder characterized by a broad variety of symptoms of autonomic nervous system dysfunction… (more)

▼ Congenital Central Hypoventilation Syndrome (CCHS, OMIM209880) is a very rare neonatal neurological disorder characterized by a broad variety of symptoms of autonomic nervous system dysfunction including inadequate control of breathing (Weese-Mayer et al., 2017). It is often associated with Hirschsprung’s disease (HSCR) and neural crest-derived tumours (i.e. neuroblastoma). Frameshift mutations (5%) and polyalanine triplet expansions (from 4 to 13 residues) (95%) have been detected in the coding region of PHOX2B, a transcription factor required for the development of neurons that regulate the cardiovascular, respiratory and digestive organs, forming the sensory and motor arms of the visceral reflex circuits. Consistent with its role as transcriptional regulator, transcriptional dysregulation might be an important mechanism of CCHS pathogenesis. CCHS is a life-long disorder for which the only treatment option is ventilatory support provided by tracheotomy, nasal mask or diaphragm pacing by phrenic nerve stimulation, as pharmacological respiratory stimulants have proved to be ineffective. A strong limitation to the comprehension of the pathogenesis of CCHS, and the development of new and effective treatment for this disease, is the missing knowledge of target genes regulated by PHOX2B, whose expression may be eventually dysregulated. Very little is known about the genes regulated by PHOX2B. Most of the genes identified so far are regulatory genes that encode for transcription factors and enzymes that control downstream processes involved in the survival and differentiation of specific neural structures, such as TH, DBH (Lo et al., 1999; Adachi et al., 2000), PHOX2A (Flora et al., 2001), TLX2 (Borghini et al.,2006), RET (Bachetti et al., 2005) MSX-1 (Revet et al., 2008), SOX10 (Nagashimada et al., 2012), ALK (Bachetti et al., 2010) and PHOX2B itself (Cargin et al., 2005). The aim of this thesis was to identify new potential pharmacological targets for the development of drugs in order to improve the respiratory symptoms and the quality of life of CCHS patients. In the first part of my project we investigated the molecular mechanisms underlying the recovery of chemosensitivity, observed in two CCHS patients, following the administration of the progestinic desogestrel (Straus et al., 2010). In SK-N-BE(2)C cell clones, stably expressing nuclear progesterone receptor isoforms PR-B and PR-A, we demonstrated that 3-KDG treatment, active metabolite of the desogestrel, reduces the expression of PHOX2B, its target genes as well as PHOX2B +7 alanine expanded protein, by means of a post-transcriptional mechanism. This finding provided the evidence of a direct molecular link between PHOX2B and desogestrel and suggested the possibility that reduction of PHOX2B mutant protein may contribute to the positive effects observed in the two CCHS patients. In the second part of my project we proposed to identify new PHOX2B target genes that can be deregulated in the pathology, in the future perspective that might be potential… Advisors/Committee Members: tutor: D. Fornasari, supervisore: R. Benfante, coordinatore: M. Locati, FORNASARI, DIEGO MARIA MICHELE, BENFANTE, ROBERTA, LOCATI, MASSIMO.

Subjects/Keywords: PHOX2B; Congenital central hypoventilation syndrome; Settore BIO/14 - Farmacologia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cardani, S. (2019). NEWLY IDENTIFIED PHOX2B-REGULATED GENES AS POSSIBLE DRUG TARGETS FOR THE PHARMACOLOGICAL INTERVENTION IN CONGENITAL CENTRAL HYPOVENTILATION SYNDROME (CCHS). (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/610106

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Cardani, S.. “NEWLY IDENTIFIED PHOX2B-REGULATED GENES AS POSSIBLE DRUG TARGETS FOR THE PHARMACOLOGICAL INTERVENTION IN CONGENITAL CENTRAL HYPOVENTILATION SYNDROME (CCHS).” 2019. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/610106.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Cardani, S.. “NEWLY IDENTIFIED PHOX2B-REGULATED GENES AS POSSIBLE DRUG TARGETS FOR THE PHARMACOLOGICAL INTERVENTION IN CONGENITAL CENTRAL HYPOVENTILATION SYNDROME (CCHS).” 2019. Web. 19 Jan 2021.

Vancouver:

Cardani S. NEWLY IDENTIFIED PHOX2B-REGULATED GENES AS POSSIBLE DRUG TARGETS FOR THE PHARMACOLOGICAL INTERVENTION IN CONGENITAL CENTRAL HYPOVENTILATION SYNDROME (CCHS). [Internet] [Thesis]. Università degli Studi di Milano; 2019. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/610106.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Cardani S. NEWLY IDENTIFIED PHOX2B-REGULATED GENES AS POSSIBLE DRUG TARGETS FOR THE PHARMACOLOGICAL INTERVENTION IN CONGENITAL CENTRAL HYPOVENTILATION SYNDROME (CCHS). [Thesis]. Università degli Studi di Milano; 2019. Available from: http://hdl.handle.net/2434/610106

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

10. L.M.J. FERREIRA ESPINOZA. ROLE OF IGE IN IMMUNOSURVEILLANCE: MECHANISM AND POTENTIAL THERAPEUTIC APPLICATIONS.

Degree: 2017, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/488915

► IgE is the class of immunoglobulins responsible for the protection against intestinal parasites and exerts a key role in the pathophysiology of allergic reactions. In… (more)

▼ IgE is the class of immunoglobulins responsible for the protection against intestinal parasites and exerts a key role in the pathophysiology of allergic reactions. In addition, it has been demonstrated its involvement in the immune response against tumors in various animal models. According to our model, the function of IgE in the anti-tumor response is mediated by the binding of IgE with its high affinity receptor FcεRI expressed, in mice, on the surface of mast cells and basophils. Activation of FcεRI receptor leads to cell degranulation with release of preformed and newly synthesized mediators able to recruit effector cells that induce the establishment of a powerful inflammation at the tumor site. This inflammation, leading to cell death, could determine the processing of tumor antigens and the resulting immune response against tumor. Based on promising data obtained previously in our laboratories, regarding the adjuvant effect of exogenous IgE in the anti-tumor vaccination and on the many controversial epidemiological studies about a possible link between allergies and cancer protection, we decided to investigate the possible role of endogenous IgE in the immunosurveillance of tumor. The use of two transgenic mouse models, one knock-out for the production of IgE (IgE-KO mice) and the other high IgE producer (KN1 mice), allowed us to investigate the possible involvement of host endogenous IgE in the immunity against cancer. Either in the absence or with a normal amount of IgE, tumor growth, preceded by vaccination with irradiated TS/A tumor cells (mammary adenocarcinoma), is not hindered and is comparable to not immunized mice. Differently, in high IgE producer mice, a single immunization was sufficient to obtain a complete anti-tumor protection. Moreover, challenging mice with a different tumor cell line, N2C tumor cells (less aggressive than TS/A tumor cells), the anti-tumor protection is observed even without immunization in 100% of KN1 mice compared to IgE-KO and wild type control mice. To demonstrate that the protection observed in KN1 mice is due to the interaction of IgE with its high affinity FcRI receptor, we decided to delete the FcRI alpha gene in KN1 mice to remove their receptor. For this purpose we crossed KN1 mice with FcRI-KO mice, in order to obtain a double-mutant mouse model (DM), characterized by elevated levels of IgE but lacking in the expression of the high affinity receptor for IgE. The inoculation of N2C tumor cells in DM mice showed that the previously anti-tumor protection, observed in KN1 mice, has been widely lost and this is the fundamental point of this study because demonstrates that IgE-FcRI axis is the basis of the role of IgE in anti-tumor immune response. We also demonstrated, through an in vitro test of mediators release, the existence of tumor-specific IgE in the serum of KN1 and DM mice that were challenged in vivo with N2C tumor cells; moreover, the depletion of IgE from sera of KN1 and DM mice validate the specific contribution played by IgE in the mediators release.… Advisors/Committee Members: tutor: D. M. Fornasari, supervisor: A. T. Brini, head of phd programm: M. Locati, FORNASARI, DIEGO MARIA MICHELE, BRINI, ANNA TERESA, LOCATI, MASSIMO.

Subjects/Keywords: Settore BIO/13 - Biologia Applicata

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

ESPINOZA, L. F. (2017). ROLE OF IGE IN IMMUNOSURVEILLANCE: MECHANISM AND POTENTIAL THERAPEUTIC APPLICATIONS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/488915

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

ESPINOZA, L.M.J. FERREIRA. “ROLE OF IGE IN IMMUNOSURVEILLANCE: MECHANISM AND POTENTIAL THERAPEUTIC APPLICATIONS.” 2017. Thesis, Università degli Studi di Milano. Accessed January 19, 2021. http://hdl.handle.net/2434/488915.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

ESPINOZA, L.M.J. FERREIRA. “ROLE OF IGE IN IMMUNOSURVEILLANCE: MECHANISM AND POTENTIAL THERAPEUTIC APPLICATIONS.” 2017. Web. 19 Jan 2021.

Vancouver:

ESPINOZA LF. ROLE OF IGE IN IMMUNOSURVEILLANCE: MECHANISM AND POTENTIAL THERAPEUTIC APPLICATIONS. [Internet] [Thesis]. Università degli Studi di Milano; 2017. [cited 2021 Jan 19]. Available from: http://hdl.handle.net/2434/488915.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

ESPINOZA LF. ROLE OF IGE IN IMMUNOSURVEILLANCE: MECHANISM AND POTENTIAL THERAPEUTIC APPLICATIONS. [Thesis]. Università degli Studi di Milano; 2017. Available from: http://hdl.handle.net/2434/488915

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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