Dissertations / Theses: 'Patologia generale'

1

Bianco, Carlo <1980&gt. "Analisi d'immagine, patologia quantitativa e dimensione frattale in patologia veterinaria: Densita' e forme." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/6833/1/ANALISI_D%E2%80%99IMMAGINE%2C_PATOLOGIA_QUANTITATIVA_E.pdf.

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Abstract:

Fino dagli albori della metodica scientifica, l’osservazione e la vista hanno giocato un ruolo fondamentale. La patologia è una scienza visiva, dove le forme, i colori, le interfacce e le architetture di organi, tessuti, cellule e componenti cellulari guidano l’occhio del patologo e ne indirizzano la scelta diagnostico-classificativa. L’osservazione del preparato istologico in microscopia ottica si attua mediante l’esame e la caratterizzazione di anomalie ad ingrandimenti progressivamente crescenti, a diverse scale spaziali, che partono dalla valutazione dell’assetto architettonico sovracellulare, per poi spostarsi ad investigare e descrivere le cellule e le peculiarità citomorfologiche delle stesse. A differenza di altri esami di laboratorio che sono pienamente quantificabili, l’analisi istologica è intrinsecamente soggettiva, e quindi incline ad un alto grado di variabilità nei risultati prodotti da differenti patologi. L’analisi d’immagine, l’estrazione da un’immagine digitale di contenuti utili, rappresenta una metodica oggettiva, valida e robusta ormai largamente impiegata a completamento del lavoro del patologo. Si sottolinea come l’analisi d’immagine possa essere vista come fase descrittiva quantitativa di preparati macroscopici e microscopici che poi viene seguita da una interpretazione. Nuovamente si sottolinea come questi descrittori siano oggettivi, ripetibili e riproducibili, e non soggetti a bassa concordanza inter operatore. La presente tesi si snoda attraverso un percorso concettuale orientato ad applicazioni di analisi d’immagine e patologia quantitativa che parte dalle applicazioni più elementari (densità, misure lineari), per arrivare a nozioni più avanzate, quali lo studio di complessità delle forme mediante l’analisi frattale e la quantificazione del pattern spaziale di strutture sovracellulari.
Until the dawn of the scientific method, observation was pivotal. Pathology is a visual science, where the forms, colors, interfaces and architectures of organs, tissues, cells and cell components direct the diagnosis. The observation of the histological preparation in optical microscopy is implemented through the examination and characterization of anomalies at progressively higher magnifications, at different spatial scales, which start from the evaluation of sovracellular architecture, then move to investigate and describe the cells and cytological fetures. In contrast to other laboratory tests that are quantitative, histological analysis is inherently subjective, and therefore prone to a high degree of variability in the results produced by different pathologists. The image analysis, extraction from a digital image of meaningful content, is an objective and robust method, now widely used to aid the pathologist. Should be stressed that image analysis can be seen as a quantitative descriptor of macroscopic and microscopic specimens, followed by an interpretation (the diagnosis). This thesis unfolds through different applications of image analysis and quantitative pathology that starts with the most basic applications (density, linear measurements), to get to more advanced concepts, such as the study of the complexity of shapes by the ' fractal analysis and quantification of the spatial patterns of sovracellular structures.

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2

Bianco, Carlo <1980&gt. "Analisi d'immagine, patologia quantitativa e dimensione frattale in patologia veterinaria: Densita' e forme." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/6833/.

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Abstract:

Fino dagli albori della metodica scientifica, l’osservazione e la vista hanno giocato un ruolo fondamentale. La patologia è una scienza visiva, dove le forme, i colori, le interfacce e le architetture di organi, tessuti, cellule e componenti cellulari guidano l’occhio del patologo e ne indirizzano la scelta diagnostico-classificativa. L’osservazione del preparato istologico in microscopia ottica si attua mediante l’esame e la caratterizzazione di anomalie ad ingrandimenti progressivamente crescenti, a diverse scale spaziali, che partono dalla valutazione dell’assetto architettonico sovracellulare, per poi spostarsi ad investigare e descrivere le cellule e le peculiarità citomorfologiche delle stesse. A differenza di altri esami di laboratorio che sono pienamente quantificabili, l’analisi istologica è intrinsecamente soggettiva, e quindi incline ad un alto grado di variabilità nei risultati prodotti da differenti patologi. L’analisi d’immagine, l’estrazione da un’immagine digitale di contenuti utili, rappresenta una metodica oggettiva, valida e robusta ormai largamente impiegata a completamento del lavoro del patologo. Si sottolinea come l’analisi d’immagine possa essere vista come fase descrittiva quantitativa di preparati macroscopici e microscopici che poi viene seguita da una interpretazione. Nuovamente si sottolinea come questi descrittori siano oggettivi, ripetibili e riproducibili, e non soggetti a bassa concordanza inter operatore. La presente tesi si snoda attraverso un percorso concettuale orientato ad applicazioni di analisi d’immagine e patologia quantitativa che parte dalle applicazioni più elementari (densità, misure lineari), per arrivare a nozioni più avanzate, quali lo studio di complessità delle forme mediante l’analisi frattale e la quantificazione del pattern spaziale di strutture sovracellulari.
Until the dawn of the scientific method, observation was pivotal. Pathology is a visual science, where the forms, colors, interfaces and architectures of organs, tissues, cells and cell components direct the diagnosis. The observation of the histological preparation in optical microscopy is implemented through the examination and characterization of anomalies at progressively higher magnifications, at different spatial scales, which start from the evaluation of sovracellular architecture, then move to investigate and describe the cells and cytological fetures. In contrast to other laboratory tests that are quantitative, histological analysis is inherently subjective, and therefore prone to a high degree of variability in the results produced by different pathologists. The image analysis, extraction from a digital image of meaningful content, is an objective and robust method, now widely used to aid the pathologist. Should be stressed that image analysis can be seen as a quantitative descriptor of macroscopic and microscopic specimens, followed by an interpretation (the diagnosis). This thesis unfolds through different applications of image analysis and quantitative pathology that starts with the most basic applications (density, linear measurements), to get to more advanced concepts, such as the study of the complexity of shapes by the ' fractal analysis and quantification of the spatial patterns of sovracellular structures.

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3

Ravaioli, Stefano <1974&gt. "Patologia ed epidemiologia molecolare delle infezioni associate all'impianto." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2010. http://amsdottorato.unibo.it/2518/1/TESI_Ravaioli_Stefano.pdf.

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Staphylococcus aureus and Staphylococcus epidermidis are leading pathogens of implant-related infections. This study aimed at investigating the diverse distribution of different bacterial pathogen factors in most prevalent S. aureus and S. epidermidis strain types causing orthopaedic implant infections. In this study the presence both of the ica genes, encoding for biofilm exopolysaccharide production, and the insertion sequence IS256, a mobile element frequently associated to transposons, was investigated in relationship with the prevalence of antibiotic resistance among Staphylococcus epidermidis strains. The investigation was conducted on 70 clinical isolates derived from orthopaedic implant infections. Among the clinical isolates investigated a dramatic high level of association was found between the presence of ica genes as well as of IS256 and multiple resistance to all the antibiotics tested. Noteworthy, a striking full association between the presence of IS256 and resistance to gentamicin was found, being none of the IS256-negative strain resistant to this antibiotic. This association is probably because of the link of the corresponding aminoglycoside-resistance genes, and IS256, often co-existing within the same staphylococcal transposon. Moreover we investigated the prevalence of aac(6’)-Ie-aph(2’’), aph (3’) IIIa, and ant(4’) genes, encoding for the three forms of aminoglycoside-modifying enzymes (AME), responsible for resistance to aminoglycoside antibiotics. All isolates were characterized by automated ribotyping, so that the presence of antibiotic resistance determinants was investigated in strains exhibiting different ribopatterns. Interestingly, combinations of coexisting AME genes appeared to be typical of specific ribopatterns. 200 S. aureus isolates, categorized into ribogroups by automated ribotyping, i.e. rDNA restriction fragment length polymorphism analysis, were screened for the presence of a panel of adhesins genes, accessory gene regulatory (agr) polymorphisms and toxins. For many ribogroups, characteristic tandem genes arrangements could be identified. Surprisingly, the isolates of the most prevalent cluster, enlisting 27 isolates, were susceptible to almost all antibiotics and never possessed the lukD/lukE gene, thus suggesting the role of factors other than antibiotic resistance and the here investigated toxins in driving the major epidemic clone to the larger success. Afterwards, .in the predominant S. aureus cluster, the bbp gene encoding bone sialoprotein-binding protein appeared a typical virulence trait, found in 93% of the isolates. Conversely, the bbp gene was identified in just 10% of the remaining isolates of the collection. In this cluster, co-presence of bbp with the cna gene encoding collagen adhesin was a pattern consistently observed. These findings indicate a crucial role of both these adhesins, able to bind the most abundant bone proteins, in the pathogenesis of orthopaedic implant infections, there where biomaterials interface bone tissues. Moreover a PCR screening for the ebpS gene, conducted on over two hundred S. aureus clinical isolates from implant related infections revealed the detection of six strains exhibiting an altered amplicon size, shorter than expected. In order to elucidate the sequence changes present in these gene variants, the trait comprised between the primers was analyzed in all six isolates bearing the modification and in four isolates exhibiting the regular amplicon size. From nucleotide translation, the corresponding encoded protein was found to lack an entire peptide segment of 60 amino acids. These variants, missing an entire hydrophobic region, could actually facilitate current structural studies, helping to assess whether the absent domain is strictly necessary for a functional adhesin conformation and its contribution to the topology of the protein. This study suggests that epidemic clones appear to pursue different survival strategies, where adhesins, when present, exhibit diverse importance as virulence factors. A practical message arising from the present study is that strategies for the prevention and treatment of implant orthopaedic infections should target adhesins conjointly present in epidemic clones. Furthermore, the choice of reference strains for testing the anti-infective properties of biomaterials should focus on a selection of the most prevalent clones as they exhibit distinct profiles of adhesins.

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4

Ravaioli, Stefano <1974&gt. "Patologia ed epidemiologia molecolare delle infezioni associate all'impianto." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2010. http://amsdottorato.unibo.it/2518/.

Full text

Abstract:

Staphylococcus aureus and Staphylococcus epidermidis are leading pathogens of implant-related infections. This study aimed at investigating the diverse distribution of different bacterial pathogen factors in most prevalent S. aureus and S. epidermidis strain types causing orthopaedic implant infections. In this study the presence both of the ica genes, encoding for biofilm exopolysaccharide production, and the insertion sequence IS256, a mobile element frequently associated to transposons, was investigated in relationship with the prevalence of antibiotic resistance among Staphylococcus epidermidis strains. The investigation was conducted on 70 clinical isolates derived from orthopaedic implant infections. Among the clinical isolates investigated a dramatic high level of association was found between the presence of ica genes as well as of IS256 and multiple resistance to all the antibiotics tested. Noteworthy, a striking full association between the presence of IS256 and resistance to gentamicin was found, being none of the IS256-negative strain resistant to this antibiotic. This association is probably because of the link of the corresponding aminoglycoside-resistance genes, and IS256, often co-existing within the same staphylococcal transposon. Moreover we investigated the prevalence of aac(6’)-Ie-aph(2’’), aph (3’) IIIa, and ant(4’) genes, encoding for the three forms of aminoglycoside-modifying enzymes (AME), responsible for resistance to aminoglycoside antibiotics. All isolates were characterized by automated ribotyping, so that the presence of antibiotic resistance determinants was investigated in strains exhibiting different ribopatterns. Interestingly, combinations of coexisting AME genes appeared to be typical of specific ribopatterns. 200 S. aureus isolates, categorized into ribogroups by automated ribotyping, i.e. rDNA restriction fragment length polymorphism analysis, were screened for the presence of a panel of adhesins genes, accessory gene regulatory (agr) polymorphisms and toxins. For many ribogroups, characteristic tandem genes arrangements could be identified. Surprisingly, the isolates of the most prevalent cluster, enlisting 27 isolates, were susceptible to almost all antibiotics and never possessed the lukD/lukE gene, thus suggesting the role of factors other than antibiotic resistance and the here investigated toxins in driving the major epidemic clone to the larger success. Afterwards, .in the predominant S. aureus cluster, the bbp gene encoding bone sialoprotein-binding protein appeared a typical virulence trait, found in 93% of the isolates. Conversely, the bbp gene was identified in just 10% of the remaining isolates of the collection. In this cluster, co-presence of bbp with the cna gene encoding collagen adhesin was a pattern consistently observed. These findings indicate a crucial role of both these adhesins, able to bind the most abundant bone proteins, in the pathogenesis of orthopaedic implant infections, there where biomaterials interface bone tissues. Moreover a PCR screening for the ebpS gene, conducted on over two hundred S. aureus clinical isolates from implant related infections revealed the detection of six strains exhibiting an altered amplicon size, shorter than expected. In order to elucidate the sequence changes present in these gene variants, the trait comprised between the primers was analyzed in all six isolates bearing the modification and in four isolates exhibiting the regular amplicon size. From nucleotide translation, the corresponding encoded protein was found to lack an entire peptide segment of 60 amino acids. These variants, missing an entire hydrophobic region, could actually facilitate current structural studies, helping to assess whether the absent domain is strictly necessary for a functional adhesin conformation and its contribution to the topology of the protein. This study suggests that epidemic clones appear to pursue different survival strategies, where adhesins, when present, exhibit diverse importance as virulence factors. A practical message arising from the present study is that strategies for the prevention and treatment of implant orthopaedic infections should target adhesins conjointly present in epidemic clones. Furthermore, the choice of reference strains for testing the anti-infective properties of biomaterials should focus on a selection of the most prevalent clones as they exhibit distinct profiles of adhesins.

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5

Sirri, Rubina <1983&gt. "Approccio multimetodologico in patologia delle specie ittiche." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2011. http://amsdottorato.unibo.it/3600/1/Sirri_Rubina_tesi.pdf.

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6

Sirri, Rubina <1983&gt. "Approccio multimetodologico in patologia delle specie ittiche." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2011. http://amsdottorato.unibo.it/3600/.

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7

Ferrara, Domenico <1977&gt. "Ruolo del Porcine Circovirus tipo 2 (PCV2) nella patologia riproduttiva del suino." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4560/2/ferrara_domenico_tesi.pdf.

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La tesi è organizzata in 4 capitoli: -nel primo vengono brevemente riferite le patologie associate all’infezione da PCV2 con particolare riferimento all’iter diagnostico ed al ruolo rivestito dall’esame istologico e dalla identificazione dell’agente eziologico in situ contestualmente alle lesioni istologiche; -nel secondo viene presentato un iter diagnostico originale da applicare in condizioni di campo, qualora si voglia accertare la presenza del PCV2 nei tessuti dei prodotti di natimortalità/aborto del suino. In specifico si riferisce all’applicazione del protocollo in 2 aziende ed i risultati vengono analizzati per una revisione critica del protocollo impiegato; -nel terzo vengono presentati i risultati di un protocollo di infezione con PCV2 per via genitale tramite seme infetto. Scrofe convenzionali sono state sincronizzate per l’estro e fecondate con un’unica dose di seme PCV2 negativo alla PCR (gruppo controlli) o sperimentalmente esposto al PCV2 (gruppo infette). I risultati vengono analizzati in funzione delle ripercussioni che l’infezione precoce in gravidanza può produrre sulla scrofa (mancata gravidanza, ritorno in calore), sui feti e sugli invogli fetali. Viene stabilito il ruolo protettivo degli anticorpi circolanti al momento dell’infezione, stante l’evenienza che un basso titolo anticorpale si associa a viremia prolungata e maggiore numero di feti positivi al virus; -nel quarto viene presentato un esperimento sovrapponibile a quello riferito nel capitolo 3, però con la presenza anche di un gruppo di soggetti convenzionali vaccinati ed infettati con PCV2 durante la fecondazione artificiale usando seme sperimentalmente esposto al virus. Nella discussione dei risultati vengono enfatizzati 2 aspetti importanti nell’epidemiologia dell’infezione da PCV2: la eliminazione di virus è fortemente ridotta dalla vaccinazione, con conseguenze verosimilmente positive sulla circolazione del virus negli effettivi dell’allevamento; l’esposizione uterina è protetta dalla vaccinazione, stante la bassa percentuale di placente infette nel gruppo dei soggetti vaccinati rispetto a quelli non vaccinati e nei controlli.
The thesis is organized into 4 chapters: -in the first chapter, it is briefly overviewed the association of PCV2 with several diseases with particular emphasis to the diagnostic protocols and to the in situ identification of the virus in histological lesions; -in the second chapter, it is presented an original diagnostic protocol to be applied in field conditions, to check for the presence of PCV2 in piglet tissues obtained from stillbirth/abortion. It refers to the application of the protocol in 2 herds and the results are analyzed for a critical review of the used protocol; -in the third chapter, it is presented an experimental trial aimed to infect gilts during artificial insemination by PCV2 infected semen. Conventional gilts were synchronized for oestrus and inseminated with a single dose of semen PCV2 PCR-negative (control group) or experimentally exposed to PCV2 (infected group). The results are analyzed to evaluate the impact that infection in early pregnancy may have on the sow (no pregnancy, return to oestrus), foetuses and foetal membranes. It emphasizes the protective role of circulating antibodies at the time of infection, given the possibility that a low antibody titre is associated with prolonged viremia and increased number of PCV2 positive foetuses; -in the fourth chapter, it is presented a protocol similar to that of Chapter 3, but with the presence of a third group of animals: gilts vaccinated and infected with PCV2 using semen experimentally exposed to the virus. In the discussion 2 important aspects are emphasized: the shedding of the virus is greatly reduced by vaccination, with positive effects on the reduction of the circulation of the virus in the herds; uterine exposure is protected by vaccination, given the low percentage of infected placentas in the vaccinated group compared with not vaccinated and control groups.

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8

Ferrara, Domenico <1977&gt. "Ruolo del Porcine Circovirus tipo 2 (PCV2) nella patologia riproduttiva del suino." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4560/.

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Abstract:

La tesi è organizzata in 4 capitoli: -nel primo vengono brevemente riferite le patologie associate all’infezione da PCV2 con particolare riferimento all’iter diagnostico ed al ruolo rivestito dall’esame istologico e dalla identificazione dell’agente eziologico in situ contestualmente alle lesioni istologiche; -nel secondo viene presentato un iter diagnostico originale da applicare in condizioni di campo, qualora si voglia accertare la presenza del PCV2 nei tessuti dei prodotti di natimortalità/aborto del suino. In specifico si riferisce all’applicazione del protocollo in 2 aziende ed i risultati vengono analizzati per una revisione critica del protocollo impiegato; -nel terzo vengono presentati i risultati di un protocollo di infezione con PCV2 per via genitale tramite seme infetto. Scrofe convenzionali sono state sincronizzate per l’estro e fecondate con un’unica dose di seme PCV2 negativo alla PCR (gruppo controlli) o sperimentalmente esposto al PCV2 (gruppo infette). I risultati vengono analizzati in funzione delle ripercussioni che l’infezione precoce in gravidanza può produrre sulla scrofa (mancata gravidanza, ritorno in calore), sui feti e sugli invogli fetali. Viene stabilito il ruolo protettivo degli anticorpi circolanti al momento dell’infezione, stante l’evenienza che un basso titolo anticorpale si associa a viremia prolungata e maggiore numero di feti positivi al virus; -nel quarto viene presentato un esperimento sovrapponibile a quello riferito nel capitolo 3, però con la presenza anche di un gruppo di soggetti convenzionali vaccinati ed infettati con PCV2 durante la fecondazione artificiale usando seme sperimentalmente esposto al virus. Nella discussione dei risultati vengono enfatizzati 2 aspetti importanti nell’epidemiologia dell’infezione da PCV2: la eliminazione di virus è fortemente ridotta dalla vaccinazione, con conseguenze verosimilmente positive sulla circolazione del virus negli effettivi dell’allevamento; l’esposizione uterina è protetta dalla vaccinazione, stante la bassa percentuale di placente infette nel gruppo dei soggetti vaccinati rispetto a quelli non vaccinati e nei controlli.
The thesis is organized into 4 chapters: -in the first chapter, it is briefly overviewed the association of PCV2 with several diseases with particular emphasis to the diagnostic protocols and to the in situ identification of the virus in histological lesions; -in the second chapter, it is presented an original diagnostic protocol to be applied in field conditions, to check for the presence of PCV2 in piglet tissues obtained from stillbirth/abortion. It refers to the application of the protocol in 2 herds and the results are analyzed for a critical review of the used protocol; -in the third chapter, it is presented an experimental trial aimed to infect gilts during artificial insemination by PCV2 infected semen. Conventional gilts were synchronized for oestrus and inseminated with a single dose of semen PCV2 PCR-negative (control group) or experimentally exposed to PCV2 (infected group). The results are analyzed to evaluate the impact that infection in early pregnancy may have on the sow (no pregnancy, return to oestrus), foetuses and foetal membranes. It emphasizes the protective role of circulating antibodies at the time of infection, given the possibility that a low antibody titre is associated with prolonged viremia and increased number of PCV2 positive foetuses; -in the fourth chapter, it is presented a protocol similar to that of Chapter 3, but with the presence of a third group of animals: gilts vaccinated and infected with PCV2 using semen experimentally exposed to the virus. In the discussion 2 important aspects are emphasized: the shedding of the virus is greatly reduced by vaccination, with positive effects on the reduction of the circulation of the virus in the herds; uterine exposure is protected by vaccination, given the low percentage of infected placentas in the vaccinated group compared with not vaccinated and control groups.

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9

Bacci, Barbara <1976&gt. "Le neoplasie del gatto. Ricerche istologiche e immunoistochimiche." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2007. http://amsdottorato.unibo.it/127/1/BacciDottorato.pdf.

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Il contributo di ricerca di questo lavoro è consistito nel rivalutare da un punto di vista diagnostico, classificativo e statistico, una casistica di neoplasie del gatto archiviate in 23 anni (1984-2006). Nei primi 20 anni sono state diagnosticate 1696 neoplasie su un totale di 3682 campioni prevenuti nello stesso periodo, con una prevalenza delle patologie di tipo neoplastico del 46,06%. Nei tre anni successivi sono state individuate 382 neoplasie su un totale di 601 campioni archiviati, con una prevalenza del 61,02%. Le neoplasie avevano per l'81,8% un comportamento maligno, e questo dato risulta coerente con il dato più recente sulla malignità (85,6%) e con quello fornito da altri autori. L'età dei soggetti affetti era simile nei due studi, compresa fra pochi mesi e 22 anni, con il maggior numero di casi fra 9 e 13 anni. Le due casistiche presentano inoltre dati simili riguardo gli organi coinvolti anche se i tumori della mammella sono notevolmente diminuiti negli ultimi anni, con un aumento corrispondente di neoplasie cutanee. I fibrosarcomi, che hanno subito un drastico aumento tra il 1993 e il 1994 si sono mantenuti costanti in tutti gli anni successivi, dato ancora oggi quasi certamente correlabile alle pratiche vaccinali. I linfomi sono risultati piuttosto infrequenti in entrambe le casistiche, comparate con i dati della letteratura in cui vengono riportate percentuali nettamente maggiori. I tumori del cavo orale e dell'intestino hanno mantenuto circa le stesse percentuali di insorgenza nel corso degli anni. Tra i tumori presenti in questo studio, sono stati approfonditi i tumori a carico delle sierose (mesoteliomi) e del polmone attraverso metodiche immunoistochimiche e ultrastrutturali. Nei 23 anni sono stati diagnosticati 10 casi di mesotelioma, di cui 8 coinvolgenti la pleura e due il peritoneo. Su questi casi è stata applicata una metodica immunoistochimica con un pannello anticorpale utilizzato di routine in patologia umana per la diagnosi di mesotelioma e per la diagnosi differenziale con i carcinomi polmonari. Tutti i casi presentavano una doppia positività per vimentina e citocheratine ad ampio spettro; anticorpi specifici come CK5/6 e HBME-1 hanno presentato una buona specificità. Anche la microscopia elettronica si è rivelata di ausilio, mettendo in evidenza la presenza di tonofilamenti citoplasmatici e di microvilli, tipici delle cellule mesoteliali. Le neoplasie polmonari, analogamente a quelle umane hanno, sono notevolmente aumentate negli ultimi anni. Dei 24 casi raccolti tra il materiale di archivio, 14 sono stati diagnosticati negli ultimi 5 anni. Si è rilevata una significativa predisposizione nei gatti di razza Persiana, e le metastasi più frequenti sono state a carico dei linfonodi, del miocardio e dei cuscinetti plantari, analogamente a quanto segnalato in letteratura. L’istotipo più rappresentato è stato il carcinoma squamoso, seguito da adenocarcinomi papillari e bronchioloalveolari. Il pannello immunoistochimico applicato, finalizzato a individuare l’origine broncogena o ghiandolare della neoplasia, è risultato utile per la diagnosi delle forme squamose poco differenziate (CK 5/6 e CK 14). Infine è stato testato l’anticorpo di elezione nella diagnosi differenziale fra le neoplasie primitive e secondarie del polmone, il TTF-1, che però non ha cross-reagito con tessuti di gatto; la diagnosi di neoplasia primitiva polmonare si è dunque basata sull’assenza, anche nei dati anamnestici, di masse in altri distretti corporei.

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10

Bacci, Barbara <1976&gt. "Le neoplasie del gatto. Ricerche istologiche e immunoistochimiche." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2007. http://amsdottorato.unibo.it/127/.

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Il contributo di ricerca di questo lavoro è consistito nel rivalutare da un punto di vista diagnostico, classificativo e statistico, una casistica di neoplasie del gatto archiviate in 23 anni (1984-2006). Nei primi 20 anni sono state diagnosticate 1696 neoplasie su un totale di 3682 campioni prevenuti nello stesso periodo, con una prevalenza delle patologie di tipo neoplastico del 46,06%. Nei tre anni successivi sono state individuate 382 neoplasie su un totale di 601 campioni archiviati, con una prevalenza del 61,02%. Le neoplasie avevano per l'81,8% un comportamento maligno, e questo dato risulta coerente con il dato più recente sulla malignità (85,6%) e con quello fornito da altri autori. L'età dei soggetti affetti era simile nei due studi, compresa fra pochi mesi e 22 anni, con il maggior numero di casi fra 9 e 13 anni. Le due casistiche presentano inoltre dati simili riguardo gli organi coinvolti anche se i tumori della mammella sono notevolmente diminuiti negli ultimi anni, con un aumento corrispondente di neoplasie cutanee. I fibrosarcomi, che hanno subito un drastico aumento tra il 1993 e il 1994 si sono mantenuti costanti in tutti gli anni successivi, dato ancora oggi quasi certamente correlabile alle pratiche vaccinali. I linfomi sono risultati piuttosto infrequenti in entrambe le casistiche, comparate con i dati della letteratura in cui vengono riportate percentuali nettamente maggiori. I tumori del cavo orale e dell'intestino hanno mantenuto circa le stesse percentuali di insorgenza nel corso degli anni. Tra i tumori presenti in questo studio, sono stati approfonditi i tumori a carico delle sierose (mesoteliomi) e del polmone attraverso metodiche immunoistochimiche e ultrastrutturali. Nei 23 anni sono stati diagnosticati 10 casi di mesotelioma, di cui 8 coinvolgenti la pleura e due il peritoneo. Su questi casi è stata applicata una metodica immunoistochimica con un pannello anticorpale utilizzato di routine in patologia umana per la diagnosi di mesotelioma e per la diagnosi differenziale con i carcinomi polmonari. Tutti i casi presentavano una doppia positività per vimentina e citocheratine ad ampio spettro; anticorpi specifici come CK5/6 e HBME-1 hanno presentato una buona specificità. Anche la microscopia elettronica si è rivelata di ausilio, mettendo in evidenza la presenza di tonofilamenti citoplasmatici e di microvilli, tipici delle cellule mesoteliali. Le neoplasie polmonari, analogamente a quelle umane hanno, sono notevolmente aumentate negli ultimi anni. Dei 24 casi raccolti tra il materiale di archivio, 14 sono stati diagnosticati negli ultimi 5 anni. Si è rilevata una significativa predisposizione nei gatti di razza Persiana, e le metastasi più frequenti sono state a carico dei linfonodi, del miocardio e dei cuscinetti plantari, analogamente a quanto segnalato in letteratura. L’istotipo più rappresentato è stato il carcinoma squamoso, seguito da adenocarcinomi papillari e bronchioloalveolari. Il pannello immunoistochimico applicato, finalizzato a individuare l’origine broncogena o ghiandolare della neoplasia, è risultato utile per la diagnosi delle forme squamose poco differenziate (CK 5/6 e CK 14). Infine è stato testato l’anticorpo di elezione nella diagnosi differenziale fra le neoplasie primitive e secondarie del polmone, il TTF-1, che però non ha cross-reagito con tessuti di gatto; la diagnosi di neoplasia primitiva polmonare si è dunque basata sull’assenza, anche nei dati anamnestici, di masse in altri distretti corporei.

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Pittioni, Eugenio <1975&gt. "Indagine istopatologica ed immunoistochimica su feti bovini abortiti in Friuli Venezia Giulia." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2007. http://amsdottorato.unibo.it/128/1/Tesi_Dott_Pittioni_Eugenio.pdf.

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12

Pittioni, Eugenio <1975&gt. "Indagine istopatologica ed immunoistochimica su feti bovini abortiti in Friuli Venezia Giulia." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2007. http://amsdottorato.unibo.it/128/.

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13

Malatesta, Daniela <1978&gt. "Sistema nervoso enterico e scrapie sperimentale in ovini di razza sarda con diversa suscettibilità genetica nei confronti della malattia." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2007. http://amsdottorato.unibo.it/129/1/Tesi_di_Dottorato_di_Malatesta_Daniela.pdf.

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Sebbene il sistema nervoso enterico (“enteric nervous system”, ENS) svolga un ruolo cruciale nella patogenesi della Scrapie ovina, non esistono tuttavia in letteratura dati sulle popolazioni cellulari progressivamente coinvolte nel corso dell’infezione, né sugli eventuali danni morfo-funzionali da esse subiti. Il presente studio è stato condotto sui plessi mienterici e sottomucosi dell’ileo di 46 pecore di razza Sarda, recanti diversi polimorfismi del gene Prnp (ARQ/ARQ, ARQ/AHQ, ARQ/ARR, ARR/ARR). I suddetti animali, infettati per os all’età di 8 mesi con un ceppo di Scrapie precedentemente caratterizzato nel topo, sono stati sacrificati mediante eutanasia a determinati intervalli di tempo post-infezione (p.i.). E’ stata quindi valutata, tramite immunoistochimica ed immunofluorescenza indiretta su sezioni tissutali e su preparati “wholemount”, l’immunoreattività (IR) nei confronti della PrPSc, del “marker” panneuronale Hu C/D, dell’ossido-nitrico sintetasi (nNOS), della calbindina (CALB) e della proteina fibrillare acida gliale (GFAP). In 8 pecore con genotipo ARQ/ARQ, clinicamente sane e sacrificate a 12-24 mesi p.i., nonché in 5 ovini clinicamente affetti (2 con genotipo ARQ/ARQ, 3 con genotipo ARQ/AHQ), questi ultimi sacrificati rispettivamente a 24, 36 e 40 mesi p.i., le indagini immunoistochimiche hanno consentito di dimostrare la presenza di PrPSc a livello sia dell’encefalo (obex), sia dell’ENS, in particolar modo nei plessi mienterici. In tali distretti il deposito della PrPSc risultava pienamente compatibile con un interessamento delle cellule enterogliali (“enteroglial cells”, EGCs), mentre occasionalmente si notava un contestuale coinvolgimento della componente neuronale ivi residente. In conclusione, i dati della presente indagine consentono di ipotizzare un verosimile coinvolgimento delle EGCs e dei neuroni residenti a livello dei plessi dell’ENS nella patogenesi della Scrapie sperimentale realizzata per os in ovini di razza Sarda.
The enteric nervous system (ENS) is believed to play a key role in the pathogenesis of sheep Scrapie infection, although no information exists on the ENS cytotypes which are progressively involved, nor on the morpho-functional damage of such cells in the time course of infection. We investigated the ileal myenteric (MPs) and submucosal plexuses (SMPs) of 46 Sarda breed sheep carrying different PrP genotypes (ARQ/ARQ, ARQ/AHQ, ARQ/ARR, ARR/ARR), which had been orally dosed with Scrapie at 8 months of age and euthanized at definite time intervals post-infection (p.i.). PrPSc immunoreactivity (IR), along with pan-neuronal marker Hu C/D, nitric oxide synthase (nNOS), calbindin (CALB) and glial fibrillary acidic protein (GFAP)-IR, were evaluated by means of immunohistochemistry (IHC) and indirect immunofluorescence (IF) on paraffin-embedded sections and wholemount preparations. Eight clinically-healthy ARQ/ARQ sheep euthanized at 12-24 months p.i., along with 2 ARQ/ARQ (euthanized at 24 months p.i.) and 3 ARQ/AHQ (euthanized at 36 and 40 months p.i., respectively) clinicallyaffected sheep, showed IHC evidence of PrPSc in both their brain (obex) and ENS, especially in MPs. PrPSc deposition was fully compatible with an involvement of enteroglial cells (EGCs) and, occasionally, also with an involvement of neurons residing within ileal ENS plexuses. In conclusion, EGCs and neurons residing within ileal ENS plexuses may be likely involved in the pathogenesis of oral experimental Scrapie infection in Sarda breed sheep.

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Malatesta, Daniela <1978&gt. "Sistema nervoso enterico e scrapie sperimentale in ovini di razza sarda con diversa suscettibilità genetica nei confronti della malattia." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2007. http://amsdottorato.unibo.it/129/.

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Sebbene il sistema nervoso enterico (“enteric nervous system”, ENS) svolga un ruolo cruciale nella patogenesi della Scrapie ovina, non esistono tuttavia in letteratura dati sulle popolazioni cellulari progressivamente coinvolte nel corso dell’infezione, né sugli eventuali danni morfo-funzionali da esse subiti. Il presente studio è stato condotto sui plessi mienterici e sottomucosi dell’ileo di 46 pecore di razza Sarda, recanti diversi polimorfismi del gene Prnp (ARQ/ARQ, ARQ/AHQ, ARQ/ARR, ARR/ARR). I suddetti animali, infettati per os all’età di 8 mesi con un ceppo di Scrapie precedentemente caratterizzato nel topo, sono stati sacrificati mediante eutanasia a determinati intervalli di tempo post-infezione (p.i.). E’ stata quindi valutata, tramite immunoistochimica ed immunofluorescenza indiretta su sezioni tissutali e su preparati “wholemount”, l’immunoreattività (IR) nei confronti della PrPSc, del “marker” panneuronale Hu C/D, dell’ossido-nitrico sintetasi (nNOS), della calbindina (CALB) e della proteina fibrillare acida gliale (GFAP). In 8 pecore con genotipo ARQ/ARQ, clinicamente sane e sacrificate a 12-24 mesi p.i., nonché in 5 ovini clinicamente affetti (2 con genotipo ARQ/ARQ, 3 con genotipo ARQ/AHQ), questi ultimi sacrificati rispettivamente a 24, 36 e 40 mesi p.i., le indagini immunoistochimiche hanno consentito di dimostrare la presenza di PrPSc a livello sia dell’encefalo (obex), sia dell’ENS, in particolar modo nei plessi mienterici. In tali distretti il deposito della PrPSc risultava pienamente compatibile con un interessamento delle cellule enterogliali (“enteroglial cells”, EGCs), mentre occasionalmente si notava un contestuale coinvolgimento della componente neuronale ivi residente. In conclusione, i dati della presente indagine consentono di ipotizzare un verosimile coinvolgimento delle EGCs e dei neuroni residenti a livello dei plessi dell’ENS nella patogenesi della Scrapie sperimentale realizzata per os in ovini di razza Sarda.
The enteric nervous system (ENS) is believed to play a key role in the pathogenesis of sheep Scrapie infection, although no information exists on the ENS cytotypes which are progressively involved, nor on the morpho-functional damage of such cells in the time course of infection. We investigated the ileal myenteric (MPs) and submucosal plexuses (SMPs) of 46 Sarda breed sheep carrying different PrP genotypes (ARQ/ARQ, ARQ/AHQ, ARQ/ARR, ARR/ARR), which had been orally dosed with Scrapie at 8 months of age and euthanized at definite time intervals post-infection (p.i.). PrPSc immunoreactivity (IR), along with pan-neuronal marker Hu C/D, nitric oxide synthase (nNOS), calbindin (CALB) and glial fibrillary acidic protein (GFAP)-IR, were evaluated by means of immunohistochemistry (IHC) and indirect immunofluorescence (IF) on paraffin-embedded sections and wholemount preparations. Eight clinically-healthy ARQ/ARQ sheep euthanized at 12-24 months p.i., along with 2 ARQ/ARQ (euthanized at 24 months p.i.) and 3 ARQ/AHQ (euthanized at 36 and 40 months p.i., respectively) clinicallyaffected sheep, showed IHC evidence of PrPSc in both their brain (obex) and ENS, especially in MPs. PrPSc deposition was fully compatible with an involvement of enteroglial cells (EGCs) and, occasionally, also with an involvement of neurons residing within ileal ENS plexuses. In conclusion, EGCs and neurons residing within ileal ENS plexuses may be likely involved in the pathogenesis of oral experimental Scrapie infection in Sarda breed sheep.

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15

Merendi, Flavia <1967&gt. "Animali terrestri come indicatori biologici dei vari ecosistemi in relazione alla salute umana." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2007. http://amsdottorato.unibo.it/550/1/Tesi_Dottorato_Dott._Flavia_Merendi_XIX_ciclo.pdf.

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16

Merendi, Flavia <1967&gt. "Animali terrestri come indicatori biologici dei vari ecosistemi in relazione alla salute umana." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2007. http://amsdottorato.unibo.it/550/.

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17

Sassi, Francesco <1980&gt. "Classificazione su base molecolare dei tumori mammari della cagna mediante metodica immunoistochimica." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2009. http://amsdottorato.unibo.it/1331/1/Sassi_Francesco_Tesi.pdf.

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Background. A new classification system of human breast tumours based on the immunohistochemical characterization has been applied to mammary tumours of the female dog with the aim to verify its association with invasion and grade, and prognostic aid in veterinary medicine. Methods. Forty-five canine mammary carcinomas with a two-year post-mastectomy follow-up were selected from our database, and the following antibodies were applied: anti-cytokeratines 14, 5/6, oestrogen receptor (ER), progesterone receptor (PR), and ERB-B2. . The tumours were grouped for phenotype as: luminal-like (ER+ and/or PR+, CK14-, CK5/6-) type A (ERB-B2-), and B (ERB-B2+); basal-like (ER-, PR-, CK14+ and/or CK5/6+, ERB-B2-); ERB-B2 (ER-, PR-, CK14-, CK5/6-, ERB-B2+). Association with invasion, grade and histotypes were evaluated and Kaplan-Meier survival curves estimated, then compared by survival analysis. Results. Thirty-five cases with luminal pattern (ER+ and PR+) were subgrouped into 13 A type and 22 B type, if ERB-B2 positive or negative . Most luminal-like A and basal-like cases were grade 1 carcinomas, while the percentage of luminal B cases was higher in grade 2 and 3 (Pearson Chi-square P=0.009). No difference in the percentage of molecular subtypes was evidenced between simple and complex/mixed carcinomas (Pearson Chi-square P=0.47). No significant results were obtained by survival analysis, even if basal-like had a more favourable prognosis than luminal-like. Conclusion. The panel of antibodies identified only 3 groups (luminal-like A and B, and basal-like) in the dog. Even though canine mammary tumours may be a model of human breast cancer, the existence of the same types of carcinoma as in the woman need to be confirmed. Canine mammary carcinomas show high molecular heterogeneity, which would benefit from a classification based on molecular differences. However, by multivariate analysis, the molecular classification appears a variable with a dependent value if compared to invasion and grade that are independent, suggesting that, at present, caution should be used in the application of such a classification to the dog, in which invasion and grade supply the most important prognostic information.

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18

Sassi, Francesco <1980&gt. "Classificazione su base molecolare dei tumori mammari della cagna mediante metodica immunoistochimica." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2009. http://amsdottorato.unibo.it/1331/.

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Background. A new classification system of human breast tumours based on the immunohistochemical characterization has been applied to mammary tumours of the female dog with the aim to verify its association with invasion and grade, and prognostic aid in veterinary medicine. Methods. Forty-five canine mammary carcinomas with a two-year post-mastectomy follow-up were selected from our database, and the following antibodies were applied: anti-cytokeratines 14, 5/6, oestrogen receptor (ER), progesterone receptor (PR), and ERB-B2. . The tumours were grouped for phenotype as: luminal-like (ER+ and/or PR+, CK14-, CK5/6-) type A (ERB-B2-), and B (ERB-B2+); basal-like (ER-, PR-, CK14+ and/or CK5/6+, ERB-B2-); ERB-B2 (ER-, PR-, CK14-, CK5/6-, ERB-B2+). Association with invasion, grade and histotypes were evaluated and Kaplan-Meier survival curves estimated, then compared by survival analysis. Results. Thirty-five cases with luminal pattern (ER+ and PR+) were subgrouped into 13 A type and 22 B type, if ERB-B2 positive or negative . Most luminal-like A and basal-like cases were grade 1 carcinomas, while the percentage of luminal B cases was higher in grade 2 and 3 (Pearson Chi-square P=0.009). No difference in the percentage of molecular subtypes was evidenced between simple and complex/mixed carcinomas (Pearson Chi-square P=0.47). No significant results were obtained by survival analysis, even if basal-like had a more favourable prognosis than luminal-like. Conclusion. The panel of antibodies identified only 3 groups (luminal-like A and B, and basal-like) in the dog. Even though canine mammary tumours may be a model of human breast cancer, the existence of the same types of carcinoma as in the woman need to be confirmed. Canine mammary carcinomas show high molecular heterogeneity, which would benefit from a classification based on molecular differences. However, by multivariate analysis, the molecular classification appears a variable with a dependent value if compared to invasion and grade that are independent, suggesting that, at present, caution should be used in the application of such a classification to the dog, in which invasion and grade supply the most important prognostic information.

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19

Vinci, Annachiara <1978&gt. "Tumori uterini e mammari della coniglia." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2009. http://amsdottorato.unibo.it/1336/1/Vinci_Annachiara_Tesi.pdf.

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20

Vinci, Annachiara <1978&gt. "Tumori uterini e mammari della coniglia." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2009. http://amsdottorato.unibo.it/1336/.

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21

Cesari, Alessandro <1981&gt. "Applicazioni Immunocitochimiche nella Citodiagnostica Oncologica Veterinaria." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2009. http://amsdottorato.unibo.it/1684/1/Cesari_Alessandro_tesi.pdf.

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22

Cesari, Alessandro <1981&gt. "Applicazioni Immunocitochimiche nella Citodiagnostica Oncologica Veterinaria." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2009. http://amsdottorato.unibo.it/1684/.

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23

Canavese, Federico <1975&gt. "Artrodesi vertebrale dorsale in conigli New-Zealand White da 1 a 18 mesi: valutazioni clinico-radiologiche e fisio-anatomo-istopatologiche." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2011. http://amsdottorato.unibo.it/3504/1/Canavese_Federico_Tesi.pdf.

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24

Canavese, Federico <1975&gt. "Artrodesi vertebrale dorsale in conigli New-Zealand White da 1 a 18 mesi: valutazioni clinico-radiologiche e fisio-anatomo-istopatologiche." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2011. http://amsdottorato.unibo.it/3504/.

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25

Fusaro, Laura <1981&gt. "Patologie da Porcine Circovirus tipo 2 (PCV2) nel suino." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2011. http://amsdottorato.unibo.it/3640/1/fusaro_laura_tesi.pdf.

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The main work involved the PMWS (Post-weaning multisystemic Wasting Syndrome), caused by PCV-2 (Porcine Circovirus type 2) that involved post-weaned pigs. Merial Italy has funded a study activity in which groups of 3-5 animals were sampled for lungs, tracheo-bronchial and superficial inguinal lymph nodes, ileum and tonsils. The protocol applied can be identified as a more diagnostic potential on the individual than on the group. PNP. Another investigation has been conducted to study proliferative and necrotizing pneumonia (PNP), a form of interstitial pneumonia in weaning and post-weaning pigs characterized by hypertrophy and hyperplasia of type II pneumocytes, coagulative necrosis and granular debris within alveolar spaces. Many studies suggest porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) as the main causes of the disease, but Aujeszky disease virus (ADV) and swine influenza virus (SIV) are also considered. An immunohistochemical study was carried out to evaluate the role of these viruses in PNP lesions in Italy. PNP results primarily associated with PRRSV, even if co-infection is characterized by more severe histological features. Reproductive pathology. A major risk factor for PCV2 infection is a viraemic episode taking place in pregnant sows with low antibody titer which is transmitted by specific PCV2 products of conception. PCV2 can infect the fetus even by vehicles through infected semen or ova, or as a result of infection of the genital tract. An investigation was carried out to identify the presence and localization of PCV2 in the genital tracts of sows experimentally infected with PCV2 and in their fetuses. The results obtained suggest that: conventional sows can be infected by intrauterine exposition; low antibody titres increase the probability of infection; PCV2 infection close to insemination time reduces the pregnancy rate; placental lesions may represent an additional cause of fetal suffering.

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26

Fusaro, Laura <1981&gt. "Patologie da Porcine Circovirus tipo 2 (PCV2) nel suino." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2011. http://amsdottorato.unibo.it/3640/.

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The main work involved the PMWS (Post-weaning multisystemic Wasting Syndrome), caused by PCV-2 (Porcine Circovirus type 2) that involved post-weaned pigs. Merial Italy has funded a study activity in which groups of 3-5 animals were sampled for lungs, tracheo-bronchial and superficial inguinal lymph nodes, ileum and tonsils. The protocol applied can be identified as a more diagnostic potential on the individual than on the group. PNP. Another investigation has been conducted to study proliferative and necrotizing pneumonia (PNP), a form of interstitial pneumonia in weaning and post-weaning pigs characterized by hypertrophy and hyperplasia of type II pneumocytes, coagulative necrosis and granular debris within alveolar spaces. Many studies suggest porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) as the main causes of the disease, but Aujeszky disease virus (ADV) and swine influenza virus (SIV) are also considered. An immunohistochemical study was carried out to evaluate the role of these viruses in PNP lesions in Italy. PNP results primarily associated with PRRSV, even if co-infection is characterized by more severe histological features. Reproductive pathology. A major risk factor for PCV2 infection is a viraemic episode taking place in pregnant sows with low antibody titer which is transmitted by specific PCV2 products of conception. PCV2 can infect the fetus even by vehicles through infected semen or ova, or as a result of infection of the genital tract. An investigation was carried out to identify the presence and localization of PCV2 in the genital tracts of sows experimentally infected with PCV2 and in their fetuses. The results obtained suggest that: conventional sows can be infected by intrauterine exposition; low antibody titres increase the probability of infection; PCV2 infection close to insemination time reduces the pregnancy rate; placental lesions may represent an additional cause of fetal suffering.

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Scarpa, Filippo <1979&gt. "Metodiche istologiche di utilità prognostica in oncologia veterinaria." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2011. http://amsdottorato.unibo.it/3793/1/Scarpa_Filippo_tesi.pdf.

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28

Scarpa, Filippo <1979&gt. "Metodiche istologiche di utilità prognostica in oncologia veterinaria." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2011. http://amsdottorato.unibo.it/3793/.

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29

Sabattini, Silvia <1982&gt. "Ruolo dei recettori tirosinchinasici in oncologia animale." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4760/1/sabattini_silvia_tesi.pdf.

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Disregolazioni dei recettori tirosinchinasici (RTK) sono di frequente riscontro nei tumori dell’uomo e in molti casi sono indicatori biologici che permettono di definire in maniera più accurata la prognosi dei pazienti. Possono rappresentare inoltre marker predittivi per la risposta a terapie antitumorali con farmaci a bersaglio molecolare. Numerosi inibitori tirosinchinasici (TKI) sono attualmente in corso di studio o già disponibili per l’utilizzo in oncologia umana, e molti di questi hanno dimostrato una significativa efficacia utilizzati singolarmente o in combinazione a terapie convenzionali. Studi recenti indicano che un quadro analogo di disregolazione dei recettori tirosinchinasici è presente anche nelle neoplasie dei piccoli animali, e ne suggeriscono in molti casi un’implicazione prognostica. Gli inibitori tirosinchinasi sono da poco entrati nell’arena dell’oncologia veterinaria, ma i primi risultati lasciano supporre che siano destinati ad essere integrati definitivamente nei protocolli terapeutici standard. La tesi consiste in una parte introduttiva in cui sono trattate le principali funzioni biologiche dei recettori tirosinchinasici, la loro struttura e il loro ruolo nell’oncogenesi e nella progressione tumorale in medicina umana e veterinaria. Si affrontano inoltre le principali metodiche di laboratorio per l’analisi molecolare in oncologia e i meccanismi d’azione dei farmaci inibitori tirosinchinasici, con un cenno ai prodotti maggiormente utilizzati e alle loro indicazioni. Segue la presentazione e la discussione dei risultati di quattro studi relativi alla valutazione delle disregolazioni del recettore tirosinchinasico Kit (espressione aberrante e mutazioni genomiche) nel mastocitoma cutaneo del gatto e del recettore del fattore di crescita epidermico (EGFR) nel carcinoma squamocellulare cutaneo del gatto e nei tumori polmonari primitivi del cane, con particolare attenzione al loro ruolo prognostico.
Protein kinases are enzymes that play key roles in cell signal transduction, regulating pathways critical in cell growth, differentiation, survival and death. Dysfunction of many protein kinases, particularly the tyrosine kinases, has been identified in a variety of human cancers, and has just begun to be investigated in spontaneous tumours of dogs and cats. We present the results of four studies aimed at characterizing the dysregulation (aberrant immunohistochemical expression and gene mutations) of Kit receptor tyrosine kinase in feline cutaneous mast cell tumors and the overexpression of the epidermal growth factor receptor (EGFR) in feline squamous cell carcinoma and in canine primary lung cancer. The potential prognostic implications of the observed dysregulation are discussed.

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Sabattini, Silvia <1982&gt. "Ruolo dei recettori tirosinchinasici in oncologia animale." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4760/.

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Disregolazioni dei recettori tirosinchinasici (RTK) sono di frequente riscontro nei tumori dell’uomo e in molti casi sono indicatori biologici che permettono di definire in maniera più accurata la prognosi dei pazienti. Possono rappresentare inoltre marker predittivi per la risposta a terapie antitumorali con farmaci a bersaglio molecolare. Numerosi inibitori tirosinchinasici (TKI) sono attualmente in corso di studio o già disponibili per l’utilizzo in oncologia umana, e molti di questi hanno dimostrato una significativa efficacia utilizzati singolarmente o in combinazione a terapie convenzionali. Studi recenti indicano che un quadro analogo di disregolazione dei recettori tirosinchinasici è presente anche nelle neoplasie dei piccoli animali, e ne suggeriscono in molti casi un’implicazione prognostica. Gli inibitori tirosinchinasi sono da poco entrati nell’arena dell’oncologia veterinaria, ma i primi risultati lasciano supporre che siano destinati ad essere integrati definitivamente nei protocolli terapeutici standard. La tesi consiste in una parte introduttiva in cui sono trattate le principali funzioni biologiche dei recettori tirosinchinasici, la loro struttura e il loro ruolo nell’oncogenesi e nella progressione tumorale in medicina umana e veterinaria. Si affrontano inoltre le principali metodiche di laboratorio per l’analisi molecolare in oncologia e i meccanismi d’azione dei farmaci inibitori tirosinchinasici, con un cenno ai prodotti maggiormente utilizzati e alle loro indicazioni. Segue la presentazione e la discussione dei risultati di quattro studi relativi alla valutazione delle disregolazioni del recettore tirosinchinasico Kit (espressione aberrante e mutazioni genomiche) nel mastocitoma cutaneo del gatto e del recettore del fattore di crescita epidermico (EGFR) nel carcinoma squamocellulare cutaneo del gatto e nei tumori polmonari primitivi del cane, con particolare attenzione al loro ruolo prognostico.
Protein kinases are enzymes that play key roles in cell signal transduction, regulating pathways critical in cell growth, differentiation, survival and death. Dysfunction of many protein kinases, particularly the tyrosine kinases, has been identified in a variety of human cancers, and has just begun to be investigated in spontaneous tumours of dogs and cats. We present the results of four studies aimed at characterizing the dysregulation (aberrant immunohistochemical expression and gene mutations) of Kit receptor tyrosine kinase in feline cutaneous mast cell tumors and the overexpression of the epidermal growth factor receptor (EGFR) in feline squamous cell carcinoma and in canine primary lung cancer. The potential prognostic implications of the observed dysregulation are discussed.

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31

Bassi, Patrizia <1984&gt. "Rilievi anatomo-patologici e batteriologici condotti sull’apparato gastroenterico di una metapopolazione di cinghiali (Sus scrofa)." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amsdottorato.unibo.it/5518/1/Bassi_Patrizia_tesi.pdf.

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Nell’ambito della patologia gastroenterica del suino sono comprese alcune malattie sostenute da batteri spirillari gram negativi, di cui sono disponibili numerose trattazioni riguardanti, soprattutto, l'aspetto epidemiologico e patogenetico. Per alcuni di questi agenti microbici, e per le relative manifestazioni patologiche, poco si conosce nel cinghiale selvatico, animale correlato filogeneticamente al suino domestico, ma compreso in un’ecologia completamente differente. Da queste premesse è nato un approccio di ricerca e studio del comportamento di questi microrganismi in una metapopolazione di cinghiali, abbattuti durante il piano di controllo della popolazione densità-dipendente nel Parco dei Gessi e Calanchi dell’Abbadessa (BO), cercando di rapportare le conoscenze riportate in letteratura sul suino domestico con quanto è scaturito dalle indagini condotte sul cinghiale selvatico. In particolare è stata indagata con metodica immunoistochimica la presenza di Lawsonia intracellularis, patogeno del suino responsabile di Enterite Proliferativa (EP), in secondo luogo sono state condotte indagini batteriologiche e istologiche da stomaco e intestino, finalizzate all’isolamento di microrganismi spirillari dei generi Campylobacter e Helicobacter, da correlare all’eventuale presenza di lesioni infiammatorie e ulcerative gastriche o enteriche valutate secondo sistemi a punteggio ottenuti dalla bibliografia o realizzati in base alla tipologia di infiltrato cellulare e alla sua localizzazione. In ultimo, a fini comparativi con uno studio condotto nel 2002-2004 nello steso Parco Regionale, sono stati monitorati i livelli di antibioticoresistenza di indicatori fecali usando metodiche internazionali standardizzate (Escherichia coli e Enterococcus faecium.) nonché su un numero significativo di isolati di Campylobacter lanienae, per ottenere indicazioni preliminari sull’andamento nei 10 anni trascorsi dello stato di inquinamento da farmaco del Parco stesso. I risultati ottenuti permettono di ampliare le conoscenze sulla flora enterica del cinghiale selvatico e pongono questioni di sicurezza pubblica sulla gestione dei mammiferi selvatici.
In the field of swine pathology many studies are available about some gastrointestinal bacteria like Lawsonia intracellularis, Helicobacter spp. and Campylobacter spp.. Less studies have been performed for the same bacteria on wild boar, which is strongly phylogenetically related with domestic swine but lives in a different ecological habitat. The aim of this study is to define if, and how, these bacteria can be related with pathological findings on gastrointestinal tracts in wild boar, and to compare these findings with those reported for domestic swine. The wild boar samples have been collected during a culling project in the Regional Park of Gessi Bolognesi e Calanchi dell’Abbadessa (BO) in Italy during the year 2011. Infection with Lawsonia intracellularis has been investigated with immunohistochemistry, while the research of Helicobacter spp. and Campylobacter spp. has been performed with culturing. The identification of isolates has been performed with PCR, multiplex-PCR or RFLP-PCR (Restriction Fragment Length Polymorphism-PCR) and the phenotypic characters has been investigated for isolates of Helicobacter genus. Slides of gastric and intestinal tracts have been evaluated with different scoring methods taken from literature or built considering cellular inflammatory types and localization. Bacteriological and pathological findings have been correlated with statistical analysis. Finally, in order to compare data with a previous study on antimicrobial resistance performed in the same area in 2002-2004 (Rossi et al. 2007), antimicrobial disk diffusion assays, performed following international standardized methods, have been realized on fecal indicators (Escherichia coli and Enetrococcus faecium) isolated from the culled wild boars. The MIC (Minimal Inhibitory Concentration) of some isolates of Campylobacter lanienae has been evaluated too. Obtained results can implement the knowledge about the gastrointestinal flora of wild boars and can put question on public safety in wild mammals.

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32

Bassi, Patrizia <1984&gt. "Rilievi anatomo-patologici e batteriologici condotti sull’apparato gastroenterico di una metapopolazione di cinghiali (Sus scrofa)." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amsdottorato.unibo.it/5518/.

Full text

Abstract:

Nell’ambito della patologia gastroenterica del suino sono comprese alcune malattie sostenute da batteri spirillari gram negativi, di cui sono disponibili numerose trattazioni riguardanti, soprattutto, l'aspetto epidemiologico e patogenetico. Per alcuni di questi agenti microbici, e per le relative manifestazioni patologiche, poco si conosce nel cinghiale selvatico, animale correlato filogeneticamente al suino domestico, ma compreso in un’ecologia completamente differente. Da queste premesse è nato un approccio di ricerca e studio del comportamento di questi microrganismi in una metapopolazione di cinghiali, abbattuti durante il piano di controllo della popolazione densità-dipendente nel Parco dei Gessi e Calanchi dell’Abbadessa (BO), cercando di rapportare le conoscenze riportate in letteratura sul suino domestico con quanto è scaturito dalle indagini condotte sul cinghiale selvatico. In particolare è stata indagata con metodica immunoistochimica la presenza di Lawsonia intracellularis, patogeno del suino responsabile di Enterite Proliferativa (EP), in secondo luogo sono state condotte indagini batteriologiche e istologiche da stomaco e intestino, finalizzate all’isolamento di microrganismi spirillari dei generi Campylobacter e Helicobacter, da correlare all’eventuale presenza di lesioni infiammatorie e ulcerative gastriche o enteriche valutate secondo sistemi a punteggio ottenuti dalla bibliografia o realizzati in base alla tipologia di infiltrato cellulare e alla sua localizzazione. In ultimo, a fini comparativi con uno studio condotto nel 2002-2004 nello steso Parco Regionale, sono stati monitorati i livelli di antibioticoresistenza di indicatori fecali usando metodiche internazionali standardizzate (Escherichia coli e Enterococcus faecium.) nonché su un numero significativo di isolati di Campylobacter lanienae, per ottenere indicazioni preliminari sull’andamento nei 10 anni trascorsi dello stato di inquinamento da farmaco del Parco stesso. I risultati ottenuti permettono di ampliare le conoscenze sulla flora enterica del cinghiale selvatico e pongono questioni di sicurezza pubblica sulla gestione dei mammiferi selvatici.
In the field of swine pathology many studies are available about some gastrointestinal bacteria like Lawsonia intracellularis, Helicobacter spp. and Campylobacter spp.. Less studies have been performed for the same bacteria on wild boar, which is strongly phylogenetically related with domestic swine but lives in a different ecological habitat. The aim of this study is to define if, and how, these bacteria can be related with pathological findings on gastrointestinal tracts in wild boar, and to compare these findings with those reported for domestic swine. The wild boar samples have been collected during a culling project in the Regional Park of Gessi Bolognesi e Calanchi dell’Abbadessa (BO) in Italy during the year 2011. Infection with Lawsonia intracellularis has been investigated with immunohistochemistry, while the research of Helicobacter spp. and Campylobacter spp. has been performed with culturing. The identification of isolates has been performed with PCR, multiplex-PCR or RFLP-PCR (Restriction Fragment Length Polymorphism-PCR) and the phenotypic characters has been investigated for isolates of Helicobacter genus. Slides of gastric and intestinal tracts have been evaluated with different scoring methods taken from literature or built considering cellular inflammatory types and localization. Bacteriological and pathological findings have been correlated with statistical analysis. Finally, in order to compare data with a previous study on antimicrobial resistance performed in the same area in 2002-2004 (Rossi et al. 2007), antimicrobial disk diffusion assays, performed following international standardized methods, have been realized on fecal indicators (Escherichia coli and Enetrococcus faecium) isolated from the culled wild boars. The MIC (Minimal Inhibitory Concentration) of some isolates of Campylobacter lanienae has been evaluated too. Obtained results can implement the knowledge about the gastrointestinal flora of wild boars and can put question on public safety in wild mammals.

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33

Berlato, Davide <1973&gt. "Cellular Proliferation in the Prognosis of Intermediate Grade Mast Cell Tumour in Dogs." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6241/1/Davide.Berlato.Dottorato.2014.pdf.

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This was a retrospective study including ninety samples of dogs with a histological diagnosis of intermediate grade cutaneous mast cell tumour (MCT). The objectives of the study were to validate Minichromosome Maintenance Protein 7 (MCM7) as a prognostic marker in MCTs and to compare the ability of mitotic index (MI), Ki67 and MCM7 to predict outcome. The median survival for the entire population was not reached at 2099 days. The mean survival time was 1708 days. Seventy-two cases were censored after a median follow up of 1136 days and eighteen dogs died for causes related to the MCT after a median of 116 days. For each sample MI, Ki67 and MCM7 were determined. The Receiver Operating Characteristic (ROC) curve was obtained for each prognostic marker to evaluate the performance of the test, expressed as area under the curve, and whether the published threshold value was adequate. Kaplan-Meier and corresponding logrank test for MI, Ki67 and MCM7 as binary variables was highly significant (P<0.0001). Multivariable regression analysis of MI, Ki67 and MCM7 corrected for age and surgical margins indicated that the higher risk of dying of MCT was associated with MCM7 > 0.18 (Hazard Ration [HR] 14.7; P<0.001) followed by MI > 5 (HR 13.9; P<0.001) and Ki67 > 0.018 (HR 8.9; P<0.001). Concluding, the present study confirmed that MCM7 is an excellent prognostic marker in cutaneous MCTs being able to divide Patnaik intermediate grade tumours in two categories with different prognosis. Ki67 was equally good confirming its value as a prognostic marker in intermediate grade MCTs. The mitotic index was extremely specific, but lacked of sensitivity. Interestingly, mitotic index, Ki67 and MCM7 were independent from each other suggesting that their combination would improve their individual prognostic value.

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34

Berlato, Davide <1973&gt. "Cellular Proliferation in the Prognosis of Intermediate Grade Mast Cell Tumour in Dogs." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6241/.

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Abstract:

This was a retrospective study including ninety samples of dogs with a histological diagnosis of intermediate grade cutaneous mast cell tumour (MCT). The objectives of the study were to validate Minichromosome Maintenance Protein 7 (MCM7) as a prognostic marker in MCTs and to compare the ability of mitotic index (MI), Ki67 and MCM7 to predict outcome. The median survival for the entire population was not reached at 2099 days. The mean survival time was 1708 days. Seventy-two cases were censored after a median follow up of 1136 days and eighteen dogs died for causes related to the MCT after a median of 116 days. For each sample MI, Ki67 and MCM7 were determined. The Receiver Operating Characteristic (ROC) curve was obtained for each prognostic marker to evaluate the performance of the test, expressed as area under the curve, and whether the published threshold value was adequate. Kaplan-Meier and corresponding logrank test for MI, Ki67 and MCM7 as binary variables was highly significant (P<0.0001). Multivariable regression analysis of MI, Ki67 and MCM7 corrected for age and surgical margins indicated that the higher risk of dying of MCT was associated with MCM7 > 0.18 (Hazard Ration [HR] 14.7; P<0.001) followed by MI > 5 (HR 13.9; P<0.001) and Ki67 > 0.018 (HR 8.9; P<0.001). Concluding, the present study confirmed that MCM7 is an excellent prognostic marker in cutaneous MCTs being able to divide Patnaik intermediate grade tumours in two categories with different prognosis. Ki67 was equally good confirming its value as a prognostic marker in intermediate grade MCTs. The mitotic index was extremely specific, but lacked of sensitivity. Interestingly, mitotic index, Ki67 and MCM7 were independent from each other suggesting that their combination would improve their individual prognostic value.

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35

Beha, Germana <1983&gt. "Phenotypic characterization of the epithelial and myoepithelial components in canine and feline mammary tumours." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6373/1/Germana_Beha_tesi.pdf.

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In veterinary medicine, the ability to classify mammary tumours based on the molecular profile and also determine whether the immunophenotype of the regional lymph node and/or systemic metastases is equal to that of the primary tumor may be predictive on the estimation of the effectiveness of various cancer treatments that can be scheduled. Therefore, aims, developed as projects, of the past three years have been (1) to define the molecular phenotype of feline mammary carcinomas and their lymph node metastases according to a previous modified algorithm and to demonstrate the concordance or discordance of the molecular profile between the primary tumour and lymph node metastasis, (2) to analyze, in female dogs, the relationship between the primary mammary tumor and its lymph node metastasis based on immunohistochemical molecular characterization in order to develop the most specific prognostic-predictive models and targeted therapeutic options, and (3) to evaluate the molecular trend of cancer from its primary location to systemic metastases in three cats and two dogs with mammary tumors. The studies on mammary tumours, particularly in dogs, have drawn gradually increasing attention not exclusively to the epithelial component, but also to the myoepithelial cells. The lack of complete information on a valid panel of markers for the identification of these cells in the normal and neoplastic mammary gland and lack of investigation of immunohistochemical changes from an epithelial to a mesenchymal phenotype, was the aim of a parallel research. While investigating mammary tumours, it was noticed that only few studies had focused on the expression of CD117. Therefore, it was decided to further deepen the knowledge in order to characterize the immunohistochemical staining of CD117 in normal and neoplastic mammary tissue of the dog, and to correlate CD117 immunohistochemical results with mammary histotype, histological stage (invasiveness), Ki67 index and patient survival time.

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36

Beha, Germana <1983&gt. "Phenotypic characterization of the epithelial and myoepithelial components in canine and feline mammary tumours." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6373/.

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Abstract:

In veterinary medicine, the ability to classify mammary tumours based on the molecular profile and also determine whether the immunophenotype of the regional lymph node and/or systemic metastases is equal to that of the primary tumor may be predictive on the estimation of the effectiveness of various cancer treatments that can be scheduled. Therefore, aims, developed as projects, of the past three years have been (1) to define the molecular phenotype of feline mammary carcinomas and their lymph node metastases according to a previous modified algorithm and to demonstrate the concordance or discordance of the molecular profile between the primary tumour and lymph node metastasis, (2) to analyze, in female dogs, the relationship between the primary mammary tumor and its lymph node metastasis based on immunohistochemical molecular characterization in order to develop the most specific prognostic-predictive models and targeted therapeutic options, and (3) to evaluate the molecular trend of cancer from its primary location to systemic metastases in three cats and two dogs with mammary tumors. The studies on mammary tumours, particularly in dogs, have drawn gradually increasing attention not exclusively to the epithelial component, but also to the myoepithelial cells. The lack of complete information on a valid panel of markers for the identification of these cells in the normal and neoplastic mammary gland and lack of investigation of immunohistochemical changes from an epithelial to a mesenchymal phenotype, was the aim of a parallel research. While investigating mammary tumours, it was noticed that only few studies had focused on the expression of CD117. Therefore, it was decided to further deepen the knowledge in order to characterize the immunohistochemical staining of CD117 in normal and neoplastic mammary tissue of the dog, and to correlate CD117 immunohistochemical results with mammary histotype, histological stage (invasiveness), Ki67 index and patient survival time.

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37

Cancedda, Simona <1978&gt. "Diagnosi e terapia dei tumori delle cavita' nasali del cane." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/7035/1/Tesi_Dottorato_Cancedda.pdf.

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Lo studio è stato condotto su pazienti affetti da carcinoma nasale trattati con radioterapia presso il Centro Oncologico Veterinario (Sasso Marconi, BO). Lo studio, prospettico, randomizzato e in doppio cieco, ha valutato l’efficacia del trattamento radioterapico in combinazione o meno con firocoxib, un inibitore selettivo dell’enzima ciclossigenasi 2 (COX-2). Sono stati inclusi pazienti con diagnosi istologica di carcinoma nasale sottoposti a stadiazione completa. I pazienti sono stati successivamente suddivisi in due gruppi in base alla tipologia di trattamento: radioterapia associata a firocoxib (Gruppo 1) o solo radioterapia (Gruppo 2). Dopo il trattamento, i pazienti sono stati monitorati a intervalli di 3 mesi sia clinicamente che mediante esami collaterali, al fine di valutare condizioni generali del paziente, un’eventuale tossicità dovuta alla somministrazione di firocoxib e la risposta oggettiva al trattamento. Per valutare la qualità di vita dei pazienti durante la terapia, è stato richiesto ai proprietari la compilazione mensile di un questionario. La mediana del tempo libero da progressione (PFI) è stata di 228 giorni (range 73-525) nel gruppo dei pazienti trattati con radioterapia e firocoxib e di 234 giorni (range 50-475) nei pazienti trattati solo con radioterapia. La sopravvivenza mediana (OS) nel Gruppo 1 è stata di 335 giorni (range 74-620) e di 244 giorni (range 85-505) nel Gruppo 2. Non si sono riscontrate differenze significative di PFI e OS tra i due gruppi. La presenza di metastasi ai linfonodi regionali condizionava negativamente PFI e sopravvivenza (P = 0.004). I pazienti trattati con firocoxib hanno mostrato un significativo beneficio in termini di qualità di vita rispetto ai pazienti trattati con sola radioterapia (P=0.008). La radioterapia può essere considerata un’efficace opzione terapeutica per i cani affetti da neoplasie nasali. Firocoxib non sembra migliorare significativamente i tempi di sopravvivenza, ma risulta utile al fine di garantire una migliore qualità di vita.
Carcinomas represent two-thirds of canine nasosinal neoplasms. Although radiation therapy (RT) is the standard of care, the incidence of local recurrence following treatment is high. Cyclooxygenase-isoform-2 (COX-2) is expressed in 71-95% of canine nasal carcinomas and has been implicated in tumor growth and angiogenesis. Accordingly, COX-2 inhibition seems rational to improve outcome. Dogs with histologically confirmed, previously untreated nasal carcinomas were randomized to receive the combination of a selective COX-2 inhibitor (firocoxib) and palliative RT (Group 1) or RT and placebo (Group 2). Patients were regularly monitored with blood tests, urinalysis, and computed tomography. Pet owners were asked to complete monthly a quality-of-life questionnaire. Twenty-four dogs were prospectively enrolled. According to Adams modified system, there were five stage 1, five stage 2, three stage 3, and 11 stage 4 tumors. Two dogs had metastases to regional lymph nodes. Median progression-free interval and overall survival were 228 and 335 days in Group 1 (n = 12) and 234 and 244 days in Group 2 (n = 12). These differences were not statistically significant. The involvement of regional lymph nodes was significantly associated with progression-free interval and overall survival (P = 0.004). Quality of life was significantly improved in Group 1 (P = 0.008). In particular, a significant difference was observed for activity and appetite. Although not providing a significant enhancement of progression-free interval and overall survival, firocoxib in combination with RT is safe and improved life quality in dogs with nasal carcinomas.

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38

Cancedda, Simona <1978&gt. "Diagnosi e terapia dei tumori delle cavita' nasali del cane." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/7035/.

Full text

Abstract:

Lo studio è stato condotto su pazienti affetti da carcinoma nasale trattati con radioterapia presso il Centro Oncologico Veterinario (Sasso Marconi, BO). Lo studio, prospettico, randomizzato e in doppio cieco, ha valutato l’efficacia del trattamento radioterapico in combinazione o meno con firocoxib, un inibitore selettivo dell’enzima ciclossigenasi 2 (COX-2). Sono stati inclusi pazienti con diagnosi istologica di carcinoma nasale sottoposti a stadiazione completa. I pazienti sono stati successivamente suddivisi in due gruppi in base alla tipologia di trattamento: radioterapia associata a firocoxib (Gruppo 1) o solo radioterapia (Gruppo 2). Dopo il trattamento, i pazienti sono stati monitorati a intervalli di 3 mesi sia clinicamente che mediante esami collaterali, al fine di valutare condizioni generali del paziente, un’eventuale tossicità dovuta alla somministrazione di firocoxib e la risposta oggettiva al trattamento. Per valutare la qualità di vita dei pazienti durante la terapia, è stato richiesto ai proprietari la compilazione mensile di un questionario. La mediana del tempo libero da progressione (PFI) è stata di 228 giorni (range 73-525) nel gruppo dei pazienti trattati con radioterapia e firocoxib e di 234 giorni (range 50-475) nei pazienti trattati solo con radioterapia. La sopravvivenza mediana (OS) nel Gruppo 1 è stata di 335 giorni (range 74-620) e di 244 giorni (range 85-505) nel Gruppo 2. Non si sono riscontrate differenze significative di PFI e OS tra i due gruppi. La presenza di metastasi ai linfonodi regionali condizionava negativamente PFI e sopravvivenza (P = 0.004). I pazienti trattati con firocoxib hanno mostrato un significativo beneficio in termini di qualità di vita rispetto ai pazienti trattati con sola radioterapia (P=0.008). La radioterapia può essere considerata un’efficace opzione terapeutica per i cani affetti da neoplasie nasali. Firocoxib non sembra migliorare significativamente i tempi di sopravvivenza, ma risulta utile al fine di garantire una migliore qualità di vita.
Carcinomas represent two-thirds of canine nasosinal neoplasms. Although radiation therapy (RT) is the standard of care, the incidence of local recurrence following treatment is high. Cyclooxygenase-isoform-2 (COX-2) is expressed in 71-95% of canine nasal carcinomas and has been implicated in tumor growth and angiogenesis. Accordingly, COX-2 inhibition seems rational to improve outcome. Dogs with histologically confirmed, previously untreated nasal carcinomas were randomized to receive the combination of a selective COX-2 inhibitor (firocoxib) and palliative RT (Group 1) or RT and placebo (Group 2). Patients were regularly monitored with blood tests, urinalysis, and computed tomography. Pet owners were asked to complete monthly a quality-of-life questionnaire. Twenty-four dogs were prospectively enrolled. According to Adams modified system, there were five stage 1, five stage 2, three stage 3, and 11 stage 4 tumors. Two dogs had metastases to regional lymph nodes. Median progression-free interval and overall survival were 228 and 335 days in Group 1 (n = 12) and 234 and 244 days in Group 2 (n = 12). These differences were not statistically significant. The involvement of regional lymph nodes was significantly associated with progression-free interval and overall survival (P = 0.004). Quality of life was significantly improved in Group 1 (P = 0.008). In particular, a significant difference was observed for activity and appetite. Although not providing a significant enhancement of progression-free interval and overall survival, firocoxib in combination with RT is safe and improved life quality in dogs with nasal carcinomas.

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39

Muscatello, Luisa Vera <1985&gt. "Fattori di crescita e recettori tirosin chinasici nelle neoplasie e displasie degli animali domestici." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7575/1/Tesi_dottorato_Luisa_Vera_Muscatello.pdf.

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Abstract:

La perdita della comunicazione cellulare può portare ad una crescita deregolata e dunque alla trasformazione neoplastica. Gli scopi dello studio di dottorato sono stati di individuare il rapporto funzionale di alcuni fattori di crescita (FC) e dei loro recettori (RTC) in tipi di neoplasie e displasie degli animali domestici, quali: 1. Amplificazione del proto-oncogene ERBB2 e sovra-espressione del RTC erb-b2. in tumori mammari della gatta. 2. Espressione di erb-b2, di recettori ormonali, di citocheratine luminali, basali e marcatori mioepiteliali in carcinomi mammari a cellule chiare del cane. 3. Proliferazione microvascolare ed espressione di FC dell’angiogenesi e RTC (PDGF, VEGF, PDGFR-alfa e PDGFR-beta) in tumori dei plessi coroidei del cane. 4. Ruolo di FGF-2 in relazione a proteine strutturali e del ciclo cellulare nella differenziazione della cartilagine di accrescimento in vitelli con condrodisplasia di Ellis van Creveld. Nei tumori mammari felini il gene HER2 era amplificato e la proteina erbB2 era sovraespressa in un sottogruppo di tumori. L’ibridazione in situ a fluorescenza è il metodo ottimale per identificare l’amplificazione genica e per riscontrare falsi positivi e negativi ottenuti con l’immunoistochimica. Il carcinoma mammario glycogen-rich può essere considerato uno nuovo sottotipo istologico di tumore mammario del cane, PAS positivo, dPAS labile, con un fenotipo triplo negativo, dunque erbB2 negativo. I carcinoma dei plessi coroidei correlavano significativamente con l’indice Ki67 e la proliferazione microvascolare glomeruloide. I corpi glomeruloidi possono essere utilizzati come marcatori istologici di malignità e il PDGFR-beta risulta coinvolto nella loro formazione. La prematura degradazione del collagene II, una perdita di collagene X, unitamente ad una perdita di FGF2, suggeriscono che la sindrome EvC bovina è un disordine di differenziazione condrocitaria, caratterizzata da una differenziazione accelerata ed un’ipertrofia prematura. L’identificazione di alterazioni patologiche dei FC e dei RTC possono indirizzare scelte terapeutiche mirate nelle displasie e nelle neoplasie animali.
The loss of cells communication can lead to a deregulated growth and therefore to the neoplastic transformation. The aims of the phD study were to identify the relationship of growth factors (GF) and their tyrosine Kinase receptors (TKR) in types of neoplasia and dysplasia of domestic animals, as: 1. Amplification of the ERBB2 proto-oncogene and over-expression of the TKR erbB2 in feline mammary carcinoma. 2. Expression of erbB2, hormonal receptors, luminal, basal and myoepithelial markers in canine mammary clear cell carcinoma. 3. Microvascular proliferation and expression of angiogenic growth factors and their TKR (PDGF, VEGF, PDGFR-alpha and PDGFR-beta) in the canine choroid plexus tumors. 4. Role of Fibroblast Growth Factor-2 in relation to the structural and cell cycle proteins and the differentiation of the growth plate in calves with chondrodysplasia of Ellis van Creveld. In feline mammary carcinoma the HER2 gene was amplified and erbB2 protein was overexpressed in a subset of tumors. Fluorescence In situ hybridization is the method to identify the gene amplification and to detect false negatives and false positives obtained with immunohistochemistry. The glycogen-rich carcinoma can be considered a new histological subtype of canine mammary tumor, PAS positive, dPAS labile, expressing a triple-negative phenotype, therefore resulting erbB2 negative. Choroid plexus carcinomas significantly correlates with the Ki67 proliferation index and with the glomeruloid microvascular proliferation. Glomeruloid bodies may be used as a marker of malignancy in the canine choroid plexus tumors and PDGFR-beta is involved in their formation. The premature degradation of collagen II, a loss of the collagen X, together with a loss of FGF2, suggest that the bovine EvC syndrome is a disorder of chondrocyte differentiation, characterized by an accelerated and premature differentiation. Identification of the GF and TKR changes may direct targeted therapeutic choices in dysplasia and neoplasia of domestic animals.

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40

Muscatello, Luisa Vera <1985&gt. "Fattori di crescita e recettori tirosin chinasici nelle neoplasie e displasie degli animali domestici." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7575/.

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Abstract:

La perdita della comunicazione cellulare può portare ad una crescita deregolata e dunque alla trasformazione neoplastica. Gli scopi dello studio di dottorato sono stati di individuare il rapporto funzionale di alcuni fattori di crescita (FC) e dei loro recettori (RTC) in tipi di neoplasie e displasie degli animali domestici, quali: 1. Amplificazione del proto-oncogene ERBB2 e sovra-espressione del RTC erb-b2. in tumori mammari della gatta. 2. Espressione di erb-b2, di recettori ormonali, di citocheratine luminali, basali e marcatori mioepiteliali in carcinomi mammari a cellule chiare del cane. 3. Proliferazione microvascolare ed espressione di FC dell’angiogenesi e RTC (PDGF, VEGF, PDGFR-alfa e PDGFR-beta) in tumori dei plessi coroidei del cane. 4. Ruolo di FGF-2 in relazione a proteine strutturali e del ciclo cellulare nella differenziazione della cartilagine di accrescimento in vitelli con condrodisplasia di Ellis van Creveld. Nei tumori mammari felini il gene HER2 era amplificato e la proteina erbB2 era sovraespressa in un sottogruppo di tumori. L’ibridazione in situ a fluorescenza è il metodo ottimale per identificare l’amplificazione genica e per riscontrare falsi positivi e negativi ottenuti con l’immunoistochimica. Il carcinoma mammario glycogen-rich può essere considerato uno nuovo sottotipo istologico di tumore mammario del cane, PAS positivo, dPAS labile, con un fenotipo triplo negativo, dunque erbB2 negativo. I carcinoma dei plessi coroidei correlavano significativamente con l’indice Ki67 e la proliferazione microvascolare glomeruloide. I corpi glomeruloidi possono essere utilizzati come marcatori istologici di malignità e il PDGFR-beta risulta coinvolto nella loro formazione. La prematura degradazione del collagene II, una perdita di collagene X, unitamente ad una perdita di FGF2, suggeriscono che la sindrome EvC bovina è un disordine di differenziazione condrocitaria, caratterizzata da una differenziazione accelerata ed un’ipertrofia prematura. L’identificazione di alterazioni patologiche dei FC e dei RTC possono indirizzare scelte terapeutiche mirate nelle displasie e nelle neoplasie animali.
The loss of cells communication can lead to a deregulated growth and therefore to the neoplastic transformation. The aims of the phD study were to identify the relationship of growth factors (GF) and their tyrosine Kinase receptors (TKR) in types of neoplasia and dysplasia of domestic animals, as: 1. Amplification of the ERBB2 proto-oncogene and over-expression of the TKR erbB2 in feline mammary carcinoma. 2. Expression of erbB2, hormonal receptors, luminal, basal and myoepithelial markers in canine mammary clear cell carcinoma. 3. Microvascular proliferation and expression of angiogenic growth factors and their TKR (PDGF, VEGF, PDGFR-alpha and PDGFR-beta) in the canine choroid plexus tumors. 4. Role of Fibroblast Growth Factor-2 in relation to the structural and cell cycle proteins and the differentiation of the growth plate in calves with chondrodysplasia of Ellis van Creveld. In feline mammary carcinoma the HER2 gene was amplified and erbB2 protein was overexpressed in a subset of tumors. Fluorescence In situ hybridization is the method to identify the gene amplification and to detect false negatives and false positives obtained with immunohistochemistry. The glycogen-rich carcinoma can be considered a new histological subtype of canine mammary tumor, PAS positive, dPAS labile, expressing a triple-negative phenotype, therefore resulting erbB2 negative. Choroid plexus carcinomas significantly correlates with the Ki67 proliferation index and with the glomeruloid microvascular proliferation. Glomeruloid bodies may be used as a marker of malignancy in the canine choroid plexus tumors and PDGFR-beta is involved in their formation. The premature degradation of collagen II, a loss of the collagen X, together with a loss of FGF2, suggest that the bovine EvC syndrome is a disorder of chondrocyte differentiation, characterized by an accelerated and premature differentiation. Identification of the GF and TKR changes may direct targeted therapeutic choices in dysplasia and neoplasia of domestic animals.

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41

Levi, Michela <1989&gt. "Expression of P-glycoprotein and Breast Cancer Resistance Protein in Canine Mammary Tumors and in a Chemoresistant Mast Cell Tumor." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2018. http://amsdottorato.unibo.it/8296/1/Levi_Michela_Tesi.pdf.

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Multidrug resistance (MDR) consists in the ability of cancer cells to become resistant towards different drugs and is frequently mediated by ABC-transporters efflux pumps, such as P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP), which are also infamous for conferring cancer cell stemness and aggressiveness, thereby imparting a poor prognosis. MDR has been extensively studied in human oncology, but less is known in veterinary medicine. The aims of the past three years of investigation on canine mammary tumors have been to determine the distribution of P-gp and BCRP in the different cellular components of hyperplasia and neoplasia, to compare P-gp and BCRP expression in the histological stages and grades of canine mammary carcinomas (CMSs), to describe P-gp and BCRP expression in the stroma associated with neoplasia, and to examine P-gp and BCRP expression in two aggressive types of CMSs, namely canine inflammatory mammary cancer and histological grade 3 non-inflammatory carcinomas. P-gp and BCRP immunohistochemical expression was significantly higher in malignant vs benign epithelial cells and hyperplastic epithelium of the mammary gland, in aggressive histotypes (simple vs complex carcinomas; inflammatory carcinoma vs non-inflammatory carcinoma, only for P-gp), and in histological grade 2 and 3 carcinomas vs grade 1. Neoplasia-associated fibroblasts showed an increased expression in stage II and grade 2 and 3 carcinomas compared with stage I and grade 1. An increased expression of P-gp and BCRP was found in a canine relapsing and chemoresistant cutaneous mast cell tumor after chemotherapy with Vinblastine e Prednisolone. Chemoresistance in this case could be related to an increased efflux of the drugs mediated by these transmembrane pumps. Evaluation of P-gp and BCRP could help in the identification of aggressive, invasive and chemoresistant canine tumors, and the dog could provide a useful spontaneous model for chemoresistant human tumors.
La resistenza multifarmaco (MDR) conferisce alle cellule neoplastiche resistenza verso diversi composti chemioterapici ed è frequentemente dovuta all’azione di pompe di efflusso transmembrana (ABC-transporters), tra le quali la glicoproteina-P (P-gp) e la Breast Cancer Resistance Protein (BCRP), conosciute inoltre, per conferire caratteristiche di malignità e “staminalità” associate ad una prognosi infausta. La MDR è oggetto di molteplici studi in oncologia umana, mentre poco è noto in veterinaria. Gli obbiettivi di questi tre anni di ricerca sui tumori mammari della cagna sono stati: determinare l’espressione di P-gp e BCRP nelle componenti cellulari della mammella iperplastica e neoplastica, confrontarne l’espressione tra i diversi gradi e stadi istologici dei carcinomi, descriverne l’espressione nello stroma associato alla neoplasia, ed esaminarne e confrontarne l’espressione in due gruppi di neoplasie mammarie aggressive quali il carcinoma infiammatorio e il carcinoma di grado istologico 3. Mediante l’immunoistochimica è emerso che l’espressione di P-gp e BCRP era significativamente più elevata nei tumori mammari maligni (nelle cellule epiteliali maligne rispetto all’epitelio iperplastico), negli istotipi più aggressivi (nei carcinomi semplici rispetto ai complessi e nei carcinomi infiammatori rispetto ai carcinomi non-infiammatori, per P-gp), e nei carcinomi di grado istologico 2 e 3 rispetto al grado 1. I fibroblasti esprimevano maggiormente P-gp e BCRP nello stroma associato ai carcinomi di stadio II e di grado 2 e 3, rispetto a quelli di stadio I e grado 1. Un aumento dell’espressione di P-gp e BCRP è stato riscontrato in un cane con mastocitoma cutaneo recidivante dopo chemioterapia con Vinblastina e Prednisolone. La chemioresistenza sviluppata potrebbe essere dovuta all’aumento dell’efflusso dei farmaci dal comparto intracellulare mediato da P-gp e BCRP. Determinare l’espressione di P-gp e BCRP potrebbe essere utile ad identificazione le neoplasie aggressive e chemioresistenti, ed il cane potrebbe fornire un valido modello spontaneo per lo studio della chemioresistenza nei tumori dell’uomo.

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42

Pellegrino, Valeria <1986&gt. "Caratterizzazione clinico-patologica dei tumori dei tessuti molli del cane: classificazione istologica, variabili patologiche, e target per terapie adiuvanti." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2019. http://amsdottorato.unibo.it/8859/5/Pellegrino_Valeria_Tesi.pdf.

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Il progetto di dottorato ha riguardato la caratterizzazione clinico-patologica dei tumori dei tessuti molli del cane esaminandone la classificazione istologica e le variabili patologiche al fine di individuare possibili target per terapie adiuvanti, concentrando la ricerca sui tumori adipocitari e muscolaturi lisci (SMT) benigni e maligni. Per quanto riguarda i tumori adipocitari maligni ho valutato l’espressione immunoistochimica di FGF2, FGFR1, PDGFB, PDGFRb, e c-kit nei liposarcomi del cane, comparandoli con conta mitotica e l'indice di proliferazione. Il pathway del PDGFB-PDGFRb sembra essere coinvolto nella proliferazione neoplastica ed è dunque un ottimo candidato come target terapeutico. Riguardo alle neoplasie adipocitarie benigne, ho descritto 6 casi di lipoma a cellule fusate (LCF), neoplasia poco caratterizzata nel cane, che è importante riconoscere per evitare diagnosi errate di sarcoma. Per quanto riguarda i SMT gastrointestinali del cane ho testato l'efficacia del Tissue Micro Array (TMA) per la loro diagnosi. Questa tecnica è stata applicata per selezionare i SMT. I criteri per la discriminazione dei SMT benigni e maligni sono scarse nella letteratura veterinaria. La casistica è stata analizzata con criteri di medicina umana e veterinaria per identificare parametri che aiutino a discriminare tra neoplasie benigne e maligne. Nei casi a carico dei tessuti molli (ST-SMT) sono infine state esaminate le caratteristiche clinico-patologiche e l'espressione dei recettori ormonali. La presenza di SMT positivi ai recettori ormonali a sede perineale, pelvica e retroperitoneali suggerisce l'esistenza di un sottogruppo distinto di ST-SMT canini che possono insorgere da leiomiociti sensibili agli ormoni in queste regioni anatomiche, come accade nell'uomo.
I focused my research on the clinical-pathological characterization of canine soft tissues tumors looking over the histological classification and the pathological variables to search possible target for adjuvant therapies, focusing on canine benign and malignant adipocytic and smooth muscle tumors (SMT). I investigated the immunohistochemical expression of FGF2, FGFR1, PDGFB, PDGFRb, and c-kit in canine liposarcomas compared with mitotic counts and proliferation index to identify whether these pathways are involved in neoplastic progression and can therefore represent potential therapeutic targets. The PDGFB-PDGFRb pathway appears to be involved in the neoplastic proliferation and could be an excellent candidate as therapeutic target. Regarding benign adipocytic neoplasms, I have described 6 cases of spindle cell lipomas (SCL), a benign neoplasm that may resemble an undifferentiated soft tissue sarcoma (STS) to characterize canine SCLs and avoid a misdiagnosis of STS. Regarding canine SMT I tested the efficacy of Tissue Micro Array (TMA) in gastrointestinal spindle cell tumors. This technique has been applied to select SMTs. The criteria for discrimination of benign and malignant SMTs are scarce in veterinary literature. The caseload was analyzed with human and veterinary criteria to identify parameters to discriminate between benign and malignant neoplasms. In soft tissues-SMT have been examined as well as clinical-pathological features also hormonal receptors expression. The finding of some ER or PR positive soft tissue SMTs in perineal, pelvic and retroperitoneal regions, suggests the existence of a distinct subset of canine ST-SMTs that may arise from hormone sensitive leiomyocytes in these anatomical regions, as occurs in humans.

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Di, Palma Stefano <1978&gt. "Canine oral malignant melanoma: genomic and immunohistochemical approaches to better characterize the metastatic dissemination to the lymph node." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2020. http://amsdottorato.unibo.it/9165/1/OMM%20thesis%2031102019%20final%202020.pdf.

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Malignant melanoma is the most common malignant tumour of the oral cavity in the dog, with high rate of metastatic dissemination to the regional lymph nodes and distant organs. There is significant overlap in regards of biologic behaviour, histological appearance and genomic alterations between canine and human OMMs. Therefore, the dog is considered a good preclinical model for this deadly tumour. In the first part of this study we aimed to identify genes that are involved in the metastatic dissemination of canine OMMs by microarray mRNA profiling of 4 pairs of primary tumours and their lymph nodal metastases. These genes could represent a future target for the control and hopefully treatment of the metastatic disease. We pointed out the presence of several genes displaying different expression between the primary and the metastatic tumour. In particular, Rac1 seems to play a key role in the dissemination of melanoma cells to the lymph node, most likely due to its regulatory activity of cell motility. In the second part of the study we assessed the potential improvement of detection of lymphatic invasion in canine primary OMMs by using immunohistochemistry for Prox-1, as the detection of lymphatic invasion in a primary tumour is generally considered an unfavourable prognostic factor for several cancers, including human and canine OMMs. We also tried to prove direct correlation between the presence of lymphatic invasion in the primary tumour and regional lymph node metastasis. Our results showed that Prox-1 IHC is not able to enhance detection of lymphatic invasion in the primary site and that the sensitivity of detection of lymphatic invasion in predicting lymph nodal metastasis is low (46.7%), despite high specificity (97%). Finally, we pointed out the presence of interobserver variability in detecting lymphatic invasion in canine primary OMMs, most likely due to interpretative variation.

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Rigillo, Antonella <1990&gt. "Tecniche biomolecolari in supporto all'esame istopatologico in oncologia veterinaria." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2020. http://amsdottorato.unibo.it/9200/1/Tesi%20Rigillo%20AMS.pdf.

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Negli ultimi vent'anni, la medicina veterinaria ha focalizzato la propria attenzione verso il benessere animale e lo sviluppo di strumenti diagnostici e terapeutici più efficienti. In particolare, in campo oncologico sono stati adottati approcci multidisciplinari finalizzati a caratterizzare al meglio le neoplasie dei piccoli animali, per poterne migliorare la prognosi e validarli come modelli spontanei di patologia dell'uomo. Alle più aggiornate conoscenze sul comportamento biologico dei tumori e le loro caratteristiche istopatologiche si stanno infatti affiancando tecnologie d'avanguardia sia nel campo della ricerca che della diagnostica quotidiana. Lo scopo del presente studio è stato quello di indagare l'utilità diagnostica di tre tecniche biomolecolari in supporto all'esame istologico ed immunoistochimico per valutare se in grado di amplificare il potenziale diagnostico delle attuali tecniche gold-standard. In particolare, abbiamo indagato: (1) L'applicazione della PCR per il riarrangiamento del recettore antigienico (PARR) per determinare la clonalità delle lesioni linfoidi iperplastico/neoplastiche nelle milze di cane. L'idoneità di questa tecnica è stata confermata nei casi istologici dubbi attraverso una critica interpretazione dei risultati sulla base dei dati clinici, morfologici e di immunofenotipo. (2) La concordanza tra il gold-standard immunoistochimica e la meno invasiva citofluorimetria a flusso nella valutazione dell'attività proliferava (Ki-67 index) dei linfomi nodali del cane. E' stata dimostrata una buona concordanza complessiva tra le due tecniche, nonostante il ruolo prognostico del Ki-67 nel linfoma del cane sia ancora dubbio. (3) I pattern genetici ed epigenetici del carcinoma squamocellulare orale del gatto, per identificare criteri biomolecolari idonei alla diagnosi precoce di questo tumore, fatale anche a causa della tardiva diagnosi, sulla base di recenti scoperte in campo umano. E' stato proposto un test non invasivo basato su un algoritmo diagnostico preliminare per discernere lesioni orali neoplastiche da quelle non neoplastiche nel gatto.
Within the last two decades, veterinary medicine has strongly increased its attention for animal best care practices and development of more efficient diagnostic and therapeutic strategies. Namely, in veterinary oncology multi-disciplinary approaches were adopted to better characterize small animals tumors, in order to improve prognosis and validate them as naturally occurring models for the human counterpart. In addition to refining the knowledge of biological behavior and histopatological features of neoplasms, cutting-edge biomolecular technologies are gaining ground in both research and everyday diagnostic workup. The aim of the present study was to investigate the diagnostic utility of three biomolecular technologies in support of histopathological and immunohistochemical examination, in order to evaluate whether they can enhance the potential of the current gold-standard diagnostic procedures. In particular, we investigated: (1) The application of PCR for antigen receptor rearrangement (PARR) for assessing the clonality of hyperplastic/neoplastic splenic lymphoid lesions in dogs. The suitability of this technique was confirmed in doubtful histological cases through a critical interpretation of the results on the basis of the clinical, morphological and immunophenotyping data. (2) The agreement between the gold standard immunohistochemistry and the less invasive flow cytometry in the evaluation of proliferative activity (Ki-67 index) of canine nodal lymphomas. We demonstrated an overall good concordance between the techniques, although the possible prognostic role of Ki-67 in canine lymphoma has still to be clarified. (3) The genetic and epigenetic modification patterns of feline oral squamous cell carcinoma, in order to provide biomolecular criteria for the early detection of this late-stage diagnosed and fatal tumor, on the basis of recent discoveries in the human counterpart. A preliminary diagnostic algorithm was proposed as a non-invasive test to discriminate between neoplastic and non-neoplastic feline oral lesions.

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45

Tura, Giorgia <1987&gt. "Molecular analysis of Papillomavirus-induced cutaneous tumors in equids." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2022. http://amsdottorato.unibo.it/10208/1/Tura_Giorgia_tesi.pdf.

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Papillomavirus associated tumors are well recognized entities in humans as well as in animals. Here is reviewed the current understanding of human papillomavirus (HPV) associated cancers to better understand the oncogenic mechanisms of Equine papillomavirus (EcPV) and Bovine Papillomavirus (BPV) in horses. In the first part of this study the interactions between Equine papillomavirus 2 (EcPV-2) and cell cycle proteins are discussed. EcPV-2 has been recognized as the cause of genital squamous cell carcinomas (SCCs) in horses, but the exact mechanism of carcinogenesis is not fully understood. The aim of the first part of this study is to assess the expression of cell cycle proteins p53, p16, pRB and Cyclin D1 in a series of equine SCCs and papillomas. Results confirm the role of EcPV-2 in the pathogenesis of genital SCCs. Moreover, in a small subset of ocular SCCs, EcPV-2 was detected for the first time. By immunohistochemistry, p53 was mostly expressed in ocular SCCs with a suprabasal localization. Regarding p16, overexpression was associated with increased mitotic index but not with viral infection. Investigation on pRB and Cyclin D1 proteins did not show significant correlation with other variables. The second part of this study is focused on the carcinogenetic mechanisms of BPV in equine sarcoids. The aim of the second part of this study was to characterize the typical histomorphological features of equine sarcoids, assess the expression of cell cycle proteins and Ki-67 proliferation index. Our results confirm that the typical histological features of sarcoids cannot be used to correctly classify the clinical types. Moreover, in a subset of sarcoids low pRB-Cyclin D1 scores were associated with simultaneous high p16 expression. The Ki-67 proliferation index confirm the low proliferative activity of sarcoids, except for tumors displaying a fascicular pattern. Finally, a subset of sarcoids recurred after excision.

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46

Cardano, Carla <1952&gt. "Le ricerche sulle tossine svolte nella Patologia generale di Bologna dalla fine del XIX secolo a oggi." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2007. http://amsdottorato.unibo.it/260/1/TESI_IMPAGINATA.pdf.

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47

Cardano, Carla <1952&gt. "Le ricerche sulle tossine svolte nella Patologia generale di Bologna dalla fine del XIX secolo a oggi." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2007. http://amsdottorato.unibo.it/260/.

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48

PICCININI, ANDREA. "Apoliprotein A-IV as a new possible molecular ''tool'' to understand feline hepatic lipidosis physiopathology." Doctoral thesis, Università degli Studi di Camerino, 2015. http://hdl.handle.net/11581/401735.

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Feline Hepatic Lipidosis (FHL) represents one of the most common metabolic disorders in cats. Apolipoprotein (apo) A-IV is a protein known to participate in the regulation of various metabolic pathways, with special regards to lipid metabolism. The present study demonstrates a relation between hepatic lipid content and apo A-IV expression in rat and cat liver, opening a fascinating innovative hypothesis on FHL pathogenesis. Livers from cats (5) and rats (8) were processed to determine hepatic lipid content using Mojonnier method. Apo A-IV liver protein expression was assessed by ELISA using liver tissue extracts. Finally, samples of all livers were processed for histopathology and immunohistochemistry to confirm previously obtained results. Data show an interesting inverse proportion between hepatic lipid content and apo A-IV liver expression, highlighting differences between cat and rat lipid metabolism. Applying this comparative experimental approach, we suggest an innovative pathogenetic hypothesis which involves apo A-IV as a ''new actor'' molecule involved in FHL determinism and its potential role as a prodromal serological diagnostic marker.

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CARTUCCIA, CRISTINA. "Immunohistochemical expression of hormonal receptors in normal and neoplastic mammary tissue in the dog." Doctoral thesis, Università degli Studi di Camerino, 2009. http://hdl.handle.net/11581/401942.

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The mammary carcinoma is the most frequent tumor in the women as well as in the bitches. In human medicine, the evaluation of immunohistochemical expression of estrogen receptors (ER) Î± and Î², progesterone receptor (PR) and androgen receptor (AR) is very useful to predict prognosis and response to endocrine therapy. However, in veterinary medicine, there is little knowledge of the role of these elements in canine mammary tumors. Especially, the information concerning the expression and significance of AR are very scant. Moreover, among the canine mammary tumors there are often complex/mixed neoplasm, characterized by neoplastic transformation of myoepithelial cells. These cells are involved in the mammary cancer progression, but to date there are not specific studies about their receptorial assessment. The aim of this work was to verify, in canine mammary tumors, the existence of correlations between biological behaviour and immunohistochemical expression of ERÎ±, ERÎ², PR and AR. A group of thirty bitches with mammary neoplasm was included in the study. Clinical and reproductive histories were obtained from their owners. The animals were subjected to physical examination and thoracic X-ray. Clinical staging of tumors was carried out according to criteria of WHO. Partial or total mastectomy was performed and the whole tissue, fixed in buffered neutral formalin, was sent to Laboratory of Animal Pathology - University of Camerino (Italy). The animals were followed during a year after the surgery. The plan of follow up included clinical examination and thoracic X-ray. Thirty-two tumors were collected and examined. Histological classification and grading were carried out according to criteria of WHO. The immunohistochemical expression of ERÎ±, ERÎ², PR and AR was assessed for each sample. Statistical analysis was performed by Student's t-test and Spearman's correlation. We found specific nuclear reaction against all the receptors in normal and neoplastic epithelial and myoepithelial cells. Only the immunodetection of ERÎ± was higher in young bitches (p minus 0,05) whereas the expression of all the other receptors was not correlated with the age. There were not correlations between receptorial assessment and reproductive variables. The expression of every receptor was higher in normal tissue and benign tumors than in malignant neoplasm. Among malignancies, the lowest levels of every receptors were detected in high grade carcinomas (p minus 0,01). Levels of ERÎ± and PR were inversely correlated with the presence of regional (p minus 0,01) and/or distant (p minus 0,05) metastasis. A lower expression of ERÎ² was found in carcinomas with nodal positive status (p minus 0,05) whereas a high level of AR seemed weakly correlated with development of distant metastasis (pmajor0,05). A high expression of ERÎ± and/or PR appeared as a good prognostic factors for the DFS (p minus 0,01). ERÎ² also displayed a positive prognostic significance (p minus 0,05). On the other hand, the levels of AR were inversely correlated only with grading but we showed a slight positive correlation with metastatic power of carcinoma (pmajor0,05). In human breast carcinoma, AR seems to be involved in metastatic development by up-regulation of metalloprotease of matrix (MMP). Therefore, evaluating the correlation among presence of AR, expression of MMP and appearance of distant metastasis also in canine mammary tumors could be very interesting. On the contrary we not found important correlations between the receptorial status of myoepithelial cells and the biological behaviour of tested cases.

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50

DI, CICCO EMILIANO. "Evaluation of the activity of the immune system and age-related tissue markers in Turquoise killifish (Nothobranchius furzeri, Jubb 1971) and their role in cell ageing." Doctoral thesis, Università degli Studi di Camerino, 2010. http://hdl.handle.net/11581/401925.

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Abstract:

Currently the Turquoise Killifish is considered the best animal model suitable for aging research. This annual fish, from south east Africa, shows an exceptionally adaptive behaviour to dry periods: indeed, due to this extreme environmental characteristics, the life cycle of Nothobranchius furzeri is very fast, with an average lifespan of just about 8-9 weeks, making this species (more similar to highly developed vertebrates than nematodes or fruit flies) highly practical for aging studies. The present study has evaluated the activity of the immune system as well as the expression of AGE-RAGE system, cell-damage related proteins (Bcl2, p53), mitosis activity marker (PCNA), and pro-apoptosis activity by T.U.N.E.L. method on the liver of four lifespan-specific strains of Turquoise Killifish (Nothobranchius furzeri, Jubb 1971), correlating the results with aging processes and tumor incidence. Some groups underwent caloric restriction in order to module their expected lifespan. The results demonstrated an increase of age-related lesions along with the age in all the strains tested, due to a decrease of cellular-turn-over. This aspect was also influenced by the strain of the fish: longest lifespan strains showed later the similar lesions than short lifespan strains. Moreover caloric restriction groups showed lower incidence and severity of hepatic degeneration than control groups. Furthermore, there was a linear correspondence between the age of the model and its expected lifespan with the incidence and severity of neoplasm. The same relationship could be found in the expression of cell-damage related proteins (p53, Bcl2), age-related markers (AGE-RAGE system) and pro-apoptosis activity, as well as in the development of neoplasms. These results demonstrated the high feasibility of this fish as an excellent model to study the effects of aging processes and cancer genesis.

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Dissertations / Theses on the topic 'Patologia generale'

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