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4. La riforma Gentile e gli studi giuridici: una palingenesi mancata

Author

Mattone, A, Moretti, M, Signori, E, Chiodi, G, Mattone, A, Moretti, M, Signori, E, and Chiodi, G

Abstract

Dal punto di vista delle Facoltà di Giurisprudenza, la riforma Gentile dell’istruzione superiore fu punto di arrivo e nello stesso tempo blocco di partenza di ulteriori progetti politici, alla ricerca di soluzioni a problemi fondamentali, spesso etichettati come generati da crisi e decadenza degli studi giuridici, quali l’autonomia dell’organizzazione; il sistema di reclutamento dei professori; la funzione della facoltà (il modello di educazione: culturale o professionale?); il valore dei titoli accademici; il metodo didattico (lezioni, esercitazioni ed esami); l’autonomia degli studenti rispetto al piano di studi; il rapporto tra laurea ed esame di stato; l’affermarsi dell’università di massa con il conseguente problema dell’affollamento dei corsi (riduzione delle facoltà o numero chiuso?); il rapporto tra Giurisprudenza e la Facoltà di scienze politiche. Per approfondire tali questioni, che assumono una peculiare curvatura nel campo giuridico, si isolano dal dibattito da una parte alcuni interventi degli addetti ai lavori più vicini al regime e dall’altra le riflessioni dei giuristi che, anche per il ruolo occupato nell’università e quindi per l’esperienza maturata, ne discussero con speciale cognizione di causa., From the point of view of the Faculties of Law, the Gentile Reform of higher education was the point of arrival and at the same time the starting block for further political projects, in search of solutions to fundamental problems, often labelled as generated by the crisis and decadence of legal studies, such as the autonomy of the organisation; the system of recruiting professors; the function of the faculty (the model of education: cultural or professional? ); the value of academic qualifications; the teaching method (lectures, tutorials and examinations); the autonomy of students with respect to the syllabus; the relationship between degrees and State examinations; the emergence of the mass university with the consequent problem of course crowding (reduction of faculties or limited number?); the relationship between Law and the Faculty of Political Sciences. In order to examine these issues, which take on a peculiar bent in the field of law, the essay isolates from the debate on the one hand some interventions by insiders closer to the regime and on the other hand the reflections of jurists who, also because of the role they occupied in the university and thus because of the experience they gained, discussed them with special insight.

Published
2023

7. Study of Attitudes of the Elderly Toward Aging & the Aged.

Author

Signori, E. I. and Kozak, J.

Abstract

This study provides a closer perspective and appreciation of what elderly people think and feel about aging and the aged. Contained herein is a summary of the recorded written responses of 200 consecutive statements received from male and female persons 65 years old and over, in response to several broad questions regarding aging and the aged. The summary statements attempt to capture the diversity of meaning found in the recorded statements about a number of issues which are of interest to the elderly surveyed. In the issues discussed, no claim is made that the trends shown are generalizable to the total population of the elderly in British Colombia. However, that the issues may be of concern to a large number of the elderly is not contraindicated by these data. The additional, though as yet unanalyzed, data at hand from approximately 400 other respondents eventually should prove useful in confirming or disconfirming the consistency of present trends. Currently an attempt is being made to relate the experimental findings reported herein to findings obtained by studies using questionnaire and/or structured interview procedure. (Author)

Published
1976

8. Expression and heterodimer-binding activity of Ku70 and Ku80 in human non-melanoma skin cancer

Author

Parrella, P., Mazzarelli, P., Signori, E., Perrone, G., Marangi, G.F., Rabitti, C., Delfino, M., Prencipe, M., Gallo, A.P., Rinaldi, M., Fabbrocini, G., Delfino, S., Persichetti, P., and Fazio, V.M.

Subjects
Gene expression -- Research, Ultraviolet radiation -- Health aspects, Ultraviolet radiation -- Research, Skin cancer -- Genetic aspects, Skin cancer -- Research, Health
Published
2006

14. EphB2 stem-related and EphA2 progression-related miRNA-based networks in progressive stages of CRC evolution: clinical significance and potential miRNA drivers

Author

De Robertis, M, Mazza, T, Fusilli, C, Loiacono, L, Poeta, M, Sanchez, M, Massi, E, Lamorte, G, Diodoro, M, Pescarmona, E, Signori, E, Pesole, G, Vescovi, A, Garcia-Foncillas, J, Fazio, V, Loiacono L, Poeta, ML, Diodoro, MG, Vescovi A, Garcia-Foncillas J, Fazio, VM, De Robertis, M, Mazza, T, Fusilli, C, Loiacono, L, Poeta, M, Sanchez, M, Massi, E, Lamorte, G, Diodoro, M, Pescarmona, E, Signori, E, Pesole, G, Vescovi, A, Garcia-Foncillas, J, Fazio, V, Loiacono L, Poeta, ML, Diodoro, MG, Vescovi A, Garcia-Foncillas J, and Fazio, VM

Abstract

EphB2 and EphA2 control stemness and differentiation in the intestinal mucosa, but the way they cooperate with the complex mechanisms underlying tumor heterogeneity and how they affect the therapeutic outcome in colorectal cancer (CRC) patients, remain unclear. MicroRNA (miRNA) expression profiling along with pathway analysis provide comprehensive information on the dysregulation of multiple crucial pathways in CRC. Through a network-based approach founded on the characterization of progressive miRNAomes centered on EphA2/EphB2 signaling during tumor development in the AOM/DSS murine model, we found a miRNA-dependent orchestration of EphB2-specific stem-like properties in earlier phases of colorectal tumorigenesis and the EphA2-specific control of tumor progression in the latest CRC phases. Furthermore, two transcriptional signatures that are specifically dependent on the EphA2/EphB2 signaling pathways were identified, namely EphA2, miR-423-5p, CREB1, ADAMTS14, and EphB2, miR-31-5p, mir-31-3p, CRK, CXCL12, ARPC5, SRC. EphA2- and EphB2-related signatures were validated for their expression and clinical value in 1663 CRC patients. In multivariate analysis, both signatures were predictive of survival and tumor progression. The early dysregulation of miRs-31, as observed in the murine samples, was also confirmed on 49 human tissue samples including preneoplastic lesions and tumors. In light of these findings, miRs-31 emerged as novel potential drivers of CRC initiation. Our study evidenced a miRNA-dependent orchestration of EphB2 stem-related networks at the onset and EphA2-related cancer-progression networks in advanced stages of CRC evolution, suggesting new predictive biomarkers and potential therapeutic targets.

Published
2018

15. Dysregulation of EGFR pathway in EphA2 cell subpopulation significantly associates with poor prognosis in colorectal cancer

Author

De Robertis, M, Loiacono, L, Fusilli, C, Poeta, M, Mazza, T, Sanchez, M, Marchionni, L, Signori, E, Lamorte, G, Vescovi, A, Garcia Foncillas, J, Fazio, V, Poeta, ML, Vescovi, AL, Fazio, VM, De Robertis, M, Loiacono, L, Fusilli, C, Poeta, M, Mazza, T, Sanchez, M, Marchionni, L, Signori, E, Lamorte, G, Vescovi, A, Garcia Foncillas, J, Fazio, V, Poeta, ML, Vescovi, AL, and Fazio, VM

Abstract

Purpose: EphA2 receptor is involved in multiple cross-talks with other cellular networks, including EGFR, FAK, and VEGF pathways, with which it collaborates to stimulate cell migration, invasion, and metastasis. Colorectal cancer (CRC) EphA2 overexpression has also been correlated to stem-like properties of cells and tumor malignancy. We investigated the molecular cross-talk and miRNAs modulation of the EphA2 and EGFR pathways. We also explored the role of EphA2/EGFR pathway mediators as prognostic factors or predictors of cetuximab benefit in patients with CRC. Experimental Design: Gene expression analysis was performed in EphA2high cells isolated from CRC of the AOM/DSS murine model by FACS-assisted procedures. Six independent cohorts of patients were stratified by EphA2 expression to determine the potential prognostic role of a EphA2/EGFR signature and its effect on cetuximab treatment response. Results: We identified a gene expression pattern (EphA2, Efna1, Egfr, Ptpn12, and Atf2) reflecting the activation of EphA2 and EGFR pathways and a coherent dysregulation of mir-26b and mir-200a. Such a pattern showed prognostic significance in patients with stage I-III CRC, in both univariate and multivariate analysis. In patients with stage IV and WT KRAS, EphA2/Efna1/Egfr gene expression status was significantly associated with poor response to cetuximab treatment. Furthermore, EphA2 and EGFR overexpression showed a combined effect relative to cetuximab resistance, independently from KRAS mutation status. Conclusions: These results suggest that EphA2/Efna1/Egfr genes, linked to a possible control by miR-200a and miR-26b, could be proposed as novel CRC prognostic biomarkers. Moreover, EphA2 could be linked to a mechanism of resistance to cetuximab alternative to KRAS mutations.

Published
2017

21. Electroporation in DNA vaccination protocols against cancer

Author

Chiarella P, Fazio VM, and Signori E.

Subjects
DNA vaccine, electroporation, tumour antigen, cancer, immune response
Abstract

Since conventional therapeutic approaches in cancer are highly invasive they hardly prolong patient survival for more than few months. Having the ability to stimulate both cellular and humoural immune responses, immunisation with naked plasmid DNA encoding tumour-associated antigens or tumour-specific antigens has recently reported a plethora of advantages, and the improvement of vaccine efficacy has emerged as a goal in the development of DNA vaccination as anti-tumour therapy. Nevertheless, because of their poor immunogenicity when administered as unformulated intramuscular injections, plasmid DNA vaccines need to be improved. Recent data suggest that the DNA vaccine efficacy may significantly be increased by electroporation. This review highlights the recent literature that supports electroporation as an effective strategy to improve DNA-based vaccination protocols, investigating the most relevant studies, recently developed for the applications of DNA vaccine electrotransfer against tumours in pre-clinical and clinical studies.

Published
2013

22. “DNA vaccines for B-cell lymphomas: towards personalised medicine and tailored drugs”

Author

Iurescia S., Fioretti D., Pierimarchi P., Signori E., Zonfrillo M., Fazio V.M., and Rinaldi M.

Abstract

DNA vaccine platform has produced exciting results in a wide array of applications, from prophylactic vaccine strategies to poten- tial therapeutics targeting cancers and infectious disease (Fioretti et al., 2010; Rinaldi et al., 2009; Rinaldi et al., 2006; Fazio et al., 2004). Many tumor antigens are excellent targets for active immunotherapy and can be presented by DNA vaccines in a molecular form suitable to engage both humoral and cellular immune responses. Our group is involved in the development of DNA vaccination strategies as active immunotherapy for the treatment of B-cell lym- phomas. The idiotype region in the immunoglobulin expressed on the surface of B-cell lymphomas is a tumour-specific as well a patient-specific antigen and an ideal target for personalised immunotherapy. We focused on the idiotypic determinants lying within the CDR3 hypervariable regions and demonstrated that immunisation with CDR3-based DNA vaccines elicited anti- idiotypic humoral response able to recognize native antigens on tumour cells (Rinaldi et al., 2001). In a highly aggressive preclinical murine B-cell lymphoma model, we evaluated the antitumour response recruited by CDR3- based DNA vaccines. We showed that a combination of CDR3-based DNA vaccines with electroporation in a homologous prime-boost approach was protective against a lethal tumour challenge (Rinaldi et al., 2008; Iurescia et al., 2010). Since a goal of our studies is the development of tai- lored immunisation strategies against previously established tumours, efforts are ongoing to optimize the DNA vaccine tech- nology platform. Strategies to improve antigen expression and immunogenicity involve epitope prediction, MHC I presentation enhancement, inclusion of pathogen-derived sequences aimed to stimulate CD4+ T cell help and immunomodulating cytokines. Preliminary results encourage the use of therapeutic protocols based on DNA vaccines as tailored drugs for the treatment of lymphoma. Optimal integration of active immunization approaches into standard therapies suggests DNA vaccination as an effective per- sonalized medicine to eradicate minimal residual diseases during clinical remission following standard chemotherapy in lymphoma patients.

Published
2010

24. Recent advances in epitope design for immunotherapy of cancer

Author

Chiarella P., Massi E., De Robertis M., Fazio V.M., and Signori E.

Subjects
clinical trials, in silico' prediction, epitope enhancement, immunotherapy, Cancer
Abstract

Eradication of cancer cells is imperative for a successful treatment of tumours. In addition to the existent chemotherapy or radiation therapy, other novel immunotherapeutic strategies to fight tumours are currently under investigation. One of these is cancer vaccination, an approach aimed at inducing effective immune responses in the host against defined tumour antigens. Among several classes of cancer vaccines, the subunit vaccines based on the single and multi epitope-approach are worthy of note as they offer an exquisite specificity in targeting only tumour cells. In this review we will focus on the significant advances made in the development and use of epitope-based cancer vaccines, reporting a selection of important and recent patents on tumour antigen discovery and epitope design for immunotherapy of cancer.

Published
2009

26. An overview of Apoe for application in gene therapy

Author

Rinaldi M., Iurescia S., Fioretti D., Massi E., and Signori E

Subjects
lipids (amino acids, peptides, and proteins)
Abstract

Atherosclerosis, one of the most prevalent and severe age-related diseases, is the leading cause of death in industrialized countries and it is becoming an increasingly worldwide risk to health. As the size of elderly population grows, the incidence of atherosclerosis will increase, necessitating the exploration of radical, but potentially powerful, therapeutic strategies. One important goal is the availability of therapeutic molecules effective against the atherosclerotic plaque progression and able to stabilize advanced lesions. This generally requires robust measures to improve plasma lipoprotein profiles. Pharmaceutical agents currently available do not support significant changes in plasma lipoprotein levels. So that, strong new agents and therapies are needed in order to treat hyperlipidemia and atherosclerosis. Apolipoprotein E (ApoE), a key regulator in cholesterol-rich lipoprotein metabolism, is considered a strong candidate for treating hypercholesterolemia and cardiovascular disease. ApoE gene therapy could be proposed as a new valid approach for the correction of hyperlipidemic conditions and atherosclerosis by using viral and non-viral vectors. In this review we discuss the major developments in both viral and non-viral gene transfer systems aimed at achieving efficient protocols for treating hypercholesterolemia and atherosclerosis by using ApoE as therapeutic gene. Key scientific advances on the ability of ApoE gene transfer to markedly improve outcome after cerebral ischemia, suggesting a potential strategy in human stroke therapy, are also described in this review. The characterization of ApoE and its many functions has provided insight into the ultimate potential of this protein as a possible therapeutic agent for the treatment of several diseases. Possible therapeutic strategies that encompass the use of ApoE in gene therapy for Alzheimer's disease and other central nervous system (CNS) diseases will be also discussed.

Published
2009

27. ICON2: randomised trial of single-agent carboplatin against three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) in women with ovarian cancer

Author

Parmar MKB, Torri V, Bonaventura A, Bonazzi C, Colombo N, Delaloye JF, Marsoni S, Mangioni C, Sandercock J, Sessa C, Williams C, Tinazzi A, Flann M, Geiser K, Scorpiglione N, Stewart JF, Chaves J, Palmeiro E, Curtain A, McCormack T, Gennatas C, Marras F, Oppo TG, Balestrino M, Malzoni C, Malzoni M, Belli M, Geminiani ML, Crestani G, Monaco A, Vavala V, Piatto E, Barattini G, Fornara PG, Chetri MC, Santeufemia G, Artioli F, Carone D, Fanizza G, Trentadue R, Priolo D, Scollo P, Nigro SC, Petrina M, Mastrantonio P, Spanna GD, Zagni R, Belloni C, Colleoni R, Redaelli L, Cavagnini A, Di Costanzo G, Perroni D, Arienti S, Orfanotti G, Cantoni FM, Secli R, Bianchi A, Martinello R, Mollica G, Maizzi D, Picchiarelli ME, Fiorini G, Borsani M, Colombo E, Garsia S, Melgrati L, Paggi G, Brunenghi GM, Casini M, Isa L, Algeri R, Prozio G, Belfiore G, Angelini F, D'Aprile M, Moreschi M, Mauri ML, Natale N, Senzani FM, Pavanato G, Poggi G, Garuti G, Luerti M, Cruciani G, Pagano F, Baccolo M, Poddi ER, Bocciolone L, Sabelli MA, Maggi R, Restelli C, D'Antona A, Locatelli MC, Pessi A, Raina A, Chiari S, Gabriele A, Pittelli MR, Iacobelli P, Dogliotti L, Gorzegno G, Musso P, Vegna G, Coco G, Alletti DG, Picciotto F, Lucchese V, Epis A, di Palumbo VS, Drudi G, Ravaioli A, Zampella D, Morandi MG, Gorga G, Zucchelli C, Cariello S, Galletto L, Sussio M, Massacesi L, Massacesi M, Carli A, Tucci E, Tajani E, Corrado G, Bumma S, Durando A, Massobrio M, Sberveglieri M, Biasio M, Guercio E, Jura R, Danese S, Wierdis T, Farnelli C, Tarantino G, Grassi R, Repetti F, Rocchi B, Grampa M, Ercoli A, Griso C, Signori E, Zanini L, Presti M, Klimek M, Urbanski K, Biswas A, Viegas O, Kochli O, Dreher E, Fey M, Beck G, Ludin J, Bonnefoi H, Krauer F, Bauer J, Delmore G, Furrer C, Lorenz U, Thurlimann B, Bronz L, Sanna P, Wyss D, Goldhirsch A, Gyr T, Leidi L, Pastorelli G, Pagani O, Rey P, Hailer U, Benz J, Kaye SB, Reed NS, Symonds RP, Atkinson RJ, Axford AT, Rustin G, Seckl MJ, Green JA, Scott IV, Guthrie D, Harper PG, Calman F, Dobbs HJ, Weir P, Cassoni A, Lederman JA, Souhami RL, Bozzino J, Adab F, Redman CWE, Scoble JE, Paterson M, Daniel F, Cowley N, Williams CJ, Spooner D, Hong A, McIllmurray M, Hendy-Ibbs P, Hall V, Iveson TJ, Whitehouse JMA, Garry R, Lamont A, Robinson A, Trask CW, Clubb AW, Murrell D, Newman G, Wilkins M, Goldthorp WO, Roberts JK, Radstone DJ, Whipp MJ, Ledermann JA, Pater J, Buyse M, Omura G, Parmar, Mkb, Torri, V, Bonaventura, A, Bonazzi, C, Colombo, N, Delaloye, Jf, Marsoni, S, Mangioni, C, Sandercock, J, Sessa, C, Williams, C, Tinazzi, A, Flann, M, Geiser, K, Scorpiglione, N, Stewart, Jf, Chaves, J, Palmeiro, E, Curtain, A, Mccormack, T, Gennatas, C, Marras, F, Oppo, Tg, Balestrino, M, Malzoni, C, Malzoni, M, Belli, M, Geminiani, Ml, Crestani, G, Monaco, A, Vavala, V, Piatto, E, Barattini, G, Fornara, Pg, Chetri, Mc, Santeufemia, G, Artioli, F, Carone, D, Fanizza, G, Trentadue, R, Priolo, D, Scollo, P, Nigro, Sc, Petrina, M, Mastrantonio, P, Spanna, Gd, Zagni, R, Belloni, C, Colleoni, R, Redaelli, L, Cavagnini, A, Di Costanzo, G, Perroni, D, Arienti, S, Orfanotti, G, Cantoni, Fm, Secli, R, Bianchi, A, Martinello, R, Mollica, G, Maizzi, D, Picchiarelli, Me, Fiorini, G, Borsani, M, Colombo, E, Garsia, S, Melgrati, L, Paggi, G, Brunenghi, Gm, Casini, M, Isa, L, Algeri, R, Prozio, G, Belfiore, G, Angelini, F, D'Aprile, M, Moreschi, M, Mauri, Ml, Natale, N, Senzani, Fm, Pavanato, G, Poggi, G, Garuti, G, Luerti, M, Cruciani, G, Pagano, F, Baccolo, M, Poddi, Er, Bocciolone, L, Sabelli, Ma, Maggi, R, Restelli, C, D'Antona, A, Locatelli, Mc, Pessi, A, Raina, A, Chiari, S, Gabriele, A, Pittelli, Mr, Iacobelli, P, Dogliotti, L, Gorzegno, G, Musso, P, Vegna, G, Coco, G, Alletti, Dg, Picciotto, F, Lucchese, V, Epis, A, di Palumbo, V, Drudi, G, Ravaioli, A, Zampella, D, Morandi, Mg, Gorga, G, Zucchelli, C, Cariello, S, Galletto, L, Sussio, M, Massacesi, L, Massacesi, M, Carli, A, Tucci, E, Tajani, E, Corrado, G, Bumma, S, Durando, A, Massobrio, M, Sberveglieri, M, Biasio, M, Guercio, E, Jura, R, Danese, S, Wierdis, T, Farnelli, C, Tarantino, G, Grassi, R, Repetti, F, Rocchi, B, Grampa, M, Ercoli, A, Griso, C, Signori, E, Zanini, L, Presti, M, Klimek, M, Urbanski, K, Biswas, A, Viegas, O, Kochli, O, Dreher, E, Fey, M, Beck, G, Ludin, J, Bonnefoi, H, Krauer, F, Bauer, J, Delmore, G, Furrer, C, Lorenz, U, Thurlimann, B, Bronz, L, Sanna, P, Wyss, D, Goldhirsch, A, Gyr, T, Leidi, L, Pastorelli, G, Pagani, O, Rey, P, Hailer, U, Benz, J, Kaye, Sb, Reed, N, Symonds, Rp, Atkinson, Rj, Axford, At, Rustin, G, Seckl, Mj, Green, Ja, Scott, Iv, Guthrie, D, Harper, Pg, Calman, F, Dobbs, Hj, Weir, P, Cassoni, A, Lederman, Ja, Souhami, Rl, Bozzino, J, Adab, F, Redman, Cwe, Scoble, Je, Paterson, M, Daniel, F, Cowley, N, Williams, Cj, Spooner, D, Hong, A, Mcillmurray, M, Hendy-Ibbs, P, Hall, V, Iveson, Tj, Whitehouse, Jma, Garry, R, Lamont, A, Robinson, A, Trask, Cw, Clubb, Aw, Murrell, D, Newman, G, Wilkins, M, Goldthorp, Wo, Roberts, Jk, Radstone, Dj, Whipp, Mj, Ledermann, Ja, Pater, J, Buyse, M, and Omura, G

Published
1998

28. ICON2: randomised trial of single-agent carboplatin against three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) in women with ovarian cancer. ICON Collaborators. International Collaborative Ovarian Neoplasm Study

Author

Parmar, MKB, Torri, V, Bonaventura, A, Bonazzi, C, Delaloye, J, Marsoni, S, Mangioni, C, Sandercock, J, Sessa, C, Williams, C, Tinazzi, A, Flann, M, Geiser, K, Scorpiglione, N, Stewart, J, Chaves, J, Palmeiro, E, Curtain, A, McCormack, T, Gennatas, C, Marras, F, Oppo, T, Balestrino, M, Malzoni, C, Malzoni, M, Belli, M, Geminiani, M, Crestani, G, Monaco, A, Vavala, V, Piatto, E, Barattini, G, Fornara, P, Chetri, M, Santeufemia, G, Artioli, F, Carone, D, Fanizza, G, Trentadue, R, Priolo, D, Scollo, P, Nigro, S, Petrina, M, Mastrantonio, P, Spanna, G, Zagni, R, Belloni, C, Colleoni, R, Redaelli, L, Cavagnini, A, Di Costanzo, G, Perroni, D, Arienti, S, Orfanotti, G, Cantoni, F, Secli, R, Bianchi, A, Martinello, R, Mollica, G, Maizzi, D, Picchiarelli, M, Fiorini, G, Borsani, M, Colombo, E, Garsia, S, Melgrati, L, Paggi, G, Brunenghi, G, Casini, M, Isa, L, Algeri, R, Prozio, G, Belfiore, G, Angelini, F, D'Aprile, M, Moreschi, M, Mauri, M, Natale, N, Senzani, F, Pavanato, G, Poggi, G, Garuti, G, Luerti, M, Cruciani, G, Pagano, F, Baccolo, M, Poddi, E, Bocciolone, L, Sabelli, M, Maggi, R, Restelli, C, D'Antona, A, Locatelli, M, Pessi, A, Raina, A, Chiari, S, Gabriele, A, Pittelli, M, Iacobelli, P, Dogliotti, L, Gorzegno, G, Musso, P, Vegna, G, Coco, G, Alletti, D, Picciotto, F, Lucchese, V, Epis, A, di Palumbo, V, Drudi, G, Ravaioli, A, Zampella, D, Morandi, M, Gorga, G, Zucchelli, C, Cariello, S, Galletto, L, Sussio, M, Massacesi, L, Massacesi, M, Carli, A, Tucci, E, Tajani, E, Corrado, G, Bumma, S, Durando, A, Massobrio, M, Sberveglieri, M, Biasio, M, Guercio, E, Jura, R, Danese, S, Wierdis, T, Farnelli, C, Tarantino, G, Grassi, R, Repetti, F, Rocchi, B, Grampa, M, Ercoli, A, Griso, C, Signori, E, Zanini, L, Presti, M, Klimek, M, Urbanski, K, Biswas, A, Viegas, O, Kochli, O, Dreher, E, Fey, M, Beck, G, Ludin, J, Bonnefoi, H, Krauer, F, Bauer, J, Delmore, G, Furrer, C, Lorenz, U, Thurlimann, B, Bronz, L, Sanna, P, Wyss, D, Goldhirsch, A, Gyr, T, Leidi, L, Pastorelli, G, Pagani, O, Rey, P, Hailer, U, Benz, J, Kaye, S, Reed, N, Symonds, R, Atkinson, R, Axford, A, Rustin, G, Seckl, M, Green, J, Scott, I, Guthrie, D, Harper, P, Calman, F, Dobbs, H, Weir, P, Cassoni, A, Lederman, J, Souhami, R, Bozzino, J, Adab, F, Redman, C, Scoble, J, Paterson, M, Daniel, F, Cowley, N, Spooner, D, Hong, A, McIllmurray, M, Hendy Ibbs, P, Hall, V, Iveson, T, Whitehouse, J, Garry, R, Lamont, A, Robinson, A, Trask, C, Clubb, A, Murrell, D, Newman, G, Wilkins, M, Goldthorp, W, Roberts, J, Radstone, D, Whipp, M, Ledermann, J, Pater, J, Buyse, M, Omura, G., COLOMBO, NICOLETTA, Parmar, M, Torri, V, Bonaventura, A, Bonazzi, C, Colombo, N, Delaloye, J, Marsoni, S, Mangioni, C, Sandercock, J, Sessa, C, Williams, C, Tinazzi, A, Flann, M, Geiser, K, Scorpiglione, N, Stewart, J, Chaves, J, Palmeiro, E, Curtain, A, Mccormack, T, Gennatas, C, Marras, F, Oppo, T, Balestrino, M, Malzoni, C, Malzoni, M, Belli, M, Geminiani, M, Crestani, G, Monaco, A, Vavala, V, Piatto, E, Barattini, G, Fornara, P, Chetri, M, Santeufemia, G, Artioli, F, Carone, D, Fanizza, G, Trentadue, R, Priolo, D, Scollo, P, Nigro, S, Petrina, M, Mastrantonio, P, Spanna, G, Zagni, R, Belloni, C, Colleoni, R, Redaelli, L, Cavagnini, A, Di Costanzo, G, Perroni, D, Arienti, S, Orfanotti, G, Cantoni, F, Secli, R, Bianchi, A, Martinello, R, Mollica, G, Maizzi, D, Picchiarelli, M, Fiorini, G, Borsani, M, Colombo, E, Garsia, S, Melgrati, L, Paggi, G, Brunenghi, G, Casini, M, Isa, L, Algeri, R, Prozio, G, Belfiore, G, Angelini, F, D'Aprile, M, Moreschi, M, Mauri, M, Natale, N, Senzani, F, Pavanato, G, Poggi, G, Garuti, G, Luerti, M, Cruciani, G, Pagano, F, Baccolo, M, Poddi, E, Bocciolone, L, Sabelli, M, Maggi, R, Restelli, C, D'Antona, A, Locatelli, M, Pessi, A, Raina, A, Chiari, S, Gabriele, A, Pittelli, M, Iacobelli, P, Dogliotti, L, Gorzegno, G, Musso, P, Vegna, G, Coco, G, Alletti, D, Picciotto, F, Lucchese, V, Epis, A, di Palumbo, V, Drudi, G, Ravaioli, A, Zampella, D, Morandi, M, Gorga, G, Zucchelli, C, Cariello, S, Galletto, L, Sussio, M, Massacesi, L, Massacesi, M, Carli, A, Tucci, E, Tajani, E, Corrado, G, Bumma, S, Durando, A, Massobrio, M, Sberveglieri, M, Biasio, M, Guercio, E, Jura, R, Danese, S, Wierdis, T, Farnelli, C, Tarantino, G, Grassi, R, Repetti, F, Rocchi, B, Grampa, M, Ercoli, A, Griso, C, Signori, E, Zanini, L, Presti, M, Klimek, M, Urbanski, K, Biswas, A, Viegas, O, Kochli, O, Dreher, E, Fey, M, Beck, G, Ludin, J, Bonnefoi, H, Krauer, F, Bauer, J, Delmore, G, Furrer, C, Lorenz, U, Thurlimann, B, Bronz, L, Sanna, P, Wyss, D, Goldhirsch, A, Gyr, T, Leidi, L, Pastorelli, G, Pagani, O, Rey, P, Hailer, U, Benz, J, Kaye, S, Reed, N, Symonds, R, Atkinson, R, Axford, A, Rustin, G, Seckl, M, Green, J, Scott, I, Guthrie, D, Harper, P, Calman, F, Dobbs, H, Weir, P, Cassoni, A, Lederman, J, Souhami, R, Bozzino, J, Adab, F, Redman, C, Scoble, J, Paterson, M, Daniel, F, Cowley, N, Spooner, D, Hong, A, Mcillmurray, M, Hendy Ibbs, P, Hall, V, Iveson, T, Whitehouse, J, Garry, R, Lamont, A, Robinson, A, Trask, C, Clubb, A, Murrell, D, Newman, G, Wilkins, M, Goldthorp, W, Roberts, J, Radstone, D, Whipp, M, Ledermann, J, Pater, J, Buyse, M, and Omura, G

Subjects
Antineoplastic Combined Chemotherapy Protocol, Ovarian Neoplasm, Alopecia, Leukopenia, Middle Aged, Thrombocytopenia, Carboplatin, Antineoplastic Agent, Doxorubicin, Proportional Hazards Model, Female, Survival Analysi, Cisplatin, Cyclophosphamide, Aged, Human
Abstract

A series of meta-analyses of randomised controlled trials raised the question of whether the three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) was more or less effective than optimal-dose single-agent carboplatin for women with advanced ovarian cancer.

Published
1998

47. Electrochemotherapy in treatment of canine oral malignant melanoma and factors influencing treatment outcome

Author

Tellado Matías Nicolás, Maglietti Felipe Horacio, Michinski Sebastián Diego, Marshall Guillermo Ricardo, and Signori Emanuela

Subjects
cancer, dog, electroporation, electrochemotherapy, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract

Oral malignant melanoma is the most common, but aggressive oral cancer in dogs with poor prognosis. Electrochemotherapy (ECT) has therapeutic potential in such tumors as effective local treatment. Therefore, the aim of this prospective clinical study was to evaluate treatment effectiveness of ECT in as first line treatment for canine oral malignant melanoma, and search for factors influencing treatment outcome.

Published
2020
Full Text
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48. Antibodies elicited by naked DNA vaccination against hypervariable VH-CDR3 idiotypic determinants of B-lymphoproliferative disorders specifically react with patients? tumor cells

Author

Rinaldi M., Ria F., Parrella P., Signori E., Serra A., Ciafrè S.A., Vespignani I., Lazzari M., Farace M.G., Saglio G., and Fazio V.M.

Subjects
B-lymphoma, idiotypic determinants, DNA vaccination
Abstract

Several reports have suggested that the mechanism of protection induced by antiidiotypic vaccination against low-grade lymphoproliferative disorders is likely to be antibody mediated.Here we test the hypothesis that DNA vaccination with the short peptide encompassing the complementary-determining region 3 hypervariable region of immunoglobulin heavy chain (VH-CDR3) may elicit a specific antibody immune response able to recognize the native antigens in the form required for therapy. As a test system, we used the VH-CDR3 sequences derived from two patients with non-Hodgkin's B lymphomas (PA, AS) and one patient with hairy cell leukemia (BA) to immunize outbred Swiss mice. This experimental model could mimic a clinical setting in which different patients present distinct HLA haplotypes. Individual tumor-specific VH-CDR3 sequences were amplified by a two-step procedure and directly cloned into multigenic plasmid vectors (pRC100 and derived) with and without mouse interleukin 2 (mIL-2). Each tumor-specific sequence was characterized by sequencing. Female Swiss mice were vaccinated i.m. with plasmids expressing the tumor-specific VH-CDR3 sequence alone (pRC101-PA), mIL-2 plus the VH-CDR3 sequence (pRC111-PA), or a different unrelated antigen (NS3 of hepatitis C virus; pRC112), the sole mIL-2 (pRC110), and the empty plasmid (pRC100). Boost injections were performed at 3 and 16 weeks from the first vaccination, and sera were drawn before each vaccination and at 6, 9, and 19 weeks. Induction of anti-VH-CDR3s antibodies in the sera and their ability to recognize native antigens on patients' tumor cells were evaluated by FACS analysis. Up to 56% (n = 25) of mice vaccinated with pRC111-PA plasmid and 20% (n = 15) of mice vaccinated with pRC101-PA developed a specific immune response that was maintained throughout 19 weeks of observation in 40% of pRC111-PA-vaccinated mice. No response was detected in sera obtained from mice vaccinated with the other plasmids (n = 45). pRC111-PA injection s.c. was less effective (13%, n = 15) than i.m. injection (53%, n = 15). Indeed, we demonstrated that antibodies elicited by naked DNA vaccination against three different patient-derived VH-CDR3 peptides (pRC111-PA or BA or AS) readily reacted with binding epitopes on the idiotypic proteins expressed on the surface of tumor cells derived from each patient; 60, 40, and 40% of, respectively, PA-, BA-, and AS-vaccinated mice developed specific antibodies. No cross-reactivity was detected among the three different CDR3s against tumor cells derived from the other two patients. The outbred mouse strategy confirmed the significant matching potential of three different VH-CDR3 peptides to be efficaciously presented through different MHCs. We conclude that individual VH-CDR3 DNA vaccination can result in a potentially effective specific immune response against non-Hodgkin's B lymphoma cells by a rapid and low-cost therapeutic approach.

Published
2001

49. Antibodies elicited by naked DNA vaccination against the complementary-determining region 3 hypervariable region of immunoglobulin heavy chain idiotipic determinants of B-lymphoproliferative disorders specifically react with patient's tumor cells

Author

Rinaldi, M., Ria, F., Parrella, P., Signori, E., Serra, A., Ciafrè, S. A., Vespignani, I., Lazzari, M., Farace, M. G., Saglio, G., and Vito Michele Fazio

Subjects
Lymphoma, B-Cell, Lymphoma, Antibodies, Neoplasm, Hairy Cell, Genetic Vectors, Molecular Sequence Data, Immunoglobulin Variable Region, Immunoglobulin Idiotypes, Epitopes, Base Sequence, Cell Line, Transformed, Animals, Leukemia, Hairy Cell, Humans, Complementarity Determining Regions, Flow Cytometry, Interleukin-2, Antibodies, Anti-Idiotypic, Mice, Cancer Vaccines, Vaccines, DNA, Amino Acid Sequence, Immunoglobulin Heavy Chains, Leukemia, B-Cell, Antibodies, Cell Line, Settore MED/04 - PATOLOGIA GENERALE, Vaccines, Leukemia, Settore BIO/13, B-Cell, DNA, Anti-Idiotypic, Transformed, Neoplasm
Abstract

Several reports have suggested that the mechanism of protection induced by antiidiotypic vaccination against low-grade lymphoproliferative disorders is likely to be antibody mediated. Here we test the hypothesis that DNA vaccination with the short peptide encompassing the complementary-determining region 3 hypervariable region of immunoglobulin heavy chain (VH-CDR3) may elicit a specific antibody immune response able to recognize the native antigens in the form required for therapy. As a test system, we used the VH-CDR3 sequences derived from two patients with non-Hodgkin's B lymphomas (PA, AS) and one patient with hairy cell leukemia (BA) to immunize outbred Swiss mice. This experimental model could mimic a clinical setting in which different patients present distinct HLA haplotypes. Individual tumor-specific VH-CDR3 sequences were amplified by a two-step procedure and directly cloned into multigenic plasmid vectors (pRC100 and derived) with and without mouse interleukin 2 (mIL-2). Each tumor-specific sequence was characterized by sequencing. Female Swiss mice were vaccinated i.m. with plasmids expressing the tumor-specific VH-CDR3 sequence alone (pRC101-PA), mIL-2 plus the VH-CDR3 sequence (pRC111-PA), or a different unrelated antigen (NS3 of hepatitis C virus; pRC112), the sole mIL-2 (pRC110), and the empty plasmid (pRC100). Boost injections were performed at 3 and 16 weeks from the first vaccination, and sera were drawn before each vaccination and at 6, 9, and 19 weeks. Induction of anti-VH-CDR3s antibodies in the sera and their ability to recognize native antigens on patients' tumor cells were evaluated by FACS analysis. Up to 56% (n = 25) of mice vaccinated with pRC111-PA plasmid and 20% (n = 15) of mice vaccinated with pRC101-PA developed a specific immune response that was maintained throughout 19 weeks of observation in 40% of pRC111-PA-vaccinated mice. No response was detected in sera obtained from mice vaccinated with the other plasmids (n = 45). pRC111-PA injection s.c. was less effective (13%, n = 15) than i.m. injection (53%, n = 15). Indeed, we demonstrated that antibodies elicited by naked DNA vaccination against three different patient-derived VH-CDR3 peptides (pRC111-PA or BA or AS) readily reacted with binding epitopes on the idiotypic proteins expressed on the surface of tumor cells derived from each patient; 60, 40, and 40% of, respectively, PA-, BA-, and AS-vaccinated mice developed specific antibodies. No cross-reactivity was detected among the three different CDR3s against tumor cells derived from the other two patients. The outbred mouse strategy confirmed the significant matching potential of three different VH-CDR3 peptides to be efficaciously presented through different MHCs. We conclude that individual VH-CDR3 DNA vaccination can result in a potentially effective specific immune response against non-Hodgkin's B lymphoma cells by a rapid and low-cost therapeutic approach.

Published
2001

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