Animal care

The Animal Facility of CAST guarantees the health and welfare of small laboratory animals (mice, rats and rabbits), housed for scientific purposes. The facility is a conventional structure of 900 square meters, authorized by the Ministry of Health according to the Italian law on the animal experimentation (D.L. 116/92), organized in several functional areas: animal housing rooms, procedure rooms, cage sanitation areas (dirty and clean sides), storage areas (feed, bedding and supplies). Rooms with individually ventilated cages for immune-compromised mice are also present.

It offers CAST researchers the space necessary to house and perform studies on chosen animal models, under the strict supervision of the Animal Welfare Organism (OPBA, Organismo Preposto al Benessere Animale) of the G. d’Annunzio University and following approval of the project by the Italian National Institute of Health (ISS, Istituto Superiore di Sanità) and the Italian Ministry of Health.  Projects are approved only after rigorous evaluation which certifies that the potential benefits to human health outweighs the discomfort or pain caused to the animals.

With the support of the facility staff members, CAST scientists can manipulate animals only in accordance with the national regulations on the protection of animals used for scientific purposes (Italian decree n. 26 dated 04/03/2014 acknowledging the European Directive 2010/63/EU). All experiments must adhere to the principle of the “3Rs” (Replacement, Reduction and Refinement). This principle is based on the rule that the smallest number of animals can be used only if all non-animal alternatives have failed, using procedures that cause less pain, distress or suffering.

The OPBA constantly monitors the development and outcome of all the projects carried out in the facility. OPBA is composed by Prof. Renato Mariani Costantini, member and scientific coordinator, Dr. Luca Fruci, veterinarian, Prof. Vincenzo De Laurenzi, Dr. Annalisa Bruno, Dr. Sara Pagotto, Dr. Alessia Lamolinara, scientific members, and Dr Cosmo Rossi, responsible of animal care and welfare.  (d.r._886_del_10.6.2019_organico_opba.pdf).

The Animal Facility provides researchers with a set of technologically advanced skills and services for the study of biological processes in whole organisms, a necessary step both in basic research, involved in understanding physiological and pathological mechanisms, and in pre-clinical research, involved in developing diagnostic and therapeutic strategies.

 

Services

  • Education and courses.

Animal Facility staff members provide animal handling and technique training classes for those who need to conduct research with laboratory animals.

  • Consultation and technical assistance. 

Facility staff provides assistance with experiment design and data analysis.  They also provide technical support for all aspects of in vivo studies, including surgeries, tumor cell implantation, tumor transplantation, drug formulation and administration (e.g., intravenous, intraperitoneal, oral, intratumor, subcutaneous), consultation and training in necropsy techniques, tissue processing, histological and immunohistochemical staining and report.

 

  • Genotyping of Transgenic Rodents by PCR.

Our staff can help to define and carry out PCR protocols to genotype transgenic rodent strains.

 

  • Cell lines and tumor xenograft.

We have a large repository of commonly used murine and human cell lines. We establish xenograft models from cell lines provided by the investigator or supplied through our repository. Cells can be grafted by subcutaneous, intraperitoneal, intravenous or orthotopic injection, with or without Matrigel.

  • Patient-derived xenografts (PDX).

We establish PDX models directly from patient tumor samples harvested at biopsy or surgery. Tissues are directly implanted into immunodeficient mice, including NOD SCID and NSG mice. Mice are monitored for evidence of successful tumor engraftment.  All tissues are engrafted with patient consent, and no patient identifiers are in any way associated with these tumor tissues lines.

  • Spontaneous and experimental metastatic models.

The spontaneous metastasis models assess the ability of cells to disseminate from a local tumor and are commonly initiated by subcutaneous or orthotopic transplants. Models of experimental metastasis evaluate the ability of the tumor cells to arrest, extravasate, and grow in various organs following intravenous injection.

 

 

 

  • Tumor and animal monitoring.

Animal body weight is measured twice weekly and weight loss, fur quality, and animal behavior are used as indicators of potential toxicity. Tumor dimensions are typically measured twice weekly and used to calculate tumor volumes.

 

 

 

  • Efficacy studies.

We evaluate in vivo efficacy of agents either alone or in combination with standard chemotherapy regimens against murine tumors, human tumor xenografts, and in transgenic mouse models of human cancer. Tumor size is monitored by caliper measurement.

  • Compound formulation/delivery.

Compounds are formulated for in vivo delivery using a variety of commonly used vehicles and are administered by a number of routes, including oral gavage, intravenous, intraperitoneal, subcutaneous, intratumor, and by food and/or drinking water.

 

  • Tissue and fluid collection.

Body fluids and tissues, such as blood, urine, feces, organs, and cells are collected as needed per experimental design.  At the close of a study, animals are euthanized and tissues and tumors are collected and processed according to the experimental design.

 

 

 

 

Example of some of the offered services: in A the experimental design, in B the percent change of body weight during treatment, in C histologic analysis of kidney, liver and lung harvested at the end of the experiment, with metastatic lesions counts and representative images.

From: EV20-mediated delivery of cytotoxic auristatin MMAF exhibits potent therapeutic efficacy in cutaneous melanoma. J Control Release. 2018 May 10;277:48-56. doi: 10.1016/j.jconrel.2018.03.016. Epub 2018 Mar 14. Capone E, Lamolinara A, D'Agostino D, Rossi C, De Laurenzi V, Iezzi M, Iacobelli S, Sala G.

Access

To gain authorized access to an animal facility, please contact the animal facility, see email address here: cosmo.rossi@unich.it

Gain access authorization to animal facilities

To gain authorized access to CAST animal facility, please contact the animal facility. Before you may gain authorized access your competence in laboratory animal science must first be assessed.

You need to show documentation that certifies your competence in Laboratory Animal Science. Scan and attach relevant documentation to the responsible of animal care and welfare Dr. Cosmo Rossi. It will be decided whether you may get access to the animal facility or if you need to make a complement.

If you do not have any competence in Laboratory Animal Science you will need to complete both the theoretical and the practical parts of the “Facility Introduction and Rodent Overview” course before access can be granted.

Facility Introduction and Rodent Overview – Required for CAST Facility Access

 

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This class provides an introduction to facilities, as well as an overview of the laboratory rodent in both a lecture and hands-on format. Basic handling, restraint, and other techniques will be demonstrated. Class participants have the opportunity to practice their newly-acquired skills under the supervision of experienced trainers.

Topics and techniques of the class include:

  • The Italian regulation of the use of animals in research
  • Ethics related to relationship between humans and animals, intrinsic value of life and arguments for and against use of animals in research
  • Basic relevant biology, anatomy, physiology, reproductions and genetics for the species in question (mice and rats)
  • Animal welfare, care and enrichment
  • Species specific handling
  • Animal health assessment
  • Recognition of species specific signs of fear, pain or other harm
  • Anesthesia, analgesia and Euthanasia
  • Humane end-points
  • 3R principles
  • Demonstration of animal handling, restraint, sexing
  • Breeding/setting up new cages
  • Sub-cutaneous, Intra-venous and Intra-peritoneal injections
  • Sub-mandibular blood collection
  • Necropsy

 

Key references

The Three Rs (3Rs) principles

 

  1. Bibbo' S, Lamolinara A, Capone E, Purgato S, Tsakaneli A, Panella V, Sallese M, Rossi C, Ciufici P, Nieddu V, De Laurenzi V, Iezzi M, Perini G, Sala G, Sala A. Repurposing a psychoactive drug for children with cancer: p27Kip1-dependent inhibition of metastatic neuroblastomas by Prozac. Oncogenesis. 2020 Jan 2;9(1):3. doi: 10.1038/s41389-019-0186-3. PMID: 31900399
  2. Mottini C, Tomihara H, Carrella D, Lamolinara A, Iezzi M, Huang JK, Amoreo CA, Buglioni S, Manni I, Robinson FS, Minelli R, Kang Y, Fleming JB, Kim MP, Bristow  CA, Trisciuoglio D, Iuliano A, Del Bufalo D, di Bernardo D, Melisi D, Draetta GF, Ciliberto G, Carugo A, Cardone L. Predictive signatures inform the effective repurposing of Decitabine to treat K-RAS-dependent Pancreatic Ductal Adenocarcinoma. Cancer Res. 2019 Sep 5. pii: canres.0187.2019. doi: 10.1158/0008-5472.CAN-19-0187. [Epub ahead of print] PubMed PMID: 31492820.
  3. Koschorke A, Faraci S, Giani D, Chiodoni C, Iorio E, Canese R, Colombo MP, Lamolinara A, Iezzi M, Ladomery M, Vernieri C, de Braud F, Di Nicola M, Tagliabue E, Castagnoli L, Pupa SM. Phenethyl isothiocyanate hampers growth and progression of HER2-positive breast and ovarian carcinoma by targeting their stem cell compartment. Cell Oncol (Dordr). 2019 Aug 2. doi: 10.1007/s13402-019-00464-w. [Epub ahead of print] PubMed PMID: 31376137.
  4. Grasso S, Cangelosi D, Chapelle J, Alzona M, Centonze G, Lamolinara A, Salemme V, Angelini C, Morellato A, Saglietto A, Bianchi FT, Cabodi S, Salaroglio IC, Fusella F, Ognibene M, Iezzi M, Pezzolo A, Poli V, Di Cunto F, Eva A, Riganti C, Varesio L, Turco E, Defilippi P. The SRCIN1/p140Cap adaptor protein negatively regulates the aggressiveness of neuroblastoma. Cell Death Differ. 2019 Jul 8. doi: 10.1038/s41418-019-0386-6. [Epub ahead of print] Erratum in: Cell Death Differ. 2019 Sep 5;:. PubMed PMID: 31285546.
  5. Fiore A, Ugel S, De Sanctis F, Sandri S, Fracasso G, Trovato R, Sartoris S, Solito S, Mandruzzato S, Vascotto F, Hippen KL, Mondanelli G, Grohmann U, Piro G, Carbone C, Melisi D, Lawlor RT, Scarpa A, Lamolinara A, Iezzi M, Fassan M, Bicciato S, Blazar BR, Sahin U, Murray PJ, Bronte V. Induction of immunosuppressive functions and NF-κB by FLIP in monocytes. Nat Commun. 2018 Dec 5;9(1):5193. doi: 10.1038/s41467-018-07654-4. PubMed PMID: 30518925; PubMed Central PMCID: PMC6281604.
  6. Bartolacci C, Andreani C, Curcio C, Occhipinti S, Massaccesi L, Giovarelli M, Galeazzi R, Iezzi M, Tilio M, Gambini V, Wang J, Marchini C, Amici A. Phage-Based Anti-HER2 Vaccination Can Circumvent Immune Tolerance against Breast Cancer. Cancer Immunol Res. 2018 Dec;6(12):1486-1498. doi: 10.1158/2326-6066.CIR-18-0179.Epub 2018 Oct 16. PubMed PMID: 30327365.
  7. De Cola A, Lamolinara A, Lanuti P, Rossi C, Iezzi M, Marchisio M, Todaro M, De Laurenzi V. MiR-205-5p inhibition by locked nucleic acids impairs metastatic potential of breast cancer cells. Cell Death Dis. 2018 Jul 26;9(8):821. doi: 10.1038/s41419-018-0854-9. PubMed PMID: 30050081; PubMed Central PMCID: PMC6062508.
  8. Ferrauto G, Di Gregorio E, Lanzardo S, Ciolli L, Iezzi M, Aime S. Generation of multiparametric MRI maps by using Gd-labelled- RBCs reveals phenotypes and stages of murine prostate cancer. Sci Rep. 2018 Jul 12;8(1):10567. doi: 10.1038/s41598-018-28926-5. PubMed PMID: 30002426; PubMed Central PMCID: PMC6043588.
  9. Gambini V, Tilio M, Maina EW, Andreani C, Bartolacci C, Wang J, Iezzi M, Ferraro S, Ramadori AT, Simon OC, Pucciarelli S, Wu G, Dou QP, Marchini C, Galassi R, Amici A. In vitro and in vivo studies of gold(I) azolate/phosphane complexes for the treatment of basal like breast cancer. Eur J Med Chem. 2018 Jun 2;155:418-427. doi: 10.1016/j.ejmech.2018.06.002. [Epub ahead of print] PubMed PMID: 29906688.
  10. Castiello L, Sestili P, Schiavoni G, Dattilo R, Monque DM, Ciaffoni F, Iezzi M, Lamolinara A, Sistigu A, Moschella F, Pacca AM, Macchia D, Ferrantini M, Zeuner A, Biffoni M, Proietti E, Belardelli F, Arico E. Disruption of IFN-I signaling promotes HER2/neu tumor progression and breast cancer stem cells. Cancer Immunol Res. 2018 Apr 5.
  11. Capone E, Lamolinara A, D'Agostino D, Rossi C, De Laurenzi V, Iezzi M, Iacobelli S, Sala G. EV20-mediated delivery of cytotoxic auristatin MMAF exhibits potent therapeutic efficacy in cutaneous melanoma. J Control Release. 2018 Mar 14.
  12. Capone E, Giansanti F, Ponziani S, Lamolinara A, Iezzi M, Cimini A, Angelucci F, Sorda R, Laurenzi V, Natali PG, Ippoliti R, Iacobelli S, Sala G. EV20-Sap, a novel anti-HER-3 antibody-drug conjugate, displays promising antitumor activity in melanoma. Oncotarget. 2017 Sep 8;8(56):95412-95424.
  13. Giuliani C, Iezzi M, Ciolli L, Hysi A, Bucci I, Di Santo S, Rossi C, Zucchelli M, Napolitano G. Resveratrol has anti-thyroid effects both in vitro and in vivo.  Food Chem Toxicol. 2017 Sep;107(Pt A):237-247. doi:  0.1016/j.fct.2017.06.044. Epub 2017 Jun 28. PubMed PMID: 28668442.
  14. Sara Sandri, Francesco De Sanctis, Alessia Lamolinara, Federico Boschi, Ornella Poffe, Rosalinda Trovato, Alessandra Fiore, Sara Sartori, Andrea Sbarbati, Attilio Bondanza, Simone Cesaro, Mauro Krampera, Maria T. Scupoli, Michael I. Nishimura, Manuela Iezzi, Silvia Sartoris, Vincenzo Bronte and Stefano Ugel. Effective control of acute myeloid leukaemia and acute lymphoblastic leukaemia progression by telomerase specific adoptive T-cell therapy. Oncotarget 2017
  15. Palladini A, Nicoletti G, Lamolinara A, Dall'Ora M, Balboni T, Ianzano ML, Laranga R, Landuzzi L, Giusti V, Ceccarelli C, Santini D, Taffurelli M, Di Oto E, Asioli S, Amici A, Pupa SM, De Giovanni C, Tagliabue E, Iezzi M, Nanni P, Lollini PL. HER2 isoforms co-expression differently tunes mammary tumor phenotypes affecting onset, vasculature and therapeutic response. Oncotarget. 2017 Apr 13. doi: 10.18632/oncotarget.17088. [Epub ahead of print] PubMed PMID: 28467963.
  16. Codagnone M, Cianci E, Lamolinara A, Mari VC, Nespoli A, Isopi E, Mattoscio D, Arita M, Bragonzi A, Iezzi M, Romano M, Recchiuti A. Resolvin D1 enhances the resolution of lung inflammation caused by long-term Pseudomonas aeruginosa infection. Mucosal Immunol. 2017 Apr 19. doi: 10.1038/mi.2017.36. [Epub ahead of  print] PubMed PMID: 28422188.
  17. Grasso S, Chapelle J, Salemme V, Aramu S, Russo I, Vitale N, Verdun di Cantogno L, Dallaglio K, Castellano I, Amici A, Centonze G, Sharma N, Lunardi S, Cabodi S, Cavallo F, Lamolinara A, Stramucci L, Moiso E, Provero P, Albini A, Sapino A, Staaf J, Di Fiore PP, Bertalot G, Pece S, Tosoni D, Confalonieri S, Iezzi M, Di Stefano P, Turco E, Defilippi P. The scaffold protein p140Cap limits ERBB2-mediated breast cancer progression interfering with Rac GTPase-controlled circuitries. Nat Commun. 2017 Mar 16;8:14797. doi: 10.1038/ncomms14797. PubMed PMID: 28300085; PubMed Central PMCID: PMC5357316.
  18. Andreani C, Bartolacci C, Wijnant K, Crinelli R, Bianchi M, Magnani M, Hysi A, Iezzi M, Amici A, Marchini C. Resveratrol fuels HER2 and ERα-positive breast cancer behaving as proteasome inhibitor. Aging (Albany NY). 2017 Feb 26;9(2):508-523. doi: 10.18632/aging.101175. PubMed PMID: 28238967; PubMed Central PMCID: PMC5361678.
  19. Corda G, Sala G, Lattanzio R, Iezzi M, Sallese M, Fragassi G, Lamolinara A, Mirza H, Barcaroli D, Ermler S, Silva E, Yasaei H, Newbold RF, Vagnarelli P, Mottolese M, Natali PG, Perracchio L, Quist J, Grigoriadis A, Marra P, Tutt AN, Piantelli M, Iacobelli S, De Laurenzi V, Sala A. Functional and prognostic significance of the genomic amplification of frizzled 6 (FZD6) in breast cancer.  J Pathol. 2017 Feb;241(3):350-361. doi: 10.1002/path.4841. Epub 2016 Dec 29. PubMed PMID: 27859262; PubMed Central PMCID: PMC5248601.
  20. Castagnoli L, Ghedini GC, Koschorke A, Triulzi T, Dugo M, Gasparini P, Casalini P, Palladini A, Iezzi M, Lamolinara A, Lollini PL, Nanni P, Chiodoni C, Tagliabue E, Pupa SM. Pathobiological implications of the d16HER2 splice variant for stemness and aggressiveness of HER2-positive breast cancer. Oncogene. 2017 Mar 23;36(12):1721-1732. doi: 10.1038/onc.2016.338. Epub 2016 Sep 19. PubMed PMID: 27641338.
  21. Bandini S, Macagno M, Hysi A, Lanzardo S, Conti L, Bello A, Riccardo F, Ruiu R, Merighi IF, Forni G, Iezzi M, Quaglino E, Cavallo F. The non-inflammatory role of C1q during Her2/neu-driven mammary carcinogenesis. Oncoimmunology. 2016 Nov 8;5(12):e1253653. doi: 10.1080/2162402X.2016.1253653. eCollection 2016. PubMed PMID: 28123895; PubMed Central PMCID: PMC5214935.
  22. Carrella D, Manni I, Tumaini B, Dattilo R, Papaccio F, Mutarelli M, Sirci F, Amoreo CA, Mottolese M, Iezzi M, Ciolli L, Aria V, Bosotti R, Isacchi A, Loreni F, Bardelli A, Avvedimento VE, di Bernardo D, Cardone L. Computational drugs repositioning identifies inhibitors of oncogenic PI3K/AKT/P70S6K-dependent pathways among FDA-approved compounds. Oncotarget. 2016 Aug 16. doi: 10.18632/oncotarget.11318. PubMed PMID: 27542212.
  23. Tilio M, Gambini V, Wang J, Garulli C, Kalogris C, Andreani C, Bartolacci C, Elexpuru Zabaleta M, Pietrella L, Hysi A, Iezzi M, Belletti B, Orlando F, Provinciali M, Galeazzi R, Marchini C, Amici A. Irreversible inhibition of Δ16HER2 is necessary to suppress Δ16HER2-positive breast carcinomas resistant to Lapatinib. Cancer Lett. 2016 Oct 10;381(1):76-84. doi: 10.1016/j.canlet.2016.07.028. Epub 2016 Jul 27. PubMed PMID: 27475932.
  24. Sandri S, Bobisse S, Moxley K, Lamolinara A, De Sanctis F, Boschi F, Sbarbati A, Fracasso G, Ferrarini G, Hendriks RW, Cavallini C, Scupoli MT, Sartoris S, Iezzi M, Nishimura MI, Bronte V, Ugel S. Feasibility of Telomerase-Specific Adoptive T-cell Therapy for B-cell Chronic Lymphocytic Leukemia and Solid Malignancies. Cancer Res. 2016 May 1;76(9):2540-51. doi: 10.1158/0008-5472.CAN-15-2318. PubMed PMID: 27197263.
  25. Montani M, Pazmay GV, Hysi A, Lupidi G, Pettinari R, Gambini V, Tilio M, Marchetti F, Pettinari C, Ferraro S, Iezzi M, Marchini C, Amici A. The water soluble ruthenium(II) organometallic compound [Ru(p-cymene)(bis(3,5 dimethylpyrazol-1-yl)methane)Cl]Cl suppresses triple negative breast cancer growth by inhibiting tumor infiltration of regulatory T cells. Pharmacol Res. 2016 Mar 30;107:282-290. doi: 10.1016/j.phrs.2016.03.032. PubMed PMID: 27038531.
  26. Chikh A, Ferro R, Abbott JJ, Piñeiro R, Buus R, Iezzi M, Ricci F, Bergamaschi  D, Ostano P, Chiorino G, Lattanzio R, Broggini M, Piantelli M, Maffucci T, Falasca M. Class II phosphoinositide 3-kinase C2β regulates a novel signaling pathway involved in breast cancer progression. Oncotarget. 2016 Feb 26. doi: 10.18632/oncotarget.7761. [Epub ahead of print] PubMed PMID: 26934321.
  27. Lamolinara A, Stramucci L, Hysi A, Iezzi M, Marchini C, Mariotti M, Amici A, Curcio C. Intradermal DNA Electroporation Induces Cellular and Humoral Immune Response and Confers Protection against HER2/neu Tumor. J Immunol Res. 2015; 2015:159145. doi: 10.1155/2015/159145. Epub 2015 Jul 13. PubMed PMID: 26247038.
  28. Barutello G, Curcio C, Spadaro M, Arigoni M, Trovato R, Bolli E, Zheng Y, Ria F, Quaglino E, Iezzi M, Riccardo F, Holmgren L, Forni G, Cavallo F. Antitumor immunization of mothers delays tumor development in cancer-prone offspring. Oncoimmunology. 2015 Feb 3;4(5):e1005500. eCollection 2015 May. PubMed PMID: 26155401.
  29. Croci S, Nanni P, Palladini A, Nicoletti G, Grosso V, Benegiamo G, Landuzzi L, Lamolinara A, Ianzano ML, Ranieri D, Dall'Ora M, Iezzi M, De Giovanni C, Lollini PL. Interleukin-15 is required for immunosurveillance and immunoprevention of HER2/neu-driven mammary carcinogenesis. Breast Cancer Res. 2015 May 22;17:70. doi: 10.1186/s13058-015-0588-x. PubMed PMID: 25997501; PubMed Central PMCID: PMC4462012.
  30. Mosley M, Knight J, Neesse A, Michl P, Iezzi M, Kersemans V, Cornelissen B. Claudin-4 SPECT Imaging Allows Detection of Aplastic Lesions in a Mouse Model of Breast Cancer. J Nucl Med. 2015 May;56(5):745-51. doi: 10.2967/jnumed.114.152496. Epub 2015 Apr 3. PubMed PMID: 25840973.
  31. Manservisi F, Gopalakrishnan K, Tibaldi E, Hysi A, Iezzi M, Lambertini L, Teitelbaum S, Chen J, Belpoggi F. Effect of maternal exposure to endocrine disrupting chemicals on reproduction and mammary gland development in female sprague-dawley rats. Reprod Toxicol. 2014 Dec 29. pii: S0890-6238(14)00324-4. doi: 10.1016/j.reprotox.2014.12.013. [Epub ahead of print] PubMed PMID: 25554385.
  32. Cornelissen B, Able S, Kartsonaki C, Kersemans V, Allen PD, Cavallo F, Cazier  JB, Iezzi M, Knight J, Muschel R, Smart S, Vallis KA. Imaging DNA damage allows detection of preneoplasia in the BALB-neuT model of breast cancer. J Nucl Med. 2014 Dec;55(12):2026-31. doi: 10.2967/jnumed.114.142083. Epub 2014 Nov 13. PubMed PMID: 25453049.
  33. Castagnoli L, Iezzi M, Ghedini GC, Ciravolo V, Marzano G, Lamolinara A, Zappasodi R, Gasparini P, Campiglio M, Amici A, Chiodoni C, Palladini A, Lollini  PL, Triulzi T, Menard S, Nanni P, Tagliabue E, Pupa SM. Activated d16HER2 homodimers and SRC kinase mediate optimal efficacy for trastuzumab. Cancer Res. 2014 Nov 1;74(21):6248-59. doi: 10.1158/0008-5472.CAN-14-0983. Epub 2014 Aug 27.  PubMed PMID: 25164009.
  34. Riccardo F, Arigoni M, Buson G, Zago E, Iezzi M, Longo D, Carrara M, Fiore A, Nuzzo S, Bicciato S, Nanni P, Landuzzi L, Cavallo F, Calogero R, Quaglino E. Characterization of a genetic mouse model of lung cancer: a promise to identify Non-Small Cell Lung Cancer therapeutic targets and biomarkers. BMC Genomics. 2014;15 Suppl 3:S1. doi: 10.1186/1471-2164-15-S3-S1. Epub 2014 May 6. PubMed PMID: 25077564; PubMed Central PMCID: PMC4083401.
  35. Kalogris C, Garulli C, Pietrella L, Gambini V, Pucciarelli S, Lucci C, Tilio M, Zabaleta ME, Bartolacci C, Andreani C, Giangrossi M, Iezzi M, Belletti B, Marchini C, Amici A. Sanguinarine suppresses basal-like breast cancer growth through dihydrofolate reductase inhibition. Biochem Pharmacol. 2014 May 27.
  36. Macagno M, Bandini S, Stramucci L, Quaglino E, Conti L, Balmas E, Smyth MJ, Lollini PL, Musiani P, Forni G, Iezzi M, Cavallo F. Multiple Roles of Perforin in Hampering ERBB-2 (Her-2/neu) Carcinogenesis in Transgenic Male Mice. J Immunol. 2014 Jun 1;192(11):5434-41. Epub 2014 Apr 30.
  37. Petrarca C, Clemente E, Toto V, Iezzi M, Rossi C, Zanotta S, Mistrello G, Zanoni I, Granucci F, Arioli S, Mora D, Guglielmetti S, Paganelli R, Di Gioacchino M. rBet v 1 immunotherapy of sensitized mice with Streptococcus thermophilus as vehicle and adjuvant. Hum Vaccin Immunother. 2014 Mar 6;10(5).
  38. De Giovanni C, Nicoletti G, Quaglino E, Landuzzi L, Palladini A, Ianzano ML, Dall'ora M, Grosso V, Ranieri D, Laranga R, Croci S, Amici A, Penichet ML, Iezzi M, Cavallo F, Nanni P, Lollini PL. Vaccines against human HER2 prevent mammary carcinoma in mice transgenic for human HER2. Breast Cancer Res. 2014 Jan 23;16(1):R10.
  39. Silvio Bandini, Claudia Curcio, Marco Macagno, Elena Quaglino, Maddalena Arigoni, Stefania Lanzardo, Albana Hysi, Giuseppina Barutello, Lorena Consolino, Dario Longo, Piero Musiani, Guido Forni, Manuela Iezzi, and Federica Cavallo. Early onset and enhanced growth of autochthonous mammary carcinomas in C3 deficient Her2/neu transgenic mice. Oncoimmunology. 2013 Sep 1;2(9):e26137. Epub 2013 Sep 12
  40. Steven A, Leisz S, Massa C, Iezzi M, Lattanzio R, Lamolinara A, Bukur J, Muller A, Hiebl B, Holzhausen HJ, Seliger B HER-2/neu mediates oncogenic transformation via altered CREB expression and function. Mol Cancer Res. 2013 Sep 11.
  41. Conti L, Lanzardo S, Iezzi M, Montone M, Bolli E, Brioschi C, Maiocchi A, Forni G, Cavallo F.  Optical imaging detection of microscopic mammary cancer in ErbB-2 transgenic mice through the DA364 probe binding αv β3 integrins. Contrast Media Mol Imaging. 2013 Jul-Aug;8(4):350-60.
  42. Nanni P., Gatta V, Menotti L., De Giovanni C.,  Ianzano M., Palladini A., Grosso V., Dall'Ora M., Croci S., Nicoletti G., Landuzzi L., Iezzi M., Campadelli-Fiume G., Lollini P.L.Preclinical Therapy of Disseminated HER-2+ Ovarian and Breast Carcinomas with a HER-2-Retargeted Oncolytic Herpesvirus. PLoS Pathog. 2013 Jan;9(1):e1003155.
  43. Bisaro B, Montani M, Konstantinidou G, Marchini C, Pietrella L, Iezzi M, Galiè M, Orso F, Camporeale A, Colombo SM, Di Stefano P, Tornillo G, Camacho-Leal MP, Turco E, Taverna D, Cabodi S, Amici A, Defilippi P. p130Cas/Cyclooxygenase-2 axis in the control of mesenchymal plasticity of breast cancer cells. Breast Cancer Res. 2012 Oct 26;14(5):R137.
  44. De Giovanni C, Nicoletti G, Landuzzi L, Romani F, Croci S, Palladini A, Murgo A,  Antognoli A, Ianzano ML, StivaniV, Grosso V, Iezzi M, Stramucci L, Barbieri E, Lemoli RM, Nanni P, and Lollini PL. Human responses against HER-2-positive cancer cells in human immune system-engrafted mice. British Journal of Cancer 2012 Oct 9;107(8):1302-9.
  45. Nanni P, Nicoletti G, Palladini A, Croci S, Murgo A, Ianzano ML, Grosso V, Stivani V, Antognoli A, Lamolinara A, Landuzzi L, di Tomaso E, Iezzi M, De Giovanni C, Lollini PL. Multiorgan Metastasis of Human HER-2(+) Breast Cancer in  Rag2(-/-);Il2rg(-/-) Mice and Treatment with PI3K Inhibitor. PLoS One. 2012;7(6):e39626. Epub 2012 Jun 21.
  46. Arigoni M, Barutello G, Lanzardo S, Longo D, Aime S, Curcio C, Iezzi M, Zheng Y, Barkefors I, Holmgren L, Cavallo F. A vaccine targeting angiomotin induces an antibody response which alters tumor vessel permeability and hampers the growth of established tumors. Angiogenesis. 2012 Jun;15(2):305-16.
  47. Iezzi M, Quaglino E, Cappello P, Toto V, Sabatini F, Curcio C, Garotta G, Musiani P, Cavallo F. HCG hastens both the development of mammary carcinoma and the metastatization of HCG/LH and ERBB-2 receptor-positive cells in mice. Int J Immunopathol Pharmacol. 2011 Jul-Sep;24(3):621-30.
  48. Berta GN, Sprio AE, Iezzi M, Spadaro M, Cappia S, Salamone P, Di Scipio F, Mognetti B, Papotti M, Musiani P, Forni G, Cavallo F. A DNA vaccine against ERBB2 impairs chemical carcinogenesis in random-bred hamsters. Cancer Prev Res (Phila). 2011 Jul;4(7):994-1001.
  49. Marchini C, Gabrielli F, Iezzi M, Zenobi S, Montani M, Pietrella L, Kalogris C, Rossini A, Ciravolo V, Castagnoli L, Tagliabue E, Pupa SM, Musiani P, Monaci P, Menard S, Amici A. The human splice variant Δ16HER2 induces rapid tumor onset in a reporter transgenic mouse. PLoS One. 2011 Apr 29;6(4):e18727.
  50. Petrarca C, Lazzarin F, Pannellini T, Iezzi M, Braga M, Mistrello G, Falagiani P, Di Giampaolo L, Di Gioacchino M. Monomeric allergoid intragastric administration induces local and systemic tolerogenic response involving IL-10-producing CD4(+)CD25(+) T regulatory cells in mice. Int J Immunopathol Pharmacol. 2010 Oct-Dec;23(4):1021-31.
  51. Marchini C, Montani M, Konstantinidou G, Orrù R, Mannucci S, Ramadori G, Gabrielli F, Baruzzi A, Berton G, Merigo F, Fin S, Iezzi M, Bisaro B, Sbarbati A, Zerani M, Galiè M, Amici A. Mesenchymal/stromal gene expression signature relates to basal-like breast cancers, identifies bone metastasis and predicts resistance  to therapies. PLoS One. 2010 Nov 30;5(11):e14131.
  52. Pannellini T, Iezzi M, Liberatore M, Sabatini F, Iacobelli S, Rossi C, Alberti S, Di Ilio C, Vitaglione P, Fogliano V, Piantelli M. A dietary tomato supplement prevents prostate cancer in TRAMP mice. Cancer Prev Res (Phila). 2010 Oct;3(10):1284-91.
  53. Bono AV, Pannellini T, Liberatore M, Montironi R, Cunico SC, Cheng L, Sasso F, Musiani P, Iezzi M. Sorafenib's inhibition of prostate cancer growth in transgenic adenocarcinoma mouse prostate mice and its differential effects on endothelial and pericyte growth during tumor angiogenesis. Anal Quant Cytol Histol. 2010 Jun;32(3):136-45.
  54. Cabodi S, Tinnirello A, Bisaro B, Tornillo G, del Pilar Camacho-Leal M, Forni G, Cojoca R, Iezzi M, Amici A, Montani M, Eva A, Di Stefano P, Muthuswamy SK, Tarone G, Turco E, Defilippi P. p130Cas is an essential transducer element in ErbB2 transformation. FASEB J. 2010 Oct;24(10):3796-808.
  55. Rolla S, Ria F, Occhipinti S, Di Sante G, Iezzi M, Spadaro M, Nicolò C, Ambrosino E, Merighi IF, Musiani P, Forni G, Cavallo F. Erbb2 DNA vaccine combined with regulatory T cell deletion enhances antibody response and reveals latent low-avidity T cells: potential and limits of its therapeutic efficacy. J Immunol. 2010 Jun 1;184(11):6124-32.
  56. De Santis R, Leoni B, Rosi A, Albertoni C, Forni G, Cojoca R, Iezzi M, Musiani P, Paganelli G, Chinol M, Carminati P. AvidinOX for highly efficient tissue-pretargeted radionuclide therapy. Cancer Biother Radiopharm. 2010 Apr;25(2):143-8.
  57. Quaglino E, Mastini C, Amici A, Marchini C, Iezzi M, Lanzardo S, De Giovanni C, Montani M, Lollini PL, Masucci G, Forni G, Cavallo F. A better immune reaction to Erbb-2 tumors is elicited in mice by DNA vaccines encoding rat/human chimeric  proteins. Cancer Res. 2010 Apr 1;70(7):2604-12.
  58. Ciraolo E, Morello F, Hobbs RM, Wolf F, Marone R, Iezzi M, Lu X, Mengozzi G, Altruda F, Sorba G, Guan K, Pandolfi PP, Wymann MP, Hirsch E. Essential role of the p110beta subunit of phosphoinositide 3-OH kinase in male fertility. Mol Biol  Cell. 2010 Mar 1;21(5):704-11.
  59. Ugel S, Scarselli E, Iezzi M, Mennuni C, Pannellini T, Calvaruso F, Cipriani B, De Palma R, Ricci-Vitiani L, Peranzoni E, Musiani P, Zanovello P, Bronte V. Autoimmune B-cell lymphopenia after successful adoptive therapy with telomerase-specific T lymphocytes. Blood. 2010 Feb 18;115(7):1374-84.
  60. Coscia M, Quaglino E, Iezzi M, Curcio C, Pantaleoni F, Riganti C, Holen I, Mönkkönen H, Boccadoro M, Forni G, Musiani P, Bosia A, Cavallo F, Massaia M. Zoledronic acid repolarizes tumour-associated macrophages and inhibits mammary carcinogenesis by targeting the mevalonate pathway. J Cell Mol Med. 2010 Dec;14(12):2803-15.
  61. De Giovanni C, Nicoletti G, Landuzzi L, Croci S, Palladini A, Antognoli A, Murgo A, Ianzano ML, Grosso V, Stivani V, Iezzi M, Musiani P, Nanni P, Lollini PL. Tamoxifen combined to anti-HER-2/neu cell vaccine does not hamper cancer immunopreventive efficacy. Vaccine. 2009 Mar 23;27(14):2065-9.
  62. De Giovanni C, Nicoletti G, Palladini A, Croci S, Landuzzi L, Antognoli A, Murgo A, Astolfi A, Ferrini S, Fabbi M, Orengo AM, Amici A, Penichet ML, Aurisicchio L, Iezzi M, Musiani P, Nanni P, Lollini PL. A multi-DNA preventive vaccine for p53/Neu-driven cancer syndrome. Hum Gene Ther. 2009 May;20(5):453-64.
  63. Sala G, Dituri F, Raimondi C, Previdi S, Maffucci T, Mazzoletti M, Rossi C, Iezzi M, Lattanzio R, Piantelli M, Iacobelli S, Broggini M, Falasca M. Phospholipase Cgamma1 is required for metastasis development and progression. Cancer Res. 2008 Dec;68:10187-96.
  64. Carmela Mennuni, Stefano Ugel, Federica Mori, Barbara Cipriani, Manuela Iezzi, Tania Pannellini, Domenico Lazzaro, Gennaro Ciliberto, Nicola La Monica, Paola Zanovello, Vincenzo Bronte, and Elisa Scarselli. Preventive Vaccination with Telomerase Controls Tumor Growth in Genetically Engineered and Carcinogen-Induced Mouse Models of Cancer. Cancer Res. Cancer Res. 2008 Dec 1;68:9865-74.
  65. Ciraolo E, Iezzi M, Marone R, Marengo S, Curcio C, Costa C, Azzolino O, Gonella C, Rubinetto C, Wu H, Dastrù W, Martin EL, Silengo L, Altruda F, Turco E, Lanzetti L, Musiani P, Rückle T, Rommel C, Backer JM, Forni G, Wymann MP, Hirsch E. Phosphoinositide 3-kinase p110beta activity: key role in metabolism and mammary gland cancer but not development. Sci Signal. 2008 Sep 9;1(36):ra3..
  66. Cristina Mastini, Pablo D. Becker, Manuela Iezzi, Claudia Curcio, Piero Musiani, Guido Forni, Federica Cavallo, and Carlos A. Guzman. Intramammary Application of Non-Methylated-CpG Oligodeoxynucleotides (CpG) Inhibits both Local and Systemic Mammary Carcinogenesis in Female BALB/c Her-2/neu Transgenic Mice. Current Cancer Drug Target. 2008 May;8(3):230-42.
  67. AV Bono, R Montironi, T Pannellini, V Mirone, P Musiani & M Iezzi.  Effects of castration on the development of prostate adenocarcinoma from its precursor HGPIN and on the occurrence of androgen-independent poorly differentiated carcinoma in TRAMP mice. Prostate Cancer Prostatic Dis. 2008 Apr 1; [Epub ahead of print] 
  68. Simona Rolla, Cristina Marchini, Silvia Malinarich,  Elena Quaglino,  Stefania Lanzardo, Maura Montani, Manuela Iezzi, Mauro Angeletti, Giorgio Ramadori, Guido Forni, Federica Cavallo, Augusto Amici.  Protective immunity against neu+ carcinomas elicited by electroporation of plasmids coding for decreasing fragments of rat neu extracellular domain. Hum Gene Ther. 2008 Mar;19:229-40.
  69. Patrizia Nanni, Giordano Nicoletti, Arianna Palladini, Stefania Croci, Annalisa Murgo, Agnese Antognoli, Lorena Landuzzi, Marina Fabbi, Silvano Ferrini, Piero Musiani, Manuela Iezzi, Carla De Giovanni and Pier-Luigi Lollini. Antimetastatic activity of a preventive cancer vaccine. Cancer Res. 2007; 67:11037-44.
  70. Shayna E. A. Street, Nadeen Zerafa, Manuela Iezzi, Jennifer A. Westwood, John Stagg, Piero Musiani and Mark J. Smyth. Host perforin reduces tumor number but does not increase survival in oncogene driven mammary adenocarcinoma. Cancer Res. 2007; 67:5454-60.  
  71. De Giovanni C, Croci S, Nicoletti G, Landuzzi L, Palladini A, Pannellini T, Borgia L, Iezzi M, Di Carlo E, Orengo AM, Kennedy RC, Lollini PL, Nanni P, Musiani P. Inhibition of prostate carcinogenesis by combined active immunoprophylaxis. Int J Cancer. 2007;121:88-94.
  72. Claudia Chiodoni, Manuela Iezzi, Cristiana Guiducci, Sabina Sangaletti, Isabella Alessandrini, Chiara Ratti, Francesca Tiboni, Piero Musiani, D. Neil Granger, and Mario P. Colombo. Triggering CD40 on endothelial cells contributes to tumor growth. J Exp Med. 2006; 203:2441-50.
  73. Elena Ambrosino, Michela Spadaro, Manuela Iezzi, Claudia Curcio, Guido Forni, Piero Musiani, Wei-Zen Wei and Federica Cavallo.  Immunosurveillance of Erbb2 Carcinogenesis in Transgenic Mice Is Concealed by a Dominant Regulatory T-Cell Self-Tolerance. Cancer Res. 2006; 66:7734-40.
  74. Holmgren L, Ambrosino E, Birot O, Tullus C, Veitonmaki N, Levchenko T, Carlson LM, Musiani P, Iezzi M, Curcio C, Forni G, Cavallo F, Kiessling R. A DNA vaccine targeting angiomotin inhibits angiogenesis and suppresses tumor growth. Proc Natl Acad Sci U S A. 2006; 103:9208-13.
  75. Pannellini T, Spadaro M, Di Carlo E, Ambrosino E, Iezzi M, Amici A, Lollini PL, Forni G, Cavallo F, Musiani P. Timely DNA Vaccine Combined with Systemic IL-12 Prevents Parotid Carcinomas before a Dominant-Negative p53 Makes Their Growth Independent of HER-2/neu Expression. J Immunol. 2006; 176:7695-7703.
  76. Piantelli M, Rossi C, Iezzi M, La Sorda R, Iacobelli S, Alberti S, Natali PG. Flavonoids inhibit melanoma lung metastasis by impairing tumor cells endothelium interactions. J Cell Physiol. 2006; 207:23-9.
  77. Zerafa N, Westwood JA, Cretney E, Mitchell S, Waring P, Iezzi M, Smyth MJ. Cutting Edge: TRAIL Deficiency Accelerates Hematological Malignancies. J Immunol. 2005; 175:5586-90.
  78. Maffucci T, Piccolo E, Cumashi A, Iezzi M, Riley AM, Saiardi A, Godage HY, Rossi C, Broggini M, Iacobelli S, Potter BV, Innocenti P, Falasca M. Inhibition of the phosphatidylinositol 3-kinase/Akt pathway by inositol pentakisphosphate results in antiangiogenic and antitumor effects. Cancer Res. 2005; 65:8339-49.
  79. Lo Iacono M, Cavallo F, Quaglino E, Rolla S, Iezzi M, Pupa SM, De Giovanni C, Lollini PL, Musiani P, Forni G, Calogero RA. A limited autoimmunity to p185neu elicited by DNA and allogeneic cell vaccine hampers the progression of preneoplastic lesions in HER-2/NEU transgenic mice. Int J Immunopathol Pharmacol. 2005; 18:351-63.
  80. Quaglino E, Mastini C, Iezzi M, Forni G, Musiani P, Klapper LN, Hardy B, Cavallo F. The adjuvant activity of BAT antibody enables DNA vaccination to inhibit the progression of established autochthonous Her-2/neu carcinomas in BALB/c mice. Vaccine. 2005; 23:3280-7.
  81. Astolfi A, Landuzzi L, Nicoletti G, De Giovanni C, Croci S, Palladini A, Ferrini S, Iezzi M, Musiani P, Cavallo F, Forni G, Nanni P, Lollini PL. Gene Expression Analysis of Immune-Mediated Arrest of Tumorigenesis in a Transgenic Mouse Model of HER-2/neu-Positive Basal-Like Mammary Carcinoma. Am J Pathol. 2005; 166:1205-16 
  82. Spadaro M, Ambrosino E, Iezzi M, Di Carlo E, Sacchetti P, Curcio C, Amici A, Wei WZ, Musiani P, Lollini PL, Cavallo F, Forni G. Cure of mammary carcinomas in Her-2 transgenic mice through sequential stimulation of innate (neoadjuvant interleukin-12) and adaptive (DNA vaccine electroporation) immunity. Clin Cancer Res. 2005; 11:1941-52.
  83. De Santo C, Serafini P, Marigo I, Dolcetti L, Bolla M, Del Soldato P, Melani C, Guiducci C, Colombo MP, Iezzi M, Musiani P, Zanovello P, Bronte V. Nitroaspirin corrects immune dysfunction in tumor-bearing hosts and promotes tumor eradication by cancer vaccination. Proc Natl Acad Sci U S A. 2005; 102:4185-90.
  84. Pupa SM, Iezzi M, Di Carlo E, Invernizzi A, Cavallo F, Meazza R, Comes A, Ferrini S, Musiani P, Menard S. Inhibition of mammary carcinoma development in HER-2/neu transgenic mice through induction of autoimmunity by xenogeneic DNA vaccination. Cancer Res. 2005; 65:1071-8. 
  85. Astolfi A, Rolla S, Nanni P, Quaglino E, De Giovanni C, Iezzi M, Musiani P, Forni G, Lollini PL, Cavallo F, Calogero RA. Immune prevention of mammary carcinogenesis in HER-2/neu transgenic mice: a microarray scenario. Cancer Immunol Immunother. 2005; 54:599-610.
  86. Gallo P, Dharmapuri S, Nuzzo M, Maldini D, Iezzi M, Cavallo F, Musiani P, Forni G, Monaci P. Xenogeneic immunization in mice using HER2 DNA delivered by an adenoviral vector. Int J Cancer. 2005; 113:67-77. 
  87. Nanni P, Landuzzi L, Nicoletti G, De Giovanni C, Rossi I, Croci S, Astolfi A, Iezzi M, Di Carlo E, Musiani P, Forni G, Lollini PL. Immunoprevention of mammary carcinoma in HER-2/neu transgenic mice is IFN-gamma and B cell dependent. J Immunol. 2004; 173:2288-96. 
  88. De Giovanni C, Nicoletti G, Landuzzi L, Astolfi A, Croci S, Comes A, Ferrini S, Meazza R, Iezzi M, Di Carlo E, Musiani P, Cavallo F, Nanni P, Lollini PL. Immunoprevention of HER-2/neu transgenic mammary carcinoma through an interleukin 12-engineered allogeneic cell vaccine. Cancer Res. 2004; 64:4001-9. 
  89. Quaglino E, Iezzi M, Mastini C, Amici A, Pericle F, Di Carlo E, Pupa SM, De Giovanni C, Spadaro M, Curcio C, Lollini PL, Musiani P, Forni G, Cavallo F.  Electroporated DNA vaccine clears away multifocal mammary carcinomas in her-2/neu transgenic mice. Cancer Res. 2004; 64:2858-64. 
  90. Quaglino E, Rolla S, Iezzi M, Spadaro M, Musiani P, De Giovanni C, Lollini PL, Lanzardo S, Forni G, Sanges R, Crispi S, De Luca P, Calogero R, Cavallo F. Concordant morphologic and gene expression data show that a vaccine halts HER-2/neu preneoplastic lesions. J Clin Invest. 2004; 113:709-17. 
  91. Nanni P, Nicoletti G, De Giovanni C, Croci S, Astolfi A, Landuzzi L, Di Carlo E, Iezzi M, Musiani P, Lollini PL. Development of rhabdomyosarcoma in HER-2/neu transgenic p53 mutant mice. Cancer Res. 2003; 63:2728-32.
  92. Cappello P, Triebel F, Iezzi M, Caorsi C, Quaglino E, Lollini PL, Amici A, Di Carlo E, Musiani P, Giovarelli M, Forni G. LAG-3 enables DNA vaccination to persistently prevent mammary carcinogenesis in HER-2/neu transgenic BALB/c mice. Cancer Res. 2003; 63:2518-25.
  93. Nanni P, Nicoletti G, De Giovanni C, Landuzzi L, Di Carlo E, Iezzi M, Ricci C, Astolfi A, Croci S, Marangoni F, Musiani P, Forni G, Lollini PL. Prevention of HER-2/neu transgenic mammary carcinoma by tamoxifen plus interleukin 12. Int J Cancer. 2003; 105:384-9.
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Manuela Iezzi

Associate Professor
in Anatomic Pathology

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Valentina Pasi

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Alessia Lamolinara

PhD Research

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Luca Fruci

Veterinary

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