bioluminescent orthotopic pancreatic-ductal- adenocarcinoma … · niccola funel1,2 elisa...

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Niccola Funel, PhD 48th Annual Pancreas Club Meeting May 2-3, 2014 (Chicago), Illinois Bioluminescent orthotopic pancreatic-ductal- adenocarcinoma (PDAC) mouse models derived from primary PDAC cells as a platform for therapeutic discovery WORKSHOP "Ricerca e Innovazione Clinica" 4 Luglio 2014 DIPINT UNIVERSITA DI PISA

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Page 1: Bioluminescent orthotopic pancreatic-ductal- adenocarcinoma … · Niccola Funel1,2 Elisa Giovannetti3 Tonny Lagerweij4 Amir Avan3 Daniela Campani2 Dieter Fuchs5 Henk M. Verheul3

Niccola Funel, PhD

48th Annual Pancreas Club Meeting

May 2-3, 2014 (Chicago), Illinois

Bioluminescent orthotopic pancreatic-ductal-

adenocarcinoma (PDAC) mouse models derived from

primary PDAC cells as a platform for therapeutic

discovery

WORKSHOP "Ricerca e Innovazione Clinica"

4 Luglio 2014

DIPINT UNIVERSITA’ DI PISA

Page 2: Bioluminescent orthotopic pancreatic-ductal- adenocarcinoma … · Niccola Funel1,2 Elisa Giovannetti3 Tonny Lagerweij4 Amir Avan3 Daniela Campani2 Dieter Fuchs5 Henk M. Verheul3

Azienda Ospedaliero-Universitaria Pisana – U.O. Chirurgia

Generale e Trapianti nell’Uremico e nel Diabetico

Azienda Ospedaliero-Universitaria Pisana – U.O. Radiologia

Azienda Ospedaliero-Universitaria Pisana – U.O Anatomia

Pathologica

Azienda Ospedaliero-Universitaria Pisana – U.O. di Oncologia

Medica

Pancreas Unit

Page 3: Bioluminescent orthotopic pancreatic-ductal- adenocarcinoma … · Niccola Funel1,2 Elisa Giovannetti3 Tonny Lagerweij4 Amir Avan3 Daniela Campani2 Dieter Fuchs5 Henk M. Verheul3

Pancreas Unit

TIME LINE

10 Years

2003 2013

Page 4: Bioluminescent orthotopic pancreatic-ductal- adenocarcinoma … · Niccola Funel1,2 Elisa Giovannetti3 Tonny Lagerweij4 Amir Avan3 Daniela Campani2 Dieter Fuchs5 Henk M. Verheul3

PPPD

PDAC

Page 5: Bioluminescent orthotopic pancreatic-ductal- adenocarcinoma … · Niccola Funel1,2 Elisa Giovannetti3 Tonny Lagerweij4 Amir Avan3 Daniela Campani2 Dieter Fuchs5 Henk M. Verheul3
Page 6: Bioluminescent orthotopic pancreatic-ductal- adenocarcinoma … · Niccola Funel1,2 Elisa Giovannetti3 Tonny Lagerweij4 Amir Avan3 Daniela Campani2 Dieter Fuchs5 Henk M. Verheul3

6 31/07/2014

Cancer Models

Ricci C., et al. 2013

Page 7: Bioluminescent orthotopic pancreatic-ductal- adenocarcinoma … · Niccola Funel1,2 Elisa Giovannetti3 Tonny Lagerweij4 Amir Avan3 Daniela Campani2 Dieter Fuchs5 Henk M. Verheul3

Materials and Methods

Page 8: Bioluminescent orthotopic pancreatic-ductal- adenocarcinoma … · Niccola Funel1,2 Elisa Giovannetti3 Tonny Lagerweij4 Amir Avan3 Daniela Campani2 Dieter Fuchs5 Henk M. Verheul3

Results: Histological Behaviour

Page 9: Bioluminescent orthotopic pancreatic-ductal- adenocarcinoma … · Niccola Funel1,2 Elisa Giovannetti3 Tonny Lagerweij4 Amir Avan3 Daniela Campani2 Dieter Fuchs5 Henk M. Verheul3

Results: ImmunoPhenotyping

Positive Staining

(A) CK8/18

(B) CK7

(C) CK19

(D) Ca19.9

(E) EGFR

(F) CEA

Negative staining

(G) Vimentin

(H) Chromogranin

Vascular Aspects

(I)Hypovascular Areas

(CD31)

(J) and hypoxic Areas

(CA IX)

CK 7 EGFR

Page 10: Bioluminescent orthotopic pancreatic-ductal- adenocarcinoma … · Niccola Funel1,2 Elisa Giovannetti3 Tonny Lagerweij4 Amir Avan3 Daniela Campani2 Dieter Fuchs5 Henk M. Verheul3

Results: Pharmacology

Page 11: Bioluminescent orthotopic pancreatic-ductal- adenocarcinoma … · Niccola Funel1,2 Elisa Giovannetti3 Tonny Lagerweij4 Amir Avan3 Daniela Campani2 Dieter Fuchs5 Henk M. Verheul3

31/07/2014 11

Surgical Resection

Ricci C., et al. 2013

Cancer Tissue Engineering: 3D Models

Page 12: Bioluminescent orthotopic pancreatic-ductal- adenocarcinoma … · Niccola Funel1,2 Elisa Giovannetti3 Tonny Lagerweij4 Amir Avan3 Daniela Campani2 Dieter Fuchs5 Henk M. Verheul3

Our orthotopic PDAC models displayed genetic,

histopathologic, and metastatic features similar to their

human tumors of origin. Moreover, their use pointed to c-

Met as a candidate therapeutic target in PDAC and

highlighted crizotinib and gemcitabine as a synergistic

combination of drugs warranting clinical evaluation for

PDAC treatment.

Conclusions

Page 13: Bioluminescent orthotopic pancreatic-ductal- adenocarcinoma … · Niccola Funel1,2 Elisa Giovannetti3 Tonny Lagerweij4 Amir Avan3 Daniela Campani2 Dieter Fuchs5 Henk M. Verheul3

Niccola Funel1,2

Elisa Giovannetti3

Tonny Lagerweij4

Amir Avan3

Daniela Campani2

Dieter Fuchs5

Henk M. Verheul3

Gerrit-Jan Schuurhuis4

Godefridus J. Peters3

Thomas Wurdinger4

Ugo Boggi1

1Division of General and Transplant Surgery 2Division of Surgical Pathology, University of Pisa

Departments of 3Medical Oncology, and 4Neurosurgery & Pediatric

Oncology/Hematology, VU University Medical Center; 5VisualSonics, Amsterdam,

the Netherlands;

Thanks

Page 14: Bioluminescent orthotopic pancreatic-ductal- adenocarcinoma … · Niccola Funel1,2 Elisa Giovannetti3 Tonny Lagerweij4 Amir Avan3 Daniela Campani2 Dieter Fuchs5 Henk M. Verheul3

UP TO DATE

2014

Page 15: Bioluminescent orthotopic pancreatic-ductal- adenocarcinoma … · Niccola Funel1,2 Elisa Giovannetti3 Tonny Lagerweij4 Amir Avan3 Daniela Campani2 Dieter Fuchs5 Henk M. Verheul3

Start-Up AIRC 2014

P.I Dr Elisa Giovannetti

Dr. Niccola Funel

Con questa iniziativa nel

campo del trasferimento

tecnologico, contiamo

inoltre di identificare

delle buone idee, che

potranno poi essere

accompagnate in un

percorso di

brevettazione, così come

di creazione di start-up

innovative in un settore

che dimostra ampi spazi

di sviluppo e di crescita”.

5 Years 2014-2018

€ 750.000,00