Cristin-prosjekt-ID: 680963
Sist endret: 18. februar 2020, 10:34

Cristin-prosjekt-ID: 680963
Sist endret: 18. februar 2020, 10:34
Prosjekt

Sonoporation of adenocarcinoma

prosjektleder

Emmet McCormack
ved Klinisk institutt 2 ved Universitetet i Bergen

prosjekteier / koordinerende forskningsansvarlig enhet

  • Sjukehusapoteka Vest HF

Finansiering

  • TotalbudsjettNOK 1.500.000
  • Helse Vest RHF
    Prosjektkode: 912162

Klassifisering

HRCS-helsekategori

  • Kreft
  • Munnhule, mage-tarm

HRCS-forskningsaktivitet

  • 4 Påvising, screening og diagnose
  • 5 Utvikling av behandlinger og terapeutiske intervensjoner

Tidsramme

Avsluttet
Start: 1. januar 2017 Slutt: 31. desember 2019

Beskrivelse Beskrivelse

Tittel

Sonoporation of adenocarcinoma

Vitenskapelig sammendrag

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in Europe and the only cancer, which has not seen an improvement in mortality figures in over 40 years. In fact, survival from PDAC is only anecdotal, with a 5- year survival rate of only 3% and a median survival of less than 6 months.Current therapy approaches often combining chemotherapy and surgery carry the only possibility of cure. However, only 15 - 20% of patients are considered resectable at the time of diagnosis, and of these patients who present with surgically amenable disease their median overall survival is still only 15 months. Consequently, this constitutes an extraordinary challenge and the urgent need to provide society with a novel, meaningful therapeutic strategy for this disease. This proposal aims to usher in the radically new concept of sonoporation-enhanced targeted therapy for combating this deadly disease. SONOPORATION is the transient formation of nanometre- to micrometre-sized pores in cell membranes by the use of ultrasound or ultrasound and microbubbles, allowing for intracellular uptake of drugs or genes. The application of sonoporation in enhancing cancer-therapies is only in its preliminary stages but our pilot preclinical and clinical data demonstrate great promise in treatment of PDAC. However, the effective clinical translation is limited by lack of preclinical modelling platforms. We propose through the innovation of multidisciplinary technology platforms and next generation preclinical modelling systems to bridge the translational divide. We will fabricate innovative microbubble drug delivery formats designed specifically to the needs of sonoporation-enhanced therapy in addition to developing radically new tissue organoid models and animal models of PDAC. Importantly, the results of this project will not only impact the future of PDAC therapy, but the novel technologies will effect all aspects of preclinical oncology drug development.

Metode

Optimisation of sonoporation Using the first of its kind, state-of-the-art sonoporation chamber the SonoCURE team has completed over 800 experiments evaluating the effect of sonoporation efficacy using different ultrasound settings, micobubble types, concentrations, and cell lines and is able to determine and predict what setting will result in the best possible drug delivery in vitro. Our results have shown that by optimising these conditions we are able to increase model drug delivery over 100-fold. These results will be translate into the animal studies and development of novel bubbles. Novel microbubble production The SonoCure team has continued it research into Antibubbles and has continuously improved their performance. In the past year we have been able to optimise the way these bubbles are made. As a result we have halved the ultrasound power required to release the drug and improved their size. They are now stable 5x longer in mice, and can be detected with commercial ultrasound systems to see where the encapsulated drug will be delivered. Patient derived xenograft models (PDX) Tumors from 9 different PDAC patients have been successfully perpetuated in immunocompromised mice and characterized in relation to their growth, metastatic potential and tissue structure. In. the near future these PDXs will be used for sonoporation studies. A biobank of immune progenitor cells has been created with samples isolated from cord blood from donors. These cells will be used in the future to humanise the immune system of the mouse models. Collection of further tumour samples is ongoing in collaboration with Surgery Department at Haukeland University Hospital, the Catalan Institute of Oncology (Barcelona), Oslo University Hospital and Saint Vincents University Hospital (Dublin). Organoid models An organoid is a 3D culture of a mixture of different kind of cells. A collaboration with Fraunhofer Institute has been stablished to develop PDAC organoid models, using natural matrixes isolated from pigs. Technology has been developed for growing cells in such matrices, for monitoring cellular growth through microscopy and for applying sonoporation treatment. Primary cells isolated from PDAC patient material will be seeded soon in these matrices to develop patient derived organoids that will be used in sonoporation studies.

prosjektdeltakere

prosjektleder

Emmet McCormack

  • Tilknyttet:
    Prosjektleder
    ved Klinisk institutt 2 ved Universitetet i Bergen

Spiros Kotopoulis

  • Tilknyttet:
    Prosjektdeltaker
    ved Nasjonal kompetansetjeneste for gastroenterologisk ultralyd ved Helse Bergen HF - Haukeland universitetssykehus
  • Tilknyttet:
    Prosjektdeltaker
    ved Klinisk institutt 1 ved Universitetet i Bergen

Ragnhild Haugse

  • Tilknyttet:
    Prosjektdeltaker
    ved Klinisk institutt 2 ved Universitetet i Bergen

Jack Alwin Panapasa

  • Tilknyttet:
    Prosjektdeltaker
    ved Universitetet i Bergen

Endre Stigen

  • Tilknyttet:
    Prosjektdeltaker
    ved Institutt for biomedisin ved Universitetet i Bergen
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Resultater Resultater

Near-Infrared Fluorescent Imaging for Monitoring of Treatment Response in Endometrial Carcinoma Patient-Derived Xenograft Models.

Fonnes, Tina; Strand, Elin; Fasmer, Kristine Eldevik; Berg, Hege Fredriksen; Espedal, Heidi; Sortland, Kristina; Stefansson, Ingunn; Bjørge, Line; Haldorsen, Ingfrid S; Krakstad, Camilla mfl.. 2020, Cancers. HAUKELAND, UIBVitenskapelig artikkel

Ultrasound- and microbubble-enhanced chemotherapy for treating pancreatic cancer: A phase I clinical trial.

Kotopoulis, Spiros; Dimcevski, Georg Gjorgji; Mc Cormack, Emmet; Postema, Michiel; Gjertsen, Bjørn Tore; Gilja, Odd Helge. 2016, Journal of the Acoustical Society of America. HAUKELAND, UIBVitenskapelig artikkel
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