Experimental pancreatic cancer develops in soft pancreas: novel leads for an individualized diagnosis by ultrafast elasticity imaging

Autor: Fernanda Ramos-Delgado, Céline Basset, Nicole Therville, Marlène Dufresne, Silvia Arcucci, Julie Guillermet-Guibert, Dina Ferreira Da Mota, Aurélie Vertut
Přispěvatelé: Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d’Excellence ‘TOUCAN’ [Toulouse], Faculté de Médecine [Rangueil], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Pathology
medicine.medical_specialty
Time Factors
pancreatic cancer
Medicine (miscellaneous)
Mice
Transgenic

[SDV.CAN]Life Sciences [q-bio]/Cancer
medicine.disease_cause
tumor rigidity
personalized medecine
Proto-Oncogene Proteins p21(ras)
03 medical and health sciences
0302 clinical medicine
Live cell imaging
Pancreatic cancer
tumor heterogeneity
medicine
Animals
quantitative live imaging
Pharmacology
Toxicology and Pharmaceutics (miscellaneous)

Cellular Senescence
Shear wave elastography
medicine.diagnostic_test
business.industry
Neoplasms
Experimental

medicine.disease
3. Good health
Pancreatic Neoplasms
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Mutation
Elasticity Imaging Techniques
Immunohistochemistry
Elastography
KRAS
Tumor Suppressor Protein p53
Pancreas
business
Preclinical imaging
Research Paper
Carcinoma
Pancreatic Ductal
Zdroj: Theranostics
Theranostics, Ivyspring International Publisher, 2019, 9, ⟨10.7150/thno.34066⟩
ISSN: 1838-7640
DOI: 10.7150/thno.34066⟩
Popis: International audience; Rapid, easy and early pancreatic cancer diagnosis and therapeutic follow up continue to necessitate an increasing attention towards the development of effective treatment strategies for this lethal disease. The non invasive quantitative assessment of pancreatic heterogeneity is limited. Here, we report the development of a preclinical imaging protocol using ultrasonography and shear wave technology in an experimental in situ pancreatic cancer model to measure the evolution of pancreatic rigidity. Methods: Intrapancreatic tumors were genetically induced by mutated Kras and p53 in KPC mice. We evaluated the feasiblity of a live imaging protocol by assessing pancreas evolution with Aixplorer technology accross 36 weeks. Lethality induced by in situ pancreatic cancer was heterogeneous in time. Results: The developed method successfully detected tumor mass from 26 weeks onwards at minimal 0.029 cm 3 size. Elastography measurements using shear wave methodology had a wide detection range from 4.7kPa to 166.1kPa. Protumorigenic mutations induced a significant decrease of the rigidity of pancreatic tissue before tumors developed in correlation with the detection of senescent marker p16-positive cells. An intratumoral increased rigidity was quantified and found surprisingly heterogeneous. Tumors also presented a huge inter-individual heterogeneity in their rigidity parameters; tumors with low and high rigidity at detection evolve very heterogeneously in their rigidity parameters, as well as in their volume. Increase in rigidity in tumors detected by ultrafast elasticity imaging coincided with detection of tumors by echography and with the detection of the inflammatory protumoral systemic condition by non invasive follow-up and of collagen fibers by post-processing tumoral IHC analysis. Conclusion: Our promising results indicate the potential of the shear wave elastography to support individualization of diagnosis in this most aggressive disease.
Databáze: OpenAIRE