Hyperthermia Reduces Irradiation‐Induced Tumor Repopulation in an In Vivo Pancreatic Carcinoma Model

Author:

Sarogni Patrizia1,Zamborlin Agata12,Mapanao Ana Katrina13,Logghe Tine4,Brancato Luigi4,van Zwol Eke4,Menicagli Michele5,Giannini Noemi16,Gonnelli Alessandra16,Linsalata Stefania7,Colenbier Robin8,Van den Bossche Johan4,Paiar Fabiola6,Bogers Johannes48,Voliani Valerio19ORCID

Affiliation:

1. Center for Nanotechnology Innovation@NEST Istituto Italiano di Tecnologia Piazza San Silvestro 12 Pisa 56127 Italy

2. NEST‐Scuola Normale Superiore Piazza San Silvestro 12 Pisa 56127 Italy

3. Center for Radiopharmaceutical Sciences Paul Scherrer Institute 5232 Villigen‐PSI, Forschungsstrasse Switzerland

4. ElmediX NV Dellingstraat 34‐1 Mechelen 2800 Belgium

5. Fondazione Pisana per la Scienza ONLUS via Ferruccio Giovannini 13, S. Giuliano Terme Pisa 56017 Italy

6. Radiation Oncology Unit Pisa University Hospital “Azienda Ospedaliero‐Universitaria Pisana” Via Roma 67 56126 Pisa Italy

7. Unit of Medical Physics Pisa University Hospital “Azienda Ospedaliero‐Universitaria Pisana” Pisa 56126 Italy

8. University of Antwerp Laboratory of Cell Biology and Histology University of Antwerp Antwerpen 2610 Belgium

9. Department of Pharmacy University of Genoa Viale Cembrano, 4 Genoa 16148 Italy

Abstract

AbstractPancreatic cancer has a poor prognosis due to its aggressive nature and ability to metastasize at an early stage. Currently, its management is still a challenge because this neoplasm is resistant to conventional treatment approaches, among which is chemo‐radiotherapy (CRT), due to the abundant stromal compartment involved in the mechanism of hypoxia. Hyperthermia, among other effects, counteracts hypoxia by promoting blood perfusion and thereby can enhance the therapeutic effect of radiotherapy (RT). Therefore, the establishment of integrated treatments would be a promising strategy for the management of pancreatic carcinoma. Here, the effects of joint radiotherapy/hyperthermia (RT/HT) on optimized chick embryo chorioallantoic membrane (CAM) pancreatic tumor models are investigated. This model enables a thorough assessment of the tumor‐arresting effect of the combined approach as well as the quantitative evaluation of hypoxia and cell cycle‐associated mechanisms by both gene expression analysis and histology. The analysis of the lower CAM allows to investigate the variation of the metastatic behaviors of the cancer cells associated with the treatments. Overall, this study provides a potentially effective combined strategy for the non‐invasive management of pancreatic carcinoma.

Publisher

Wiley

Subject

General Medicine

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