Generation of a syngeneic orthotopic graft murine model of peritoneal carcinomatosis for studying in vivo nsPEF anticancerous effects - Archive ouverte HAL Accéder directement au contenu
Poster De Conférence Année : 2018

Generation of a syngeneic orthotopic graft murine model of peritoneal carcinomatosis for studying in vivo nsPEF anticancerous effects

Abdelkader Taibi
  • Fonction : Auteur
Marie-Laure Perrin
  • Fonction : Auteur
Lynn Carr
  • Fonction : Auteur
Catherine Yardin
Sylvaine Durand-Fontanier
Sylvia M. Bardet

Résumé

Carcinoma of the colon and rectum known as colorectal cancer (CRC) is a common cancer that causes around 700 000 deaths from CRC annually and more than 3.5 millions of patients living with it [1]. In addition to the liver, which is the most commonly affected organ, the peritoneum (the membrane that covers the entire abdominal cavity and viscera) is another common metastatic site. Indeed, peritoneal metastases are found in 10 to 25% of cases of CRC [2,3]. The localization remains only peritoneal in about 25% of these cases. Until recently, oncologists and digestive surgeons have considered peritoneal carcinomatosis (CPc, the implantation of tumor cells throughout the peritoneal cavity) as an incurable disease [4]. Currently, the only treatment for validated CPc is based on a complete cytoreduction associated with intraperitoneal hyperthermia chemotherapy (CHIP), supervised by systemic chemotherapy [5]. This treatment has improved the long-term survival of these highly selected patients with a median survival of between 22 and 60 months [6,7]. However, this curative surgical treatment is only available to patients with resectable CPc. The majority of patients with CPc is considered unresectable at the time of diagnosis [8] and will not be able to access this curative treatment despite systemic neoadjuvant chemotherapy. In addition, this surgical treatment is associated with a morbidity of 30% in these already fragile patients [9] and any complication may delay the introduction of post-operative systemic chemotherapy which is equally important in their management. It is for these reasons that it is imperative to work on therapeutic alternatives to treat these many patients with unresectable peritoneal carcinomatosis. High-intensity pulsed electric fields with nanosecond durations (3-300ns; nsPEFs) have emerged as a promising tool for tumor ablation [10-12]. The physical mechanisms and specific type of cell death that occurs following the application of nsPEFs is under investigation by several groups and initial studies have shown effects on cell signaling through calcium and cell death pathways [13-14], mitochondria [15] and cytoskeleton [17-19]. In order to develop a new model of peritoneal colorectal cancer in mouse suitable for studies on nsPEF treatment, we grafted murine colon carcinoma CT-26 cells expressing luciferase in immunocompetent BALB-c mice by intravenous, subcutaneous, intraperitoneal or laparotomy injection and followed the tumoral growth by bioluminescence over 15 days post-grafting. In vitro CT-26 cells were analyzed by flow cytometry for their sensitivity to nsPEFs (survival, mitochondrial potential and permeabilization). In parallel, human and mice peritoneal tumoral tissue were observed by multiphoton microscopy in order to evaluate the tumor microenvironment.
Fichier principal
Vignette du fichier
2018 TAIBI ET AL BIOEM PORTOROZ.pdf (2.12 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03031472 , version 1 (30-11-2020)

Identifiants

  • HAL Id : hal-03031472 , version 1

Citer

Abdelkader Taibi, Marie-Laure Perrin, Lynn Carr, Catherine Yardin, Sylvaine Durand-Fontanier, et al.. Generation of a syngeneic orthotopic graft murine model of peritoneal carcinomatosis for studying in vivo nsPEF anticancerous effects. BioEM2018, 2018, Portoroz, Slovenia. 2018. ⟨hal-03031472⟩

Collections

UNILIM CNRS XLIM
19 Consultations
10 Téléchargements

Partager

Gmail Facebook X LinkedIn More