Mohammad-Javad Mohseni1, Saeid Amanpour2, Samad Muhammadnejad2, Shabnam Sabetkish1, Ahad Muhammadnejad2, Reza Heidari1, Mahnaz Haddadi2, Zohreh Mazaheri2, Mohammad Vasei3, Abdol-Mohammad Kajbafzadeh4. 1. Pediatric Urology Research Center, Children's Center of Excellence, Department of Pediatric Urology, Islamic Republic of Iran. 2. Department of Experimental Research, Cancer Research Center, Iranian Cancer Institute, Islamic Republic of Iran. 3. Department of Pathology, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran. 4. Pediatric Urology Research Center, Children's Center of Excellence, Department of Pediatric Urology, Islamic Republic of Iran. Electronic address: kajbafzd@sina.tums.ac.ir.
Abstract
OBJECTIVE: Lack of appropriate approaches that reliably predict response of Wilms' tumor (WT) to anticancer agents remains a major deficiency in clinical practice of individualized cancer therapy. The aim of this study was to establish a patient-derived tumor tissue (PDTT) xenograft model of WT for individualized chemotherapeutic regimen selection in accordance with the patient's tumor nature. MATERIAL AND METHODS: Tumor specimens of a primary WT were orthotopically implanted into three nude mice, and after 4 weeks xenografts were harvested for serial heterotopic transplantation in 20 nude mice that were divided into three experimental groups and one control group. In vitro and in vivo chemosensitivity to doxorubicin, actinomycin-D, and vincristine were evaluated. Hematoxylin and eosin (H&E) staining and immunohistochemical examination with desmin, vimentin, myogenin, and neuron-specific enolase (NSE) were also applied to determine histological stability of the xenograft during serial transplantation compared with the original tumor tissue. RESULTS: The xenograft model was successfully established. Histopathologic characteristics of the xenograft tumors were similar to the patient's tumor. Early passage of the PDTT showed a similar chemosensitivity pattern to the original tumor tissue. CONCLUSIONS: PDTT xenograft of WT provides an appropriate model for individualized cancer therapeutic regimen selection by means of its biological stability compared with original patient's tumor.
OBJECTIVE: Lack of appropriate approaches that reliably predict response of Wilms' tumor (WT) to anticancer agents remains a major deficiency in clinical practice of individualized cancer therapy. The aim of this study was to establish a patient-derived tumor tissue (PDTT) xenograft model of WT for individualized chemotherapeutic regimen selection in accordance with the patient's tumor nature. MATERIAL AND METHODS:Tumor specimens of a primary WT were orthotopically implanted into three nude mice, and after 4 weeks xenografts were harvested for serial heterotopic transplantation in 20 nude mice that were divided into three experimental groups and one control group. In vitro and in vivo chemosensitivity to doxorubicin, actinomycin-D, and vincristine were evaluated. Hematoxylin and eosin (H&E) staining and immunohistochemical examination with desmin, vimentin, myogenin, and neuron-specific enolase (NSE) were also applied to determine histological stability of the xenograft during serial transplantation compared with the original tumor tissue. RESULTS: The xenograft model was successfully established. Histopathologic characteristics of the xenograft tumors were similar to the patient's tumor. Early passage of the PDTT showed a similar chemosensitivity pattern to the original tumor tissue. CONCLUSIONS: PDTT xenograft of WT provides an appropriate model for individualized cancer therapeutic regimen selection by means of its biological stability compared with original patient's tumor.
Authors: Claire E Wakefield; Emma L Doolan; Joanna E Fardell; Christina Signorelli; Veronica F Quinn; Kathy F Tucker; Andrea F Patenaude; Glenn M Marshall; Richard B Lock; Gabrielle Georgiou; Richard J Cohn Journal: BMJ Open Date: 2018-08-08 Impact factor: 2.692