The effect of gefinitb (Iressa) on radiation of lung-analysis of anti-cancer effect and radiation pneumonia

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 15591262
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• Research Institution: University of Yamanashi
• Principal Investigator: ONISHI Hiroshi University of Yamanashi, Department of Research Interdisciplinary Graduate School of Medicine and Engineering, Associate Professor, 大学院医学工学総合研究部, 助教授 (30213804)
• Co-Investigator(Kenkyū-buntansha): MARINO Kan University of Yamanashi, University of Yamanashi Hospital, Research Associate, 医学部附属病院, 助手 (70372505) ; ARAYA Masayuki University of Yamanashi, University of Yamanashi Hospital, Instructor, 医学部附属病院, 医員 (90418715) ; AOKI Shinichi University of Yamanashi, University of Yamanashi Hospital, Instructor, 医学部附属病院, 医員 (70418713)
• Project Period (FY): 2003 – 2006
• Keywords: rat / radiation pneumonitis / gefinitib / cisplatin / lung fibrosis / blood count and chemistry / histopathology / respiratory function

Research Abstract

We conducted the respiratory function determination, pulmonary function determination, blood biochemistry and histological study in irradiated rats, and studied the effect of irradiation on their respiratory and pulmonary functions.
Rats were divided into the following four groups; 25Gy left lung irradiation group, 17Gy bilateral lung irradiation group, 20Gy bilateral lung irradiation group and 25Gy bilateral lung irradiation group. The rats, having had their lungs irradiated in the Yamanashi University School of Medicine, were accepted in this research institute. We determined the body weight, body temperature and respiratory function every week and conducted pulmonary function determination, measurement of differential leukocyte counts of bronchoalveolar lavage fluid (BALF), arterial blood gas analysis, hematology, blood biochemistry and histopathological study every two weeks.
Based on the results, changes in respiratory function, pulmonary function, hematological parameters, differen tial leukocyte counts of BALF and pulmonary fibrosis were confirmed following the irradiation of lungs in rats. To study the therapeutic effect of drugs on these irradiation-linked changes, a study conducted 6-8 weeks after irradiation including the 20Gy bilateral lung irradiation group, among the 25Gy left lung irradiation, 17Gy bilateral lung irradiation, 20Gy bilateral lung irradiation, and 25Gy bilateral lung irradiation groups, may be suitable.
Next, we administrated 5 days of gefinitib(50mg/kg/body weight) and/or once cisplatin(10mg/kg/body weight) just before irradiation of 20Gy for bilateral rat lungs. The lung inflammation and fibrosis was increased by the administration of gefinitib and more by the addition of cisplatin in the findings of physiological pulmonary function and histopathology.
In conclusion, a study conducted 6-8 weeks after irradiation including the 20Gy bilateral lung irradiation is a good model for a evaluation of a drug effect on rat radiation lung interstitial change, and we have to pay attention to the addition of gefinitib and/or cisplatin to lung radiotherapy.