Akademik Veri Yönetim Sistemi
Teke K. (Yürütücü)
Türkiye Sağlık Enstitüleri Başkanlığı (TÜSEB) Araştırma Projesi, 2021 - 2022
ABSTRACT
Purpose: We aimed to investigate the antitumoral and inflammatory effect of Boron Neutron Capture Therapy (BNCT) generated by neutron irradiation following systemic or intravesical Boron administration, and to compare it with conventional radiotherapy (RT) in an orthotopic bladder cancer (BC) model.
Methods: Sixty-four Wistar rats were used; half of them were exposed to carcinogen for 16 weeks to induce BC. In the 22nd week, 4 animals with and 4 without BC induction were sacrificed following systemic (2 animals) or intravesical (2 animals) borophenylalanine (BPA) administration, and Boron measurement in bladder tissues was performed with Inductively Coupled Plasma-Mass Spectrometry (ICP/MS). The remaining animals were categorized as follows: control (n=4), control+RT (n=8), control+BNYT-Syst (n=8), control+BNYT-IV (n=8), cancer (n=4), cancer+RT (n=8), cancer+BNYT-Syst (n=8), and cancer+BNYT-IV (n=8). Irradiations were done in the 23rd week. Sacrification was performed at the 25th-28th weeks, and bladder and perivesical tissues were collected. WHO 2016 classification was used for staging and bladder weight was used for tumor burden evaluation. The number of inflammatory cells and the TNF-alpha expressions within them were determined by H&E and immunohistochemistry. Additionally, TNF-alpha expressions in all bladder tissues among all cancer groups were examined by Western blot. Finally, perivesical tissues were evaluated for inflammation.
Results: The levels of boron in carcinogen-received animals were 4.39 ppm for systemic and 10.89 ppm for intravesical administration, whereas the levels in those that did not received carcinogen were 1.51 ppm for systemic and 1.82 intravesical administration. Papillary urothelial carcinomatous lesions were observed in 100%, 100%, 87.5%, and 71.4% of the Cancer, Cancer+RT, Cancer+BNCT-Syst, and Cancer+BNCT-IV groups, respectively. The decrease of tumor burden in Cancer-RT, Cancer+BNCT-Syst, and Cancer+BNCT-IV groups compared with the Cancer group varied from 15 to 25%. The incidence of bladder inflammation in all animals receiving RT, and systemic and intravesical BNCT was 50%, 33.3%, and 20%, respectively. In the intravesical BNCT arms, the rate of inflammation was 7.7% in the colon and 6.6% in the uterus, while it varied from 25% to 37.5% in the systemic BNCT groups and RT groups. Immunohistochemistry and Western blot revealed that TNF-alpha expressions were lower in Cancer+BNCT-IV group compared with Cancer-RT and Cancer+BNCT-Syst groups.
Conclusion: Like RT, systemic or intravesical BNCT has resulted in a partial decrease in the tumor burden. Lower adverse effects had also been observed in BNCT following intravesical BPA administration. Our study suggests that intravesical BNCT may be a potential radiotherapeutic alternative in BC in the future.
Keywords: boron, boron neutron capture therapy, bladder cancer, radiotherapy