Investigation of chemoradiation sensitivity based on the DNA repair mechanism in esophageal carcinoma

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461980
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: Ito Shuhei 九州大学, 大学病院, 講師 (10706914)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: DNA2重鎖修復 / 染色体不安定性 / 姉妹染色分体交換 / PARP阻害剤 / 腫瘍免疫 / PD-L1 / HLA ClassⅠ

Outline of Final Research Achievements

We quantified cytogenetic alterations of human cells exposed to PARPi by both sister chromatid exchange (SCE) assays and chromosome spreading. Clinically relevant doses of the FDA-approved olaparib led to a marked increase of SCEs (5-10-fold) and chromatid aberrations (2-6-fold). Genomic instability arising from PARPi warrants consideration, especially if these agents will be used in people with early stage cancers, in prevention strategies or for non-oncologic indications.
Programmed cell death 1 ligand 1 (PD-L1) and human leukocyte antigen (HLA) class I molecules on malignant cell surfaces are pivotal for tumor immunity. PD-L1 and HLA class I protein expression was investigated by immunohistochemical staining of resected specimens from 90 ESCC patients who underwent radical surgery without preoperative therapy. High PD-L1 expression was a significant independent prognostic factor in ESCC patients with high HLA class I expression.

Free Research Field

消化器外科学