Carbon-ion beam irradiation in combination with cisplatin effectively suppresses xenografted malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare aggressive cancer. This study investigated the growth-inhibitory effects of the combination of carbon ion beam irradiation (IR) and cisplatin (CDDP) on MPM xenografts. Carbon-ion beam IR at 15 Gy effectively inhibited tumor growth and decreased the tumor volume more than 90% after 9 weeks. However, tumor regrowth was observed after 17 weeks. The combination of carbon-ion beam IR (15 Gy) and CDDP significantly suppressed tumor growth after 9 weeks, with tumor regression being observed for more than 18 weeks. In contrast, X-ray IR (30 Gy) alone or in combination with CDDP effectively suppressed tumor growth and decreased the tumor volume after 11 weeks, but tumor growth was observed after 15 weeks. Carbon-ion beam IR at 25 Gy resulted in complete tumor regression without tumor regrowth in the 20-week follow-up period. Histopathological analysis revealed that combination of carbon-ion beam IR and CDDP exerted effective cytotoxic effects on MPM xenograft tumor cells and significantly promoted tumor cell necrosis, cavitation, and fibrosis when compared with individual treatment with carbon-ion beam, X-ray IR, or CDDP. Immunohistochemical analysis revealed that the expression levels of tumor cell migration and invasion-related proteins such as CXCL12, MMP2 and MMP9 were not significantly affected upon low dose (15 Gy) carbon-ion beam IR alone or in combination with CDDP but were markedly upregulated upon treatment with CDDP alone relative to control. However, IR with a high dose (25 Gy) carbon-ion beam inhibited tumor growth without upregulating these proteins. In conclusion, the combination of IR with a low dose (15 Gy) carbon ion beam and CDDP effectively suppressed MPM tumor in vivo without significantly upregulating CXCL12, MMP2 and MMP9, suggesting that combination therapy of carbon ion beam IR and chemotherapy is a promising therapeutic strategy for MPM.

7bgzf: Replacing samtools bgzip deflation for archiving and real-time compression.

BACKGROUND: Genomic sequence data are not only massive but also increasing rapidly every day; therefore, it is essential to compress such data for sharing. Though there are some specific compressors, they lack interoperability. In this study, a SAMtools bgzip variant named 7bgzf has been developed, incorporating several compression and deflation algorithms other than the widely used zlib algorithm. An extensive benchmarking study has been carried out with available data compression software. RESULTS: On both x64 and ARM machines, igzip performed very rapidly. For high compression, using libdeflate on the x64 platform achieved high compression with tolerable speed loss. CONCLUSIONS: Based on appropriate algorithm selection, the proposed compression method performed better than the original bgzip method while maintaining interoperability with existing software. Therefore, this software is useful for both distribution of genomic sequence archives and real-time compression in mobile computing.

Significance of PD-L1 expression in carbon-ion radiotherapy for uterine cervical adeno/adenosquamous carcinoma.

OBJECTIVE: Programmed cell death-ligand 1 (PD-L1) is expressed in tumor cells and has been shown to predict clinical outcomes of several types of malignancies. The aim of this study was to investigate the effects of carbon-ion (C-ion) beam irradiation on PD-L1 expression in human uterine cervical adeno/adenosquamous carcinoma (UCAA) cells and clinical samples and to identify the prognostic factors for outcomes after C-ion radiotherapy (CIRT). METHODS: The effects of C-ion irradiation on PD-L1 expression in human UCAA and cervical squamous cell carcinoma cells were examined by flow cytometry. We examined PD-L1 expression in UCAA biopsy specimens from 33 patients before CIRT started (pre-CIRT) and after 12 Gy (relative biological effectiveness [RBE]) irradiation (post-12Gy-C) in 4 fractions of CIRT to investigate the correlation between PD-L1 status and clinical outcomes. RESULTS: The PD-L1 expression was upregulated by C-ion beam in a dose-dependent manner in HeLa and SiHa cells through phosphorylated Chk1. The overall frequencies of pre-CIRT and post-12Gy-C PD-L1 positivity were 45% (15/33) and 67% (22/33), respectively. The post-12Gy-C PD-L1 expression was significantly elevated compared to the pre-CIRT PD-L1 expression. There was no significant relationship between the pre-CIRT PD-L1 status and clinical outcomes, such as local control (LC), progression-free survival (PFS), and overall survival (OS). However, the post-12Gy-C PD-L1 expression had better correlation with PFS, but not with LC and OS. CONCLUSION: CIRT can induce PD-L1 expression in UCAA and we propose that PD-L1 expression after starting CIRT may become as a predictive prognostic marker in CIRT for UCAA.