Exposure to high-doses of ionizing radiation leads to development of an acute radiation syndrome (ARS) in mammals. It is important to develop fast prognostic biomarkers for its early detection and assessment as ARS manifests after a latency period. Analysis of chromosomal aberrations in peripheral blood lymphocytes is the gold standard of biological dosimetry, but it takes time in assessment. Therefore, it is important to establish novel biomarkers of exposure that are fast. Here, we introduce the applicability of microRNA (miRNA) levels in blood serum of mice. We found significantly increased levels of miR-375-3p at 48 h and 72 h following whole body exposure to 7 Gy of X-rays. In this study, we conclude that high expressing pancreas of miR-375-3p may secrete this miRNA in serum by exposure to 7 Gy. Therefore, increasing miR-375-3p in serum has the potential to be used as a biomarker for early diagnosis of strong ARS.

External beam radiotherapy is a high-precision cancer therapeutic tool that utilizes 3D- multi-detector computed tomography to both confirm target position and administer radiation dose. In addition, the administration of radiation dose is calculated by Monte Carlo simulation, using computed calculation software. Despite these calculations, individual variation in therapeutic dose and adverse effects are often observed in patients with cancer. To resolve this issue, the use of biomarkers can optimize a dose while evaluating a therapeutic effect and adverse reaction in real time. In the present review, we describe the use of radiotherapy in colorectal cancer treatment, the use of biomarkers until now, and the efficacy of the extracellular release micro RNA as radiation-dose optimization. To fully utilize noninvasiveness radiotherapy, we recommend investigation of the biomarker with high precision, which indirectly evaluates the biological information at the side of a target tissue.

Metastatic brain tumor is the most common intracranial malignant brain tumor. Although the development of molecular target drugs improved the regulation of clinical features of primary tumor in patients, the incidence of brain metastases is increasing. Because brain metastasis by the primary tumor become a major limitation of quality of life for many cancer patients, understanding the mechanism of brain metastasis is required for development of effective therapies. On the other hand, accumulating evidence indicated that individual tumors display the cellular heterogeneity generated by the cancer stem cells. This cancer stem cell model leads us to consider how cancer stem cells are associated with tumor metastasis. Here we review the metastatic process so-called multistep metastatic cascade including detachment from the primary tumor, invasion, intravasation, transit to distant organ, extravasation and proliferation at secondary site, and the involvement of cancer stem cells in each process. In addition, we also introduce the recently emerging evidence for brain metastasis initiating cells with our current research.

Regulatory T cells (Tregs) possess the ability to suppress chronic graft-versus-host disease (cGVHD). Hence, the in vivo expansion of Tregs can be used as therapy against cGvHD. In addition to IL-2, Tregs require TCR and costimulatory signals from antigen presenting cells such as dendritic cells (DCs) for their optimal proliferation.

Both fms-like tyrosine kinase 3 ligand (FLT3-L) and granulocyte macrophage colony stimulation factor (GM-CSF) induce the development of DCs and promote the proliferation of Tregs in a DC-dependent manner. GM-CSF preferentially increases CD8α- DCs, whereas FLT3L more equally supports the development of many DC subsets. However, it is unknown whether GM-CSF-mediated CD8α- DC expansion leads to the proliferation of Tregs and contributes to the inhibition of allo-immune responses against host antigens.

To test whether the injection of GM-CSF augments Tregs and ameliorates cGVHD, we used a MHC-matched mouse cGVHD model (B10.D2 → BALB/c). BALB/c mice were lethally irradiated and transplanted with T cell-depleted bone marrow cells and CD4+ T cells from either syngeneic or B10.D2 mice. Host mice were treated with vehicle or GM-CSF for 3 days and monitored for skin GVHD.

The administration of GM-CSF to allogeneic host mice significantly protected against GVHD-induced skin diseases. GM-CSF increased Tregs in peripheral lymph node and peripheral blood. This results indicate that GM-CSF mitigates cGVHD via proliferation of Tregs.

T cells play a central role in cell-mediated immunity. Abnormalities in T cells have been reported in a number of diseases and several drugs that alter T cell activity have emerged in the fields of cancer, autoimmune diseases, allergies, and others. The need for T cell function tests has increased; however, the long measurement time and low reproducibility of these tests are a major concern.

Recent studies have shown that T cells induce receptor aggregation to form an immune synapse (IS) within two minutes of stimulation. Theoretically, IS formation within a short time. Here, we attempted to establish a rapid and accurate T cell function test based on this principle.

We used human monoclonal T cells, which secrete interferon gamma (IFN-γ) via antibody stimulation, as a stimulus-responsive T cell control. We examined various conditions that determined the induction of IS formation and detection of the formed IS. As a result, we induced IS formation and detected it in monoclonal T cells. Furthermore, the IS formation rate correlated with the results of the existing cytokine flow cytometry assay. Using this method, we measured the stimulus response of blood mononuclear cells and observed that the variation was less than 10%. Based on these results, we believe that the principle of a new T cell function test has been established.

The study focuses on a novel automated system used for cervical cancer testing, which utilizes flow cytometry (FCM). The feasibility of applying the system for cervical cancer testing was examined. The study was approved by the Ethics Committees of the Japanese Red Cross Society Musashino Hospital, and Sysmex Corporation.746 of Liquid based cytology specimens were collected from patients who were treated at our department between September 2011 and February 2013. Informed consent was obtained from the patients to participate in this study.

The system automatically performed the pre-treatment, DNA staining and FCM measurements. It also analyzed the measurement data of the equivalent amount of DNA in epithelial cell populations. Finally, the cell proliferation index based on the analysis was outputted. The median of CPIx for each specimen was compared with Histology results: 0.186 for < CIN1 (n = 32), 0.238 for CIN1 (n = 47), 0.351 for CIN2 (n = 18), 0.534 for CIN3, (n = 24), and 0.759 for squamous cell carcinoma (n = 15). The positive rate in patients exhibiting CIN2 or higher (CIN2+) in the study (n = 61) was observed as being favorable at 95.1% (95% confidence interval [CI], 86.5-98.3%). The negative rate observed in patients negative for intraepithelial lesion or malignancy) as well as < CIN1 patients was 76.3 % (95% CI, 72.8-79.6% [455/596]).

The system showed a favorable performance to detect CIN2+. This shows that it might be utilized to provide a support information for the diagnosis of cervical cancer.

The exposure of radiation workers to ionizing radiation is controlled by attaching physical or chemical dose measurement devices to their body and performing regular medical examinations. In contrast, because a personal dosimeter is rarely used for the general public, it is almost impossible to perform a real-time estimation of radiation exposure. Therefore, a detailed health evaluation method in case of unexpected radiation exposure is not established. Recently, radiation biodosimetry using biogenic substances has become the area of focus, and some researchers have investigated the basics of this approach for further development with high precision. To comprehensively understand these radiation exposure phenomena, urine components, 8-Hydroxy-2’-Deoxyguanosine (8-OHdG), which can be easily extracted and is a marker of oxidative DNA damage was considered as biomarkers. Urine sample was collected after 72 h of X-ray irradiation (1.0 Gy/min) from a male mouse (C57BL/6N). The influence on bone marrow cells, due to acute radiation syndrome, was evaluated using flowcytometry. The urinary concentration of 8-OHdG was 36.5 ± 6.0 (ng/mg, normalized by creatinine), and the concentration remained similar upto 4 Gy exposure. An approximate 2.5~3.8-fold significant increase in 8-OHdG under >7 Gy exposure was observed. These results suggested that 8-OHdG are urinary biomarkers of lethal/sublethal ionizing radiation doses.