Esophageal cancer is still the worst malignant disease, and its prognosis is still poor. To improve the outcome of esophageal cancer, a novel therapy is needed. Here, we demonstrate some novel therapeutic modalities. 1) Immunotherapy: We developed a novel immunotherapy using both intratumoral administration of dendritic cell and radiation for esophageal squamous cell carcinoma. By using radiation, abscopal effect can be induced and this phenomenon enhances immune-reaction and anti-tumor effect mediated by T-cell reaction. A phase I clinical trial is now progressing. 2) New drugs: We have tested some drugs whether some drugs can enhance antitumor effect. From the results of our research, we found that COX2-inhibitor has a capacity to enhance antitumor effect of 5-FU, cisplatin or radiation. On the other hand, newly developed HDAC-inhibitor strongly suppressed tumor growth. HDAC-i modifies epigenetic structure and elucidates anti-tumor effect. 3) MicroRNA: We found that some microRNAs have an anti-tumor effect. For example, we found that miR-145, miR-133a and miR-133b are tumorsuppressive miRNA which targets FSCN1 in esophageal squamous cell carcinoma. Additionally, miR-203 can inhibit migration and invasion activity by regulating LASP1. 4) A newly developed nano-particle: We developed nano-particle which consisted of liposome and ICG. Nano-particles are accumulated in the tumors by EPR effect (Enhanced permeation and retention effect). Using this effect we successfully developed a combination therapy using ICG-liposome and near infrared radiation. 5) Modulated electro-hyperthermia (mEHT): The 13.56 MHz radio frequency was used for mEHT. MEHT can induce apoptosis and suppress tumor growth. This anti-tumor effect is tumor specific and the mechanism is explained by Warburg effect, Szentgyorgyi effect and Fractal effect. We further developed a combination therapy of dendritic cells and mEHT. A phase I study of mEHT for esophageal cancer is now progressing. From these translational approaches, we have been developing novel therapeutic modalities to improve the outcome of esophageal squamous cell carcinoma.

During the 1970's many cases of serious silicosis occurred among migrant workers doing tunnel construction.
We studied the prevalence of silicosis in the eastern part of Toyama prefecture. Questionnaires were sent to all male inhabitants aged 30 or over in the five selected areas. Eight hundred and eighty-five of respondents (41%) had worked as migrant workers. Of these, 580 men (66%) had worked on the job with exposure to dust such as tunnel construction. Of this number, 482 men were examined by chest roentgenography. Of the 482 migrant workers whose job exposed them to dust, 424 silicosis cases (88%) were found. These patients included 195 cases of category 1, 123 cases of category 2, 59 cases of category 3 and 47 cases of category 4 silicosis.
Most of the patients retired and returned to their home villages without having been given any diagnosis and medical care at their places of employment. The silicosis in 297 cases (70% of the total number of disease patients) was first detected in the course of our research.
Two thousand and seventy-seven of the respondents for questionnaire in 1977 and 1978 were followed-up until the end of 1983. For those who died, the causes and dates of death were confirmed by death certificates. The mean person-years of observation per a person was 5.9. The subjects were divided into three groups.
The mortality rate per 1, 000 person-years of migrant workers who had worked in jobs with exposure to dust was 22.3. The mortality rate was significantly higher than that of migrant workers who had not worked in jobs with exposure to dust (14.9) and those who were not migrant workers (9.1). Especially significance is the excess mortality rate of migrant workers whose jobs exposed them to dust in ages 40 to 69.
The mortality rates for pulmonary tuberculosis, pneumonia & bronchitis and pneumoconiosis among migrant workers whose jobs exposed them to dust were higher than those among non-migrant workers.

We previously reported that treatment with tricin (4’,5,7-trihydroxy-3’,5’-dimethoxyflavone) after human cytomegalovirus (HCMV) infection significantly suppressed both infectious virus production and HCMV replication in human embryonic lung fibroblast (HEL) cells. Moreover, we recently revealed that HCMV infection can increase the expression of CC-motif ligand 2 (CCL2/MCP-1) and CCR2, a specific receptor for CCL2, which can enhance HCMV infection and replication, in turn. In this study, we examined whether CCL2 and/or CCR2 are involved in the anti-HCMV effects of tricin in HEL cells. Exposure of fibroblasts to tricin inhibited infectious HCMV production, with concomitant decreases in CCL2 and CCR2 transcript levels and CCL2 protein levels in a dose-dependent manner. Propagermanium, an inhibitor of CCR2 function, has also been shown to inhibit infectious HCMV production with concomitant decreases in CCL2 protein levels. We further observed that tricin and propagermanium reduced mRNA expression of HCMV immediate early gene and DNA polymerase in a dose-dependent manner. These results suggest that tricin is a novel anti-inflammatory compound with potential anti-HCMV activity, and CCL2/CCR2 interactions are associated with HCMV replication.