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The clinical application of carbon ions generated by the heavy ion medical accelerator in Chiba (HIMAC) reached its 20th anniversary in 2014. More than 9,000 cancer patients have been treated at the National Institute of Radiological Sciences (NIRS). Carbon-ion radiotherapy has been applied for treating various types of tumors that were considered difficult to control with existing modalities. Our experience to date has indicated that carbon-ion radiotherapy is advantageous for head and neck cancer, non-small cell lung cancer, pancreatic cancer, prostate cancer, bone/soft tissue sarcomas of the pelvis, uterine cervix adenocarcinomas, and other cancers. However, some cancer types (such as those in close proximity to radiosensitive normal organs) require additional treatments to sensitize the target cancer because of limitation of the irradiation dose. Furthermore, systemic combined therapy is also utilized to suppress possible metastasis. Currently, some anticancer agents are utilized with carbon-ion radiotherapy, including dacarbazine, nimustine hydrochloride, vincristine (DAV), gemcitabine, cisplatin, and 5-fluorouracil. Interesting reagents such as PARP and HSP90 inhibitors have been proposed as cancer cell- specific sensitizers for carbon-ion irradiation during basic biological studies, especially those from the Research Project with Heavy Ions at NIRS-HIMAC. In our laboratory, we have focused our studies on the suppression of metastasis. We have proposed the concurrent use of reagents to inhibit the invasive potential of cancer cells under carbon-ion irradiation. Recently, we have also shown that combining carbon-ion radiotherapy with the local injection of dendritic cells inhibits lung metastases in an in vivo murine model.

We explored a principle of advance directives. Advanced directives are a tool to help execute a broader concept of advance care planning, which is included in advance life planning. Advance directives should be formed by consent with inter- and multi-disciplinary care teams on the basis of patient's intension, passing process such as medical treatment, patient care and mental supports. The contents can update according to patient's health condition and environment. A definition of advance directives is, "oral or written statement in which people declare their treatment preferences in the event that they lose decision-making capacity". Under the present conditions in Japan, we show two problems that the process which reaches to the consent formation is neglected, and the document preparation is excessively considered. Advance directives are of two principle types: instructional directives and proxy consent. There are advantages and disadvantages to each type, and people often used a combination of both types. We conclude an interpretation process of instructional directive with proxy (key person), which assumes the patient's intention, is important for advance directives.

The controversy of the specific and non-specific theories of general anesthesia continues. Recently, non-specific theory began to have the persuasive power again. Molecular dynamics of target protein of the anesthesia and hydrophobic dehydration due to anesthetic binding to the protein have been drawing researcher's attention. Clarification of relation between the action site and the molecular dynamics modification of target protein has been an increasingly important problem. With these contexts, I believe that the research in anesthetic mechanisms will shift to a new paradigm.

Human health conditions are largely determined by a complex interplay among genetic susceptibility, environmental factors, and aging. The RadGenomics project, which began in April 2001, promotes analysis of genes in response to irradiation, identification of their allelic variants in the human population, development of an effective procedure for quantitating individual radio-sensitivity, and analysis of the interrelationship between genetic heterogeneity and susceptibility to irradiation. Major groups of genes with which the project will concern itself include DNA repair genes, cell cycle genes, oncogenes, tumor suppressor genes, genes for programmed cell death, genes for signal transduction, and genes for oxidative processes. The outcome of the RadGenomics project should lead to improved protocols for personalized radiotherapy and reduce the possible side effects of treatment. The project will contribute to future research on the molecular mechanisms of radiation sensitivity in humans and stimulate the development of new high-throughput technology for a broader application of the biological and medical sciences. Identification of functionally important polymorphisms in the radiation response genes may determine individual differences in sensitivity to radiation exposure. The staff members, who are specialists in a variety of fields including genome science, radiation biology, medical science, molecular biology, and bioinformatics, have come to the RadGenomics project from various universities, companies, and research institutes.