• The currently approved fibrynolytic therapy is only alteplase, but the use of it has been limited to 5% of patients with acute cerebral infarction due to possible side effects including hemorrhagic infarction that may be life-threatening. TMS-007 is a novel drug that has both fibrynolytic activity and brain protective effects. The aim of this project is to perform a clinical trial of this drug and to further achieve a commercial-based clinical use. We believe that this drug would contribute significantly in the treatment of acute cerebral infarction.

• Maximal resection and functional preservation, are often conflicting, but are both important factors to improve patient’s quality of life. Pulsed jet system is designed to achieve this goal by removing lesions without impairing small diameter vessels (100 μm - ). Standardization and specialization of surgical procedures is expected to achieve more easily compared to conventional surgical device using pulsed jet system. We have already reported significant increase of tumor removal rate, significant reduction of intraoperative blood loss and operation time in difficult lesions in the vicinity of sella turcica and skull base through expanded transsphenoidal approach. The system can eject small amount ( - 2 μl) of high speed liquid (- 50 m/s) for minimally invasive surgery, such as endoscopic, catheter, and microscopic surgery. The system is now under stage to expand clinical application outside the field of neurosurgery, and we are expecting new collaboration who can deal with increasing safety, effectiveness, differentiation from conventional instruments, accessibility.

• Effective drug delivery to central nervous system is promising as a new therapeutic strategy against various central nervous system disorders. However, it represents a challenge because systemic delivery is always hindered by blood brain barrier, and local delivery cannot be effective because of the restricted distribution. Recently, local drug delivery system that can achieve robust distribution of the infusates by maintaining a pressure gradient at the tip of the infusion catheter during infusion has developed. Although this method is promising, there still exist several problems as loss of infusates by backflow through catheter tract or inconsistent distribution. We recently developed a method to deliver agents with this method under MRI guidance, and now performing clinical trial to treat recurrent gliomas.

Focal central nervous system disorders such as tumor, epilepsy, and parkinson's disease can be the target for application of this technique. Developments of the new catheters and pre-infusional similation systems are on their way. We are searching for effective collaborative research in this field.

• (1) The amount of anticancer drug required to treat one metastatic lymph node is 1/1,000 to 1/10,000 of the systemic dose.
• (2) The drug can be administered into the lymph node under ultrasound guidance.
• (3) An international patent has been filed for the solvent of the administered drug.

1. Treatment and prophylactic therapy of affiliated lymph nodes in head and neck cancer, breast cancer, etc.
2. Pharmaceutical companies aiming to develop drugs by drug repositioning and generics
3. Medical device manufacturers aiming to develop a dosing system

• 1. pressure sensor (needle, optical fiber, etc.) can be inserted into the lymph node to evaluate the risk of lymph node metastasis and treatment.
• 2. domestic patent obtained

Joint research with a medical device manufacturer to develop a diagnosis and treatment system for lymph node metastasis

• Eleven strains of recombinant inbred (RI) mice derived from MRL/lpr and C3H/lpr mice were established. This RI is the only one in the world that randomly develops lesions such as nephritis, arthritis, sialadenitis, vasculitis, and production of autoantibodies in each strain. The genomes of the two strains of mice are randomly held in homozygous condition, and the phenotypes of each strain and the effects of administered drugs could be compared based on their genotype maps. It is possible to identify the regions of gene loci involved in the phenotype and drug sensitivity.

Development of diagnostic and therapeutic agents for autoimmune diseases. It can be applied to the elucidation of the mechanism of onset of immunological adverse events caused by immune checkpoint inhibitors and the development of drugs to prevent the onset of such events, and industry-academia collaboration with pharmaceutical companies, test reagent companies, etc. is possible.

• McH/lpr-RA1 mice are recombinant congenic mice descended from MRL/lpr and C3H/lpr mice and develop arthritis, vasculitis, and sialadenitis with high frequency and severity, with severe pannus formation similar to rheumatoid arthritis, polyarteritis nodosa, and Sjogren's syndrome. On the other hand, McH/lpr-RA1 mice do not develop systemic lymphadenopathy and severe nephritis as seen in MRL/lpr mice, so they are easy to breed and maintain and can be used for long-term drug administration experiments.

Development of diagnostic and therapeutic agents for collagen diseases. It can be applied to the elucidation of the mechanism of onset of immunological adverse events caused by immune checkpoint inhibitors and the development of drugs to prevent the onset of such events, etc. Industry-academia collaboration with pharmaceutical companies, test reagent companies, etc. is possible.