Keio University · Medicine
Professor Masahiro Toda's research lab specializes in viral oncolytic therapy and cancer immunotherapy, focusing on the development of replication-competent herpes simplex virus (HSV) vectors for targeted tumor destruction and immune activation. The lab investigates how oncolytic viruses like G207 and defective HSV amplicon vectors can induce both direct cytotoxicity and systemic anti-tumor immune responses, particularly through the delivery of immunostimulatory cytokines such as IL-12 and GM-CSF. A key research direction involves enhancing the therapeutic efficacy of these viral vectors in preclinical models of brain metastases and solid tumors, including breast and colorectal cancers. The lab also explores the interplay between lifestyle factors and health behaviors, as seen in studies linking mobile phone use to health-related lifestyles among young adults.
Figures are computed from collected data and may differ slightly.
The success of cancer gene therapy is likely to require the targeting of multiple antitumor mechanisms. One strategy involves the use of attenuated, replication-competent virus vectors, such as herpes simplex virus type 1 (HSV-1) mutant G207, which is able to replicate in human tumor cells with resultant cell death and tumor growth inhibition, yet is nonpathogenic in normal tissue. In this study, we demonstrate that infection of established tumors with G207 also induces a highly specific systemi
This study investigated the associations between the intensity of mobile phone use and health-related lifestyle. For 275 university students, we evaluated health-related lifestyle using the Health Practice Index (HPI; Hagihara & Morimoto, 1991; Kusaka, Kondou, & Morimoto, 1992) and analyzed responses to a questionnaire (MPDQ; Toda, Monden, Kubo, & Morimoto, 2004) designed, with a self-rating scale, to gauge mobile phone dependence. For males, there was a significant relationship betw
Tumor cells arising from a particular tissue may exhibit the same gene expression patterns as their precursor cells. To test this proposition, we have analyzed the expression of a neural RNA-binding protein, Musashi1, in primary human central nervous system (CNS) tumors. In rodents, Musashi1 is expressed predominantly in proliferating multipotent neural precursor cells, but not in newly generated postmitotic neurons. The expression of Musashi1 is downregulated with the successive progression of
Intratumoral inoculation of replication-competent, attenuated herpes simplex virus (HSV) mutants inhibits tumor growth by direct cytotoxic viral replication and induction of a tumor-specific immune response. To boost the antitumor response, we describe a defective HSV vector encoding IL-12 as an adjuvant to in situ vaccination by the replication-competent HSV helper virus. The defective HSV vector system consists of defective particles containing tandem repeats of the cytokine genes (p40 and p35
We investigated the therapeutic efficacy of G207, a replication-competent multimutated herpes simplex virus type 1, for the treatment of human malignant mammary tumors metastatic to the brain. In vitro studies demonstrated that G207 efficiently destroyed three of four human malignant breast cancer cell lines. MDA-MB-435 was most susceptible and MDA-MB-231 was least susceptible to G207. In athymic mice harboring subcutaneous or intracerebral MDA-MB-435 cells, intraneoplastic inoculation of G207 c
To evaluate the potential of defective herpes simplex virus (HSV) amplicon vectors as in vivo cytokine gene transfer vehicles for active immunotherapy, we generated a defective HSV vector that encodes the murine granulocyte-macrophage colony-stimulating factor (GM-CSF) gene, using a replication-defective HSV as helper virus. A variety of murine tumor cell lines were efficiently infected in vitro with the defective GM-CSF vector (dvGM), and this led to the synthesis and secretion of murine GM-CSF
These findings suggest that the CPDQ is a useful scale for rating cellular phone dependence.
Cavernous sinus (CS) invasion is an aggressive behavior exhibited by pituitary neuroendocrine tumors (PitNETs). The cause of CS invasion in PitNETs has not been fully elucidated. The tumor immune microenvironment, known to promote aggressive behavior in various types of tumors, has not been examined for PitNETs. Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) signaling is strongly associated with the tumor immune microenvironment. In the present study, these molecular and histopa
Tumor-initiating cells thought to drive brain cancer are embedded in a complex heterogeneous histology. In this study, we isolated primary cells from 21 human brain tumor specimens to establish cell lines with high tumorigenic potential and to identify the molecules enabling this capability. The morphology, sphere-forming ability upon expansion, and differentiation potential of all cell lines were indistinguishable in vitro However, testing for tumorigenicity revealed two distinct cell types, br
We report a treatment for spinal cord injury involving implantation of dendritic cells (DCs), which act as antigen-presenting cells in the immune system. The novel mechanisms underlying this treatment produce functional recovery. Among the immune cells tested, DCs showed the strongest activity inducing proliferation and survival of neural stem/progenitor cells (NSPCs) in vitro. Furthermore, in DC-implanted adult mice, endogenous NSPCs in the injured spinal cord were activated for mitotic de novo
We assessed the stress relief effect of spa bathing by measuring sensitive salivary stress markers, cortisol and chromogranin A (CgA). From 12 healthy males, saliva samples were collected immediately before and after spa bathing, and 30 min after that. Salivary cortisol and CgA levels were determined by ELISA. Salivary cortisol levels decreased after spa bathing. This tendency was more pronounced in individuals with higher levels of stress. The high-stress group showed lower salivary CgA levels
Using a written questionnaire we surveyed a sample population of 155 female students, and investigated the associations between mobile phone dependence and perceived parental rearing attitudes. Participants completed the Mobile Phone Dependence Questionnaire (MPDQ; Toda, Monden, Kubo, & Morimoto, 2004) and the Parental Bonding Instrument (PBI; Parker, Tupling, & Brown, 1979). In relation to maternal rearing attitudes, analysis of responses revealed a statistically significant difference
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