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Biomedical subjects

Satoshi Wada

Publications and source records attributed to Satoshi Wada.

11 recordsLinked to original sources
PubMed2006

Inhibition of tumor growth with antiangiogenic cancer vaccine using epitope peptides derived from human vascular endothelial growth factor receptor 1.

PURPOSE: Antiangiogenic therapy is now considered to be one of promising approaches to treat various types of cancer. In this study, we examined the possibility of developing antiangiogenic cancer vaccine targeting vascular endothelial growth factor receptor 1 (VEGFR1) overexpressed on endothelial cells of newly formed vessels in the tumor. EXPERIMENTAL DESIGN: Epitope-candidate peptides were predicted from the amino acid sequence of VEGFR1 based on their theoretical binding affinities to the corresponding HLAs. The A2/Kb transgenic mice, which express the alpha1 and alpha2 domains of human HLA-A*0201, were immunized with the epitope candidates to examine their effects. We also examined whether these peptides could induce human CTLs specific to the target cells in vitro. RESULTS: The CTL responses in A2/Kb transgenic mice were induced with vaccination using identified epitope peptides restricted to HLA-A*0201. Peptide-specific CTL clones were also induced in vitro with these identified epitope peptides from peripheral blood mononuclear cells donated by healthy volunteers with HLA-A*0201. We established CTL clones in vitro from human peripheral blood mononuclear cells with HLA-A*2402 as well. These CTL clones were shown to have potent cytotoxicities in a HLA class I-restricted manner not only against peptide-pulsed target cells but also against target cells endogenously expressing VEGFR1. Furthermore, immunization of A2/Kb transgenic mice with identified epitope peptides restricted to HLA-A*0201 was associated with significant suppression of tumor-induced angiogenesis and tumor growth without showing apparent adverse effects. CONCLUSIONS: These results strongly suggest that VEGFR1 is a promising target for antiangiogenic cancer vaccine and warrants further clinical development of this strategy.

Angiogenesis Inhibitors↗
PubMed2006

Automatic continuous scanning and random-access switching of mid-infrared waves generated by difference-frequency mixing.

We report the rapid tuning of mid-infrared waves beyond 5 microm emitted in difference-frequency mixing with an electronically tuned dual-wavelength Ti:Al2O3 laser used as a pumping source. Simultaneous rapid tuning of the dual wavelengths, which satisfy phase matching in AgGaS2, allows rapid random access switching and continuous tuning of mid-infrared wavelengths. In random-access switching, the mid-infrared wavelength is tuned every pulse shot at a repetition rate of 1 kHz. Mid-infrared wavelengths continuously tuned from 5.2 to 7.2 microm, from 7.0 to 9.1 microm, and from 8.9 to 12.0 microm are achieved at phase-matched angles of 55 degrees, 50 degrees, and 45 degrees, respectively.

Journal Article↗
PubMed2006

Colonic pseudolipomatosis, microscopically classified into two groups.

BACKGROUND: Colonic pseudolipomatosis is rare and the pathogenesis is controversial. The purpose of the present paper was to clarify endoscopic and histological characteristics of colonic pseudolipomatosis and to discuss the etiology. METHODS: A total of 15 lesions from 14 patients was reviewed. They were able to be histologically classified into two groups on the basis of variety in size of the vacuoles: Group A, the ratio of largest vacuole to smallest vacuole in size is less than three, Group B, the ratio is more than four. RESULTS: Four of 15 lesions were group A, and were endoscopically polypoid or flat lesions covered with normal-looking mucosa. They were microscopically characterized by (i) predominant location in the upper portion of the lamina propria; (ii) no submucosal involvement; (iii) less variation in vacuolar size; and (iv) no association with lymph follicles. The vacuoles of group A contained proteinaceous materials in two of four lesions. Group B (11 lesions) had small elevated mucosa with normal-looking surface or non-elevated reddish mucosa. Microscopically, the lesions were mainly located in the lower portion of the lamina propria, occasionally also in the submucosa, had variable-sized vacuoles, and were related to lymph follicles. CONCLUSION: It is suggested that the vacuoles in group A contain fluid, and may indicate an abnormal stagnation of interstitial fluid. Microscopic appearance of group B is essentially similar to that of pneumatosis coli. It is thought that group B probably results from penetration of gas from the crypts into the mucosa during colonoscopy. It is unclear why group B had a preference for ileocecal valve and an association with lymph follicles.

Adult↗
PubMed2005

Rationale for antiangiogenic cancer therapy with vaccination using epitope peptides derived from human vascular endothelial growth factor receptor 2.

Angiogenesis is a critical mechanism for tumor progression. Multiple studies have suggested that tumor growth can be suppressed if tumor angiogenesis can be inhibited using various types of antiangiogenic agents. Recent studies in mouse systems have shown that tumor angiogenesis can also be inhibited if cellular immune response could be induced against vascular endothelial growth factor receptor 2 (VEGFR2), which is one of the key factors in tumor angiogenesis. In this study, we examined the possibility of developing this novel immunotherapy in clinical setting. We first identified the epitope peptides of VEGFR2 and showed that stimulation using these peptides induces CTLs with potent cytotoxicity in the HLA class I-restricted fashion against not only peptide-pulsed target cells but also endothelial cells endogenously expressing VEGFR2. In A2/Kb transgenic mice that express alpha1 and alpha2 domains of human HLA-A*0201, vaccination using these epitope peptides in vivo was associated with significant suppression of the tumor growth and prolongation of the animal survival without fatal adverse effects. In antiangiogenesis assay, tumor-induced angiogenesis was significantly suppressed with the vaccination using these epitope peptides. Furthermore, CTLs specific to the epitope peptides were successfully induced in cancer patients, and the specificities of the CTLs were confirmed using functional and HLA-tetramer analysis. These results in vitro and in vivo strongly suggest that the epitope peptides derived from VEGFR2 could be used as the agents for antiangiogenic immunotherapy against cancer in clinical settings.

Amino Acid Sequence↗
PubMed2005

808-nm diode-pumped continuous-wave Tm:GdVO4 laser at room temperature.

A high-quality gadolinium vanadate (GdVO4) crystal with 7-at. % thulium as the starting material was grown by the Czochralski technique. The measured absorption spectra exhibited sufficient absorption coefficients for laser diodes (LDs) for neodymium laser pumping: 6.0 cm(-1) for pi polarization and 6.2 cm(-1) for sigma polarization at 808 nm. Laser oscillation was carried out with single-stripe 808-nm LDs in an end-pumping configuration. A slope efficiency of 28% and a threshold of 750 mW were exhibited with respect to the absorbed pump power. An output power of 420 mW was achieved at an absorbed power of 2.4 W. It was demonstrated that Tm:GdVO4 is a useful material for 2-microm lasers, particularly in a compact LD-pumped system.

Journal Article↗
PubMed2005

Neural control mechanisms of the pheromone-triggered programmed behavior in male silkmoths revealed by double-labeling of descending interneurons and a motor neuron.

Male silkmoths, Bombyx mori, exhibit a characteristic zigzagging behavior consisting of straight-line walking, zigzagging turns, and looping. The timing for shifting the turning direction is synchronized to the sideways head movements controlled by neck motor neurons (NMNs) including a cervical ventral NMN (cv1-NMN). It has been suggested that this programmed behavior is instructed by two types of activity patterns descending from the brain and the thoracic ganglion: one is a phasic excitation and the other is a state-dependent activity similar to the flipflop in electric memory circuits. These activities are shown by certain descending interneurons contained in two subsets of DNs, Group-I and -II DNs. However, it is not yet well understood which DNs are directly related to instructing this behavior. In order to understand neural control mechanisms of this programmed behavior, we investigated the morphological relationship between these DNs and the cv1-NMN, which is an index of this programmed behavior. We applied a double-labeling technique combining backfilling of the cv1-NMN and intracellular staining of single DNs. 3D confocal images revealed overlapping regions between the Group-I, -II DNs and the cv1-NMN. Group-IIA and -IID, which showed typical flipflop activities, Group-IIC DNs, which showed phasic excitation, and Group-IB DNs, which showed long-lasting inhibition had many overlapping regions on the cv1-NMNs. Our results indicate that the programmed behavior is instructed by these types of DNs.

Action Potentials↗
PubMed2004

Ring finger protein 43 as a new target for cancer immunotherapy.

We have performed genome-wide exploration by using cDNA microarray profiling, and successfully identified a new tumor-associated antigen (TAA) that can induce potent cytotoxic T lymphocytes (CTLs) specific to tumor cells. In our preceding study, we identified multiple new genes by using gene expression profiling with a genome-wide cDNA microarray containing 23,040 genes. Among them, we selected RNF43 (ring finger protein 43) as a promising candidate for a TAA expressed by colon cancer cells. In this study, we examined whether the RNF43 protein contains antigenic epitope peptides restricted to HLA-A*0201 or HLA-A*2402. The CTL clones were successfully induced with stimulation by using the peptides binding to HLA-A*0201 (ALWPWLLMA and ALWPWLLMAT) and HLA-A*2402 (NSQPVWLCL), and these CTL clones showed the cytotoxic activity specific to not only the peptide-pulsed targets but also the tumor cells expressing RNF43 and respective HLAs. Lytic activities mediated by two HLA-A2-restricted epitopes were marginal, whereas tumor lysis mediated by the HLA-A24 epitope was clearly better. These findings might be caused by the poor natural presentation of RNF43-11(IX) and RNF43-11(X) by tumors or poor T-cell receptor avidity for these specific epitopes. These results strongly suggest that RNF43 is a new TAA of colon cancer. Furthermore, these results also suggest that our strategy might be a promising one to efficiently discover clinically useful TAAs.

Antigens, Neoplasm↗
PubMed2004

Colorectal xanthomas with polypoid lesion: report of 25 cases.

Little attention has been paid to colorectal xanthoma. To clarify the clinical and pathological features of colorectal xanthoma, we report 28 colorectal xanthomas biopsied from 25 patients. All were composed of typical xanthoma cells and showed polypoid configuration. Median age of the patients was 64 years and there were 15 men and 10 women. Diabetes mellitus, constipation, and hyperlipidemia were found in two, one, and seven patients, respectively. Seventeen (60.7%) of the 28 polyps were located in the sigmoid colon and the remaining 11 in the rectum. Twenty-three polyps (82.1%) were sessile. Twelve (60.0%) of twenty polyps that were recorded were reddish in color. Only two polyps revealed a yellowish tone. Microscopically, foamy cells were present in the lamina propria, but the submucosa did not contain foamy cells. Immunohistochemically, the foamy cells invariably expressed extensive positivity for CD68. The colonic glands showed a deformity in the case with moderate to intense density of the foamy cells. The surface epithelium showed a hyperplastic change in 22 (78.6%) xanthomas. The colonic glands in four xanthomas were also associated with hyperplastic changes. The basement membrane of the surface epithelium was often thickened. Cell debris and proliferation of the capillaries were observed just below the surface epithelium in 19 (67.9%) and 22 (78.6%) xanthomas, respectively. Previous mucosal minute injury was suggested as the pathogenesis of colorectal xanthomas. Colorectal xanthomas were not identical to gastric and esophageal xanthoma, endoscopically or microscopically. We prefer the term "xanthomatous polyp" rather than xanthoma in the colorectal region. They may be regarded as a novel type of colorectal non-neoplastic polyp.

Adult↗
PubMed2003

Efficient laser performance of Nd:GdVO4 crystals grown by the floating zone method.

Efficient laser performance is demonstrated with Nd:GdVO4 crystals grown by the floating zone method. With a 2-at. % Nd-doped crystal a slope efficiency of 67% is achieved with pumping at 808 nm. We also find that pumping at 879 nm with a bandwidth of 1.8 nm is practical for laser diode pumping. With this pumping level the slope efficiency reaches 78%. High-quality Nd:GdVO4 crystals are successfully grown with as much as 15-at.% Nd concentration by the floating zone method without inclusions or macroscopic defects. Homogeneity and high reproducibility of crystal growth are confirmed.

Journal Article↗
PubMed2003

Projections to higher olfactory centers from subdivisions of the antennal lobe macroglomerular complex of the male silkmoth.

The macroglomerular complex (MGC) is the first-order center for synaptic processing of olfactory information about the female sex pheromone in the male moth brain. We have investigated the MGC subdivisions of the male silkmoth Bombyx mori by use of three-dimensional reconstruction of the MGC from sequential series of confocal slice images. The B. mori MGC consists of three subdivisions similar to those of Manduca sexta: the cumulus, toroid and horseshoe. Intracellular recording and staining revealed that responses of MGC projection neurons to pheromonal stimulation correlate with their dendritic arborizations in the subdivisions of the MGC (the cumulus, toroid and horseshoe) and each subdivision specific projection neuron transmits information to different regions in the calyces of the mushroom body and the inferior lateral protocerebrum. We revealed that major pheromone component information is transferred to the medial part of the inferior lateral protocerebrum through three different antennocerebral pathways. Although it is generally accepted that the calyces of the mushroom body and the inferior lateral protocerebrum are the target sites for pheromone information from the MGC in moths, our results suggest that the medial part of the inferior lateral protocerebrum may be a more important processing site for major pheromonal information in B. mori.

Animals↗