Biomedical subjects

Hiroyuki Yoshida

Publications and source records attributed to Hiroyuki Yoshida.

At least 19 recordsLinked to original sources

PubMed2026

Long-Term Outcomes in Patients With Recurrent Ovarian Cancer and Exceptional Response to PARP Inhibitors.

IMPORTANCE: A subset of patients with platinum-sensitive recurrent ovarian cancer (PS-ROC) treated with maintenance poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have exceptional response. Although licensing recommends continuing PARP inhibitors until progression or unacceptable toxic effects, the optimal duration of PARP inhibitors, and the risks of late progression, myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML) in patients with exceptional response are unknown. OBJECTIVE: To determine the long-term outcomes of patients with PS-ROC who have exceptional response to PARP inhibitors, and to explore genotype-phenotype associations. DESIGN, SETTING, AND PARTICIPANTS: This was an international, multicenter, retrospective cohort study of patients with exceptional response to PARP inhibitors, defined as patients with PS-ROC and progression-free survival (PFS) of 5 years or longer from PARP inhibitor commencement. The study was conducted across 41 sites in 14 countries from January 11, 2023, to November 10, 2025. EXPOSURES: Treatment with PARP inhibitors. MAIN OUTCOMES AND MEASURES: The primary end point was PFS, and secondary end points included overall survival, toxic effects, and dose reductions. RESULTS: A total of 320 patients with exceptional response (mean [SD] age, 56.4 [9.4] years) were included, with a median follow-up of 6.8 years (95% CI, 6.6-7.0 years). The median (IQR) PARP inhibitor duration was 75.0 (64.0-91.0) months. Of patients with exceptional response, 211 (65.9%) received continuous PARP inhibitors, but 109 (34.1%) discontinued: 34 (10.6%) due to physician recommendation, 2 (7.5%) had disease progression beyond 5 years, 22 (6.9%) had toxic effects, 17 (5.3%) for patient preference, and 12 (3.8%) for another reason. The 7.5-year and 10-year PFS rates were 88.8% (95% CI, 84.5%-93.3%) and 78.7% (95% CI, 70.5%-87.9%), respectively. Among the patients, 85 (26.6%) discontinued PARP inhibitors for reasons other than disease progression, with a 10-year PFS of 90.1% (95% CI, 80.6%-100%) vs 72.5% (95% CI, 60.3%-87.2%) for those who continued taking PARP inhibitors. Five patients (1.6%) were diagnosed with late-onset MDS/AML. Patients with exceptional response were enriched for variants in the BRCA1 RING domain and the BRCA2 DNA-binding domain. CONCLUSIONS AND RELEVANCE: In this cohort study, most patients with exceptional response to PARP inhibitors remained progression free, including those who discontinued PARP inhibitors without progression. The risk of late-onset MDS/AML was low. These results can guide counseling on the duration of maintenance PARP inhibitors in patients with exceptional response and suggest that functional cure may be possible in patients with PS-ROC and exceptional response to PARP inhibitors.

Humans↗

PubMed2006

Structural and functional conversion of molecular chaperone ClpB from the gram-positive halophilic lactic acid bacterium Tetragenococcus halophilus mediated by ATP and stress.

In this study, we report the purification, initial structural characterization, and functional analysis of the molecular chaperone ClpB from the gram-positive, halophilic lactic acid bacterium Tetragenococcus halophilus. A recombinant T. halophilus ClpB (ClpB(Tha)) was overexpressed in Escherichia coli and purified by affinity chromatography, hydroxyapatite chromatography, and gel filtration chromatography. As demonstrated by gel filtration chromatography, chemical cross-linking with glutaraldehyde, and electron microscopy, ClpB(Tha) forms a homohexameric single-ring structure in the presence of ATP under nonstress conditions. However, under stress conditions, such as high-temperature (>45 degrees C) and high-salt concentrations (>1 M KCl), it dissociated into dimers and monomers, regardless of the presence of ATP. The hexameric ClpB(Tha) reactivated heat-aggregated proteins dependent upon the DnaK system from T. halophilus (KJE(Tha)) and ATP. Interestingly, the mixture of dimer and monomer ClpB(Tha), which was formed under stress conditions, protected substrate proteins from thermal inactivation and aggregation in a manner similar to those of general molecular chaperones. From these results, we hypothesize that ClpB(Tha) forms dimers and monomers to function as a holding chaperone under stress conditions, whereas it forms a hexamer ring to function as a disaggregating chaperone in cooperation with KJE(Tha) and ATP under poststress conditions.

Adenosine Triphosphate↗

PubMed2006

Dehydration of fructose to 5-hydroxymethylfurfural in sub-critical water over heterogeneous zirconium phosphate catalysts.

Dehydration of fructose to 5-hydroxymethylfurfural in a batch-type process with sub-critical water (sub-CW) was performed in the presence of different laboratory-made zirconium phosphate solid acids at 240 degrees C. A direct relation was found between increasing the crystallinity and decreasing the surface area of solid acids. However, irrespective of the different surface areas, similar catalytic behaviors were observed. Meanwhile, calcination of the samples showed no improvement in the activity of the solid acids. In the presence of the amorphous form of zirconium phosphate, about 80% of fructose was decomposed in sub-critical water at 240 degrees C after 120 s, and the selectivity of the dehydration reaction of fructose to 5-hydroxymethylfurfural rose to 61%. No rehydration products were identified. Soluble polymers and furaldehyde were the only major and minor side products found, respectively. Finally it was found that zirconium phosphate solid acids were stable under sub-CW conditions, and they can easily be recovered without changing their catalytic properties.

Acids↗

PubMed2006

Deposition of acrylonitrile cluster ions on solid substrates: thin film formation by intracluster polymerization products.

Cluster anions of acrylonitrile (AN), known to give intracluster anionic polymerization products, were deposited on solid substrates. The obtained films were examined by using infrared absorption spectroscopy, X-ray photoemission spectroscopy, and gel permeation chromatography with the aid of quantum chemical calculations. The acquired spectroscopic data are similar to those of polyacrylonitrile (PAN), while the normal polymerization of AN or reactions related to PAN seemed not to occur noticeably. On the contrary, the product analysis shows that most of the constituent molecules of the films are formed via cyclohexane-1,3,5-tricarbonitrile (CHTCN), a dominant product of the intracluster polymerization of AN, accompanied by fragmentation and dimerization.

Journal Article↗

PubMed2006

Deregulation of the HOXA10 homeobox gene in endometrial carcinoma: role in epithelial-mesenchymal transition.

Homeobox genes encode transcription factors that control cell differentiation and play essential roles in developmental patterning. Increasing evidence indicates that many homeobox genes are aberrantly expressed in cancers, and that their deregulation significantly contributes to tumor progression. The homeobox gene HOXA10 controls uterine organogenesis during embryonic development and functional endometrial differentiation in the adult. We investigated whether HOXA10 expression is deregulated in endometrial carcinomas, and how counteracting this aberrant expression modifies tumor behavior. We found that down-regulation of HOXA10 expression in endometrial carcinomas strongly correlates with increased tumor grade and is associated with methylation of the HOXA10 promoter. Enforced expression of HOXA10 in endometrial carcinoma cells inhibited invasive behavior in vitro and tumor dissemination in nude mice. The inhibitory effect of HOXA10 on invasive behavior was attributable at least in part to the ability of HOXA10 to induce expression of the epithelial cell adhesion molecule E-cadherin by down-regulating expression of Snail, a repressor of E-cadherin gene transcription. These findings reveal a novel role for HOXA10 deregulation in the progression of endometrial carcinoma by promoting epithelial-mesenchymal transition.

Animals↗

PubMed2006

Possible involvement of calpain activation in pathogenesis of chronic heart failure after acute myocardial infarction.

Changes in proteolytic activity of the myocardium during the development of heart failure after left coronary artery ligation (CAL) of rats were examined. Hemodynamics of the rats at the eighth week (8w-CAL rat), but not at the second week (2w-CAL rat), after CAL showed the symptoms of chronic heart failure. Contents of mu-calpin and m-calpain, but not an intrinsic calpain inhibitor calpastatin, in the viable left ventricular muscle (viable LV) and the right ventricular muscle (RV) of the 2w-CAL and 8w-CAL rats were increased, which was associated with an elevation of intrinsic activities of leupeptin-sensitive, Ca(2+)-activated proteolysis in the cytosolic fractions of the viable LV and RV. Oral administration of 3 mg/kg/d trandolapril or 1 mg/kg/d candesartan from the second to eighth week after CAL improved the hemodynamics of 8w-CAL rats. The drug treatment attenuated the increases in mu-calpain and m-calpain contents and the elevation of the proteolytic activity of the viable LV and RV in the 8w-CAL rat. The drug treatment increased calpastatin content of the RV in the 8w-CAL rat. These results suggest that sustained activation of calpain is involved in the development of chronic heart failure and that trandolapril and candesartan prevent the activation of calpains after CAL.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2006

Massive-training artificial neural network (MTANN) for reduction of false positives in computer-aided detection of polyps: Suppression of rectal tubes.

One of the limitations of the current computer-aided detection (CAD) of polyps in CT colonography (CTC) is a relatively large number of false-positive (FP) detections. Rectal tubes (RTs) are one of the typical sources of FPs because a portion of a RT, especially a portion of a bulbous tip, often exhibits a cap-like shape that closely mimics the appearance of a small polyp. Radiologists can easily recognize and dismiss RT-induced FPs; thus, they may lose their confidence in CAD as an effective tool if the CAD scheme generates such "obvious" FPs due to RTs consistently. In addition, RT-induced FPs may distract radiologists from less common true positives in the rectum. Therefore, removal RT-induced FPs as well as other types of FPs is desirable while maintaining a high sensitivity in the detection of polyps. We developed a three-dimensional (3D) massive-training artificial neural network (MTANN) for distinction between polyps and RTs in 3D CTC volumetric data. The 3D MTANN is a supervised volume-processing technique which is trained with input CTC volumes and the corresponding "teaching" volumes. The teaching volume for a polyp contains a 3D Gaussian distribution, and that for a RT contains zeros for enhancement of polyps and suppression of RTs, respectively. For distinction between polyps and nonpolyps including RTs, a 3D scoring method based on a 3D Gaussian weighting function is applied to the output of the trained 3D MTANN. Our database consisted of CTC examinations of 73 patients, scanned in both supine and prone positions (146 CTC data sets in total), with optical colonoscopy as a reference standard for the presence of polyps. Fifteen patients had 28 polyps, 15 of which were 5-9 mm and 13 were 10-25 mm in size. These CTC cases were subjected to our previously reported CAD scheme that included centerline-based segmentation of the colon, shape-based detection of polyps, and reduction of FPs by use of a Bayesian neural network based on geometric and texture features. Application of this CAD scheme yielded 96.4% (27/28) by-polyp sensitivity with 3.1 (224/73) FPs per patient, among which 20 FPs were caused by RTs. To eliminate the FPs due to RTs and possibly other normal structures, we trained a 3D MTANN with ten representative polyps and ten RTs, and applied the trained 3D MTANN to the above CAD true- and false-positive detections. In the output volumes of the 3D MTANN, polyps were represented by distributions of bright voxels, whereas RTs and other normal structures partly similar to RTs appeared as darker voxels, indicating the ability of the 3D MTANN to suppress RTs as well as other normal structures effectively. Application of the 3D MTANN to the CAD detections showed that the 3D MTANN eliminated all RT-induced 20 FPs, as well as 53 FPs due to other causes, without removal of any true positives. Overall, the 3D MTANN was able to reduce the FP rate of the CAD scheme from 3.1 to 2.1 FPs per patient (33% reduction), while the original by-polyp sensitivity of 96.4% was maintained.

Algorithms↗

PubMed2005

Steroid receptor coactivator-3, a homolog of Taiman that controls cell migration in the Drosophila ovary, regulates migration of human ovarian cancer cells.

Border cell migration is a process that occurs during Drosophila ovarian development in which cells derived from a simple epithelium migrate and invade neighboring tissue. This process resembles the behavior of cancerous cells that derive from the simple epithelium of the human ovary. One important regulator of border cell migration is Taiman, a homolog of steroid receptor coactivator-3 (SRC-3). Because increasing evidence indicates that similarities exist between the molecular control of migration of border cells and of cancer cells, we investigated whether SRC-3 controls ovarian cancer cell migration. Little or no SRC-3 expression was detected in normal ovarian surface epithelium, ovarian cysts and borderline ovarian tumors that lack stromal invasion. In contrast, SRC-3 was abundantly expressed in high-grade ovarian carcinomas. Inhibiting SRC-3 expression in ovarian cancer cells markedly reduced cell spreading and migration, and altered intracellular localization of focal adhesion kinase. This inhibitory effect on cell migration was independent of the estrogen receptor (ER) status of the cells. These studies reveal a novel role for SRC-3 in ovarian cancer progression by promoting cell migration, independently of its role in estrogen receptor signaling.

Acetyltransferases↗

PubMed2005

Fine resolution of human sperm nucleoproteins by two-dimensional electrophoresis.

Human sperm nucleoproteins consist of protamines and histones. Changes in composition of these proteins are thought to correlate with spermatogenesis and may be involved in some instances of male infertility. We sought to separate sperm nucleoproteins including variants of protamine using an improved two-dimensional electrophoretic method, with the aim of comprehensively analysing all sperm nucleoprotein constituents. After extracting nuclear basic proteins from the sperm of normal volunteers, we analysed these proteins on a gel sheet by a radical free, highly reducing method based on Kaltschmidt and Whittmann's two-dimensional electrophoresis. Basic proteins from sperm nuclei were separated clearly into 12 spots. By amino acid sequence analysis, these spots corresponded to protamine 1 (P1)- (five spots), protamine 2 (P2)-related proteins (six spots) and testis-specific histone H2B (one spot). The N-terminal amino acid sequences of the six P2-related proteins were compatible with those of HPI1, HPI2, HPS1, HPS2, HP2 and HP3, and quantitative comparison could be performed. In conclusion, human sperm nucleoproteins including all P2-related variants could be analysed quantitatively with high resolution on a single electrophoretic gel.

Amino Acid Sequence↗

PubMed2005

Effects of angiotensin I-converting enzyme inhibitor and angiotensin II type 1 receptor blocker on the right ventricular sarcoglycans and dystrophin after left coronary artery ligation.

We examined the effects of trandolapril and candesartan on changes in the levels of sarcoglycans and dystrophin in the right ventricle of rats with the left coronary artery ligation. Hemodynamic and morphological alterations suggested the development of hypertrophy of the right ventricle and chronic heart failure by the 8th week. By the end of the 8th week, alpha- and beta-sarcoglycans and dystrophin were decreased. Increases in mu- and m-calpains in the hypertrophied right ventricle were associated with an elevation of casein-proteolytic activity in the cytosolic fraction. Oral administration of 3 mg/kg/day trandolapril or 1 mg/kg/day candesartan from the 2nd to 8th week after the left coronary artery ligation attenuated decreases in alpha-sarcoglycan and dystrophin and reduced the increased proteolytic activity. The results suggest that attenuation of decreases in sarcoglycans and dystrophin is a possible mechanism underlying trandolapril- and candesartan-mediated improvement of structural and functional alterations of the right ventricle in the coronary artery-ligated rat.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2005

Computer-aided detection for virtual colonoscopy.

Colon cancer is one of the leading causes of cancer deaths in the developed countries. Most colon cancers can be prevented if precursor colon polyps are detected and removed. Virtual colonoscopy, or CT colonography, has shown promise to be the future screening tool for polyp detection, with a number of studies performed at academic institutions showing high sensitivity and specificity. Two main factors limiting CT colonography in general use are its excessive interpretation time and the variable sensitivity among readers. This article discusses the potential of computer-aided detection to address these problems. We also review the current state of research in this field and the future roles and challenges of CAD for CT colonography.

Algorithms↗

PubMed2005

Lineage infidelity of epithelial ovarian cancers is controlled by HOX genes that specify regional identity in the reproductive tract.

Although epithelial ovarian cancers (EOCs) have been thought to arise from the simple epithelium lining the ovarian surface or inclusion cysts, the major subtypes of EOCs show morphologic features that resemble those of the müllerian duct-derived epithelia of the reproductive tract. We found that HOX genes, which normally regulate mullerian duct differentiation, are not expressed in normal ovarian surface epithelium (OSE), but are expressed in different EOC subtypes according to the pattern of mullerian-like differentiation of these cancers. Ectopic expression of Hoxa9 in tumorigenic mouse OSE cells gave rise to papillary tumors resembling serous EOCs. In contrast, Hoxa10 and Hoxa11 induced morphogenesis of endometrioid-like and mucinous-like EOCs, respectively. Hoxa7 showed no lineage specificity, but promoted the abilities of Hoxa9, Hoxa10 and Hoxa11 to induce differentiation along their respective pathways. Therefore, inappropriate activation of a molecular program that controls patterning of the reproductive tract could explain the morphologic heterogeneity of EOCs and their assumption of müllerian-like features.

Animals↗

PubMed2005

Effective recovery of harmful metal ions from squid wastes using subcritical and supercritical water treatments.

The Japanese common squid wastes contained high concentration of metal ions such as 31.7 ppm Cd(II), 264.0 ppm Cu(II), and 140.0 ppm Zn(II). The use of sub- and supercritical water treatment has been investigated as a new method of recovering heavy metals from squid wastes. The reactions were carried out in the temperature range of 443-653 K, a pressure range of 0.792-30 MPa, and reaction times of 1-40 min. The wastes were decomposed into soluble proteins, organic acids, amino acids, and so on in the aqueous phase, and the fat and oil were extracted by sub- and supercritical water. The maximum yields on concentration of Cd(II), Cu(II), and Zn(II) in the solid, fat, and oil phases were found at 653, 573, and 513-573 K, respectively. The aqueous phase showed the lowest concentration of the metal ions (0.05-0.5 ppm). The distribution coefficient of metal ions in the fat, solid, and oil phases to aqueous phase were examined and found highest in the fat phase (max. 48 000). The solid phase (max. 39,000) and oil phase (max. 245) showed the second and third highest. Moreover, the fat and oil phases produced during this method act as chelating agents to catch metal ions with an order of recovery of Cu2+ > Zn2+ > Cd2+ and Zn2+ > Cu2+ > Cd2+, respectively.

Animals↗

PubMed2005

Mechanisms of analgesic action of neurotropin on chronic pain in adjuvant-induced arthritic rat: roles of descending noradrenergic and serotonergic systems.

Neurotropin((R)), a non-protein extract from the inflamed skin of rabbits inoculated with vaccinia virus, has been clinically used as an analgesic drug for treatment of chronic pain. In this study, we investigated the analgesic mechanisms of Neurotropin in the adjuvant-induced arthritic rat, a chronic pain model with inflammation. Neurotropin caused dose-dependent inhibition of hyperalgesia in the adjuvant-induced arthritic rat after single intravenous (10 - 100 NU/kg) and oral (30 - 200 NU/kg) administration. The analgesic effect of Neurotropin (intravenous 100 NU/kg and oral 200 NU/kg) was significantly inhibited by intrathecal injections of the alpha(2)-adrenoceptor antagonist yohimbine (30 nmol/animal) and the selective 5-HT(3) serotonin receptor antagonist MDL72222 (30 nmol/animal), and slightly inhibited by the non-selective serotonin receptor antagonist methysergide (100 nmol/animal). The results suggest that the analgesic action of Neurotropin is at least in part due to the enhancement of noradrenergic and serotonergic descending pain inhibitory pathways. Neurotropin may be useful for the clinical management of chronic pain diseases such as a rheumatoid arthritis and osteoarthritis.

Administration, Oral↗

PubMed2005

Effects of ACE inhibitor and AT1 blocker on dystrophin-related proteins and calpain in failing heart.

OBJECTIVES: Genetic depletion of dystrophin-related protein (DRP) complex causes cardiomyopathy in animals and humans. We found in a previous study that some types of DRP were degraded and that calpain content was increased in rats with non-genetically induced heart failure. The present study was aimed at examining the effects of an angiotensin-I-converting enzyme inhibitor (ACEI) trandolapril (Tra) or an angiotensin II type 1 receptor blocker (ARB) candesartan (Can), both of which are known to improve the pathophysiology of chronic heart failure (CHF) on degradation of DRP in failing hearts. METHODS: Coronary artery-ligated (CAL) and sham-operated rats (Sham rats) were treated orally with 3 mg/kg/day trandolapril (Tra) or 1 mg/kg/day candesartan (Can) from the 2nd to 8th week after surgery. RESULTS: Hemodynamic parameters of CAL rats at the 8th week after CAL (8w-CAL) indicated heart failure. alpha-Sarcoglycan (SG) and dystrophin in the surviving left ventricle (surviving LV) of 8w-CAL rats decreased, whereas beta-, gamma-, and delta-SGs remained unchanged. Calcium-activated neutral proteases mu-calpain and m-calpain increased in the surviving LV at the 8th week of postmyocardial infarction. Proteolytic activity in the presence of 5 mM Ca2+ markedly increased at the 2nd and 8th weeks, whereas 50 microM Ca2+ slightly but significantly increased proteolysis of casein. Tra or Can treatment improved the hemodynamic parameters, attenuated changes in alpha-SG and dystrophin, and reversed both calpain contents and activities of the failing heart back to sham levels. CONCLUSION: These results suggest that attenuation in calpain-induced degradation of DRP complex is a possible mechanism for the Tra- or Can-mediated improvement of the pathogenesis of CHF following myocardial infarction.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2005

Region-based supine-prone correspondence for the reduction of false-positive CAD polyp candidates in CT colonography.

RATIONALE AND OBJECTIVES: Radiologists often compare the supine and prone data sets of a patient to confirm potential polyp findings in computed tomographic (CT) colonography (CTC). We developed a new automated method that uses region-based supine-prone correspondence for the reduction of false-positive (FP) polyp candidates in computer-aided detection (CAD) for CTC. MATERIALS AND METHODS: Up to six anatomic landmarks are established by use of the extracted region of the colonic lumen. A region-growing scheme with distance calculations is used to divide the colonic lumen into overlapping segments that match in the supine and prone data sets. Polyp candidates detected by means of a CAD scheme are eliminated in colonic segments that have sufficient diagnostic quality and contain polyp candidates in only one of the data sets of a patient. The method was evaluated with 121 CTC cases, including 42 polyps of 5 mm or greater in 28 patients, obtained by use of single- and multidetector CT scanners with standard pre-colonoscopy cleansing. RESULTS: Complete or partial correspondence was established in 71% of cases. Based on a leave-one-patient-out evaluation, application of the method reduced 19% of FP results reported by our CAD scheme at a 90.5% by-polyp detection sensitivity, without loss of any true-positive results. The resulting CAD scheme yielded 2.4 FP results per patient, on average, with the use of the correspondence method, whereas it yielded 3.0 FP results per patient without the use of the method. CONCLUSION: The correspondence method is potentially useful for improving the specificity of CAD in CTC.

Colonic Polyps↗

PubMed2005

Virtual endoscopic visualization of the colon by shape-scale signatures.

We developed a new visualization method for virtual endoscopic examination of computed tomographic (CT) colonographic data by use of shape-scale analysis. The method provides each colonic structure of interest with a unique color, thereby facilitating rapid diagnosis of the colon. Two shape features, called the local shape index and curvedness, are used for defining the shape-scale spectrum. When we map the shape index and curvedness values within CT colonographic data to the shape-scale spectrum, specific types of colonic structures are represented by unique characteristic signatures in the spectrum. The characteristic signatures of specific types of lesions can be determined by use of computer-simulated lesions or by use of clinical data sets subjected to a computerized detection scheme. The signatures are used for defining a two-dimensional color map by assignment of a unique color to each signature region. The method was evaluated visually by use of computer-simulated lesions and clinical CT colonographic data sets, as well as by an evaluation of the human observer performance in the detection of polyps without and with the use of the color maps. The results indicate that the coloring of the colon yielded by the shape-scale color maps can be used for differentiating among the chosen colonic structures. Moreover, the results indicate that the use of the shape-scale color maps can improve the performance of radiologists in the detection of polyps in CT colonography.

Algorithms↗

PubMed2005

Orirubenones D to G, novel phenones from the Tricholoma orirubens mushroom.

In the course of isolating hyaluronan-degradation inhibitors from the Tricholoma orirubens mushroom, new phenones, orirubenones D to G, were isolated. Although none of the compounds had the inhibitory activity, this result and the result in the previous paper allow us to conclude that the catechol moiety in the molecules was indispensable for exhibiting inhibitory activity.

Agaricales↗