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Biomedical subjects

Hiroyuki Kato

Publications and source records attributed to Hiroyuki Kato.

At least 73 records · Page 4Linked to original sources

Characterization of the upper pathway genes for fluorene metabolism in Terrabacter sp. strain DBF63.

Genes involved in the degradation of fluorene to phthalate were characterized in the fluorene degrader Terrabacter sp. strain DBF63. The initial attack on both fluorene and 9-fluorenone was catalyzed by DbfA to yield 9-fluorenol and 1,1a-dihydroxy-1-hydro-9-fluorenone, respectively. The FlnB protein exhibited activities against both 9-fluorenol and 1,1a-dihydroxy-1-hydro-9-fluorenone to produce 9-fluorenone and 2'-carboxy-2,3-dihydroxybiphenyl, respectively. FlnD is a heteromeric protein encoded by flnD1 and ORF16, being a member of the class III two-subunit extradiol dioxygenase. FlnE was identified as a serine hydrolase for the meta-cleavage products that yield phthalate.

Actinomycetales↗

Cell density modulates the metastatic aggressiveness of a mouse colon cancer cell line, colon 26.

OBJECTIVE: Although cell density in cultured cells has demonstrated several alterations in the nature of cell kinetics, the changes in the metastatic aggressiveness of cancer lines under different cell densities have not yet been studied. METHODS: In the current study, we investigated the influence of changing the cell density of cultured cancer cells (colon 26 and B16-F10) injected into the tail vein in BALB/c mice on the metastatic activity by evaluating the number of lung metastases, and the possible mechanisms of this phenomenon were discussed based on the basis of the results of an invasion assay and a cell adhesion assay. RESULTS: The number of metastatic nodules was significantly higher in the high-density group than in the low one in colon 26 (p < 0.005), however, this phenomenon was not seen in B16-F10. Next, we performed the same experiment by changing the environment to the opposite conditions for the cells in the low- and high-density groups, and the results showed the metastatic activities to be always higher in the high-density group. Moreover, although no difference was seen regarding the invasive activity between the high- and low-density groups, an adhesion assay showed the difference in the adhesion cell rate to be significantly higher in the high-density group especially in early period after coculture with human umbilical vein endothelial cells (HUVEC) (p < 0.05). CONCLUSION: In some cell types, the metastatic activity could be altered and reversed by changing the environment, such as the cell density, during a relatively short period. As a result, the epigenetic changes of cancer cells are thus suggested to play a certain role in the malignant potentiality.

Animals↗

Imaging of ancient schwannoma.

OBJECTIVE: We surveyed the clinical symptoms and radiologic features of ancient schwannoma, a rare variant of schwannoma characterized by degenerative changes. MATERIALS AND METHODS: We present the clinical, radiologic, and pathologic features in seven patients with ancient schwannoma (mean age, 62 years; range, 45-80 years) treated at our department between 1998 and 2003. RESULTS: The most characteristic clinical features were a sign like Tinel's sign and a long interval between the onset of symptoms and surgery (mean interval, 8.3 years). Ancient schwannomas can grow large; the biggest tumor seen in our study was 14 cm long. The highly accurate radiologic assessment made possible with contrast-enhanced MRI and CT scanning showed enhancement at a peridegenerative area and sometimes at a capsule. These findings differ from those of the typical schwannoma and neurofibroma patterns reported to date. Furthermore, bone scintigraphy showed uptake in the tumor, but no accumulation was seen on gallium-67 citrate scintigraphy. CONCLUSION: The characteristic clinical and radiologic findings of ancient schwannoma should make it possible to differentiate it from malignant tumors.

Aged↗

Histiocytic sarcoma associated with idiopathic myelofibrosis.

We describe the case of a 39-year-old man with idiopathic myelofibrosis, who developed histiocytic sarcoma (true histiocytic lymphoma) 6 months after diagnosis. The patient developed generalized lymphadenopathy. A lymph node biopsy showed pronounced distension of the sinuses in the medulla and periphery, caused by the accumulation of large tumor cells. The tumor cells had abundant clear or eosinophilic cytoplasm. The nuclei were of various sizes and shapes, with condensed chromatin and prominent nucleoli. Some tumor cells displayed erythrophagocytosis. Immunohistochemically, the tumor cells were positive for CD68, alpha(1)-antitrypsin, CD45, CD45RO, and S100 protein, and were negative for B- and T-cell markers, CD30, CD1a, lysozyme, myeloperoxidase, factor VIII-related antigen, CAM 5.2, and HMB-45. Despite multiagent chemotherapy, the patient died of disease 25 months after diagnosis. Although histiocytic sarcomas are very rare, their recognition may be important for clinical and prognostic reasons.

Adult↗

Body fat accumulation and postoperative complications after abdominal surgery.

The contribution of subcutaneous or intra-abdominal fat (SCF, IAF) accumulation to postoperative mortality or morbidity after elective gastric or colorectal cancer surgery was studied. One hundred thirty-nine patients who underwent gastric or colorectal cancer surgery were investigated. Data were collected on the following preoperative comorbid conditions: lung dysfunction, cardiovascular dysfunction, liver dysfunction, or diabetes mellitus (DM). The IAF and SCF areas were determined at the umbilical level by preoperative CT scanning. We investigated whether IAF or SCF was independently associated with postoperative mortality or morbidity. The mortality rate was 0.7 per cent (1/139). Nineteen (14%) of 139 patients had medical complications (pneumonitis or arrhythmia) and 27 (19%) had surgery-related complications (anastomotic leakage, intra-abdominal collections, or abdominal wound infection) postoperatively. Age (> or =70 years), lung dysfunction, cardiovascular dysfunction, and IAF were significantly associated with medical complications, and surgical site (gastric/colorectal), DM, body mass index, IAF, and SCF were significant for surgery-related complications by univariate analysis. Multilogistic regression analysis showed that age, cardiovascular dysfunction, and IAF were significant for medical complications, and surgical site, DM, and SCF were independently related with surgery-related complications. Body fat accumulation is independently associated with postoperative morbidity after gastric or colorectal surgery, and assaying it may be useful for predicting postoperative complications.

Adipose Tissue↗

Sentinel lymph nodes with technetium-99m colloidal rhenium sulfide in patients with esophageal carcinoma.

BACKGROUND: The authors assessed the detection of sentinel lymph nodes in patients with esophageal squamous cell carcinoma (SCC) using technetium-99m colloidal rhenium sulfide. They studied whether an analysis of sentinel lymph nodes using cytokeratin (CK) immunohistochemistry increased the accuracy of staging. METHODS: The authors observed 25 patients with thoracic esophageal carcinomas who underwent radical esophagectomy. The day before surgery, technetium-99m colloidal rhenium sulfide was injected into the submucosa at four sites around the primary tumor. Lymphoscintigraphy was performed. Esophagectomy and regional lymph node dissection were performed 17 hours after the technetium-99m injection. After surgery, the resected lymph nodes were evaluated by CK staining. RESULTS: Lymphoscintigraphy detected sentinel lymph nodes in 92% of the patients (23 of 25 patients). The accuracy of sentinel lymph node was 91.3% (21 of 23 patients), the sensitivity was 86.7% (13 of 15 patients), and the false-negative rate was 8.7% (2 of 23 patients). A comparison of the number of sentinel lymph nodes and clinicopathologic factors showed that there was a significant association between the number of sentinel lymph nodes and lymph node status (P < 0.01), pathologic stage (P < 0.05), and the number of metastatic lymph nodes (P < 0.05). Occult metastasis was detected by CK staining in 14 (56%) of the 25 patients and in 23 (1.7%) of 1406 lymph nodes. Because the 2 false-negative (sentinel lymph node-negative and nonsentinel lymph node-positive) patients who had occult metastases in the sentinel lymph nodes, the accuracy of sentinel lymph node evaluation using CK staining was 100% (23 of 23). CONCLUSIONS: Lymphatic mapping with technetium-99m colloidal rhenium sulfide was used to identify the lymphatic basin and was feasible in patients with esophageal SCC. An analysis of sentinel lymph nodes using CK immunohistochemistry increased the accuracy of sentinel lymph node.

Aged↗

Second-line chemotherapy with low-dose CPT-11 and cisplatin for colorectal cancer resistant to 5-FU-based chemotherapy.

PURPOSE: With the aim of reducing the toxicities of irinotecan (CPT-11) while maintaining its antitumor effect, we treated colorectal cancer patients resistant to chemotherapy based on 5-fluorouracil (5-FU) with low-dose CPT-11 and cisplatin (CDDP). METHODS: CPT-11 (27 mg/m2) and CDDP (6 mg/m2) were administered on days 1, 8 and 15 every 4 weeks to 20 patients with recurrent or metastatic colorectal cancer. When toxicities were noted, administrations were delayed or the dose was reduced. RESULTS: No severe toxicity (i.e. grade 3 or more) was observed in this study. Nausea was observed in 50% of patients (10/20) and fatigue in 30% (6/20). Only four patients developed leukopenia (three grade 1 and one grade 2). Although the overall response rate was 15% (three partial response, seven no change, and ten progressive disease), the median time to progression was 7.0 months and the median survival time was 18.0 months. The treatment was well tolerated as outpatient therapy. CONCLUSION: Low-dose CPT-11 and CDDP treatment should be considered as second-line chemotherapy for patients with recurrent or metastatic colorectal cancer resistant to 5-FU-based chemotherapy.

Adult↗

Cell cycle protein expression in proliferating microglia and astrocytes following transient global cerebral ischemia in the rat.

Cerebral ischemia induces microglial and astroglial activation, which may play a crucial role in the development of ischemic neuronal damage. In this study, we examined the role of cell cycle proteins in glial proliferation in the hippocampus following 10min of global cerebral ischemia in the rat. Proliferating cells were identified with immunostaining for proliferating cell nuclear antigen (PCNA), and glial cells were visualized with immunostaining for microglial response factor-1 (microglia/macrophages) and glial fibrillary acidic protein (astrocytes). Expression of cyclin D1 and cyclin-dependent kinase-4 was also examined with double label immunohistochemistry. Proliferating cells in the CA1 region after ischemia consisted of microglia and much fewer astrocytes. Microglial activation and proliferation (7.6-fold increase in number after 7 days) were preceded by an increase in PCNA-positive microglia; 83% of microglia were PCNA-positive after 2 days. Astrocytes increased by 1.8-fold after 7 days, and only 6% of astrocytes became PCNA-positive by day 7. Cyclin D1 and cyclin-dependent kinase-4 immunoreactivity appeared in these glial cells in parallel with the expression of PCNA. The findings suggest that the accumulation of brain macrophages elicited by transient cerebral ischemia is caused predominantly by activation and proliferation of resident microglia through the upregulation of cell cycle proteins.

Analysis of Variance↗

Protection of dopaminergic neurons with a novel astrocyte modulating agent (R)-(-)-2-propyloctanoic acid (ONO-2506) in an MPTP-mouse model of Parkinson's disease.

We examined the neuroprotective effects of a novel astrocyte-modulating agent, (R)-(-)-2-propyloctanoic acid (ONO-2506), in a mouse model of Parkinson's disease. Male C57BL/6 mice received four intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (10 mg/kg) at 1-h intervals. Dopamine content in the striatum, measured with HPLC 3 days after MPTP injection, was reduced to 23% of control. But this dopamine depletion was dose-dependently prevented by repeated treatments with ONO-2506 (3, 10 and 30 mg/kg, i.p.) administered 1, 6, 24 and 48 h after MPTP injection (51% of control in 30 mg/kg group, p<0.01). ONO-2506 treatment (30 mg/kg) started after 6 h, followed by treatments at 24 and 48 h, also prevented the reduction of dopamine content (42% of control vs. 11% of control in the saline-treated group, p<0.01). We also performed immunohistochemistry for tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP). The MPTP injection resulted in a loss of TH-positive dopaminergic neurons (42% of control, p<0.01) in the substantia nigra after 7 days, but ONO-2506 treatment prevented this neuronal loss (70% of control, p<0.01). The MPTP injection led to reactive astrocytosis in the striatum after 7 days, but ONO-2506 induced earlier, moderate astrocytic activation after 3-7 days. These findings show that ONO-2506 protects dopaminergic neurons against MPTP neurotoxicity probably through facilitating astrocytic support for neuronal recovery from injury. Pharmacological modulation of astrocytes may offer a novel therapeutic strategy for Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗

Reduced expression of transforming growth factor-beta receptors is an unfavorable prognostic factor in human esophageal squamous cell carcinoma.

Transforming growth factor-beta (TGF-beta) inhibits epithelial cell proliferation. Inactivation of the TGF-beta signaling pathway is thought to play a role in tumorigenesis. Our purpose was to clarify the correlation between TGF-beta receptors or TGF-beta 1 expression and the clinicopathologic characteristics of patients with esophageal squamous cell carcinoma (SCC). Immunohistochemical staining for TGF-beta type I receptor (TGF-beta R-I), TGF-beta R-II and TGF-beta 1 was performed on surgical specimens obtained from 80 patients with esophageal SCC. Preoperative plasma TGF-beta1 levels were measured and correlated with pathologic features and clinical outcomes. Expression of TGF-beta R-I and TGF-beta R-II was reduced in 43 (53.8%) and 23 (28.8%) specimens, respectively. TGF-beta 1 was overexpressed in 29 (36.3%). Reduced expression of TGF-beta R-I and TGF-beta R-II showed a significant association with depth of invasion (p = 0.0015 and p = 0.0012), lymph node metastasis (p = 0.0309 and p = 0.0059) and pathologic stage (p = 0.0103 and p = 0.0401). Overexpression of TGF-beta 1 had a significant association with depth of invasion only (p = 0.0335). Reduced expression of TGF-beta R-I and TGF-beta R-II was correlated with cancer-specific survival (p = 0.0324 and p = 0.0243). The mean preoperative plasma TGF-beta 1 level was 10.5 +/- 0.8 ng/ml in patients with esophageal carcinoma and was significantly higher compared to healthy controls (p < 0.01). We demonstrate that reduced expression of TGF-beta receptors in esophageal SCC appears to be correlated with depth of invasion, lymph node metastasis, pathologic stage and poor prognosis. TGF-beta receptor expression may play a key role in the progression of this cancer.

Adult↗

EphA2 overexpression correlates with poor prognosis in esophageal squamous cell carcinoma.

EphA2 is a member of the Eph family of receptor tyrosine kinases, which interact with cell-bound ligands known as ephrins. EphA2 expression was investigated by immunohistochemistry with an anti-EphA2 monoclonal antibody in 80 patients with esophageal squamous cell carcinoma (ESCC) who had undergone surgery. EphA2 overexpression was positive in 40 of the 80 patients (50%). A significant correlation was observed between EphA2 expression and regional lymph node metastasis (p=0.023), number of lymph node metastases (p=0.011) and poor degree of tumor differentiation (p=0.004). The survival rates of EphA2-positive patients were poorer than those of EphA2-negative patients (p=0.014). The 5-year survival rate of patients without EphA2 overexpression was 68%, whereas that of patients with EphA2 overexpression was 29%. EphA2 expression was also investigated in 7 ESCC cell lines (TE-1, -2, -8, -13, -15, TT and TTn) and 1 immortalized human esophageal keratinocyte cell line (CHEK-1). Western blotting revealed different levels of EphA2 expression in the 8 cell lines. EphA2 was expressed at a high level in the ESCC cell lines compared to CHEK-1. EphA2 phosphorylation was demonstrated in all cell lines. Northern blot analysis showed that EphA2 mRNA expression in TE-1 was greater than that in the other ESCC cell lines. The observation of small gaps on Western blot analysis of the ESCC cell lines suggests that there may be a mechanism for EphA2 regulation at the point of translation. In conclusion, EphA2 overexpression appears to be related to poor degree of tumor differentiation and lymph node metastasis in ESCC. Consequently, patients with EphA2 overexpression have a poorer prognosis than those without. EphA2 is a potential target to prevent ESCC cells spreading into the lymphatic drainage.

Adult↗

Enhanced expression of B7.2 (CD86) by percutaneous sensitization with house dust mite antigen.

House dust mite antigen is a well-known allergen in the pathogenesis of atopic dermatitis (AD), a chronic relapsing inflammatory skin disease. We evaluated the AD model mice sensitized with house dust mite antigen and observed a Th2-dominant immune response. In this experiment, BALB/c mice were sensitized percutaneously with house dust mite antigen three times with 7 days interval after skin barrier disruption. A remarkable infiltration of polymorphonuclear granulocytes and monocytes in the cutis was observed in mice treated with this antigen, high serum IgE levels and IL-4 mRNA expression in local lymph node cells was also observed. CD19(+) B cell numbers overturned to CD4(+) helper T cells. In these mice, there was significant increase of B7.2 (CD86) expression on CD19(+) B cells. These results indicate that house dust mite antigen sensitizes BALB/c mice and skews their Th1/Th2 balance toward Th2.

Administration, Cutaneous↗

A new proliferation marker, minichromosome maintenance protein 2, is associated with tumor aggressiveness in esophageal squamous cell carcinoma.

BACKGROUND: Our aim was to determine whether minichromosome maintenance protein (MCM) 2 expression is useful in predicting tumor proliferation rates and outcome after therapy in patients undergoing surgery for esophageal squamous cell carcinoma (SCC). In addition, we evaluated whether the expression of this proliferation marker was correlated with that of another marker, Ki-67, in esophageal SCC. METHODS: We examined immunohistochemical expression of MCM2 and Ki-67 in surgically resected tissues from 93 patients with esophageal SCC. RESULTS: The mean nuclear labeling index of MCM2 was markedly higher in SCC than in normal epithelia (P < 0.0001). A comparison of MCM2 labeling index and clinicopathological characteristics in 93 patients with esophageal cancer revealed significant associations between MCM2 labeling index and tumor status (P < 0.05), lymph node status (P < 0.01), metastatic status (P < 0.01), pathologic stage (P < 0.01), histologic grade (P < 0.05), and poor prognosis (P < 0.05). A comparison of Ki-67 labeling index and clinicopathological characteristics revealed significant associations between Ki-67 labeling index and lymph node status (P < 0.01), metastatic status (P < 0.05), pathologic stage (P < 0.05), histologic grade (P < 0.05), and poor prognosis (P < 0.05). The relationship between MCM2 and Ki-67 labeling indices in the primary tumor showed a significant correlation (P < 0.05), but the MCM 2 labeling index was considerably higher. CONCLUSIONS: MCM2 may be a more reliable and useful marker than Ki-67 in assessing the growth of normal and tumor cells and in evaluating tumor aggressiveness and prognostic value in patients with esophageal SCC.

Adult↗

Prediction of hematogenous recurrence in patients with esophageal carcinoma.

OBJECTIVES: Despite recent advances in diagnosis and treatment of esophageal carcinoma, the future risk of hematogenous recurrence is still unpredictable. To identify risk factors of hematogenous recurrence in esophageal carcinoma, we used pathological and immunohistochemical analysis to examine relationships among clinical outcomes, clinicopathological features, and E-cadherin expression. METHODS: Subjects were 102 patients with thoracic esophageal cancer who had undergone curative esophagectomy without preoperative treatment. We used univariate and multivariate logistic regression analyses to examine the relationship among clinical outcomes, clinicopathological features, and E-cadherin expression. RESULTS: There was no significant relationship between E-cadherin expression and clinicopathological features at operation. However, the survival rates of patients with E-cadherin-negative tumors were significantly lower than those of patients with E-cadherin-weak and E-cadherin-positive tumors (P < 0.01). Disease recurrence had occurred in 49 (48.0%), with hematogenous recurrence in 29 (28.4%), of the 102 patients at the time of analysis. Metastasis occurred in liver in 14 patients, lung in 13, bone in 6, and brain in 2. Comparisons of hematogenous recurrences and clinicopathological features by multivariate regression analyses revealed significant associations between hematogenous recurrences; particularly in liver and lung metastasis and negative E-cadherin expression. With regard to the associations between the organ with the recurrence and the number of positive nodes; hematogenous recurrence, equal to or higher than lymphatic recurrence, was more likely to have occurred in patients with high numbers of positive nodes. Interestingly, with regard to the sites of positive nodes, liver metastasis was closely correlated with lymph node metastasis in the mid-thoracic as opposed to the abdominal region. Further, lung metastasis was most likely to occur in patients with cervical lymph node metastasis. CONCLUSIONS: Esophageal carcinoma with negative E-cadherin expression tended to be associated with hematogenous recurrence, particularly with liver and lung metastasis. Hematogenous recurrences were significantly associated with high numbers and the site of positive nodes, as well as with lymphatic recurrence.

Adult↗

Ten-year results of a randomized trial on adjuvant chemo-endocrine therapy with tamoxifen for stage II breast cancer.

BACKGROUND: A prospective randomized multi-center study was undertaken for 2 years and 3 months from November 1982, with the aim of examining the significance of using a combination of futraful (FT) and tamoxifen (TAM) for postoperative adjuvant therapy for stage II breast cancer after curative surgery. METHODS: Patients were divided into two groups and received one of the following treatment protocols: treatment A, intravenous administration of doxorubicin (DOX) 20 mg/body on the day of surgery and 10 mg/body the next day, followed by oral FT 600 mg/day for 2 years from the 14th day after surgery; treatment B, the same pattern of DOX administration followed by combined therapy with FT and TAM 20 mg/day for 2 years. The number of patients was 428 (treatment A 210 and treatment B 218), of whom 418 (97.7%) were followed for 10 years for analysis. RESULTS: Significantly higher 5- and 10-year overall survival (OS) rates were observed with treatment B compared with treatment A (p=0.0101 and 0.0219). Node-positive patients appeared to derive more benefit from TAM than node-negative patients. The difference in 10-year OS between treatment A and treatment B was more evident than that of the 5-year OS in patients with more than 4 positive nodes (p=0.0313 vs. 0.0479). No increase in adverse reactions was seen as a result of combining TAM with FT. CONCLUSION: The study results demonstrate that for stage II breast cancer concomitant administration of FT and TAM is superior to FT alone for postoperative adjuvant therapy, and administration of TAM for 2 years may contribute not only to 5-year survival rates but also to 10-year survival rates of node-positive patients.

Adenocarcinoma↗

Positive response to oral chemoendocrine combination therapy using 5"-deoxy-5-fluorouridine for locally advanced breast cancer with carcinomatous pleurisy: report of a case.

A 60-year-old postmenopausal woman presented with an ulcerating and bleeding tumor in her right breast. On physical examination, the tumor was found mainly in the D area of the right breast, and was associated with ulceration and thoracic rigidity. Chest X-ray showed a pleural effusion in her right chest and a computed tomography scan after thoracentesis showed multiple bilateral pleural nodules. Thus, a diagnosis of unresectable advanced breast cancer (T4cN2M1b, PLE) was made. She was given oral 5"-deoxy-5-fluorouridine (5"-DFUR) with medroxyprogesterone acetate, followed by tamoxifen, without any severe adverse reactions, and was subsequently followed up as an outpatient. Her tumor gradually decreased in size, the thoracic rigidity disappeared, and the pleural dissemination and effusion resolved. Thereafter, a radical mastectomy was performed and histologically, the tumor was Grade 1a. She had no signs of recurrence or metastasis 14 months postoperatively. Therefore, oral chemoendocrine combination therapy with 5"-DFUR resulted in a favorable quality of life, there were no severe adverse reactions, and the patient was able to be managed as an outpatient.

Administration, Oral↗