Biomedical subjects

K Sugihara

Publications and source records attributed to K Sugihara.

At least 19 recordsLinked to original sources

PubMed2006

Successful delivery after the transfer of twice-vitrified embryos derived from in vitro matured oocytes: a case report.

We report here the first case of successful pregnancy and delivery after the blastocyst transfer of twice-vitrified embryos produced following in vitro maturation (IVM) and ICSI. The patient received 5000 IU hCG on day 12 of the treatment cycle, and oocyte retrieval was carried out 36 h after hCG injection. A total of 22 immature oocytes were obtained. Following incubation for 26 h in IVM medium, 15 oocytes (68.2%) reached metaphase II stage. In total, 13 oocytes (86.7%) were fertilized after ICSI with the husband's sperm, and 11 embryos at the pronuclear stage and two cleaved embryos on day 2 were vitrified because of thin endometrial thickness. Eight cryopreserved embryos at the pronuclear stage were warmed and cultured until the day 3 stage. Three embryos were transferred, and three embryos were twice vitrified. Unfortunately, these transferred embryos did not implant. Three twice-vitrified embryos were rewarmed and cultured until the day 5 stage, and two embryos were transferred. The second transfer attempt of twice-vitrified embryos resulted in the full-term delivery of a healthy infant. This case report demonstrates that twice-vitrified embryos, developed using an IVM protocol, retain the developmental competence for full-term, healthy infants.

Adult↗

PubMed2006

Phase I/II study of S-1 combined with irinotecan for metastatic advanced gastric cancer.

A dose-escalation study of irinotecan (CPT-11) combined with S-1, an oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). S-1 was administered orally at 80 mg m-2 day-1 from day 1 to 14 of a 28-day cycle and CPT-11 was given intravenously on day 1 and 8 at an initial dose of 70 mg m-2 day-1, stepping up to 100 mg m-2. The treatment was repeated every 4 weeks, unless disease progression was observed. In the phase I portion, the MTD of CPT-11 was presumed to be 100 mg m-2, because 66.6% of patients (two of three) developed DLTs. All three patients at the initial RD of CPT-11 (90 mg m-2) experienced grade 4 haematological or grade 3 nonhaematological toxicities at second course, followed by the dose reduction of CPT-11 from the third course. Considering safety and the ability to continue treatment, the final RD was determined to be 80 mg m-2. In the phase II portion, 42 patients including seven patients in the final RD phase I portion were evaluated. The median treatment course was five (range: 1-13). The incidences of severe (grade 3-4) haematological and nonhaematological toxicities were 19 and 10%, respectively, but all were manageable. The RR was 62% (26 of 42, 95% confidence interval: 47.2-76.6%), and the median survival time was 444 days. Our phase I/II trial showed S-1 combined with CPT-11 is effective for AGC and is well tolerated, with acceptable toxicity.

Administration, Oral↗

PubMed2006

Immunohistological evaluation of Ki-67, p63, CK19 and p53 expression in oral epithelial dysplasias.

BACKGROUND: Oral squamous cell carcinoma develops through a multistep of genetic mutations, and the process can be morphologically recognized as oral epithelial dysplasia. To evaluate the hypothesis that distributional alterations of proliferating and stem cells may be a useful index to estimate the grading and development of epithelial dysplasia, we examined the distribution patterns according to stratified cell layers. METHODS: Sixty-two oral dysplasia cases according to the histological grades were immunohistologically examined and the nuclear expression of Ki-67 and p63 antigens was counted according to epithelial layers as labeling index. RESULTS: The Ki-67 labeling index in the basal and suprabasal layers and that of p63 in the basal layer showed a significant difference between low- and high-grade groups of epithelial dysplasia. CONCLUSION: The architectural alteration of proliferating cell and stem cell distribution in the layers of epithelial dysplasias may provide useful information to evaluate the grading of oral epithelial dysplasias.

Adult↗

PubMed2006

Interpretation of scintigraphic findings of oral malignant tumours with a new scanning agent of technetium-99m-hexakis-2-methoxy-isobutyl-isonitrile (Tc-99m-MIBI).

OBJECTIVES: The purpose of this study was to investigate the usefulness of a new scanning agent of technetium-99m-hexakis-2-methoxy-isobutyl-isonitrile (Tc-99m-MIBI) for the diagnosis of malignant tumours of the head and neck. METHODS: Scintigraphy with Tc-99m-MIBI was performed in 19 patients with malignant tumours of the head and neck. Factors of the early and delayed static scans (hot, warm or cold uptake), the early and delayed retention indexes, the blood flow index and the tumour retention index were obtained from Tc-99m-MIBI scintigraphy. Tumour retention indexes were classified into three grades; slightly (>0.9), moderately (0.9-0.8) and severely (0.8>) decreased. Grade of tissue differentiation of tumour (well, moderately or poorly differentiated) and tumour size (T1 approximately T4) were examined using the excised tumour. Scintigraphic indexes and tumour characteristics were compared. RESULTS: The early static scan and tumour size showed a correlation with the blood flow index. However, the delayed static scan did not show any relationship with blood flow index and tumour size. The tumour retention index had a tendency to decrease in malignant tumours, and showed a significant correlation with the grade of tissue differentiation of the tumour. CONCLUSIONS: The tendency of the tumour retention index to decrease in Tc-99m-MIBI scintigraphy showed the malignancy of tumour and would be useful for the diagnosis of malignant tumours of the head and neck.

Adult↗

PubMed2005

Intratumoural expression of thymidylate synthase is an independent predictor of prognosis in patients with squamous cell carcinoma of the tongue: results from a retrospective study.

The aim of this study was to assess the importance of immunohistochemical thymidylate synthase (TS) expression level as a prognostic marker in tongue cancer patients. In 140 patients with primary squamous cell carcinoma (SCC) of the tongue, intratumoural TS expression was evaluated by immunohistochemistry. The level of TS expression was determined by a semiquantitative scoring system, ranging from 1+ to 3+ according to the ratio of TS-positive cells. Of 140 patients, 64 (45.7%), 49 (35.0%) and 27 (19.3%) were assessed as 1+, 2+ and 3+, respectively. Univariate analyses demonstrated that both disease-free survival (DFS) and overall survival (OS) were significantly lower in patients with a TS 3+ tumour than in those with a TS 1+/2+ tumour (DFS: P = 0.0082, OS: P = 0.0100). In a multivariate analysis using the Cox regression model, cervical lymph-node status and TS expression level were selected as independent factors for DFS and OS. Maintenance adjuvant chemotherapy by oral 5-fluorouracil (5-FU) significantly improved DFS and OS in patients with a TS 1+/2+ tumour (DFS: P = 0.0027, OS: P = 0.0398). These data suggest that the level of immunohistochemical TS expression is an independent prognosticator in patients with tongue SCC, and may be useful in the selection of patients who would benefit from oral 5-FU adjuvant chemotherapy.

Adult↗

PubMed2005

A monoclonal antibody that recognizes Epstein-Barr virus nuclear antigen 2 (EBNA 2) amino acids 1-58 does not react with EBNA 2 in native form, consistent with the self-association of EBNA 2 through the amino-terminus.

We have generated a mouse IgG1 monoclonal antibody (mAb) that recognizes amino acids 1-58 of Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA 2) of type 1 EBV strain B95-8. mAb Y101 also reacted with EBNA 2 of EBV type 2 strains MISP and Jijoye in immunoblots, whereas Jijoye EBNA 2 was not detected by the widely used mAb PE2. mAb Y101, in contrast to mAb PE2, reacted with faster migrated, hypophosphorylated proteins of type 1 EBNA 2 as intensely as slower migrated, hyperphosphorylated ones. mAb Y101 did not react in fixed-cell immunostaining or cell extract immunoprecipitation. The results implicate that the amino-terminal epitope is not exposed in a native form, consistent with the previously reported idea of self-association of EBNA 2 through the amino-terminus. mAb Y101 is the first mAb to the EBNA 2 amino-terminus and will be useful for further analyses of the structure and function of EBNA 2.

Amino Acid Sequence↗

PubMed2005

Demographic and pathological characteristics of serrated polyps of colorectum.

AIMS: To characterize a series of colorectal polyps, focusing on the clinicopathological features of serrated adenoma (SA), mixed polyp (MP) and the recently recognized sessile serrated adenoma (SSA). METHODS AND RESULTS: Eight hundred and ninety-one conventional adenomas (AD), 298 hyperplastic polyps (HP), 27 SSA, 10 MP and 24 traditional SA were obtained from patients during colonoscopic examination. SSA were more likely to be proximally located than other polyps. All SA, MP and SSA and a randomly selected subset of HP (n = 61) and ADs (n = 93) were assessed for expression of mucin, MLH1, MGMT, and Ki67. SSA expressed more MUC5AC than either HP or SA. Loss of MLH1 was not observed in any serrated polyps and in only one AD. Loss of MGMT occurred in 13% of AD, and showed no correlation with histological type, size or location. Loss of MGMT occurred in 24% of SSA, MP and SA (combined), and was more frequent in proximal lesions and larger lesions. SSA had a higher proliferative index than HP. In MP, the proliferative index of the non-dysplastic component was closer to HP than SSA, while the dysplastic component was intermediate between SA and AD. CONCLUSIONS: SSA differ from other serrated polyps of colorectum in terms of location, morphology and immunophenotype.

Adenoma↗

PubMed2005

Thallium-201 chloride (Tl-201) accumulation and Na+/K+-ATPase expression in tumours of the head and neck.

OBJECTIVES: The purpose of this report was to evaluate the relationship between the tumour retention index of thallium-201 chloride (Tl-201) scintigraphy and the Na+/K+-ATPase expression in tumours of the head and neck. METHODS: Tl-201 scintigraphy was performed in 146 patients (129 with malignant tumours, ten with benign tumours and seven with inflammation). The tumour retention index was obtained from the early and delayed dynamic Tl-201 scans. The Na+/K+-ATPase expression was evaluated immunohistochemically in 61 of 129 patients with malignant tumour. Furthermore, another 22 patients with benign tumour were evaluated immunohistochemically as a benign control. Comparison of the correlations between the grade of histopathological differentiation of tumour, the tumour retention index of Tl-201 scintigraphy and the Na+/K+-ATPase expression was performed. RESULTS: The grade of histopathological differentiation of tumour, the tumour retention index of Tl-201 scintigraphy and the expression of Na+/K+-ATPase showed a good correlation indicating that Na+/K+-ATPase plays an important role in transportation for Tl-201 to go through the tumour cell membrane. CONCLUSIONS: Na+/K+-ATPase is one of the most important factors for Tl-201 accumulation in tumour.

Adenocarcinoma↗

PubMed2005

Expression of permeability-glycoprotein (P-gp) and uptake of technetium-99m-hexakis-2-methoxy-isobutyl-isonitrile (99Tcm-MIBI) in malignant tumour of the head and neck.

OBJECTIVES: The purpose of this study is to estimate the role of permeability-glycoprotein (P-gp) in the technetium-99m-hexakis-2-methoxy-isobutyl-isonitrile (99Tc(m)-MIBI) scintigraphy. METHODS: 71 patients with squamous cell carcinoma (39 patients with well differentiated, 19 with moderately differentiated and 13 with poorly differentiated tumour) were examined. Eighteen of these patients underwent 99Tc(m)-MIBI scintigraphy (early and delayed scans). The tumour retention index, obtained from the ratio of the accumulation of the delayed scan to that of the early scan, was divided into three groups. The immunohistochemical evaluation of P-gp expression was performed in all 71 patients. Levels of the P-gp expression were classified into three grades (score 0, 1 and 2). Correlations among the tumour retention index, the P-gp expression and the tumour tissue differentiation were evaluated. RESULTS: 17 of 18 patients showed a decreasing of the tumour retention index ranging from 0.70 to 0.93 (mean+/-SD=0.850+/-0.071). The tumour retention index showed a statistical correlation with the P-gp expression and the tumour tissue differentiation (chi-squared=7.802>7.779, P=0.10 and 16.835>14.860, P=0.005, respectively). Moreover, there was a statistical correlation between the P-gp expression and the tumour tissue differentiation (chi-squared=14.863>14.860, P=0.005). CONCLUSION: There is a possibility that the P-gp expression is high in the high-grade malignant tumours and P-gp causes the decrease of tumour retention index.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

A trial for histopathological subclassification of papillary cystadenoma lymphomatosum by 99Tcm-pertechnetate in a patient with multiple bilateral lesions of the parotid glands.

OBJECTIVES: The purpose of this report was to evaluate the possibility of subclassification of papillary cystadenoma lymphomatosum (PCL) with 99Tc(m)-pertechnetate. METHODS: A patient with multiple bilateral PCLs in the parotid glands was examined by using 99Tc(m)-pertechnetate. RESULTS: All PCLs of the present case, which were diagnosed as the subtype-II histopathologically, showed similar radioactive indexes in scintigraphy (the mean radioactive index = 3.62), although tumours were different in size. The mean radioactive index corresponded well with that from four cases of subtype-II of our previous report (the mean radioactive index = 3.84). CONCLUSIONS: The results of the present report suggest a possibility of histopathological subclassification of PCLs into subtypes by 99Tc(m)-pertechnetate scintigraphy.

Adenolymphoma↗

PubMed2004

Mucin expression in pleomorphic adenoma of salivary gland: a potential role for MUC1 as a marker to predict recurrence.

BACKGROUND: Pleomorphic adenoma of the salivary gland (PA) is essentially a benign neoplasm. However, patients with recurrent PA are difficult to manage. There are rare reports on useful immunohistochemical markers to detect a high risk of recurrence when the primary lesions are resected. AIMS: To find a new marker to predict the recurrence of PA. METHODS: Primary lesions of PA were collected from nine patients showing subsequent recurrence and from 40 patients without recurrence during at least 10 years of follow up of the disease. Paraffin wax embedded tumour samples of the two groups were examined for the expression profiles of MUC1 (differentially glycosylated forms), MUC2, MUC4, MUC5AC, and MUC6 using immunohistochemistry. Several clinicopathological factors were also examined. RESULTS: In univariate analysis of the factors examined, MUC1/DF3 high expression (more than 30% of the neoplastic cells stained) in the primary lesions was seen more frequently in patients with recurrence (four of nine) than in those without recurrence (three of 40; p = 0.011). Larger tumour size (more than 3.0 cm) of the primary PA was also a significant (p = 0.035) risk factor for the recurrence of PA. In multivariate analysis, only high expression of MUC1/DF3 was found to be a significant independent risk factor for the recurrence of PA (p = 0.021). CONCLUSIONS: Expression of MUC1/DF3 in PA is a useful marker to predict its recurrence. Those patients with PA showing positive MUC1/DF3 expression should be followed up carefully.

Adenoma, Pleomorphic↗

PubMed2003

Both gene expression for orotate phosphoribosyltransferase and its ratio to dihydropyrimidine dehydrogenase influence outcome following fluoropyrimidine-based chemotherapy for metastatic colorectal cancer.

Activation of 5-fluorouracil into its nucleotides requires phosphorylation by three pathways involving orotate phosphoribosyl-transferase (OPRT), uridine phosphorylase (UP), or thymidine phosphorylase (TP). In this study, we investigated the association between gene expressions of these three enzymes and antitumour effect. Gene expressions in primary colorectal tumours were analysed by a real-time reverse transcriptional-polymerase chain reaction method in 37 patients receiving oral treatment of tegafur-uracil and leucovorin for metastatic diseases. The median values of OPRT mRNA expressions were 1.39 and 0.85 for responding tumours and nonresponding tumours, respectively, showing a statistically significant difference (P=0.0008). Responding tumours had statistically lower expressions of TP mRNA than nonresponding tumours (P=0.006). However, there was no difference in UP mRNA expression between responding and nonresponding tumours. Patients with high OPRT (>/=1.0) gene expression survived longer than those with low OPRT (<1.0) expression. Dihydropyrimidine dehydrogenase (DPD) gene expressions were measured. Responding tumours had a statistically higher OPRT/DPD ratio than the nonresponding ones (P=0.003). When the median value of the OPRT/DPD ratio was selected as the cutoff value, patients with a high OPRT/DPD ratio survived statistically longer than those with a low ratio (P=0.0014). In conclusion, both the expression of OPRT gene and the OPRT/DPD ratio might be useful as predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy for metastatic colorectal cancer.

Adult↗

PubMed2002

Secretory carcinoma of the breast: a tumour analogous to salivary gland acinic cell carcinoma?

AIMS: Acinic cell-like breast carcinoma is a newly recognized entity, and few acinic cell-like breast carcinoma cases have been reported. All reported acinic cell-like breast carcinomas were counterparts of the solid type of acinic cell carcinoma of the salivary gland. We report here three cases of secretory breast carcinoma with acinic cell differentiation, and discuss the similarity between secretory breast carcinoma and acinic cell carcinoma of the salivary gland. METHODS AND RESULTS: The cases were histologically identical to acinic cell carcinoma of the salivary gland: papillary-cystic type in case 1, a mixture of papillary-cystic, microcystic and follicular type in case 2, and microfollicular type in case 3. Immunohistochemically, the tumour cells were positive for salivary-type amylase, lysozyme, S100 protein and alpha 1-antitrypsin, and negative or less reactive for gross cystic disease fluid protein-15 and oestrogen receptor. All three cases did not reveal metastasis or recurrence. CONCLUSIONS: These cases were typical of secretory breast carcinoma, and were clinically, histologically and immunohistochemically analogous to acinic cell carcinoma of the salivary gland. We emphasize that secretory breast carcinoma and acinic cell carcinoma of the salivary gland may be identical lesions.

Adult↗

PubMed2002

Hypoxia and etanidazole alter radiation-induced apoptosis in HL60 cells but not in MOLT-4 cells.

PURPOSE: To examine how hypoxia influences ionizing irradiation-induced apoptosis in cultured mammalian cells and how a hypoxic cell radiosensitizer sensitizes apoptosis under hypoxic conditions. MATERIALS AND METHODS: Two cell lines derived from human lymphocytes, HL60 and MOLT-4, were exposed to 15 Gy X-rays under aerobic and hypoxic conditions. Etanidazole was used as a hypoxic cell radiosensitizer. The apoptotic morphological changes of nuclei and the induction of ladder-like DNA fragmentation were assessed by fluorescence microscopy and agarose gel electrophoresis, respectively. RESULTS: In HL60 cells, apototic cell death and the activation of caspases 8, 9 and 3 were less induced under the hypoxic conditions than under the aerobic ones. Treatment of hypoxic cells with etanidazole enhanced X-ray-induced apoptosis and caspase activation. However, in MOLT-4 cells, neither hypoxia nor etanidazole influenced X-ray-induced apoptosis and caspase activation. In both cell lines, the frequency of X-ray-induced DNA double-strand breaks (DSB) under hypoxia was significantly smaller than that in aerobic conditions. Treatment of hypoxic cells with etanidazole enhanced them. CONCLUSION: These results suggested that X-ray-induced apoptosis in HL60 cells was initiated by DNA DSB and the treatment of hypoxic cells with etanidazole sensitized them through the enhancement of DSB induction, whereas X-ray-induced apoptosis in MOLT-4 cells occurred through damage other than to DNA.

Apoptosis↗

PubMed2001

Depth of invasion parallels increased cyclooxygenase-2 levels in patients with gastric carcinoma.

BACKGROUND: Nonsteroidal anti-inflammatory drugs may reduce the incidence of intestinal carcinoma, presumably through inhibition of cyclooxygenase-2 (COX-2). The authors correlated tumor expression of COX-2 with clinicopathologic features in tissues from patients with gastric carcinoma. METHODS: Thirty-three surgical specimens, including carcinomas and corresponding noncancerous mucosa, were sampled. Reverse transcription-polymerase chain reaction analysis was performed concomitantly for COX-1 and COX-2. A COX-2 index was determined from the band density ratio of COX-2 to constitutively expressed COX-1. Immunohistochemical staining with COX-2 antibody and routine histologic assessment were performed in the same specimens. RESULTS: The COX-2 index in gastric carcinoma was significantly higher than in normal mucosa (3.4 +/- 0.7 vs. 2.2 +/- 0.7; P < 0.05). COX-2 indices were significantly higher in gastric carcinoma tissues with deep invasion; indices for pT1, pT2, pT3, and pT4 carcinomas were 0.8 +/- 0.3, 2.8 +/- 0.5, 4.3 +/- 1.0, and 8.8 +/- 5.5, respectively (P < 0.05). Immunohistochemistry demonstrated COX-2 protein diffusely in the cytoplasm of tumor cells but not in surrounding stroma or in noncancerous mucosa. CONCLUSIONS: COX-2 mRNA expression in gastric carcinoma tissue is correlated closely with depth of invasion, indicating that COX-2 is involved in the growth of gastric carcinoma.

Adenocarcinoma↗

PubMed2001

Aryl hydrocarbon receptor (AhR)-mediated induction of xanthine oxidase/xanthine dehydrogenase activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an environmental contaminant, induced xanthine oxidase and xanthine dehydrogenase (XO/XDH) activities, in addition to ethoxyresorufin-O-dealkylase and methoxyresorufin-O-dealkylase activities in liver of mice. When TCDD was given to mice as a single oral dose of 40 microg/kg, the activities of XO and XDH increased about threefold within 3 days and the increased levels were maintained for 4 weeks. The treatment of mice with 3-methylcholanthrene also induced XO/XDH activities, but phenobarbital and dexamethasone had no effect. The level of aldehyde oxidase, a molybdenum flavoenzyme related to XO/XDH, in mouse liver was also enhanced about 1.5-fold by TCDD treatment. The inducing effect of TCDD and 3-methylcholanthrene was not observed in null mice (AhR(-/-)), which lack the AhR gene. XO and XDH activities were induced by TCDD in heterozygous mice (AhR(+/-)). The lipid peroxidation in liver was stimulated by TCDD. The induction of XO and XDH, which produces reactive oxygen species, may contribute to the various toxicities of TCDD.

Animals↗

PubMed2001

Iatrogenic implantation of malignant meningioma to the abdominal wall.

We report a case of malignant meningioma that occurred in the abdominal operation scar of a 71-year-old woman. This tumor was a 13 x 8 cm gray-tan soft tumor, consisting of multiple nodules. Histologically, tumor cells proliferated in the subcutaneous tissue, displaying mostly a storiform pattern and a focal whorl formation with high mitotic figures. The immunohistochemical positivity for epithelial membrane antigen and negativity for CD34 enabled us to differentiate this tumor from a dermatofibroma protuberance or hemangiopericytoma. The patient had a history of operation for a recurrent orbital lesion of a malignant meningioma that initially developed in the frontal skull base. The present case probably resulted from iatrogenic transplantation of the orbital malignant meningioma to the lower abdominal wall, which had served as a donor site for adipose tissue used to pack the orbital defect.

Abdominal Muscles↗

PubMed2001

Expression of cyclooxygenase-2 (COX-2) mRNA in human colorectal adenomas.

Cyclooxygenase-2 (COX-2) is an important target for the suppression of colorectal tumorigenesis by non-steroidal anti-inflammatory drugs (NSAIDs). To evaluate the role of COX-2 in human sporadic colorectal adenomas, COX-2 mRNA expression was examined by reverse transcription-polymerase chain reaction (RT-PCR) in 63 adenomas. COX-2 mRNA was detected in all the adenomas at higher levels than in normal colorectal mucosa (P<0.001). Levels of expression in the adenomas were correlated with their size (P=0.019), but no relationships were demonstrable between COX-2 expression and adenoma location, macroscopically observed configuration or microscopic degree of dysplasia. These findings suggest that COX-2 plays an important role in the growth of sporadic colorectal adenomas.

Adenoma↗