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T Kaku

Publications and source records attributed to T Kaku.

At least 19 recordsLinked to original sources

Sclerosing stromal tumor of the ovary: a clinicopathologic, immunohistochemical, ultrastructural, and cytogenetic analysis with special reference to its vasculature.

Sclerosing stromal tumor (SST) is a rare ovarian neoplasm occurring predominantly in young women and is histologically characterized by cellular heterogeneity, prominent vasculature, and a pseudolobular appearance composed of cellular and hypocellular areas. In the current study, three cases of SST were ultrastructurally examined and the tumors were found to be composed of several kinds of cells, i.e., luteinized thecalike cells, spindle-shaped fibroblastic cells, and primitive mesenchymal cells. These findings thus supported the ovarian stromal origin of SST. Twelve cases of SST also were analyzed immunohistochemically and demonstrated an expression of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) in the luteinized thecalike cells and its receptor, fms-like tyrosine kinase 1 (flt-1), in capillary to medium-sized blood vessels. Reverse transcription-polymerase chain reaction (RT-PCR) also showed an expression of VPF/VEGF messenger RNA in SSTs. Accordingly, the characteristic vasculature and edema of SSTs were considered to be associated with the expression of VPF/VEGF. In addition, a fluorescence in situ hybridization (FISH) analysis also showed cells with three copy number of chromosome 12 in 13-21% of all examined SST cells, which suggested the presence of chromosome 12 trisomy in SSTs as well as in other ovarian stromal tumors.

Adolescent

Human placental extract stimulates liver regeneration in rats.

The effect of human placental extract (HPE) on liver regeneration in rats was investigated. After intravenous administration of HPE to a-naphthylisothiocyanate (ANIT)-intoxicated rats, the labeling index in hepatocytes was significantly increased to a level 16.5 times higher than that of the control. A 1/500 dilution of HPE directly stimulated DNA synthesis of the hepatocytes in primary culture. HPE heated at 121 degrees C did not stimulate the labeling index in vivo or hepatocyte DNA synthesis in primary culture, suggesting that HPE contains heat-unstable but potent mitogens for hepatocytes. HPE contains hepatocyte growth factor (HGF), but the mitogenic effect of HPE cannot be explained by the effect exerted by HGF alone, since both the labeling index in vivo and hepatocellular DNA synthesis in vitro stimulated by HPE were much higher than those stimulated by HGF alone when the applied doses of HGF were set to be almost the same level between each case. When HPE was fractionated on a heparin-sepharose column, the mitogenic effect of HPE was found to be located mainly in the heparin-bound fraction. Hepatocyte DNA synthesis induced by this fraction was enhanced cooperatively by the heparin-unbound fraction, suggesting that there are some modulators in the heparin-unbound fraction which enhance the proliferative activity of the heparin-bound fraction by a synergetic mechanism. Both HPE and heated HPE completely recovered the biochemical marker activity for liver function (glutamic-pyruvic transaminase, GPT; alkaline phosphatase, ALP; lactate dehydrogenase, LAP; gamma-glutamyltransferase, gamma-GTP activities and the bilirubin concentration) almost to the control level in the serum of ANIT-intoxicated rats, indicating that HPE also contains a heat-stable fraction which repairs liver function.

Animals

Tumor-associated antigen 22-1-1 expression in the uterine cervical squamous neoplasias.

We have reported that a novel tumor-associated antigen (Ag), 22-1-1, was expressed in cancer cells derived mainly from the uterus and ovary [K. Sonoda et al., Cancer (Phila.), 77: 1501-1509, 1996]. The 22-1-1 Ag existed not only in adenocarcinomas but also in squamous cell carcinomas in the uterine cervix. Here, a relationship between tumor progression and invasion and 22-1-1 Ag expression was investigated in squamous cell neoplasms of the uterine cervix using immunohistochemical staining. The 22-1-1 Ag was not detected in normal uterine cervix (0 of 10 total cases) and dysplasias (0 of 47 total cases). However, 20% of carcinoma in situ (4 of 20 total cases) and 16.7% of microinvasive carcinomas (2 of 12 total cases) stained positively for 22-1-1 Ag. Moreover, areas depicting microinvasion on histology in uterine cancers (stage Ia) were more strongly stained than carcinoma in situ lesions. 22-1-1 Ag expression was found to be more frequent in invasive squamous cell carcinomas (82.6%; 57 of 69 total cases). The 22-1-1 Ag existed both in the cytoplasm and on the membrane of cancer cells. These findings suggest that 22-1-1 Ag expression might be related to tumor cell progression and invasion in the uterine cervical squamous cell epithelium.

Antibodies, Monoclonal

Alteration of proto-oncogenes during apoptosis in the oral squamous cell carcinoma cell line, SAS, induced by staurosporine.

Staurosporine (ST) has been reported to induce apoptosis in many kinds of cultured cells. The pathway of the apoptosis induced by ST is still not clear. Certain proto-oncogene expressions have been shown to be involved in the apoptotic pathway. The present study characterized apoptosis induced by ST in the oral squamous cell carcinoma cell line, SAS, focusing on the alteration of proto-oncogene expression. SAS showed typical apoptotic features upon exposure to ST. We compared the level of gene expression in apoptosis induced by ST with that by withdrawal of serum, which is a common system to induce apoptosis. By RT-PCR analysis, ST-induced apoptosis showed c-fos and c-jun up-regulation, whereas serum withdrawal-induced apoptosis showed c-jun up-regulation and the same levels of p21/waf-1 and c-myc. These results indicate that ST can rapidly induce apoptosis in SAS, possibly via a c-fos and c-jun pathway.

Apoptosis

Angiogenesis in endometrial carcinoma.

BACKGROUND: Tumor angiogenesis is essential for tumor growth and metastases. Recently, microvessel density (MVD), a measure of tumor angiogenesis, has been found to have prognostic significance for predicting metastasis and survival in many tumor types. This study was conducted to determine how MVD was related to several clinicopathologic parameters and correlated with metastasis and survival in patients with endometrial carcinoma. METHODS: From 1979 through 1989, 85 cases of clinical Stage I and II endometrial carcinomas treated initially by hysterectomy with pelvic lymph node dissection were reviewed histologically. All hysterectomy specimens were stained immunohistologically for factor VIII-related antigen. MVD was counted in a x200 field (x20 objective lens and x10 ocular lens, 0.785 mm2 per field) in the most active area of neovascularization. Results were expressed as the highest number of microvessels identified within any single x200 field. Statistical analysis included the Mann-Whitney U test, Kruskal-Wallis test of variance, and the Spearman rank correlation test. Survival was calculated using the Kaplan-Meier method and differences in survival were analyzed using the log rank test. MVD and several other prognostic parameters were examined for their correlation with progression free survival (PFS) and overall survival (OS) by a multivariate analysis according to the Cox proportional hazards model. RESULTS: MVD was significantly correlated with tumor grade (P = 0.0281), myometrial invasion (P = 0.0282), and lymph-vascular space invasion (P = 0.0073). There was no correlation between microvessel count and lymph node status and stage. Patients with a high MVD (> or =60) had significantly worse PFS and OS than those with a low MVD (<60) (log rank test, P = 0.0116 and P = 0.0096, respectively). Multivariate analysis showed that MVD correlated significantly and independently with PFS and OS. CONCLUSIONS: In this study, MVD was found to be an independent prognostic factor for PFS and OS in patients with endometrial carcinoma.

Adult

Adenocarcinoma of the uterine cervix with predominantly villogladular papillary growth pattern.

We reviewed the clinical and pathological features of seven cases of adenocarcinoma of the uterine cervix with predominantly villogladular papillary growth pattern. The patients, who ranged in age from 33 to 54 (mean, 45) years, underwent radical hysterectomy. In all seven cases, the tumors were papillary exophytic architecture lined by stratified epithelial cells with mild to moderate nuclear atypicality. In one of seven cases, the majority of the tumor showed villogladular papillary component, but the small foci of small cell carcinoma was present in the endocervical end of the tumor. The lymph vascular invasion was demonstrated in two of seven cases, and these two had pelvic lymph node metastases. One of these two patients had recurrence 30 months after the initial treatment and died of disease after 46 months. The follow-up ranged from 9 to 169 (median, 46) months. The presence or absence of lymph vascular invasion and minor components of this tumor such as small cell carcinoma, serous cell carcinoma, and clear cell carcinoma with a poor prognosis may be important histological findings before deciding to manage this tumor by the conservative treatment.

Adenocarcinoma

Relationship between pelvic lymph node involvement and other disease sites in patients with ovarian cancer.

In 109 patients with epithelial ovarian cancer, 25 (23%) had pelvic lymph node (PLN) metastasis. Positive rates of PLN metastasis according to the clinical stage based on disease distribution except retroperitoneal lymph node were 2% for stage I, 6% for stage II, 44% for stage III, and 64% for stage IV. The nine disease sites, such as subdiaphragmatic surface, liver and spleen capsule, intestine and mesentery, omentum, pelvic peritoneum, sigmoid colon and rectum, uterus and tubes, peritoneal cytology, and paraaortic lymph node (PAN), were found to have a statistically significant relationship with PLN metastasis by univariate analysis. Multivariate analysis using a logistic regression model selected the omentum and PAN as independent factors with a statistical significance. The incidence of PLN metastasis in epithelial ovarian cancer with the above two parameters can be assumed to be greater than that without the two parameters by 42.6 times. The present data suggested that for the disease with PAN and/or omental metastasis, removal of the PLN may be mandatory from the standpoint of cytoreduction.

Adolescent

Early adenocarcinoma of the uterine cervix.

The purpose of this study was to evaluate the prognostic significance of the tumor depth, horizontal spread, and volume in early cervical adenocarcinoma while excluding adenocarcinoma in situ. Thirty cases who had been treated at our institution having cervical adenocarcinoma with a tumor depth of less than 5 mm were clinicopathologically reviewed. The volumes were estimated based on the portion with the largest tumor surface area by multiplying three dimensions: depth, horizontal spread, and a third dimension. The third dimension was calculated by the method of Burghardt to be 1.5 times the largest measured depth or spread. Two of the 30 patients recurred in the vagina at 18 and 163 months after the initial operation; the former patient died of disease 87 months postoperatively. The remaining 28 patients are all doing well without recurrence (range of follow-up from 24 to 232 months; median 79 months). No pelvic or paraaortic lymph node metastases were seen in 25 and 22 cases, respectively. None of the 21 cases with a lesion measuring less than 3 mm in depth had recurrence. On the other hand, 1 of 23 with a tumor volume up to 500 mm3 had recurrence. The estimated 5-year progression-free survival rates for patients with cervical adenocarcinoma with a depth of less than 3 mm and those with a depth of more than 3 mm were 100 and 88.89%, respectively (P = 0.116). The depth of stromal invasion may therefore be a good predictor of lymph node metastasis and recurrence in early cervical adenocarcinoma.

Adenocarcinoma

The significance of peritoneal cytology in uterine cervix and endometrial cancer.

OBJECTIVE: The purpose of this study was to determine the incidence of positive peritoneal cytology and to elucidate the prognostic value of peritoneal cytology in patients with uterine cervix and endometrial cancer. MATERIALS AND METHODS: The incidence of positive peritoneal cytology was investigated in 642 patients including 339 uterine cervix and 303 endometrial cancers. Survival was estimated by the Kaplan-Meier method in a subgroup of 116 stage II cervix and 199 stage I endometrial cancers, and multivariate analysis using Cox's proportional hazards model was used to identify an independent prognostic factor. RESULTS: The incidence of positive peritoneal cytology was found to be 9% in uterine cervix cancer and 15% in endometrial cancer. The incidence was higher in patients with some clinicopathologic status such as advanced stage, lymph node metastasis, ovarian metastasis, and deeper myometrial invasion. The 5-year survival rate for patients with positive or negative peritoneal cytology was 44 or 80% in stage II cervix cancers and 80 or 92% in clinical stage I endometrial cancers, respectively. Multivariate analysis revealed that independent prognostic determinants were pelvic and paraaortic lymph node metastasis and peritoneal cytology in stage II cervix cancer and peritoneal cytology in stage I endometrial cancer. Proper treatment protocol should be scheduled for patients with positive peritoneal cytology.

Endometrial Neoplasms

Changes in the expression of gap junction proteins (connexins) in hamster tongue epithelium during wound healing and carcinogenesis.

We examined changes in the expression and localization of connexin proteins and transcripts by means of immunofluorescence and in situ hybridization in normal conditions, wound healing and carcinogenesis using hamster tongue epithelium, in which differentiation, migration and growth of keratinocytes takes place physiologically and pathologically. In normal hamster tongue epithelium, immunofluorescent staining showed that Cx26 and Cx43 proteins were localized differently during differentiation of keratinocytes, but in in situ hybridization, the localization of Cx26 and Cx43 transcripts overlapped considerably, suggesting that the different localization of Cx26 and Cx43 proteins in squamous epithelium is largely regulated at post-transcriptional levels. During wound healing, the expression and localization of connexin proteins and transcripts were changed drastically. Shortly (6 h) after injury the expression of Cx26 and Cx43 proteins decreased at wound edges, but by 1-3 days after injury the expression of both proteins increased and both proteins co-localized to the same spots in the epithelium near wound edges. During carcinogenesis, the increased expression of Cx26 and Cx43 proteins and their transcripts and co-localization of both proteins occurred in papillomas, and the expression of Cx26 was reduced as cancer cells became morphologically less differentiated. We also found, that during wound healing in papillomas, squamous cell carcinomas and keratinocytes, Cx26 and Cx43 proteins were localized aberrantly in the cytoplasm, especially around nuclei, rather than on plasma membranes. These results indicate that quantitative and qualitative changes in connexin expression are associated with differentiation, migration and proliferation of keratinocytes in squamous epithelium.

Animals

Basaloid-squamous cell carcinoma of the floor of the mouth: characterization of a cell line.

Since it was first described in 1986, basaloid-squamous cell carcinoma (BSC) has been considered a distinct variant of squamous cell carcinoma that occurs in a variety of anatomic sites, including the head and neck region. We report the characterization of the first cell line established from a basaloid-squamous cell carcinoma of the floor of the mouth. The cell line exhibited a highly invasive capacity, indicating that BSC has very aggressive behavior. This cell line may be a useful model for elucidation of the biological characteristics of BSC.

Actins

Long-term treatment of indomethacin reduces vertebral bone mass and strength in ovariectomized rats.

We investigated the effect of the long-term treatment of indomethacin, on lumbar spinal bone mineral density (LSBMD), cancellous bone mass, structure, and strength of vertebral body in old ovariectomized (OVX) rats. Ten-month-old female Wistar rats were divided into five groups: the sham operated + vehicle (sham + VEH) group, the OVX + vehicle (OVX + VEH) group, the OVX + indomethacin (IN) 1.5 mg/kg/week (OVX + IN1.5) group, the OVX + IN 6.0 mg/kg/week (OVX + IN6.0) group, and the OVX + IN 15.0 mg/kg/week (OVX + IN15.0) group. IN or vehicle were given by subcutaneous injection (s.c.) three times per week. The treatments were started at 1 week after operation and continued for 24 weeks. LSBMD (L2-L5) was measured at 0, 12, and 24 weeks after the beginning of treatment. At the end of the experimental period, the animals were sacrificed, and bone histomorphometrical and biomechanical analysis of lumbar vertebral body were done. LSBMD, trabecular bone volume (BV/TV), and trabecular thickness (Tb.Th) decreased significantly in a dose-related manner with IN. In the OVX + IN15.0 group, LSBMD decreased by 12.7%, BV/TV decreased by 65.5%, and Tb.Th decreased by 32.8%, compared with the OVX + VEH group. In addition, the maximum stress in a compressive mechanical test of L4 vertebral body in OVX groups was also decreased in a dose-related manner with IN, and this value in the OVX + IN15.0 group was 31.3% lower than in the OVX + VEH group. We conclude that long-term treatment with IN accentuated the OVX-related decrease in trabecular bone mass and the compressive strength of lumbar vertebrae.

Analysis of Variance

[Benefit of monitoring the level of blood flecainide acetate in an elderly patient with ventricular premature contractions].

A 67-year-old woman without organic heart, disease had symptomatic ventricular premature contractions. Because class Ia, Ib and IV antiarrhythmic drugs did not prevent the premature contractions, the patient was treated with flecainide acetate at a dose of 50 mg t.i.d. Adverse reactions were noted. After measurement of the blood drug level, the dose was reduced to 50 mg b.i.d. The adverse reactions disappeared, and the arrhythmia was controlled. Flecainide acetate has a relatively long blood elimination half-life and a narrow safety margin. When some antiarrhythmic drugs are used in elderly patients, blood drug level monitoring is useful in preventing adverse reactions and in designing appropriate therapy.

Aged

Adenosine transport inhibitors enhance high K(+)-evoked taurine release from rat hippocampus.

We examined the effects of Ca(2+)-free medium containing 20 mM Mg2+, a non-selective adenosine receptor antagonist, theophylline, and adenosine transport inhibitors, dipyridamole and nitrobenzylthioinosine, on high K(+)-evoked spreading depression, glutamate, and taurine release from the rat hippocampus using brain microdialysis. High K+ alone perfusion evoked spreading depression and increased glutamate release followed by taurine efflux. Perfusion of Ca(2+)-free medium with high K+ never evoked spreading depression and decreased the high K(+)-evoked taurine release. Perfusion of theophylline (1 mM) increased the occurrence of high K(+)-evoked spreading depression and glutamate release, but did not modify taurine release. In contrast, simultaneous perfusion of dipyridamole (100 microM) and nitrobenzylthioinosine (50 microM) reduced the occurrence of spreading depression and the high K(+)-evoked glutamate release, but enhanced significantly the taurine efflux. These findings suggest that endogenous taurine with adenosine may have neuroprotective actions against high K(+)-evoked glutamate release and spreading depression in the rat hippocampus, in addition to its osmoregulatory action.

Adenosine

A novel tumor-associated antigen expressed in human uterine and ovarian carcinomas.

BACKGROUND: A large number of monoclonal antibodies (MoAbs) against human tumor cells have been generated and it has been shown that these MoAbs are useful tools in the diagnosis and treatment of cancer patients, as well as in the basic investigation of the oncogenesis and characterization of cancer cells. METHODS: The 22-1-1 MoAb was established by cell fusion between mouse myeloma cells and spleen cells derived from mice immunized with the human uterine cervical adenocarcinoma cell line, SiSo. The tissue distribution and biologic characteristics of the 22-1-1 antigen (Ag) were examined. RESULTS: The 22-1-1 Ag was distinct from the known tumor-associated antigens such as YH 206, GA 733, CA 125, carcinoembryonic antigen, and sialyl Le(x) molecules in an expression pattern in human tumor cell lines. An immunohistochemical study revealed that 22-1-1 Ag was expressed in 87.5% of uterine cervical adenocarcinomas, 66% of uterine endometrial adenocarcinomas, and 58.8% of ovarian carcinomas. Moreover, 22-1-1 Ag was detected in 87.7% of uterine cervical squamous cell carcinomas; however, it was not detected in 87.7% of uterine cervical or ovarian tissues, except in uterine endometrial glands, in which its expression was observed at low levels. The 22-1-1 Ag was secreted into cell culture supernatant fluids and was also detected in the vaginal discharges of uterine cervical carcinoma patients. The antigenic epitope of 22-1-1 Ag was shown to be a protein with a molecular weight of 78 kilodaltons using sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. CONCLUSIONS: The 22-1-1 MoAb reactive to a novel tumor-associated antigen was generated. This Ag was expressed in cancer cells derived mainly from the uterus and ovary. Moreover, 22-1-1 Ag was associated in the vaginal discharges of uterine cervical carcinoma patients. 22-1-1 MoAb is a potential tool for the study of oncogenesis and the management of cancer patients.

Adenocarcinoma

Endometrial carcinoma associated with hyperplasia.

The aim of this study was to clarify the relationship of endometrial hyperplasia to endometrial carcinoma. From 1979 through 1990, 115 cases of stage I-IV endometrial carcinomas treated initially by hysterectomy were reviewed histologically. Forty-two of 115 (36.3%) patients had hyperplasia in the endometrium adjacent to the carcinoma. Women with both endometrial carcinoma and hyperplasia were significantly younger than those with carcinoma without hyperplasia (P < 0.05). In a comparison of patients with carcinoma without hyperplasia, those with hyperplasia were better differentiated (P = 0.0072), and lacked deep myometrial invasion (P < 0.0001), cervical involvement (P = 0.0192), lymph-vascular space invasion (P = 0.0102), and para-aortic lymph node metastases (P = 0.0434). The presence of endometrial metaplasia (P = 0.0001). The estimated 5-year survival rates for patients with carcinoma with hyperplasia and those with carcinoma without hyperplasia were 96.55 and 73.33%, respectively (P = 0.0016). In endometrial carcinomas, the presence of endometrial hyperplasia may demonstrate a more favorable prognosis.

Adult

Reconstruction of the posterior inferior cerebellar artery in the treatment of giant aneurysms. Report of two cases.

Two techniques of revascularizing the posterior inferior cerebellar artery (PICA) during aneurysm surgery are presented. One involves transposition of the PICA to the vertebral artery proximal to the aneurysm using a superior temporal artery (STA) as a graft. This is used in cases in which the PICA has branched off from the wall of the giant vertebral artery aneurysm. The other technique involves end-to-end anastomosis of the PICA after excision of a giant distal PICA aneurysm located at the cranial loop near the roof of the fourth ventricle. The reconstructions of the PICA described here are surgical procedures designed to preserve normal blood flow in the PICA in patients treated for giant aneurysms involving that artery.

Aged