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Biomedical subjects

T Shimura

Publications and source records attributed to T Shimura.

At least 19 recordsLinked to original sources

Chondroblastoma of the temporal bone.

A rare case of chondroblastoma arising from the temporal bone that occurred in a 60-year-old woman is reported. The tumor appeared well demarcated and osteolytic on the radiographs. CT scan clearly depicted marginal and central calcification in the tumor. MR imaging demonstrated two components in the tumor: a solid component with predominantly low signal intensities on both T1- and T2-weighted sequences, and a multilocular cystic component with T1- and T2-elongation and fluid-fluid levels on the T2-weighted images. Postcontrast MR imaging revealed marked enhancement in the solid component and the septa of the cystic component.

Chondroblastoma↗

Animal model of para-aortic lymph node metastasis.

The purpose of this study was to establish a model of experimental lymph node metastasis by intra-rectal implantation of human cancer cells in nude mice. Four types of human cancer cell lines (TE-1, MKN-45, HT-29, and MIAPaca-2) were investigated. Tumor cells suspended in Matrigel were injected into the submucosal layer of the rectum. All cancer cell lines produced locally aggressive rectal tumors and, subsequently, para-aortic lymph node metastasis. We were unable to produce other distant metastases in the dying state in such locations as the liver, spleen, lung, and peritoneum. However, using this method, we were able to evaluate the effect of the anti-cancer agent uracil/tegafur (UFT) on primary tumor growth and lymph node metastasis. Oral intake of UFT significantly suppressed implanted tumor volume and inhibited lymph node metastasis. We expect that the process of lymph node metastasis shown in this model will be studied as an experimental model of lymph node metastasis simulating human cancers.

Adenocarcinoma↗

Significance of contracted cholecystitis lesions as high risk for gallbladder carcinogenesis.

A precancerous change has been identified incidentally in resected specimens from patients who have undergone cholecystectomy. We focused on chronic cholecystitis, showing a thick and sclerotic wall caused by recurrent inflammation, e.g. contracted cholecystitis, and examined the malignant potential of these lesions. We studied 88 patients who had undergone cholecystectomy. Contracted cholecystitis was diagnosed, using our criteria, in 28 of these cases. Ordinary chronic cholecystitis was diagnosed in 50 cases and gallbladder carcinoma in ten cases. We examined the expression of p53, Ki-67, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) immunohistochemically. Severe dysplasia or carcinoma in situ in a very small portion of the specimen was identified with hematoxylin-eosin staining in four cases (14.3%) of contracted cholecystitis. These specimens revealed a positive expression of not only p53, but also Ki-67, iNOS, and COX-2. Statistical significance was shown among the three disease groups in terms of the incidence of p53 overexpression, respectively (P<0.05). The results of this study suggest that contracted cholecystitis could be an early change leading to carcinogenesis.

Cholecystitis↗

A novel ligation forceps can be used as a ligature carrier and knot pusher during laparoscopic surgery.

BACKGROUND: To extend the usefulness of laparoscopic operations, a secure and easy method for the ligation of large vessels is needed. Herein we describe a novel ligation forceps that can be used as a ligature carrier and knot pusher. METHODS: A 2-0 suture thread with a knot already tied near one end is hooked in the upper jaw of a novel ligation forceps. After the lower jaw is passed under the vessel or cystic duct, the forceps is closed. When one end of the thread is withdrawn, the knot is trapped in the indentation built into the lower jaw; the ligature is then passed under the pedicle. An extracorporeal ligation can then be performed continuously by the same forceps. RESULTS: The origins of large vessels were ligated safely and easily with this device during 65 laparoscopic procedures (four total colectomies, 12 colectomies, and 49 gastrectomies). Following temporary hemostasis of accidental bleeding with clamping forceps, ligation hemostasis can also be performed using this instrument. CONCLUSION: This novel ligation forceps permits the secure ligation of vessels or a cystic duct without the need for another device. The proposed method is both easy and inexpensive.

Gastrectomy↗

A case of solitary fibrous tumor of the meninges.

We report a rare case of solitary fibrous tumor (SFT) of the meninges of the posterior fossa presenting as an intracerebellar hemorrhage. A 29-year-old woman was admitted with sudden-onset severe headache, nausea, and vomiting. A computed tomographic (CT) scan of the brain revealed an intracerebellar hemorrhage 3.5cm in diameter. Gadolinium-enhanced magnetic resonance imaging (MRI) showed a heterogeneous enhancement mass. A posterior craniotomy found a firm, highly vascular tumor attached to the meninges. Histologically, the tumor showed mostly sclerotic tissues with spindle cells. In few areas, the tumor had a more compact arrangement of spindle-shaped cells with vascular spaces and highly cellular components. Immunohistochemical study revealed strong CD-34 immunopositivity in many tumor cells. The tumor was diagnosed as SFT of the meninges. We report the clinical and histological features of this newly described tumor with a heterogeneous component.

Adult↗

Clinical significance of soluble form of HLA class I molecule in Japanese patients with pancreatic cancer.

In recent studies a soluble form of human leukocyte antigen class I (sHLA-I) has been found in blood, urine, ascitic fluid, and various other tissues. Research has been focused on the role of sHLA-I in the induction of immunotolerance in organ transplantation. To examine the role of sHLA-I in the immune system of patients with malignancy, we examined serum sHLA-I levels in patients with pancreatic, biliary, hepatic malignancy, and other diseases. We examined sHLA-I levels in the sera of patients with pancreatic cancer (n = 19), benign biliary disease and chronic pancreatitis (n = 20), hepatocellular carcinoma (n = 51), gallbladder cancer (n = 6), cholangiocellular carcinoma (n = 6), and in normal controls (n = 22), using enzyme-linked immunosorbent assay (ELISA). In patients with pancreatic cancer we also analyzed the relationship between sHLA-I and CA19-9, and the specificity and sensitivity of sHLA-I. When patients with acute or chronic hepatitis were excluded from analysis, the mean sHLA-I level in patients with pancreatic cancer was significantly higher than that of normal controls (p < 0.01) and patients with benign disease (p < 0.01), hepatocellular carcinoma (p < 0.01), gallbladder cancer (p < 0.05), and cholangiocarcinoma (p < 0.05). We determined a serum sHLA-I cutoff level for normal controls of 2000 ng/ml; serum levels of sHLA-I were higher than the cutoff in ten patients with pancreatic cancer, and serum levels of CA19-9 were lower than 37 IU/l in 9 of 14 patients; sensitivity and specificity were 88.2% and 85.5%, respectively. Serum levels of sHLA-I in pancreatic cancer patients were higher than in the other diseases, although we found that pancreatic cancer cell lines did not produce the sHLA-I. The evaluation of serum sHLA-I levels could have clinical significance in pancreatic cancer.

Biomarkers↗

Effect of duodenectomy on gastric motility and gastric hormones in dogs.

OBJECTIVE: To test the hypothesis that the duodenum is required to coordinate interdigestive insulin secretion with gastrointestinal motility and to determine whether duodenectomy alters the interdigestive cycles of plasma motilin and insulin levels and their relations to insulin secretion and motility. METHODS: Adult mongrel dogs were chronically implanted with force transducers in the stomach, duodenum, and upper jejunum to monitor contractile activity. Eight healthy mongrel dogs were divided into control and duodenectomized dogs. Insulin secretion, gastrointestinal motility, and plasma concentrations of motilin during the interdigestive period were measured in normal and duodenectomized dogs. RESULTS: After duodenectomy, no obvious phase III contractions were seen in the gastric antrum, but migrating phase III contractions were seen in the upper jejunum. The plasma motilin concentration did not fluctuate as it does in normal dogs, and remained low. After duodenectomy, insulin secretory cycles were not coordinated with either cycles of interdigestive motility or the plasma concentration of motilin. Exogenous motilin administration stimulated endogenous insulin release significantly compared with saline-treated controls. The contractile response of the stomach to exogenous motilin after duodenectomy was similar to that of intact dogs. CONCLUSIONS: Duodenectomy disrupts the relation between cycles of both interdigestive gastrointestinal motility and insulin secretion. These effects of duodenectomy may be attributable to interruption of the duodenopancreatic neural connections, hormonal abnormalities, or loss of vagus-sensitive humoral factors. The duodenum, which stores motilin, seems to play an important role in the relations between gastric migrating motor complexes and the concomitant increase of insulin secretion in fasted dogs. The mechanism responsible for the effect of motilin in both duodenectomized and normal dogs may involve a cholinergic pathway.

Animals↗

Circulating soluble Fas ligand in patients with gastric carcinoma.

BACKGROUND: The Fas/Fas ligand (FasL) system is involved in cancer cell death induced by the immune system. Most of the tumors may escape the host immune attack by imitating themselves as immune-privileged sites by overexpressing FasL. FasL is synthesized as a membrane-bound protein that can be cleaved to the soluble isoform (sFasL). The objectives of this work were to determine whether the serum concentrations of sFasL in patients with gastric carcinoma were correlated with clinicopathologic features and survival rates. METHODS: The authors examined the circulating sFasL concentration in 43 healthy people and 166 primary gastric carcinoma patients at the time of diagnosis by enzyme linked immunoadsorbent assay. The results were categorized by clinical and histopathologic variables. RESULTS: The serum sFasL levels of healthy subjects were all less than 0.1 ng/mL. Among the 166 gastric carcinoma patients, the median concentration of sFasL was 0.04 ng/mL. There were no significant differences between the healthy controls and the gastric carcinoma patients group (P = 0.738). The sFasL levels were significantly increased in patients with gastric carcinoma in a manner reflective of the disease stages such as the depth of tumor invasion, lymph node metastasis, and distant metastasis. The authors determined the cutoff value (0.08 ng/mL) as a 90th percentile of healthy controls. The survival analysis demonstrated that patients with high sFasL levels had a worse prognosis than those with low levels (P < 0.001). Multivariable analysis confirmed that the sFasL concentration was an independent prognostic indicator of overall survival (P = 0.041). CONCLUSIONS: Our results indicated that sFasL concentrations could not be a new marker for early detection of gastric carcinoma but a prognostic tumor marker for the assessment of the progression of advanced gastric carcinoma.

Adult↗

A novel model for invasion of cancer cells using the submucosal layer of the human stomach.

An in vitro model for studying the invasion mechanism of cancer cells was established using the submucosal layer of the human stomach. Submucosa prepared from a surgical specimen was maintained in an organ culture. The cytoarchitecture of the cultured submucosa remained well preserved; viability remained for over 2 weeks. When human gastric cancer cell lines MKN45, MKN74, and Kato III were seeded onto the submucosal slices, cancer cells of MKN45 and KATO III invaded the submucosa 3 days after inoculation. However, MKN74 cells were not seen in the submucosal slices. Our invasion model, which mimics the in vivo conditions of the submucosa of human stomach, may make it possible to analyze actual events of human gastrointestinal malignant cell invasion in normal submucosa in vitro. The usefulness of our invasion model lies in the choice of the submucosal layer of the human stomach as the host tissue. The histarchitecture of the submucosal slices indicates that the model has potential for studies of the mechanism of interactions between carcinoma cells and host tissue similar to interactions that may occur in vivo. Moreover, this method allows the continuous microscopic observation of cells within the living submucosa. Using this model, a novel approach to controlling the local invasion of tumor cells may lead to a promising, radical cure for these intractable neoplasms. Our model system is an in vitro model that is facile, inexpensive, and experimentally manipulative.

Adult↗

Expression of Ets-1 angiogenesis-related protein in gastric cancer.

The Ets-1 transcription factor plays important roles in invasiveness and angiogenesis. Using automated immunodetection, we investigated Ets-1 expression and tumor microvessel density (MVD) in relation to the clinical significance of gastric cancer. The MVD of Ets-1-positive tumors was higher than that of Ets-1-negative tumors, but the difference was insignificant. The survival rate of patients with high-MVD tumors was significantly poorer than those with low-MVD tumors, and the survival rate of patients with Ets-1-positive tumors was significantly poorer than that of those with negative ones. These results indicate that Ets-1 expression is a useful marker for predicting the outcome for patients with gastric cancer.

Adenocarcinoma↗

Selective elimination of acentric double minutes from cancer cells through the extrusion of micronuclei.

Several lines of evidences from us or other authors had shown that tumor cells revert their phenotypes and differentiate by the elimination of oncogenes amplified on the acentric double minutes (DMs). The selective incorporation of DMs into the cytoplasmic micronuclei was thought to be involved in this elimination, however, the mechanism by which the content of micronuclei was eliminated from the cells remains to be discovered. In this report, we show the finding and the characterization of the extruded micronuclei in the culture fluid of human COLO 320DM tumor line, and suggest that the extrusion of micronuclei mediates the selective elimination of DMs. The extracellular micronuclei enriched with DMs had an apparently normal cytoplasmic membrane, decondensed chromatin and nuclear lamin protein, and their DNA did not suffer any extensive degradation. These characteristics were closely related to their cytoplasmic counterpart and clearly differentiated from the apoptotic bodies. We also developed a method for purifying the extracellular micronuclei. In this paper, the implications of the micronuclear extrusion are discussed.

Cell Nucleus↗

A novel rapid colorimetric assay of carcinoembryonic antigen levels in the abdominal cavity to detect peritoneal micrometastasis during gastric cancer surgery.

We showed that the carcinoembryonic antigen (CEA) level in a peritoneal washing is an indicator of the postoperative survival of gastric cancer patients. On the premise that the polyvinylidine difluoride membrane adsorbs a fixed quantity of protein, this study was designed to produce a rapid, colorimetric, semi-quantitative assay of peritoneal CEA levels by using anti-CEA antibodies. At the time of laparotomy, peritoneal washings were collected from 60 gastric cancer patients, and CEA levels were determined by our assay and by an enzyme immunoassay (EIA) method. The accuracy of our method corresponded with the results of the EIA method. All the cases with high levels of CEA in the peritoneal washings showed positive color changes. Our new assay had no relation to protein concentrations of the samples. The assay makes use of diluted peritoneal washings without adaptation by protein concentration. The measurement can be completed in the operating room within 30 min. As a result, this assay can detect peritoneal microdissemination easily during surgery, and it can be used as an indication of intraoperative chemotherapy against peritoneal micrometastasis.

Abdomen↗

Loss of standard type of CD44 expression in invaded area as a good indicator of lymph-node metastasis in colorectal carcinoma.

PURPOSE: Recent advances have made possible the treatment of small invasive colorectal cancer by means of polypectomy or endoscopic mucosal resection. CD44 expression in cancer cells was identified as an indicator of lymph-node metastasis, which could be evaluated in specimens removed by colonoscopy. METHODS: The correlation between lymph-node metastasis and the expression of standard-type CD44 in cancer cells was examined immunohistologically using the invaded cancer cells of 61 tissue samples of superficially invasive colorectal cancer. We defined the above as invasive cancer restricted within the colorectal wall. Of the 61 samples, 31 had submucosal invasion and 30 had muscular invasion. RESULTS: Standard-type CD44 expression in the area of invasion in cases with lymph-node metastasis was remarkably down-regulated. In 43 cases with no lymph-node metastasis, 36 (83.7 percent) of patients had CD44 expression in invaded cells, whereas only two of 18 cases (11.1 percent) with lymph-node metastasis had expression of standard-type CD44 in the same area (P < 0.0001). A total of 69.6 percent (16/23) of patients with loss of standard-type CD44 expression in invaded sites were found to have positive metastasis in the lymph nodes. These results suggest that standard-type CD44 in invasive colon cancer cells could suppress metastasis to the regional lymph nodes. CONCLUSION: In cases of invasive colorectal cancer, the loss of standard-type CD44 expression in the invaded area is a sensitive marker for metastasis to the lymph nodes. Further investigation with larger patient groups is required to clarify the reliability of loss of standard-type CD44 expression as an indicator for additional surgery after endoscopic resection of submucosal invasive colorectal carcinoma.

Biomarkers, Tumor↗

Drug-induced apoptosis by anti-microtubule agent, estramustine phosphate on human malignant glioma cell line, U87MG; in vitro study.

The drug effect of estramustine phosphate (EMP), an anti-microtubule agent on human glioma cells has been studied with the focus being mainly its cytotoxity or its targeting of organelles. However, the pharmacological knowledge of estramustine with respect to its cytotoxity and mechanism is limited. To acquire such knowledge, the present study investigates the ability of EMP to induce apoptosis in a human malignant glioma cell line. Transmission electron microscope (TEM) images were examined to monitor periodic changes. Agarose gel electrophoresis was also examined. Cellular DNA fragmentation ELISA was performed to investigate the DNA fragmentation rates and an MTT assay was studied to evaluate the ID50. A TEM study revealed condensing and fragmentation of the chromatin. Laddering of the bands was observed in all EMP exposure groups in agarose gel electrophoresis. DNA fragmentation in all EMP groups began at 0.5 h following an exposure with EMP and increased in a dose- and time-dependent manner as revealed by DNA ELISA fragmentation. ID50 at 24 h was 5.0 microM according to the MTT assay, a value close to 4.8 microM of ID50 was revealed by the DNA fragmentation assay. None of the above mentioned changes was observed in the control group. These results indicated that EMP caused a drug-induced apoptosis in the human malignant glioma cell line, U87MG.

Antineoplastic Agents, Alkylating↗

Intracranial malignant meningioma with abdominal metastases associated with hypoglycemic shock: a case report.

A thirty-year-old male with an intracranial malignant meningioma, first diagnosed 9 years ago, with three recurrences was admitted with a hypoglycemic shock. The blood glucose level was 17 mg/dl, requiring treatment with high doses of intravenous and oral dextrose for improvement. A large metastatic tumor in the liver was noted. All hormones and peptides influencing blood glucose levels were in their normal levels. Chemo-embolization and injection of anti-cancer drugs was employed in the management of the metastatic tumor. Positron emission tomography was performed to measure the glucose metabolism of the abdominal tumor and it indicated that glucose consumption within the tumor was much elevated than the surrounding abdominal organs. Hypoglycemia secondary to primary hepatoma or islet-cell cancer has been frequently described, but a complication of metastatic meningioma is an exceedingly rare event. Elevated glucose consumption within the tumor might be addressed as one of the reasons for hypoglycemia, not due to the elevated serum levels of insulin or IGF, but due to the closely related blood glucose level.

Abdominal Neoplasms↗

Increased frequencies of gene and chromosome mutations after X-irradiation in mouse embryonal carcinoma cells transfected with the bcl-2 gene.

Preimplantation stage mouse embryos are known to be highly sensitive to the killing effect of DNA-damaging agents such as radiation. Interestingly, however, this stage of development is well protected from radiation induction of malformation and carcinogenesis in postnatal life. In recent years, it has become clear that the stem cells of preimplantation stage embryos undergo extensive apoptosis after DNA damage. It has been postulated that this apoptosis is likely to be responsible for the resistance to malformation, by excluding cells carrying deleterious DNA damage. We have tested the possible role of apoptosis in elimination of gene and chromosome mutations in undifferentiated mouse embryonal carcinoma cell line, F9, transfected with human bcl-2 cDNA. The colony radiosensitivity of F9 cells was not affected by overexpression of the bcl-2 gene, but the apoptotic cell death was suppressed, as examined by DNA ladder assay and Hoechst staining. This suppression was accompanied by an increase in the frequencies of hprt mutation and micronucleus formation after X-irradiation. These results support the idea that maintenance of genomic integrity during early development is likely to be executed by apoptotic elimination of cells at risk.

Animals↗

The effect of caffeine on p53-dependent radioresponses in undifferentiated mouse embryonal carcinoma cells after X-ray and UV-irradiations.

The effect of caffeine was studied on the radioresponses of undifferentiated mouse embryonal carcinoma cells (EC cells) with or without the functional p53. The radioresponses studied included radiosensitivity, the activation of p53, apoptosis with characteristic DNA ladder formation and cell cycle progression. An undifferentiated mouse EC cell line, ECA2, and a newly established p53-deficient EC cell line, p53 delta, were used in the present study. The status of the p53 gene did not significantly affect the colony survivals of undifferentiated EC cells to X-rays and UV. Although a post-irradiation treatment with caffeine sensitized both lines to X-rays marginally, the sensitization was prominent for UV regardless of the p53 status of the cells. The activation of a p53 responsible lacZ reporter construct was observed in stably transfected ECA2 cells after X-ray and UV irradiations. Caffeine suppressed the X-ray induced activation of the lacZ reporter, while it drastically enhanced the activation after UV irradiation. X-rays and UV readily triggered the apoptosis of ECA2 cells with the characteristic DNA ladder. Although UV-induced DNA ladder formation was enhanced by caffeine, that induced by X-rays was unaffected. Therefore, the effects of caffeine on the p53-dependent radioresponses were found to be agent specific: suppression for the X-ray induced and augmentation for the UV induced. In contrast to p53-proficient ECA2 cells, smear-like DNA degradation was observed for irradiated p53 delta cells, suggesting the presence of a mode of cell death without DNA ladder formation. UV induction of the smear-like DNA degradation was enhanced in the presence of caffeine. Regardless of the state of the p53 gene, G1/S arrest was not observed in X-ray and UV irradiated EC cells. X-ray induced G2/M arrest in both lines, which was abrogated by caffeine, while G2/M arrest after UV was unaffected by a caffeine treatment. These results indicate that the radioresponses of undifferentiated EC cells differ considerably from those of somatic cells, and that these radioresponses were modulated by a post-irradiation treatment with caffeine.

Animals↗