Biomedical subjects
Publications and source records attributed to T Tsunoda.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We recently developed a new model for rapid and reproducible induction of biliary carcinoma in hamsters. In the present study, we evaluated the effects of cholecystokinin (CCK), which has a trophic action on the gastrointestinal tract and on the pancreaticobiliary system, on biliary carcinogenesis in this hamster model. Hamsters treated with N-nitrosobis (2-oxopropyl) amine (BOP) were divided into four groups: In Group I, hydrolyzed gelatin, a solvent of CCK, was injected subcutaneously. In Groups II and III, CCK 2.5 and 25 microgram/kg were administered, respectively. In Group IV loxiglumide, a CCK receptor antagonist, was administered. CCK significantly promoted the carcinogenetic effect of BOP in the intra- and extrahepatic bile ducts but not in the gallbladder or pancreas. Loxiglumide exerted an inhibitory effect on carcinogenesis in the intrahepatic bile duct.
A total of 143 patients who underwent hepatic resection for hepatocellular carcinoma in our department were reviewed. The review was conducted for two periods: 1970-1982 (early period) and 1983-1990 (late period), that is, the periods before and after introduction of the hepatic surgical technique involving the use of a microwave tissue coagulator and ultrasonic dissector. One patient underwent extended lobectomy, 12 lobectomy, 9 segmentectomy, and 26 partial hepatectomy during the early period. Two patients underwent extended lobectomy, 7 lobectomy, 9 segmentectomy, 36 subsegmentectomy, and 41 partial hepatectomy during the late period. Operative mortality and hospital mortality were 16.7% and 22.9% during the early period and 1.1% and 8.4% during the late period, respectively. The overall mortality rate was significantly lower during the late period than during the early period. Postoperative complications developed in 62.5% of the patients with hepatic resection during the early period and in 48.4% of the patients during the late period. The size of tumors during the early period was significantly greater than that during the late period. Intraoperative blood loss during the late period was significantly lower than that during the early period. The survival curve was better among patients who underwent hepatic resection during the late period than among those during the early period. The satisfactory results during the late period are due to the introduction of intraoperative ultrasonography, microwave tissue coagulation, and ultrasonic dissection for hepatic surgery.
Is tumor size a predictive factor in carcinoma of the pancreas? In order to answer this question, the data of the Japan Pancreatic Cancer Registry from 1981 to 1987 were retrospectively analyzed. Of the 7687 cases that were registered, 5826 cases (75.7%) were laparotomized. Out of the 5826, 2311 (39.7%) underwent resection. Postoperative deaths within 1 mo among resected cases numbered 104, and the operative mortality rate was 4.5%. The postoperative survival rates were calculated by Kaplan-Meier's method. They clearly showed that the rates for small carcinomas (greater than 2 cm [T1]) were significantly higher than those for the tumors larger than 2 cm (T2, T3, T4) according to the Greenwood formula. Although the survival-rate calculation excluded operative deaths and deaths of causes other than pancreatic cancer, and included islet cell carcinoma, cystadenocarcinoma, and acinar cell carcinoma, it seems that tumor size may be a predictive factor for postoperative prognosis. However, our previous study on long-term survivors (more than 5 yr) after resection on the exocrine pancreatic cancer) revealed that there was no relation between the size of tumor and the postoperative prognosis. In those long-term survivors, there was no definite or severe cancerous invasion of either the retroperitoneal tissue or the portal venous system. It is concluded that a tumor 2 cm or smaller has a significantly better prognosis after resection than does a tumor larger than 2 cm, and it seems, in general, that tumor size may be a predictive factor. However, if the tumor does not invade the retroperitoneal tissue or the portal venous system, tumor size per se is not always a predictive factor.
We describe a case of pancreatic cancer in which the spread pattern of injectate during neurolytic celiac plexus block was evaluated by three-dimensional helical computed tomography. Three-dimensional images provide excellent visualization of the spread patterns of injectate in a target site, which appears to provide patients with effective relief from intractable pain.
Explore the source record for details and available documents.
Activation of the Wnt-signaling pathway is known to play a crucial role in carcinogenesis of various human organs including the colon, liver, prostate, and endometrium. To investigate the mechanisms underlying hepatocellular carcinogenesis, we attempted to identify genes regulated by beta-catenin/Tcf complex in a human hepatoma cell line, HepG2, in which an activated form of beta-catenin is expressed. By means of cDNA microarray, we isolated a novel human gene, termed MARKL1 (MAP/microtubule affinity-regulating kinase-like 1), whose expression was downregulated in response to decreased Tcf/LEF1 activity. The transcript expressed in liver consisted of 3529 nucleotides that contained an open reading frame of 2256 nucleotides, encoding 752 amino acids homologous to human MARK3 (MAP/microtubule affinity-regulating kinase 3). Expression levels of MARKL1 were markedly elevated in eight of nine HCCs in which nuclear accumulation of beta-catenin were observed, which may suggest that MARKL1 plays some role in hepatocellular carcinogenesis.
In spite of intensive and increasingly successful attempts to determine the multiple steps involved in colorectal carcinogenesis, the mechanisms responsible for metastasis of colorectal tumors to the liver remain to be clarified. To identify genes that are candidates for involvement in the metastatic process, we analyzed genome-wide expression profiles of 10 primary colorectal cancers and their corresponding metastatic lesions by means of a cDNA microarray consisting of 9121 human genes. This analysis identified 40 genes whose expression was commonly upregulated in metastatic lesions, and 7 that were commonly downregulated. The upregulated genes encoded proteins involved in cell adhesion, or remodeling of the actin cytoskeleton. Investigation of the functions of more of the altered genes should improve our understanding of metastasis and may identify diagnostic markers and/or novel molecular targets for prevention or therapy of metastatic lesions.
MOTIVATION: Precise analysis of the genetic network, gene function and transcription regulation requires accurate prediction of transcription factor (TF) bindability on DNA. For calculating the matching score between an input sequence and a set of known TF binding sites, we use positional weight matrices (PWMs) and Bucher's calculating method (Bucher, J. Mol. Biol., 212, 563-578, 1990). Since estimating TF binding sites requires cut-off values, we propose a robust cut-off value determining algorithm. RESULTS: We generalize the concept of local overrepresentation with statistics, and propose a new algorithm for determining the cut-off value using the background rate estimated on non-promoters. The algorithm iteratively determines parameters separating instances into phenomena-dependent and phenomena-independent subsets. Our system includes the method of re-estimating cut-off values of TFs that mis-recognize other TF preferred regions. Our data source comprised 433 non-redundant vertebrate promoters including viral promoters, from Eukaryotic Promoter Database (EPD) R.50. The method is applied to 205 vertebrate TFs that have frequency matrices in TRANSFAC Ver.3. 4 and the cut-off values of all of them can be determined. AVAILABILITY: The cut-off values and TF binding site predicting tool are available at http://www.hgc.ims.u-tokyo.ac. jp/service/tooldoc/TFBIND. We also provide the cut-off value estimating programs.
Sixteen long-term (more than 5 years) survivors after hepatic resection performed for hepatocellular carcinoma (HCC) from 1970 to 1988, were reviewed. The mean age of the patients was 51 years. There were 11 males and 5 females. HBs antigen was positive in 9 patients. Liver cirrhosis was associated with 11 patients but its severity was designated as Child's A in all patients except one. The mean tumour diameter was 2.8 cm and was relatively small. At the first operation, limited procedures (i.e. partial hepatectomy and subsegmentectomy) were employed in 87.5% of patients. A large percentage of tumours were located in S5 and S6 segments. A recurrence of HCC occurred in 9 patients after the first resection. A second resection was carried out in 7 patients, in 2 of which a third resection was done. Transcatheter arterial embolization (TAE) was performed on 4 patients. These results show that, in addition to detection of small tumours and early resection, repeated operation or TAE for treatment of recurrent HCC was important in achieving long-term survival after HCC resection.
To assess the postoperative outcome of jaundiced patients and to select the optimal timing for surgical intervention, indocyanin green (ICG) concentrations in the bile were measured after biliary decompression in patients with obstructive jaundice. The maximal excretion rate of ICG in the bile was calculated as a function of time (ICG Bmax). Among 59 patients with positive ICG Bmax values, morbidity was 15.2% and postoperative hospital mortality was 3.3%. However, the morbidity and mortality in nine patients with values between -0.5 and 0 were 88.8 and 44.4%, respectively. The 13 patients with in ICG Bmax below -0.5 had a 76.9% morbidity and a 61.5% mortality. The patients with ICG Bmax values below 0 showed a significantly higher morbidity and mortality than positive ICG Bmax patients. In patients showing ICG Bmax values below -0.5, surgery is contraindicated despite intensive postoperative care. The ICG Bmax value improved according to the increasing effect of biliary decompression. The index is useful not only as a prognostic index in the early phase of biliary decompression but also as an index of bile secretory capacity at a given time. By means of time course measurement of this index, the suitable time for operation can be determined. The ICG Bmax is a useful and reliable indicator in the assessment of hepatobiliary functional reserve in jaundiced patients after biliary decompression and prior to further surgical intervention.
An umbilical cord pseudocyst was detected in the 28th week of gestation in a fetus complicated with growth restriction and polyhydramnios. The combination of cord pseudocysts, growth restriction, and polyhydramnios prompted us to perform a detailed ultrasonographic examination (gray scale and three-dimensional), which revealed the presence of micrognathia, overlapping fingers, and congenital heart defects, features characteristic of trisomy 18. Karyotyping confirmed a diagnosis of trisomy 18. After spontaneous labor onset, the infant was delivered at 31 weeks of gestation, and died soon after delivery. An umbilical cord pseudocyst is a good marker for the prenatal detection of trisomy 18.
Resistance to doxorubicin (DOX) is mainly due to the effect of P-glycoprotein encoded by the multidrug resistance (MDR) gene. Cepharanthine (CEP) has been shown to circumvent multidrug resistance in P-glycoprotein-expressing cell lines. In the present study, we investigated the augmentation of DOX sensitivity by CEP using an MTT assay, and assessed the correlation between DOX sensitivity and P-glycoprotein expression by flow cytometry, in highly purified fresh human tumor cells obtained from 73 cancer patients. DOX sensitivity was decreased in proportion to P-glycoprotein expression. The cytotoxicity of DOX was increased by CEP in tumor cells possessing low DOX sensitivity. Moreover, there was a significant correlation between the effect of CEP on cytotoxicity and P-glycoprotein expression. Thus, CEP might be able to circumvent DOX resistance in cancer patients.
BACKGROUND: Intraductal papillary-mucinous carcinoma of the pancreas is a new diagnostic term proposed by the 1996 World Health Organization classification of the exocrine pancreas. So far, there have been only a few reports concerning its cytologic findings, especially in noninvasive cases. CASES: The clinical and cytohistologic findings in two cases of noninvasive intraductal papillary-mucinous carcinoma of the pancreas were reviewed. Cytologic specimens were obtained from pure pancreatic juice in the dilated main pancreatic duct during the operation (case 1) and during endoscopic retrograde pancreatography (ERP) (case 2). Both cases showed three-dimensionally or individually scattered tumor cells with an increased nuclear/cytoplasmic ratio and prominent nucleoli. CONCLUSION: Our cases suggest that pancreatic juice cytology during ERP or surgery is useful in diagnosing pancreatic cancers and that it may detect noninvasive intraductal papillary-mucinous carcinoma of the pancreas.
For clinical islet cell transplantation, short-term storage of islet cells is likely to be necessary, and it is imperative that the islet cells be kept as viable as possible during the period. However, there are little data on which preservative solutions are most suitable for the storage of islet cells after isolations or before transplantation. To estimate islet cell viability and transplantation success rate in the present study, adenylylcyclase activity was measured with a rapid new fluorometric assay in rat islet cells prior to transplantation, because cAMP plays an essential role in determining islet beta-cell viability and responsiveness to various hormonal stimuli. Adenylylcyclase activity was measured in islet cells stored for different periods of time 0, 3, 16, 24, 48, 96 h) and in different preservative solutions. Approximately 1,000 islet cells from each preservation group using University of Wisconsin (UW) solution were transplanted to streptozotocin-induced diabetes mellitus (DM) rats. Transplant success was evaluated by measuring blood glucose levels. Preoperative adenylylcyclase activity was compared with posttransplant islet cell function. The adenylylcyclase activity of UW solution was significantly higher than that of Euro-Collins solution and lactate-Ringer's solution through the different preservation time periods. Preoperative adenylylcyclase activity correlated well with posttransplant islet cell function in a rat model of DM. We conclude that adenylylcyclase activity can be used as a marker to assess islet cell viability as well as differences in preservation media and may predict islet cell transplant success.