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Biomedical subjects

M Sowa

Publications and source records attributed to M Sowa.

At least 109 records · Page 6Linked to original sources

Alterations of O-glycan biosynthesis in human colon cancer tissues.

Human colon cancer is associated with antigenic and structural changes in mucin-type carbohydrate chains (O-glycans). To elucidate the control of the biosynthesis of these O-glycans is colon cancer, we have studied glycosyltransferase and sulphotransferase activities involved in the assembly of elongated O-glycan structures. We analysed homogenates prepared from cancer tissue, adjacent normal and distal normal tissue from 20 patients. Several transferase activities showed pronounced changes in cancer tissue. The changes correlate with previous findings of a loss of O-glycans in cancer mucins, but did not always correlate with levels of Tn, sialyl-Tn, T and Lex antigens in homogenates or with the differentiation status and Duke's stages of the cancer tissue or the patient's blood type, sex and age. UDP-GlcNAc: Gal NAc-R beta 3-N-acetylglucosaminyltransferase (where GlcNAc is N-acetyl-D-glucosamine and GalNAc is N-acetyl-D-galactosamine) synthesizing O-glycan core 3, GlcNAc beta 1-3GalNAc-, CMP-sialic acid: GalNAc-peptide alpha 6-sialyltransferase synthesizing the sialyl-Tn antigen and sulphotransferase activities towards O-glycan core 1, Gal beta 1-3GalNAc-, were found to be decreased in cancer. UDP-GlcNAc: Gal beta 1-3GalNAc beta 6-N-acetylglucosaminyltransferase was also decreased in cancer concomitant with a loss of the ability to synthesize the I antigen and core 4, GlcNAc beta 1-6(GlcNAc beta 1-3) GalNAc-, CMP-sialic acid: Gal beta 1-3GalNAc-R alpha 3-sialyltransferase and GDP-fucose: Gal beta-R alpha 2-fucosyltransferase, synthesizing the blood group H determinant, were found to be 4- and 3- to 8-fold increased, respectively, in cancer compared to normal tissue. The data suggest that the biosynthesis of antigens and mucin-bound O-glycan structures in colon cancer is subject to complex control mechanisms.

Adult↗

Effect of a new cholecystokinin receptor antagonist (KSG 504) on the early stage of the healing process in acute pancreatitis induced in rats by the closed duodenal loop technique.

Creation of a closed duodenal loop produced edematous acute pancreatitis within 6 h and hemorrhagic acute pancreatitis within 12 h in male Sprague-Dawley rats. The pancreatitis thus established tended to improve after releasing the loop. We investigated the effect of a new cholecystokinin receptor antagonist, KSG 504, on the healing process in edematous and hemorrhagic acute pancreatitis after releasing the loop. Serum amylase and lipase levels in the control group decreased gradually after releasing the loop, but the reductions were not significant. In both the group treated with KSG 504 intravenously and the group treated subcutaneously, serum amylase and lipase levels decreased markedly upon release of the loop in edematous acute pancreatitis. Furthermore, the histologic changes in edematous acute pancreatitis improved more rapidly than in the control group. However, no such biochemical or histologic evidence of improvement was observed in hemorrhagic acute pancreatitis. The new cholecystokinin receptor antagonist, KSG 504, displayed a therapeutic effect in edematous acute pancreatitis but not in hemorrhagic acute pancreatitis. These findings suggest that endogenous cholecystokinin release induced by the closed duodenal loop may have a contributory role in the development of edematous acute pancreatitis but not of hemorrhagic acute pancreatitis.

Acute Disease↗

Role of orthotopic fibroblasts in the development of scirrhous gastric carcinoma.

We examined the interaction between scirrhous gastric cancer cells and organ-specific fibroblasts in vivo and in vitro. Co-inoculation of scirrhous gastric cancer cells with gastric fibroblasts into nude mice specifically increased tumorigenicity, compared with that of gastric cancer cells alone. Furthermore, the histologic findings of the xenograft produced by co-inoculation with gastric fibroblasts was similar to that of human scirrhous gastric carcinoma. Conditioned medium from gastric fibroblasts significantly stimulated the growth of gastric cancer cells. These findings suggest that the growth of scirrhous gastric cancer cells was affected by orthotopic fibroblasts.

Adenocarcinoma, Scirrhous↗

[Establishment and characterization of a human breast cancer cell line, OCUB-1].

We established new human breast cancer cell line, OCUB-1 derived from the pleural effusion of 53-year old female with recurrent breast cancer. Two sub-cell lines were also established with cloning technique from OCUB-1. Investigating the differences of characteristics between OCUB-1M and 1F, OCUB-1M shows a monolayered growing and OCUB-1F grows in floating. OCUB-1M and 1F revealed Modo 84 and 41 by chromosomal analysis and flow cytometric analysis showed OCUB-1M had twice amount of DNAs as -1F. OCUB-1M revealed higher expression of E-cadherin and laminin receptor against-1F, and activity of 92kDa type IV collagenase could be seen only in OCUB-1M. Estorogen and progesteron receptor were negative in either OCUB-1M and -1F, and no production of tumor markers in the spent media (CEA, CA19-9, CA15-3 and NCC-ST439) was detected in both cells. Both cells could be hetero-transplanted in nude mice, but they showed different histology.

Animals↗

[Nuclear DNA ploidy pattern and proliferating cell nuclear antigen labeling index in gastric cancer with mucosal involvement].

The DNA ploidy pattern and the expression of proliferating cell nuclear antigen (PCNA) were investigated in 72 gastric carcinoma patients to determine the possible correlation between proliferation kinetics and biological behavior. The diploid pattern was more often observed in cases with mucosal invasion (m cancer) than other cases (sm or advanced cancer). The PCNA labelling index in cases with mucosal invasion was significantly lower than in other cases. The sm cancer was more often observed in patients with high PCNA labelling index (> or = 30%) and aneuploid pattern, while m cancer was more common in patients with low PCNA labelling (< 20%) index and diploid pattern. As a result of this study, we conclude that proliferating kinetics of m cancer may differ from that for sm or advanced cancer. Furthermore, DNA ploidy pattern and PCNA labelling index may be useful as a parameter of depth of invasion.

Adult↗

Biphasic effect of cell surface sialic acids on pancreatic cancer cell adhesiveness.

Partial removal of cell surface sialic acids, by enzymatic hydrolysis or by reducing sialylation, increased both adhesion to Matrigel and cellular aggregation in the pancreatic cancer cell line, SW1990. In contrast, a greater reduction in cell surface sialic acids decreased cellular adhesiveness below that of untreated cells. Cellular adhesion and homotypic cellular aggregation were enhanced by reducing O-linked glycosylation. Addition of purified SW1990 mucins reversed the effect of the inhibition of O-glycosylation. Both adhesion to extracellular matrix proteins and cellular aggregation were generally unaffected or decreased by inhibition of N-linked glycosylation. These results suggest that although certain sialic acids are required for the adhesion, sialic acids on oligosaccharides O-linked to surface glycoproteins inhibit SW1990 cellular aggregation and adhesion to the substratum.

Acetylgalactosamine↗

A flow cytometric bromodeoxyuridine/DNA analysis for cytokinetics of the pancreatic cancer cell line Capan-2 after irradiation.

The cytokinetics of the human pancreatic adenocarcinoma cell line Capan-2 were analyzed by a bromodeoxyuridine (BrdUrd)/DNA analysis with flow cytometry (FCM). The reproducibility of data was shown to be superior to that achieved using a DNA analysis program with FCM. The perturbation of cytokinetics following irradiation was examined. Bivariate distribution was able to distinguish each cell phase cohort, even following as strong an irradiation as 10 Gy, a condition for which DNA analysis proved unusable. BrdUrd/DNA analysis showed the G2M phase population after irradiation with 2 Gy to be significantly greater (P < 0.005) than that of the untreated cells. This difference was not detectable by the DNA analysis program due to the large standard deviation (SD) of the data. BrdUrd/DNA analysis has a sufficient quantitative accuracy that strongly perturbed cytokinetics in patients treated with various therapeutic agents, for example, with combined therapies, can thus be analyzed by this approach.

Adenocarcinoma↗

Diagnosis and treatment of proximal tubal obstruction by fluoroscopic transcervical fallopian tube catheterization.

The efficacy of fluoroscopic transcervical Fallopian tube catheterization in treating patients with proximal tubal obstruction was investigated. In 11 (15.9%) of the 69 patients who entered the study, patency of the proximal Fallopian tubes was shown by a pre-treatment hysterosalpingogram or an ostial selective salpingogram. Transcervical Fallopian tube catheterization attested to the success of recanalization in at least one of the obstructed tubes in 41 of our 58 patients (70.7%). Of 92 obstructed tubes, 56 (60.9%) were successfully recanalized. However, normal tubal visualization was possible in only 13 tubes (23.2%). Most of the recanalized tubes were considered to be peritubal adhesions (64.3%). Eight of 36 (22.2%) patients who had been successfully recanalized achieved pregnancies; 12 patients demonstrated normally appearing salpingograms after the procedure, and five (41.7%) had an intra-uterine pregnancy. Suspected peritubal adhesions were exhibited on post-operative salpingograms of 24 patients, one of whom had an intra-uterine pregnancy, while two had tubal pregnancies. Transcervical Fallopian tube catheterization is a simple and effective method for evaluating and treating proximal tubal obstruction. Most of the patients (70.7%) in whom recanalization was successful showed significant signs of distal tubal damage. This procedure can also be used to arrive at a prognosis regarding conception.

Adult↗

Renal microcirculation in experimental acute pancreatitis of dogs.

In order to understand the mechanism of acute renal failure frequently observed in severe acute pancreatitis, renal microcirculation and renal hemodynamics were investigated during experimental acute pancreatitis in dogs induced by autologous bile and trypsin mixture into the pancreatic duct. Renal tissue blood flow (hydrogen gas clearance method), renal arterial blood flow, and cardiac output (transonic blood flow meter) were each measured for 5 h after induction of pancreatitis. The effect on renal hemodynamics of a new synthesized protease inhibitor--E-3123; 4-(2-succinimidoethylthio)phenyl-4-quanidinobenzoate methane sulfonate--intravenously infused at the rate of 3 mg/kg/h was also investigated. The mean blood pressure and pulse pressure decreased after induction of pancreatitis. Renal microcirculation and renal artery blood flow decreased during the experiment. However, in dogs with treated by E-3123, renal microcirculation was preserved during the first hour of the experiment and decreased gradually afterward, but it was significantly higher than that of the dogs without E-3123 during 3-5 h. The mean blood pressure and pulse pressure were preserved nearly at preoperative levels during the experimental period. We concluded that renal microcirculation decreased concomitantly with a deterioration of acute pancreatitis, and that the new pancreatic protease inhibitor E-3123 may have some beneficial effect to improve renal hemodynamics in the early period of acute pancreatitis.

Acute Disease↗

Early cancer of the gastric remnant with special reference to the importance of follow-up of gastrectomized patients.

Seven patients with early cancer of the gastric remnant (group 1) and nine with gastric remnant cancer that developed after surgery for early gastric cancer (group 2) were studied clinicopathologically. In group 1, the great majority of cases were classified as type I by gross type. Most lesions existed in the posterior wall of the remnant stomach. All lesions were differentiated carcinomas. In group 2, six of the nine early gastric tumors resected at the initial surgery were present in site A and three in site M. Gross tumours were of various types. Six patients underwent Billroth II resection and two underwent Billroth I resection. At second surgery (for gastric remnant cancer) four lesions were found to be located in the gastric stump or anastomosed region and five in the posterior wall of the stomach remnant. Histologically, the lesions included four undifferentiated carcinomas and five differentiated carcinomas. Of the nine lesions involving the gastric remnant, only two were early stage: the remaining seven were in an advanced stage. Prognosis was extremely poor in the group, many patients dying of carcinomatous peritonitis. In summary, most group 1 patients had a type I lesion in the remnant stomach. In group 2, more than half of the lesions were present in the gastric stump or anastomosed site and most were in an advanced stage. These observations suggest that it is very important to follow up patients operated on for early gastric cancer in order to detect malignant lesions, if any, in the remnant stomach before disease progresses to a stage at which radical resection is no longer possible. Follow-up will no doubt improve long-term results following surgery for early gastric cancer. We consider endoscopic examination and biopsy, especially of the gastric stump and anastomosed site, of great importance for gastrectomized patients.

Aged↗

[Analysis of cell proliferation in endoscopically biopsied specimen of the stomal mucosa of the remnant stomach--with special reference to cell cycle and ODC activity].

An attempt was made to investigate the status of cell proliferation in the remnant stomach, using endoscopically biopsied specimens, with cell cycle analysis by flow cytometry (FCM) and ornithine decarboxylase (ODC) activity determination. Fifty-three partially gastrectomized patients (male 33, female 20) were examined. Their mean age was 60.5, and 22 underwent Billroth I (BI), and 30 Billroth II (B II) operation. The mean time elapsing from the initial operation was 4.0 years. Almost all specimens showed DNA diploidy by FCM. The S phase cell percentage was higher in the stomal area, especially in the B II group. Significantly higher ODC activity was recognized in the stomal mucosa especially in the B II group. A significant positive relationship was noted between postoperative duration and ODC activity in the B II group. These results suggest activated cell proliferation in the stomal area of the remnant stomach. Especially in the B II group, cell proliferation increased with time after initial operation. This activated cell proliferation may play some role in the carcinogenesis of the remnant stomach.

Biopsy↗

A case of jejunal gastrinoma diagnosed by percutaneous transhepatic portal venous sampling.

A 63-year-old male was admitted to our department for further examination of hypergastrinemia. Secretin provocation test and calcium infusion test suggested Zollinger-Ellison syndrome and percutaneous transhepatic portal venous sampling (PTPVS) demonstrated gastrinoma in the jejunum, although CT, ultrasonography and angiography could not accurately detect the location of the gastrinoma. Laparotomy findings showed a solid tumor 1.5 cm in diameter in the jejunal mesentery 5 cm distal to the ligament of Treitz, and primary gastrinoma was confirmed in the submucosa of the jejunum immediately adjacent to this tumor. An immunohistochemical study using the PAP method revealed gastrin secreting cells in the tumor. In addition to this case of jejunal gastrinoma, a review of literature in Japan and other countries was presented.

Gastrinoma↗

Flow cytometric bromodeoxyuridine/DNA analysis of hyperthermia and/or adriamycin for human pancreatic adenocarcinoma cell line Capan-2.

The effects of hyperthermia, adriamycin (ADM), and hyperthermia combined with ADM on pancreatic cancer cells were investigated from the viewpoint of cytokinetics using flow cytometric bromodeoxyuridine (BrdUrd)/DNA analysis. Human pancreatic adenocarcinoma cell line Capan-2 was used. The untreated cells could be clearly divided into G1, S, G2M phases on contour plots of BrdUrd/DNA distribution. After heat treatment at 41-43 degrees C, there was an accumulation of cells in the G2M phase which was correlated with the increase in temperature. After heat treatment at 44 or 45 degrees C, there was marked increase in non BrdUrd-labeled cells in the S phase. ADM caused no change in the percent of non BrdUrd-labeled cells in the S phase, even after treatment with a concentration of 1.0 micrograms/ml, though that concentration of ADM caused a marked increase in the percent of cells in the G2M phase. After hyperthermia combined with ADM, the accumulation of the G2M phase increased remarkably, and was significantly higher than that after each treatment alone (P less than 0.005); however, non BrdUrd-labeled cells in the S phase did not increase. In this study the synergistic effect of hyperthermia combined with ADM in increasing the percent of cells in the G2M phase could be observed by flow cytometry. The study illustrates the importance of performing in vitro flow cytometric BrdUrd/DNA analysis of combined therapy prior to the use of the combined therapy in patients.

Adenocarcinoma↗