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Biomedical subjects

S Ohwada

Publications and source records attributed to S Ohwada.

At least 91 records · Page 5Linked to original sources

c-erbB-2 status is an independent predictor of survival after first recurrence.

We studied retrospectively the interaction between c-erbB-2 overexpression and the prognosis in 239 invasive breast cancer patients who underwent radical operations between January 1984 and April 1991. The c-erbB-2 protein was overexpressed in 42 (17.6%) of 239 patients. There was no correlation between c-erbB-2 overexpression and age at operation, tumor size, lymph node involvement, or clinical stage. Only an inverse correlation was found between c-erbB-2 overexpression and hormone receptor levels. Patients with c-erbB-2 overexpression had a significantly worse overall survival than those without c-erbB-2 overexpression. In relation to lymph node involvement or estrogen receptor status, a significant difference in overall survival between the c-erbB-2-positive and -negative groups was found in patients with lymph node metastasis or in those with estrogen receptor-negative tumors. Out of 237 patients (two were lost to follow-up), 42 recurred and 25 died of breast cancer. The c-erbB-2-negative patients survived significantly longer after the time of first recurrence than the c-erbB-2-positive patients. In a multivariate analysis using Cox proportional-hazard regression model, c-erbB-2 status and disease-free interval were independent predictors of survival after first recurrence. In conclusion, c-erbB-2 status is an independent prognostic indicator of survival after first recurrence.

Biomarkers, Tumor↗

Low MIB-1 labeling index in anti-HCV positive hepatocellular carcinoma.

It has been reported that hepatitis C virus-related hepatocellular carcinoma (HCC) patients survive longer than hepatitis B virus-related patients. In this study, since HCC patients positive for anti-HCV antibody had significantly longer disease-free survival (p<0.05), we evaluated the proliferative activity of 58 resected HCCs and the status of their viral infections. Ki-67 (MIB-1) immunostaining, argyrophilic nucleolar organizer regions and c-myc gene amplification were examined as parameters of proliferation, and p53 overexpression was examined in relation to clinicopathologic features and prognosis. Thirty-nine patients with HCC (67%) were positive for anti-HCV antibody alone, five (9%) were negative for both anti-HCV and HBV antibodies, two (3%) were positive for both anti-HCV and HBV antibodies, and 12 (21%) had HBsAg alone. HCC patients with anti-HCV antibody had a lower MIB-1 labeling index (LI) than HCC patients negative for the antibody (p<0.05), irrespective of the serum HBsAg status. However, there was no significant correlation between anti-HCV antibody and other proliferative parameters. MIB-1 could simply be related to cellular proliferation. On the other hand, the other parameters may be related to tumor progression as well as proliferation. HCV-related HCC does have lower proliferative activity and a better prognosis.

Adult↗

Inhibitory effects of an antiestrogen, toremifene, on the phorbol ester-induced adhesive capacity of breast carcinoma cells.

Previous studies have revealed that protein kinase C (PKC) is responsible for malignant progression. In the present study, we investigated the potent inhibitory effects of an antiestrogen, toremifene, on PKC-mediated cellular adhesion. A phorbol ester, phorbol 12-myristate 13-acetate (PMA), significantly enhanced alpha2beta1 integrin-dependent adhesion of MCF-7 breast carcinoma cells. This PMA-induced adhesion was partially inhibited by incubating cells with toremifene prior to PMA exposure in a time- and dose-dependent manner. FACS analysis demonstrated that the PMA-induced alpha2beta1-dependent cellular adhesion was accompanied with elevated expression of alpha2beta1+integrin subunit on the cell surface. However, toremifene did not affect the elevated expression levels of these integrins but rather the avidity of alpha2beta1 integrin. We concluded that toremifene inhibited cellular adhesion activated by PMA, probably through mechanism which inhibits PKC.

Breast Neoplasms↗

[A case of multiple liver metastasis of gastric cancer responding to hepatic arterial infusion chronotherapy].

A 64-year-old man underwent total gastrectomy and placement of the hepatic arterial catheter for advanced gastric cancer with multiple liver metastasis. After the operation, repeated hepatic arterial infusion chemotherapy was performed. Treatment consisted of a 5-day course of continuous arterial infusion of 5-FU. (500 mg/body), leucovorin (21 mg/body) intravenous infusion at 4:00 p.m. on days 1-5, mitomycin C (2 mg/body) arterial infusion at 9:00 a.m. on day 5, and cisplatin (40 mg/body) arterial infusion at 4:00 p.m. on day 5. A total of 13 courses of this chemotherapy diminished liver metastasis. During this therapy, the patient's condition was good, with no experience of nausea or leukopenia.

Adenocarcinoma↗

[Advanced gastric cancer curatively resected following combined neoadjuvant chemotherapy--report of a case].

An advanced gastric cancer patient with T3N1M0 successfully underwent a curatively total gastrectomy combined with distal pancreatectomy and lymphnode dissection following ELF-P combined chemotherapy. The patient received two courses of etoposide (75 mg/m2, Day 1-5, i.v.), leucovorin (30 mg/body, Day 2-5, i.v.), 5-FU (500 mg/m2, Day 2-5, i.v.) and CDDP (60 mg/m2, Day 1, i.v.). A partial response for the primary lesion and lymphnode metastasis was obtained, and a successful curative resection of the stomach was performed. No drug adverse responses occurred. The effect of ELF-P chemotherapy was confirmed with grade 1b by histopathological examinations. Neoadjuvant chemotherapy with ELF-P may be useful as an inductive approach for advanced gastric cancer.

Adenocarcinoma↗

Cloning of a human homolog of the yeast OGG1 gene that is involved in the repair of oxidative DNA damage.

We report the cloning of a human homolog of the yeast OGGC1 gene, which encodes a DNA glycosylase that excises an oxidatively damaged form of guanine, 8-hydroxyguanine (also known as 7,8-dihydro-8-oxoguanine). Since the deduced amino acid sequence (68 amino acids) of a human expressed sequence tag, N55394, matched a short stretch of yeast OGG1 protein with greater than 40% amino acid identity, a full length cDNA clone was isolated from a HeLa cell cDNA library with the N55394 clone as a probe. The cDNA clone encodes a predicted protein of 345 amino acids which is homologous to yeast OGG1 protein throughout the entire polypeptide sequence and shares 38% amino acid identity with yeast OGG1 protein. Moreover, we found that both a human homolog and yeast OGG1 protein possess two distinct DNA binding motifs, a helix-hairpin-helix (HhH) motif and a C2H2 zinc finger like motif, and a domain homologous to human and E. coli MutY proteins. Expression of a human homolog suppressed spontaneous mutagenesis of an E. coli (mutM mutY) mutant as in the case of yeast OGG1 protein. The gene was ubiquitously expressed in a variety of human organs and mapped to chromosome 3p26.2. These results strongly suggest that the gene isolated here is a human counterpart of the yeast OGGI gene and is involved in the repair of oxidative DNA damage in human cells.

Amino Acid Sequence↗

Mucosal changes in interposed colon segment as gastric substitute following gastrectomy in rats.

BACKGROUND: An interposed colon segment has been clinically reconstructed as a gastric substitute. The purpose of this study is to establish a rat model of colonic interposition and to investigate serial mucosal changes and adaptation of interposed colon mucosa under prolonged exposure to bile and pancreatic juice reflux. METHODS: About 80% of the glandular stomach was resected, and a 3-cm segment of the transverse colon interposed isoperistaltically between the remnant stomach and duodenum. Epithelial proliferation, aberrant crypt foci (ACF), and tumors in the interposed colon segment were investigated after 4 months of administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) to rats (ENNG-treated rats). RESULTS: In the interposed colon, crypt lengths increased significantly, and the number of goblet cells per crypt per 1 mm decreased significantly compared to those in the remnant colon, whether ENNG was administered or not. Both crypt lengths and the number of goblet cells in the interposed colon of controls and ENNG-treated rats showed no significant difference. A proliferating cell nuclear antigen (PCNA) labeling index (LI) of the remnant colon was almost 30% in both controls and ENNG-treated rats. In controls, the PCNA LI in the interposed colon at 4, 8, and 12 months after surgery was 30.8, 31.8, and 47.8%. In ENNG-treated rats, the PCNA LI in the nontumorous mucosa of the interposed colon was 44.9, 55.4, and 61.5% at the above postsurgical intervals. ACF and carcinoma were observed only in the interposed colon of ENNG-treated rats. ACF was observed as early as 4 months after surgery, and its incidence increased serially. Both the incidence of carcinogenesis and the number of tumors had increased 8 months after surgery. CONCLUSIONS: We established a rat model of colonic interposition following gastrectomy. The adaptation of interposed colon mucosa was well conducted. A malignant condition, however, was induced in the interposed colon segment serving as a gastric substitute because of both carcinogen predisposition and prolonged exposure to bile and pancreatic juice reflux.

Adaptation, Physiological↗

Growth inhibition of human pancreatic cancer cells by sphingosylphosphorylcholine and influence of culture conditions.

Sphingosylphosphorylcholine (SPC) has been shown to be a potent mitogen for Swiss 3T3 fibroblasts and also to be an inhibitor of cell growth of some cancer cells, suggesting cell-selective action of the lipid. We examined the effects of SPC, and its structurally-related sphingosine (SP), sphingosine 1-phosphate (S1-P) and membrane-permeable derivatives of ceramides on cell growth of four strains of human pancreatic cancer cells, MLA PaCa-2, PANC-1, PK-1 and PK-9. Under the reported conditions for SPC-induced stimulation of 3T3 fibroblasts, where cells were grown to confluency in the presence of 10% fetal bovine serum (FBS) in culture prior to experiments and insulin was supplemented in experimental culture, none of the agents tested stimulated DNA synthesis in MIA PaCa-2 cells and ceramide at high concentration even inhibited it. On the other hand, in reduced FBS concentration in preculture and in the absence of insulin in experimental culture, SP, S1-P and ceramides suppressed cell growth of all the cells tested including Swiss 3T3 fibroblasts. However, under these conditions, SPC inhibited three out of four species of pancreatic cancer cells but stimulated Swiss 3T3 fibroblasts in terms of both DNA synthesis and cell proliferation. Cell cycle analysis showed that SPC stimulated cell cycle progress from the G1 to the S phase in Swiss 3T3 fibroblasts but inhibited it in PANC-1 cells in reduced FBS concentrations. We suggest that extracellular SPC can inhibit cell growth of human pancreatic cancer cells through regulation of the cell cycle process depending upon both the cell species and environmental conditions.

3T3 Cells↗

Gastric mucosal blood flow and gastric secretion following intravenous administration of 5-fluorouracil in anesthetized rats.

Acute gastric mucosal lesions are often observed after the intravenous administration of high doses of anticancer drugs. To investigate the acute toxic effects of such anticancer therapy on the gastric mucosa, 5-fluorouracil (5-FU) was administered intravenously to anesthetized rats. Gastric mucosal blood flow (GMBF) was measured continuously using laser Doppler velocimetry. Acid secretion was measured using a perfusion method for 1 h after the administration of 5-FU. No significant change was observed with a low dose of 5-FU (50 mg/kg), but a high doses of 5-FU (100 or 200 mg/kg) caused a significant decrease in GMBF in a dose-dependent manner. The selective antagonist of the muscarinic acetylcholine receptor, pirenzepine, prevented the decrease in GMBF with high doses of 5-FU. Acid secretion decreased after the administration of 5-FU, but not significantly. This study indicates that a decrease in GMBF may be an important factor in gastric mucosal injury induced by chemotherapy. Pirenzepine may prevent the gastric mucosal lesions which are induced by the administration of 5-FU.

Animals↗

New model of colon interposition following distal gastrectomy in rats.

An interposed colon segment has been clinically used as a gastric substitute following an esophagogastric resection for benign or malignant esophageal and gastric cardia disease. The purpose of this study is to establish a rat model of colonic interposition following distal gastrectomy and to investigate its serial mucosal changes. About 80% of the glandular stomach was resected, and a 3-cm segment of the transverse colon interposed isoperistaltically between the remnant stomach and duodenum. Epithelial proliferation and aberrant crypt foci in the interposed colon segment were investigated serially. Crypt lengths in the interposed colon increased significantly (P < 0.05) compared to the remnant colon. The number of goblet cells per crypt per 1 mm in the interposed colon also decreased significantly (P < 0.05) compared to the remnant colon. A PCNA labeling index (LI) of the remnant colon was almost 30%. A PCNA LI in the interposed colon at 4, 8, and 12 months after surgery was 30.8%, 31.8%, and 47.8%, respectively. The PCNA LI in the interposed colon increased significantly (P < 0.05) 12 months after surgery compared to the remnant colon at 4, 8, and 12 months after surgery. Aberrant crypt foci were not detected in the interposed colon segment. In conclusion, we established a rat model of colonic interposition following distal gastrectomy. The interposed colon mucosa adapted well. Long-term mucosal changes of the interposed colon segment should now be studied.

Anastomosis, Surgical↗

Spindle cell carcinoma of the breast.

Spindle cell carcinoma is a rare breast tumor. We present herein three cases of spindle cell carcinoma of the breast and review its characteristics from the literature. Spindle cell carcinoma frequently forms a large and well-circumscribed tumor with gross cyst formation. Histologically, its dominant component is of sheets of spindle shaped cells, and it includes such contiguous carcinoma components as squamous differentiation or invasive ductal carcinoma. Estrogen receptor expression and lymph node metastasis tend to be low. Despite the sarcomatous features, spindle cells are likely to be derived from epithelial cells of mammary glands. Immunohistochemical and ultrastructural examination demonstrated the expression of keratin and the desmosome-like junctional structure in the spindle cell components. Relatively favorable prognosis is expected in spindle cell carcinoma of the breast compared to common breast carcinoma.

Aged↗

Left-sided approach to renal cell carcinoma tumor thrombus extending into suprahepatic inferior vena cava by resection of the left caudate lobe.

A new operative approach to resecting tumor thrombus originating from a right renal cell carcinoma extending into the suprahepatic inferior vena cava (IVC) is reported. Complete local control of the IVC must be obtained above and below the tumor thrombus to remove it under direct vision. The caudate lobe of the liver was resected to expose the retrohepatic IVC and open the lesser omentum. The subhepatic IVC was encircled just below the confluence of the hepatic veins. Caval tumor thrombus was removed en bloc, including the right kidney, by use of the total hepatic vascular exclusion technique (THVE) and IVC exclusion. The retrohepatic IVC was clamped just below the confluence of the hepatic veins once the thrombus was removed, and the suprahepatic IVC clamp was then released and the THVE was terminated. The sequential clamping from the suprahepatic IVC to the retrohepatic IVC below the confluence of the hepatic veins shortened the THVE time.

Carcinoma, Renal Cell↗

[Hemobilia after percutaneous transhepatic gallbladder drainage for cholecystitis in a patient undergoing aortic valve replacement].

A 50-year-old man with hemobilia after percutaneous transhepatic gallbladder drainage (PTGBD) for cholecystitis is presented. PTGBD had been performed for acute cholecystitis following aortic valve replacement. A combination of aspirin and warfarin as anticoagulant therapy had been administrated with the prothrombin time of approximate 40%. Six months later, the patient was again admitted to our hospital because of jaundice, high fever and digestive bleeding. PTGBD was again attempted under the diagnosis of acute cholecystitis. Endoscopic retrograde cholangiopancreatography revealed coagula which were excreted from the papilla of Vater, thus followed by a cholecystectomy accompanying with a choledochotomy. Three ulcers were observed in the cut surface of the resected gallbladder. Microscopic examinations of the gallbladder showed hemorrhage and inflammation. We reported out patient because hemobilia in the chronic phase after aortic valve replacement is rare.

Acute Disease↗

[Moderately differentiated adenocarcinoma of the rectum: a case report of remarkable response to preoperative administration of FT suppository].

A 50-year-old man with moderately differentiated adenocarcinoma of the rectum was operated upon following preoperative administration of FT suppository. Digital examination, colonoscopy, and barium enema showed an elevated lesion with central ulcer of the rectum. Microscopically, the biopsy specimen demonstrated moderately differentiated adenocarcinoma. FT suppository (1,500 mg/day for 52 days, total 78 g) was administered on an outpatient basis. Rectal amputation including lymph node dissection was performed. The tumor markedly reduced in size and changed into a small ulcer in the resected specimen. Microscopically, the tumor degenerated and changed into xanthogranulomatous tissue with foamy histiocytes. Only two tubules of degenerated adenocarcinoma remained. FT suppository for rectal cancer is considered to be safe and effective.

Adenocarcinoma↗

Percutaneous transhepatic gallbladder drainage for acute acalculous cholecystitis following cardiovascular surgery.

Four (1.2%) out of 321 patients required percutaneous transhepatic gallbladder drainage (PTGBD) following cardiovascular surgery. Cholecystitis was initially suspected based upon the occurrence of postoperative fever and the results of abdominal X-ray films. The main physical finding was tenderness of the right upper quadrant abdomen in all patients. Spontaneous pain and Blumberg's sign were not apparent. Distension of the gallbladder and sludge in the gall-bladder were detected in all four patients by ultrasonography, but calculi were not observed. Thickening and edema of the gallbladder wall, generally suggestive of cholecystitis, were observed in only one patient. PTGBD was performed from 5 to 43 (mean 16) days after surgery. The drained fluid was concentrated bile and not purulent. High fever dropped and serum transaminase and C-reactive protein levels decreased within three days after PTGBD. Bacteriologic examinations of the bile and arterial blood were negative in all cases. No complications as a result of PTGBD introduction occurred. PTGBD is a safe and effective procedure, and therefore should be actively performed even in the early phase of acute cholecystitis.

Acute Disease↗