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Biomedical subjects

J Sakamoto

Publications and source records attributed to J Sakamoto.

At least 145 records · Page 8Linked to original sources
PubMed1990

Quantitative analysis of antibody localization in human metastatic colon cancer: a phase I study of monoclonal antibody A33.

A33 is a mouse immunoglobulin G2a (IgG2a) monoclonal antibody (mAb) that detects a heat-stable, protease- and neuraminidase-resistant epitope. The antigen is homogeneously expressed by virtually all colon cancers and in the colon mucosa but not other epithelial tissues. The biodistribution and imaging characteristics of iodine-131 (131I)-mAbA33 were studied in colorectal carcinoma patients with hepatic metastases. Antibody labeled with 2 to 5 mCi of 131I was administered intravenously (IV) 7 to 8 days before surgery at five dose levels, ranging from 0.2 mg to 50 mg, with three or more patients entered at each dose level. In addition, three patients received 2 mg 131I-mAbTA99 (an isotype-matched control mAb) together with 125I-mAbA33. Evaluation included whole-body imaging with a gamma camera, technetium-99 (99mTc)-human serum albumin blood pool scans, liver/spleen scans, abdominal computed tomographic (CT) scans, hepatic arteriograms, antibody pharmacokinetics, and assessment of antibody distribution in biopsied malignant and normal tissues. Selective mAbA33 localization to tumor tissue was demonstrated in 19 of 20 patients, and external imaging correlated with surgical inspection, pathologic examination, and tissue radioactivity. One week after antibody administration, tumor:liver ratios ranged from 6.9:1 to 100:1 and tumor:serum ratios from 4.1:1 to 25.2:1. 99mTc-albumin blood pool studies showed that liver metastases were hypovascular, emphasizing the selective localization of mAbA33 despite poor tumor-blood flow. Control mAbTA99 studies showed mAbA33 localization was antigen-specific; tumor:liver ratios were 2.3- to 45-fold higher for specific antibody. In metastatic lesions, radioisotope was localized primarily in the viable periphery; however, even the necrotic tumor core concentrated specific antibody. External imaging showed isotope visualization in some patients' large bowel; whether this represents specific antibody uptake or gastric iodine secretion is unclear.

Adult↗
PubMed1990

[A case of long surviving gastric cancer with an malignant acanthosis nigricans].

Reported the case of a 73 year old female who was diagnosed as having a gastric cancer with malignant acanthosis nigricans and had a long survival, totaling about 8 years 6 months after operation. Further, her skin lesion completely disappeared. In general, a gastric cancer with malignant acanthosis nigricans is said to have a very poor prognosis and an analysis of recent cases has indicated that the average survival is about 10 months. The reason for such a bad prognosis is thought to be that the diagnosis of a gastric cancer with malignant acanthosis nigricans is usually determined only after the cancer is far advanced.

Acanthosis Nigricans↗
PubMed1989

Evaluation of the teratogenic potential of the rubber accelerator dibenzthiazyl disulphide in rats.

The teratogenic potential of dibenzthiazyl disulphide (MBTS) was studied in Wistar rats. Pregnant rats were given MBTS at a dosage of 0, 0.04, 0.2 or 1% in the diet from day 0 to day 20 of pregnancy. Daily intakes of MBTS were 26 mg kg-1 for the 0.04% group, 127 mg kg-1 for the 0.2% group and 596 mg kg-1 for the 1% group. Maternal body weight gain during day 0 to day 14 of pregnancy in the 1% group was significantly lowered, but no significant changes induced by MBTS were observed in any other maternal parameters, such as food consumption and clinical sign of toxicity. There were no significant compound-related effects on the incidences of pre- and postimplantation losses and the number, sex ratio and body weight of live fetuses. Morphological examinations of the fetuses revealed no evidence of teratogenesis. In the postnatal development of the offspring from the dams given MBTS, a high survival rate and good growth of the offspring were seen. It could be concluded that MBTS possesses no adverse effects on the pre- and postnatal development of the offspring in rats at the doses employed in the present study.

Animals↗
PubMed1989

Application of the immunoperoxidase method for rapid intraoperative pathological diagnosis of pancreatic cancer.

Intrapancreatic extension of pancreatic duct cell carcinoma in 19 resectable cases was evaluated by both hematoxylin and eosin (H&E) staining and quick immunostaining using antibodies against cancer-associated antigens--e.g., CA19-9, DUPAN 2, and CEA--on the intraoperative frozen-section biopsy during the course of laparotomy. By H&E staining, malignant lesions were identified in four of 19 cases (21%). By the immunostaining method, however, cancer cells were detected in 10 of 19 cases (52.6%). This immunostaining method was particularly useful in defining cancer cells surrounded by dense fibrous connective tissue, in which cancer cells are usually difficult to evaluate by H&E staining. Thus, the application of such immunostaining, together with H&E staining, on the cryostat sections of biopsy specimens may provide important information for the appropriate operative method. Retrospective study of permanent sections revealed that pathological diagnosis by quick immunostaining was more accurate than diagnosis by H&E staining.

Biomarkers, Tumor↗
PubMed1989

Improvement of the rapid immunoperoxidase staining method for intraoperative pathological diagnosis of pancreatic cancer using microwave irradiation.

The rapid immunostaining of gastrointestinal cancer-associated antigens, CA19-9, CEA, DUPAN2, and CA50, for intraoperative pathological diagnosis of pancreatic cancer can be completed in only 13 min by applying microwave irradiation, which was used to accelerate the incubation of the primary antibody. Only 3 s irradiation at 500 W for fresh-frozen sections produced specific antigen staining of greater intensity than that obtained with longer incubation, and tissue preservation was satisfactory with minimal non-specific background staining. This rapid immunoperoxidase staining method on the cryostat section of pancreatic biopsy specimens can provide important information for determining an appropriate operative method for pancreatic cancer patients.

Antigens, Neoplasm↗
PubMed1989

[The correlation between preoperative pathologic diagnosis of a biopsy specimen and postoperative pathologic diagnosis of a tissue specimen involving colorectal cancer patients].

An endoscopic biopsy was performed on specimens taken from 374 patients with a large bowel cancer, who had received a colo-rectal resection between 1980 and 1984. An average of three to four biopsy specimens was taken from each patient. The pathological diagnosis of these specimens revealed a carcinoma with an identifiable pathological classification in 280 patients (74.9%), a carcinoma without an identifiable classification in 54 (14.4%), a suspect cancer in 7 (1.9%), and no sign of a cancer in 33 (8.8%). The diagnosis of the 33 cases in which no cancer was detected were adenoma in 11 patients, inflammation in 8, necrosis in 1, and no clear pathological determination in 11. The correspondence rates between a biopsy specimen and a tissue specimen diagnoses were 57.9% in a well differentiated adenocarcinoma; 77.4% in a moderately differentiated adenocarcinoma; 85.5% in a poorly differentiated adenocarcinoma; and 100% in a mucoid carcinoma.

Adenocarcinoma↗
PubMed1989

[Radioimmunodetection of colorectal cancer, using anti-CEA monoclonal antibodies].

Aiming at radioimmunodetection of colorectal cancer, anti-CEA monoclonal antibodies (CEA102) were produced by immunization with purified CEA. CEA102 showed high specificity with colorectal cancer by mixed hemadsorption assay and immunoperoxidase technique. The antigen detected by CEA102 was confirmed to be carcinoembryonic antigen (CEA) and its molecular weight was estimated to be ca. 180,000 by biochemical analysis. The in vivo study using nude mice grafted a human colorectal cancer or a human malignant melanoma showed greater accumulation of 125I-labeled CEA102 in CEA-positive colorectal cancer than in nude mouse tissues and CEA-negative malignant melanoma. Moreover we successfully obtained scans with good localization of the grafted colorectal cancer on FCR (Fuji Computed Radiography). Using 131I-labeled CEA102 liver metastasis in the patient with colorectal cancer was successfully detected by external scanning with gamma-camera. These results suggest that radiolabeled CEA102 is useful for the detection of colorectal cancer.

Aged↗
PubMed1989

[Alteration of phenotype, morphology and drug sensitivity in colon cancer cell lines under various culture conditions].

Thirteen colorectal cancer cell lines were established from 120 fresh colon cancer specimens. Expression of colon cancer-related antigens and blood group-related antigens on these cell lines were evaluated by Mixed Hemadsorption test (MHA) and Immune Adherence test (IA). The results were compared with the results of immunohistological analysis of the antigen expression in sections of the original tissues, and deletions of several blood group-related antigens in cell lines were observed. Colon cancer cell line HT-29, cultured in different lots of FCS or in different types of serum-free medium showed various antigen expression, suggesting the effect of culture medium on phenotypic expression. In glucose-free medium, HT-29 cells showed the characteristic "dome formation" which is typical of enterocytic differentiation forming brush borders in such cells. HT-29 cells cultured on bovine corneal endothelial extracellular matrix (BCE-ECM) coated plates showed similar enterocytic changes under phase-contrast microscope. Also, irradiated HT-29 cells cultured under 8-Azaguanine containing medium retained their strong resistance to 8-Azaguanine. These results suggest that these cancer cell lines might alter their phenotype, morphology, differentiation, growth pattern and drug sensitivity depending on the culture environment.

Antigens, Neoplasm↗
PubMed1988

Immunohistochemical localization of CA 19-9 and CEA in pancreatic carcinoma and associated diseases.

The distribution of carbohydrate antigen 19-9 (CA 19-9), on pancreatic carcinomas and associated diseases correlated with carcinoembryonic antigen (CEA) localization is described. Immunohistochemical examinations were made on pancreatic specimens from 45 patients with pancreatic carcinoma. In normal pancreatic duct, the antigens were restricted to the luminal surface. In some hyperplastic epithelium, however, they were localized not only to the basolateral plasma membranes but also to the cytoplasm. In neoplastic glands, the antigens were distributed over the entire surface of the cells and in the surrounding stroma adjacent to the basal membranes of the malignant cells. The findings were compatible with previous observations of CEA and secretory component (SC) localization in gastric and colonic mucosa. In addition, the staining intensity of CA 19-9 in the routine formalin-fixed and paraffin-embedded sections was much superior to that of CEA. The relationship between CA 19-9 and other blood group antigens, such as Lewis a and Lewis b, also was discussed. Localizations of these antigens in pancreatic tissues are useful for the biologic analysis of abnormalities of the pancreatic duct epithelium, and may well facilitate pathologic diagnosis of pancreatic carcinoma.

Antigens, Neoplasm↗
PubMed1988

Effects of N,N'-methylene-bis-acrylamide (MBA) on mouse germ cells--sperm count and morphology, and testicular pathology.

The sperm count and morphology, and testicular histopathology were studied in mice over a period of 75 days following a single oral administration of 50, 100, and 200 mg/kg N.N'-methylene-bis-acrylamide (MBA). With a 50 and 100 mg/kg dose, the sperm abnormality reached a maximum at 30 days, whereas the sperm count reached a minimum at 35 days. The abnormality and decrease in sperm count were both dose dependent. Following the administration of 200 mg/kg MBA, the appearance of abnormal sperm showed a diphase pattern, i.e., first at 7-15 days without any reduction of the sperm count and second at 30 days after treatment. Testicular histopathological changes showed that resting spermatocytes, succeeding leptotene and zygotene spermatocytes were either absent or reduced 1-3 days after treatment with 200 mg/kg MBA. These early histopathological changes seemed to precede both the increase in abnormal sperm and the decrease in sperm count observed 30-35 days post-treatment, and also suggested that resting spermatocytes were most sensitive to MBA exposure among various spermatogenic cells.

Acrylamides↗
PubMed1988

Characteristics of three human gastric cancer cell lines, NU-GC-2, NU-GC-3 and NU-GC-4.

Three human gastric cancer cell lines, NU-GC-2, NU-GC-3 and NU-GC-4 were established in vitro from the cancer tissues obtained from 3 patients during surgery. The pathological findings of the gastric tumors of these cases revealed poorly differentiated adenocarcinoma (and partial signet-ring cell carcinoma in the case of NU-GC-4). NU-GC-2 and NU-GC-4 were originally obtained from metastatic paragastric lymph nodes and NU-GC-3 was obtained from a metastatic tumor in the brachial muscle. The cells of NU-GC-2 and NU-GC-3 are polygonal in shape and grow as a monolayer sheet. NU-GC-4 cells, however, are mainly spherical in shape with a few free floating cells. Electron microscopy revealed epithelial characteristics in all 3 cell lines. The average doubling time of NU-GC-2 was 36.1 hours, that of NU-GC-3 was 38.2 hours and that of NU-GC-4 was 29.9 hours. The modal chromosome number of NU-GC-2 was 62, that of NU-GC-3 was 58 and those of NU-GC-4 grown in in vitro and in vivo were 52-54 and 53, respectively. In vitro and in vivo lines of NU-GC-4 were established from the same tumor. These two cell lines are quite similar in morphology, but slightly different in karyotype. The in vitro sensitivity to anticancer agents was highest in NU-GC-4 and lowest in NU-GC-2. Of the anticancer agents, mitomycin C and adriamycin were most effective on the cells of all 3 cell lines.

Adenocarcinoma↗
PubMed1988

Histological changes of acrylamide-induced testicular lesions in mice.

The effects of a single oral dose of 150 or 100 mg/kg acrylamide on the testis were studied histopathologically in prepubertal and adult mice over a period of 10 days following treatment. In the prepubertal mice, severe testicular damage such as vacuolation and swelling of the round spermatids, necrosis of the late elongated spermatids in stages I to VIII, abnormal meiosis in stage XIX, and a marked cellular exfoliation into the lumen were detected 1 day after administration of the 150 mg/kg dose. On Day 2, the damage was more pronounced. However, the testicular damage was repaired 7 to 10 days after treatment. In the adults, many tubules from stages I to VIII were affected, showing nuclear vacuolation in most of the round spermatids 1 day after administration of the 150 mg/kg dose. Meiosis in stage XIV was normal. In the prepubertal mice, nuclei of the round spermatids in stage I-III, especially step 1 spermatids had degenerated 1 day after administration of the 100 mg/kg dose. In the adults, the round spermatids had degenerated in stages I-II and IV-VIII 1 day after administration of the 100 mg/kg dose. These results suggested that the most vulnerable cell type among the spermatogenic cells was the round spermatid, especially that in the Golgi phase (stage I-III). Other stages and spermatogenic cells were relatively resistant to acrylamide testicular toxicity.

Acrylamide↗
PubMed1988

[Nd:YAG laser treatment of recurrent adenomas in the preserved rectum in patients with a ileo-rectal anastomosis in familial polyposis coli].

Eight patients with ileo-rectal anastomosis following a total colectomy for familial polyposis coli underwent Nd: YAG laser therapy to treat recurrent adenomas in the preserved rectum after the operation. The median follow-up period for these eight patients has been 4 years and 7 months. Of the eight patients, one underwent a mucosectomy of the preserved rectum and an ileo-anal pull-through five years after the first operation because of recurrent diffuse polyposis of the preserved rectum. In the remaining seven patients, Nd:YAG laser therapy was found to be effective in the abration of recurrent polyps.

Adenoma↗
PubMed1988

High serum levels of DUPAN2 antigen and CA19-9 in pancreatic cancer: correlation with immunocytochemical localization of antigens in cancer cells.

We determined the concentration of serum DUPAN2 and CA19-9 in 43 pancreatic cancer patients by enzyme immunoassay, and compared the staining patterns of the antigens in the tissues of pancreatic cancer in order to clarify the mechanism of the elevation of serum DUPAN2 and CA19-9 levels in the patients. In 26 patients (60%), the serum DUPAN2 concentration was higher than 300 U/ml. This positive rate was not so high as that of CA19-9. However, seven out of the twelve CA19-9-negative patients were DUPAN2-positive. Using a combined assay of serum DUPAN2 and CA19-9, the diagnostic sensitivity for pancreatic cancer was 88% (38/43). Immunocytochemically, both DUPAN2 and CA19-9 were restricted to the apical surface and/or supranuclear cytoplasm in the normal pancreatic duct epithelia. In cancerous glands, however, the two were found over the entire surface and cytoplasm of the cancer cells--losing the polar distribution pattern of the antigen--and in the surrounding stroma adjacent to the cancer cells. DUPAN2 was detected in 47 (89%) out of 53 adenocarcinomas of the pancreas, and CA19-9 in 44 cases (83%). Cases with high serum antigen levels tended to display high proportions of stromal staining in the cancer tissues. These findings suggest that shedding of the antigen into the stroma adjacent to the malignant glands is one of the major mechanisms in the elevation of high serum DUPAN2 and CA19-9 levels.

Adenocarcinoma↗