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Biomedical subjects

I Miyazaki

Publications and source records attributed to I Miyazaki.

At least 235 records · Page 13Linked to original sources

Clinicopathological studies on solid and cystic tumors of the pancreas.

Three cases of pancreatic tumor in two females (case 1, case 3) and one male (case 2) were reported. Macroscopically cases 1 and 3, which were surrounded by a thick fibrous capsule, developed toward the outside of the pancreas and the cut surface showed mainly cystic degenerative areas filled with necrotic and hemorrhagic materials. In contrast with these two cases, case 2 was buried in the pancreatic tissue and the cut surface showed cystic degenerative areas in its center with a thick fibrous capsule and tumor cell nests invading beyond the capsule to the parenchyma of the pancreas. Microscopically each tumor was identical. The solid areas on the periphery were composed of sheets of polygonal uniform cells subdivided by delicate fibrovascular stalks. Near the degenerative areas, tumor cells lay on a delicate fibrovascular core in one or two layers, with pseudopapillary patterns. Mitotic figures were very rare. All three cases demonstrated immunoreactivity for alpha-1-antitrypsin, but not for islet hormones, tumor markers nor neuron-specific enolase. Although electronmicroscopically, zymogen granules were detected in cases 2 and 3, and annulate lamellae in cases 1 and 3, ductal cell character features were not so developed. From the above, these tumors were diagnosed as solid and cystic tumors of the pancreas. Furthermore, it was suggested that they differentiated in the direction of acinar cells.

Adolescent↗

Clinicopathological study of pancreatic carcinoma with particular reference to the invasion of the extrapancreatic neural plexus.

A clinicopathological study of 44 ductal carcinomas of the head of the pancreas revealed 39 with retroperitoneal invasion, of which 27 showed extrapancreatic plexus involvements. The second portion of the plexus pancreaticus capitalis was the most frequent site of invasion. A statistically significant correlation was found between neural invasion in the pancreatic tissue and plexus invasion, but no clear correlation was found between plexus invasion and lymphatic invasion or tumor size. Even small-sized tumors (t1) showed plexus invasion. The cases with plexus invasion had a statistically higher incidence of lymph-node involvement around the superior mesenteric artery than those without plexus invasion. These results indicate that complete dissection of extrapancreatic plexus around the superior mesenteric artery, including lymph nodes and soft tissue, could prolong the survival of patients with ductal carcinoma of the pancreas, even in cases of small-sized carcinomas.

Humans↗

Patterns of neural and plexus invasion of human pancreatic cancer and experimental cancer.

Specimens from four patients who underwent resection of cancer of the pancreatic head were examined histologically by serial sections to study the patterns of extrapancreatic nerve plexus invasion of cancer. To understand the mode of neural invasion and its specificity for pancreatic cancer, we also examined retropancreatically transplanted virus-induced rabbit papilloma (VX2) cells in six rabbits. Histological evaluation of the specimens from patients revealed neural invasion near the primary lesion, where cancer cells broke the perineurium and showed communication of cancer cells between the inside and outside of the perineurium. Tumor cells found distant from the primary cancer were confined to the perineurium, grew in a continuous pattern, and followed the branches of nerves. When the rabbit's VX2 cells were implanted into the retropancreatic region of recipient rabbits we also observed neural invasion. This study shows that neural invasion is a common, but not a specific, feature of pancreatic cancer, and it suggests that en bloc excision of the retropancreatic tissue, including fat tissue and the extrapancreatic nerve plexus, should be the basic procedure of radical surgery in the treatment of pancreatic cancer.

Animals↗

Surgical treatment of pancreatic cancer. The Japanese experience.

Since 1973, 194 patients with pancreatic carcinoma have undergone surgery in our clinic, including 134 with carcinoma of the head of the pancreas. Of these 134 patients, resections were performed on 61 (45.5%), 49 (36.6%) of whom underwent a curative resection based on macroscopic evidence. Seven of the patients who underwent macroscopic curative resection survived for five years, giving a five-year survival rate of 26.4% by the Kaplan-Meier method after excepting seven operative deaths. We compared the extent of pancreatic cancer by constructing survival curves according to the General Rules published by the Japan Pancreas Society. There was no statistical difference in survival based on tumor size or stage; however, there was a significant difference in the survival curves of so and se, being the absence or presence of the anterior capsule of the pancreas; rpo and rpe, being the absence or presence of invasion of the retroperitoneal tissue; ew(-) and ew(+), being the absence or presence of invasion at the surgical margin of resection; and n0 and n1, being the extent of lymph node metastasis. The results of this comparison suggest that extended radical pancreatectomy may be indicated for the treatment of pancreatic cancer, since the standard radical operation for pancreatic cancer may miss tumors that have spread to the retroperitoneum and extrapancreatic nerve plexus.

Adult↗

Effects of hormones on tumor growth and immunoreactive insulin-like growth factor-1 of estrogen receptor-positive human breast cancer (MCF-7) transplanted in nude mice.

The effects of estrogens and tamoxifen were analyzed on estrogen receptor-positive human breast cancer (MCF-7) transplanted into athymic nude mice. It was found that (1) the tumor growth and the proportion of 3H-thymidine-labeled cells were significantly increased in the 17 beta-estradiol dipropionate (E2) group, but significantly decreased in the tamoxifen (TAM) group with respect to the control group, and (2) the tumor content of insulin-like growth factor-1 (IGF-1) and the rate of IGF-1-positive cells were significantly lower in the E2 group, but significantly higher in the TAM group than in the control group. It was concluded that the tumor content of IGF-1 and the proportion of IGF-I-positive cells were inversely correlated to the tumor growth and the 3H-thymidine labeling index in vivo.

Animals↗

Discrimination of mitotic cells using anti-p105 monoclonal antibody to analyze the mode of action of etoposide and podophyllotoxin in human gastric cancer cells.

Anti-p105 monoclonal antibody was used to discriminate between M-phase and G2-phase of gastric cancer cells. p105 is a proliferation-associated nuclear antigen and its expression increases with cell cycle progression, especially in the mitotic phase. As an example of cell cycle analysis, the modes of action of etoposide and podophyllotoxin were examined by multiparameter flow cytometry. We found that etoposide caused G2 block and retarded S phase transit and podophyllotoxin caused potential M phase block in gastric cancer cells. This cell cycle analysis by using anti-p105 monoclonal antibody should be useful for analysis of the actions of anti-tumor agents, especially for M phase analysis, because of its convenience and reliability.

Antibodies, Monoclonal↗

In vitro chemosensitivity test of human gastric carcinomas using collagen gel matrix.

We retrospectively evaluated the usefulness of an in vitro human tumor culture system using a specialized collagen gel matrix derived from pig skin as a chemosensitivity test for human gastric carcinomas, especially for scirrhous gastric carcinomas. Seven xenograft tumors derived from human gastric cancers were examined by using this system and the results were compared with the data obtained from a nude mouse assay. Xenograft tumors exhibited three-dimensional growth on the collagen gel matrix like that in vivo. The drug sensitivity as measured by this assay at 10 times therapeutic peak plasma concentrations of the drugs corresponded with that measured by the nude mouse assay for all xenograft tumors. The correlation coefficients were 0.873 for cisplatin, 0.919 for etoposide, 0.880 for mitomycin C and 0.932 for adriamycin. In the case of scirrhous gastric carcinoma, the drug sensitivity could be measured successfully in all 12 patients. This in vitro assay system has advantages as a chemosensitivity test because of its convenience, rapidity, and in vivo-like three-dimensional tumor growth. This system should contribute to the development of chemotherapy for scirrhous gastric carcinomas.

Adenocarcinoma, Scirrhous↗

Expression of c-myc gene product in gastric carcinoma.

The expression of c-myc oncogene product was studied in 213 cases with gastric carcinoma by an immunoperoxidase method using a monoclonal antibody (MYC-1). Fifty (23.5%) of 213 tumors showed immunoreactivity to MYC-1. The distribution of c-myc-product-positive cells was observed mainly at the marginal area of the tumor. Excess reactivity to c-myc product occurred more frequently in invasive cancers than in localized cancers, and c-myc production expression in cancer tissue correlated well with peritoneal dissemination. Patients with c-myc-protein-positive tumor had significantly poorer prognosis than those with c-myc-protein-negative tumor in invasive gastric carcinomas, and the c-myc product status correlated well with the recurrence of cancer by peritoneal dissemination. These results suggest that the expression of c-myc gene product might be related to the proliferative activity of gastric carcinoma and serve as a new biologically relevant tumor marker for determining the prognosis.

Animals↗

Immunocytochemical staining of proliferating cells in endoscopically biopsied tissues of gastric carcinomas with monoclonal antibody Ki-67.

The growth fractions in endoscopically biopsied materials from 121 patients with gastric carcinomas were determined by immunohistochemical staining with the monoclonal antibody Ki-67 and the results correlated with the histopathologic findings and clinical outcome. The Ki-67 labeling rates ranged from 4.6 to 52% (mean: 22%). A significant correlation was found between Ki-67 labeling rates of biopsied materials and those of resected specimens. The tumors showing Ki-67 labeling rates of greater than 22% are more likely to have lymph node metastasis, lymphatic invasion of serosal invasion than those with the rates below 22%. In addition, Ki-67 labeling rates were closely associated with prognosis. Tumors with high Ki-67 labeling rates (greater than 22%) were related to poor prognosis, whereas those with low Ki-67 labeling rates were associated with favorable prognosis. The immunohistochemical staining of proliferating cells in endoscopically biopsied specimens of gastric carcinomas using the Ki-67 monoclonal antibody may be useful in assessing prognosis in carcinoma of the stomach.

Antibodies, Monoclonal↗

Adenomatous hyperplasia of the bile duct epithelium of the canine liver, caused by bacterial infection.

Morphologic changes of the intrahepatic bile ducts after induction of bile stasis and bacterial infection of the biliary tract in two lobes of the liver in mongrel dogs were studied to examine the pathophysiology of hepatolithiasis. Three groups of dogs were prepared by cannulation of the bile duct branch draining the left lateral lobes of the liver and were treated as follows: in group 1 the cannula was clamped after injection of 10(7) Escherichia coli (aerobic bacteria) and 10(7) Bacteroides fragilis (anaerobic bacteria) organisms; in group 2 the cannula was clamped after injection of E. coli only; and in group 3 the cannula was clamped without injection of bacteria. Three months later the livers of killed dogs were examined. In group 1 epithelial adenomatous hyperplasia was noted in association with chronic cholangitis characterized by moderate to severe periductal fibrosis with a large number of inflammatory cells. In group 2 periductal fibrosis was severe, but epithelial hyperplasia was found to a much lesser degree than in group 1. In group 3 no periductal fibrosis or epithelial adenomatous hyperplasia was demonstrated. These findings suggest that adenomatous hyperplasia of the bile duct epithelium may be caused by bacterial infection of the biliary tract in combination with bile stasis.

Animals↗

[Correlation of p105 expression and malignancy in gastric cancers].

The expression of proliferation-associated nuclear antigen p105 of gastric carcinomas was studied by multiparameter flow cytometry and immunohistochemical technique. Content of p105-antigen in cancer cells increased with cell cycle progression, and increased more rapidly in cells in late-S phase than in cells in G0 and early S-phases. Cells in M-phase exhibited a dramatic increase in the amount of the antigen, and the amount of IF intensity of mitotic cells were approximately 5-10-fold greater than that of cells in G1- and S-phases. Immunohistochemical technique demonstrated that patients with lymph node metastasis are more likely to have high p105 positive rates than node-negative patients. The mean p105 positive rates of aneuploid tumors were significantly higher than those of diploid tumors. These results indicate that the measurement of p105 positive rates may be a powerful prognostic indicator of gastric carcinoma.

Aneuploidy↗

[Expression of proliferation associated nuclear antigen P-105 in human gastric cancers: as a new marker for metastasis].

Expression of proliferation associated nuclear antigen P-105 was examined with flow cytometry in forty-three patients with advanced gastric cancer. Expression of P-105 was observed abundantly in cancer, about four times than normal mucosa, but little in normal gastric mucosa. We evaluated the expression of P-105 in cancer as P-105 intensity: mean FITC levels of G0G1 of the cancer cells/those of normal cells. The P-105 intensity did not correlate with DNA index or S-phase fraction. Furthermore, it did not correlate with histologic type, stromal type, infiltrating type, and gross appearance. However, P-105 intensity was significantly higher in the patients with hepatic metastasis, and lower in those with peritoneal dissemination than those without metastasis, respectively. From the results, it was supposed that P-105 intensity might be a useful indicator for metastatic type different from those previously reported in human gastric cancers.

Antigens, Neoplasm↗

[Visual functions of optic neuritis in children caused by demyelinating disease].

Optic neuritis in childhood caused by demyelinating disease is very rare, and its effect on visual function has not been well documented. The visual function of 11 patients treated in the last 11 years was retrospectively studied and the results were compared with 15 cases of optic neuritis of unknown etiology. Optic neuritis in children with demyelinating disease was characterized as follows. 1. abnormal visual evoked cortical potentials (VECP) and color vision were found not only in the affected eye but also in the non-affected fellow eye, 2. VECPs became normal long after the recovery of visual acuity, 3. full recovery of visual function took longer, 4. at onset, vision was more severely affected, but showed a good outcome. These findings provide useful information to make a diagnosis of multiple sclerosis even at the first attack of optic neuritis.

Adolescent↗

Tissue status of epidermal growth factor and its receptor as an indicator of poor prognosis in patients with gastric cancer.

An immunohistological study of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) was made with 157 specimens of stomach cancer. EGF stained positively in 70 specimens (45%), and EGFR in 53 specimens (34%). The cancers were classified into three groups; Group 1 with neither EGF nor EGFR staining positively (67 tumors); Group 2 with either EGF or EGFR staining positively (57 tumors); and Group 3 with both EGF and EGFR staining positively (33 tumors). The incidence rates of tumors of macroscopically infiltrative, poorly differentiated, deep invading and node-positive types were significantly higher for Group 3 than for Groups 1 and 2. The bromodeoxyuridine labeling indices (BrdU LIs) were significantly higher for Group 3 (median: 15.1%) than for Group 1 (median: 10.7%) or Group 2 (median: 11.4%). Patients with synchronous expression of EGF and EGFR (Group 3) had the poorest prognosis. From the results, it may be concluded that tumors with synchronous expression of EGF and EGFR have the highest malignant potentials and this phenomenon may cause autocrine secretion for self-replication.

Adult↗