Immunohistochemical study of epidermal growth factor and epidermal growth factor receptor in gastric carcinomas.
Explore the source record for details and available documents.
Antibodies, Monoclonal↗
Biomedical subjects
T Tobe
Publications and source records attributed to T Tobe.
Experimental studies on the interrelationship between organs mediated by peptide YY: effect on splanchnic circulation and exocrine pancreas in dogs.
Peptide YY (PYY) which is most likely to mediate colonic inhibition on digestive organs is also a potent vasoconstrictor. However, very little is known about the effect of circulating PYY on splanchnic blood flow. This study examined the effect of systemic administration of peptide YY on splanchnic circulation and exocrine pancreas in dogs. Under secretin stimulation, intravenous administration of PYY (0.1, 0.5, 1 and 2 micrograms/kg) significantly decreased pancreatic secretion volume and blood flows in the pancreatic tissue, the superior mesenteric artery and the celiac artery in a dose-related manner. At the same time, PYY increased mean blood pressure. Under secretin plus cholecystokinin stimulation, PYY (1 micrograms/kg) significantly inhibited pancreatic secretion volume and protein output. This study first shows that PYY potently reduces celiac arterial blood flow as well as intestinal blood flow at such doses that PYY inhibits exocrine pancreatic secretion.
Animals↗
[A double blind study of the evaluation of the optimal dose and its frequency in oral administration of OK-432 (Picibanil) by immunological parameters (the 1st report)].
A biological response modifier, OK-432 (Picibanil) administered by injection has been used for cancer immunotherapy. The present study was designed to determine the optimal dose and frequency of oral administration of OK-432. Ninety-one stomach cancer patients were randomly assigned into 7 groups and were administered a placebo or OK-432 at a dose of 5, 20 or 40 KE, once or 3 times a week before their operation (5 KE X 1/W, 20 KE X 1/W, 40 KE X 1/W, or X3/W). ++Missregistration excluded 3 patients and the data of 88 patients were analysed. There was no significant difference in the background status of the patients in each group. The NK activity of PBL was augmented by the administration of 40 KE X 1/W or 20 KE X 3/W and that of RNL was augmented by the administration of 5 KE X 3/W or 40 KE X 1/W, in conjunction with an increase in the number of % positive cells of leu 11a+ or leu 19+ analysed by flow cytometry. The killing activity of PBL, RNL, or MNL against allogeneic lined gastric cancer cells (KATO III) was not augmented by the oral administration of OK-432 for one week. The skin reactivity to Su-PS or PPD, serum levels of tumor markers, or serum levels of immunoglobulins did not help in determining the optimal dose or its frequency. These results suggest that 5 KE X 3/W may be the optimal regimen to augment the antitumor immunity of RNL.
Administration, Oral↗
[Chemotherapy with fluoropyrimidines for MOPC-104E plasmacytoma transplanted in mice with CCl4 induced chronic liver dysfunction].
The masked compounds of 5-fluorouracil (5-FU) have been widely used for chemotherapy in digestive organ cancer. Among them it has been considered that FT (Tegafur) is metabolized into the active form by the drug-metabolizing enzyme P-450 in the microsomes of hepatocytes, and that their activation and anti-tumor activity may decrease under the condition of chronic liver dysfunction. However, this hypothesis has never been experimentally proved. In the present study the therapeutic effect and metabolism of 5-FU and its masked compounds: FT, UFT (uracil + FT), HCFU (Carmofur), 5'-DFUR (Doxifluridine) were assessed by using MOPC-104E plasmacytoma transplanted subcutaneously in BALB/c mice with CCl4-induced chronic liver dysfunction. Agents were administered daily directly into the stomach with stainless steel canule over days 7 to 13 after tumor transplantation, and the tumor weights, drug concentrations in the liver or the tumor, and serum levels of GOT, GPT and LDH were measured on day 14. In mice with chronic liver dysfunction the tumor-inhibitory effect of 5-FU, FT, UFT and HCFU did not necessarily decrease and serum levels of GOT, GPT and LDH of mice administered with 5-FU, FT, HCFU and 5'-DFUR were higher than in normal animals treated with them. By contrast UFT had no influence on them. The most remarkable difference was observed in uracil concentrations, which were significantly lower in the tumor and the liver of mice with chronic liver dysfunction than in those of normal mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Adoptive immunotherapy against peritoneal metastases from stomach cancer--application of regional lymph node lymphocytes].
Twenty-four patients with advanced stomach cancer were treated with OK-432 combined adoptive immunotherapy [AIT] as prophylaxis or therapy against peritoneal metastases. Lymphocytes isolated mainly from regional lymph nodes were cultured for 9-13 days with T cell growth factor and sonicated tumor extract. OK-432 administration and cell transfer were performed via a catheter inserted into the abdominal cavity at surgery. The proliferation rate of regional lymph node lymphocytes was higher than that of peripheral blood lymphocytes (p less than 0.01). Cultured regional lymph node lymphocytes expressed CD25 and CD4+45R- more frequently than those of peripheral blood lymphocytes. On the other hand, cytotoxic activity of regional lymph node lymphocytes were slightly lower than that of peripheral blood lymphocytes. These results suggest that regional lymph node lymphocytes could be used in AIT because of their different function from that of peripheral blood lymphocytes. Survival of the patients with peritoneal metastasis at primary laparotomy was higher than that of the historical control group (4-9 months after surgery). These results show that OK-432 combined adoptive immunotherapy appears to be a new therapeutic approach to peritoneal metastases from stomach cancer.
Adult↗
Chemosensitivity correlation between the primary tumors and simultaneous metastatic lymph nodes of patients evaluated by DNA synthesis inhibition assay.
The chemosensitivities of primary tumors (PT) and simultaneous metastatic lymph nodes (MN) to mitomycin C (MMC), 5-fluorouracil (5-FU), Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH), carboquone (CQ), or cisplatin (CDDP) were assessed in a group of 29 patients (11 gastric, 8 colorectal, 4 breast, and 6 other cancers) by a DNA synthesis (3H-thymidine incorporation) inhibition assay. PT and MN from the same patient showed heterogeneity in chemosensitivity. MN were more sensitive to the agents than PT. PT were sensitive to 5-FU, whereas MN were sensitive to CDDP. An analysis of the sensitivity correlations showed that the sensitivities of PT to MMC, 5-FU, CQ, and CDDP correlated with each other, but ADR sensitivity correlated with only CQ sensitivity. The sensitivities of MN correlated with each other, except for those to ADR and CDDP. In contrast, MMC, ADR, or CQ sensitivity showed a correlation between PT and MN. These results suggest that patients should be treated according to the sensitivity of the target lesion. However, if the sensitivity assay is not available, the sensitivity correlation may be useful when choosing the agent. It also may be important that ADR sensitivity does not correlate with the sensitivities of other agents.
Breast Neoplasms↗
Receptor binding of cholecystokinin analogues in isolated rat pancreatic acini.
The receptor binding of CCK analogues was determined in terms of the inhibition of [125I]CCK binding in isolated rat pancreatic acini. The inhibition curve produced by CCK-8 showed the same feature as that produced by synthetic human CCK-33. The relative potency values of CCK analogues to half-maximally inhibit specific CCK binding were calculated; CCK-8 was equal to human CCK-33, 3-fold stronger than natural porcine CCK-33 and 39, and 700-fold stronger than the unsulphated form of synthetic human CCK-33. Our data suggest that CCK-33, one of the longer molecular forms of CCK, is as important as CCK-8 in the mechanism of physiological actions of CCK.
Animals↗
Comparison between crude interleukin-2 and recombinant interleukin-2 in maintaining killing activity of cultured lymphocytes.
Peripheral blood lymphocytes, regional lymph node lymphocytes or malignant effusion lymphocytes from cancer patients were incubated with crude IL-2 (cIL-2) for 13 days. These effectors, which frequently expressed IL-2 receptor (IL-2R), proliferated well and possessed augmented killing activity against fresh autologous tumor cells and K562. However, when recombinant IL-2 (rIL-2) was added for the last 4 days of culture instead of cIL-2, IL-2R expression and killing activity against fresh autologous tumor cells decreased significantly (P less than 0.05). Phenotypic analysis indicated that cIL-2 significantly promoted the expansion of the cytotoxic population (CD8+.11b-)(P less than 0.05). The decreases in killing activity and IL-2R expression were restored by 0.004% PHA plus rIL-2, but not in the presence of rIFN-gamma, rIL-1 alpha, rIL-1 beta, rIL-4 or rIL-6. PHA-free cIL-2 maintained killing activity, but not IL-2R expression. We conclude that some factors in cIL-2 and a low dose of PHA-P are necessary for the maintenance of killing activity and IL-2R expression of cultured lymphocytes in the late phase of culture.
Cell Division↗
Orally administered streptococcal preparation, OK-432 augments the antitumor immunity of patients with gastric or colorectal cancer.
A streptococcal preparation, OK-432, was orally administered at a dose of 5 KE to patients with gastric or colorectal cancer for 7-14 days before their operations, and its immunomodulatory effects on peripheral blood lymphocytes (PBL), regional node lymphocytes (RNL) and tumor infiltrating lymphocytes (TIL) were assessed. The group treated with OK-432 included 8 gastric and 6 colorectal cancer patients, and the control group included 8 gastric and 8 colorectal cancer patients. The NK cell activity of PBL was significantly augmented by the oral administration of OK-432, and the proportions of Leu 7+ and Leu 11+ cells in PBL also increased. The responses of PBL and TIL to autologous tumor extracts in the presence of interleukin-2 were enhanced after the oral administration of OK-432. The proportion of OKT8+ cells in PBL increased after treatment with oral OK-432, whereas the proportion in RNL significantly decreased. These results indicate that oral OK-432 affects NK and T cells and may augment the antitumor immunity of patients with gastrointestinal cancer.
Administration, Oral↗
Production of monoclonal antibody to human esophageal cancer cell line.
The immunization of Balb/C mice with esophageal cell line KYSE-50 established from poorly-differentiated esophageal squamous cell carcinoma, resulted in obtaining the monoclonal antibody KYMN-28-5. This monoclonal antibody is of the IgM class and recognizes a carbohydrate antigen contained in glycoproteins with molecular weights of 53 and 56K, and in neutral glycolipids extracted from teratomas. Tissue staining revealed that this monoclonal antibody reacts strongly with malignant tumors but only weakly, or not at all, with normal tissues, apart from squamous epithelial tissue. KYMN-28-5 is thus a useful tumor marker which will improved the accuracy of serological diagnosing squamous cell carcinoma when combined with the measurement of SCC antigen.
Animals↗
Changes of in vivo pancreatic amylase output in the early stage after partial hepatectomy in rats.
Explore the source record for details and available documents.
Amylases↗
Depressed function of Kupffer cells in rats with CCl4-induced liver cirrhosis.
In the present study, the Kupffer cell function of rats with CCl4-induced liver cirrhosis was tested by analyzing the changes in the host defense system. In rats without liver cirrhosis injected with CCl4 for 3 weeks concomitant with the high opsonic activity the endocytic index was significantly increased. Rats treated for 9 and 13 weeks developed cirrhosis, and their endocytic indices were not increased despite the rise in their opsonic activity. Particularly, the endocytic index of 13-week-treated rats with advanced liver cirrhosis was significantly lower than that of the other groups. The organic distribution of 51Cr-endotoxin injected intravenously exhibited characteristic changes in 9-week- and 13-week-treated rats: decreased hepatic uptake and increased splenic uptake. In contrast, pulmonary uptake was increased in all CCl4-treated rats. The superoxide production by Kupffer cells from 13-week-treated rats was greatly reduced, accompanied by the decreased superoxide dismutase activity of liver homogenate. Thus, results of this study suggest that Kupffer cell dysfunction is one of the main factors affecting host defenses in liver cirrhosis.
Animals↗
Effect of a new synthetic free radical scavenger, 2-octadecyl ascorbic acid, on the mortality in mouse endotoxemia.
Oxygen-derived free radicals have been implicated as mediators of cellular injury in several model systems. In order to clarify the role of oxygen radicals in endotoxemia, we measured the serial lipid peroxide changes resulting from systemic radical reactions using a newly developed colormetric method. To determine the effect of a free radical scavenger on mortality in endotoxemia, a new synthetic scavenger, 2-Octadecylascorbic acid (CV-3611), which overcome the detrimental properties (circulation half-life and cell penetration) of native SOD, was used in the model of mouse endotoxemia induced by the i.p. administration of E-coli endotoxin (10 mg/kg). Serial LPO (Lipid Peroxide) changes revealed significant elevations from the basal level of 4.52 +/- 0.79 nmol/ml to 10.5 +/- 2.04 nmol/ml at 2h (P less than 0.05), 12.0 +/- 2.44 nmol/ml at 8h (P less than 0.05), 32.8 +/- 12.5 nmol/ml at 12h (P less than 0.05) and 13.6 +/- 2.40 nmol/ml at 24h (P less than 0.05) following i.p. administration of E-coli. The circulation half life of CV-3611 was checked by a reversed-phase HPLC after 10 mg/kg s.c. administration. The level of CV-3611 reached peak levels of 0.54 +/- 0.10 micrograms/ml at 1h and 0.52 +/- 0.20 micrograms/ml at 2h then gradually decreased to the level of 0.04 +/- 0.004 micrograms/ml at 6h and to a non-detectable level at 24h after s.c. administration. Increased survival was seen at 2 days (P less than 0.001) after E-coli endotoxin administration in the CV-3611 treated group compared to the control group. These results suggest that oxygen derived free radicals contribute to mortality in mouse endotoxemia and that antioxidants such as CV-3611 may provide a new therapeutic avenue by improving survival of patients with gram-negative bacterial sepsis.
Animals↗
High dose, external beam and intraoperative radiotherapy in the treatment of resectable and unresectable pancreatic cancer.
Ninety patients with pancreatic cancer were treated by external beam radiotherapy (EBRT) and/or intraoperative radiotherapy (IORT) with or without surgical resection of the tumor, and the results were compared with those of a historical control comprising 112 patients treated by surgery alone. At an early stage of this study, postoperative EBRT (50-60 Gy) or IORT (25-33 Gy) was given alone, but recently the two modalities have been combined. The combination of high doses of EBRT and IORT was well tolerated provided that the gastrointestinal tract was not irradiated during IORT. Although EBRT plus IORT appeared to yield better results than either EBRT or IORT alone, the difference was not significant on multivariate analysis, and patients receiving EBRT, IORT, or EBRT + IORT were grouped together. Patients receiving radiotherapy in addition to macroscopically curative surgery had a slightly longer median survival time (14 months) than those receiving curative surgery alone (10 months), but the 3-year survival rate was similar (21% vs. 19%). In patients who underwent noncurative resection, the median survival time was significantly longer for the irradiated group (12 months) than for the control group (6.5 months). Also, in patients with unresectable lesions but no distant metastases, irradiation prolonged the median survival time significantly (8 vs. 3.5 months). In this group, there was one 5-year survivor, who received EBRT of 55 Gy plus IORT of 30 Gy to his unresectable pancreatic body lesion. Patients with metastases were also treated for palliation of symptoms, but it was found that irradiation prolonged the median survival time even in such cases (4.5 vs. 2.5 months). Based on these results, we plan to use EBRT plus IORT in all pancreatic cancer patients with no metastases.
Adult↗
Incorporation of SP-40,40 into the soluble membrane attack complex (SMAC, SC5b-9) of complement.
When SC5b-7 was prepared from the C8-depleted serum activated with inulin, it contained SP-40,40 as well as S-protein. From the densitometry of each component in SC5b-9 after SDS-PAGE, it was estimated that SC5b-9 was constituted of one molecule each of C5b, C6, C7, C8, S-protein, and SP-40,40 and two molecules of C9. SP-40,40 was depleted from normal serum with an affinity column using mouse monoclonal anti-SP-40,40 antibody. When the resulting SP-40,40-depleted serum was activated with inulin, SC5b-9 lacking SP-40,40 could be formed. S-Protein-depleted serum was also prepared with an affinity column using mouse monoclonal anti-S-protein antibody. Similarly, SC5b-9 lacking S-protein could be formed by the inulin activation of the S-protein-depleted serum. These results indicate that either SP-40,40 or S-protein should be able to form a soluble C5b-9 complex.
Blood Proteins↗
Effects of percutaneous transhepatic biliary drainage on blood-bile permeability and selective IgA transport in patients with biliary obstructions.
Biliary obstruction induces a increase in the permeability between blood and bile, and a decrease in the rate of immunoglobulin A (IgA) transport into bile. We investigated the effects of percutaneous transhepatic biliary drainage (PTBD) on these derangements. PTBD reduced the extent of elevation of the bile-to-serum ratio of Immunoglobulin G (IgG; IgG-BS ratio) in patients with obstructive jaundice. Because IgG is known to be passively transported from serum to bile, the results indicate that PTBD restores the blood-bile barrier function. The IgA-BS ratio/IgG-BS ratio index (IgA/IgG index) and the IgM/IgG index, which indicated the function of selective transport of IgA and IgM into bile, initially decreased and then returned to the normal range 17 days after PTBD in patients who experienced a rapid resolution of hyperbilirubinemia. However these indices remained low in patients who did not experience this resolution. The serum secretory IgA levels in patients who did not experienced rapid resolution of hyperbilirubinemia markedly increased before PTBD. The serum secretory IgA levels in the patients who did and those who did not experience rapid resolution of hyperbilirubinemia, after initially increasing, decreased after PTBD. However the level returned to the control range only in patients who experienced a rapid resolution. These results indicate that the secretory IgA level is a sensitive indicator of hepatobiliary function, and measurement of the level of secretory IgA could predict the effect of PTBD.
Bile↗
Unresponsiveness of insulinoma cells to secretin: significance of the secretin test in patients with insulinoma.
It is well known that B cells in the pancreas release insulin when stimulated by secretin, but there have been few reports on the response of insulinoma cells to secretin. In five patients with insulinoma, changes in serum immunoreactive insulin (IRI) concentration were measured after the intravenous injection of secretin into the peripheral vein before and after extirpation of the insulinoma. The extirpated insulinomas were cultured and tested for their response to secretin. The rise in serum IRI in response to secretin in patients with insulinoma was significantly slower and smaller than in normal volunteers. After removal of the insulinoma, the response to secretin became prompt and increased with time. Cultured insulinoma cells did not release insulin when stimulated by secretin. Therefore, it is concluded that the response of insulinoma cells to secretin is quite different from that of normal beta cells, and that the function of beta cells in the insulinoma-bearing pancreas is suppressed by the autonomous hypersecretion of insulin by the insulinoma. The extent of the decrease in function of the beta cells in patients with insulinoma can be estimated by the intravenous secretin test. Thus, the secretin test is sometimes useful in the differentiation of hypoglycemia due to insulinoma from that due to beta cell hyperplasia or alimentary hyperinsulinemia.
Adenoma, Islet Cell↗
Effect of synthetic human cholecystokinin-33 on pancreatic blood flow in dogs.
We have examined the effect of synthetic human cholecystokinin (CCK-33 and CCK-8) on pancreatic blood flow and protein output in anesthetized dogs. Human CCK-33 and CCK-8 increased pancreatic blood flow and protein output in a dose-related manner. There were no significant differences in increasing pancreatic blood flow between human CCK-33 and CCK-8, and increases in blood flow were closely related to the increase of the pancreatic enzyme secretion. L-364,718 (20 nmol/kg) caused a potent inhibition of CCK-stimulated pancreatic blood flow as well as protein output. The degree of inhibition by L-364,718 was dependent on the amount of CCK infused. This study demonstrates that increasing effect on pancreatic blood flow may be one of the biological actions of CCK mediated via CCK receptor. The CCK-33, one of longer molecular forms of CCK, is an important biological stimulator of pancreatic blood flow as well as of exocrine pancreatic secretion.
Animals↗