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Biomedical subjects

T Yamao

Publications and source records attributed to T Yamao.

28 records · Page 2Linked to original sources
PubMed1996

An early phase II study of etoposide (VP-16) in advanced gastric cancer.

An early phase II study was conducted to evaluate the anti-tumor effects and toxicity of etoposide in patients with unresectable or relapsed advanced gastric cancer. From April 1991 to December 1992, 13 patients were enrolled into this study; one was subsequently considered ineligible. Before enrollment, all the patients had been treated with chemotherapy which did not include etoposide. Etoposide (100 mg/m2/day) was administered as an intravenous infusion over 120 min for five consecutive days and was repeated every four weeks. Seven patients received one course of this therapy and the remaining five received two. No patient showed a complete or a partial response. No change and progressive disease were observed in three and nine patients, respectively. The clinical toxicities (grade 3-4; WHO) of leukocytopenia, anemia and alopecia occurred in 50, 42, and 42% of the patients, respectively. We conclude that this dose of etoposide administered according to the present schedule is ineffective in previously treated patients with advanced gastric cancer.

Adenocarcinoma↗
PubMed1996

A novel membrane glycoprotein, SHPS-1, that binds the SH2-domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion.

Protein tyrosine phosphatases (PTPases), such as SHP-1 and SHP-2, that contain Src homology 2 (SH2) domains play important roles in growth factor and cytokine signal transduction pathways. A protein of approximately 115 to 120 kDa that interacts with SHP-1 and SHP-2 was purified from v-src-transformed rat fibroblasts (SR-3Y1 cells), and the corresponding cDNA was cloned. The predicted amino acid sequence of the encoded protein, termed SHPS-1 (SHP substrate 1), suggests that it is a glycosylated receptor-like protein with three immunoglobulin-like domains in its extracellular region and four YXX(L/V/I) motifs, potential tyrosine phosphorylation and SH2-domain binding sites, in its cytoplasmic region. Various mitogens, including serum, insulin, and lysophosphatidic acid, or cell adhesion induced tyrosine phosphorylation of SHPS-1 and its subsequent association with SHP-2 in cultured cells. Thus, SHPS-1 may be a direct substrate for both tyrosine kinases, such as the insulin receptor kinase or Src, and a specific docking protein for SH2-domain-containing PTPases. In addition, we suggest that SHPS-1 may be a potential substrate for SHP-2 and may function in both growth factor- and cell adhesion-induced cell signaling.

Amino Acid Sequence↗
PubMed1995

Clinical trial of continuous infusion of 5-fluorouracil using an ambulatory pump for metastatic colorectal cancer.

A clinical trial was conducted in order to evaluate the anti-tumor effect and toxicity of a continuous infusion of 5-fluorouracil (5-FU) for metastatic colorectal cancer. Two-hundred and fifty mg/m2/day 5-FU was administered as a continuous infusion through an indwelling central venous catheter with ambulatory pump. Twenty patients with metastatic colorectal cancer which could be measured or evaluated were enrolled in the trial. The objective response rate was 35% (95% confidence interval, 14-56%). The response rates by site were 33% in liver, 17% in lung, 60% in lymph nodes, 50% in adrenal gland and 50% in primary lesion. The major toxicity was stomatitis (50%; grades 2 and 3 on Eastern Cooperative Oncology Group (ECOG) criteria) and hand-foot syndrome (40%; grades 2 and 3 on ECOG criteria). The sequence of toxicity was stomatitis first, followed by hand-foot syndrome. The median cumulative dose of 5-FU from the initiation of therapy to the onset of toxicity was 7125 mg in stomatitis and 17,875 mg in hand-foot syndrome. These toxicities were mild and reversible after a short interruption to the 5-FU infusion. Neither hematological toxicity nor serious catheter-related complications were observed. We concluded that continuous infusion of 5-FU was a feasible treatment for the patient with metastatic colorectal cancer, and manageable on an out-patient basis.

Adult↗
PubMed1994

Insulin stimulates the phosphorylation of Tyr538 and the catalytic activity of PTP1C, a protein tyrosine phosphatase with Src homology-2 domains.

PTP1C is a non-transmembrane protein-tyrosine phosphatase and contains two Src homology-2 (SH2) domains. Insulin stimulated the tyrosine phosphorylation of PTP1C in human 1M-9 lymphoblast cells, in rat H35 hepatoma cells and in Chinese hamster ovary cells over-expressing both insulin receptors and PTP1C. Insulin also stimulated the tyrosine phosphorylation of a mutant PTP1C lacking SH2 domains in Chinese hamster ovary cells, suggesting that the SH2 domains are not required for insulin-stimulated tyrosine phosphorylation of PTP1C. The insulin receptor tyrosine kinase catalyzed the tyrosine phosphorylation of PTP1C in a cell-free system. Peptide mapping of phosphorylated PTP1C showed that Tyr538 in the C-terminal region was phosphorylated in response to insulin. The tyrosine phosphorylation of PTP1C by the insulin receptor kinase increased phosphatase activity. Furthermore, PTP1C was shown to bind to autophosphorylated insulin receptors through its C-terminal region, but PTP1C did not bind to unphosphorylated receptors. These results suggest that PTP1C is a target protein for the insulin receptor tyrosine kinase and that the C-terminal region of PTP1C may function both in the regulation of phosphatase activity and in the association of PTP1C with autophosphorylated insulin receptors.

Amino Acid Sequence↗
PubMed1994

Pharmacokinetics of tolbutamide following intravenous and oral administrations in rats with obstructive jaundice.

The pharmacokinetics of tolbutamide (TB) following intravenous and oral administration was compared between normal rats and rats with experimentally-induced obstructive jaundice (OJ). The plasma concentration-time curve of i.v. administered TB was lower in rats with OJ, in comparison with normal rats. The result of the pharmacokinetic analysis showed no change in the elimination rate constant, but a significant increase in the volume of distribution in the OJ state. The increase in the volume of distribution of TB could be explained by the decreased protein binding in plasma. In the case of oral administration, the elevation of the plasma concentration was slow and the plasma concentration profile was remarkably low in rats with OJ. The rate of TB disappearance from the small-intestinal lumen was delayed in the OJ state, and its marked accumulation in the tissues of the small intestine and the liver was observed. This retarded uptake by the small-intestinal mucosa and subsequent pre-systemic accumulation might, at least in part, be the reason for the slow appearance in the systemic plasma in the OJ state.

Administration, Oral↗
PubMed1993

Pharmacokinetics of indocyanine green in rats with experimentally induced hepatic diseases.

The pharmacokinetics of indocyanine green (ICG) following intravenous administration was compared between normal rats and rats with experimentally induced acute hepatic diseases; namely D-galactosamine-intoxicated (GAL) rats, CDl4-intoxicated (CCl4) rats and rats with obstructive jaundice (OJ). The total body clearance of ICG was decreased in all rats with these hepatic diseases, especially in the rats with OJ. Hepatic plasma flow was also decreased in all rats with the three hepatic diseases. The profile of biliary excretion of ICG was characteristic of rats with each hepatic disease. The cumulative biliary excretion of ICG was markedly low in GAL rats, almost unchanged in CCl4 rats and the appearance of ICG was markedly delayed in rats with OJ. The pharmacokinetic analysis of these data showed that the decreased total plasma clearance of ICG in GAL and CCl4 rats results from both lowered influx across the sinusoidal plasma membrane of hepatocytes and the decreased hepatic plasma flow. In rats with OJ, the decreased total plasma clearance results only from a markedly lowered influx across the sinusoidal plasma membrane of hepatocytes without any relation to the decreased hepatic plasma flow. The decreased biliary recovery in GAL rats might relate to the decreased bile flow. The time lag of the appearance of ICG into the bile of rats with OJ was due to its slow efflux across the bile canalicular membrane, in addition to its slow influx across the sinusoidal membrane of the hepatocyte and its remarkably long period of stay in the hepatocyte.

Acute Disease↗
PubMed1990

Analysis of hepatic transport of cefpiramide in rats with obstructive jaundice by using isolated hepatocytes.

The mechanism of the diminished biliary clearance of cefpiramide (CPM) in rats with obstructive jaundice (OJ) was investigated by using isolated hepatocytes. The kinetics of CPM uptake by hepatocytes isolated from normal rats and rats with OJ could be explained by the combination of saturable carrier-mediated and nonsaturable first-order rate processes. The maximum uptake rate (Vmax) of the carrier-mediated process was significantly decreased in OJ, compared with normal hepatocytes, while the Michaelis constant (Km) and the first-order rate constant (kd) were not significantly different. This result indicated that the number of CPM transport carriers was decreased in OJ hepatocytes. Further, no CPM uptake occurred from the serum of OJ rats into normal hepatocytes. Partial recovery of CPM uptake after treatment of OJ serum with activated charcoal suggested the accumulation of inhibitors of CPM uptake in OJ serum.

Animals↗
PubMed1988

Pharmacokinetics of cefpiramide in rats with obstructive jaundice.

Changes in the mode of drug excretion in obstructive jaundice (OJ) were investigated in rats with experimentally induced OJ using a non-metabolized, highly-biliary-excreted antibiotic, cefpiramide (CPM). In OJ rats, biliary excretion of the drug was markedly diminished, while the urinary excretion was increased. The change in the mode of CPM excretion was examined in detail. It seems that the biliary excretion of CPM was decreased owing to the diminished biliary clearance in OJ rats. On the other hand, CPM binding to plasma proteins was decreased in the disease state. This change in the protein binding would be due to both the decreased albumin concentration and the accumulation of binding inhibitors in the plasma of diseased rats, and the decreased protein binding would be related not only to the increase in the volume of distribution but also to the increase in the renal clearance.

Animals↗