PubMed Health⌕ Search

Biomedical subjects

T Nishisato

Publications and source records attributed to T Nishisato.

At least 19 recordsLinked to original sources
PubMed2001

Long-term survival and late-onset complications of cancer patients treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation.

The antitumor effect of high-dose chemotherapy (HDC) followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) is considered superior to that of conventional chemotherapy. However, the long-term benefits of this strategy in Japan remain unclear. Therefore, in this study, 109 cancer patients enrolled between 1989 and 1999 were treated with HDC and auto-PBSCT. Patients were evaluated for long-term survival and late-onset complications, including secondary malignancy. The mean number of CD34+ cells harvested per apheresis was larger in the group receiving high-dose cytosine arabinoside or high-dose etoposide plus granulocyte colony-stimulating factor (G-CSF) than in the group receiving conventional chemotherapy plus G-CSF. The 5-year overall survival rates for non-Hodgkin's lymphoma patients in first complete remission (CR) (83.2%), second or subsequent CR (74.1%), or first partial remission (PR) (66.7%) at the time of transplantation were significantly higher than those with no remission (35.7%) at the time of transplantation (first CR, P < .05; second or subsequent CR, P < .05; first PR, P < .05). The 5-year overall survival (OS) rates for breast cancer was 40.8%, and the disease-free survival rate was extremely low (8.8%). The 5-year OS rates for chemotherapy-sensitive and chemotherapy-resistant diseases at the time of transplantation were 32.7% and 35.7%, respectively, a difference that was not considered significant. The 5-year OS for germ cell tumor was 80.0%, and the disease-free survival rate was 77.9%. The rate of therapy-related death was 8.2%. The occurrence rate of secondary malignancy was 0.9%. Late-onset complications were observed in 4 cases (glomerulonephritis, interstitial pneumonitis, ulcerative colitis, and acute myelogenous leukemia). At 3.7%, the occurrence rate was not very high, but most complications of auto-PBSCT were life threatening and interfered with patients' quality of life. A careful follow-up is required for at least 2 years after transplantation, because the mean occurrence time of late-onset complications is 16.7 months posttransplantation.

Adult↗
PubMed1992

Circulating transferrin receptor in acute leukemias.

Serum transferrin receptor (s-TR) levels in acute leukemia patients were measured by a recently developed sandwich radioimmunoassay. The mean s-TR level for normal subjects (n = 205) was 246 +/- 79 (mean +/- 1 SD) ng/ml. The values for patients with untreated acute myelocytic leukemia (AML, n = 18) and untreated acute lymphocytic leukemia (ALL, n = 14) were 398 +/- 175 ng/ml and 479 +/- 176 ng/ml, respectively, both of which were significantly higher than those for the normal subjects (AML, p < 0.02; ALL, p < 0.05). When complete remission was achieved with initial remission induction therapy, s-TR decreased to 262 +/- 47 ng/ml (n = 22, 12 AML and 10 ALL), returning to normal levels. There was a good correlation between s-TR levels and the number of leukemic cells in peripheral blood (r = 0.743, n = 32, p < 0.01). In two patients with AML, serial changes of s-TR values and numbers of blast cells in the peripheral blood and bone marrow occurred in a parallel manner. If, therefore, this assay for s-TR can be made more sensitive, it may become useful for assessing acute leukemia activity and for monitoring the effects of therapy.

Acute Disease↗
PubMed1990

Kinetics of internalization and cytotoxicity of transferrin-neocarzinostatin conjugate in human leukemia cell line, K562.

Human serum transferrin was conjugated with an anticancer-active polypeptide, neocarzinostatin, by using N-succinimidyl 1-3-(2-pyridyldithio)propionate. The conjugate consisted of 1.8 mol of neocarzinostatin per 1 mol of transferrin on average and retained cytotoxic activity against human tumor cells. This conjugate was capable of binding to the transferrin receptor of human myelogenous leukemia K562 cells and was internalized by endocytosis. The LD50 values of the conjugate and neocarzinostatin alone in the presence of excess native bovine transferrin were 0.20 microgram/ml and 1.80 micrograms/ml, respectively, suggesting that the effect of the conjugate was greater than that of neocarzinostatin alone. A pulse-chase experiment using 125I-labeled conjugate revealed that 25% of the internalized conjugate was degraded in lysosomes and the rest was recycled back to the cell surface without degradation. About 75% of this conjugate recycled back to the cell surface in 18.3 min (3.4 min for receptor binding and 14.9 min for recycling to the cell surface through the acidosomes), while the rest was delivered from the cell surface to the lysosome in 19.6 min. This phenomenon was confirmed by chasing the radioactivity in subcellular fractions separated by Percoll density gradient centrifugation. Therefore, it was concluded that this conjugate is internalized specifically by transferrin receptors and is at least partly transferred to and accumulated in lysosomal compartments, resulting in the inhibition of cellular DNA synthesis.

Antibiotics, Antineoplastic↗
PubMed1988

Quantitation and characterization of serum transferrin receptor in patients with anemias and polycythemias.

Serum transferrin receptor concentration in patients with anemias and polycythemias was determined. The mean normal value was 258 +/- 82 ng/ml. Comparing with normal values, the higher values were obtained in patients with iron deficiency anemia, autoimmune hemolytic anemia, and polycythemias, while the lower values were obtained in patients with aplsatic anemia. During treatments of patients with iron deficiency anemia and autoimmune hemolytic anemia, serial change of serum receptor was paralleled with that of peripheral reticulocyte counts, suggesting that the circulating receptor values may reflect the activity of bone marrow erythropoiesis. The immunoreactive receptor was migrated at the position of alpha 1-globulin by agarose gel electrophoresis and the isoelectric point(pl) was 3.57 by isoelectric focusing. SDS-polyacrylamide gel electrophorogram of various patients' sera revealed that the autoradiographed band was migrated at the molecular weight of 110,000 daltons in the non-reducing condition and 46,000 and 23,000 daltons in the reducing condition. These bands were also capable of binding to 131I-labelled diferric transferrin. The proposed model of circulating transferrin receptor may be the nicked dimers of 55,000 daltons in which inter- and intra-disulfide bridges were present.

Anemia↗
PubMed1987

Externalization of transferrin receptor in established human cell lines.

The externalization of transferrin receptors was found in established human tumor cell lines at the rate of 10-35 ng/hour/10(6) cells, when they were incubated with transferrin at 37 degrees C. This externalization is inhibited by lowering the incubation temperature to 4 degrees C or eliminating the ligand from the culture medium. Metabolic inhibitors such as sodium azide, colchicine, cytochalasin B and chloroquine also decreased the rate of externalization. Almost 95% of released transferrin receptors were precipitated by centrifugation at 100,000 x g for 30 min, suggesting that transferrin receptor is externalized into the medium as a vesicular form.

Biomarkers, Tumor↗
PubMed1987

Transferrin receptors in human cancerous tissues.

The clinical significance of radioreceptor assay for transferrin receptors of human cancerous tissues was evaluated. Fresh surgical specimens from various carcinoma tissues were solubilized with 1% Triton X-100 and the extracts were mixed with 125I-labelled diferric transferrin. The free transferrin and the receptor-bound transferrin were separated by 15% polyethylene glycol precipitation. The % specific transferrin binding to gastric, colonic, lung and mammary carcinoma tissues ranged between 3.9 and 13.9%, whereas those for normal stomach and colon were less than 2%. The concentrations of transferrin receptors in these cancerous tissues ranged between 3.7 and 28.3 pmole/g tissues. It was concluded that the amounts of transferrin receptors were significantly increased in all of the tumor tissue extracts examined and may thereby provide a useful marker for the diagnosis of malignancies.

Humans↗
PubMed1987

Serum transferrin receptor as a new index of erythropoiesis.

Serum transferrin receptors were measured by a sandwich radioimmunoassay procedure in patients with iron deficiency anemia, autoimmune hemolytic anemia and aplastic anemia. The mean circulating transferrin receptor concentration of normal subjects and patients with iron deficiency anemia, autoimmune hemolytic anemia and aplastic anemia are 253 +/- 82 ng/mL, 730 +/- 391 ng/mL, 1,426 +/- 1,079 ng/mL, and 182 +/- 39 ng/mL, respectively. The values for those with iron deficiency anemia and autoimmune hemolytic anemia were significantly higher than that of normal controls and the values for those with aplastic anemia were lower than that of normal controls. After iron supplementation in iron deficiency anemia, the serum transferrin receptor values increased twofold over those of pretreatment values. This increase parallels an increase in peripheral reticulocytes. Therefore, the number of circulating transferrin receptors in anemic patients may reflect the level of bone marrow erythropoiesis and is a potentially useful new index for red cell production.

Anemia↗
PubMed1986

Interaction of transferrin with iron-loaded rat peritoneal macrophages.

Rat peritoneal macrophages are capable, in vitro, of processing and releasing iron derived from phagocytosed, immunosensitized red cells. From 20% to 60% of the red cell iron can be returned to the culture medium in 24 h, with resident macrophages more active than inflammatory, peptone-induced macrophages. When apotransferrin is present in the culture medium, from 39% to 72% of iron released from macrophages is bound to the protein, with most of the remainder in a ferritin-like form. No distinct preference of released iron for either site of transferrin could be observed. The absence of apotransferrin depresses iron release only slightly, with much of the iron then released in a form readily available to the protein in vitro. Pronase treatment of macrophages, which abolishes their ability to bind transferrin, depresses iron release no more than 10-15%. It appears, therefore, that binding of apotransferrin to macrophages may not be essential for iron excretion by the cells.

Animals↗
PubMed1986

Circulating transferrin receptor in human serum.

Circulating transferrin receptor has been detected in human serum with a sensitive immunoassay. The mean concentrations of the serum transferrin receptor in healthy males and females were 251 +/- 94 (mean +/- SD) ng/ml and 256 +/- 99 ng/ml, respectively. The serum receptor concentration in patients with haematological malignancies, including acute leukaemia, multiple myeloma and malignant lymphoma, varied widely, from normal to 1100 ng/ml. A single band with an approximate molecular weight between 80,000 and 100,000 daltons was obtained by polyacrylamide gel electrophoresis-immunoblotting analysis of serum.

Acute Disease↗
PubMed1982

Molecular aspects of the binding of absorbed iron to transferrin.

To study the molecular aspects of the binding of absorbed iron to plasma transferrin, 59Fe with high specific activity was administered via intragastric tube to iron-deficient rabbits. The distribution of the absorbed 59Fe among the molecular forms of iron-transferrin was analysed using urea-polyacrylamide gel electrophoresis. Absorbed iron was bound to circulating transferrin one atom at a time. In four out of five animals, absorbed iron was predominantly bound to the site in the N-terminal domain of the protein. Thus, the two sites of transferrin may differ in their ability to load absorbed iron.

Animals↗