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Biomedical subjects

K Orita

Publications and source records attributed to K Orita.

At least 271 records · Page 15Linked to original sources
PubMed1989

Effects of anti-interleukin-2 receptor antibody and cyclosporin A on human T cell proliferation in primary mixed lymphocyte reaction.

Effects of anti-IL2 receptor antibody (anti-IL2 RAb) and cyclosporin A (CsA) on human T cell proliferation in primary mixed lymphocyte reaction (MLR) were investigated. Both agents inhibited the proliferative response induced by alloantigen in a dose dependent manner when they were added at the initiation of culture. We also analyzed the expression of activation antigen on responder cells and the kinetics of T lymphocyte subset proliferation during MLR using two-color flow cytometry. Cells expressing activation antigens, such as IL-2 receptor and HLA-DR, were found less frequently in anti-IL2 RAb-treated MLR culture (4.8%) than in CsA-treated MLR culture (16.5%) on day 6. Furthermore, proliferation of CD8+CD11- cells, considered a cytotoxic T cell subset, were inhibited significantly more in anti-IL2 RAb-treated MLR culture than in CsA-treated MLR culture. We further demonstrate that CsA inhibits preferentially IL-2 production and anti-IL2 RAb inhibits T cell proliferation by blocking an absorption of IL-2 by activated lymphocytes. These data suggest that anti-IL2 RAb selectively inhibits alloantigen-activated T cells and may prove to be of significant value as an immunosuppressive agent in clinical organ transplantation.

Antibodies↗
PubMed1989

Histopathologic evaluation of response to treatment of human tumors implanted under the renal capsule of normal immunocompetent mice.

The histopathologic changes following chemotherapy treatment of fresh human tumors implanted under the renal capsule of normal immunocompetent mice were evaluated. On the basis of the histopathologic profile of the xenografts, four parameters were recognized: (1) cancer area (C), (2) necrosis area (N) (each measured by image analysis), (3) pathologic effect of cancer cells (P) (assessed histopathologically), and (4) number of mitoses (M) (counted microscopically), and were scored in a semiquantitative fashion from 0 to 2 or 4. The drug sensitivity (S) was scored using the following formula: S = C + P + M - N; this score varied from -4 to 10. Histopathologic changes represent a sensitive indicator of the response of implanted human tumors under the renal capsule to anticancer drugs. Availability and correct interpretation of the post-treatment histopathologic picture is of importance in selecting the proper combination treatment which would maximize tumor response.

Adenocarcinoma↗
PubMed1989

[Estrogen and androgen receptors in hepatocellular carcinoma and in noncancerous liver tissue].

We have assayed both estrogen and androgen receptors in hepatocellular carcinomas, in the surrounding noncancerous liver tissue, and in normal liver tissue. Estrogen receptors (ERs) were detected in 5 out of 22 HCC tissues, 14 out of 22 surrounding noncancerous tissues, and in 5 out of 6 normal liver tissues. Androgen receptors (Ars) were detected in 4 out of 21 HCC tissues, in 7 out of 21 surrounding noncancerous tissues, and in 2 out of 5 normal liver tissues. These results suggest that the pathogenesis of some HCC may be dependent on estrogen or androgen. Hence, it may be beneficial to provide hormonal therapy for HCC, especially in cases that show high concentrations of ER and/or AR.

Adult↗
PubMed1989

[HCFU and 5-fluorouracil levels in the blood and tissue of hepatocellular carcinoma after oral administration of HCFU].

HCFU was orally administered to 14 patients with hepatocellular-carcinoma, (including 11 patients with liver cirrhosis) and evaluated of HCFU and 5 fluorouracil (5-FU) levels. Blood and tissue 6-8 hr. after oral administration. The concentration of 5-FU in tissue was almost in the effective levels. In addition, the 5-FU level in the tissue of hepatocellular carcinoma tended to be higher than in non cancerous portion of the liver. 5-FU tissue concentration was not correlated with various laboratory data for the liver function (K-ICG, T. bil, GOT, GPT, etc.) From these results, it is suggested that HCFU is a useful anticancer agent for hepatocellular carcinoma especially for the cases accompanied liver cirrhosis.

Administration, Oral↗
PubMed1989

[The effect of endoscopical intratumoral injection of OK-432 in gastric carcinoma].

Many BRMs (biological response modifiers) have been used for post-operative immunochemotherapy. And their usefulness were also reported. Nevertheless it is still unknown that which route, how much doses and which timing are the most effective to administer these drugs. We used BRMs intratumorally and preoperatively. To reconfirm the efficacy of intratumoral injection therapy randomized study was performed in gastric carcinoma. Three hundred and ninety-five cases were entered, 199 cases in group A which were treated preoperatively with OK-432 intratumorally and 196 cases in group B which were control, respectively. In the cases which had marked infiltration of lymphoid cells in tumor sites, the two year survival rate of group A was significantly better than that of group B (p less than 0.05). On the study of recurrent forms, the distal lymph node metastasis was markedly decreased in group A. The ratio of metastasis to the distal lymph nodes in group A was 5-10% lesser than that in group B on the each depth of tumor invasion. The ratio of lymph nodes metastasis was almost similar in the each group, but the number of metastatic lymph nodes was significantly reduced in high grade tumor infiltrated cases in group A (p less than 0.005). These results suggest that preoperative endoscopically intratumoral administration of OK-432 suppresses the lymph node metastasis and improves the postoperative survival rate.

Biological Products↗
PubMed1989

[The metastatic tumor and immunotherapy].

Metastasis is one of the great characteristics of malignant tumors. On the basis of our data, we reported here the immunotherapy for hematogenous metastasis. A randomized controlled study of preoperative transendoscopic intratumoral injection of BRM into gastro-intestinal cancer, which was performed in our Department, revealed a decreasing tendency of distant metastases in lymph node for the injection group, suggesting the disappearance of micro-metastasis due to the injection, namely, systemic immuno-enhancement due to the local effect, leading to diminution of hematogenous metastasis. Next, a mixture of natural human TNF-alpha (nHuTNF-alpha) and natural human IFn-alpha(nHuIFN-alpha), the so-called OH-1, was described. The results of a clinical study dealing with the antitumor effect on advanced and recurrent malignant tumors made it clear that all of the effective results (72 cases) such as CR and PR were obtained by an administration schedule with a maintenance dose of more than 200 X 10(4)U; rate of efficacy was 19.4% (4 cases of CR, 10 of PR and 4 of MR). By disease, breast cancer, renal cancer and liver cancer evidenced the most remarkable effects. Examination of the antitumor effect by metastatic organ revealed the effectiveness on hematogenous metastasic tumor of lung, bone and liver, though dependent upon underlying diseases. Finally, being based on our in vitro and in vivo results, we discussed the role of these immunotherapies for metastatic tumors.

Humans↗
PubMed1989

[On the activity of the Japanese Research Society for Surgical Cancer Immunology].

The recent progress in immunology has shown depression of immunological competence, especially cellular immunity in tumor bearing host due to anesthesia, blood transfusion and operative trauma itself and disappearance of host's concomitant immunity caused by removal of primary tumor, resulting the enhancement of growth of residual tumor or metastatic foci. The prophylactic lymph node dissection in cancer operation must be reconsidered through immunological studies of lymph node as immunological surveillance system. Splenectomy combined with the operation of stomach cancer must also be reconsidered. Therefore, the main aims of this society are to suppress the negative aspect in connection with the cancer operation by means of immunotherapeutic approach and to prevent the recurrence and/or metastasis of cancer. Research society, met for the first time in 1980, and has since discussed the following main themes at 9 occasions of meetings up to 1988: 1. Pre- and postoperative immunological competence in cancer patients. 2. Surgery and immunological competence for cancers. 3. Antitumor activity of regional lymph nodes. 4. Splenectomy and tumor growth. 5. Surgical treatment and immunochemotherapy. 6. Serum immunosuppressive factors in cancer patients. 7. BRM and immunotherapy. 8. Diagnosis and treatment of cancer using monoclonal antibody. 9. Cancer treatment using IL-2, TNF. 10. Host defense factors and cancer metastasis. In addition, 14 educational lectures dealing with recent immunology have been given by immunological specialists.

Humans↗
PubMed1989

Clinical application of cascade filtration combined with glassbead adsorbents in cancer patients.

Cascade filtration (CF) was applied to patients with advanced cancers. To selectively remove immunosuppressive factors with molecular weight lower than albumin, adsorbents combined with CF were examined. Among 11 kinds of adsorbents, glassbead adsorbents with pore size 100A were the most effective in adsorbing such substances. Clinically, a column packed with glassbead adsorbents was concomitantly used with CF. The second filtrate was passed through the column and returned to the patient. The removal rate of immunosuppressive substances with molecular weight lower than albumin was only 20% by CF alone, but more than 50% by CF combined with glassbead adsorbents. Clinical symptoms such as severe back pain and general malaise were drastically improved during and after therapy. These results suggest that CF combined with glassbead adsorbents is an effective adjunctive modality to cancer therapy.

Adsorption↗
PubMed1989

Suppression of lymphokine activated killer (LAK) cells by immunosuppressive substance.

We investigated the effect of immunosuppressive substance (ISS) on the immune responses mediated by interleukin 2 (IL 2). The induction of LAK cells was intensely inhibited by a high concentration of ISS (1000 micrograms/ml), but a low concentration of ISS (250-500 micrograms/ml) had no affect on the generation of LAK cells. ISS had no ability either to neutralize the activity of IL 2, or to compete with IL 2. Endogenous production of IL 2 in PHA response was not reduced by ISS, but the expression of the IL 2 receptor in the PHA response was significantly suppressed by ISS. These results suggest that ISS exerts its inhibitory effect on immune response-mediated IL 2 through modification of the IL 2 receptor.

Cell Division↗
PubMed1989

Comparison of the subrenal capsule assay and succinate dehydrogenase inhibition test.

Fresh surgical explants of solid tumors obtained from 50 patients were tested against the same chemotherapeutic agents in both the in vivo subrenal capsule (SRC) assay and the in vitro succinate dehydrogenase inhibition (SDI) test. Control growth adequate to meet evaluable assay criteria was obtained in 36 of 50 tumors tested in the SRC assay (72.0%). In the SDI test, 46 of 50 tumors were evaluable (92.0%). Correlations between the two test systems were dependent upon the activity criteria established for each system. With activity criteria set at current drug screening levels as a change of less than or equal to -2.0 in modified PAPAN score (S) for the SRC and an inhibition of greater than or equal to 50.0% in succinate dehydrogenase activity (SD) for the SDI, 12.5% of the drugs tested were active in the SRC and 22.3% were active in the SDI. Correlations of tumor response between the two test systems were 31.7% for sensitive (13/41) and 95.1% for resistant (98/103).

Antineoplastic Agents↗
PubMed1989

Effects of bile duct ligation and dietary change on hepatic carbohydrate metabolism in rats.

Effects of bile duct ligation and dietary change on hepatic carbohydrate metabolism in rats were studied by analyzing the levels of fructose 2,6-bisphosphate (fructose-2,6-P2) and other metabolites. There was no significant difference in the levels of fructose-2,6-P2 and glycolytic intermediates between rats with and without bile duct ligation when rats were in a fed state. However, the levels of fructose-2,6-P2, hexose monophosphates, and triose phosphates increased and the level of plasma glucose decreased in rats with bile duct ligation in a starved state. The crossover analysis of gluconeogenic intermediates in rats with bile duct ligation showed accumulations of hexose monophosphates together with fructose-2,6-P2 in spite of the starved state of rats, indicating an impaired conversion of glucose 6-phosphate to glucose. Despite the activation of the fructose 6-phosphate-fructose 1,6-bisphosphate futile cycle as indicated by these findings, the energy charge levels were not reduced. The block at the level of glucose production may explain the relative predominance of insulin effect on glycolysis.

Adenine Nucleotides↗
PubMed1988

Interferon-gamma activates the voltage-gated calcium channel in RPMI 4788 cells.

Interferon (IFN) increases cytoplasmic free calcium ([Ca2+]i) in RPMI 4788 cells, a human colon cancer cell line. Addition of IFN to the cells loaded with Fura-2, a fluorescent Ca2+ indicator, causes an immediate increase in [Ca2+]i, which is the earliest event after IFN stimulation. A cyanine dye, dis-C3- (5) was used to determine the effects of IFN on the membrane potential in cancer cells. The depolarization was seen with IFN-gamma, but not with IFN-beta. These results taken together, suggest that the IFN-gamma and -beta induced [Ca2+]i mobilization are clearly different in their dependence on Ca2+ entry through voltage-gated Ca2+ channels.

Calcium↗
PubMed1988

Alterations in key carbohydrate-metabolizing enzyme activities in rat livers following bile duct ligation and its release.

Activities of key carbohydrate-metabolizing enzymes in the livers of rats after bile duct ligation were studied during the recovery phase, after releasing the bile duct from ligation as an external biliary drainage. Enzyme activities were analyzed on the 3rd and 7th days after ligation and on the 3rd and 7th days after releasing the ligation. The altered enzyme activities, which resulted from the ligation of the bile duct, recovered after its release, although the recovery was delayed as when compared with those in the serum liver function tests. Glucokinase was the enzyme which was most delayed in recovery. The decreased activity of glucokinase had not returned to normal, even on the 7th day after release of the bile duct from its 7 day-ligation, whereas all the other enzyme activities had returned to normal by this time. It was also suggested that the decreased activity of glucokinase, which regulates the glucose uptake by the liver, was related to the glucose intolerance in obstructive jaundice. Accordingly, glucokinase can be used as a marker for determining the time of operation after biliary drainage.

Animals↗