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Biomedical subjects

E Yanagawa

Publications and source records attributed to E Yanagawa.

At least 37 records · Page 2Linked to original sources
PubMed1986

[Immune reactivities of lymphocytes from peripheral blood, regional lymph nodes and tumor-infiltrating lymphocytes in breast cancer].

Immune reactivities in 174 breast cancer patients were investigated. Immune reactivities were assessed by lymphocyte responsiveness to phytohemagglutinin (PHA), suppressor cell activities, sera-induced suppressor cell activities, NK activities and autologous tumor-killing activities. Low responsiveness of peripheral blood lymphocytes (PBL) to PHA mitogen and an increase in the inductive activity of suppressor cells by sera were observed in breast cancer patients as compared with normal volunteers or patients with benign breast diseases. These impairments of immune reactivities were compared with those of patients with cancer of the digestive tract. Cytotoxicities against both K562 and autologous tumor cells were low or absent in the regional lymph node lymphocytes (LNL). Cytotoxicities against autologous tumor cells were absent in tumor-infiltrating lymphocytes. The low NK activity of LNL was not due to coexistent suppressor cells but to a lack of active NK cells and/or their precursors. NK activities of LNL were augmented by IL-2 and OK-432, suggesting usefulness for local immune therapy.

Breast Neoplasms↗
PubMed1986

[Microangiopathic hemolytic anemia associated with gastric cancer].

A case of advanced gastric cancer associated with metastatic carcinomatosis of the bone marrow, microangiopathic hemolytic anemia (MAHA) and disseminated intravascular coagulation (DIC) was reported. A 71-year-old woman complained of lumbago and general fatigue. At the time of admission, besides anemia, jaundice and a tendency to bleeding, the laboratory data showed, hyperbilirubinemia, elevated FDP and hemolytic anemia with fragmented red cells. The bone marrow was infiltrated by carcinoma, and an upper GI series examination showed Borrmann II type gastric cancer on the greater curvature of the antrum. After remission of both MAHA and DIC by mitomycin C, neothramycin and FOY, the patient successfully underwent subtotal gastrectomy. However, she died of cerebral hemorrhage on the 96th postoperative day.

Adenocarcinoma↗
PubMed1986

[Development of cancer immunotherapy by a combination of biological response modifiers on the basis of their mechanism of action].

The enhancement of antitumor effects by combination of biological response modifiers (BRM) was investigated on the basis of their action mechanisms. Experimentally, significant inhibition of tumor growth by combination treatment with BRM, which eliminated immune suppressive mechanisms and in turn enhanced immune responses, was observed. Furthermore, inhibition of tumor growth was observed under conditions of uniform biorhythm in mice and the effect of modification of biorhythm was enhanced by combination with BRM. Clinically, combination treatment of plasma exchange and LAK-cell adoptive immunotherapy was discussed.

Animals↗
PubMed1985

Autologous tumor killing and natural cytotoxic activity of tumor-associated macrophages in cancer patients.

Tumor-associated macrophages (TAM) isolated from pleural effusions and ascites fluids of cancer patients were tested for cytotoxicity against freshly isolated autologous tumor cells and K562 in a 4-h 51Cr-release assay, and in vitro effects of OK432 (a streptococcal preparation) and partially purified human leukocyte interferon (IFN) on their cytotoxicities were examined. Positive cytotoxicities against K562 were recorded for TAM samples from 2 of 23 pleural effusions and 3 of 10 ascites specimens. Tumor-associated macrophages were not cytotoxic to autologous tumor cells, while low but significant lysis was observed with tumor-associated lymphocytes (TAL) samples from 2 of 13 pleural effusions and 1 of 6 ascites specimens. In vitro treatment with OK432 resulted in an enhancement of natural cytotoxicity in 4 of 13 TAM and 10 of 15 TAL samples. An induction or augmentation of autologous tumor killing activity by OK432 was observed in 2 of 10 TAM and 8 of 11 TAL samples. In contrast, IFN failed to induce autologous tumor killing activity, although IFN-enhanced lysis of K562 was detected in 1 of 7 TAM and 2 of 9 TAL samples. These results indicated that autologous tumor killing and natural cytotoxic activities were defective in macrophages and lymphocytes at the site of the tumor growth, and both activities were strongly enhanced by OK432 rather than IFN.

Antibodies, Monoclonal↗
PubMed1984

Natural cytotoxicity of lymphocytes and monocytes and its augmentation by OK432 in melanoma patients.

Lymphocytes and monocytes from the peripheral blood of 30 patients with malignant melanoma were tested for natural cytotoxicity against K562 cells in a 3-h 51Cr-release assay, and the effects of OK432 (a streptococcal preparation) on the cytotoxicity were examined. The lymphocyte cytotoxicity of melanoma patients was similar to that of normal donors and control patients with benign skin disease. Furthermore, the lymphocyte cytotoxicity of melanoma patients was not correlated to the stage of the disease. Similarly, lysis of K562 cells by monocytes isolated by adherence to autologous serum-coated plastic dishes in melanoma patients was comparable to that of controls and not associated with the stage of the disease. Positive monocyte reactions were recorded in 10 of 30 (33%) melanoma patients, seven of 21 (33%) normal donors and three of 10 (30%) control patients. There was no correlation between lymphocyte cytotoxicity and monocyte cytotoxicity. Overnight treatment of monocytes and lymphocytes with OK432 resulted in an increase in cytotoxicity. Significant augmentation of cytotoxicity by OK432 was observed in 28% of the monocyte samples and 86% of the lymphocyte samples, while partially purified human interferon augmented cytotoxicity in 63% of the monocyte samples and all the lymphocyte samples. These results suggest that neither lymphocyte nor monocyte cytotoxicities are depressed in melanoma patients as compared with normal donors and patients with benign disease and that OK432 has a stronger stimulatory effect on lymphocytes than on monocytes.

Adult↗
PubMed1984

Natural cytotoxicity of lymphocytes from lymph nodes draining breast carcinoma and its augmentation by interferon and OK432.

Lymphocytes isolated from axillary lymph nodes draining breast carcinoma were tested for natural killer (NK) activity against K562 in a 4-h 51Cr-release assay, and the in vitro effects of interferon (IFN) and OK432 (a streptococcal preparation) on their cytotoxicity were examined in comparison with NK activity of autologous peripheral blood lymphocytes (PBL). The levels of NK activity were lower in lymph node lymphocytes (LNL) than in PBL of the same patients. Significant levels of LNL-mediated lysis were recorded in 14 of 42 (33%) lymph node samples and in nine of 14 (64%) patients. Purification of large granular lymphocytes (LGL) from lymph node cells by discontinuous Percoll density gradient centrifugation resulted in an induction or enhancement of cytotoxic activity, with no reactivity in LGL-depleted, small T-lymphocyte populations. Positive reactions were observed with 10 of 13 (77%) LGL samples. The low reactivity of LNL was not attributable to coexistent suppressor cells for NK function, since lymph node cells failed to suppress NK activity of normal PBL. Partially purified human IFN and OK432 augmented NK activity of patients' PBL in approximately 70% and 90% of the cases, respectively, while LNL-mediated lysis was augmented in only 7% and 36% of the lymph node samples by IFN and OK432, respectively. These results indicate that K562-reactive NK cells and/or their precursors may frequently be present at subthreshold levels in the lymph nodes draining breast carcinoma, and that the augmentation of LNL-mediated cytotoxicity by OK432 might provide a local potentiation of natural immune function at the host-tumor interface rather than IFN.

Axilla↗
PubMed1984

Natural cytotoxicity of human blood monocytes: production of monocyte cytotoxic factors (MCF) during interaction with tumor cells.

Human blood monocytes obtained by EDTA-reversible adherence to autologous serum-coated plastic dishes expressed natural cytotoxicity against NK-sensitive K562 cells in a 4-h 51Cr release assay. These monocytes released soluble cytotoxic factors, termed monocyte cytotoxic factors (MCF), when cultured with target cells. In contrast, blood monocytes obtained by adherence to fetal calf serum-coated plastic surfaces failed to kill K562 cells and to produce MCF. Although some lysis could be detected at 18 h, optimal lysis of K562 cells by MCF was observed after 48 h incubation in a microcytotoxicity assay using trypan blue dye exclusion. The addition of actinomycin D to the cytotoxicity assay enhanced the sensitivity and then NCF activity was detectable in a 18-h Cr release assay. Neither supernatants produced by culture of monocytes alone nor lysates of monocytes were cytotoxic. In addition, cytochalasin A inhibited both direct cell-mediated lysis and generation of MCF. Optimal production of MCF occurred after 6-24 h of interaction with K562 cells, although significant activity was already present by 3 h. Treatment of monocytes with OKM1 monoclonal antibody plus complement abrogated both cell-mediated lysis and MCF generation, whereas Leu-11b plus complement were ineffective. These results indicate that human blood monocytes can release MCF during interaction with tumor cells and that this may be involved in the lytic mechanism of monocyte-mediated natural cytotoxicity.

Cells, Cultured↗
PubMed1984

In vitro modulation of human natural killer cell activity by interferon: generation of adherent suppressor cells.

The in vivo and in vitro effects of human alpha-interferon (IFN) on blood natural killer (NK) cell activity were studied in patients with malignant melanoma. The initial response to an i.m. injection of IFN was a depression of blood NK cell activity, being detectable at 4 h and reaching a nadir at 12 h. Blood NK cell activity returned to or exceeded pretreatment levels within 24 h. The frequency of large granular lymphocytes among peripheral blood lymphocytes (PBL), however, remained unchanged during the first 24 h of IFN treatment. In a single cell cytotoxicity assay in agarose the number of lymphocytes forming conjugates with K562 target cells was not affected at 12-h points of IFN treatment, while the frequency of lytic conjugates with dead target cells was decreased by 12 h. Thus, the number of active NK cells was reduced by IFN administration. While in vitro exposure to IFN resulted in an augmentation of NK cell activity of PBL from untreated patients, IFN failed to enhance the activity of PBL obtained 12 h post IFN injection. When PBL obtained 12 h after IFN injection were cultured overnight, they recovered their responsiveness to NK-boosting effects of IFN. Blood monocytes obtained at 12-h points from IFN-treated patients suppressed IFN-induced enhancement of NK cell activity, although these monocytes did not inhibit the base line level of NK cell activity. In contrast, the streptococcal preparation OK432 was able to augment NK cell activity of PBL obtained 12 h post IFN administration and of control PBL even in the presence of suppressor monocytes. PBL obtained 24 h post IFN injection expressing enhanced NK cell activity were also unresponsive to IFN in vitro. However, monocytes obtained 24 h after IFN injection were no longer able to inhibit IFN-induced augmentation of NK cell activity. These results indicate that in vivo administration of IFN-alpha to cancer patients results in rapid and transient generation of suppressor monocytes capable of inhibiting IFN-dependent development of functional NK cell activity, which could be responsible for the initial and transient decline in blood NK cell activity.

Cells, Cultured↗
PubMed1984

Natural killer cell activity and autologous tumor killing activity in cancer patients: overlapping involvement of effector cells as determined in two-target conjugate cytotoxicity assay.

The relationship between natural killer (NK) cell activity and autologous tumor killing activity was examined in patients with carcinomatous pleural effusions (PE) by means of a two-target conjugate cytotoxicity assay. Enrichment of large granular lymphocyte(s) (LGL) by discontinuous Percoll gradient centrifugation resulted in an augmentation of cytotoxicity against both K562 cells and tumor cells freshly isolated from PE of the same patients in a 4-hour 51Cr release cytotoxicity assay. At the single-cell level, the LGL-enriched fraction contained an increased number of effector cells that bound to autologous tumor cells and to K562 cells, as well as an increased frequency of cells cytotoxic to these target cells. In the two-target conjugate cytotoxicity assay, a single lymphocyte in the LGL population simultaneously bound to both a fluorescein-labeled K562 cell and a nonfluorescent autologous tumor cell. A significant number of lymphocytes in these mixed two-target conjugates lysed both autologous tumor cells and K562 cells after 6 hours' incubation, although overall lysis of K562 cells was higher than that of autologous tumor cells. These results indicate that a single LGL is involved in the lysis of both autologous tumor cells and K562 cells and thus provide direct evidence of involvement of subsets of NK cells in autologous tumor cell killing.

Cell Line↗
PubMed1982

Prognostic significance of lymphocyte proliferative responses to mitogens in gastric cancer patients.

In 501 Japanese patients with gastric cancer, the relationships between preoperative lymphocyte proliferative (LP) responses to mitogens and prognosis of patients were evaluated. Peripheral blood lymphocytes were cultured in the presence of either autologous or allogeneic serum and their LP responses to phytohemagglutinin (PHA) and pokeweed mitogen were investigated. An apparent inverse relationship between LP responses and stage of the disease was found in LP responses to PHA in the presence of autologous serum. The survival rate of patients with higher responses was significantly greater than those with lower responses, when LP responses to PHA in the presence of autologous serum served as the criterion. Probabilities of staging which were computed on the basis of LP response to PHA affirmed the reciprocal relationship between LP responses and stage of the disease. From these results, it is concluded that evaluation of LP responses may be a valuable tool in the assessment of the clinical stage and in the prediction of prognosis.

Adult↗
PubMed1982

[The relationship between serum immunosuppressive acidic protein (IAP) and cellular immunity in the patients with gastric cancer].

IAP (immunosuppressive acidic protein), one of the serum immunosuppressive factors, was investigated in the preoperative patients with gastric cancer. IAP values in sera from patients increased in accordance with advances of the disease. In the study of quantitative correlation of IAP with immunological parameters, IAP values correlated slightly with lymphocyte proliferative response to PHA, while a significant correlation between IAP values and spontaneous suppressor T cell activities was noted (p less than 0.01). These results suggested that IAP as well as immune complex might serve as a signal for the activation of suppressor T cells in vivo.

Concanavalin A↗
PubMed1981

Combined treatment of syngeneic murine tumors and xenotransplanted human lung cancer by immunotherapy and radiotherapy.

The synergistic effect of nonspecific immunotherapy with cell-wall skeleton of BCG on radiotherapy against two syngeneic murine tumors, a methylcholanthrene-induced tumor (MCA) and a spontaneous well-differentiated mammary adenocarcinoma (Br-1), was studied in (+/+) balb/c mice and (nu/nu) mice of BALB/c background. Single irradiation of tumors with a dose of 2000 rad induced complete shrinkage in about 18% of MCA and Br-1 tumors in (+/+) mice. Single irradiation did not induce complete shrinkage of tumors in (nu/nu) mice. When immunotherapy was combined with radiotherapy, the rates of complete shrinkage of MCA and Br-1 tumors increased to 82 and 61%, respectively. In contrast, such a strong synergistic effect was not observed in (nu/nu) mice. Moreover, human lung cancers (two squamous cell carcinomas and two small cell carcinomas) xenotransplanted to nude mice were treated with the combined therapy. The effect was stronger on squamous cell carcinomas than on small cell carcinomas.

Animals↗
PubMed1981

Scanning electron microscopic studies on the surface structure of activated macrophages and on their interaction with tumor cells.

Experiments on peritoneal macrophages obtained from Corynebacterium parvum (C. parvum)-treated or untreated normal mice were performed in order to quantitate the cytotoxic activities and surface morphological modifications. The cytotoxic activities of activated macrophages were significantly higher than those or normal macrophages. There were prominent differences in surface morphology between C. parvum-activated and normal macrophages as seen by scanning electron microscopy. The activated macrophages were larger and exhibited higher surface membrane activities than normal macrophages. In interaction between macrophages and tumor cells, both activated and normal macrophages were observed to come into contact with target tumor cells during the first 24 hr. The surfaces of tumor cells entirely lost their microvilli and showed pores. Tumor cells finally died after interaction with activated macrophages for 48 hr. In contrast, no significant alterations were observed on the surfaces of tumor cells incubated with normal macrophages. In conclusion, it seems that the cytotoxic activities of macrophages correlate with the extent of macrophage activation, and the activation correlates with the surface membrane alterations.

Animals↗
PubMed1980

Concanavalin A-activated suppressor cell activity in gastric cancer patients.

Peripheral blood lymphocytes from both normal donors and gastric cancer patients contained suppressor cells which could be activated by concanavalin A (Con A) to suppress the proliferative response of lymphocytes from a normal donor. Con A-activated suppressor cells resided in the E rosette-forming cell fraction. An apparent inverse relationship was found between Con A-activated suppressor cell activity and lymphocyte proliferative response to phytohemagglutinin. Significant increases of suppressor cell activities were found in advanced gastric cancer patients. These activities decreased remarkably after surgical resection of the primary tumors. It is likely that nonspecific suppressor cells represent one of the major factors inducing immunosuppression in gastric cancer patients.

Adult↗