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Biomedical subjects

K Orita

Publications and source records attributed to K Orita.

At least 415 records · Page 23Linked to original sources

Immunotherapy of gastrointestinal cancer patients with levamisole.

Levamisole was administered to 177 patients with gastrointestinal cancer (88 curative resection, 58 noncurative resection and 31 without resection). It was administered at a daily dose of 150 mg for three consecutive days every other week. The administration was started, as a rule, 3 days before operation. This medication was repeated as frequently as possible at least for one month. The cellular immunity and 18-month survival rate of treated and control groups were compared. Levamisole effectively improved peripheral lymphocyte blastformation against phytohemagglutinin and increased the numbers of peripheral blood lymphocytes. Levamisole caused extremely high blastformation rates, in general, enhanced PPD reactions in non-curative resection cases 7 months after operation and showed no influence upon the number of peripheral blood lymphocyte. The effect of levamisole on the 6-month survival rate was most marked in patients without resection. Increased 12-month survival rate was marked in non-curative resection cases and, to a lesser extent, curative resection cases. Patients without resection had a slightly improved 12-month survival rate. Levamisole improved the 18-month survival rate in resectable cases; however, there were no significant differences in 18-month survival between levamisole and control groups of patients not undergoing resection. The results suggest that levamisole is effective in the patients whose tumor cells have been decreased by any method.

Esophageal Neoplasms↗

Cancer immunotherapy with levamisole.

Levamisole, an agent acting upon depressed cellular immunity, enhancing and normalizing it and consequently showing antitumor activity in the cancer-bearing body, was administered to patients with gastrointestinal cancer at a daily dose of 150 mg for three consecutive days every other week, starting as a rule, three days before operation. The patients were evaluated for survival. Of the 143 patients (66 with curative resection, 40 with noncurative resection and 37 without resection) who received levamisole therapy for one month or more, 57 survived postoperatively six months and of 44 treated 37 survived one year. In this study, 185 patients with gastrointestinal cancer were used for comparison purposes. The six-month survival rate was 100% (23/23) in the levamisole treated group and 95.3% (102/107) in the control group after curative resection (p greater than 0.5), 100% (23/23) and 90.5% (49/54) after noncurative resection (p less than 0.01), and 72.5% (8/11) and 33.3% (9/24), respectively, in non-resectable patients (p less than 0.01). The one-year survival rate was 100% (21/21) and 95.3% (102/107) after curative resection (p greater than 0.5), 77.8% (14/18) and 59.3% (32/54) after noncurative resection (0.05 less than p less than 0.1), and 40% (2/5) and 8.3% (2/24) in non-resectable patients (0.05 less than p than 0.1) in the levamisole group and in the control group, respectively. The difference in survival in survival rates between levamisole-treated and control groups was most prominent in the non-resectable patients followed by those undergoing noncurative resection and curative resection.

Clinical Trials as Topic↗

Immunotherapy of gastric cancer with levamisole.

Ninety-nine gastric cancer patients initially received levamisole at a daily dose of 150 mg for three consecutive days before operation. This therapy was repeated fortnightly (3-day administration followed by 11-day withdrawal period) for more than one month as long as possible and the survival rate up to 18 months was compared with thas of control patients. The 18 month survival rate of advanced Stage IV patients was significantly higher in patients receiving levamisole than that of control patients. The effects of levamisole in cases of advanced cancer have been discussed in relation to the literature available.

Humans↗

Change of macrophage migration inhibitory factor: possible indicator for postoperative prognosis.

Sixty three cancer cases who received minimum of the removal of the main tumor constitute the subjects of the present study. Macrophage migration inhibitory factor (MIF) of peripheral blood lymphocytes was studied using extirpated autochthonous tumor tissues as antigen and guinea-pig peritoneal exudative cells as indicator cells immediately before the operation and the fourth postoperative week. The results indicated that in those cases of relatively early stage, i.e. Stages I and II, whose tumor was believed to have been removed completely, MIF turned negative in 7/9 (77.8 per cent) after the operation, while in others with advanced cancer of Stage IV in which the tumor bearing tissue was probably not completely removed, MIF turned positive in most cases (13/17: 75.6 per cent) postoperatively, even though it was negative before the operation. In the cases of Stage III with cancer progressed to an intermediate degree, in about half of the cases (7/11: 63.6 per cent) MIF turned negative after the operation and in the other half (7/10: 70 per cent) MIF became positive postoperatively, suggesting that for MIF to persist the presence of certain amount of tumor tissue is necessary.

Adult↗

Early diagnosis of acute renal allograft rejection: efficacy of macrophage migration inhibition test as an immunological diagnosis.

1. Three cases of acute rejection were detected by macrophage migration inhibition tests (MIT) conducted directly on seven patients who had received renal allografts. The macrophage migration inhibitory factor (MIF) activity was positive in all cases 1-2 days before the appearance of acute rejection. 2. After the administration of a high dose of Solu-Medrol (1g/day for 3 days) to suppress the acute rejection, MIF activity recovered to its normal level 3 days later. These findings seem to indicate that MIT yields immunologically useful criteria for the early detection of an acute rejection.

Adult↗

Cancer immunotherapy with surgery.

With the recent advances in the immunological surveillance system, an understanding of the role of host immunity has become essential to the management of carcinogenesis, tumor proliferation, recurrence and metastasis. Although it is important to continue chemical and surgical treatment of cancer, support of the anti-tumor immune system of the host should also be considered. Long term remission has been reported in leukemia by treating with BCG after chemotherapy whereas surgical treatment is usually more effective in preventing cancer recurrence in digestive organ cancer. The first step is extirpating the tumor as thoroughly as possible and the second step is chemo-immunotherapy. Cancer immunity, however weak, constitutes the basis for other treatments in selectively attacking cancer cells remaining after surgery, chemotherapy or irradiation. Immunotherapy should thus not replace chemotherapy or radiotherapy, but these methods should be employed in combination to attain more favorable results.

Aged↗

Preoperative blastformation rate in gastrointestinal cancer patients.

The rate of blastformation of peripheral blood lymphocytes in response to stimulation by phytohemagglutinin (PHA) was assessed preoperatively in 393 patients with gastrointestinal cancer. The series consisted of 291 cases of gastric cancer and 102 cases of colon cancer, all patients being under 70 years of age. The blastformation rate was related to the stage of cancer ground at operation. Preoperative blastformation rates for both colon cancer and gastric cancer decreased as the cancer progressed. With Stage I gastric cancer 81.4% of those that underwent curative resection had preoperative blastformation rates greater than 40%. However, the number of those with blastformation rates over 40% decreased markedly in the curative cases of gastric cancer Stage II to stage IV. Eighty three percent of cases that underwent curative resection with colon cancer, including advanced cancer, had preoperative blastformation rates of over 40%. These results indicated that the correlation of the preoperative blastformation rate with success of curative resection better for colon cancer than for gastric cancer.

Aged↗

Reactivating effect of levamisole on cell-mediated immunity in gastrointestinal cancer patients.

Cell-mediated immunity was studied in 23 cases of advanced gastrointestinal cancer. The patients received levamisole at 150 mg/day for three consecutive days each week for four weeks. In cases at the terminal stage of gastrointestinal cancer, the blastformation rate of peripheral blood lymphocytes against phytohemagglutinin (PHA) after the administration of levamisole showed a slight increase, but cases with blastformation rates over 40% increased markedly three or four weeks after the initial administration of levamisole. The peripheral blood lymphocyte count showed little change in these cases.

Gastrointestinal Neoplasms↗

Correlation between postoperative prognosis in gastrointestinal cancer patients and blastformation rate of lymphocytes.

Gastrointestinal cancer patients were followed up for up to 30 months postoperatively and their clinical status related to a parameter of nonspecific immunity, the blastformation rate of peripheral blood lymphocytes against phytohemagglutinin. By the fourth postoperative week, the blastformation rate had recovered from the effect of the operation. In patients who had undergone curative resection, the postoperative level rose to exceed the preoperative level, whereas whereas in those in whom resection had not been possible, the blastformation rate failed to show this rise by the fourth week, and continued at the decreased immediate postoperative level. Results for long-term follow-up (30 months postoperatively) showed that the blastformation rate continued at high levels (almost all over 40%) in cases of curative resection without recurrence, but remained low (under 40%) in those in which the tumor could not be removed. The 40% level of the blastformation rate test thus correlated well with the prognosis. The blastformation rate, therefore, proved a very good parameter for following the pre-and post-operative clinical course of gastrointestinal cancer patients.

Gastrointestinal Neoplasms↗

Effect of splenectomy in tumor-bearing mice and gastric cancer patients.

In order to investigate the effect of splenectomy on tumor growth, splenectomy was performed in DDS mice transplanted subcutaneously with Ehrlich ascites tumor cells before and after the transplantation. It was found that, in the first control group receiving sham operation, all the mice died of tumor; in the second group that underwent splenectomy 1 week before the transplantation the tumor regressed in every case; in the third group that received splenectomy 5 days after transplantation when tumor became established, the tumor regression was observed in 85% of the animals, and in the fourth group that underwent splenectomy 10 days after transplantation, all the animals died of tumor earlier than the sham-operated first group. In the follow-up observations of 389 patients with gastric cancer who underwent gastrectomy alone and 89 cases who received gastrectomy combined with splenectomy, the 5-year survival rate of the latter group tended to show a better prognosis in a relatively early stage. It was concluded that splenectomy might inhibit the growth of tumor in a certain early stage, in both animals and humans, and the possible mechanism of this effect of splenectomy was discussed from the immunological aspects.

Animals↗

Preoperative cell-mediated immune status of gastric cancer patients.

The status of cell-mediated immunity was studied in 360 patients with gastric cancer before surgery. For the skin test, tuberculin and DNCB were employed. For the in vitro test, the blastogenesis of peripheral blood lymphocytes to phytohemagglutinin (PHA), the ratio of rosette-forming T cells to sheep blood red cells, and the macrophage migration inhibiotry factor against autochthonous tumor antigens were measured. As a result, it was found that in progressive gastric cancers the cell-mediated immunity decreased specifically or nonspecifically, especially the DNCB reaction; and the blastogenesis against PHA showed an inverse correlation to the advance of gastric cancer.

Adult↗

Blastformation rate of peripheral blood lymphocytes before and after recurrence of cancer.

Following curative resection for gastrointestinal cancer, it has been demonstrated that the blastformation rate rises slightly 3-4 months before the recurrence of cancer and that, during the two months prior to recurrence, the blastformation rate of peripheral blood lymphocytes to PHA decreases rapidly. The blastformation rate, therefore, if monitored routinely postoperatively, should be a significant improvement in predicting any recurrence of the cancer.

Gastrointestinal Neoplasms↗

HLA antigens in Japanese populations.

HLA antigens in 841 healthy, unrelated Japanese from nine widely separated geographic localities were studied. The five most common antigens observed in order of decreasing frequency were for the HLA-A locus: HLA-A9, A2, A10, AW32 and A11; and for the HLA-B locus: HLA-'B5' (= HLA-B5+B17), BW40, B12, B14 and B8. The allelic frequency of undetected antigens of the HLA-A locus was .14-.37, and that of the HLA-B locus, .32-.67, indicating that there were serological difficulties in typing for Japanese antigens using antisera from Caucasians. Marked gene frequency clines were observed for HLA-A9 and HLA-A2 from south (Okinawa) to north (Nagoya). Two haplotypes, HLA-A9, B5 and HLA-A10, BW40 were shown to be in linkage disequilibrium in four of the nine subpopulations.

Alleles↗

Time-lapse changes in the concomitant immunity of lymphocytes from different sites of mice isografted with methylcholanthrene-induced tumor.

As a step in the elucidation of the mutual relationship between the degree of cancer progress and the antitumor activity of lymphocytes from different sites in cancer-bearing body, we isografted methylcholanthrene-induced tumor (MC-tumor) subcutaneously on the back of mice. The regional axillary lymph nodes, spleen and distant mesenteric lymph nodes were removed from these animals one, two, three, and four weeks later. We mixed lymphocytes prepared from these lymphatic tissues with primary MC-tumor culture cells and cultured together to estimate antitumor acitivity of lymphocytes from different sites. It has been found that a strong antitumor activity can be seen only in those regional axillary lymph node cells taken out one or two weeks after tumor transplatation and such an activity is weakened by three or four weeks. On the other hand, distant mesenteric lymph node cells one or two weeks after the transplantation have no antitumor activity as yet, while at the terminal cancer stage of four weeks there appears a stronger antitumor activity than that of regional lymph nodes. In the spleen, a strong antitumor activity can be observed in the third week after tumor transplantation, but the activity disappears by the fourth week. These findings support our previous findings in that for the tumor onset after the transplantation the antitumor activity seems to appear first in the regional lymph nodes, and when the tumor grows beyond a certain size, such an activity diminishes while it appears in further distant lymphatic tissues.

Animals↗

Allogeneic inhibitory activity of regional lymph node cells in the mouse isografted with methylcholanthrene-induced tumor.

In mouse bearing progressive cancer a decrease was present in the allogeneic inhibitory activity of T-lymphocytes, which constitutes the core of immunological surveillance system in mammalians. For tests, methylcholanthrene-induced tumor (MC-tumor) was isografted subcutaneously on the back between scapulae of C3H mice, and the lymphocytes were prepared from the regional axillary lymph nodes removed from these mice at 1, 2, 3, or 4 weeks after grafting. These lymph nodes cells were cultured together with 40-fold numbers of allogeneic JTC-11 cells derived from Ehrlich cancer cells in a culture medium containing 2.0% (v/v) PHA for 24 or 48 hours. The proliferation rate of JTC-11 cells (increased numbers) at weekly interval was considered the allogeneic inhibitory activity of lymph node cells. As a result it was demonstrated that in the early stage after tumor transplantation, i.e., in the first or second week, regional lymph node cells showed a strong allogeneic inhibitory activity, as in the case with lymph-node cells from normal mice, but at progressive stage of cancer, i.e., the third or fourth week when tumors were larger, such activity was completely lost. It seems that mice with progressive cancer showed a decrease of allogeneic inhibitory activity, i.e., a disruption of homeostasis was present.

Animals↗