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Biomedical subjects

M Sakita

Publications and source records attributed to M Sakita.

At least 19 recordsLinked to original sources

Effects of acupuncture and moxibustion on intestinal motility in mice.

To study the effects of acupuncture and moxibustion on intestinal motility, the distance of intra-intestinal movement of a carbon solution injected into the stomach of a mouse was evaluated. Intestinal motility was also evaluated using several drugs to accelerate or reduce intestinal motility. Our results indicate that intestinal peristalsis was accelerated significantly by acupuncture at the abdomen, but suppressed by moxibustion. The intestinal peristalsis acceleration by vagostigmin was reduced significantly by both acupuncture and moxibustion, while the reduction of intestinal peristalsis by atropine was accelerated significantly. However, no remarkable changes of intestinal peristalsis were observed with treatment by acupuncture and moxibustion after reduction by epinephrine.

Acupuncture Therapy

[Enhancing effect by anti-cancer drugs on growth inhibition of colon carcinoma in nude mice by monoclonal antibody and complement].

We investigated the possible sero-therapeutic application of monoclonal antibody-A7 against human colorectal cancer. In complement dependent cytotoxicity, A7 showed 59% cytotoxicity against SW1116 cells. In addition, the killing of tumor cells by A7 and C was enhanced when the tumor cells were pretreated with 2 micrograms/ml mitomycin and 40 micrograms/ml adriamycin. Next, we evaluated the in vivo antitumor effect of A7 alone and combined with MMC on human colon cancer (Colon-6) bearing nude mice. The group injected with A7 alone showed definite antitumor effect compared with the non-treated group. The A7+MMC group (MMC: 4mg/kg, A7: 1 mg/body, two times) showed enhanced antitumor effect compared with the groups administered A7 alone or MMC alone.

Animals

Effect of intraperitoneal injection of mitomycin C adsorbed on activated carbon particles on induction of cytolytic peritoneal macrophages of mice.

The effects of the intraperitoneal injection of mitomycin C adsorbed onto activated carbon particles (MMC-CH) were assessed on the host immune status and the induction of cytolytic peritoneal macrophages (PM) in mice in comparison with an aqueous MMC solution (MMC-AQ). PM from inbred C57BL/6 mice and syngeneic B16 melanoma cells were used as the effector and target cells for the PM-mediated cytotoxicity assay. After a single injection of MMC-AQ (at the dose of 1/2 LD50), the weights of thymus and spleen and the 3H-thymidine uptake of spleen cells stimulated by concanavalin A were markedly decreased compared to those following injection of MMC-CH containing the same dose of MMC. A significant difference was found in the chronological changes of peritoneal exudate cell (PEC) numbers and PM cytolytic activity between the MMC-AQ- and MMC-CH-treated mice. One day after MMC-AQ injection, the PEC numbers were decreased markedly. However, they increased ten-fold after MMC-CH injection and the PM cytolytic activity was significantly higher after MMC-CH injection than after MMC-AQ injection during the first 3 days. The present results suggest the possible superiority of MMC-coated charcoal over free MMC both because of a lessening of the effects on host immunity due to prolonged slow drug release and because of the increase in cytolytic macrophages that was induced.

Adsorption

[Effect on immunological response of host by mitomycin C adsorbed into activated carbon particles (MMC-CH) in mice].

Mitomycin C adsorbed onto activated carbon particles (MMC-CH) has been administered intraperitoneally for C57BL/6 mice. The weight of the spleen and thymus of the mice given MMC-CH was decreased lesser than those of the mice given mitomycin C aqueous solution (MMC-AQ). The number of peritoneal exudate cells (PEC) in the mice given MMC-AQ was decreased remarkably on 1st day after MMC-AQ administration and recovered within normal range on the 7th day. On the other hand, the number of PEC in the mice given MMC-CH was increased remarkably on the 1st day and then gradually decreased to normal range on the 7th day. Reactivity of spleen cells by Con A was inhibited in the spleen cells from the mice given MMC-AQ more than those from the mice given MMC-CH. Fifth percent lethal dose was 8.0mg/kg in the mice given MMC-AQ, and 18.2mg/kg in the mice given MMC-CH.

Absorption

[Clinical application of monoclonal antibody-drug conjugates in colorectal carcinoma].

Monoclonal antibody, A7, produced from a mouse splenocyte immunized against human colon cancer was used as drug carrier for colon cancer. A7 had not ADCC and ADMC activity but had ACD activity. Anticancer drug, mitomycin C (MMC), and neocarzinostatin (NCS), were covalently bound to A7 to form the conjugates, A7-MMC, and, A7-NCS. In vitro cytotoxic effect of the conjugates on SW1116 was much stronger than that of free MMC or free NCS. The conjugates, A7-NCS, administered in nude mice brought about the highest NCS concentration in tumor, while normal IgG-NCS distributed evenly in all the tissues. The conjugates showed strong antitumor effect on colon cancer transplanted in nude mice. Forty one patients with colorectal cancer including 10 patients with postoperative metastasis were given A7-NCS. The immunoperoxidase and drug concentration studies of the resected specimens revealed that NCS was found to be localized specifically in cancer. There was no serious adverse effect in the patients receiving the conjugate. Of eight patients with postoperative liver metastasis, three showed evidence of tumor reduction on CT scan and three claimed pain relief. The conjugate was of no benefit to the patients with multiple lung metastasis and peritoneal metastasis.

Adult

Leiomyosarcoma of the kidney: report of a patient with favorable response to doxorubicin and cisplatin suspended in a lipid contrast medium and cyclophosphamide.

A man who had unresectable leiomyosarcoma of the left kidney with skin and lung metastases was treated with intra-arterial infusion chemotherapy consisting of cisplatin and doxorubicin suspended in lipid contrast medium, lipiodol, and oral administration of cyclophosphamide. The tumor responded well to this treatment three times. He is alive and well in remission, the renal tumor decreased in size, and lung metastases became unclear more than 50 weeks after treatment was completed.

Aged

[Missile therapy using monoclonal antibody drug conjugates in colorectal carcinoma].

For targeting chemotherapy of colorectal carcinoma, mitomycin C (MMC) and neocarzinostatin (NCS) were covalently bound to monoclonal antibody A7 which is highly specific to human colon cancer. The in vitro cytotoxic effects of the conjugates A7-MMC and A7-NCS on SW1116 were 77 times and 4 times stronger than those of the free MMC and free NCS, respectively. An in vivo study in nude mice bearing human colon carcinoma revealed that monoclonal antibody A7 alone had no effect, and that A7-MMC and A7-NCS had greater inhibitory effects than the free MMC and NCS, respectively. Thirty-five patients with carcinoma of the colon and rectum including 6 with postoperative liver metastasis, one with postoperative lung metastasis and one with postoperative peritoneal metastasis, were given the A7-NCS conjugate consisting of between 15 and 90 mg of antibody and between 1,000 and 6,000 units of NCS. Immunoperoxidase study of resected specimens revealed selective localization of NCS in the cancer cells. The conjugate had no serious adverse effects. Five of the six patients with postoperative liver metastasis responded favorably to the conjugate, showing a decrease in tumor size on CT scan or relief of pain. The conjugate was of no benefit to patients with multiple lung metastasis or peritoneal metastasis. The effect on other patients with surgically resected carcinoma remains to be determined by a follow-up study.

Adenocarcinoma

Comparative studies between liposomes containing muramyl dipeptide and various immunomodulators on activation of mouse peritoneal macrophages and NK cells.

We compared the effects among muramyl dipeptide (MDP), liposome-encapsulated MDP (liposome MDP), bacillus Calmette-Guérin (BCG) and OK-432 on cytotoxic activity of mouse peritoneal macrophages (PM) and natural killer (NK) cells in vitro and in vivo, and their tumor-inhibitory effects against MH134 ascitic tumors in C3H/He mice. The cytotoxicity of PM induced by free MDP was lower than that induced by BCG, but a significantly higher cytotoxicity was induced by liposomes containing MDP and OK-432. The peritoneal NK cells were not activated by MDP, liposome MDP or BCG, but OK-432 profoundly augmented peritoneal NK activity. Growth inhibition of ascitic tumor was not observed in free MDP and BCG intraperitoneally treated mice, but moderate growth inhibition was noted in liposome-MDP-treated mice; and in OK-432-treated mice, marked tumor growth inhibition and prolongation of survival time were observed. These results suggested that OK-432 is more advantageous in controlling malignant tumor growth in vivo than free MDP, liposome MDP or BCG because of its ability to activate both macrophages and NK cells.

Acetylmuramyl-Alanyl-Isoglutamine

Eradication of microscopic metastases with intratumoral injection of bacillus Calmette-Guerin.

The studies reported here were designed to examine the effects of intratumoral preoperative administration of Bacillus Calmette-Guerin (BCG) on the cure rates of C3H mice transplanted with MH134 tumor cells and on the metastatic rates in the regional lymph nodes. Furthermore, the morphological findings occurring in the regional lymph nodes were monitored during tumor growth using H-E stain and non-specific esterase staining. The cure rate of the Group treated with BCG intratumoral injection and surgery was significantly higher than that of the Group treated with surgery alone, and in the BCG + surgery group metastatic rates of regional lymph nodes decreased consistently after operation. Moreover, in this group, extensive sinus histiocytosis and marked swelling of the regional nodes were frequently observed. Quantitative studies of the cell kinds using the esterase staining indicated that intratumoral injection of BCG has an effect on the influx of lymphoid cells into the regional nodes, but does not aid specific cell lineage to flow into the regional nodes. In cytostatic assays, it was shown that the regional lymph node cells and spleen cells in the BCG + surgery group always have a greater per cent of inhibition than those in the surgery alone group.

Animals

Immunosuppressive activity of sera from gastric cancer patients.

Sera from 60 gastric cancer patients and 20 patients with benign gastric diseases and 8 healthy controls were tested for inhibitory effects on the humoral response to sheep erythrocytes (SRBC) by the plaque forming cell assay (PFC R.I.) using mouse spleen cells and on the phytohemagglutinin (PHA)-induced blastogenesis of normal mouse spleen cells (PHA S.R.). Gastric cancer patient sera showed a significantly lower PFC R.I. than did sera from benign gastric disease patients and from the healthy controls. However, there was no appreciable interstage difference in the degree of depression. The PHA-induced blastogenesis of normal spleen cells was also decreased in the presence of sera from cancer patients, as compared to that in the presence of sera from benign disease patients and from the healthy controls. The depression progressed with advancing stage of cancer. The PHA S.R. showed significant negative correlations with serum levels of IAP, IS, alpha 1-acid glycoprotein and alpha 1-antitrypsin, but there were no such correlations between PFC R.I. and these glycoproteins in serum. There was also no correlation between the values of the PHA S.R. and the PFC R.I. These results suggest that these two assays may depict immunosuppressive activities operating through entirely different mechanisms.

Animals

[Endoscopic preoperative intralesional injection of OK-432 in early gastric cancer].

The study group consisted of 35 patients with early gastric cancer, 16 of whom were admitted for preoperative immunotherapy. Ten to 40 K.E. of OK-432 was injected intralesionally by endoscope, and then gastrectomy was performed. After the intralesional injection, fever, nausea, vomiting and epigastralgia occurred. In cancer lesion and regional lymph node, histological findings from OK-432 treated group were compared to those of the control group. Lymphoid cell infiltration at cancer lesion was marked in OK-432 treated group, and degenerated cancer cells were found in 3 cases. On the other hand, lymphoid follicles showed a marked statistical increase in OK-432 treated group. Also the cases with marked lymphoid follicle showed increased numbers of peripheral blood lymphocyte. From the results, intralesional injection of OK-432 may confirm the tumor-associated antigenicity and serves as a useful method to potentiate the specific and/or non-specific immunity in regional lymph nodes.

Adult

Conservative surgery for regional lymphadenectomy in the treatment of early gastric carcinoma.

The relationship between lymph node metastases and postoperative prognosis in 209 patients with early gastric cancer was studied. As to the postoperative prognosis in relation to the extent of lymph nodes dissection, no significant difference was observed among the age-corrected 5-year survival rates following three surgical procedures in patients with early gastric cancer. Age-corrected 5-year survival rates were 0.92 +/- 0.44 R1-resection, 0.95 +/- 0.44 in R2-resection, and 1.00 +/- 0.06 in R3-resection, respectively. In addition, in 71 patients including 33 with early gastric cancer and 38 patients with advanced but relative early gastric carcinoma, the relationship between the immunostatus and postoperative prognosis was investigated. Postoperative age-corrected 5-year survival rate (0.904 +/- 1.153) of the optimal responders with good immunostatus was significantly higher than that (0.582 +/- 1.153) of the suboptimal responders with impaired immunostatus (P less than 0.01). Thus, conservative surgery for regional lymphadenectomy may be an effective procedure for cure of early gastric carcinoma, particularly in cases of a carcinoma limited to the mucosal area of the stomach.

Adult

Effects of prostaglandin E2 and D2 on gastric somatostatin and gastrin secretion.

The effects of PGE2 and PGD2 on gastric somatostatin and gastrin releases were investigated using the isolated perfused rat stomach. In the presence of 5.5 mM glucose, the infusion of PGE2 elicited a significant augmentation in somatostatin release, but suppressed gastrin secretion from the perfusate. On the other hand, PGD2 did not affect somatostatin release, although the gastrin secretion decreased significantly, the same as after PGE2 infusion. These results suggest that PGE2 and PGD2 may be important in the regulation of gastric endocrine function, but that PGD2 does not affect gastric somatostatin secretion.

Animals

Intratumor chemoimmunotherapy with mitomycin C and BCG in C3H/He mice transplanted with MH134.

Experiments were performed to explore the influence of local chemoimmunotherapy by intratumoral administration of mitomycin C (MMC) and/or BCG on the survival rate, lymph-node metastasis, growth pattern of rechallenge tumor, and host immune function, using a host-tumor system consisting of C3H/He mice and syngeneic tumor MH134. Combined intratumoral regimens of MMC plus BCG yielded a significantly higher survival rate than those achieved with BCG or MMC alone. Furthermore, the incidence of metastatic involvement of regional lymph nodes was also remarkably reduced in the combined regimen group. The group given the combined MMC-BCG regimen also showed a marked suppression of the growth of rechallenge tumor after surgical removal of the primary tumor and showed a greater induction of tumor-specific immunity than that seen in the group given intratumoral BCG injection alone. Both the delayed-type hypersensitivity, as measured by the footpad swelling assay, and the antibody response in spleen lymphocytes, as estimated by the plaque-forming cell assay, were found to be substantially depressed following a systemic injection of MMC, whereas the intratumoral administration of MMC had little or no effect on these parameters.

Animals

Effect of a protein-bound polysaccharide preparation, PS-K, on dimethyl hydrazine induction of intestinal tumors in rats.

The effect of a protein-bound polysaccharide preparation, PS-K, on the induction of intestinal tumors by dimethyl hydrazine (DMH) was assessed in Wistar rats. One hundred and fifty-one rats were randomly divided into two groups. Seventy-two rats were treated with DMH alone and 79 rats were treated with DMH and PS-K. All animals were subjected to a sequential autopsy and all lesions within the gastro-intestinal tract were examined macroscopically and histologically. Tumor incidence in the DMH plus PS-K-treated group was significantly lower than that in the group treated with DMH alone. The most interesting histological finding was marked lymphoid infiltration in and around the tumors of the rats in the PS-K-treated group. The number of circulating lymphocytes dropped below the control range in the 25th and 35th weeks for the group treated with DMH alone, but the drop in the PS-K-treated group was smaller. Delayed-type hypersensitivity reaction to purified protein derivative was well maintained in the PS-K-treated rats. The most interesting findings in these experiments were differences in the serum blocking activities and serum immunosuppressive substance in these two groups; they were markedly reduced in the PS-K-treated rats. The present results may be explained in terms of competitive action of PS-K against the immunosuppressive factor produced by a tumor-bearing host.

Animals

Intratumor immunochemotherapy with 5-fluorouracil emulsion and BCG in C3H/HE mice transplanted with MH134.

Responses to intratumor immunochemotherapy by intralesional injections of BCG and 5-fluorouracil (5-FU) emulsion, prior to resection of a transplanted primary tumor, were investigated using a host-tumor system consisting of C3H/He mice and MH134. A significant prolongation of survival and suppression of lymph node metastasis were attained by the combined use of BCG and 5-FU emulsion, compared to treatment with either BCG or 5-FU emulsion alone. However, this did not alter the survival rate of the combined regimen group as compared with those of the latter treatment groups. When rechallenged with the same tumor cells after resection of the primary lesion, mice treated with BCG alone exhibited a marked tumor growth suppression while the control and BCG + 5-FU emulsion group showed a less effective suppression. No such effects were observed in the group given 5-FU emulsion alone. Assessment by the splenic plaque-forming cell assay with sheep erythrocytes revealed a marked inhibition in the development of humoral immunity in the animals treated with 5-FU emulsion alone. Concomitant administration of BCG was effective to some extent in preventing the depression of these immune functions. The data obtained indicate that the clinical response to immunochemotherapy is determined by a balance between the antitumor effect of the antitumor agent administered and its influence on the host's immune functions.

Animals

[Follow-up study of preoperative oral administration of an antineoplastic agent as an adjuvant chemotherapy in stomach cancer].

Based on the propensity of fat emulsion to be absorbed mainly into lymphatic capillaries and regional lymph nodes, preoperative oral administration of 5-FU emulsion was attempted as an adjuvant chemotherapy to surgery for gastric carcinoma. In our previous studies, it was demonstrated that the mean 5-FU level in the regional lymph nodes was higher in patients who received the 5-FU solution. Since 1974, we have administered 5-FU emulsion preoperatively to 167 patients with gastric cancer (500 mg X 10 days) and examined histologically the effect of this regimen on the metastatic foci in the lymph nodes. A positive change, such as marked necrosis or marked degeneration, was found in 58% of the metastatic lesions. Sixty-four patients with advanced cancer who received the preoperative 5-FU emulsion also received a curative resection between 1974 to 1977 in addition to postoperative chemotherapy (MMC 40 mg and 5-FU more than 5000 mg) (Group A). Their survival rate was compared with that of the curatively operated advanced cancer patients from 1959 to 1973 who received the same postoperative chemotherapy only (Group B, N = 59) and with that of patients, from 1959 to 1970, who received no chemotherapy (Group C, N = 222). The 5 year survival rate of Group A was 0.53 +/- 0.07, which was higher than that (0.49 +/- 0.07) of Group B and that (0.40 +/- 0.10) of Group C. Comparing the 5-year survival rates of the 3 groups from several points of view, such as a stage of cancer progress absence of serosal invasion, the 5-year survival rate of group A was higher than that of other groups. Although these differences between Group A and B were not statistically significant, but those between Group A and B were significant. From these results it is suggested that preoperative oral 5-FU emulsion might be effective as an adjunct to surgery for gastric cancer.

Administration, Oral