Suppression of natural killer activity by ascitic fluid from patients with gastrointestinal cancer.
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Ascitic Fluid↗
Biomedical subjects
K Okui
Publications and source records attributed to K Okui.
Intra-arterial administration of heated albumin microspheres containing mitomycin C to rabbits with VX-2 tumor.
In an attempt to enhance antitumor effects, we prepared heated albumin microspheres containing mitomycin C (MMC). These MMC microspheres have an average diameter of 45 +/- 8 micrometers and contain about 5 per cent of MMC. The intra-arterial MMC microsphere treatment, for albino rabbits with implanted VX-2 tumor, increased remarkably the tissue MMC levels, compared to that with conventional MMC, and resulted in conspicuous antitumor efficacy. This approach to antitumor chemotherapy should be effective for selected patients with malignant tumor receiving a blood supply from an end-artery.
Animals↗
Effects of intravenous infusion of a ten percent soybean emulsion on hormones, amino acids and other substrates in blood.
Acute responses in hormone and substrate concentrations to intravenous administration of a fat emulsion were studied in metabolically normal subjects. Eight subjects were infused with either a fat emulsion or an aqueous solution of glycerol for 3 h. Serum triglycerides (TG), free fatty acids (FFA), glucose, glycerol, 3-hydroxybutyrate (3-OH butyrate), insulin, thyroid hormones, plasma glucagon, norepinephrine, and amino acids were measured. The infusion of a fat emulsion induced a 30% increase in glucose and a 22% decrease in alanine together with significant elevations of TG (> 10 mM) and FFA (> 1 mM). A small increase in insulin (4 microU/ml) and a reduction in glucagon (40 pg/ml) were observed. Eight-fold increases in glycerol occurred with both the fat emulsion and glycerol infusions. The administration of a fat emulsion resulted in a 4-fold increase in 3-OH butyrate, whereas glycerol infusion reduced its level by 50%. Glycerol infusion produced no measurable effects on the substrates other than glycerol or 3-OH butyrate. No significant changes were observed in thyroid hormones or norepinephrine after either solution was given. The data suggest that acute elevation of FFA by means of intravenous fat emulsions leads to preferential oxidation of FFA and stimulates hepatic ketogenesis with resulting glucose conservation as well as inhibition of alanine production without many alterations in hormonal concentrations.
Journal Article↗
[Preclinical studies of intra-arterial chemotherapy using mitomycin C microspheres].
Heated albumin microspheres 45 +/- 8 microns dia. containing 5% mitomycin C were infused into rabbit femoral artery to assess the depot effects. MMC levels were measured in the muscle and VX -2 tumor tissues fed by the femoral artery as well as in the drainage vein blood. Furthermore, the histologic changes in the VX -2 tumor and the MMC microspheres entrapped in the arterioles were surveyed microscopically. Drug concentration in the case of MMC microspheres was maintained at high levels in both tissue and venous blood over 4 hours, but in the rabbits infused conventional MMC, drug levels decreased below the assay limitation 2 hours after injection. The microscopic findings 2 weeks later revealed necrotic VX -2 tumor tissue as well as the MMC microspheres remaining in the arterioles .
Animals↗
Continued in vitro and in vivo release of an antitumor drug from albumin microspheres.
Heated albumin microspheres with an average diameter of 45 +/- 8 microns and containing mitomycin C, released, in vitro, about 20% of this antibiotic over a 3-day period. VX-2 tumors were implanted into the hind leg of rabbits and the drug-containing microspheres were injected into the femoral artery of these animals. High levels of the drug were maintained for several hours in the tumor and growth of the tumor was inhibited considerably, compared to findings in control rabbits given the conventional mitomycin C. Half the number of the rabbits treated with our new method are alive with no evidence of tumor.
Animals↗
Clinical evaluation of prolonged chemotherapy combined with induction of hepatic drug-metabolizing enzymes as an adjuvant for treating patients with gastric cancer.
A clinical trial of a protracted adjuvant cancer chemotherapy was carried out on 207 patients with operable gastric cancer, from April, 1977, in the First Department of Surgery, Chiba University Hospital and two closely related hospitals. These patients were given intravenously 0.4 mg/kg and 0.2 mg/kg of mitomycin C on the day of operation and the next day, respectively, and then 16 mg/kg intravenously of Futraful (FT-207) daily from the 10th postoperative day until discharge, followed by oral administration of FT-207, 12 mg/kg, for 24 to 36 months after discharge. Two mg/kg of phenobarbital and 30 mg/kg of glutathione were administered randomly to half the number of patients (induction group) to induce hepatic drug-metabolizing enzymes. Significantly higher levels of serum 5-Fluorouracil (5-FU) released from FT-207 were found in the induction group than in the controls. Five-year overall survival rates in the induction and control groups revealed no difference. However, the survival rates in Stage III patients in the induction group were significantly superior in the 3-5 postoperative years, compared to those in the Stage III of the control group, while Stage I, II and IV patients apparently received no benefit from this induction treatment.
Clinical Trials as Topic↗
[Studies on biodegradable microspheres containing mitomycin C].
For the purpose of enhancing antitumor effects, we prepared heated albumin microspheres containing an antitumor drug, mitomycin C. The biodegradable MMC microspheres which have an average diameter of 45 +/- 8 mum contain approximately 10% of MMC and release in vitro approximately 20% of the MMC over 3-day period. The microspheres were injected into albino rabbit femoral artery of the hind leg into which a VX-2 tumor had been implanted. Peripheral blood levels of MMC were reduced as compared to the conventional MMC group, within 60 minutes after injection. Subsequently in the MMC-microsphere administered rabbits, the level was higher than in the conventional MMC administered group. The survival of VX-2 tumor-bearing rabbits prolonged markedly with MMC microspheres.
Animals↗
[Combined antitumor therapy with polyamine biosynthesis inhibitors and mitomycin C].
A combined effect of the polyamine biosynthesis inhibitors, alpha-difluoromethylornithine (DFMO) and methyglyoxal-bis-guanylhydrazone (MGBG) with mitomycin C (MMC) was studied. DFMO, MGBG and MMC were given intraperitoneally to nude mice xenotransplanted human gastric cancer. This new combination of the three drugs resulted in the complete halt of the xenotransplanted tumor growth and marked decline of spermine levels in the tumor tissues. The other treatments with DFMO and MGBG as well as MMC alone were inferior to this new combined therapy in suppression in both tumor growth and tissue spermine level. These data suggest that this new combined treatment be effective against human gastric cancer.
Animals↗
[Effect of fat emulsion (intralipid) on essential fatty acid deficiency during total parenteral nutrition in pediatric patients. Part 1. Experimental study].
Experimental studies were performed to confirm the effect of TPN with and without fat emulsion, Intralipid, on fat metabolism in weanling rats and puppies. Long-term fat-free TPN induced essential fatty acid (EFA) deficiency in weanling rats and the intravenous fat emulsion which accounted for 10% of the total caloric intake could prevent EFA deficiency. In the long-term TPN in growing puppies, fatfree TPN and induced EFA deficiency within two weeks, and Intralipid which accounted for 4% of the total caloric intake (2% as linoleate) satisfied the EFA requirement.
Animals↗
[Effect of fat emulsion (intralipid) on essential fatty acid deficiency during total parenteral nutrition in pediatric patients. Part 2. Clinical study].
Thirteen infants who received total parenteral nutrition (TPN) in four different ways were studied in order to determine the essential fatty acid (EFA) requirement in pediatric TPN. The serum fatty acid composition of the infants who received fat-free TPN showed EFA deficiency within one week. This deficiency was cured by administering fat emulsion which accounted for 4% of the total caloric content of the infusate. Fat emulsion which accounted for 2% of the total calories neither improved nor prevented EFA deficiency. This means that intravenous fat emulsion, Intralipid, which accounted for 2% of the total calories as linoleic acid, still satisfies the EFA requirement.
Arachidonic Acids↗
[Occult rupture and delayed rupture of the spleen].
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Adult↗
[Effect of cancerous ascites on natural killer activity].
The effect of cancerous ascites on NK activity was evaluated by a 12-hr exposure method. Erythroleukemia cell line, K 562, was used as the target cells, the effector cells were isolated from 34 healthy volunteers. The final protein concentration of ascites was adjusted to 0.02, 0.2 and 2.0 mg/ml, after centrifugation and membrane filtration. When ascites was added at the start of assay, NK activity was almost completely suppressed by cancerous ascites of 2.0 mg/ml; it was not suppressed by 0.02, 0.2 mg/ml. No suppression was found when cancerous ascites was added 6 hrs after the start of assay. Our results suggest that the lowered NK activity of cancer patients may be attributable to unknown factor (s) released from cancer cells.
Ascites↗
[Antitumor treatment for synchronous hepatic metastasis from stomach cancer].
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Adult↗
Fine spontaneous contractions of the arterial wall of the rat in vitro.
Fine spontaneous contractions of the vascular wall were recorded from the isolated carotid artery of the rat. The amplitude and/or frequency of these fine contractions decreased in lower temperature and increased in norepinephrine. It was suggested that there is an important relationship between these fine contractions and vascular "tone" of the artery.
Animals↗
[Antitumor effects of polyamine synthesis inhibitors based on major premise of treatment for human malignant tumor].
The polyamine synthesis inhibitors--alpha-difluoromethylornithine (DFMO) and methylglyoxal bis (guanylhydrazone) (MGBG)--were put to antitumor tests based on the premise of treatment for human gastrointestinal cancer. The both drugs were administered intraperitoneally to BALB/c nude mice xenoplanted human gastric cancer for 10 consecutive days. Both marked antitumor effects and side effects were observed in mice treated at the dosage of DFMO 500 mg/kg/day and/or MGBG 50 mg/kg/day and/or MGBG 30 mg/kg/day brought about significant antitumor effects as well as less side effects. Microscopic observation revealed antitumor actions of these drugs as cytostatic rather than cytocidal. Tumor regrowth after the termination of this combined treatment, however, was noticed. Judging from these data, the both drugs may be effective against human gastrointestinal cancer with minor side effects.
Animals↗
[Immunologic studies on the patients with gastrointestinal cancer--with particular reference to correlation between T lymphocyte and macrophage].
Correlation of monocyte with T lymphocyte or IgG-FcR+ T lymphocyte was studied in 57 gastrointestinal cancer patients and 24 healthy volunteers as control. In 24 volunteers, no correlation was found between them. Forty gastrointestinal cancer patients with curative tumor showed pre-and postoperatively a close correlation between monocyte and T lymphocyte, but there was little correlation, both pre-and postoperatively, between monocyte and IgG-FcR+ T lymphocyte. Seventeen patients with recurrent and/or inoperable gastrointestinal cancer, had a reverse correlation of monocyte with IgG-Fc R+T lymphocyte. It was suggested from these data that mononuclear phagocyte system (monocyte), which fulfils its function as an antigen presentation, has an intimate relationship, both directly and indirectly, to T lymphocyte.
Adult↗
[Immunological study of the actions of auxiliary antitumor agents--effects on lymphocyte transformation reaction and natural cytotoxicity activity in nude mice].
P-aminobenzoic acid-N-xyloside (K-247) and dimethyl-2- (tetrahydro-2-furanyl) ethylsulfonium-p-toluene sulfonate (GT-101) were tested their in vivo effects on both mitogen-induced lymphoproliferative reactions and natural cell-mediated cytotoxicities in BALB/c nude mice (homozygous and heterozygous) spleen lymphocytes. The animals were injected i.p. either 400 mg/kg of K-247 or 5 mg/kg of GT-101 (for 7 days consecutively). GT-101 caused a positive increase in lymphoproliferations by PHA and SPA, while the administration of K-247 had no effect on PHA-and SPA-induced lymphoproliferations. Furthermore, in a 12-hour 51Cr release assay, both drugs had no effect on the natural cell-mediated cytotoxicity against YAC-1 cells.
4-Aminobenzoic Acid↗
[Clinical evaluation of anticancer therapy combined with p-aminobenzoic acid-N-xyloside].
Paraaminobenzoic acid-N-xyloside (K-247) is a new antitumor drug, which has no direct effect on immunologic status. Clinical trial of K-247 was performed in 8 patients with for advanced or recurred gastrointestinal cancer, who had short life expectancy. Oral administration of K-247, 600 to 900 mg/day, was carried out in combination with antitumor treatments using MMC, FT-207, 5-FU, PSK or irradiation. No toxic symptoms were observed in all patients. Of the 8 patients studied, one showed an encouraging response, while the remaining 7 patients were too far advanced to respond to these treatments.
4-Aminobenzoic Acid↗