Combination chemotherapy with anticancer agents and OK-432

Antitumor effects of the combination chemotherapy with hemolytic streptococcus preparation, OK-432, and various anticancer agents were observed on experimental tumors and human cancers. Experimental studies revealed that combined use of OK-432 with Mitomycin C, Nitrogen mustard N-Oxide or Bleomycin was remarkably effective on rodent transplantable tumors such as Ehrlich carcinoma, sarcoma-lOO and rat ascitic hepatoma AH-66. As for the mode of action of OK-432, besides a direct action on cancer cells, a host-mediated action appears to be also involved. Clinical trials were made on 14 cases with various advanced cancers, and favorable response was obtained in 5 with lung cancer. Fever was the major side effect of OK-432 and there was no evidence of bone marrow suppression.</p

Studies on the host-mediated action of the streptococcal preparation, OK-432, in cancer chemotherapy

The streptococcal preparation, OK.432, with predominant host-mediated mode of action, was studied. By giving OK-432 to mice intraperitoneally prior to transplantation of Ehrlich carcinoma, a host-mediated action to increase life-span was clearly confirmed. Pretreatment with OK-432 was also effective against the development of Rauscher leukemia. The host-mediated action of OK-432 varied with the interval between its pretreatment and the inoculation of tumor cells. The effect was most marked when the transplant was performed immediatedly after the pretreatment, and became less marked when the transplant was made one week and two weeks after pretreatment. The host-mediated action can be observed even with a single dose of pretreatment, and becomes more potent as pretreatment was given repeatedly. The host-mediated action was weakened by concomitant pretreatment with cyclophosphamide or roentgen irradiation, and the mechanisms of such action was supposed to be associated with the function of the reticulo-endothelial system.</p

Increase in the calculated resistance of anatomically fixed stenosis in vitro in association with decrease in distal resistance.

The effects of changes in distal resistance on stenotic resistance were studied in vitro. Physiological saline was passed through the left carotid artery obtained from the dog, flexible rubber tubing, or through solid polyethylene tubing with a constant perfusion pressure or with a constant flow rate. Various stenotic resistances were established using a screw type constrictor and the distal resistance was varied by allowing physiological saline to pass through either a 23 gauge hypodermic needle (high peripheral resistance) or 23 and 20 gauge needles (low peripheral resistance ). For arteries with anatomically fixed stenosis, the calculated resistance was increased in association with reduction of the distal resistance. The stenotic resistance in the flexible rubber tubing changed in the same manner as that of the carotid artery, while the solid polyethylene tubing showed no significant stenotic resistance changes due to altering the distal resistance. These findings suggest that the stenotic resistance change of the artery correlates with the elasticity of the vessel wall and also indicate that resistance values were of little usefulness for evaluating the effects of vasodilating stimuli on the vessel segment with a significant stenosis.</p

Immunological studies of the streptococcal preparation, OK-432, on neoplasm Part III. Comparative studies on the effect for the host and the antitumor action of the streptococcal preparation, OK-432, and Bacillus Calmette Guerin

Effect for the host and the tumor of the streptococcal preparation, OK-432, and Bacillus Calmette Guerin (B.C.G.) were comparatively studied. Its results are described below: 1) Granulomatous hepatitis with giant cells was observed in 4 of 5 mice (80%) receiving 5×10(7) B.C.G. organisms by i.p. injection. But there are no pathological findings in liver receiving the same bacterial counts of OK-432 as those of B.C.G.. 2) Neutrophilia in mice receiving 4×10(5) B.C.G. organisms i.p. is more remarkable than in mice receiving i.p. OK-432 containing 5×10(7) streptococcal hemolyticus. 3) By administrating OK-432 or B.C.G. i.p. at the same quantity mentioned above, peritoneal cells, particularly macrophages and neutrophils, are exudated more markedly in mice receiving OK-432 than B.C.G.. 4) At the same dosage, the survival rate of the C3H mice pretreated i.p. with OK-432 was more prolonged than the rate of the C3H mice pretreated i.p. inoculation of methylcholanthrene-induced sarcoma. The results stated above lead to the conclusions that B.C.G. has a liver damage, i.e., granulomatous hepatitis as the side effect by administrating the massive dose in contrast to OK-432. B.C.G. is stronger than OK-432 as the general stimulant to the host, and OK-432 is stronger than B.C.G. as the local stimulant. And consequently the host-mediated antitumor action of OK-432 is more predominant than B.C.G. at the dose that the author investigated in this paper

Studies on biological status in patients with lung cancer

Serum α(1)-acid glycoprotein (α(1)-AG) content, lactic dehydrogenase (LDH) activity, cholinesterase (Ch-Ease) activity, plasma fibrinogen (Fbg) content, hemoglobin content, serum albumin content and erythrocyte sedimentation rate were measured in 117 patients with lung cancer. Significant difference was observed in α(1)-AG as well as Fbg between stage Ⅰ and Ⅱ, in Ch-Ease between stage Ⅱ and Ⅲ and in LDH between stage Ⅲ and Ⅳ. In inoperable cases who did not obtain any clinical improvement during chemotherapy, significant positive correlation was observed between their life spans and α(1)-AG as well as Fbg measured prior to chemtherapy, and as for Ch-Ease negative correlation was observed. More close correlation was obtained between life spans and biological status which was set up following their laboratory data as stated above. Therefore, it seems that biological status are reliable index for estimating life spans of inoperable cases

A cardiovascular epidemiologic survey in three different areas in Okayama prefecture (Sakuto-cho, Sanyo-cho and Osafune-cho) in 1980. V. Special reference to HDL-cholesterol and total cholesterol.

A cardiovascular epidemiologic study was performed in three different areas in Okayama prefecture in 1980. The relationship between serum total and HDL-cholesterol and blood pressure, ECG findings, clinical disorders, obesity, drinking and smoking was examined in a total of 1092 subjects, with an age-range 49-79 years. The following results were obtained: 1) Along with an elevation of blood pressure, Code 1-0 in the ECG decreased and the code for left ventricular hypertrophy (a combination of two or more subcategories of Code 3 or of Code 3 with Code 4 or 5) increased. Code 4+5 increased in parallel with the systolic blood pressure and Code 5 increased directly with the diastolic blood pressure. 2) In the group of essential hypertension and coronary arterial disorders, HDL cholesterol/total cholesterol ratios were significantly low, and total cholesterol and the Atherogenic Index were in high compared with the normal group. 3) Along with an increase in body weight, the HDL-cholesterol/total cholesterol ratio decreased, while total cholesterol and the Atherogenic Index increased significantly. 4) The group with a drinking habit showed high HDL-cholesterol values but HDLcholesterol showed lower values in the group with a smoking habit

A cardiovascular epidemiologic survey in three different areas in Okayama prefecture (Sakuto-cho, Sanyo-cho and Osafune-cho) in 1980. V. Special reference to HDL-cholesterol and total cholesterol.

A cardiovascular epidemiologic study was performed in three different areas in Okayama prefecture in 1980. The relationship between serum total and HDL-cholesterol and blood pressure, ECG findings, clinical disorders, obesity, drinking and smoking was examined in a total of 1092 subjects, with an age-range 49-79 years. The following results were obtained: 1) Along with an elevation of blood pressure, Code 1-0 in the ECG decreased and the code for left ventricular hypertrophy (a combination of two or more subcategories of Code 3 or of Code 3 with Code 4 or 5) increased. Code 4+5 increased in parallel with the systolic blood pressure and Code 5 increased directly with the diastolic blood pressure. 2) In the group of essential hypertension and coronary arterial disorders, HDL cholesterol/total cholesterol ratios were significantly low, and total cholesterol and the Atherogenic Index were in high compared with the normal group. 3) Along with an increase in body weight, the HDL-cholesterol/total cholesterol ratio decreased, while total cholesterol and the Atherogenic Index increased significantly. 4) The group with a drinking habit showed high HDL-cholesterol values but HDLcholesterol showed lower values in the group with a smoking habit