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Biomedical subjects

S Saji

Publications and source records attributed to S Saji.

At least 163 records · Page 9Linked to original sources

Antitumor effect in peritoneal carcinomatosis of intraperitoneal administration of a streptococcal preparation, OK-432: I. Experimental study in the rat.

The effect of intraperitoneal OK-432 administration and its mechanism of action were investigated using an experimental rat tumor. On day 4 or 6 of intraperitoneal inoculation of tumor cells, 50 Klinische Einheit (KE)/kg of OK-432 was intraperitoneally administered, and intraperitoneal exudate cells were microscopically examined daily. Distribution of peritoneal exudate cells: A marked increase in neutrophils was noted in ascites at 24 hours after intraperitoneal administration of OK-432, with macrophages and lymphocytes appearing later than neutrophils. A subsequent decrease in neutrophils was accompanied by a gradual increase in tumor cells. Findings of tumor cells: When OK-432 was intraperitoneally administered on day 4 of tumor inoculation, aggregation of neutrophils around tumor cells was observed on day 6, and rosette formations around tumor cells were noted on day 7 or 8. Subsequently tumor cells that formed the centers of the rosettes were destroyed and disappeared. These reactions were not observed when OK-432 was administered on day 6, nor were they observed in untreated cases. These results suggest that cytotoxic effects of intraperitoneally administered OK-432 were displayed mainly by rosette formation by neutrophilic cells, as far as this model was concerned.

Animals↗

[Monthly changes in serum alpha 2-globulin and immunoglobulin levels in chronic hemodialysis patients--with special reference to the occurrence of cancer and blood transfusion].

Thirty-eight patients with chronic renal failure who were treated by hemodialysis more than 100 times each, including 13 cancer patients, were examined for serum alpha 2-globulin and immunoglobulin values monthly, the relationship between the possibility of cancer occurrence and the frequency of blood transfusion during hemodialysis was discussed. The alpha 2-globulin value of the patients treated with blood transfusion more than 20 times was significantly higher than that of the patients not receiving blood transfusion. Moreover, the IgA value was reduced and the IgM value was increased. The IgA values of cancer patients found before or during hemodialysis were significantly higher than those of patients without cancer. There was no significant difference between the group who had undergone hemodialysis more than 500 times those who had received it less than 500 times.

Adult↗

[Clinical study on serum immunosuppressive factors in gastric cancer patients--with special reference to preoperative IAP values and the influence of surgical stress].

Serum IAP values were measured preoperatively in 83 gastric cancer patients. The levels were significantly higher in cases of total, stage III and IV, n (+) and non-curative resection than in normal subjects, stage I, n (-) and curative resection. There was a significant correlation between IAP on the one hand, and IgG FcR (+) T cell, alpha 2-globulin and CEA on the other. OK-432 was serially administered pre- and postoperatively (A) and only postoperatively (B). IAP was examined at one, two and four weeks postoperatively, and the findings were compared. It was increased markedly at one week and was slightly reduced at two and four weeks. These changes in IAP showed no significant differences between groups A and B.

Carcinoembryonic Antigen↗

[Relations of tumor-specific cytotoxicity to nonspecific immunological parameters and to clinical course in various surgical cancer patients].

Human malignant cells, obtained from surgical specimens or pleuro-peritoneal exudate in 105 cases, were cultivated. Tumor-specific immunity was estimated by cytotoxicity assay using mixed autologous lymphocyte-tumor cell culture in 27 cases (40 times in all). Relations of the observed specific immunity to various nonspecific immunological parameters and to clinical responses to immunotherapy were examined. Positive reaction was observed in 14 examinations. Eight of 25 digestive tract cancers and 6 of 15 other cancers were positive. Cytotoxic activity was significantly higher in the group of favorable clinical response than in the group of progressive disease. In the group of positive cytotoxicity, incidence of clinical response was significantly higher than in the group of negative cytotoxicity. A significant positive correlation was found between cytotoxicity and T cell ratio. Incidence of positive cytotoxicity tended to be higher in the cases of single OK-432 administration (6/11). Incidence of clinical response was higher in the cases of combined OK-432 and PSK administration group (4/14). In the positive cytotoxicity group, 3 examinations showed progressive disease and 5 showed no change. It has been suggested that a higher incidence of favorable clinical response is to be expected in case of positive cytotoxicity, if some therapy will be combined with the conventional immunotherapy.

Adjuvants, Immunologic↗

[Clinical study on serum immunosuppressive factors in gastric cancer patients--with special reference to preoperative ferritin levels and influence of surgical stress].

Serum ferritin values were measured preoperatively in 83 patients with gastric cancer and were found to be significantly higher than in normal subjects and mammary cancer patients. They were also significantly higher in healthy men than in women and in gastric cancer patients at stages I and IV than in those at stage III. There was no significant correlation between the serum ferritin value and various immunologic parameters. OK-432 serially administered pre- and postoperatively (A) and only postoperatively (B). The ferritin value increased markedly at one week postoperatively, reaching a peak at two weeks; at four weeks, it was reduced toward the value at one week. However, these changes in ferritin value showed no significant difference between groups A and B.

Blood Transfusion↗

[Observation on natural killer cell activity in gastric cancer patients and effect of nonspecific immunopotentiator administration on its postoperative reduction].

Natural killer cell (NK) activity, together with various nonspecific immunologic parameters, was measured preoperatively, and its changes induced by operative stress were examined in gastric cancer patients. Effect of administration of a nonspecific immunopotentiator, OK-432, was evaluated by postoperative changes in NK activity. Peripheral blood NK activity was measured by 51Cr-release assay against K-562 target cells. It was found that NK activity in the gastric cancer patients was significantly lower than that in healthy subjects. The reduction was specially marked in the cases of cancer at stages I and IV. NK activity in the cases with hepatic or peritoneal metastasis was significantly lower than that in the cases without such metastasis. NK activity in the cases of noncurative gastric resection or non-resection was significantly lower than that in the cases of curative gastric resection. NK activity in the cases of stage IV and "por" in histology was significantly lower than that in the cases of stage IV and "tub1" in histology. In the cases at stages I + II, there was a positive correlation between NK activity and IgG FcR(+) T cell ratio. There was a negative correlation between NK activity and alpha 2-globulin ratio and the correlation was especially significant in the cases at stages III + IV. In the cases at stages III + IV, receiving administration of OK-432 only postoperatively, NK activity was significantly reduced or tended to be reduced at 1 through 4 week(s) postoperatively, while such a reduction was not seen in the cases receiving administration of OK-432 pre- and postoperatively. This phenomenon was more marked in the cases showing a serum albumin level lower than 3.5 g/dl or in the cases undergoing operations longer than 4 hours in duration.

Adjuvants, Immunologic↗

Monoclonal antibodies specific for two different histological types of human lung carcinoma.

Hybridomas secreting monoclonal antibodies specific for human lung cancer were produced by fusing immunized mouse spleen cells with mouse myeloma line X63-Ag8.653. Prior to fusion, BALB/c mice were immunized with two different histological types of human lung cancer (Squamous cell carcinoma and adenocarcinoma) obtained from surgery. An immunocytoadherence test was used to select hybridomas secreting antibodies that bound the patient's lung tumor, but did not bind to a B-lymphoblastoid cell line derived from the same patient. Five stable antibody-producing hybrids have been established and cloned. The antibodies produced by these clones have been characterized according to their light and heavy chain isotypes and for their specificity. In addition to binding to the tumor used for immunization, the antibodies bound to other lung tumors of the same histological type (i.e., squamous cell or adenocarcinoma). This reactivity was observed with both established lung tumor cell lines and with fresh tumors obtained from biopsy of patients in our clinic. Some significant reactivity was also observed with large cell carcinoma but the antibodies did not react with small cell carcinomas of the lung, bronchiolo-alveolar cell carcinoma, cancer of the esophagus and stomach, melanomas, several types of leukemias, normal human lung tissue, fibroblasts, or erythrocytes of type A, B, or O. Two of the five antibodies, 5C7 and 5E8 cross-reacted with one breast cancer obtained from surgery, and 5C7 also cross-reacted with one melanoma biopsy specimen. These results suggest that we have generated monoclonal antibodies that recognize a set of antigenic determinants that are commonly expressed on a portion of human lung tumors that are not detectable on a variety of other human tumors or normal human tissue.

Adenocarcinoma↗

Facilitation of tumor metastasis by operative stress and participation of cell-mediated immunity. Experimental study.

5-week-old syngeneic female SD rats were inoculated subcutaneously at the dorsal flank with 200 mg of a metastasizing rat's mammary tumor, MRMT-1. A significantly higher incidence of lung metastasis was observed in the cases in which tumor excision on day 14 was accompanied by 30 min laparotomy than in the cases of simple tumor excision. PHA lymphoblastogenesis on day 17 was significantly lower in the cases of tumor excision plus laparotomy on day 14 than in the cases of simple tumor excision. Winn's assay using splenocytes revealed a postoperative enhanced suppressor activity in the cases undergoing laparotomy stress. Possible participation of the raised suppressor activity to facilitation of metastasis was discussed.

Animals↗

Quantitative evaluation of fatty liver by computed tomography in rabbits.

Biochemical, histologic, and computed tomographic (CT) examinations of the liver were performed in 32 rabbits in which fatty liver was induced by prolonged intravenous fat infusion. In two groups of rabbits, in which 2 and 4 g/kg/day of fat emulsion was administered, respectively, posttreatment reduction in CT value of mild degree was observed, but the reduction was insignificant from the standpoint of diagnosis from CT images. In the group that received 8 g/kg/day of fat emulsion, posttreatment change in CT value was -14.9 +/- 5.1 H, a sufficient reduction for a diagnosis of fatty liver of moderate degree. No significant change in CT value was seen in the no-treatment group or in the group in which 80 ml/kg/day of normal saline solution was infused for 4 weeks. Reduction in CT value in fatty liver might be due largely to accumulation of triglyceride and cholesterol in the liver cells. Significant correlation was found between changes in CT value of the liver and degrees of histologic fat accumulation in the liver cells. Consecutive measurement of CT values of the liver during prolonged intravenous hyperalimentation is a nonaggressive method of diagnosing fatty liver.

Animals↗

[Clinical studies on preoperative nonspecific immunological parameters and radical operation in stomach cancer].

Ratio of IgG Fc receptor positive T (Fc R(+) T) cell, PHA-induced blastogenesis and serum alpha 2-globulin ratio were examined in 90 preoperative cases with gastric cancer and were analyzed according to various stages of cancer and compared with normal controls. Moreover, on the basis of correlations among these parameters, operative radicality and prognosis were discussed. Fc R(+) T cell ratio was significantly elevated. PHA- blastogenesis was significantly reduced. Alpha 2-globulin ratio tended to increase as the stage progressed. A significant negative correlation was found between Fc R(+) T cell ratio and PHA- blastogenesis. In a scattergram indicating this correlation, the group of noncurative resection or exploratory laparotomy was divided into two areas, B1 and B2. The group of curative resection (A1) was located between B1 and B2, and the normal control group was located in the area common to B1 and A1, Cases succumbing to cancer within one year postoperatively were found to accumulate either in the area B2 or in the area B1 minus the area common with A1. No significant correlation was found between Fc R(+) T cell ratio and alpha 2-globulin ratio. However in a scatter gram, the almost same relationship between these three groups was noted. Thus it has suggested that postoperative prognosis (at least for two years) is good in cases which an immunological harmony among these parameters is maintained preoperatively.

Adult↗

[Production of monoclonal antibodies specific to human lung cancer--squamous cell carcinoma and adenocarcinoma].

UNLABELLED: Hybridomas secreting monoclonal antibodies specific for human lung cancer were produced by fusing immunized mouse spleen cells with mouse myeloma line 653. METHODS: BALB/c mice were hyperimmunized with two different histological types of human lung cancer (squamous cell carcinoma and adenocarcinoma) obtained from surgery. An immunocytoadherence test was used to select hybridomas secreting antibodies that bound to the patient's lung tumor but did not bind to a B-lymphoblastoid cell line derived from the same patient. Five stable antibody-producing hybrids (2C6, 5D7 and 5E8 derived from squamous cell carcinoma, 5C7 and 2B7 derived from adenocarcinoma) have been established and cloned. RESULTS: The antibodies bound to other lung tumors and established lung tumor cell lines of the same histological type. Also, some significant reactivity was observed with large cell carcinoma, but the antibodies did not react with small cell carcinoma of the lung, bronchiolo-alveolar cell carcinoma, cancer of the stomach and esophagus, melanoma, several types of leukemias, normal human lung tissue, fibroblasts, or erythrocytes of type A, B or O. Two of the five antibodies, 5C7 and 5E8 cross-reacted with one breast cancer obtained from surgery and 5C7 also cross-reacted with one melanoma biopsy specimen. Moreover, the antibodies have been characterized according to their light and heavy chain isotypes by ouchterlony and radioimmunoassay.

Adenocarcinoma↗

[Experimental study on quantitative evaluation of fatty liver by computed tomography].

Biochemical, histological and CT examinations of the liver were performed in 32 rabbits on significance of measuring CT values in the diagnosis of fatty liver. In 2 groups of rabbits, in which 2g/kg/day and 4g/kg/day of fat emulsion were administered intravenously for 4 weeks respectively, post-treatment reduction in CT value of light degree was observed. In a group, in which 8g/kg/day were given, there was a sufficient reduction in CT value for giving diagnosis of fatty liver of moderate degree. Significant correlation was found between changes in CT value of the liver on the one hand and contents of triglyceride, total cholesterol and cholesterol ester in the liver on the other hand, while there was, no significant correlation between changes in CT value and contents of phospholipid, protein and water. Significant correlation was found between changes in CT value of the liver and degrees of histological fat accumulation in the liver cells. It has been evidenced experimentally that prolonged administration of fat emulsion may cause fatty liver, and that measurement of CT values of the liver is a non-aggressive method of diagnosing fatty liver.

Animals↗

Experimental study on merits and demerits of splenectomy in tumor bearers.

Immunologic merits and demerits of splenectomy were studied using a rat's experimental tumor. When splenectomy was done on day - 14, 2, or 14 of tumor inoculation, subsequent tumor growth was inhibited, but when it was done on day 7, tumor enhancement was observed. On day 2, cpm values of phytohemagglutinin (PHA)-induced blastogenesis of splenocytes was lower than in normal rats, on day 7 they significantly increased as compared with day 2, and on day 14 they significantly decreased as compared with day 7. Stimulation index (SI) ratio of PHA-induced blastogenesis and natural cell-mediated killing (NK) activity were also investigated using splenocytes, thymocytes, and peripheral lymphocytes. The results indicated that immunological competency of splenocytes of tumor bearers was reduced in the early, late, and final tumor-bearing periods, while it was increased in the middle tumor-bearing period. Tumor growth following splenectomy was considered to be controlled by these changes in immunological competency of splenocytes.

Adenocarcinoma↗

[A study on postoperative long-term continuous immuno-chemotherapy with PSK and 5-FUDS for advanced gastric and colo-rectal cancers].

Since 1976, postoperative long term immunochemotherapy (PLIC) with PSK and 5-FU Dry Syrup (5-FUDS) was performed after tumor resection in gastric and colorectal cancer patients. Successful continuation over one year of the therapy was done in 40 cases at stages III and IV (+V) in the period between January 1976 and April 1979. These cases were analyzed and following results were obtained. Two-and 3-year survival rates were 80% and 65% respectively when the total cases of one year survival was taken as 100%. However, there were recurrent or tumor-bearing patients being treated by PLIC and, if they had died within the respective years, 2-and 3-year survival rates would have been reduced to 67.5% and 32.5%, respectively. These survival rates were roughly similar as those of historical control group, in which no immuno-chemotherapy was done. Characteristic features of non-specific immunological parameters seen in the recurrent or tumor-bearing cases of relatively good clinical course were improvement in T cell percentage, reduction or stop of in IgG-FcR (+) T cell percentage and maintenance of a good nutritional condition.

Aged↗

[Antitumor immunity in the relatively early period after cryosurgery. Experimental study using rat's metastasizing mammary tumor].

Six-week-old female Sprague-Dawley rats were inoculated with a mammary tumor, MRMT-1. At 2 weeks after inoculation, one of the following 4 treatments was done: surgical tumor excision (SE), cryosurgery (CR), surgical excision plus re-inoculation of freezing-thawing-produced vaccine (FT), and surgical excision plus fasting for 72 hours (FA). In FT and FA groups, incidence of metastatic death were higher than in SE group, while that in CR group was similar as in SE group. Specific footpad reactivity at 2 and 3 weeks after treatment was lower in CR than in SE group. Winn's neutralization assay revealed that antitumor activity of spleen cells at 1 and 3 week(s) after treatment was lower in CR than in SE groups. In vivo observation on effect of inactivated serum at 1 week after treatment showed tumor enhancement in SE group and tumor inhibition in CR group. In conclusion, the observed mild reduction in antitumor immunity in the relatively early period after cryosurgery might not be due to blocking action of superfluous tumor antigens, but probably due to activation of suppressor cells consequent on cryosurgical stress or on slow absorption of tumor antigens.

Animals↗

[Immunological effect of splenectomy in tumor-bearing rat].

UNLABELLED: Immunologic merit and demerit of splenectomy were studied, using experimental model in rat. ANIMALS: SD rat. Tumor: Metastasizing Rat's Mammary Tumor No. 1 (MRMT-1) originally induced by 3-MC administration to SD rat. Experimental study: Splenectomy was done on day before and after subcutaneous inoculation of 200mg of MRMT-1 at the back of 4 week-old female SD rats. Tumor growth following splenectomy and immunological competency of rat's peripheral lymphocytes, spleen cells and thymus cells was investigated and following results were obtained. When splenectomy was done pre-operatively or on the 2nd or 14th day after tumor inoculation, subsequent tumor growth was inhibited, however, when it was done on the 7th day after the inoculation, tumor enhancement and shortening of survival period were observed. When it was done on the 21st day, tumor growth was almost the same as in the rats without splenectomy. The results of cpm values and SI ratio of PHA-induced blastogenesis, and NK-activity indicated that immunological competency of spleen cells of tumor bearers was reduced during the early tumor-bearing period and the late tumor bearing period, while it was increased in the middle tumor bearing period. Tumor growth following splenectomy was considered to be controlled by immunological competency of spleen cells. Thus, it may not be unreasonable that tumor growth is inhibited on some occasions and it is facilitated on other occasions after splenectomy.

Animals↗

[Experimental study on immunological effect of splenectomy on tumor-bearers].

In view of popularity of splenectomy in combination with gastrectomy for gastric cancer, immunological effect of splenectomy was studied experimentally, using SD rats and 3-methylcholanthrene-induced mammary cancer, MRMT -1. Splenectomy was performed on day -14, 2, 7, 14 or 21 of sc inoculation of 200 mg (about 4 X 10(6) cells) of MRMT -1 at the back of 4-week-old female rats. Tumor growth and immunocompetence of peripheral lymphocytes, spleen cells and thymus cells were examined. Tumor growth on day 35 tended to be inhibited in rats splenectomized on day -14, 2, or 14, while it tended to be promoted in rats splenectomized on day 7. PHA-induced blastogenesis and NK activity of spleen cells were reduced on day 2, rose on day 7 and gradually decreased on days 14 and 21. Winn's neutralization assay revealed that spleen cells on days 2, 14 and 21 of tumor inoculation had suppressor activities. In conclusion, spleen cells of tumor-bearing rats showed a reduced immunocompetence on day 2 (the early tumor-bearing stage) and on day 14 and later (the late tumor-bearing stage), while they showed a raised immunocompetence on day 7 (the middle tumor-bearing period).

Animals↗

Influences of operative stress on cell-mediated immunity and on tumor metastasis and their prevention by nonspecific immunotherapy: experimental studies in rats.

Influences of operative stress on nonspecific cell-mediated immunity and on liability to tumor metastasis and preventive effects thereon of a nonspecific immunopotentiator OK-432 were examined. Syngeneic female SD rats were inoculated SC with 200 mg of a transplantable mammary carcinoma MRMT-1 at the dorsal flank. After 2 weeks the tumor was surgically excised simply or combined with 30-min laparotomy. It was revealed by follow-up examination that the laparotomy stress significantly increased incidence of postoperative lung metastasis. It was found that PHA-induced blastogenesis of peripheral lymphocytes was markedly reduced in the early period following laparotomy. Preoperative or post-operative (especially the former) administration of OK-432 was effective for preventing both the postlaparotomy facilitation of lung metastasis and the postlaparotomy reduction in PHA lymphoblastogenesis.

Animals↗