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Biomedical subjects

H Takao

Publications and source records attributed to H Takao.

At least 55 records · Page 3Linked to original sources

[Experimental studies on induction of various lymphokine-activated killer cells using recombinant interleukin 2].

Fundamental studies were performed on adoptive immunotherapy, especially on promotion of cell proliferation and on augmentation of cytotoxicity of various lymphokine-activated killer cells, induced by recombinant interleukin 2(R-IL2) with (P-LAK) or without (LAK) PHA, from peripheral blood lymphocytes (PBL) of healthy volunteers. The following results were obtained. 1) In LAK induced by culturing normal PBL with R-IL2, a cell proliferation was observed in 14 days. Their cytotoxic activity against all the strain cells examined, was higher than PBL already on the third day of culture. 2) Culturing normal PBL with PHA (with or without R-IL2) for 3 days, followed by culturing with R-IL2 for 11 days, caused a marked increase in cell number by about 65 times in 14 days. Cytotoxicity of these cells against MKN-28, MKN-45 and KATO III was found to increase with lapse of culture time. 3) On the 14th day of culture, cytotoxicity of LAK was higher than that of P-LAK. 4) Surface phenotype analysis of LAK revealed that OKT3+ (cell ratio) tended to increase, OKT8+ increased significantly, OKT4+ and Leu7+ tended to decrease, and OKT4+/OKT8+ ratio decreased significantly. Analysis of P-LAK revealed that OKT3+ and OKT8+ increased significantly and OKT4+, Leu7+, and OKT4+/OKT8+ ratio decreased significantly. 5) The rate of total increase in cytotoxicity, calculated in multiplying the rate of cell number increase by the rate of increase in cytotoxicity, was higher in P-LAK than in LAK. The above results showed that P-LAK induced by addition of PHA for the first few days, could cause marked increase both in cell number and in total cytotoxicity.

Adult↗

Effects of serum immunosuppressive factors on antitumor cytotoxicity of interleukin 2-induced lymphocytes.

The cytotoxic ability of interleukin 2 (IL2)-induced T cells and the effect on their cytotoxicity of serum suppressive factors obtained from cancer patients were examined. Peripheral blood mononuclear cells (PBL) of healthy adults were IL2-cultured for 72 h either together with a gastric carcinoma cell line MKN-28 or with phytohemagglutinin, then IL2-cultured for another 11 days. Cytotoxicity of the MKN-28 precultured lymphocytes against MKN-28 was particularly increased. Presence during preculture or during cytotoxicity assay of sera from gastric cancer patients having the same histological type as MKN-28 suppressed the cytotoxicity. However, the serum suppressive effect on cytotoxicity of the IL2-cultured lymphocytes was far milder than that on PBL cytotoxicity.

Adenocarcinoma↗

[Experience with CDDP therapy in advanced and recurrent gastric cancer cases].

For 3 years beginning in 1984, 14 advanced and recurrent gastric cancer cases with measurable lesions (8 unresected cases, 3 cases of recurrence, 2 cases with non-curative resection, 1 case of no operation) were treated by CDDP therapy alone or in combination with other chemotherapies. CR was obtained in 2 of the 8 non-resected cases, radical gastrectomy being feasible in these 2 cases by second-look operation. Five of the 8 cases showed PD, and in 1 case the effect was rather obscure. One of the 2 non-curative resection cases achieved PR, and the other case was MR. One of the 3 recurrent cases was NC, the remaining cases being PD. The one case given no operation showed PD. Overall effectiveness of CDDP therapy for advanced and recurrent gastric cancer cases was seen in 3 (21.4%) of the 14 cases. All of these 3 cases showing effective CDDP therapy was elevated serum CEA values before the therapy, which was markedly reduced after starting the therapy, the reduction rate being very remarkable.

Adult↗

Clinical studies on serum immunosuppressive acidic protein (IAP) and ferritin in gastric cancer patients: with special reference to preoperative value and influence of surgical stress.

Serum IAP and ferritin values were measured preoperatively in 83 resectable gastric cancer patients. IAP was significantly higher in them than in normal subjects, and increased gradually with progression of cancer, and the values at stages III and IV were significantly higher than that at stage I. It was significantly higher in the cases of n(+) than in those of n(-), and in the cases of noncurative resection than in those of curative resection. Ferritin was significantly higher in them than in normal subjects and mammary cancer patients, and in males than in females, and the values at stages I and IV were significantly higher than that at stage III. OK-432 was serially administered pre- and postoperatively in 83 cases and only postoperatively in 33 cases. IAP increased markedly at 1 week postoperatively and was reduced gradually at 2 and 4 weeks. Ferritin increased markedly at 1 week after operation and reached the maximum value at 2 weeks and was reduced toward the value of 1 week at 4 weeks. However, these changes showed no significant difference between the both groups.

Breast Neoplasms↗

Immunological response of regional lymph nodes after tumor cryosurgery: experimental study in rats.

Seven days after inoculation of metastasizing rat mammary tumor No. 1 into the thigh of 5-week-old female Sprague-Dawley rats, the tumor was treated cryosurgically by two-cycle freezing and by contact methods at -170 degrees C. Weights of the thymus and the spleen, histological findings of the lumbar lymph nodes, phytohemagglutinin (PHA)-induced blastogenesis of lymphocytes obtained from the lumbar lymph nodes and peripheral blood, and resistance rate to tumor rechallenge were examined 1, 3, 6, 10, and 17 week(s) after cryosurgery, with the following results: Thymus weight gradually decreased by 3 weeks after cryosurgery, while spleen weight increased by 1 week, recovering the preoperative level at 6 weeks. Paracortical hyperplasia of the lumbar lymph nodes markedly increased in 1 week and sinus histiocytosis increased after 3 weeks, both remaining at high values until 10 weeks, while germinal center hyperplasia showed a high value at 3 weeks and thereafter decreased gradually. PHA-induced blastogenesis of the lumbar lymph nodes significantly increased 1 week after cryosurgery and remained at its high value until 10 weeks. PHA-induced blastogenesis of peripheral lymphocytes showed the lowest value at 3 weeks and then significantly increased at 6 weeks. Resistance rate to rechallenge showed the lowest value at 3 weeks, reaching the highest level 10 weeks after cryosurgery. From the above results, it was suggested that anti-tumor immunity (resistance to tumor rechallenge) induced by cryosurgery was at the lowest level at 3 weeks after cryosurgery, and gradually increased starting at 6 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Experimental study on the absorption mechanism of cryo-necrotized tumor antigens].

On day 7 of MRMT-1 tumor inoculation at the thigh in 5 week-old female SD rats, the tumor was treated cryosurgically by contact method at -170 degrees C and 2 cycle freezing. Postoperative changes in local blood circulation were observed by colloidal carbon perfusion and hydrogen-clearance methods, and pathway and time course of tumor antigen absorption were observed by measuring 3H-thymidine (injected intra-tumorally) uptake in various organs. The observations were done at 0.5, 1, 2, 3, 6, 9, 12, 24, 48, 72, 120 and 168 hour(s) after cryosurgery. The following results were obtained. At 0.5 to 1 hour after cryosurgery: vascular stasis, dilatation and tortuosity were observed. There were no inflow of colloidal carbon and almost no uptake of 3H-thymidine. At 6 hours: vascular stasis and sludging became more marked. There was no inflow of carbon, while uptake of 3H-thymidine was markedly increased. At 24 hours: some carbon inflows in fine vessels and partial recovery of blood circulation in the peritumoral region were observed. Rate of 3H-thymidine uptake was more increased. At 72 hours: carbon inflow and blood circulation were further increased, while the cryo-necrotized tumor showed hyaline degeneration. At 168 hours: increase of newly formed vessels and recovery of blood circulation were remarkable, but uptake rate of 3H-thymidine was decreased according to increased demarcation of the cryo-necrotized tumor. From the above results, it was suggested that the absorption of cryo-necrotized tumor antigens was starting through lymphatic channels in the early period, then also through newly formed capillaries surrounding the tumor at 24 hours after cryosurgery and continued until 72 hours after cryosurgery.

Absorption↗

[Cytotoxicity of interleukin 2-induced lymphocytes and effects of serum immunosuppressive factors].

IL2-induced lymphocytes (IIL) obtained from normal subjects were examined as to a possibility for induction of tumor-specific killer cells. Moreover, effects of serum on their cytotoxic activity were observed. The IIL which were pre-sensitized with mitomycin C-treated MKN-28 (IILM), showed a markedly increased cytotoxic activity against MKN-28. The IIL which were either pre-cultured with PHA or not, showed augmentation of cytotoxic activity against various human cancer cell lines, although their cytotoxic activity against MKN-28 was lower than that of IILM. The cytotoxic activity of IILM was suppressed by addition to the medium of non-specific immunosuppressive factors (IAP, ferritin, alpha-fetoprotein) or of various sera obtained from gastric cancer patients, in whom histological diagnosis was tub1, por or sig, but the suppression to the IILM activity was significantly milder than that to the activity of peripheral lymphocytes. The degree of suppression by tub1 serum was significantly higher than that by the serum from por or sig. When tub1 serum was added to the medium during pre-sensitization, the cytotoxic activity of IILM against MKN-28 was reduced significantly. However, addition of por or sig serum showed no significant reduction in cytotoxic activity of IILM.

Adenocarcinoma↗

[Studies on adoptive immunotherapy using recombinant interleukin 2].

Lymphokine activated killer (LAK) cells derived from normal subjects were examined as to the following points: 1) monoclonal analysis of LAK, 2) cytotoxic ability of LAK, 3) effect on LAK cytotoxic ability of the presence in the medium of either serum obtained from gastric cancer patients or nonspecific immunosuppressive factors (ferritin, IAP, AFP), 4) effect, on induction of their cytotoxicity, of the presence in the medium during culture of sera from gastric cancer patients, simulating the conditions of in vivo administration and 5) augmentation of cytotoxic ability of LAK by simultaneous IL2 administration. The following results were obtained. 1) Monoclonal marker analysis of LAK revealed that the ratios of OKT3+, OKT4+, OKT8+ and OKIa1+ lymphocytes were all significantly higher than those in peripheral blood lymphocytes (PBL). 2) Cytotoxic ability of LAK against various tumor cell lines (MKN-28, MKN-45, KATOIII, PC-10 and K562) was found to be higher than that of PBL. 3) Addition to medium of ferritin, IAP or AFP significantly reduced the cytotoxic ability of both PBL and LAK against various tumor cell lines. However, the degree of reduction was significantly milder in the case of LAK than in PBL. 4) The cytotoxicity-suppressing effects of gastric cancer sera (untreated, at stages III and IV) were significantly milder in the case of LAK than in PBL. 5) When gastric cancer serum was added to medium, instead of normal AB serum during induction of LAK, its cytotoxic ability against various tumor cell lines was significantly reduced. Its cytotoxic ability was nevertheless significantly higher than that of PBL. 6) When IL2 was added to medium during cytotoxicity assay, cytotoxic ability of LAK was augmented. When LAK was cultured for 1 hour before assay in fresh medium containing 1,000 U/ml IL2, its cytotoxic ability was further augmented.

Adult↗

[Immunological response of regional lymph nodes after cryosurgery in rats].

At 7 days after MRMT-1 inoculation at the thigh of 5 week-old female SD rats, the tumor was treated cryosurgically by 2 cycle freezing, contact method at -170 degrees C. Weights of thymus and the spleen, histological findings of lumbar lymph nodes, PHA-induced blastogenesis of lymphocytes obtained from lumbar lymph nodes or peripheral blood, and resistance rate to tumor re-challenge were examined at 1, 3, 6, 10 and 17 week(s) after cryosurgery. Following results were obtained. (1) Weight of the thymus gradually decreased by 3 weeks after cryosurgery, while that of the spleen increased by 1 week, recovering the preoperative level at 7 weeks. (2) Paracortical hyperplasia of lumbar lymph nodes markedly increased at 1 week and sinus histiocytosis increased after 3 weeks, both keeping their high values till 10 weeks, while germinal center hyperplasia showed a high value at 2 weeks, thereafter decreasing gradually. (3) PHA-induced blastogenesis of lumbar lymph nodes significantly increased at 1 week, keeping its high value till 10 weeks. (4) PHA-induced blastogenesis of peripheral lymphocytes showed the lowest value at 3 weeks, then significantly increasing at 6 weeks. (5) Resistance rate to re-challenge showed the lowest value at 3 week, reading the highest level at 10 weeks after cryosurgery. From the above results, it was suggested that anti-tumor immunity induced by cryosurgery was at the lowest level at 3 weeks, and gradually increased starting at 6 weeks. Augmentation of helper T cell and cytotoxic T cell functions at the regional lymph nodes was also suggested to occur from 1 week to 10 weeks after cryosurgery.

Animals↗

[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↗

[Evaluation of treatment planning of radiotherapy for lung cancer].

Treatment of lung cancer in radiotherapy was evaluated by considering damages to normal tissues. Small and large tumors were examined for two portals, rotational and conformation irradiation. The considered damages were irreversible late effects in lung and injury to spinal cord. For the small tumor of 3.5 cm in diameter, rotational irradiation showed the smallest damage. For the large tumor of 12 cm X 10 cm in cross section, conformation irradiation resulted in the smallest damage.

Evaluation Studies as Topic↗

[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↗