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Biomedical subjects

Y Teramura

Publications and source records attributed to Y Teramura.

34 records · Page 2Linked to original sources

[Adoptive immunotherapy against peritoneal metastases from stomach cancer--application of regional lymph node lymphocytes].

Twenty-four patients with advanced stomach cancer were treated with OK-432 combined adoptive immunotherapy [AIT] as prophylaxis or therapy against peritoneal metastases. Lymphocytes isolated mainly from regional lymph nodes were cultured for 9-13 days with T cell growth factor and sonicated tumor extract. OK-432 administration and cell transfer were performed via a catheter inserted into the abdominal cavity at surgery. The proliferation rate of regional lymph node lymphocytes was higher than that of peripheral blood lymphocytes (p less than 0.01). Cultured regional lymph node lymphocytes expressed CD25 and CD4+45R- more frequently than those of peripheral blood lymphocytes. On the other hand, cytotoxic activity of regional lymph node lymphocytes were slightly lower than that of peripheral blood lymphocytes. These results suggest that regional lymph node lymphocytes could be used in AIT because of their different function from that of peripheral blood lymphocytes. Survival of the patients with peritoneal metastasis at primary laparotomy was higher than that of the historical control group (4-9 months after surgery). These results show that OK-432 combined adoptive immunotherapy appears to be a new therapeutic approach to peritoneal metastases from stomach cancer.

Adult↗

The therapeutic effect of OK-432-combined adoptive immunotherapy against liver metastases from breast cancer.

We studied the therapeutic effect of OK-432 combined with adoptive immunotherapy in 19 cases of liver metastases from breast cancer. Of the 14 patients who received intraarterial OK-432 injection and transfer of cultured lymphocytes, 9 responded to this therapy, whereas no patients responded to intravenous administration. The minimum cell number for a therapeutic response was 8 x 10(8) cells. Metastatic lesions other than those in the liver regressed after therapy in 4 patients. The serum carcinoembryonic antigen level paralleled the therapeutic effect. There were no severe side-effects accompanying this therapy. These results indicate that intraarterial adoptive immunotherapy combined with OK-432 is effective as a new therapeutic approach against liver metastases from breast cancer.

Adult↗

Comparison between crude interleukin-2 and recombinant interleukin-2 in maintaining killing activity of cultured lymphocytes.

Peripheral blood lymphocytes, regional lymph node lymphocytes or malignant effusion lymphocytes from cancer patients were incubated with crude IL-2 (cIL-2) for 13 days. These effectors, which frequently expressed IL-2 receptor (IL-2R), proliferated well and possessed augmented killing activity against fresh autologous tumor cells and K562. However, when recombinant IL-2 (rIL-2) was added for the last 4 days of culture instead of cIL-2, IL-2R expression and killing activity against fresh autologous tumor cells decreased significantly (P less than 0.05). Phenotypic analysis indicated that cIL-2 significantly promoted the expansion of the cytotoxic population (CD8+.11b-)(P less than 0.05). The decreases in killing activity and IL-2R expression were restored by 0.004% PHA plus rIL-2, but not in the presence of rIFN-gamma, rIL-1 alpha, rIL-1 beta, rIL-4 or rIL-6. PHA-free cIL-2 maintained killing activity, but not IL-2R expression. We conclude that some factors in cIL-2 and a low dose of PHA-P are necessary for the maintenance of killing activity and IL-2R expression of cultured lymphocytes in the late phase of culture.

Cell Division↗

[Experimental study on the optimal treatment schedule for combination of BRM (immunostimulators, cultured killer cells or interleukin-2) and chemotherapy].

In the present study we tried to reevaluate the optimal combination timing in the experimental treatment with BRM and chemotherapeutic agents. BALB/c mice with advanced malignant ascites tumor (MOPC 104 E) were treated with cyclophosphamide (CPA, 2 mg/kg) and BRM such as immunostimulator (OK-432, Lentinan or Bestatin), interleukin-2 (IL 2) or cultured killer cells. The survival of mice was prolonged when immunostimulators were given before CPA. However, no combined effect was seen when immunostimulators were administered after CPA. Treatment with cultured killer cells and in vivo IL 2 after immunochemotherapy (immunostimulator followed by CPA) was the most effective protocol in which immunostimulator, chemotherapy, killer cells and IL 2 respectively seemed to induce, regulate, supplement and amplify anti-tumor effector cells.

Adjuvants, Immunologic↗

Therapeutic efficacy of sequential therapy with OK-432, cyclophosphamide, IL2-cultured lymphocytes and in vivo IL2 against advanced murine plasmacytoma.

BALB/c mice inoculated IP with a syngeneic plasmacytoma MOPC104E were treated with a combination of a streptococcal preparation, OK-432 (1 KE, 0.1 mg/mouse), low-dose of cyclophosphamide (CPA, 1 mg/kg) and adoptive transfer of tumor-bearer-spleen cells (2 x 10(7) cells) cultured with IL2 and sonicated tumor extract (adoptive immunotherapy; AIT). The consecutive protocol of OK-432 (day 8, 9 post inoculation) - CPA (day 10) - AIT (day 11) was the most effective. Rate of complete remission was highest when recombinant (r-) IL2 was injected to the mice after AIT. Moreover, another bacterial preparation, Nocardia rubra cell wall skeleton and another low-dose chemotherapy, Mitomycin C could be used successfully instead of OK-432 or CPA. Transfer test of intraperitoneal cells (tumor cells plus host cells) of mice on day 11 post inoculation (on the day of AIT) revealed that OK-432 augmented the susceptibility of peritoneal cells to cultured lymphocytes in inhibition of transplantability, and that CPA after OK-432 augmented the anti-tumor effect of tumor-bearer-spleen cells which act synergistically with cultured lymphocytes. This therapy schedule seems to be the best model to augment the effect of AIT with minimal side effect.

Animals↗

[The therapeutic effects of OK-432 combined adoptive immunotherapy (AIT) against liver metastases of breast cancer].

We studied the effect of OK-432 combined AIT in 24 cases of liver metastases of breast cancer. Eleven of the 16 patients (69%) who received intraarterial transfer responded to this therapy. On the other hand, no patients responded to intravenous or intraportal transfer. The minimum cell number for a therapeutic response was 10(9) cells. Four patients had abscopal effects after therapy. The serum CEA level paralleled the therapeutic effects. There were no severe side effects accompanying this therapy. These results indicate that intra-arterial OK-432 combined AIT should be the first choice therapy against liver metastases of breast cancer.

Biological Products↗

[Experimental and clinical study of adoptive immunotherapy combined with preadministration of OK-432: a method to augment the therapeutic effect].

Our previous method of adoptive immunotherapy using IL2-cultured autologous lymphocytes consists of (1) in vitro sensitization by sonicated autologous tumor extract, (2) the induction and proliferation of active CTL by crude IL2, and (3) the preadministration of OK-432 for the augmentation of the therapeutic effect. Here we describe a new method to augment the therapeutic effect of OK432-combined AIT. In BALB/c mice with advanced malignant ascites (MOPC 104E), serial therapy with OK-432, cyclophosphamide and AIT significantly prolonged the survival compared with other therapeutic schedules through synergism between host's effector cells induced by immuno-chemotherapy and transferred killer cells. Many patients with advanced malignancies, for example, unresectable gastrointestinal cancer, locally advanced breast cancer or lung metastases of breast cancer, respond to such immuno-chemo-lymphocytotherapy, while previous OK432-combined AIT was effective only in malignant pleural effusion or metastatic liver tumor from breast cancer or peritoneal dissemination of gastric cancer.

Adult↗

Selective determination of alpha 2-plasmin inhibitor activity in plasma using chromogenic substrate.

In determination of antiplasmin activity of alpha 2-plasmin inhibitor (alpha 2 PI) using an amidolytic method, alpha 2-macroglobulin (alpha 2 M) in concentrations present in normal plasma inhibits the cleavage of chromogenic substrates by plasmin even if the reaction time between alpha 2M and plasmin is shortened as much as possible. The purpose of this study was to develop a new method to assay alpha 2 PI selectively with the chromogenic substrate S-2251 using an end-point method. The antiplasmin activity of alpha 2 M was destroyed by the addition of methylamine hydrochloride. In a case of congenital alpha 2 PI deficiency, antiplasmin activity determined with the previous method without the addition of methylamine was 20% of normal plasma, whereas the results obtained using this newly developed method was 5%. A statistically significant correlation between alpha 2 PI levels determined with this method and with a single radial immunodiffusion method was observed in plasma samples collected from 40 healthy subjects and 11 patients with disseminated intravascular coagulation (DIC). In two cases of DIC, in which markedly depleted levels of alpha 2 PI and normal concentrations of alpha 2 M were observed, antiplasmin activities measured without the addition of methylamine were higher than the ones measured immunologically, whereas the results obtained with the method described here were in accordance with the antigenicities of alpha 2 PI.

Aged↗

[Intraoperative dual-mode independent lung ventilation for open-chest surgery: conventional volume-set ventilation in healthy lung and high frequency jet ventilation in diseased lung].

An effort by the anesthesiologist to maintain adequate ventilation during thoracic surgery is sometimes disturbing for the operative procedures of the surgeon. Unilateral ventilation with a large tidal volume, leaving the operative site unventilated, may provide an adequate and quiet operative field, but is opposed by the problem of disturbance in pulmonary gas exchange. The application of high frequency jet ventilation has recently been introduced to solve these problems. However, the disadvantage inherent to this technique is the tendency to produce carbon dioxide retention although it provides adequate oxygenation. In the present study, using a double lumen endobronchial tube, the large-tidal volume ventilation of the non-operative site and the high frequency jet ventilation with small tidal volume of the operative site were performed simultaneously. This technique provided the satisfactory condition of operative field, i.e., "quiet lung". Also, the serial gas analysis of the arterial and mixed venous blood samples indicated the satisfactory condition of pulmonary gas exchange.

Aged↗

Synthesis of multiacyl poly(ethylene glycol) for the conjugation of cytochrome c to phospholipid vesicle.

To conjugate water-soluble macromolecules on the surface of phospholipid vesicles, we synthesized a poly(ethylene glycol) (PEG)-lipid having four acyl chains using a lysine (Lys)-type monodendron structure. One end of the diamino-PEG was amidified with Lys, and then two amino groups of the Lys moiety were amidified with two Lys derivatives which had been acylated with two stearoyl groups. The other end of the PEG was activated with a triazine group or a pyridyldithio group. The hydrate of the lipid mixture of dipalmitoylphosphatidylcholine, cholesterol, dipalmitoylphosphatidylglycerol, and the PEG-lipid at a molar ratio of 5/5/1/0.3 was extruded in order to prepare the phospholipid vesicles with the average diameter of 270 +/- 20 nm. The coupling ratio of cytochrome c with the PEG-lipid was monitored by HPLC, detecting the pyridyl 2-thione liberated from the pyridyldithio group and determining it to be 26% on the basis of the incorporated PEG-lipid.

Cytochrome c Group↗