Id-anti-Id interaction constitutes an immune network that is involved in the regulation of the immune response. We prepared several anti-Id mAb to anti-CEA mAb MA 208 which was found to recognize the peptide of CEA. These anti-Id mAb were then used for idiotope mapping and for developing anti-anti-Id antibodies to analyze the Id network system relating to CEA. Anti-anti-Id mAb M 7-625 antisera (Ab 3) reacted with purified CEA in binding assay and in Western blot analysis, and competed with Ab1 binding to CEA. It is indicated that Ab2 mimicks the structure of the epitope in CEA which was recognized with Ab1. These serologic findings suggest that anti-Id mAb M 7-625 carries the internal image of the Ag. According to the amino acid sequences of CDR 1, 2, and 3 of the mAb M 7-625 variable region, there exists a homology of amino acid sequences between CDR 2 in the H chain (5 amino acids of 10) and CDR 3 in the L chain (3 amino acids of 9) of mAb M 7-625 and domain III of CEA (545-554). Internal image bearing anti-Id antibodies may be useful for the induction of a host's immune response against tunors.

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The clinical evaluation (i. e., survival rate of patients) and pharmaceutical characteristics of CELE for HCC were examined. Using image analyzer or scanning electron microscope with cryosystem, it appeared that CELE were maintained emulsion for 24 hours after preparation. In metalic ion elution test from vial or syringe including CELE, a few metalic ions were detected. In a bacteriological examination, CELE was a germ-free. In rat mesentery artery preparation, CELE was passed through the artery smoothly. For tumor stages II, III, and IV, 1-, 2- and 3-years survival values were 90%, 67% and 67%, respectively (treatment with CELE arterial injection and transcatheter arterial embolization), while for tumor stage II, 1-, 2-years survival values were 59% and 27%, respectively (CELE arterial injection only). No severe side effects were observed with CELE. A combination treatment of HCC appears to be more effective.

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Tegafur(Futraful, FT)is well absorbed from GI tract, and metabolized to 5-FU mainly in the liver microsomal enzyme, P-450. Biochemical modulation of FT was attempted to enhance 5-FU delivery in tumor tissues by mean of the increase in 5-FU production from FT and the inhibition of the catabolism of produced 5-FU, and the pharmnacokinetics were investigated in S. 180 bearing mice and VX2 bearing rabbits. Phenobarbital (PB) +glutathione+FT : PB is known as an inducer of P-450. This combination resulted a higher level of 5-FU in the blood and tissues. Uracil(U)+FT ; UFT : U inhibits an inactivating enzyme of 5 FU, dihydrouracil dehydrogenase. In an appropriate dose of UFT, 5-FU level in tumor was selectively elevated. 5-chloro-2, 4-dihydroxypyridine (CDHP)+Oxonic acid(Oxo)+FT ; S-1 : CDHP inhibits the catabolism of 5-FU by dihydrouracil dehydrogenase very strongly and enhanced 5-FU level especially in tumor tissues. Oxo persisted in GI tract and inhibits the anabolism of 5-FU, and protected GI toxicities.

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The immunological response in intratumor administrated anticancer polymer-composites were studied in the human malignant gliomas. Patients with glioblastoma and anaplastic astrocytoma were treated by local chemotherapy with 5Fu or ACNU polymer composites and radiotherapy, Surgical specimens of pretreated and posttreated with maligant glioma were investigated by immunohistochemistry using GFAP, Vim, LCA, UCHIL-1, L-26, EMA, Leu7, CR3/43, KP-1, and MAC-387. LCA and MAC 387 in pretreated glioma tissue were not seen. UCHL-1 and MCA-387 were infiltrated in the peritumorous region of posttreated glioma. The natural immunological response dose not work in the glioma tissue, but after local therapy, cellular response were increased in the peritumorous area of recurrent glioma

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Various forms of hydroxyapatite(HAP) materials have been extensively developed for orthopedic and dental applications as bone grafts and bone substitutes. It seems useful to incorporate cancer chemotherapeutic agents into implant materials used in the sites of the bony defect postoperation of bone tumors, to control local recurrence. This study was conducted to investigate whether porous HAP is appropriate as a drug carrier for adriamycin(ADR) by determining the anticancer effects of ADR-HAP beads and release behavior of ADR from HAP beads. Porous HAP bead (8.48 mm in diameter, 531±0.7mg in weight) was used as a model material, Various ADR-HAP beads(ADR 0.4∼6.0mg/bead)were implanted s. c. into Sprague-Dawley rats at 6 day postinoculation of Swarm rat chondrosarcoma. ADR levels were determined using HPLC. ADR in the tumors released from ADR-HAP beads(6.0mg/bead) were observed over a 13-week period. However, the diffusion of the drug to other organs such as heart and liver was very low compared with the level in the tumors. ADR HAP beads more than the dose of 1.0mg/bead showed strong antitumor activities with dose of ADR. The dose of 6.0mg/bead showed most efficacy, and no toxic death caused, which 98% growth inhibition on Day 31, and the survival advantage of 339% increase in life span were obtained. HAP is thus concluded to be usable not only as a bone graft but as an anticancer drug carrier for achieving high sustained local levels of the anticancer drug in the implanted site, together a low systemic level.

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Permeation of insulin across the nasal mucosa, a desirable absorption site for peptide and protein drugs to avoid their first-pass effect and gastrointestinal degradation, excised from rabbits and the effect of bile salts as permeation enhancers on it were evaluted by using Ussing chamber system. Insulin was degraded in this system, and the degradation in the mucosal side was slightly sooner than that in the serosal side. Every bile salt (0.5%) used in this study reduced transmucosal electrical resistance (Rm) and enhanced insulin permeation. The degradation of insulin in the mucosal side was inhibited by addition of a bile salt, sodium taurodihydrofusidate. These results suggest that the Ussing chamber system becomes a useful tool to evaluate the enzymatic barrir function of nasal mucosa.

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Hydroxyapatite small crystals(HAp-sol)applied as a drug carrier are being developed. The HAp-sol was synthesized by a wet method and amounts of drug adsorbed onto the hydroxyapatite small crystals were measured. The HAp-sol was characterized by X-ray powder diffraction, transmission electron microscopy, and infrared absorption. From the TEM observation, the crystal had a stick-like shape(average length was 730 Å and width was 140 Å).The amount of drug adsorbed onto the crystals was measured by an ultraviolet-visible radiation spectrophotometer. The drugs used were doxorubicin hydrochloride, mitomycin C, and fluorouracil (Kyowa Hakkao) which are glycoside antibiotics. An adsorption curve as a function of time, adsorption isotherm, and eluted amount of adsorbed drug were measured. Investigation of the adsorption was carried out at pH 7.50 (1.0 mmol/1 phosphoric buffer solution) and incubated at 37°C. The concentration of HAp-sol was 5mg/ml. The saturation time of doxorubicin-hydrochloride-adsorption onto HAp-sol required 2 hours. The amount of doxorubicin hydrochloride saturated adsorption was 0.2 mg per 1 mg HAp-sol. In the measurement of the eluted amount of doxorubicin hydrochloride, half of the saturated adsorbed drug was eluted into the phosphoric buffer solution. This result indicates that HAp-sol adsorbed with doxorubicin hydrochloride is useful as a drug delivery system.

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A MFGM emulsion containing vitamin D₃ was administered to rate whose pancreatic duct was ligated or intact. The recovered percentage of vitamin D₃ in lymph decreased to 1/70 when pancreatic duct was ligated. Three kinds of MFGM microemulsion, one was with both taurocholate and lipase, one with taurocholate alone, and the other without taurocholate or lipase, were administered to pancreatic duct-ligate rats and the lymphatic absorptions of vitamin D₃ were compared. It was found that the absorption is significantly different among them. The microemulsion containing both taurocholate and lipase showed the highest promotion effect of lymphatic absorption of vitamin D₃. In gel filtration experiment, we confirmed the difference in composition among three kinds of microemulsion. The properties of MFGM emulsion and tween 80 emulsion were also compared. Lipase was added in MFGM emulsion and tween 80 emulsion and the amout of fatty acid in emulsions was determined. It was found that the lipolysis occurs more easily in MFGM emulsion than in tween 80 emulsion. The ESR analysis of microemulsions, containing taurocholate and lipase, indicated that the membrane fluidity of MFGM microemulsion was higher than that of tween 80 microemulsion. These results suggested that the lipase plays an important role in the promotion effect of lymphatic drug absorption by MFGM, which resulting in the difference of lymphatic absorption of vitamin D₃ between MFGM and tween 80 dosage forms.

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