Enhancement of various non-specific immune effector functions in mice by local injection of aclacinomycin A adsorbed onto activated carbon particles (ACR-CH).

Local injections of aclacinomycin A adsorbed onto activated carbon particles (ACR-CH) augmented the cytotoxic activities of regional lymph node cells for 7 days. In contrast NK-activity was only slightly augmented by injections of aclacinomycin A (ACR) solution or activated carbon suspension. The effects were found in lymphocytes from all regions tested. NK-activity could only be detected when both adherent and non-adherent cells were present. The cell number of L3T4+ cells in each type of lymph node tested increased, and subset analysis of the lymphocyte subpopulations revealed an increase in the ratio of L3T4+/Lyt2+ cells, suggesting that the ACR-CH selectively increased and stimulated L3T4+ cells. Enhanced capacity of lymph node cells to produce cytokines, tumor necrosis factor (TNF) and interleukin-1 (IL-1) upon restimulation (with LPS) in vitro in the ACR-CH treated group was found. From these results, it appears that the new dosage form of aclacinomycin A, ACR-CH, with superior therapeutic efficacy against lymph node metastases, can also enhance the immune response of regional lymph node cells. The findings reported here will be valuable in the establishment of novel chemoimmunotherapeutic protocols using ACR-CH.

Enhancement of cytotoxicity in mouse regional lymph nodes by local tissue injection of aclacinomycin A.

The effect of local tissue injection of activated carbon particle adsorbing aclacinomycin A (ACR-CH) on the cytotoxicity in popliteal, inguinal, paraaortic, and axillary lymph nodes was investigated in mice. Aclacinomycin (0.2 mg/kg), a potent antineoplastic drug was injected subcutaneously into the footpad of mice in the form of ACR-CH or as an ACR solution. After a single injection of ACR-CH, the regional nodal cytotoxic response against mouse YAC-1 lymphoma cells was markedly increased and sustained for 7-10 days. The immune response was also increased after ACR solution but to a much lesser extent. These effects were found in popliteal, inguinal, and paraaortic lymph nodal effector cells but not in the more remote axillary nodes. Absorption of adherence cells largely abrogated the cytotoxic response. These results suggest that ACR-CH did not impair but rather stimulated nodal immunoregulatory cells. Potentially ACR-CH may enhance immune responsiveness of regional lymph nodes after subcutaneous administration while concomitantly curtailing neoplastic growth in these same lymph nodes.

[Enhancement of therapeutic efficacy of aclarubicin against lymph node metastases using a new dosage form: aclarubicin adsorbed on activated carbon particles].

Seven days after a subcutaneous inoculation of 5 x 10(5) P388 leukemia cells into the foot pad of the left hind paw of donor mouse, aclarubicin (0.2mg/kg body weight) was injected subcutaneously into the hind paw of the opposite foot pad in the form of ACR-CH or aclarubicin aqueous solution. On day 10, the left popliteal and the lower para-aortic lymph nodes taken from each donor were transferred intraperitoneally to a normal recipient mouse. The combined survival time of recipients and the viable P388 leukemia cell number in popliteal and para-aortic lymph nodes were estimated with a calibration formula. Our results showed that the survival curve of recipients given ACR-CH was statistically improved compared with that of other treatment groups.

Enhancement of therapeutic efficacy of aclarubicin against lymph node metastases using a new dosage form: aclarubicin adsorbed on activated carbon particles.

Seven days after a subcutaneous inoculation of 5 x 10(5) P388 leukemia cells into the foot pad of the left hind paw of donor mouse, aclarubicin (0.2 mg/kg body weight) was injected subcutaneously into the hind paw of the opposite foot pad in the form of ACR-CH or aclarubicin aqueous solution. On day 10, the left popliteal and the lower para-aortic lymph nodes taken from each donor were transferred intraperitoneally to a normal recipient mouse. The combined survival time of recipients and the viable P388 leukemia cell number in popliteal and para-aortic lymph nodes were estimated with a calibration formula. Our results showed that the survival curve of recipients given ACR-CH was statistically improved compared with that of other treatment groups.

Toxicity of a new dosage format, cisplatin incorporated in lactic acid oligomer microspheres, in mice.

A new drug delivery system, cisplatin incorporated into lactic acid oligomer microspheres (CDDP-MS), was developed for the treatment of peritoneal carcinomatoses. We studied the acute toxicity and pathological effects of CDDP-MS injected intraperitoneally in mice. The 50% lethal dose was 23.8 mg/kg (21.3-26.7 mg/kg at 95% level of confidence), which was 1.76 times that of the cisplatin aqueous solution of 13.5 mg/kg (11.9-15.3 mg/kg at 95% level of confidence). The duration for the restoration of the body weight loss was prolonged when CDDP-MS at doses close to the 50% lethal dose was administered, as compared with the cisplatin aqueous solution at doses close to its 50% lethal dose. On autopsy there were no macroscopic or microscopic differences between the two dosage forms.

Enhanced therapeutic efficacy of intralymph-nodal etoposide on distal lymph node metastases using a new dosage format--activated carbon particles adsorbing etoposide.

Small activated carbon particles adsorbing etoposide were injected into the proximal lymph nodes of mice and tested for therapeutic effect on distal lymph node metastases. Eight days after s.c. inoculation of 5 x 10(5) P388 leukemia cells in the left hind foot pad of mice, when metastases had been established in the secondary draining lymph nodes (lower paraaortic nodes), etoposide (5 mg/kg) was injected into the primary draining node (left popliteal node) in the form of activated carbon particles adsorbing etoposide (ETOP-CH group) or etoposide aqueous solution. After drug administration, the primary lesion was removed so that lymph node metastases were not affected by the primary lesion. Two days after drug administration, the secondary draining nodes were extirpated, and the P388 leukemia cell number in these nodes was estimated by an i.p. transference method. The estimated number of P388 leukemia cells in the lymph nodes in the ETOP-CH group was statistically significantly (by Student's t-test, P less than 0.05-0.005) less than the number of P388 leukemia cells in the other treatment groups.

Enhanced anti-cancer effects of intralymphatic aclarubicin on distal lymph node metastases: quantitative evaluation using a new experimental model in mice.

The anti-cancer drug aclarubicin (2.0 mg/kg body weight) was injected into the left popliteal lymph node (the primary draining node of the foot-pad region) or into the tail vein, 8 days after a subcutaneous inoculation of 5 x 10(5) P388 leukemia cells/mouse in the left hind paw foot-pad of mouse (donor). During this time, metastases were established in the lower para-aortic nodes (the secondary draining nodes of this region). On day 10, the lower para-aortic nodes taken from each donor were transferred intraperitoneally to a normal mouse (recipient). From the recipients' survival time, the viable P388 leukemia cell number in the para-aortic nodes per donor mouse was estimated with a calibration line. The recipients' survival curve in the intralymphatic chemotherapy group was statistically significantly better than that in the intravenous chemotherapy group.

[Toxic reduction and superior therapeutic effects on peritoneal carcinomatosis of etoposide particles suspended in oil in mice].

Two dosage forms of etoposide diluted by saline solution (Etp-sol) and etoposide particles suspended in oil (Etp-oil) were examined for the toxicity and therapeutic effects when injected intraperitoneally (ip) in mice. The 50% lethal dose (LD50) values for two weeks observation were 135 mg/kg in Etp-oil and 108 mg/kg in Etp-sol. Two days after intraperitoneal transplantation of 10(6) cells/mouse of P388 leukemia to CDF1 male mice, etoposide was injected intraperitoneally in the form of Etp-oil or Etp-sol. In the mice receiving 20mg/kg of etoposide, 11 of 19 mice given Etp-oil and 3 of 20 given Etp-sol survived to day 60. In the mice receiving 80 mg/kg of etoposide, 1 in 20 treated with Etp-oil and 8 of 20 treated with Etp-sol died from by the toxicity.

[A case of pseudolymphoma of the lung with cough and fever].

This case report presents a 48-year-old woman who had been suffering from cough and fever for 5 years. A large mass in the right lung was pointed out. Even after various examinations, we couldn't resolve the difficult diagnostic problems involved, but it was clear that there were no signs of a malignant tumor. We suspected a large benign tumor or pulmonary sequestration. Right lower lobectomy was performed and histological examinations of the resected tumor revealed lymphoproliferative disorder. Microscopic examinations of the specimen disclosed monotonous lymphoid cells proliferation (small to medium size) without definite lymph follicles or germinal centers. Lymph follicles were clearly demonstrated with the immunoperoxidase method. These findings were interpreted to be consistent with what has been recently called pseudolymphoma of the lung and prompted discussions on the reasonableness of criteria for the diagnosis of various pseudolymphoma and effective immunological examinations for the clarification of the etiology.