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Biomedical subjects

H J Rapp

Publications and source records attributed to H J Rapp.

At least 55 records · Page 3Linked to original sources
PubMed1980

Influence of surfactant concentration on the antitumor activity of emulsified components of mycobacteria.

The influence of Tween 80 content on the antitumor activity of emulsified mycobacterial components administered intralesionally was studied in mice. The number of treated animals in which there was complete regression of tumor depended on the concentration of Tween in each of the emulsions. An additional variable was the size distribution of the mineral oil droplets, which depended on whether the emulsions were prepared by ultrasonication or by mechanical grinding. Emulsions of mycobacterial components (cell walls of Bacillus Calmette-Guérin and trehalose-6,6'-dimycolate) prepared by ultrasonication contained smaller oil droplets than did those prepared by grinding. Ground emulsions retained antitumor activity over a wider range of Tween concentrations than did ultrasonically prepared emulsions. The latter required Tween at concentrations in an optimal range above which the tumor-regressive potency was diminished. Emulsions of trehalose-6,6'-dimycolate containing the lowest concentration of Tween needed to produce a relatively stable preparation contained larger oil droplets and were immunotherapeutically less active than were those prepared with an optimal concentration of Tween. Emulsions of B. Calmette-Guérin cell walls retained antitumor activity even in the absence of added Tween.

Animals↗
PubMed1980

Adjuvant-antigen requirements for active specific immunotherapy of microscopic metastases remaining after surgery.

We studied the conditions required for eradication by immunization of occult lymph node metastases which remained after surgical removal of an intradermally transplanted cavian hepatoma. Guinea pigs that received no postsurgical treatment all died with progressively growing lymph node metastases. The growth of these metastases could be prevented in a significant proportion of the animals by postsurgical treatment with vaccines containing oil-in-water emulsions of Mycobacterium bovis strain Bacillus Calmette-Guérin (BCG) cell walls admixed with live or irradiated tumor cells. Vaccines containing living tumor cells cured most of the guinea pigs but produced tumors at the vaccine sites in a few animals. Irradiated tumor cell vaccines were not tumorigenic but required more tumor cells for successful therapy. Therapy was dependent both on the dose of tumor cells and on that of BCG cell walls. Microgram doses of BCG cell walls were required for a therapeutic effect; milligram doses of BCG cell walls inhibited the therapeutic response. Animals rendered tumor free by postsurgical vaccine therapy rejected an intradermal challenge with living tumor cells.

Adjuvants, Immunologic↗
PubMed1979

Safety and efficacy of living BCG or BCG cell walls (CW) in the treatment of guinea pig hepatoma.

Guinea pigs with established intradermal tumors and microscopic lymph node metastases were treated by intralesional injection of graded doses of living BCG or BCG CW. The lowest dose of living BCG used produced a significant cure rate and no grossly evident toxicity. An intermediate and the highest dose of living BCG used cured some animals but others lost weight and a significant number died as a result of the treatment. Histologic examination of animals with significant weight loss showed fatty degeneration of the liver, granulomatous hepatitis and histiocytic infiltration of the spleen. None of the doses of BCG CW used was toxic and they were at least as effective as living BCG in intralesional treatment. In some experiments in which treatment was delayed it was found that the extent of disease required to render treatment ineffective was about the same for living BCG and for BCG CW.

Animals↗
PubMed1979

Regression of established oral tumors after intralesional injection of living BCG or BCG cell walls.

Oral tumors with associated cervical lymph node metastases developed after injection of tumor cells into buccal pads of inbred guinea pigs. Intralesional injection of living BCG or BCG cell walls (CW) caused regression of established tumors, prevented the development of cervical lymph node metastases and led to the development of host resistance to the growth of subsequent tumor transplant.

Animals↗
PubMed1979

Regression of a transplanted guinea pig hepatoma after intralesional injection of an emulsified mixture of endotoxin and mycobacterial sulfolipid.

Mycobacterial sulfatides (sulfolipids) in admixture with endotoxin had tumor regressive activity comparable to trehalose-6,6'-dimycolate (TDM) and endotoxin in guinea pigs, but unlike TDM were neither toxic nor granulomagenic and had no antitumor activity in mice. The increased endotoxin lethality in mice pretreated with BCG was not observed in mice pretreated with sulfolipids or TDM instead of BCG.

Animals↗
PubMed1979

Immunotherapy of guinea pigs with a transplanted hepatoma: comparison of intralesionally administered killed BCG cells and BCG cell walls.

Heat-killed whole BCG cells (KC) and BCG cell walls (CW) were each tested in emulsified form for their potency to cause regression of a transplanted guinea pig hepatoma. On a weight basis, KC were at least as effective as CW in causing tumor regression and elimination of microscopic lymph node metastasis, and they, as well as purified protein derivative of mycobacteria, provoked delayed cutaneous hypersensitivity reactions in animals immunized with CW or with KC. On a weight basis, KC were as active as CW in eliciting delayed cutaneous hypersensitivity in sensitized guinea pigs whether the animals were immunized with CW or with KC. In unimmunized animals the inflammatory response to intradermally administered KC was similar to that induced by CW. Because KC are easier to prepare than CW, it is suggested that whole killed BCG might be used instead of CW in clinical trials of cancer treatment requiring administration of nonliving mycobacteria.

Animals↗
PubMed1979

Regression of a murine fibrosarcoma after intralesional injection of a synthetic C39 glycolipid related to cord factor.

Intratumoral injection of ultrasonically prepared emulsions of the synthetic glycolipid methly 6-O-(2-tetradecyl-3-hydroxyoctadecanoyl)-alpha-D-glucopyranoside (designated C39) induced complete regression of transplants of a syngeneic murine fibrosarcoma in most of the treated animals as did 6,6'-di-O(2-tetradecyl-3-hydroxyoctadecanoyl)-alpha,alpha,-trehalose (designated C76) in a previous study. The C76 compound, about twice the molecular weight of C39, was more effective therapeutically than the smaller molecule. Ultrasonically prepared emulsions of C39 and C76 were not toxic when given intravenously. Intravenously administered emulsions of C39 prepared by mechanical grinding were more toxic, but less granulomagenic, than those containing C76. Squalane and squalene, but not peanut oil, were effective substitutes for mineral oil as carriers of C39 in the treatment of the tumor.

Animals↗
PubMed1979

Local tumor regression after intralesional injection of croton oil.

Intralesional administration of emulsified croton oil into established syngeneic transplants of murine firosarcoma no. 1023 caused complete regression of the injected tumors in C3H mice without recurrence during the period of observation. In Sewall Wright strain 2 guinea pigs, in contrast to BCG cell wall vaccine which eradicated regional lymph node metastasis as well as dermal transplants, croton oil treatment only delayed the development of metastatic disease despite the fact that the injected skin tumors did not recur. 12-O-Tetradecanoylphorbol 13-acetate (TPA), the active principle of croton oil, incorporated in mineral oil droplets in aqueous suspension, caused regression of murine tumors when injected intralesionally. Aqueous suspensions of TPA failed to eliminate the tumors. Our results suggest that tumor regression induced by croton oil of TPA emulsions was due to indiscriminate destruction of the injected tissue.

Animals↗
PubMed1979

Tumor regression after intralesional injection of mycobacterial components emulsified in 2,6,10,15,19,23-hexamethyl-2,6,10,14,18,22-tetracosahexaene (squalene), 2,6,10,15,19,23-hexamethyltetracosane (squalane), peanut oil, or mineral oil.

The influence of mineral oil, squalane, squalene, or peanut oil on the antitumor activity of emulsified Bacillus Calmette-Guérin cell walls or emulsified trehalose-6,6'-dimycolate was studied in mice, each with an established transplant of a syngeneic fibrosarcoma. Each animal received an intratumoral injection of Bacillus Calmette-Guérin cell walls (0.6 mg/mouse) or trehalose-6,6'-dimycolate (0.1 mg/mouse) emulsified in 1 to 10% oil. Emulsions of squalene or squalane but not peanut oil were effective substitutes for mineral oil as carriers of Bacillus Calmette-Guérin cell walls in the treatment of the tumor. Trehalose-6,6'-dimycolate was therapeutically active when it was incorporated in any of these four oils. The number of animals in which tumor regressed completely depended on the concentration of oil in the emulsion.

Animals↗
PubMed1979

Influence of oil concentration on the efficacy of tumor regression by emulsified components of mycobacteria.

The influence of mineral oil content on the antitumor activity of emulsified Bacillus Calmette-Guérin cell walls (CW) was studied in mice each with an established transplant of a syngeneic fibrosarcoma. Animals received intratumoral injections of CW (0.02 to 0.6 mg/mouse) emulsified in 1 to 9% oil. The number of animals in which tumor regressed completely depended on the concentration of oil in the emulsion. The methanol extraction residue (MER) of Bacillus Calmette-Guérin administered intratumorally in oil in water emulsion was also immunotherapeutically active. Neither CW nor MER was active when given as aqueous suspensions without oil. Guinea pigs with transplanted hepatomas growing in their skin and with tumor cells in the draining lymph node could be cured of malignant disease by a single intralesional injection of CW or MER (1 mg per guinea pig) if these agents were emulsified in oil (3.3%) and water. Aqueous suspensions of CW and MER were not therapeutically active in the guinea pig.

Animals↗
PubMed1978

Immunotherapy with an intralesionally administered synthetic cord factor analogue.

Injection of emulsified 6,6'-di-O-2-tetradecyl-3-hydroxyoctadecanoyl-a, a trehalose designated C76, a synthetic analogue of the mycobacterial glycolipid trehalose-6,6'-dimycolate (TDM), into transplants of an established, syngeneic murine fibrosarcoma induced complete regression of tumor in a number of animals. The number of animals in which tumor regressed completely dependent on the amount of oil in the emulsion. On a weight basis, C76 was at least as active as TDM. Intralesional injection of an emulsified mixture of C76 and endotoxin (ET) or of TDM and ET caused regression of an established transplant of a guinea-pig hepatoma in syngeneic animals. In mice, intravenously administered emulsions of C76 were less toxic and less granulomagenic than those made with TDM.

Animals↗