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Biomedical subjects

H J Rapp

Publications and source records attributed to H J Rapp.

At least 73 records · Page 4Linked to original sources
PubMed1978

Cytotoxic activity of guinea-pig lymph node cells stimulated in vitro.

Guinea-pig lymph-node cells (LNC) cultured for 5 days in medium containing fetal calf serum (FCS) were cytotoxic to various target cells. LNC cultured in medium supplemented with fresh, autologous guinea-pig serum (GPS) instead of FCS were not detectably cytotoxic unless agents that stimulate lymphocyte proliferation were added to the culture medium. The stimulating agents we studied were 2-mercaptoethanol (2-ME), syngeneic tumor cells, allogeneic peritoneal exudate cells (PEC) and the T-cell mitogens concanavalin A (Con A) and phytohemagglutinin (PHA). LNC cultured in the presence of these agents were cytotoxic to normal syngeneic fibroblasts and to syngeneic, allogeneic or xenogeneic tumor cells but not to PHA-induced lymphoblasts. Potentiation of cytotoxicity in vitro was accompanied by a marked proliferation of the cultured LNC; the combination of several stimulatory agents had an additive effect on the generation of cytotoxicity in culture.

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PubMed1978

Glucan: attempts to demonstrate therapeutic activity against five syngeneic tumors in guinea pigs and mice.

Animals with established syngeneic tumor transplants were treated with glucan to study the therapeutic potential of this agent under well-defined experimental conditions. The tumors used were a guinea pig hepatoma, 2 murine fibrosarcomas, a murine melanoma, and a murine adenocarcinoma. All tumors were syngeneic to the host. Living BCG, administered directly into guinea pig tumors, cured all animals, whereas glucan, administered under the same conditions, had no significant antitumor activity. Neither BCG nor glucan, when administered iv, was active against the guinea pig hepatoma. An emulsion prepared with endotoxin, a fraction of mycobacteria related to cord factor, and mineral oil when administered intratumorally was also effective in treatment of line 10 tumor. A similar emulsion, in which glucan was substituted for endotoxin, was inactive, intralesional, ip, or iv administration of glucan was ineffective against the murine tumors. Previous reports of glucan-induced activity against a B16 murine melanoma were not confirmed. BCG was tested against the 2 murine fibrosarcomas and, when given either intratumorally or iv, was found to be effective against one of them.

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PubMed1978

Immunotherapy of bilateral lymph node metastases in guinea pigs by intralesional or paralesional injection of Mycobacterium bovis (BCG).

Bilateral axillary lymph node metastases occurred after intradermal (id) injection of line 10 hepatocellular carcinoma cells over the thoracic spine of inbred guinea pigs. Excision of the dermal tumor 7 days after injection of tumor cells did not prevent the development of metastases. Injection of BCG into dermal tumors without surgery led to their regression and prevented the growth of microscopic metastases in both right and left superficial distal axillary lymph nodes. Bilateral id injection of BCG between the dermal transplant and each of the regional lymph nodes followed by excision of the dermal tumor also prevented progression of metastases. Unilateral id injection of BCG before excision of dermal tumors failed to retard metastases in contralateral superficial distal axillary lymph nodes. These results suggested that elimination of microscopic lymph node metastases required delivery of adjuvant to or near each metastatic site. Systemic tumor immunity alone may be inadequate to eradicate lymph node metastases.

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PubMed1978

Toxicity of emulsified trehalose-6,6'-dimycolate (cord factor) in mice depends on size distribution of mineral oil droplets.

Toxicity of emulsified trehalose-6,6'-dimycolate administered intravenously into mice depended on the size distribution of the mineral oil droplets. Emulsions containing the greatest number of the largest oil droplets were the most toxic. Emulsions of trehalose-6,6'-dimycolate made with peanut oil or with olive oil were less toxic than those made with mineral oil.

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PubMed1978

Immunotherapy of a guinea pig hepatoma with mycobacterial vaccines: comparison of BCG cell walls and cell wall skeletons.

BCG cell wall skeletons (SK) derived from BCG cell walls (CW) by treatment with proteolytic enzymes and organic solvents were tested for their potency to cause regression of a transplanted guinea pig hepatoma. On a weight basic, SK were as effective as CW in causing tumor regression, and they, as well as purified protein derivative of mycobacteria, provoked delayed cutaneous hypersensitivity reactions in animals immunized with CW or with SK. On a weight basis, CW were more active than SK in eliciting delayed cutaneous hypersensitivity in sensitized guinea pigs whether the animals were immunized with CW or with SK. In unimmunized animals the inflammatory response to intradermally administered CW was greater than that evoked by SK. CW and SK provoked delayed cutaneous hypersensitivity reactions of similar strength in animals immunized with living BCG. This study provided no compelling reasons for using SK instead of CW in clinical trials of cancer treatment by mycobacterial vaccines.

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PubMed1977

Tumor regression after intralesional injection of emulsified trehalose-6,6'-dimycolate (cord factor): efficacy increases with oil concentration.

Injection of emulsified trehalose-6,6'-dimycolate (TDM), a mycobacterial glycolipid, into transplants of an established, syngeneic murine fibrosarcoma induced complete regression of tumor in a number of animals. The number of animals in wich tumor regressed completely depended on the amount of oil in the emulsion. The anti-tumor activity of the TDM emulsion containing the highest concentration of oil was equivalent to that of living BCG.

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PubMed1977

Immunotherapy of a guinea pig hepatoma with living BCG: a frozen liquid and a lyophilized preparation are equally active.

A freeze dried preparation of BCG with a low ratio of living to dead organisms (LV) was compared to a frozen liquid preparation with high viability (HV) for its ability to eradicate established dermal tumors and microscopic lymph node metastases in guinea pigs. The cure rate achieved by the intralesional injection of LV-BCG did not differ significantly from that of HV-bcg when similar numbers of viable organisms were injected.

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PubMed1977

Regression of established intradermal tumors and lymph node metastases in guinea pigs after systemic transfer of immune lymphoid cells.

Strain-2 male guinea pigs with established intradermal (id) tumors and microscopic regional lymph node metastases were treated by systemic transfer of syngeneic peritoneal exudate (PE) cells from tumor-immune guinea pigs. This treatment produced complete regressions of established id tumor nodules (10-11 mm in diameter) and prevented the growth of lymph node metastases in 32 (80%) of the 40 treated animals. All untreated animals died with progressive id and lymphatic tumor growth. Lymph node tumor metastases that remained after id tumor excision were also suppressed by immune cell transfer. PE cells from guinea pigs immune to an antigenically distinct tumor line (line-1), BCG, or PE cells from nonimmune guinea pigs failed to produce tumor regression or prolongation of survival time. PE cells from allogeneic guinea pigs and from sheep immune to line-10 failed to transfer tumor immunity to strain-2 guinea pigs. The effectiveness of therapy was reduced by increasing the tumor burden or decreasing the number of transferred lymphoid cells. This study demonstrated that systemic transfer of cells from syngeneic immune donors could effectively eliminate tumors as well as early metastases.

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PubMed1977

Regression of bovine ocular carcinoma by treatment with a mycobacterial vaccine.

Hereford cows with naturally occurring ocular squamous cell carcinoma were treated by injection of BCG cell-wall vaccine into the tumor. Regression or arrest of disease was observed in 71% of treated animals. The disease progressed in all untreated animals and animals treated with improperly compounded vaccine. At autopsy, most animals with progressive disease had lymph node metastases.

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PubMed1977

Immunotherapy of metastatic cancer in guinea pigs: failure of intralesional BCG to influence the results of radical surgery.

Guinea pigs with growing intradermal transplants of a syngeneic hepatoma treated by intralesional injection of living BCG at a time when lymph node metastases were detectable by palpation were not cured but survived longer than did the controls. Treatment of the animals by excision of the transplant and draining lymph nodes, instead of by BCG, resulted in a significant number of cures. The cure rate of animals receiving both treatments was not demonstrably greater than that obtained in animals receiving surgery alone.

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PubMed1977

Granuloma formation in lungs of mice after intravenous administration of emulsified trehalose-6,6'-dimycolate (cord factor): reaction intensity depends on size distribution of the oil droplets.

The intensity of the granulomatous reaction evoked in lungs of mice by trehalose-6,6'-dimycolate administered intravenously in oil-water emulsion depended on the size distribution of the oil droplets. Emulsions containing the greatest number of the largest oil droplets were the most granulomagenic.

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PubMed1976

Intralesional immunotherapy of melanoma with BCG.

Treatment of recurrent cutaneous melanoma nodules with BCG is an effective and relatively nonmorbid method for eliminating these tumor nodules. Injected nodules can be made to disappear about 90 per cent of the time and in about 20 per cent of patients non-injected nodules in the same drainage area may also regress. Subcutaneous melanoma nodules are far more resistant to melanoma injection. Although cutaneous nodules can be made to regress there is no evidence that a systemic effect against disseminated melanoma exists and no responses of distant visceral disease have been seen following intralesional therapy of cutaneous nodules. The regression of cutaneous nodules following BCG injection appears to be an immunologic phenomenon and is related to the immunocompetence of the patient. The molecular mechanisms of this tumor regression are unknown and are the subject of intensive study. Several new approaches such as the use of BCG for the treatment of poor prognosis primary malignant melanomas, as well as the use of nonviable, nonbacteriologic agents for intralesional treatment are under investigation.

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PubMed1976

Prevention of tumor growth after intradermal injection of BCG extracts: a comparison of results in strain-2 guinea pigs from the National Institutes of Health and from the National Jewish Hospital and Research Center.

Line 10, a transplantable hepatocellular carcinoma, was obtained originally from an NIH strain-2 male guinea pig fed diethylnitrosamine. The antitumor activity of BCG and BCG extracts was evaluated in strain-2 guinea pigs obtained both from NIH and the National Jewish Hospital and Research Center (NJH). Animals were immunized with these materials and then tested for their capacity to resist the growth of intradermally injected line-10 tumor cells. Tumor growth was not prevented in 18 NIH animals immunized with living BCG. No tumor growth occurred in 1 of 22 NIH animals immunized with a residue that remained after exhaustive methanol extraction of BCG and in 1 of 44 NIH guinea pigs immunized with BCG extracts. In contrast, tumor growth was prevented in 13 of 22 similarly immunized NJH guinea pigs.

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PubMed1976

Regression of established tumors and induction of tumor immunity by intratumor chemotherapy.

The inoculation of a mixture of drugs and guinea pig hepatoma cells (line-10) induced tumor-specific immunity in about 20% of guinea pigs. When guinea pigs with established intradermal tumors were given various drugs ip, no cures were observed; in contrast, multiple intralesional injections of actinomycin D, 1,3-bis(2-chlorethyl)-1-nitrosourea, adriamycin, mitomycin C, and melphalan were effective in curing animals of their intradermal tumors at a time when there were tumor cells in the draining lymph nodes; dimethyl-triazenoimidazole carboxamide, methotrexate, 5-fluorouracil, and 6-mercaptopurine were not effective. More than 80% of the cured animals were immune to rechallenge with 10(6) line-10 tumor cells.

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