Therapeutic effect of immune ribonucleic acid in an adjuvant setting: prevention of pulmonary metastases after primary melanoma resection.
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Biomedical subjects
Publications and source records attributed to G Steele.
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The authors studied the effects of a week's viewing of five types of television programs, including those with predominantly helpful or hurtful content, on the aggressive mood and hurtful behavior of adult men. They found, within the population studied, a significant decrease in aggressive mood and lower levels of hurtful behavior in viewers of helpful programs as compared with a control group, as well as some evidence that emotional arousal in response to helpful programs is negatively correlated with aggressive mood.
Chemically induced bowel tumors in Wistar/Furth (W/F) rats possess surface antigens analogous to those demonstrated in humans with colon carcinoma. To determine if these in vitro tumors markers have any in vivo significance, tumor isograft challenge experiments were performed. Groups of animals received three immunizing doses of 10(7) cells from chemically induced colon carcinomas NG-W1, DMH-W49, or DMH-W9 or small-bowel adenocarcinoma DMH-W7. Control rats were immunized with a noncross-reacting, virally induced mammary fibroadenoma A9-W1. Six weeks after immunization, all animals were challenged with 1 X 10(5) or 3 X 10(4) colon carcinoma NG-W1 cells. None of the NG-W1-immunized animals developed tumors after either NG-W1 challenge dose. In contrast to this strong protection by "private" tumor rejection antigen (TRA), protection by common or "tissue type specific" antigens was evident only if tumor volumes were measured. Twenty-two days after low-dose NG-W1 challenge, mean tumor volume (m) in animals immunized with colon tumor DMH-W9 (m=0.25 cu cm) and DMH-W49 (m=0.17 cu cm) were less (p less than 0.05) than in animals untreated (m=1.0 cu cm) or immunized with mammary fibroadenoma A9-W1 (m=0.9 cu cm). Embryonic antigens also may function as weak TRAs. NG-W1 challenge tumor volumes in fetal-gut-immunized (m=0.9 cu cm) and whole embryo-immunized animals (m=0.9 cu cm) were less (p less than 0.05) than in fetal-kidney-immunized (m=2.5 cu cm) or adult-colon-immunized animals (m=1.8 cu cm). Low-dose NG-W1 challenge tumor volumes were less (p less than 0.01) in multiparous females (m=0.3 cu cm) than in either untreated (m=1.2 cu cm) or age-matched virgins (m=1.4 cu cm). In vitro tumor markers in this model may serve an important function in vivo as TRAs.
A case of persistent sciatic artery aneurysm in a 65-year-old woman was treated by exclusion and reconstruction with a saphenous vein graft. When cases such as this present as pulsatile buttock masses, arteriography is the most important diagnostic aide. It will indicate when the circulation must be reconstructed and when it is safe to simply ligate an aneurysm.
In a series of consecutive 51chromium (51Cr) assays, 21 melanoma and 14 colo-rectal carcinoma patients were tested for their in vitro cell-mediated immune reactions to melanoma, rectal adenocarcinoma, and normal fibroblast target cells. Blood lymphocytes (BL) from four individuals were included in each experiment. In 9/14 experiments the BL effects of 2 melanoma patients were compared to BL effects of 2 colorectal carcinoma patients. In two experiments, BL from 1 melanoma patient and 1 colorectal carcinoma patient were compared for cytotoxic effect with each other and with BL from 2 normal healthy donors, and in the remaining 3 experiments BL from 2 melanoma patients were compared with BL from 1 healthy donor and one patient bearing a tumor which was neither a melanoma nor a colorectal carcinoma. Eleven out of 14 experiments were performed in a criss-cross manner. Target cells in the first three tests of this series consisted of tumor cells and fibroblasts explanted from a single melanoma patient. In all of the remaining experiments, each BL population was tested for cytotoxicity against both a tumor-fibroblast target cell pair explanted from one of two melanoma patients and a tumor-fibroblast target cell pair explanted from a rectal adenocarcinoma patient. Out of 35 tumor patients, 27 (77%) demonstrated a selective cytotoxic effect on the tumor target cells compared to the corresponding fibroblasts, while 4 patients (11%) showed a selective effect on the fibroblasts, and 6/29 patients showed a selective effect on the other type of tumor cells compared to matching fibroblasts. In 8/11 experiments (including two repeat tests) tumor-specific BL effects were demonstrated in a criss-cross manner. BL separations and 51Cr tests were repeated in 11 of the 35 patients 2-4 weeks after their original tests. BL populations from these 11 patients reproduced their individual earlier effects, whether these effects showed specific, non-specific, or no cytotoxicity. In each assay, differences in sensitivity between fibroblasts and tumor target cells in matched pairs were analyzed by comparing the effects of BL from the two controls. No differences in target-cell sensitivity could be demonstrated.
In vitro assays of cell-mediated tumor immunity utilizing 51Chromium (51Cr) labelling of cultured adherent solid tumor cells were designed which allowed an effector cell/target cell incubation time of 48 h without overriding spontaneous 51Cr release. In a series of 16 consecutive experiments, blood lymphocytes from healthy human donors, from patients with tumors unrelated to the cultural tumor target cells, and from colon carcinoma and melanoma patients were tested for their cytotoxic effects on various target cell pairs, human colon carcinoma, melanoma, or skin fibroblasts. The same reagents were used in simultaneously performed microplate and 51Cr assays. Results obtained by visual counting of microplate tests and by 24-h assays of 51Cr release or 51Cr retention correlated in 20/25 effector-cell/target-cell combinations. In a series of six consecutive experiments, lymph-node cells from untreated Wistar/Furth rats, and rats bearing either chemically-induced colon carcinoma NG-W1 or polyoma virus-induced sarcoma P-W13 were tested for their cytotoxicity on syngeneic rat colon carcinoma and sarcoma target cells. Criss-cross type experiments were performed by microplate and 15Cr techniques done in parallel. Results obtained by visual counting of microplate tests and by 48 h assays of 51Cr release or 51Cr retention correlated in 15/18 effector-cell/target-cell combinations.
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Soluble intracytoplasmic protein fractions and solubilized tumor membrane preparations produced by 3 M KC1 or papain treatment were isolated from a 1,2 dimethylhydrazine-HC1 (DMH)-induced rat colon carcinoma, DHM-BU 1. Solubilized preparations were fractionated by DEAE cellulose and Sephadex G200 column Chromatography. Crude extracts and fractionated materials were tested for their ability to inhibit the cytotoxicyt of lymph-node cells (LNC) from rats bearing isografts of an N-methyl-N-nitro-N-nirosoguanidine (NG)-induced colon carcinoma, ng-W1...
Staphylococcus aureus, strain Cowan I, contains a cell-wall substance, protein A, which combines with the Fc part of IgG in most mammalian species. It can therefore be used as a solid-phase immunoabsorbant for elimination of the reacting immunoglobulins. Since it has been shown that Cowan I could absorb out the blocking activity of sera from rats bearing isografts of polyoma-virus-induced sarcomas or chemically induced colon carcinomas, we investigated what effects Cowan I absorption of human tumor-bearer sera might have. In all tumor-bearer sera tested, from patients with melanomas or colon carcinomas, treatment with protein-A-containing staphylococci decreased the sera's ability to inhibit lymphocyte-mediated cytotoxicity in vitro. Cowan-I-treated sera from healthy controls had no effect on lymphocyte cytotoxicity. Nor did Cowan-I-treated tumor-bearer sera potentiate or "arm" normal lymphocytes against tumor target cells. There was no evidence of complement-dependent cytotoxicity with added human complement in sera from melanoma and colon carcinoma bearing patients either before or after absorption with Staphylococcus aureus, Cowan I, The concentrations of IgA, IgG and IgM were determined in sera used for in vitro tests of blocking activity and complement-dependent cytotoxicity before and after absorption. No reduction of IgA, reduction to undetectable levels of IgG and 20-30 percent reduction of IgM immunoglobulins as compared to unabsorbed sera were demonstrated.
A rat large bowel carcinoma model has been established with close similarities to the immunological features of the corresponding human neoplasms as far as those are presently known: (1) common antigens with tissue-type specificity, (2) expression of immunogenic gut-specific embryonal antigens, (3) cell-mediated immunity present in tumor bearers, whose sera are capable of blocking the lymphocyte effect specifically, and (4) rapid disappearance of the serum blocking activity after tumor excision. It is suggested that this model is therefore particularly suitable for further detailed analysis of the potential function in vivo of tissue-type specific antigens. In addition, this model appears to be applicable to correlating alterations in immune status with tumor course after various modes of intervention such as chemotherapy and immunotherapy alone, or in combination with surgery.
Full-thickness skin grafts from either BN (Ag-B3) or WF (Ag-B2) rats were transplanted to WF recipients of the same sex. Six to seven days after grafting, recipients were challenged with isografts of a chemically induced rat colon carcinoma, NG-W1. In three of four experiments, mean challenge tumor volumes were greater after allografting than after skin isografting. Tumor incidences, however, were no different in rats after skin allograft or isograft placement. When isografts of a polyoma virus-induced sarcoma, P-W13, were used to challenge WF rats after skin grafting, tumor incidence was significantly greater in animals which has received allografts, whether or not they also had been immunized to P-W13 before challenge. Thus, in otherwise untreated inbred rats, grafting of full-thickness skin from donors differing at a major histocompatibility locus led to facilitated growth of solid tumor isografts in animals undergoing allograft rejection.
Colon and small-bowel tumors were induced in WF rats by treatment with one of three chemical carcinogens. Tumor occurrence and growth were monitored by multiple double-contrast examinations. Roentgenologic diagnoses and histologic examination of tumors were verified at tumor resection or autopsy. Serial serum samples from each of 11 rats were tested in microcytotoxicity assays for their ability to block the cytotoxicity of lymph node cells from rats with isografts of colon carcinoma NG-W1 against NG-W1 target cells. Sera from all tumor-bearing rats demonstrated specific blocking activity. With two exceptions, serum blocking activity preceded roentgenologic evidence of tumor. Sera of the 2 exceptional rats lacked blocking 2 and 8 weeks before tumor detection, respectively. The sera of only one animal specifically inhibited lymphocyte cytotoxicity despite consistently negative double-contrast examinations. At autopsy this rat was found to have an adenocarcinoma of the distal rectum, impossible to visualize by the roentgenologic technique used. In serum samples obtained from animals after successful tumor excision and with no radiologic evidence of recurrence, blocking activity could no longer be demonstrated. Rats that had received carcinogen but developed no tumor and had no abnormalities on double-contrast examination demonstrated no serum blocking activity.
The effects of cyclophosphamide (CY) on tumor immunity against isografts of rat sarcomas induced by polyoma virus were studied using in vitro techniques. Groups of sarcoma-bearing animals received CY (250 mg/kg intraperitoneally 11 days after isografting) CY (150 mg/kg IP 8 days after isografting), or IP injections of 0.9% NaCl. In control rats tumor growth was progressive. All CY-treated animals showed transient tumor regression of at least 50% of their pretreatment tumor volume. Despite a drastic depression in numbers of blood leukocytes as well as lymph-node cells following CY treatment, animals treated with 150 mg/kg CY were shown to have blood lymphocyte and lymph-node cell cytotoxicity in vitro against plated sarcoma target cells comparable to untreated sarcoma-bearing animals. Sera obtained from sracoma-bearing rats prior to CY treatment specifically blocked lymphocyte cytotoxicity against sarcoma target cells. After CY treatment serum blocking activity could not be demonstrated during the period of tumor regression, but reappeared in parallel with tumor regrowth. Antibodies cytotoxic to sarcoma target cells when homologous complement was added could not be demonstrated in sera obtained from animals before CY treatment, but were present after treatment during tumor remission. Following CY treatment, sera obtained from treated animals, when mixed with blocking sera from control animals, could counteract or unblock the blocking activity of tumor-bearer sera. Unblocking capacity was present only in sera obtained during CY-induced tumor remission. Serum IgG concentration was significantly and temporarily decreased after CY treatment.
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