Investigations of T-lymphocyte subpopulations in the rat using alloantigenic markers.
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Biomedical subjects
Publications and source records attributed to D M Lubaroff.
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The development of a tissue culture line of human prostate adenocarcinoma has been described. The culture (HPC-36), derived from tumor tissue explants, is purely epithelial, with characteristics of neoplastic cells. These include a large nuclear size relative to the amount of cytoplasm, multiple nucleoli within the nucleus, many mitotic figures, the formation of multinucleated giant cells, and loss of contact inhibition. The cells also stained positively for acid phosphatase and have been grown in monolayer and suspension cultures. The HPC-36 cells are presently being studied to determine whether they are true descendants of the cancer cells.
We report here the development of the Dunning R-3327 prostate adenocarcinoma of the Copenhagen rat as a suitable model of human prostate cancer. Tumors, produced by sc or intraprostate injection of viable cells, had the macroscopic and microscopic characteristics of the human disease. The histologic picture of these tumors was of a well-differentiated adenocarcinoma with the formation of glands and acid secretions within the acini. The intraprostate tumor, although initially confined to the injected lobe, grew to involve the surrounding tissues and eventually metastasized to the lymph nodes and lungs. Occasional metastatic lesions were found in other organs as well. During investigation of the tumor, a fast-growing line arose that grew equally well in females as in males. The histology of this tumor was of an undifferentiated anaplastic tumor. A tissue culture line derived from R-3327 was capable of producing tumors in recipient rats with characteristics similar to the original Dunning tumor.
In patients with prostate cancer, cryosurgery has been highly effective in eradication of the primary tumor. Certain clinical observations have suggested the presence of an additional systemic anticancer effect, presumably immunologic in nature, but proof is lacking. To study this problem further, we developed two animal tumor models. Instead of using the classical subcutaneous site, we transplanted the 11095A and R-3327 prostate tumors into rat prostate, the 4909 bladder tumor into rat bladder. In these respective orthotopic locations, the 3 tumors displayed favorable growth characteristics with good accessibility for cryosurgery. This model should be considered for studies involving any localized treatment of an established urologic tumor.
We report herein on the destruction by cryosurgery of the Dunning R3327 adenocarcinoma grown in the prostate. Tumors less than 1,000 mm.3 were destroyed by a single freezing procedure within 2 to 4 weeks, whereas tumors greater than 1,000 mm.3 could not be destroyed completely. We also have been able to demonstrate antibody and cellular immune responses to antigens on the R3327 cells. Species, organ and tumor specific antigens were identified by xenogeneic antiserum produced in the rabbit, while major and minor antigens were identified by alloantisera produced in the rat. Tumor antigens were characterized by a variety of in vitro and in vivo immune responses. In addition to the rabbit xenoantisera used in cytotoxicity assays, mixed lymphocyte tumor interaction produced a demonstrable in vitro immune response, lymphocytes from rats immunized with tumor cells were cytotoxic to radiolabeled tumor cells in culture, rats immunized with tumor cells in adjuvant demonstrated protection against subsequent challenge and immunological stimulation of lymph nodes draining the site of tumor cell inoculation was demonstrated by an increase in lymphocyte trapping. Clearing, the R3327 tumor system in the rat is suitable for immunological studies of prostatic cancer.
The 11095-A squamous cell tumor is a transplantable prostate carcinoma of the F344 rat. No tumor-specific antigens could be demonstrated for this carcinoma by serologic tests or in host protection experiments. Preliminary data from two other assay systems indicate that tumor-specific antigens may be weakly expressed in this model.
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The development of a tissue culture line of human prostatic adenocarcinoma is described. The culture (HPC-36), derived from tumor tissue explants, is a pure epithelial culture with characteristics of neoplastic cells, including a large nuclear size relative to the amount of cytoplasm, multiple nucleoli within the nucleus, many mitotic figures, the formation of multinucleated giant cells and the loss of contact inhibition. The cells also stained positively for acid phosphatase and have been grown in monolayer and suspension cultures. The HPC-36 cells presently are being studied to determine whether they are true descendants of the cancer cells.
The Dunning R3327 prostate adenocarcinoma of the Copenhagen rat was developed as a suitable model of human prostate cancer. Inoculation of tumor tissue mince or cells sc in the flanks of recipient rats produced tumors that had the macroscopic and microscopic characteristics of the human disease. The histologic picture of these tumors was that of a well-differentiated adenocarcinoma with the formation of glands and acid secretions within the acini. Tumors were also produced in the dorsolateral lobe of the prostate by the injection of cells. The intraprostate tumor, although initially confined to the injected lobe, grew to involve the surrounding tissues and eventually metastasized to the lymph nodes and lungs. Occasional metastatic lesions were found in other organs also. Acid phosphatase could be domonstrated by histochemical staining of frozen tumor sections, and elevated levels of the enzyme were seen in the sera of rats bearing long-term subcutaneous tumors. During investigation of the tumor, a fast-growing tumor line arose that grew equally as well in females as in males. The histology of this tumor was that of an undifferentiated anaplastic tumor.
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We report on the development of the Dunning R3327 prostatic adenocarcinoma of the Copenhagen rat as a suitable model for human prostatic cancer. Tumors produced by the subcutaneous or intraprostatic injections of viable cells had the macroscopic and microscopic characteristics of human disease. Histologically, these tumors were well differentiated adenocarcinomas with the human disease. Histologically, these tumors were well differentiated adenocarcinomas with the formation of glands and acid secretions within the acini. The intraprostatic tumor, although initially confined to the injected lobe, grew to involve the surrounding tissues and eventually metastasized to the lymph nodes and lungs. Occasional metastatic lesions were found in other organs as well. Acid phosphatase could be demonstrated by histochemical staining of frozen tumor sections and elevated levels of the enzyme were seen in the serum of rats bearing long-term subcutaneous tumors. During investigation of the tumor a fast growing line arose that grew equally as well in female as in male rats. The histology of this tumor was of an undifferentiated anaplastic tumor. Treatment by cryosurgery completely destroyed the prostatic tumor within 2 weeks. A tissue culture line derived from R3327 was capable of producing tumors in recipient rats with characteristics similar to the original Dunning tumor.
The role of bone marrow-derived cells in the rejection of skin allografts in rats was investigated. Lewis rats, rendered tolerant of BN antigens and bearing healthy grafts, were thymectomized, irradiated with 900 rad, and injected with varying doses of either normal isologous bone marrow, normal lymph node cells, and/or lymph node cells presensitized to BN antigens. In some experiments rats were also adoptively sensitized to tuberculin. Results showed that, although necessary for the elicitation of tuberculin skin reactions, bone marrow cells are not needed for the rejection of previously tolerated skin allografts. Rats receiving lymph node cells alone rejected their grafts in about 6-7 days. In addition, rats injected with bone marrow alone also rejected their grafts, although significantly later than did lymph node cell recipients, indicating that rat marrow contains a population of cells capable of reacting to transplantation antigens. These cells were found capable of reacting to major transplantation antigens but not minor as they were ineffective in causing the rejection of Ag-B compatible Fischer skin grafts. From experiments utilizing bone marrow from neonatally thymectomized donors and cells treated with an antiserum to rat T cells, these competent cells in the marrow were shown to be thymus derived.
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Rats of the BN strain, inoculated at birth with (Lewis x BN)F(1) hybrid lymph node cells are not tolerant of Lewis skin grafts but do display high degrees of tolerance of Lewis hearts.
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