Immunoregulatory markers in rats carrying Dunning R3327 H, G, or MAT-LyLu prostatic adenocarcinoma variants (original) (raw)
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International Urology and Nephrology, 1998
Prostatic epithelium basically consists of secretory-luminal, basal and endocrine-paracrine cells. Immunohistochemical procedures are frequently used for showing the cells reflecting different differentiations. In this study, 40 prostatic tissue specimens submitted to the Department of Pathology of In0niJ University, Research Hospital, between 1991 and 1996 were examined. Half of the cases were diagnosed as cancer and the other half had various benign lesions. Of the cases 22.5% (n = 9) were needle biopsy material whereas the remainder, 47.5% (n = 19), were from prostatectomy and 30% (n = 12) were transurethral resection of the prostate (TURP) specimens. High molecular weight anti-cytokeratin antibodies (HMW anti-cytokeratin) stained basal cells both in all normal prostatic tissue and benign prostatic lesions, but in the majority of cancers (70%, n = 14) negative immunoreactivity was seen. Nevertheless, in some of the cancer cases (30%, n = 6) basal cell anti-cytokeratin staining was shown. Negative immunoreactivity with HMW anti-cytokeratin is important in distinguishing between malignant and benign lesions, whereas positive staining is not every time in favour of benign lesions. With the usage of prostate specific antigen (PSA) it was seen that all of the malignant and benign prostatic lesions stained positively. Basal cells in hyperplastic glands were not stained with this stain. Irregular, and in some areas, intense (PSA) immunoreactivity is present in precancerous and malignant lesions. Endocrine cells, which are represented with Chromogranin-A (Chr-A) immunoreactivity and reflecting neuroendocrine differentiation, are present in 75% (n = 15) of benign lesions and in 50% (n = 10) of cancer cases. It was thought that the lesser number of these cells in neoplastic lesions in comparison to the non-tumoral lesions is correlated with the disorder of mechanism that regulates the cell growth. Both in neoplastic and nontumoral tissues the prostatic epithelial cells showed the three markers, namely HMW anti-cytokeratin, PSA, and Chr-A, which may reflect the multidirectional differentiation of these cells from a pluripotent origin.
Establishment of a Syngeneic Orthotopic Model of Prostate Cancer in Immunocompetent Rats
Journal of Toxicologic Pathology, 2014
We previously established 3 cell lines (PLS10, PLS20 and PLS30) from a chemically-induced prostate carcinoma in F344 rats, and demonstrated high potential for metastasis in nude mice. In the present study, we investigated the feasibility of establishing an orthotopic model using the 3 rat prostate cancer cell lines in immunocompetent rats with the aim of resolving species-mismatch problems and defects of immune systems. The PLS10, PLS20 and PLS30 cell lines were injected into the ventral prostates of 6-weekold rats, which were then sacriiced at experimental weeks 4 and 8. Tumor mass formation was found in rats with PLS10, but not in those with PLS20 or PLS30. Additionally, metastatic carcinomas could be detected in lymph nodes and lungs of PLS10-inoculated rats. Genetic analysis demonstrated K-ras gene mutations in PLS10 and PLS20, but not in PLS30 cells. There were no mutations in p53 and KLF6. In conclusion, we established a syngeneic orthotopic model for prostate cancer in immunocompetent rats simulating human castration-resistant prostate cancer (CRPC), which should prove useful for development and validation of therapeutic agents, especially with immunotherapy. (
Research in Veterinary Science
The aim of this study was to characterise T and B lymphocyte density in 6 normal prostates, 15 benign prostatic hyperplasia (BPH) and 24 prostate carcinomas (PCs) in dogs by immunohistochemistry. Results revealed a statistically significant increase of T and B cells in PC compared to normal specimens and BPH. Regarding PC histological variants, lower number of CD3 + and CD79 + lymphocytes were observed in the most undifferentiated (solid) type. CD3 + cell density was positively correlated with survival time. These results may help in understanding the immunological mechanisms regulating BPH and PC development and progression, as well as providing background data for future immunotherapeutic trials.
Immunostaging in carcinoma of prostate
Urology, 1976
Immunostaging is a new method of assessing patients immunologically before and after immunotherapy. Twenty-eight patients with adenocarcinoma of the prostate were immunostaged independently by two investigators. There was a positive correlation between both immunostagings. There was also a positive correlation between the patient's immunostage and the clinical stage of his cancer.
PAIII prostate tumors express prostate specific antigen (PSA) in Lobund-Wistar rats
Canadian journal of veterinary research = Revue canadienne de recherche vétérinaire, 2009
Prostate cancer has been modeled in various species, including dogs, mice, and rats. A common method involves the use of transplanted prostate cancer cell lines. The Lobund-Wistar (LW) rat model of prostate cancer allows for the use of models involving either autochthonous prostate cancer or transplantation of a cell line (PAIII), originally derived from a LW rat. The origin of autochthonous prostate tumors in the LW rat is unknown, though suspected to originate from the seminal vesicles. Likewise, the prostatic origin of the PAIII cell line is also uncertain. To determine if the PAIII cell line is derived from the prostate, subcutaneous PAIII tumors from LW rats underwent immunohistochemical labeling for prostate specific antigen (PSA), a prostate-specific serine protease. All 5 PAIII tumors demonstrated labeling for PSA, supporting a prostatic origin for the PAIII cell line.
The response of Dunning R3327 prostatic adenocarcinoma to IL-2, histamine and radiation
British journal of cancer, 1998
A syngeneic, androgen-sensitive Dunning R3327 rat prostatic adenocarcinoma was transplanted bilaterally in the flanks of male Copenhagen Fisher rats. Approximately 3 months after implantation, when the tumours had a median volume of 150 mm3, one group of rats was treated with histamine alone (4 mg kg(-1) subcutaneously on week days), another group with human recombinant interleukin 2 (IL-2) alone (425 IU kg(-1) continuous infusion) and a third group with both histamine and IL-2 during 6 weeks. Tumours on one flank were irradiated (6 Gy once daily for 3 days to a total dose of 18 Gy) beginning 1 week after the onset of treatment with histamine and/or IL-2. The contralateral tumour served as the intra-animal control. The tumour volumes were determined weekly. The growth curves showed that all three drug treatments were effective in delaying growth, but when used individually did not cause tumour shrinkage. Radiation was the most effective single agent, but when used alone the shrinkag...
Monoclonal antibody-defined antigens of human prostate cancer cell line PC3
Cancer Immunology Immunotherapy, 1986
Over 600 hybridomas were derived from the immunization of mice with live cells and aqueous extracts of the human prostatic carcinoma cell line PC3. A total of 26 hybridomas with restricted reactivities were selected, subcloned and antibodies tested on a variety of tumor and normal cells. Seven monoclonal antibodies showed reactivity for prostate cancer and other tumor cell lines, including breast carcinomas. Three of the antibodies obtained after immunization with live cells reacted with live cells only and three of the four antibodies obtained after immunization with cell extract reacted with cell extracts and spent culture media. The fourth antibody in the latter group was reactive only in the immunoperoxidase staining assay. Antibody PrS5 recognized a 90,000 molecular weight molecule from 125I-surface-labeled cells in immunoprecipitation analysis. Antibodies PrE3 and PrD8 detected a nonacid glycolipid pentasaccharide from PC3 cells and meconium, and a glycoprotein of 115,000 molecular weight from 12SI-surface-labeled red blood cells. The similar patterns of reactivity in RIAs and antigen analysis suggest that antibodies PrE3 and PrD8 recognize the same molecule. The results emphasize the usefulness of immunohistochemistry in the testing of monoclonal antibodies and the impact of the form in which the antigen is presented on the resultant antibody specificity
British journal of cancer, 1990
The prostate gland is said to be immunologically privileged because it lacks afferent lymphatics and because of the immunosuppressive properties of seminal fluid. To elicit the presence or absence of an immune response within the diseased prostate gland, the infiltrate in prostate glands affected by hyperplasia or adenocarcinoma was phenotypically characterised, using immunohistochemical techniques. An infiltrate, composed mainly of T-lymphocytes (CD-3+), was demonstrated in all glands examined. No difference in the type, level of activation or degree of infiltration was found between those glands affected by hyperplasia (n = 20) and those affected by adenocarcinoma (n = 20). In the malignant cases, there was no correlation between grade (Gleason) or stage (TNM) and the type or degree of mononuclear cell infiltrate. Our findings suggest that the host response, in situ, to hyperplasia and adenocarcinoma is similar and may reflect the fact that the two diseases are often found concurr...
Immune rejection in a humanized model of murine prostate cancer
Anticancer research, 2010
We attempted to develop a humanized mouse model for prostate cancer to study immune recognition and responses to human prostate-tumor antigens in mice. Our study was based on cell lines derived from transgenic adenocarcinoma of the mouse prostate (TRAMP) tumors. TRAMP cells were modified to express a chimeric MHC I molecule comprising the extracellular domains of human HLA-A2.1 with the transmembrane and intracellular domain of K(b). These modified TRAMP cells were immunologically rejected following recognition of human tumor epitopes known to be immunodominant in the context of HLA-A2.1. Immune-compromised SCID-beige mice did not reject these tumors. We conclude that epitopes derived from endogenous murine homologs were being presented by the chimeric MHC class I molecules due to a lack of central tolerance to these epitopes in the mice.