Biomedical subjects
A J Papadopoulos
Publications and source records attributed to A J Papadopoulos.
Cholera toxin-induced alteration of the phenotype and behaviour of an ovarian carcinoma cell line, SR8.
Cholera toxin (CT) has been reported to cause a variety of effects on several different cell types. Recently, CT has been shown to increase the susceptibility of ovarian carcinoma cells to cytotoxicity mediated by a variety of effector cells (natural killer, lymphokine-activated killer cells and tumour-associated lymphocytes derived from ascites of ovarian cancer patients) of both autologous and allogenic background. In the present study, CT demonstrated several effects on a newly established ovarian carcinoma line (SR8)1 when added to the culture medium at a concentration of 12.5 ng/mL for 2 days. Cholera toxin altered SR8 morphology to a uniform polygonal cellular shape, with less cell dispersion than the non-CT treated cells. Cholera toxin prolonged the population doubling time by approximately 10 h. The CT-treated SR8 cells exhibited reduced epidermal growth factor receptor expression (39 versus 50%), and increased carbohydrate antigen 125 expression (45 versus 2%) in both immunocytochemical and quantitative flow cytometric analyses. These changes in morphology and tumour marker expression were reversible when CT was removed from the culture. The CT-treated SR8 cells showed reduced capacity to generate tumours in female nude mice in comparison with non-CT treated cells, which produce both subcutaneous and intraperitoneal xenografts with local invasion in an animal model. Cytogenetic analysis of the cell line SR8 before and during treatment with CT showed no new clonal rearrangements. The possible mechanisms involved and the influence of CT on the biological behaviour of ovarian tumour cells are discussed.
Fluorescence spectroscopy of normal, SV40-transformed human keratinocytes, and carcinoma cells.
Native fluorescence emission and excitation spectra of SV40 infected human keratinocytes, A431 and SCC324 carcinoma cells, and normal human keratinocytes were measured and compared. A difference in the intracellular metabolic state of NADH was found between the normal cells and the cancer or virus-transformed cells. The observed difference, namely an increased proportion of bound, mitochondrial NADH in the cancer and virus-infected cells, manifests as a blue spectral shift in the emission spectra.
Tumor lymphocytes in patients with advanced ovarian cancer: changes during in vitro culture and implications for immunotherapy.
Tumor specimens and ascites of patients with advanced ovarian cancer were utilized to obtain both primary ovarian carcinoma cell cultures and lymphocytes: tumor-infiltrating lymphocytes (TILs) from solid tumor tissue and tumor-associated lymphocytes (TALs) from peritoneal fluid. Tumor lymphocytes were grown in coculture with autologous tumor cells and recombinant human IL-2 (rhIL-2) for up to 4 weeks and at weekly intervals these were examined with respect to phenotype and cytotoxicity. The phenotype was studied using flow cytometry for a variety of human immunocompetent cell surface markers (CD3, CD4 CD8, CD16, CD56, TCR alphabeta, TCRgammadelta). Cytotoxicity was investigated using 4-hr 51Cr-release assays with the primary ovarian carcinoma cell cultures and the K562 cell line as target cells. The tumor lymphocytes did not demonstrate any obvious trend in phenotype changes during culture, although for different cultures a large range was noted for the various lymphocyte populations studied. Cytotoxicity against both autologous and allogeneic targets declined with culture length for the majority (6/7) of the lymphocyte cell lines tested (greatest at 1 week and least at 3 weeks). These initial results indicate that an in vitro non-MHC-restricted cytotoxic function of peritoneal lymphocytes can be effectively activated with IL-2 and autologous tumor cells. However, if activated lymphocytes are to be employed as a form of immunotherapy, they should be given within the first week of culture for maximum cytotoxic effect.
Polarization filter for biomedical tissue optical imaging.
A technique based on the degree that light is depolarized when propagating inside tissues is demonstrated for optical imaging in biomedical systems. The difference in the degree of polarization of the emerging light allows for the discrimination of different types of tissues. The technique was investigated in the transillumination and back-scattering geometry and in both cases the potential of this method to image and separate out different types of tissues is demonstrated.
Caecocystoplasty and bilateral oophorectomy followed by chemotherapy for diffuse, non-Hodgkins lymphoma of the ovary involving the bladder. Case report.
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SR8--the establishment and characterisation of a new ovarian carcinoma cell line and xenograft model.
A new cell line, SR8, and xenograft model of ovarian carcinoma has been established in this laboratory over the past 20 months from a patient with advanced ovarian cancer. Electron microscopic examination of SR8 cells demonstrated the presence of desmosomes and tonofilaments; SR8 cells expressed epithelial membrane antigen (EMA) and glandular associated cytokeratin, all of these confirmed the epithelial origin of this cell line. In addition, SR8 cells expressed CA125, as did the original ovarian tumour. EGF-R and TP53 expression was identified by immunocytochemistry (ICC) in this line. Nearly all the SR8 cells (93%) expressed HLA-class I antigen while 13.5% expressed HLA-DR. SR8 cells showed near-diploid and -triploid chromosome populations with several clonal and non-clonal rearrangements. Subcutaneous and intraperitoneal xenografting of SR8 cells resulted in invasive tumour production at both sites in 3/4 and 4/4 female nude mice, respectively. These xenografts exhibited similar morphology as that of original tumour and were found to express EMA, cytokeratin, CA125 and TP53. The potential research applications of this cell line are discussed.
High grade non-Hodgkins stage IEB primary malignant lymphoma of the cervix and upper vagina. A case report.
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Induction of immunocellular resistance to IL-2-activated lymphocytes within ovarian carcinoma cells.
The development of resistance within ovarian carcinoma cells to activated cytotoxic lymphocytes was the objective of this study. Primary ovarian carcinoma cells were obtained from the ascites of a patient. These cells were cocultured with IL-2-activated autologous tumor-associated lymphocytes (TALs) for 1 week. The resulting selected cells underwent a second coculture for 3 days with IL-2-activated autologous TALs or tumor-infiltrating lymphocytes (TILs). Phenotype analysis of the lymphocytes was performed prior to selection and 4-hr chromium release assays were used to detect resistance induction. Resistance to all effector cells could be demonstrated for the selected cells. However, selected cells maintained in culture demonstrated no difference in cytotoxic susceptibility from unselected cells. The following conclusions were made: (i) rapid immunoselection can occur for ovarian carcinoma in vitro; (ii) the resistance induced is not MHC-restricted; (iii) resistance induced by one type of cytotoxic cell results in general resistance to other types of cell from the same patient; and (iv) this resistance is not maintained during in vitro culture. These results may have direct implications on the future immunotherapy for this condition.