Search PubMed⌕ Search

Biomedical subjects

R C Rees

Publications and source records attributed to R C Rees.

At least 91 records · Page 5Linked to original sources
PubMed1992

Circulating prostate specific antigen-positive cells correlate with metastatic prostate cancer.

Analytical flow cytometry was used to study circulating prostate specific antigen (PSA)-positive cells in 40 consecutive patients with newly diagnosed, untreated prostate cancer; 25 patients (63%) had metastatic disease confirmed by a positive bone scan. Cell suspensions were prepared for each patient from both the primary tumour and peripheral blood samples. The cells were stained with a monoclonal antibody against PSA, and analysed by flow cytometry; PSA-positive cells were sorted according to their immunofluorescence and light scatter properties. The cellular deoxyribonucleic acid (DNA) content of each specimen was also analysed to establish ploidy status. PSA-positive cells were detected in the peripheral blood of 33 patients (83%). The presence of these cells in the circulation showed a higher degree of sensitivity and specificity in predicting positive bone scans than did serum PSA levels. Circulating PSA-positive cells may represent either a subpopulation of tumour cells with distinct metastatic properties or, alternatively, host immunocytes which take up PSA in an active or passive manner.

Aged↗
PubMed1992

Production of interleukin-6 by human retinal pigment epithelium in vitro and its regulation by other cytokines.

Interleukin-6 (IL-6) is a pleiotropic cytokine which produces uveitis if administered intraocularly. It has been demonstrated in the aqueous of patients with various uveitis entities. We have investigated the ability of human retinal pigment epithelium (RPE) to produce IL-6 in vitro, both unstimulated, and in the presence of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF), interferon (IFN) gamma, and lipopolysaccharide (LPS). Five human RPE cell lines were cultured over a 6-day period, both unstimulated and in the presence of these cyokines. IL-6 in the supernatants was measured using an ELISA assay. Unstimulated RPE produced small amounts of IL-6. IL-1 at 100 or 10 U/ml markedly upregulated IL-6 production, and TNF at 1000, 100 or 10 U/ml did so to a lesser extent. Neither IFN gamma or LPS alone increased IL-6 expression, but together gave significant upregulation. Thus human RPE can produce IL-6 and may be the source of this cytokine in ocular inflammatory states.

Cell Line↗
PubMed1992

Gelatinolytic metalloproteinase secretion patterns in ocular melanoma.

Fifteen posterior uveal melanoma cell lines were analyzed qualitatively for gelatinolytic and caseinolytic proteinase activity after one to five in vitro passages. All 15 cell lines secreted a gelatinolytic metalloproteinase, with an apparent molecular weight of 72 kD, into protein-free culture media; nine of these secreted an additional gelatinolytic metalloproteinase with an apparent molecular weight of 92 kD. Neither species had the ability to degrade casein. This approach may provide insight into the mechanisms of tumor metastasis in uveal melanoma.

Aged↗
PubMed1991

Apoptosis: a potential role for cytosolic transglutaminase and its importance in tumour progression.

The relationship between transglutaminase activity, apoptosis and the propensity of a tumour to metastasise, was investigated in a series of metastatic variants of an HSV-2 induced hamster fibrosarcoma and two metastatic variants of the B16 mouse melanoma. The data suggest an inverse relationship between metastatic potential and cytosolic transglutaminase activity. A direct relationship was found between measured cytosolic activity and the levels of the endogenous product of transglutaminase, the protein crosslink epsilon(gamma-glutamyl)lysine. Increasing metastatic potential and decreasing cytosolic transglutaminase activity was accompanied by a corresponding decrease in the number of detergent-insoluble apoptotic envelopes isolated from variant cell lines. These apoptotic envelopes were found to be highly crosslinked structures, containing more than 85% of the cells content of epsilon(gamma-glutamyl)lysine. These data are in keeping with the idea that a major role for the cytosolic transglutaminase is in the formation of the highly crosslinked apoptotic envelope during programmed cell death and that perturbation of this function may be an important determinant in the development of the metastatic phenotype.

Animals↗
PubMed1991

Malignant melanoma and renal cell carcinoma: immunological and haematological effects of recombinant human interleukin-2.

The immunological and haematological effects of continuous infusion of recombinant human interleukin-2 (rhIL-2) in 6 patients with metastatic melanoma and 6 with disseminated renal cell carcinoma are reported. In patients with malignant melanoma dacarbazine was given before IL-2; in renal cell carcinoma IL-2 alone was given. In malignant melanoma, 1 complete (CR) and 1 partial response (PR) were seen; 2 patients had stable disease (SD) and 2 progressive disease (PD). In renal cell carcinoma 4 patients had SD and 2 PD. Toxicity of IL-2 therapy was minimal. All patients showed increased cytotoxicity, that was not major histocompatibility complex restricted, towards target cells sensitive and insensitive to natural killer cells. These activities varied between individual patients and were less marked in cases of renal cell carcinoma. Cellular proliferative responses increased in all patients, being consistently higher following the first course of therapy, as did HLA-DR, CD16 and CD25 activation marker expression. Hypersegmentation of neutrophils and eosinophilia were commonly observed, and in renal cell carcinoma these changes were accompanied by abnormal lymphocyte morphology.

Aged↗
PubMed1991

Factors influencing the establishment of tumour-infiltrating lymphocyte cultures from human breast carcinoma and colon carcinoma tissue.

Tumour-infiltrating lymphocytes (TIL) were obtained from breast and colon tumour tissue and cultured in vitro in the presence of recombinant human interleukin-2. Seven of 35 breast tumours and five of 41 colon TIL cultures were established in vitro: proliferation rates of greater than 10(3) were achieved. The cytotoxic capacity of these cells was determined against the cell lines K562 and SW742, and percentage cytotoxicity levels of greater than 97% and 79%, respectively, were seen. An inverse relationship between the ability of TIL to kill and their proliferative capacity was observed in all cultures. The prominent phenotype was CD3 positive, with greater than 55% of TIL expressing this antigen; there was no expression of CD16. The expression of CD56 and CD25 varied, being maximumly expressed on 64% and 38% of TIL, respectively. When greater than 90% of TIL expressed CD3, the ability of the culture to kill the target cell lines was low; only when there was an increase in the proportion of cells expressing CD56 and a decrease in the expression of CD3 was there high cytotoxicity. This study indicates that the TIL which proliferate in vitro in the presence of interleukin-2 are not necessarily the mediators of cytotoxicity.

Adult↗
PubMed1991

Loss of monomorphic and polymorphic HLA antigens in metastatic breast and colon carcinoma.

MHC class I antigens are intimately involved in intercellular communication, and recognition by cytotoxic T cells. Thus tumour cells that fail to express them may be at a growth or metastatic advantage. A series of ten colorectal and ten breast carcinomas, and their respective lymph node metastases, were examined immunohistologically using monoclonal antibodies (mAb) against both monomorphic and A2 polymorphic determinants, and beta-2-microglobulin (beta 2m). Four colon polypoid adenomas stained positively throughout, but 6/10 primary tumours had partial or complete loss of expression of monomorphic determinants using mAb W6/32: two node and the liver metastasis showed less, four more expression. Similar results were seen for beta 2m. HLA-A2 expression was absent or reduced in 4/4 colon tumours and all their metastases. Among the breast tumours, W6/32 staining was absent or reduced in 2/10, and node deposits showed two with less reactivity than their primary. Beta 2m staining was reduced or absent in 8/10 primaries and all the node metastases; in every case in which beta 2m was detected in the primary tumour their corresponding lymph node metastasis showed a decreased expression. HLA-A2 expression was absent or reduced in 3/4 primary breast carcinomas, and all their metastases. These results show that individual human colon and breast carcinomas often have a reduced HLA class I antigen expression, which apparently confers a metastatic advantage.

Adenoma↗
PubMed1991

Natural killer cell activity following cryosurgery of normal and tumour bearing liver in an animal model.

Cryosurgery is a useful tool to treat unresectable liver carcinoma. In addition to the local effects of freezing, cryosurgery is thought to affect host immune response. We tested this by measuring natural killer (NK) cell cytotoxicity following cryosurgery of normal liver and an implanted liver tumour in the rat. Controls underwent sham cryosurgery. NK cytotoxicity was enhanced following cryosurgery of normal liver and liver tumour.

Animals↗
PubMed1990

The existence of an inactive form of transglutaminase within metastasising tumours.

Separation by anion exchange chromatography of detergent extracts from a poorly metastatic HSV-2-induced hamster fibrosarcoma, its highly metastatic variant and a highly metastatic rat fibrosarcoma indicated the presence of an inactive form of transglutaminase antigen, when eluent fractions were assayed for transglutaminase activity and antigen. This inactive antigenic transglutaminase was clearly separable from the particulate and cytosolic forms of the transglutaminase enzyme. Unlike tumours, its presence could not be demonstrated in extracts from normal rat liver. Measurement of activity levels during tumour growth indicated that the progression of the two highly metastatic tumours was accompanied by a decrease in cytosolic transglutaminase activity, whilst the activity of this enzyme form remained constant in the poorly metastatic tumour. Measurement of antigen levels indicated an inverse relationship between the level of inactive transglutaminase and the level of cytosolic transglutaminase activity, suggesting that the two forms are inter-related. Gel filtration indicated the molecular weight of the inactive form to be greater than both the particulate and cytosolic forms, and it was estimated to be 120,000. Partial proteolysis of the semi-purified inactive form, by either trypsin or thrombin, led to its activation and to the appearance of a transglutaminase similar in molecular weight and ionic mobility, both by anion-exchange chromatography and electrophoresis, to the cytosolic transglutaminase.

Animals↗
PubMed1990

Immunological similarities between cytosolic and particulate tissue transglutaminase.

At the present time it is uncertain whether or not the cytosolic and particulate forms of tissue transglutaminase are distinct and discrete enzymes. In this study a number of physical and immunological similarities between the two forms are demonstrated, indicating that they share some common epitopes, although their native confirmations may differ.

Animals↗
PubMed1990

Chromosome studies in eleven colorectal tumors.

Cytogenetic analysis is presented on seven freshly derived colorectal tumors and four established cell lines (SW 742, SW 480, SW 948, and HT 29). No chromosome change was common to all tumors, although previous nonrandom findings were confirmed. Single chromosome abnormalities were identified in two cases, 47,XX,+i(7p) and 46,XX,-17,+der(17),t(17;?)(p;?), and their relevance to tumor origin and development is discussed. The association of i(8q) with tumors of the rectosigmoidal region is confirmed, and it is suggested that other rearrangements involving loss of 8p may have the same association. Abnormalities resulting in loss of 20p and duplication of 20q, not previously reported as a nonrandom change, were seen in seven out of 11 cases.

Adenocarcinoma↗
PubMed1990

MHC restricted and non-restricted killer lymphocytes.

Cytotoxic lymphocytes are either MHC-restricted (cytotoxic T-cells) or nonrestricted (natural killer NK-cells), although cells of the monocyte/macrophage lineage are also cytotoxic, and lymphocytes or phagocytic cells expressing Fc-receptors for immunoglobulin can function as antibody-dependent killer cells (referred to as antibody-dependent cellular cytotoxicity: ADCC). Antigen-specific T-lymphocytes recognise their target antigen in the context of MHC class I components, focusing their attack only against those cells expressing the relevant antigen specificity on their cell surface. A more primitive and alternative mechanism exists whereby NK-cells, classified as large granular lymphocytes (LGL), are able to kill in a non-specific manner, not requiring prior sensitisation to antigen. Both antigen-specific T-cells and LGL mediate their cytotoxicity through the release of cytotoxic molecules at the target-effector cell interface. LGL also have a regulatory role in the immune system through the release of cytokines, and can be distinguished from T-lymphocytes by the expression of distinct phenotypic markers (CD16+, CD56+) and they lack CD3 antigen expression or rearranged alpha/beta or gamma/delta T-cell receptor gene products. Cytotoxic activity is positively regulated by interleukin-2 (IL-2) and interferon (IFN), whilst prostaglandins and transforming growth factor-beta (TGF beta) diminish activation and effector pathways. Cytotoxicity mediated by NK- and T-cell populations are principally involved in the defence against microbial infections and neoplasia; the abrogation of cytotoxicity either by direct interaction of 'suppressor factors' with effector cells, or indirectly by reducing cytokine production can inevitably lead to the proliferation of the disease.

Animals↗
PubMed1990

Suppression of lymphokine-activated killer (LAK) cell induction mediated by interleukin-4 and transforming growth factor-beta 1: effect of addition of exogenous tumour necrosis factor-alpha and interferon-gamma, and measurement of their endogenous production.

Recombinant human interleukin-4 (rhIL-4) and transforming growth factor-beta 1 (TGF-beta 1) suppressed the induction of lymphokine-activated killer (LAK) activity induced by recombinant human interleukin-2 (rhIL-2) in peripheral blood lymphocytes. DNA synthesis and the expression of the p55 alpha chain of the IL-2 receptor (Tac antigen) were also inhibited. The inhibitory effect was greatest when these factors were added during the first 48 h of a 4-day culture, with reduced cytolytic activity against both natural killer (NK) resistant and NK-sensitive tumour cell line targets. The suppressive action of both cytokines was accompanied by a reduction in tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) levels in lymphocyte culture supernatants. Recombinant human IFN-gamma (rhIFN-gamma), but not recombinant human TNF-alpha (rhTNF-alpha) was able to overcome the inhibitory effect of recombinant human interleukin-4 (rhIL-4) on LAK induction and DNA synthesis but not Tac antigen expression. However, cytotoxicity induced by rhIFN-gamma alone was also suppressed by rhIL-4 and TGF-beta 1, inferring that rhIFN-gamma-mediated abrogation of rhIL4 suppression was not simply a direct IL-2-independent effect on cytotoxicity. In addition, rhIL-4 did not increase TGF-beta production from rhIL-2-activated peripheral blood mononuclear cells, suggesting that rhIL-4 did not mediate reduction of rhIL-2 responses through the induction of TGF-beta release.

Cell Division↗