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Biomedical subjects

B Gusterson

Publications and source records attributed to B Gusterson.

At least 55 records · Page 3Linked to original sources
PubMed1991

c-erbB-2 protein overexpression in breast cancer is a risk factor in patients with involved and uninvolved lymph nodes.

The c-erbB-2 gene is overexpressed in about 20% of human breast cancers. Four hundred and eighty-three cases previously examined by immunohistochemical staining for c-erbB-2 expression were analysed to assess the risk associated with the elevated protein expression. Oncoprotein expression was correlated with increasing tumour grade but not with oestrogen receptor status, nodal involvement, tumour size or age. There was an increased risk of relapse and death associated with c-erbB-2 expression irrespective of nodal involvement. This marker thus appears to be a significant prognostic factor in the early as well as the late stages of breast cancer.

Adult↗
PubMed1990

Duct carcinoma in situ: predictors of local recurrence and progression in patients treated by surgery alone.

Between 1972 and 1982, 60 patients with histologically proven duct carcinoma in situ (DCIS) without evidence of invasive disease were treated by surgery alone. Treatment was not randomised and was total mastectomy (19), subcutaneous mastectomy (6) or local excision (35). Follow-up was by clinical examination and mammography with a median follow-up of 9 years (range 4-16 years). Twenty-six patients (43%) have recurred locally. The estimated proportion recurrence free at 7 years is 59% (95% CI 46-72%). Local recurrence on the chest wall occurred in one patient having total mastectomy and in the chest wall or nipple in three patients having subcutaneous mastectomy. Twenty-two patients recurred locally in the breast after conservative surgery. The 7-year recurrence-free rates were 94%, 44% and 45% respectively in the three groups. Of those patients who recurred locally 14/26 (54%) did so with invasive disease. Of the 34 who did not develop local recurrence, two developed metastases. The only factor which correlated with local recurrence and invasive local recurrence on multivariate analysis was conservative surgery (hazard ratio 4.71 (1.59-14.0), P = 0.001, and 4.05 (1.00-18.7), P = 0.03, respectively). DCIS can be an aggressive local disease and local excision may be inadequate treatment.

Breast Neoplasms↗
PubMed1989

Bone resorption and circulating PTH-like bioactivity in an animal model of hypercalcaemia of malignancy.

An in vivo model of humoral hypercalcaemia of malignancy has been used to examine the role of circulating PTH-like bioactivity in the development of bone resorption and hypercalcaemia. After inoculation of cells from a renal carcinoma cell line into nude mice, circulating PTH-like bioactivity as measured by the sensitive renal and metatarsal cytochemical bioassays for PTH was elevated in only 18% and 53% of the mice respectively. Bone resorption was elevated in all the mice investigated irrespective of the level of PTH-like bioactivity. Thus, in this model, while the circulating PTH-like moiety is more potent when acting on bone, it did not correlate with the degree of bone resorption suggesting that it may not be the sole cause of the hypercalcaemia.

Animals↗
PubMed1989

Intratumoral aromatase as a prognostic factor in human breast carcinoma.

Intratumoral aromatase activity (AA) was measured in 145 samples of human primary breast carcinoma using the tritiated water release assay which quantifies the tritium lost to water during the aromatization of 1 beta-[3H]androstenedione to estrone. Significant AA was detected in 91/145 (63%) tumors. The possibility of a relationship between AA and a variety of clinical prognostic factors such as estrogen receptors, menopausal status, site, size, and histological grade of tumor was investigated. Possible relationship with time to relapse, overall survival, and survival of patients after relapse were also studied to determine whether intratumoral AA itself was of any prognostic value. There was no relationship between AA and tumor size, site, nodal status, menopausal status or estrogen receptors. However there was a significant correlation between AA and histological grade with an excess of AA-positive tumors having high grade (P = 0.03). There was no significant relationship between AA and overall survival (P greater than 0.1), but there was a marginal inverse correlation between AA and time to relapse (P less than 0.1). A statistically significant correlation was found between AA and survival of patients after relapse (P less than 0.05).

Aromatase↗
PubMed1989

Expression of membrane glycoproteins in normal keratinocytes and squamous carcinoma cell lines.

Con A acceptor glycoproteins were analyzed by 2D-PAGE and 125I-Con A overlay in three squamous carcinoma cell lines and compared with those in the simian virus (SV40)-transformed keratinocyte cell line SVK-14 and in normal keratinocytes. The majority of the glycoproteins identified by this technique were expressed at similar levels in all of the cells examined, independent of the culture conditions used. A cell surface glycoprotein gp34 (MW 34 kDa, pI 5.1) was increased in the tumor cells compared with normal keratinocytes and expression varied with the culture density. Another glycoprotein, gp21 (MW 21 kDa, pI 6.3), was found to be increased in expression in normal keratinocytes and stratified hyperconfluent cultures of squamous carcinoma cell lines. This paper describes the potential of this technique to identify membrane glycoproteins which may be expressed as a function of proliferation or differentiation.

Carcinoma, Squamous Cell↗
PubMed1989

Expression of the common acute lymphoblastic leukaemia antigen (CALLA) in the human breast.

A biochemical and immunohistological study has been carried out to characterize the antigen in human breast reacting with antibodies to the common acute lymphoblastic leukaemia antigen (CALLA). Four different monoclonal antibodies to the CALLA antigen all stain the membrane of adult human myoepithelial cells. Surface labelling studies of freshly prepared human breast cells demonstrate that the anti-CALLA antibody, J5, immunoprecipitates a 100 kDa protein that co-electrophoreses with the CALLA antigen identified in the leukaemia cell line NALM-6. These results indicate that the CALLA antigen is expressed on myoepithelial cells and that the staining is not due to reactivity with a shared epitope on an unrelated molecule.

Antibodies, Monoclonal↗
PubMed1989

The histogenesis of mammary and extramammary Paget's disease.

The histogenesis of mammary and extramammary Paget's disease has been studied by immunohistochemical staining of paraffin-embedded tissue using a panel of epithelial cell markers, which react with secretory or ductal epithelium, but not stratified epithelium. These markers included a monoclonal antibody E29 to epithelial membrane antigen EMA, the cytokeratin marker CAM 5.2 and three new monoclonal antibodies raised to human milk fat globule membrane (LICR-LON-TW19 and H.10.A) and a human bladder cell cancer line (3.77). The findings demonstrate that both mammary and extramammary Paget's disease are of epithelial cell origin and share antigens expressed by simple epithelia. Some antigens, such as EMA and low molecular weight cytokeratins are consistently present in both diseases, whereas other antigens, identified by H.10.A and TW19 are found more frequently in cases of extramammary Paget's disease. This panel of monoclonal antibodies also proved useful in distinguishing Paget's disease from pagetoid melanoma and clear cell Bowen's disease.

Adult↗
PubMed1987

Cultured epithelium as a skin substitute.

Twenty-five burn patients with full or partial thickness skin loss received cultured epithelium (CE), allografts or autografts as part of their treatment. Overall, a 30 per cent graft 'take' was achieved irrespective of whether the CE was autograft or allograft, fresh or frozen. In the case of deep dermal burns this figure improved to 50 per cent. The surviving grafts merged with split thickness skin grafts (SSG) and advancing wound edges. When full thickness skin loss was grafted, only a patchy take could be achieved and the surviving islands of CE tended not to spread across the wound. No rejection of CE allograft was recorded either clinically or histologically up to 6 months. The technical problems and clinical implications are discussed.

Adult↗
PubMed1986

Biological studies of ten human squamous carcinoma cell lines: an overview.

Ten cell lines established from surgical specimens of human squamous carcinomas of the tongue and larynx have been investigated with respect to their motility, ultrastructure, karyotypes, certain biochemical features, interaction with normal epithelial and stromal elements and capacity to infiltrate three-dimensional organoid systems. All the cell lines have maintained several morphological and biochemical characteristics indicating a common origin, although the extent to which each line displays this heritage is variable. The phenotypes of each of the individual cell lines are, however, notably stable. Data are provided for epithelial surface markers (including epidermal growth factor, EGF) and for the synthesis and release of prostaglandins and proteases which may be involved in invasive mechanisms. Encounters between the cell lines and organoid substrata (embryonic chick heart spheroids, human amnion, chick chorioallantoic membrane) are described: the results indicate a scale of invasiveness ranging from lack of penetration to full-thickness infiltration by cells showing various distinctive growth patterns. Correlation between in vitro and in vivo findings is discussed, and it is suggested that the biological heterogeneity of the lines may reflect inherent properties of the original carcinoma cell populations which are more distinctly expressed in vitro.

Aged↗
PubMed1985

Evidence for increased epidermal growth factor receptors in human sarcomas.

The results of an immunocytochemical study of the epidermal growth factor receptor (EGFR) in 35 human soft-tissue sarcomas, using a murine monoclonal antibody (MAb) EGF-R1, are reported. In many of the tumours staining was stronger than in the adjacent stroma, suggesting increased levels of receptor. Particularly strong staining was seen in one epithelioid sarcoma and in the spindle-cell component of a synovial sarcoma. Binding studies carried out on an epithelioid sarcoma cell line established from one of the specimens, using radiolabelled EGF, showed that approximately 8% of the receptors were of high affinity with a dissociation constant (KD) of approximately 10(-10)M, while the remainder were of lower affinity with a KD of 10(-9)M. The cells expressed a total of 1.7 X 10(6) receptors/cell which is equivalent to that found in some epidermoid tumours where gene amplification has been demonstrated. These data suggest that, as with other tumours recently reported, increased levels of epidermal growth factor receptor may be related to transformation.

Antibodies, Monoclonal↗
PubMed1985

Production of beta-human chorionic gonadotrophin by human squamous carcinoma cell lines.

Eight out of 9 human squamous carcinoma cell lines ectopically secrete the beta subunit of human chorionic gonadotrophin (beta-HCG) in amounts detectable by radioimmunoassay. In contrast, both normal and SV40-transformed keratinocytes show no such evidence of beta-HCG secretion. Ectopic beta-HCG is identical in its gel exclusion and high-performance liquid chromatographic properties to placental beta-HCG and, in radioimmunoassay, yields a dilution curve parallel to that of placental beta-HCG. Dibutyryl cyclic AMP, but not sodium butyrate, stimulates beta-HCG secretion by the one human cell line examined, LICR-LON-HN-5, suggesting that ectopic production by these cells is similar to trophoblastic beta-HCG secretion, and differs from most other non-trophoblastic cell lines previously examined.

Bucladesine↗
PubMed1985

Monoclonal antibodies specific for subsets of epidermal keratins: biochemical and immunocytochemical characterization--applications in pathology and cell culture.

Keratin composition has been widely used as a biochemical marker of differentiation in normal epithelia, cell culture systems and tumours of epithelial tissues. We have been developing a model system for the study of human squamous epithelial cell differentiation, and among a panel of monoclonal antibodies we have generated for analysing this system are two antibodies recognizing subsets of epidermal keratins. The two antibodies, designated LICR-LON-16a and LICR-LON-29b, were raised to the human squamous carcinoma cell line LICR-LON-HN-5, and we describe here their biochemical and immunocytochemical characterization. Antibody 16a reacts with only epidermal basal cells in normal human skin and shows specificity for the 45 and 46 kdalton keratins. Antibody 29b stains all living layers of the epidermis, and reacts with a broad range of ketain polypeptides, (45-56 kdaltons) in immunoblotting analyses. We have investigated the alterations of cellular staining that occur in chronic hyperproliferative skin diseases and carcinomas and compared this with the staining of multilayered cultures of normal keratinocytes and the HN-5 cell line. We show that in squamous cell carcinomas and in HN-5 cell xenografts 16a and 29b stain only the well-differentiated cell types. Furthermore we found that the basal cell specificity of 16a was lost in all of the hyperproliferative skin lesions examined including psoriasis and eczema. This transition to suprabasal staining pattern was also seen in the cultures of normal keratinocytes and HN-5 cells. We conclude that aberrant keratin synthesis or abnormal post-translational processing of keratins associated with an increased rate of cell turnover could account for the altered expression of the epitope recognized by antibody 16a.

Antibodies, Monoclonal↗
PubMed1985

Immunocytochemical identification of cell types in pleomorphic adenoma, with particular reference to myoepithelial cells.

An immunocytochemical study was carried out on normal salivary gland tissue and ten salivary gland pleomorphic adenomas. Antibodies to myosin were used to stain myoepithelial cells. Duct cells were stained using an antibody to total keratin and a subpopulation of basal duct cells with an antibody to 45/46K keratins. Basement membranes were stained with anti-type IV collagen. The results demonstrated that myoepithelial cells are relatively rare in the majority of pleomorphic adenomas and that many of the cells which have been classically described as myoepithelial in routine histological preparations do not clearly show this type of differentiation. However, the tumors presented a spectrum of differentiation patterns from those that were mainly ductal to the rare tumour which was largely myoepithelial. It is further suggested that the 45/46K keratin antibody is capable of identifying a subpopulation of cells which could possibly be important in the histogenesis of this tumour.

Adenoma, Pleomorphic↗
PubMed1985

Abnormal deposition of basement membrane and connective tissue components in dimethylbenzanthracene-induced rat mammary tumours: an immunocytochemical and ultrastructural study.

Dimethylbenzanthracene-induced rat mammary tumours consist of lobules of tumour cells surrounded by connective tissues. The interstitial connective tissue proteins, collagen types I, III and V, fibronectin and elastin are largely restricted to the interlobular connective tissue. The tumour lobules are surrounded by a basement membrane that stains with antiserum to laminin. Electron microscopy reveals a greatly thickened basement membrane to which striated interstitial collagen fibres are closely juxtaposed. The lumina within the tumour lobules are of two types. In the first type, the luminal surface is characterized by the presence of microvilli and tight junctions and reacts with antiserum to rat milk fat globule membrane. In the second type, the luminal surface is flattened and lined by a thickened basement membrane that stains with antiserum to laminin and type IV collagen. These abnormal patterns of growth and differentiation may be partly a consequence of the disorganization of extracellular matrix components at the interface between the tumour epithelial cells and the surrounding stroma.

9,10-Dimethyl-1,2-benzanthracene↗