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B Angus

Publications and source records attributed to B Angus.

At least 73 records · Page 4Linked to original sources
PubMed1996

The detection of nodal metastasis in breast cancer using neural network techniques.

Identification and treatment of involved axillary lymph nodes is important in the planning of strategies for adjuvant treatments of breast cancer. With the advent of the National Health Service Screening Programme, an increasing number of women with the disease are detected at an early stage, when the lymph nodes are not involved. In whom, therefore, is it necessary to carry out a formal axillary dissection? Are there accurate surrogates for lymph node involvement in the form of tumour markers or characteristics? This study, carried out on over 81 patients, examines the use of neural networks to predict the involvement of lymph nodes using readily available clinical and pathological data and also more specialized markers of possible prognostic significance. The study shows that neural networks are capable of providing strong indicators as to lymph node status using only basic measurements of the primary breast tumour. However, accuracy can be improved by the addition of less common markers.

Biomarkers, Tumor↗
PubMed1996

Antimalarial drugs reduce cytoadherence and rosetting Plasmodium falciparum.

The in vivo and in vitro effects of antimalarials on cytoadherence and rosette formation were studied in 17 patients with severe and 46 with uncomplicated falciparum malaria. Cytoadherence was increased in severe malaria (P<.001). Artesunate and artemether were more potent than quinine in inhibiting both adherence properties. Artesunate was the most rapidly acting drug tested, producing >50% inhibition of both cytoadherence and rosetting in vivo and in vitro within 2 hr of drug exposure. Exposure to quinine for > or = to 4 h in vivo reduced rosetting by >50%, but not cytoadherence. Quinine did not reduce cytoadherence or rosetting significantly in vitro with exposure times of < or = to 8 h. These results suggest that artemisinin derivatives are more effective than quinine in preventing pathologic processes in parasitized erythrocytes that contribute to microvascular obstruction in severe malaria.

Adolescent↗
PubMed1996

OCT embedded sections of pathological specimens as a source of high quality RNA for reverse transcriptase/polymerase chain reaction.

OCT embedded cryostat sections of stored pathological specimens of non-Hodgkin's lymphoma were used to provide RNA. After reverse transcription to produce cDNA, the polymerase chain reaction was performed with primers for standard and variant forms of the CD44 molecule. Using Southern transfer and hybridisation with a probe specific for exon 4 of the CD44 gene, both standard and variant forms were visualised by autoradiography. This method was shown to be applicable to other gene products by using primers specific for the abl and bcr genes. This technique permits retrospective analysis of RNA from small amounts of stored pathological samples.

Biomarkers, Tumor↗
PubMed1996

Proliferative compartments in the normal nail unit.

The main distinction between the germinal matrix and the nail bed is that the former is the origin of all or most of the nail plate and the latter provides an epithelial surface to which the emerging nail can adhere. It has been argued that the nail bed may contribute substance to the nail plate and it is likely that if this was the case, epithelial proliferation in the nail bed would match that in the germinal matrix by a proportion appropriate to its contribution. We have measured the labelling index (LI) in the three major anatomical sites of the nail unit using two antibodies to antigens expressed in cycling cells. Using Ki-67 (MIB-1) and proliferating cell nuclear antigen (PCNA) as markers of cell proliferation we have defined the LI in the germinal matrix (MIB-1: 22.1%, PCNA: 33%), nail bed (MIB-1: 0.75%, PCNA: 1%) and digit pulp (MIB-1: 16.8%, PCNA: 17.4%). This suggests a low degree of proliferation in normal nail bed consistent with a minimal or non-existent contribution to the nail plate. This may change in hyperkeratotic nail dystrophies, where the nail bed LI is raised (MIB-1: 31%, PCNA: 29%), illustrating how nail bed behaviour can alter with disease.

Adolescent↗
PubMed1995

Determination of the prognostic value of cyclin D1 overexpression in breast cancer.

Cyclin D1 plays a critical role in the timing of the initiation of DNA synthesis in the normal cell cycle of mammalian cells. Deregulated expression of this protein has been seen in a variety of tumours either as a result of gene amplification or chromosomal translocation, in breast cancer and B cell malignancies respectively. In order to determine the role this putative oncoprotein plays in breast cancer, we have applied a new monoclonal antibody, recently produced in our laboratory, in an immunohistochemical study of 93 primary breast carcinomas. We show that approximately 28% of the cases displayed enhanced expression of the cyclin D1 protein. Furthermore, either cyclin D1, cyclin D3, or both, were expressed in 69% of cases, suggesting that overexpression of any one member of this family may relieve cancer cells of their mitogenic stimulatory requirement. In addition, we show that those patients whose breast cancers co-express cyclin D1 with either epidermal growth factor receptor (EGFR) or the retinoblastoma protein (pRB) have a significantly poorer prognosis in comparison to those expressing cyclin D1 alone. Our observations indicate that, in a subset of breast cancers, aberrant cyclin D1 expression is a contributory factor to tumorigenesis and in association with EGFR or pRB expression, identify those tumours which may require more aggressive therapy.

Animals↗
PubMed1995

Use of the biotinylated antibody DAKO-ER 1D5 to measure oestrogen receptor on cytokeratin positive cells obtained from primary breast cancer cells.

A method for the use of a biotinylated antibody (DAKO-ER 1D5) to quantify oestrogen receptors (ER) on tumour cells by flow cytometry is described. ER quantification was determined after treatment with saponin rendering cells permeable to ER antibody. Use of dual parameter labelling was performed utilizing a FITC-conjugated antibody (NCL-5D3) directed against cytokeratin 8/18. This allowed selection of breast cancer cells of epithelial origin by gating to exclude contaminating inflammatory and stromal cells. Use of such a gating technique was seen to identify cells with a higher level of ER expression. Using QC quantum bead standards, the number of ER binding sites per cell was assessed. Results were compared with conventional ER quantification using a radio-ligand binding assay. A high degree of correlation was found between the two methods. The flow cytometric method for ER quantification described is simple, rapid, and reproducible. The assay may be of particular value in measuring ER on urgent clinical samples. Advantages of this assay over the radio-ligand binding assay include reduction in use of radio-labelled iodine compounds, a decrease in analysis time, and reduced cost and quantity of material needed for assay.

Antibodies, Monoclonal↗
PubMed1995

Loss of heterozygosity in sporadic primary cutaneous melanoma.

Difficulties in obtaining clinical samples from primary melanomas have meant that most genetic analyses of melanoma have concentrated on cell lines and metastases. Because the Breslow thickness of the primary tumour is the single best prognostic indicator, it is important to identify genetic abnormalities in primary melanomas and relate these changes to the thickness of the lesion. We have investigated 47 sporadic melanomas, of which 41 were primary lesions, for loss of heterozygosity (LOH) on several chromosomal arms, including areas where genes involved in familial melanoma and other relevant hereditary syndromes map, and where LOH has previously been reported in cell lines, or metastatic lesions. LOH was identified at 66 (18%) of 358 informative loci in primary melanomas, and there was a significant relationship between the overall frequency of LOH and Breslow thickness (P < 0.0005). Loss of chromosome arm 9p was most frequent, occurring in 15 (47%) of 32 informative primary tumours, and was observed in 3 of 11 informative lesions < or = 1.5 mm in depth. LOH on chromosome arms 3p, 6q, 10q, 11q, and 17p was also relatively frequent, with loss of 3p and 10q heterozygosity in lesions < or = 1.5 mm in depth, while LOH on 6q, 11q, and 17p was only detected in more invasive tumours. The results suggest that loss of these chromosome regions are important in sporadic cutaneous melanoma, and are consistent with chromosome arm 9p loss occurring before loss of other chromosome arms.

Chromosome Deletion↗
PubMed1995

A flow cytometric study of c-erbB-3 expression in breast cancer.

In order to assess the specificity of biotinylated anti-c-erbB-3 antibody, screening was performed on a series of tumour cell lines and lymphocytes. Staining was found to be consistent, with good reproducibility. Twenty-nine consecutive breast cancer samples were obtained from women treated with tamoxifen and undergoing elective mastectomy. Twenty-eight invasive ductal carcinomas and 1 DCIS were stained for c-erbB-3 expression: 2 were grade I (Bloom and Richardson), 15 grade II, and 11 grade III tumours, 1 being unclassified; 16 were axillary node positive and 10 node negative; in 2 cases no nodes were sampled. Tumours examined by flow cytometry were stained with cytokeratin FITC antibody and the cytokeratin-positive population gated. Using Mann-Whitney analysis no association was seen between c-erbB-3 expression and Bloom and Richardson grade or axillary node status. In the tumour samples c-erbB-3 expression was found to show as association with EGF-R (P = 0.021 r2 = 0.16), PgR (P = 0.02, r2 = 0.16), c-myc (P < 0.0001, r2 = 0.5), c-jun (P = 0.001, r2 = 0.4) and c-fos (P = 0.001, r2 = 0.5) but not with c-erbB-2 (P = 0.2, r2 = 0.06), ER (P = 0.4, r2 = 0.02) or p53 1801 (P = 0.05, r2 = 0.2). Expression of c-erbB-3 may not be an independent marker of prognosis, but it is associated with other markers of poor prognosis and early cellular events linked with aberrant growth and differentiation.

Breast Neoplasms↗
PubMed1995

The relationship between flow-cytometric and immunohistochemically detected c-erbB-2 expression, grade and DNA ploidy in breast cancer.

Quantification of c-erbB-2 and its relationship with other prognostic markers using flow cytometry has been examined. In this study a level for c-erbB-2 expression above which tumours are classified as positive by flow cytometry has been determined by employment of positive cut-off threshold levels. c-erbB-2 expression by both flow cytometry and immunohistochemistry was studied using the monoclonal antibody NCL-CBII. The relationship of c-erbB-2 quantification by flow cytometry was then compared with ploidy, axillary node status, tumour size and grade. Increased c-erbB-2 expression was seen using flow cytometry. Correlation between immunohistochemistry and flow-cytometry methods just failed to reach significance (P = 0.06). Immunohistochemistry revealed a significant relationship between c-erbB-2 expression and aneuploidy (P = 0.04). Cytokeratin-positive cells from 110 samples obtained from patients with breast cancer were assayed for DNA content and c-erbB-2 expression by flow cytometry. No correlation was seen between these parameters upon application of Mann Whitney analysis. However, examination of fluorescence thresholds showed a positive correlation between grade and c-erbB-2 expression at a level of more than 3200 molecules (P < or = 0.03). At the level of 3600 molecules significance was increased (P = 0.004). These levels equated with between 15% and 19% of the samples being classified as c-erbB-2-positive. Application of these cut-off points showed no correlation between c-erbB-2 expression and ploidy, tumour size or axillary node status. Comparison of ploidy and grade showed a significant association (P = 0.0015), increased grade correlating with aneuploidy.

Adult↗
PubMed1995

p53 expression measured by flow cytometry. A comparison of three monoclonal antibodies and the relationship with grade and DNA ploidy in breast cancer.

The aim of this study was to quantify p53 expression by flow cytometry. A panel of three monoclonal antibodies: NCL-p53-240, NCL-p53-1801 and NCL-p53-DO7, was tested on breast cell lines and primary breast cancers. The relationships between ploidy, tumour grade and p53 expression for each antibody, were examined. Methodology was assessed using a variety of breast cell lines. Staining patterns were confirmed and the quantification technique qualified. Cytokeratin-positive cells from 58 samples obtained from patients with breast cancer were assayed for DNA content and p53 expression. p53 quantification was performed using calibrated fluorescent beads on cytokeratin-positive cells. Bloom and Richardson grading revealed 20 grade I and 38 grade II/III breast cancers. Examination of fluorescence thresholds showed a positive correlation between grade and DO7 (P = 0.003) at a level of 8900 molecules, 240 (P = 0.005) at a level of 2900 molecules and 1801 (P = 0.005) at a level of 1850 molecules. These levels equated with 34% (DO7), 43% (240) and 43% (1801) of the samples being classified as p53-positive. Examination of ploidy revealed 23 diploid and 35 aneuploid breast cancers. Application of p53 threshold levels on diploid and aneuploid tumours showed correlation between aneuploidy and p53 expression for DO7 at a level of 9000 molecules, 240 at a level of 1900 molecules and 1801 at a level of 1800 molecules. These levels equated with 34% (DO7), 52% (240) and 52% (1801) of the samples being classified as p53-positive. We conclude that measurement of p53 by flow cytometry may be of clinical importance by indicating levels of positivity using fluorescence thresholds. p53 expression has been shown to correlate with both grade and ploidy. Flow-cytometric measurement of p53 may be a useful prognostic assay.

Aneuploidy↗
PubMed1995

Prognostic significance of quantitative bacteremia in septicemic melioidosis.

Pour-plate blood cultures were performed for 418 adult patients with suspected septicemic melioidosis in order to determine the relationship between quantitative bacterial counts in blood and mortality. Of 108 patients whose hemocultures yielded Burkholderia pseudomallei, 53% had < 10 cfu/mL and 24% had > 100 cfu/mL. High blood bacterial counts were more common than reported previously with regard to other gram-negative septicemias and were significantly associated with the development of hypotension (P = .008) and a fatal outcome (P = .0001). The overall mortality was 63% (95% CI, 53%-72%); however, counts of < or = 1 cfu/mL were associated with a mortality of 42% (95% CI, 28%-58%), compared with 96% (95% CI, 80%-100%) with counts of > 100 cfu/mL. Heavy bacteremia (> 50 cfu/mL) is common in septicemic melioidosis and is usually fatal.

Adolescent↗
PubMed1995

Prognostic value of Ki67 antigen expression in basal cell carcinomas.

Recurrence of basal cell carcinoma (BCC) following treatment is a common event and long-term follow-up of all patients presenting with a primary BCC has been recommended. Proliferation indices have been recognized as important prognostic factors in several tumour types in a variety of cancer systems, being significantly elevated in more aggressive lesions. We have examined 51 BCCs (17 non-recurrent tumours [group 1], 17 original tumours which later recurred [group 2-O], and the corresponding 17 recurrent specimens [group 2-R]) for Ki67 antigen expression, a proliferation-associated antigen using immunohistochemistry with the monoclonal antibody MIB1. There was a significant increase in the percentage positive for MIB1 in the Group 2-O as compared with the group 1 BCCs (P < 0.05). p53 protein expression, as assessed by immunohistochemistry with the monoclonal antibody DO7, was similar in each group. These results show that Ki67 antigen expression differs between BCCs which later recur and BCCs that do not recur.

Aged↗
PubMed1995

c-MYC gene abnormalities in high grade and centroblastic-centrocytic non-Hodgkins lymphoma.

Fifty nine cases of high grade and centroblastic-centrocytic (cc) Non Hodgkins Lymphoma (NHL) were investigated for mutations and gross gene rearrangements in the 5' region of the c-MYC gene. Mutations in this region, and the presence of hypermutated c-MYC genes, have been associated with poor prognostic groups. All cases showed normal c-MYC gene organisation on Southern blot analysis indicating absence of gross gene rearrangements. PCR amplification and restriction digest analysis of the exon 1/intron 1 region revealed point mutations in 7 cases. No evidence for hypermutation was found. Mutations were relatively more common in high grade NHL (6/39) than in cc-NHL (1/20). There was no correlation with disease status at presentation or relapse or the presence of extranodal disease. The cc-NHL case with a c-MYC mutation subsequently transformed to high grade disease. These data suggest that hypermutation of the c-MYC gene is a relatively rare event in cc-NHL and high grade NHL and does not contribute to the aetiology in the majority of cases. Mutation of c-MYC in cc-NHL may predict transformation to high grade disease.

Adolescent↗
PubMed1994

Flow cytometric method for the measurement of epidermal growth factor receptor and comparison with the radio-ligand binding assay.

A method for the purification, conjugation, and use of EGF-R antibody to quantify EGF receptors on tumour cells by flow cytometry is described. The quantification of both internal and external EGF receptors was determined by treatment with saponin, rendering the cells permeable to the EGF-R antibody. Using QCS bead standards, the number of EGF-R binding sites per cell was assessed. Results were compared with conventional EGF-R quantification using a radio-ligand binding assay. A high degree of correlation was found between the two methods. The flow cytometric method for EGF-R quantification described is simple, rapid, and reproducible. The assay may be of particular value in measuring EGF-R on urgent clinical samples or those that are too small (such as breast aspirates) for measurement by the radio-ligand binding assay. Advantages of this assay over the radio-ligand binding assay include reduction in use of radio-labelled iodine compounds, a decrease in analysis time, and reduced cost and quantity of material needed for assay. In addition, flow cytometry offers the possibility of selecting cell phenotypes by gating as well as live/dead cells by using multi-parameter flow cytometry.

Antibodies, Monoclonal↗
PubMed1994

NDP-K/nm23 expression in human breast cancer in relation to relapse, survival, and other prognostic factors: an immunohistochemical study.

The nm23 gene was originally identified by Steeg et al. by screening of cDNA libraries from murine melanoma cell lines of varying metastatic potential. An inverse relationship between metastatic potential and nm23 RNA and/or protein was found in four different metastatic model systems. It was proposed that nm23 may function as a suppressor gene for tumour metastasis. It has recently been found that the sequence of nm23 and NDP-kinase (NDP-K) is identical. Using an immunohistochemical technique and employing a polyclonal antibody to purified NDP-K A, we have determined NDP-K expression in a series of 197 breast carcinomas. One hundred and sixty (81.2 per cent) of these tumours were scored positive for NDP-K and 37 (18.8 per cent) scored negative. No relationship was found between NDP-K/nm23 expression and patient relapse or survival. Furthermore, no relationship was found between NDP-K/nm23 expression and a number of other prognostic factors including tumour grade, oestrogen receptor, progesterone receptor, and p53 expression. Our results contradict the hypothesis concerning the possible role of NDP-K/nm23 as a metastatic suppressor gene in human breast cancer, but further studies using antibodies specific for NDP-K/nm23 subtypes are clearly indicated.

Breast Neoplasms↗
PubMed1994

A family with adult-onset cerebral adrenoleucodystrophy.

A family in which three members presented with cerebral adrenoleucodystrophy in adulthood is described. The implications on our understanding for the mechanisms controlling the phenotypic expression of this genetic disorder are discussed.

Adrenoleukodystrophy↗
PubMed1994

Autologous bone marrow transplantation in poor-risk high-grade non-Hodgkin's lymphoma in first complete remission. Newcastle and Northern Lymphoma Group.

We report the safety and efficacy of autologous bone marrow transplantation (ABMT) in 30 patients with high-grade non-Hodgkin's lymphoma (NHL) in first complete remission (CR1) following remission induction chemotherapy. Two patients relapsed prior to ABMT. All patients were conditioned with high-dose melphalan. In Addition, ten received fractionated total body irradiation, one hemi-body irradiation and four high-dose etoposide. Unmanipulated non-cryopreserved autologous marrow was reinfused within 56 h of harvesting. Engraftment occurred in all patients with a median of 11 days of neutropenia (< 0.5 x 10(9) l-1), a median requirement for platelet transfusion of 3 days and packed red cell transfusion of 2 units, with a median hospital stay of 18 days post transplant. There was no procedure-related mortality and only minor morbidity was observed. Two patients relapsed at 1 and 2 months post transplantation, and one patient died of carcinoma of the lung 33 months after transplantation. The remaining 25 patients remain alive, well and in CR1 with a median follow-up of 44 months. The event-free survival at 3 years for all patients considered for ABMT was 83%. We conclude that ABMT for high-grade NHL in CR1 with non-cryopreserved marrow results in rapid haematological recovery without growth factor support. It is safe and is associated with high survival when used as consolidation of CR in high-risk patients.

Adolescent↗