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Biomedical subjects

R E Mansel

Publications and source records attributed to R E Mansel.

At least 19 recordsLinked to original sources
PubMed2002

Litigation for pneumothorax as a complication of fine-needle aspiration of the breast.

BACKGROUND: Pneumothorax is a rare but recognized complication of diagnostic needle aspiration of the breast. Two recent court cases alleging negligence have reached opposing opinions on very similar findings. METHODS: A Medline literature search was carried out. RESULTS: The reported incidence of pneumothorax after diagnostic aspiration of the breast in seven series varied between three in 100 and one in 10 000, but the weight of evidence tended towards the latter rate. Two studies reported that the complication is more common in the hands of trainees. It is not always possible to maintain the aspirating needle parallel or tangential to the chest wall. Pleural puncture may be more common than is apparent, and is most common in the tail of the breast in a thin woman. CONCLUSION: It is important that breast clinicians are aware of the risk of pneumothorax but, provided proper care has been taken, this complication is not the result of a negligent act.

Biopsy, Needle↗
PubMed2001

Lymphangiogenesis quantification using quantitative PCR and breast cancer as a model.

The detection of lymphangiogenesis (formation of new lymphatics) has previously been difficult to measure, primarily due to the lack of specific markers for lymphatic endothelium. Using conventional PCR (polymerase chain reaction), DNA sequencing, plasmid synthesis, and real-time quantitative PCR (RTQPCR), we report a new approach to enable the measurement of lymphangiogenesis using LYVE-1, a novel, specific lymphatic marker in breast cancer tissue. By using a Scorpion-based probe system with the RTQPCR analyser, a highly sensitive and specific detection and quantitation of LYVE-1 was possible. It was found that lymphangiogenesis occurred in all breast specimens and that higher levels were found in tumours which had spread to the lymph nodes.

Biomarkers↗
PubMed2001

Sentinel node biopsy in breast cancer: ALMANAC trial.

Sentinel node biopsy of breast cancer is becoming an increasingly popular topic. The concept of the sentinel node being the first lymph node to contain metastatic cancer within a tumor's lymphatic basin was introduced by Cabanas, a South American surgeon, following his work on carcinoma of the penis. Morton and his colleagues then applied this principle to malignant melanomas, and more recently this concept has gained popularity for carcinoma of the breast. In breast cancer patients, the fact that a sentinel node can be localized and the suggestion that the sentinel node is representative of the axillary nodal status has been confirmed by a number of studies across the world. Most authors writing on this subject, however, end with a caution that the results of randomized trials are needed before this new surgical technique can be accepted as part of routine breast cancer management. The Medical Research Council of the United Kingdom has funded the audit phase of a multicenter, two phase, randomized trial called the Axillary Lymphatic Mapping Against Nodal Axillary Clearance (ALMANAC) trial, which will compare standard axillary management with sentinel node-guided axillary management. The aims and protocol of the trial are discussed in detail here.

Axilla↗
PubMed2001

A hammerhead ribozyme suppresses expression of hepatocyte growth factor/scatter factor receptor c-MET and reduces migration and invasiveness of breast cancer cells.

PURPOSE: Hepatocyte growth factor/scatter factor (HGF/SF), via its receptor c-MET, has been implicated to play a pivotal role in breast cancer development and progression. This study examined a transgene-consisting of a combination of U1snRNA, hammerhead ribozyme, and antisense, designed to inhibit c-met expression-and its impact on the migration and in vitro invasion of breast cancer cells. EXPERIMENTAL DESIGN: A hammerhead ribozyme targeting human c-MET was cloned into a modified pZeoU1EcoSpe vector and transfected into breast cancer cells MDA MB 231 and MCF-7 by electroporation. Expression of MET mRNA and protein was determined. Migration and in vitro invasiveness of transfected cells were also analyzed. RESULTS: Breast cancer cells were transfected with the ribozyme-containing plasmids. Stable transfectants manifested an almost complete loss of MET mRNA and protein, as shown by reverse transcription-PCR, Northern blotting, and Western blotting, respectively, whereas the wild-type plasmid had no effects. Met-ribozyme transfected cells exhibited reduced migration and in vitro invasiveness through extracellular matrix (Matrigel), compared with the wild-type cells and cells transfected with empty plasmid. CONCLUSIONS: These data show that targeting c-MET by way of a hammerhead ribozyme encoding antisense to c-MET is an effective approach in reducing the invasiveness of breast cancer cells.

Base Sequence↗
PubMed2000

E-cadherin complex and its abnormalities in human breast cancer.

E-cadherin and its adhesion complex play an essential role in the adhesion of breast cancer cells and tissues. Members of the complex, such as beta-catenin, act as regulators on cell adhesion, and are involved in cell signalling and transcription regulation. The adhesion complex is a known structure in the control of tumour progression and metastasis. Recent years have seen a rapid expansion in the understanding of the biology and clinical relevance of the complex in breast cancer. The current article summarises recent progresses in the molecular/cellular biology of E-cadherin and its complex and the clinical, diagnostic, prognostic, and therapeutic value of this complex in breast cancer.

Breast Neoplasms↗
PubMed2000

Inhibition of HGF/SF-induced breast cancer cell motility and invasion by the HGF/SF variant, NK4.

NK4 is a variant form of HGF/SF, comprising the N-terminal and subsequent four kringle domains of mature HGF/SF. HGF/SF is a multifunctional cytokine that enhances the metastatic behaviour of tumour cells in vitro by stimulation of the c-met receptor tyrosine kinase and has been implicated in the development of tumour metastasis in vivo. The aims of this study were to further investigate the potential antagonistic effects of the recently described variant form of HGF/SF, NK4, on HGF/SF activity in breast cancer cells. All cell lines used expressed both the HGF/SF receptor gene and protein as shown by RT-PCR and Western blotting. NK4 inhibited HGF/SF-induced tumour cell invasion through an artificial basement membrane. Tumour cell motility and scattering induced by HGF/SF were also dramatically reduced by the inclusion of NK4. Immunoprecipitation studies revealed that NK4 inhibited the phosphorylation of the c-met receptor in response to HGF/SF. Treatment of these cells with NK4 alone did not have any significant effects on their metastatic behaviour. From this data we conclude that NK4 demonstrates significant antagonistic properties towards HGF/SF, inhibiting HGF/SF-stimulated breast tumour cell invasion, motility and migration. NK4 may therefore be of potential benefit in the development of anti-metastasis therapies.

Blotting, Western↗
PubMed2000

The pathology of essential fatty acid deficiency: is it cell adhesion mediated?

For almost 70 years, essential fatty acid deficiency has been known to be associated with skin disorders, vessel abnormalities, and increased tumorigenesis. However, the underlying molecular and cellular mechanism is largely unknown. Recently, it has been reported that essential fatty acids regulate cell adhesion by modifying the expression of cell adhesion molecules. These findings may provide molecular explanations for those phenomena seen in EFAD and this paper aims to discuss these relationships and raise points for further discussion.

Animals↗
PubMed2000

Peroxisome proliferator activated receptor-gamma (PPAR-gamma) mediates the action of gamma linolenic acid in breast cancer cells.

Gamma linolenic acid (GLA) is a polyunsaturated fatty acid, which induces cytotoxicity and regulates cell adhesion in cancer cells. The molecular mechanism of these actions is not clear. We have shown that GLA acts via peroxisome proliferator activated receptors (PPARs), by stimulating their phosphorylation and translocation to the nucleus. Removing PPAR gamma with antisense oligos abolished the effect of GLA on the expression of adhesion molecules and tumour suppressor genes, whereas removal of PPAR alpha had no effect. Tissues from patients with breast cancer showed a reduction of expression of both PPARs in cancer tissues, as compared with normal. Thus, PPAR gamma serves as the receptor for GLA in the regulation of gene expression in breast cancer cells.

Blotting, Western↗
PubMed2000

History, present status and future of sentinel node biopsy in breast cancer. The Mary Béves Lecture.

The word Sentinel' is defined in The Oxford English Dictionary as 'a guard, one who keeps watch or a sentry'. When translated to the concept of a tumour and its lymph node drainage, the sentinel node could be interpreted to mean the lymph node that guards or keeps watch over a tumour. The sentinel lymph node can thus be defined as the first lymph node that drains a primary tumour within the regional lymphatic basin of that tumour. We know that tumour progression in breast cancer often occurs in an orderly, progressive fashion. So in theory, if the sentinel node is tumour free then the rest of the nodes in the lymphatic basin should also be uninvolved by the tumour.

Biopsy↗
PubMed1999

Duplicate acronyms.

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Abbreviations as Topic↗
PubMed1999

Inhibition of the expression of VE-cadherin/catenin complex by gamma linolenic acid in human vascular endothelial cells, and its impact on angiogenesis.

Gamma linolenic acid (GLA) has been recently shown to inhibit tumour-induced angiogenesis. The present study investigated the effects of GLA on the HUVEC-specific adhesion. After treatment with GLA, HUVECs decreased the amounts of Triton soluble and insoluble VE-cadherin and beta-catenin and reduced tube formation in matrix in a concentration-dependent manner. An anti-VE-cadherin antibody dissociated HUVECs' colonies and exerted similar inhibitory effects on tube formation of HUVECs. These data indicate that the VE-cadherin/catenins complex is essential for formation and maintenance of new capillaries. It is concluded, therefore, that GLA inhibits tumour-induced angiogenesis partly via the decrease in the expression of VE-cadherin and beta-catenin.

Antigens, CD↗
PubMed1999

Hepatocyte growth factor/scatter factor decreases the expression of occludin and transendothelial resistance (TER) and increases paracellular permeability in human vascular endothelial cells.

Hepatocyte growth factor/scatter factor (HGF/SF), a multi function cytokine has been shown to regulate the expression of cell adhesion molecules in endothelial cells. In the current study, we examined the effects of HGF/SF on the function of tight junctions and the expression of occludin in these cells. Stimulation of human vascular endothelial cells with HGF/SF resulted in a concentration dependent increase in the paracellular permeability as measured using fluorescence labelled dextran but a decrease in the transendothelial cell resistance (TER) of the endothelial cells. Western blotting revealed that HGF/SF decreased the level of occludin in the cells, a primary tight junction forming protein. Immunofluorescence study indicated that shortly after treatment with HGF/SF there was a disturbance of the distribution of occludin and then a reduction in the staining of the molecule. It is concluded that HGF/SF decreases the expression of occludin, resulting in the functional change of tight junction.

Cell Line↗
PubMed1999

The immunohistochemical expression of desmoplakin and its role in vivo in the progression and metastasis of breast cancer.

Desmoplakin (DP) is a protein located at the inner plaque of desmosomes where it associates with the desmosomal cadherins to form a cell adhesion complex. Reduced expression of DP has been correlated with the progression of several cancers, but its role in in vivo breast cancer is yet to be established. The aim of this present paper was to determine the immunohistochemical (IHC) expression of DP in breast cancer specimens (n = 75) in comparison with ductal carcinoma in situ (DCIS) (n = 26), tumour associated normal (n = 29) and normal breast tissue (n = 7). DP expression was correlated with that of desmosomal cadherin, Desmoglein 2 (Dsg2) and other clinical and IHC prognostic markers. DP staining occurred at the sub-plasma membrane level. There was no significant correlation between the level of DP (as assessed by the H-score) and that of Dsg. Significantly stronger staining was demonstrated in normal breast tissue and well differentiated tumours compared with more moderately or poorly differentiated tumours (P = 0.04). A significant inverse correlation was seen between DP staining and tumour size (P = 0.01). In a limited series of 8 cases, primary tumours demonstrated significantly stronger staining than the matched metastatic lymph nodes (P = 0.046). Of all the IHC markers examined, only Ki-67 showed a significant inverse relationship with DP staining (P = 0.01). In summary, the data suggest that loss of DP may be of potential importance in progression of breast cancer in vivo from normal, DCIS, well differentiated through to poorly differentiated, large tumours. In addition, this loss may be associated with metastasis.

Breast Neoplasms↗
PubMed1999

Follow-up of patients with a thin melanoma.

BACKGROUND: The aim of this study was to determine the value of follow-up in two subgroups of patients with a thin melanoma less than 0.76 mm and 0.76-1.5 mm thick. METHODS: The study group comprised all patients presenting to the Cardiff Melanoma Clinic from its introduction in 1976 to the end of 1994. All patients attend follow-up according to a strict protocol, determined by the thickness of the original melanoma (less than 0.76 mm, annually; more than 0.76 mm, every 2 months for 2 years, 3 monthly for 2 years, 4 monthly for 1 year and then annually). RESULTS: In total there were 306 patients with a thin melanoma: 178 with a melanoma thinner than 0.76 mm (group 1) and 128 with a melanoma of 0.76-1.5 mm (group 2). The groups were well matched for age (mean 50.6 (range 8-87) versus 50.6 (range 19-89) years respectively) and length of follow-up (mean 88.6 (range 4-296) versus 80.4 (range 2-296) months). Four patients (2.2 per cent) developed recurrence in group 1 and 16 (12.5 per cent) in group 2. The mean time to recurrence was 84.5 (range 49-143) months in group 1 and 45.3 (range 2-74) months in group 2. All patients in group 1 and 14 of 16 in group 2 died from recurrent disease. CONCLUSION: Follow-up of patients with a melanoma less than 0.76 mm thick is not worthwhile. All recurrences would have been detected by annual review for 7 years in patients with melanomas between 0.76 and 1.5 mm thick.

Adolescent↗
PubMed1999

Peer-reviewed publication following presentation at a regional surgical meeting.

OBJECTIVES: The aim of the study was to investigate the proportion of publications arising from work presented at a regional surgical meeting. DESIGN: A list of all presentations to the Welsh Surgical Society 1983-95 was compiled and a detailed search made of the Medicine Database. The surgical topic of each presentation, the date of presentation, the date of publication and the journal of publication were recorded. SETTING: University Hospital of Wales. RESULTS: Four hundred and ninety-six papers were presented to the society, of which 402 (81%) were by trainees. The most frequent topics of presentation were colorectal (15%), vascular (15%) and hepato-pancreatico-biliary (11%). Two hundred and thirty-three papers (47%) have been published in peer-reviewed journals. The most popular journals for publication were Annals of the Royal College of Surgeons of England (19%), British Journal of Surgery (16%) and Journal of the Royal College of Surgeons of Edinburgh (8%). The median time from presentation to publication was 17.0 months (interquartile range 10.0-27.5 months). CONCLUSIONS: Regional surgical meetings have an important role in the annual surgical calendar and they are the ideal initial setting for presentation by trainees.

Education, Medical, Continuing↗
PubMed1999

The National Breast Referral Guidelines have cut down inappropriate referrals in the under 50s.

AIMS: When the National Breast Referral Guidelines were applied to our local GPs letters immediately prior to their release in January 1996, it was shown that on the basis of the GPs own conclusions that 29% of symptomatic women could have been managed initially by their own GP without missing any carcinomas. We conducted this study at the Rapid Access Breast Clinic at the University Hospital of Wales to determine if the breast referral practices of local GPs have altered due to the breast referral guidelines. METHODS: We studied 2332 referrals from the inception of the Rapid Access Clinic in May 1995 to the issue of the guidelines, and 2421 referrals from May 1996 to the end of the year. Random samples of 600 patients were drawn from each year and the referral letters were scored as within or outside the guidelines. Family history patients were excluded. RESULTS: There was an 11% fall in referrals outside the guidelines in the under 50s (chi-squared=<0.001) but the 7% fall in the over 50s was not significant. CONCLUSIONS: The Breast Referral Guidelines seem to have been effective in reducing the higher level of inappropriate referrals in younger patients at less risk of carcinoma.

Age Factors↗