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Biomedical subjects

R E Mansel

Publications and source records attributed to R E Mansel.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1999

Is there a role for surgery in the treatment of mastalgia?

Breast pain is a common condition affecting most women at some stage in their reproductive life. Mastalgia is resistant to treatment in 6% of cyclical and 26% non-cyclical patients. Surgery is not widely used to treat this condition and only considered in patients with severe mastalgia resistant to medication. The aims of this study were to audit the efficacy of surgery in severe treatment resistant mastalgia and to assess patient satisfaction following surgery. This is a retrospective review of the medical records of all patients seen in mastalgia clinic in the University Hospital of Wales, Cardiff since 1973. A postal questionnaire was distributed to all patients who had undergone surgery. Results showed that of the 1054 patients seen in mastalgia clinic, 12 (1.2%) had undergone surgery. Surgery included 8 subcutaneous mastectomies with implants (3 bilateral, 5 unilateral), 1 bilateral simple mastectomy and 3 quadrantectomies (1 having a further simple mastectomy). The median duration of symptoms was 6.5 years (range 2-16 years). Five patients (50%) were pain free following surgery, 3 developed capsular contractures and 2 wound infections with dehiscence. Pain persisted in both patients undergoing quadrantectomy. We conclude that surgery for mastalgia should only be considered in a minority of patients. Patients should be informed of possible complications inherent of reconstructive surgery and warned that in 50% cases their pain will not be improved.

Journal Article↗
PubMed1999

Psychological distress associated with waiting for results of diagnostic investigations for breast disease.

This paper presents the results of a multi-method research project investigating the psychological distress associated with waiting for results of diagnostic investigations in a delayed-results breast clinic. A cohort of 126 women completed standardized psychometric instruments to assess anxiety, mood and coping over 3 days. Semi-structured interviews were conducted with 20 respondents. The findings indicate that waiting sustained but did not exacerbate psychological distress. Peri-diagnostic anxiety, depression, uncertainty and confusion were associated with anxiety levels immediately following triple assessment. Women leaving the clinic with low anxiety retained this composure throughout the peri-diagnostic period. Those in the moderate and high anxiety groups recorded sustained anxiety, depression, uncertainty and confusion, with mean scores comparable to and exceeding those reported by psychiatric out-patients. Coping during the waiting period was typically accomplished by emotion-focused strategies. Qualitative data suggested the delayed-results clinic structure may facilitate psychological preparation for test results.

Journal Article↗
PubMed1999

Inhibition of angiogenic factor- and tumour-induced angiogenesis by gamma linolenic acid.

Angiogenesis, the formation of new blood vessels, is an essential feature of malignant tumour development. Gamma linolenic acid (GLA), a n-6 polyunsaturated fatty acid (PUFA), inhibits the growth and metastasis of a variety of tumour cells, including breast, prostate, pancreatic cancer and hepatoma cells and also has anti-metastatic effects on endothelial cells. In the current study, we tested whether GLA inhibited angiogenesis induced by tumour cells. A rat aortic ring assay and in vitro tube formation of human vascular endothelial cells were used to determine angiogenesis (spontaneous, angiogenic factor- and tumour cells-induced). Inclusion of GLA in this 3-D matrix culture system significantly inhibited angiogenesis from aortic rings in a concentration-dependent manner. The results from tube formation of vascular endothelial cell further confirmed that GLA suppressed angiogenesis. Furthermore, in the cell motility assay (phagokinetic assay and endothelial wounding assay), a significant reduction of the motility of vascular endothelial cells by GLA was seen. It is concluded that gamma linolenic acid inhibits angiogenic factor and tumour-induced angiogenesis in vitro at least in part via its inhibitory effect on the motility of vascular endothelial cells.

Angiogenesis Inducing Agents↗
PubMed1999

Phosphorylation and disorganization of vascular-endothelial cadherin in interaction between breast cancer and vascular endothelial cells.

Adherens junctions of the endothelium play a key role in the maintenance of endothelial permeability and are composed of the vascular endothelial (VE)-cadherin/catenin adhesion complex. We report that following tumour cell (MDA MB231 cells) adherence to the HUVECs, there was a rapid (within 5 min) redistribution of VE-cadherin, resulting in its transient loss from regions of endothelial cell-cell contact. The molecule gradually reorganised within the endothelial cell contacts after this time. It was further shown that the overall expression of VE-cadherin did not change, however, the amount of alpha- and beta-catenins coprecipitated with VE-cadherin markedly decreased after 5 min of tumour cell adhesion to the HUVECs. Immunoprobing of these samples with anti-phosphotyrosine antibodies demonstrated that the tyrosine phosphorylation of VE-cadherin was significantly increased following 5 min of tumour cell adhesion. Together, these results suggest that the adhesion of tumour cells to HUVEC promotes the redistribution of VE-cadherin from interendothelial adherens junctions, an effect that may be attributed to the increase in tyrosine phosphorylation of members of the VE-cadherin/catenin adhesion complex. This, in turn, may increase vascular endothelial permeability and facilitate the transendothelial migration of tumour cells during extravasation.

Breast Neoplasms↗
PubMed1999

The specialist registrar puzzle: do all the pieces fit?

The review of medical training by the Working Party headed by Sir Kenneth Calman culminated in the introduction of the specialist registrar (SpR) training grade. Surgery and Radiology were the vanguard specialties, with the SpR post being introduced in December 1995.

Consumer Behavior↗
PubMed1999

Antagonistic effect of NK4, a novel hepatocyte growth factor variant, on in vitro angiogenesis of human vascular endothelial cells.

Hepatocyte growth factor (HGF), also known as scatter factor (SF), is known to act on cancer cells as well as endothelial cells and stimulate angiogenesis, thus playing an unwanted role in the development and progression of cancer. The current study examined the effects of a newly discovered HGF variant, NK4, on angiogenesis in vitro. Chemically generated NK4 (from recombinant human HGF/SF) was found to be able to inhibit HGF-induced activation (tyrosine phosphorylation) of the HGF/SF receptor cMET but was itself unable to activate cMET. Furthermore, NK4 was demonstrated to inhibit tubule formation from human umbilical vein endothelial cells that was induced by both HGF/SF and a HGF/SF-producing fibroblast (MRC5). Under the same settings, NK4 failed to increase tubular formation. NK4 had no effects on interleukin 8- and vascular endothelial growth factor-induced tubule formation. Using computer-assisted motion analysis, it was further shown that NK4 inhibited HGF-induced migration of human umbilical vein endothelial cells in a migration assay and in an endothelial wounding assay. These data show that NK4 is a complete antagonist to HGF. It inhibits HGF-induced endothelial movement and tubule formation. Thus, NK4 may have an important bearing on the control of cancer progression through its role in angiogenesis. Additional in vivo studies are warranted.

Cell Movement↗
PubMed1998

Regulation of tight junction permeability and occludin expression by polyunsaturated fatty acids.

Tight junctions (TJ) are the topical most structure in epithelial and endothelial cells and play a key role in the control of permeability and prevention of tumour cell invasion of endothelium. In this study we examined the effects of a range of polyunsaturated fatty acids on the function of TJs and the expression of occludin, a key molecule in the TJs of the human vascular endothelial cell line, ECV304. Treatment of the endothelial cells with gamma linolenic acid, an anti-cancer PUFA, increased the transendothelial cell resistance (TER) and reduced the paracellular permeability to large molecules. The effects were seen without any changes in the viability of the endothelial cells. Occludin, a recently identified molecule, which plays a major role in tight junctions was up-regulated by this fatty acid as revealed by both Western blotting and immunofluorescence. Other fatty acids were also tested. Eicosapentaenoic acid (EPA) also exerted an up-regulatory effect, but LA and AA down-regulated the expression. We conclude that GLA and EPA which also have other anti-cancer effects, regulate the expression of occludin in endothelial cells and thus contribute to the modification of the TER of these cells.

Arachidonic Acid↗
PubMed1998

Complications of latissimus dorsi myocutaneous flap breast reconstruction.

AIMS: To review the experience of a single unit in post-mastectomy reconstruction using the latissimus dorsi flap. METHODS: A retrospective review of 111 cases treated between 1984 and 1993. The notes were evaluated for type of procedure, associated treatment and complications. RESULTS: A significant morbidity of this procedure was demonstrated with 41 (37%) patients requiring a second operation during the period of the study. The majority of these second operations were related to the prosthesis used to achieve symmetry. Second operations were more common in those who had saline-filled prostheses. Other complications seen included wound infection, small areas of flap necrosis, hypertrophic scars and problems with the donor scar. No differences in complication rates were demonstrated for delayed vs immediate procedures or for patients receiving or not receiving radiotherapy. No life-threatening complication were seen during the study. CONCLUSIONS: The latissimus dorsi reconstruction is reliable but the overall programme is beset with considerable morbidity. This factor needs to be taken into consideration when discussing reconstructive options with the post-mastectomy patient.

Adult↗