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Biomedical subjects

M D Mason

Publications and source records attributed to M D Mason.

At least 37 records · Page 2Linked to original sources
PubMed2001

A systematic review of intravesical bacillus Calmette-Guérin plus transurethral resection vs transurethral resection alone in Ta and T1 bladder cancer.

OBJECTIVE: To assess, in a systematic review, the effectiveness of intravesical bacillus Calmette-Guérin (BCG) in preventing tumour recurrence in patients with medium/high risk Ta and T1 bladder cancer. PATIENTS AND METHODS: An electronic database search of Medline, Embase, DARE, the Cochrane Library, Cancerlit, Healthstar and BIDS was undertaken, plus hand searching of the Proceedings of ASCO, for randomized controlled trials, in any language, comparing transurethral resection (TUR) alone with TUR followed by intravesical BCG in patients with Ta and T1 bladder cancer. RESULTS: The search identified 26 publications comparing TUR with TUR + BCG. Six trials were considered acceptable, representing 585 eligible patients, 281 in the TUR-alone group and 304 in the TUR + BCG group. The major clinical outcome chosen was tumour recurrence. The weighted mean log hazard ratio for the first recurrence, taken across all six trials, was -0.83 (95% confidence interval -0.57 to -1.08, P < 0.001), which is equivalent to a 56% reduction in the hazard, attributable to BCG. The Peto odds ratio for patients recurring at 12 months was 0.3 (95% confidence interval of 0.21-0.43, P < 0.001), significantly favouring BCG therapy. Manageable toxicities associated with intravesical BCG were cystitis (67%), haematuria (23%), fever (25%) and urinary frequency (71%). No BCG-induced deaths were reported. CONCLUSION: TUR with intravesical BCG provides a significantly better prophylaxis of tumour recurrence in Ta and T1 bladder cancer than TUR alone. Randomized trials are still needed to address the issues of BCG strain, dose and schedule, and to better quantify the effect on progression to invasive disease.

Administration, Intravesical↗
PubMed2001

The effects of induced hypogonadism on arterial stiffness, body composition, and metabolic parameters in males with prostate cancer.

Sex hormones appear to play a pivotal role in determining cardiovascular risk. Androgen deprivation therapy for males with prostate cancer results in a hypogonadal state that may have important, but as yet undetermined, effects on the vasculature. We studied the effects of androgen deprivation therapy on large artery stiffness in 22 prostate cancer patients (mean age, 67 +/- 8 yr) over a 6-month period. Arterial stiffness was assessed using pulse-wave analysis, a technique that measures peripheral arterial pressure waveforms and generates corresponding central aortic waveforms. This allows determination of the augmentation of central pressure resulting from wave reflection and the augmentation index, a measure of large artery stiffness. Body compositional changes were assessed using bioelectrical impedance analysis. Fasting lipids, glucose, insulin, testosterone, and estradiol were measured. After a 3-month treatment period, the augmentation index increased from 24 +/- 6% (mean +/- SD) at baseline to 29 +/- 9% (P = 0.003) despite no change in peripheral blood pressure. Timing of wave reflection was reduced from 137 +/- 7 to 129 +/- 10 msec (P = 0.003). Fat mass increased from 20.2 +/- 9.4 to 21.9 +/- 9.6 kg (P = 0.008), whereas lean body mass decreased from 63.2 +/- 6.8 to 61.5 +/- 6.0 kg (P = 0.016). There were no changes in lipids or glucose during treatment. Median serum insulin rose from 11.8 (range, 5.6-49.1) to 15.1 (range, 7.3-83.2) mU/liter at 1 month (P = 0.021) and to 19.3 (range, 0-85.0 mU/liter by 3 months (P = 0.020). There was a correlation between the changes in fat mass and insulin concentration over the 3-month period (r = 0.56; P = 0.013). In a subgroup of patients whose treatment was discontinued after 3 months, the augmentation index decreased from 31 +/- 7% at 3 months to 29 +/- 5% by 6 months, in contrast to patients receiving continuing treatment in whom the augmentation index remained elevated at 6 months compared with baseline (P = 0.043). These data indicate that induced hypogonadism in males with prostate cancer results in a rise in the augmentation of central arterial pressure, suggesting large artery stiffening. Adverse body compositional changes associated with rising insulin concentrations suggest reduced insulin sensitivity. These adverse hemodynamic and metabolic effects may increase cardiovascular risk in this patient group.

Adipose Tissue↗
PubMed2001

HGF/SF modifies the interaction between its receptor c-Met, and the E-cadherin/catenin complex in prostate cancer cells.

The effect of HGF/SF on the association between the E-cadherin/catenin complex and the tyrosine kinase receptor c-Met, was examined in prostate cancer cells LNCap FGC. Stimulation by HGF/SF showed E-cadherin and beta-catenin to be co-precipitated and located at areas of cell-cell contact with the HGF/SF receptor c-Met, as detected by immunoprecipitation and immunofluorescence respectively. Furthermore, continued exposure to this motogen increased the level of co-precipitations between the E-cadherin/catenin complex with c-Met, and also increased tyrosine phosphorylation of c-Met. In contrast, continued stimulation by HGF/SF decreased the level of co-localised peripheral staining and increased the level of cytoplasmic staining. In conclusion, the association between the E-cadherin/catenin complex with the HGF/SF receptor c-Met, may influence or regulate intercellular adhesion in prostate cancer following stimulation by HGF/SF.

Cadherins↗
PubMed2001

The interaction between beta-catenin, GSK3beta and APC after motogen induced cell-cell dissociation, and their involvement in signal transduction pathways in prostate cancer.

The effect of HGF/SF was examined on the interactions between APC, GSK3beta and beta-catenin in prostate cancer cells LNCapFGC (E-cadherin positive) and PC-3 (E-cadherin negative). Using immunoprecipitation, APC was found to be co-precipitated with either GSK3beta or beta-catenin in both cell lines. Stimulation with HGF/SF showed no change in the co-precipitation status of these protein molecules. In contrast, co-precipitation between GSK3beta and beta-catenin was only observed in LNCapFGC cells, and increased upon continued exposure to the motogen HGF/SF. Furthermore, using immunofluorescence, stimulation with HGF/SF was found to increase the level of co-localised cytoplasmic staining between beta-catenin and GSK3beta, in prostate cancer cells. RT-PCR revealed that there were no mutations within the binding regions between beta-catenin and GSK3beta. It is concluded, that uncomplexed cytoplasmic pools of beta-catenin associate more readily with the Axin complex in the absence of E-cadherin. Whereas, in the presence of E-cadherin, beta-catenin is stabilised by forming tight cell-cell contacts which may influence the invasive potential of cancer cells.

Adenomatous Polyposis Coli Protein↗
PubMed2001

Matrilysin mediates extracellular cleavage of E-cadherin from prostate cancer cells: a key mechanism in hepatocyte growth factor/scatter factor-induced cell-cell dissociation and in vitro invasion.

PURPOSE: The current study examined the effects of hepatocyte growth factor/scatter factor (HGF/SF) on cell-cell dissociation, invasion, and its association with the mediated release of matrix metalloproteinase-7 (Matrilysin) on the extracellular cleavage of E-cadherin in prostate cancer cells. EXPERIMENTAL DESIGN: The effects of HGF/SF on cell-cell dissociation, in vitro invasion, and on the expression of E-cadherin at both protein and mRNA levels were assessed in cells whose expression of Matrilysin was altered by treatment with antisense oligonucleotide. RESULTS: Incubation with HGF/SF mediated the release of active Matrilysin (M(r) 19,000), resulting in extracellular cleavage of E-cadherin from prostate cancer cells. This resultant soluble M(r) 80,000 fragment of E-cadherin was subsequently recognized upon immunoprobing with an anti-E-cadherin antibody. Both recombinant human Matrilysin (rh-Matrilysin) and/or HGF/SF increased the level of soluble E-cadherin and decreased the level of full-length (M(r) 120,000) E-cadherin as detected by Western blotting. The effects of rh-Matrilysin and HGF/SF were inhibited by an antisense oligonucleotide specifically directed toward human Matrilysin. In addition, stimulation with either rh-Matrilysin or HGF/SF resulted in disruption to the E-cadherin/beta-catenin complex, as shown by a significant increase (P < 0.05) in both cell scattering and invasion index. CONCLUSIONS: Treatment with HGF/SF induced Matrilysin-mediated cleavage to the extracellular domain of E-cadherin, resulting in its dissociation from the cadherin/catenin complex. This provides a new mechanism in HGF/SF-induced cell scattering, resulting in a switch to a more invasive phenotype in LNCapFGC cells, as demonstrated by in vitro invasion.

Cadherins↗
PubMed2000

Systemic treatments for metastatic cutaneous melanoma.

BACKGROUND: Systemic therapies for metastatic cutaneous melanoma, the most aggressive of all skin cancers, remain disappointing. Few lasting remissions are achieved and the therapeutic aim remains one of palliation. Many agents are used alone or in combination with varying degrees of toxicity and cost. It is unclear whether evidence exists to support these complex regimens over best supportive care / placebo. OBJECTIVES: To review the benefits from the use of systemic therapies in metastatic cutaneous melanoma compared to best supportive care/placebo, and to establish whether a 'standard' therapy exists which is superior to other treatments. SEARCH STRATEGY: Randomised controlled trials were identified from the MEDLINE, EMBASE and CCTR/CENTRAL databases. References, conference proceedings, and Science Citation Index/Scisearch were also used to locate trials. Cancer registries and trialists were also contacted. SELECTION CRITERIA: Randomised controlled trials of adults with histologically proven metastatic cutaneous melanoma in which systemic anti-cancer therapy was compared with placebo or supportive care. DATA COLLECTION AND ANALYSIS: Study selection was performed by two independent reviewers. Data extraction forms were used for studies which appeared to meet the selection criteria and, where appropriate, full text articles were retrieved and reviewed independently. MAIN RESULTS: No randomised controlled trials were found comparing a systemic therapy with placebo or best supportive care in metastatic cutaneous melanoma. REVIEWER'S CONCLUSIONS: There is no evidence from randomised controlled clinical trials to show superiority of systemic therapy over best supportive care / placebo in the treatment of malignant cutaneous melanoma. Given that patients with metastatic melanoma frequently receive systemic therapy, it is our pragmatic view that a future systematic review could compare any systemic treatment, or combination of treatments, to single agent dacarbazine.

Antineoplastic Agents↗
PubMed2000

Apoptosis is a mode of cell death in the polykaryon-forming unit assay.

In the polykaryon-forming unit (PFU) assay, which defines cell survival as the ability to form a cytochalasin-induced polykaryon of predetermined ploidy, the mode of PFU deletion is not known. Incubation of L5178Y-S PFU in cytochalasin resulted in polyploidy (> or =32C) and most polykaryons (>75%) ultimately underwent apoptosis, detected using chromatin condensation and externalised phosphatidylserine. However, large polykaryons carrying terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL)-labelled DNA strand breaks were not observed, presumably due to rapid loss of DNA. Gamma irradiation of PFU prior to cytochalasin exposure caused a reduction in the frequency of highly polyploid cells (>16C), consistent with either a supra-induction of apoptosis or a reduction in the ability of PFU to reach high ploidies. We conclude that L5178Y-S PFU are deleted by apoptosis.

Animals↗
PubMed2000

Cell-cell adhesion molecules and signaling intermediates and their role in the invasive potential of prostate cancer cells.

PURPOSE: The highly variable natural history of prostate carcinoma may be reflected in heterogeneity of invasive potential between tumors. MATERIALS AND METHODS: We have examined two prostate cancer cell lines of low invasive potential (CAHPV10 and PZHPV7) and three cell lines of high invasive potential (DU-145, PC-3, LNCapFGC), to determine whether specific adhesion molecule profiles correlated with their invasive behavior. RESULTS: Using an in vitro invasion assay, we demonstrated that DU-145, LNCapFGC and PC-3 cells were highly invasive compared with CA-HPV-10 and PZ-HPV-7 cells. LNCapFGC cells expressed high levels of E-cadherin, alpha-, beta- and gamma-catenin, desmoglein, desmoplakin and GSK3beta using immunoblotting. This was, in general, comparable to immunohistochemical staining. PC-3 cells had no E-cadherin or alpha-catenin, but expressed a high level of the HGF/SF receptor c-Met. In contrast, DU-145 cells were found to express E-cadherin and low levels for all other protein molecules, except c-Met. The DU-145 cell line also lacked alpha-catenin expression. In CA-HPV-10 and PZ-HPV-7 cells, there was no detection of APC, PECAM-1, P-cadherin or Wnt-1. DU-145, LNCapFGC and PC-3 cells formed cell-cell aggregates, which were reduced by inclusion of anti-E-cadherin antibody and the motogen HGF/SF. CONCLUSION: These results show that prostate cancer cells exhibit a diverse expression of cell-cell adhesion molecules and their signaling intermediates. The expression of these adhesion molecules bears an important relationship with the invasive phenotype of these cells.

Adenomatous Polyposis Coli Protein↗
PubMed1999

Kinematic total knee arthroplasty: a 10- to 14-year prospective follow-up review.

To understand better the type and incidence of long-term complications in total knee replacement, 306 primary Kinematic total knee arthroplasties performed between June 1978 and December 1982 were prospectively reviewed in detail. The Kinematic knee is a nonconstrained, posterior cruciate-retaining prosthesis that has right and left femoral components to afford anatomic tracking of the patella. The overall revision rate was 6.5%. The most common cause for revision surgery was patellar complications. Ten revisions (3.06%) were for patellar component loosening. Two knees were revised for patella subluxation (0.65%); 1 was in a resurfaced rheumatoid patella, and 1 in an unsurfaced osteoarthritic patella. Stair climbing was better with an unsurfaced patella. Anterior knee pain was 21.8% in the unsurfaced patella and 11.2% in the replaced patella. These data suggest patella replacement is not appropriate with this design.

Arthroplasty, Replacement, Knee↗
PubMed1999

Accuracy of patient positioning during radiotherapy for bladder and brain tumours.

We report the results of a prospective study to quantify inaccuracies in patient set-up during routine radiotherapy for tumours of the brain and bladder, which took place as part of our departmental development. Knowledge of these inaccuracies is required to put into practice the ICRU 50 recommendations regarding clinical target volume and planning target volume. We measured inaccuracies in two dimensions by comparing portal beam films with the simulator check film. Our method used manual measurements, proved to be a very laborious technique, and demonstrated the need for portal imaging. Ninety-five brain and 97 bladder portal films from 30 brain and 30 bladder patients were examined. Displacements greater than 0.5 cm were seen in 13% of brain treatments in the supero-inferior direction and 1% in the anteroposterior direction. With bladder treatments, displacements greater than 0.75 cm were seen in 12% in the supero-inferior direction and 5% in the lateral direction. These results are consistent with other previous studies. We identified a very small systematic error in the department, which was not [corrected] considered to be clinically significant. These results are discussed with reference to other similar studies and the ICRU 50 recommendations.

Adolescent↗
PubMed1998

Rice body formation in bicipito-radial bursitis: ultrasound, CT, and MRI findings.

The bicipito-radial bursa, which lies at the biceps tendon insertion on the radial tuberosity, is a rare site of chronic bursitis. We describe the clinical, radiological, and pathological findings in a case complicated by multiple rice body formation. In so doing, we describe MR appearances that allow discrimination of this entity from both synovial chondromatosis and pigmented villonodular synovitis.

Adult↗
PubMed1998

Assessment of neuroforaminal decompression in degenerative spinal stenosis.

Surgical decompression of spinal stenosis is a balance between adequate removal of bone and soft tissue for an effective decompression of neural structures and a sufficient retention of bone to maintain mechanical stability of the spine. To develop an objective, reproducible technique for the assessment of neuroforaminal decompression in the adult lumbar spine, facet sparing laminectomies were performed from L1-S1 on the lumbar spines of 59 human cadavers. A series of semirigid probes in 0.5-mm increments were passed into each successive intervertebral foramen bilaterally, beginning at L2-L3. The minimum space available for the nerve root within the foramen of the lumbar spine is 3.5 mm at L2-L3, 3.9 mm at L3-L4, 4.3 mm at L4-L5 and 5.1 mm at L5-S1, as determined by three independent observers. There were no significant differences in interobserver or intraobserver measurements. There were no complications related to passage of the probes. This study provides a method for the intraoperative determination of the adequacy of neuroforaminal decompression.

Adult↗
PubMed1997

Hypofractionated radiotherapy for muscle invasive bladder cancer in the elderly.

BACKGROUND AND PURPOSE: We have retrospectively investigated a hypofractionated regimen in a cohort of 65 elderly patients (median age 78 years), designed to minimise acute radiation affects and maximise patient tolerance and convenience in this frail group. MATERIALS AND METHODS: All patients were CT planned to a small volume. Once weekly fractions (6 Gy) prescribed to the 100% isodose as a target minimum to 30 Gy (n = 53) and 36 Gy (n = 12) were administered. Palliation of symptoms before, during, and 1 month from completion of radiotherapy were graded using the urinary and bowel symptom and toxicity index. RESULTS: Fifty-five patients had persisting urinary symptoms following trans urethral resection of bladder. Twenty-eight (51%) were completely palliated of symptoms and 7 (13%) noticed an improvement at a 1 month review. Ninety-two percent of patients with haematuria were completely palliated compared to only 24% of those with dysuria and frequency. The median symptom free interval was 7 months (range 2-40months). Median overall survival was 9 months (range 2-41months). Twelve percent of patients required inpatient admission and only three failed to complete the prescribed course due to bowel toxicity. Grade 3 acute urinary and bowel treatment related toxicity, were recorded in 18% and 9% of patients, respectively. In total, 43% of patients noticed a transient worsening of their presenting symptoms on treatment. To date no significant late toxicity (>grade 2) has been recorded. CONCLUSIONS: This regimen is generally well tolerated and offers reasonable palliation of symptoms on an outpatient basis for this frail poor prognosis group. Haematuria is particularly well palliated although only a quarter of patients presenting with dysuria and frequency were rendered symptom free.

Aged↗
PubMed1997

Ganglioside expression in lung cancer cell lines.

Gangliosides are complex glycolipid constituents of cell membranes. They are involved in many biological functions including cell-cell recognition, cell-matrix attachment, cell growth and cell differentiation. Analysis of tumor associated gangliosides may aid in the characterisation of tumour cells and their degree of malignant transformation. We have characterised a total of eight lung cancer cell lines (four small cell and four non-small cell lung cancer) with respect to ganglioside and alpha v integrin receptor expression. Ganglioside GD3 was detected using the monoclonal antibody R24. Ganglioside GM1 was detected using the beta-subunit of cholera toxin. Ganglioside 9-O-acetyl GD3 and the alpha v integrin receptor were measured using commercially available monoclonal antibodies. Our results indicate that small cell lung cancer cell lines express significant levels of GD3 and 9-O-acetyl GD3. Ganglioside GM1 and alpha v integrin receptor were not specific to any histological subtype. The expression of ganglioside GM1 and GD3 was independent of cell-cycle phase. We conclude that GD3 and 9-O-acetyl GD3 expression may be additional markers of the Small Cell Lung Cancer phenotype, but their significance is unknown. Therefore a characteristic ganglioside pattern cannot be defined according to histological subtype. alpha v integrin receptor expression is not unique to cells expressing GD3.

Antibodies, Monoclonal↗
PubMed1997

The aetiology and pathogenesis of prostate cancer.

The incidence of prostate cancer is increasing, particularly in western countries, but, despite this, its aetiology and pathogenesis remain unclear. Epidemiological studies have suggested a range of possible aetiological factors (e.g. high saturated fat intake, low intake of carotenoids, vasectomy and other sexual factors, high serum androgen levels, and a family history of prostate cancer), although results have been contradictory in many cases. A review of the literature suggests that there may be differences in the importance of these factors in younger (< 60 years) and older patients. In particular, there is growing evidence for the existence of an hereditary form of prostate cancer, with an early age of onset, an independence for dietary and other environmental factors, and an aggressive natural history. There is also increasing evidence to suggest that the pathogenesis of the disease in Japan, with its markedly different incidence rates for clinical disease (as opposed to 'latent' or 'histological' disease), may be different to that in North America. The evidence for a 'two-disease' theory of prostate carcinogenesis is discussed.

Androgens↗