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S M Edwards

Publications and source records attributed to S M Edwards.

At least 37 records · Page 2Linked to original sources
PubMed1999

BCL10 is rarely mutated in human prostate carcinoma, small-cell lung cancer, head and neck tumours, renal carcinoma and sarcomas. MPT Collaborators, St George's Hospital Collaborators.

We have used single-strand conformation polymorphism (SSCP) analysis to screen for mutations in the BCL10 gene in 81 primary prostate carcinomas, 20 squamous cell cancers of the head and neck, 15 small-cell lung cancer cell lines, 24 renal carcinoma cell lines and 13 sarcoma cell lines. We failed to find evidence of somatically acquired mutations of the BCL10 gene suggesting that BCL10 does not play a major role in the development of these malignancies.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Immunohistochemical expression of BRCA2 protein and allelic loss at the BRCA2 locus in prostate cancer. CRC/BPG UK Familial Prostate Cancer Study Collaborators.

Many epidemiological studies have reported an association between breast and prostate cancer. BRCA2 functions as a tumour-suppressor gene in about 35% of large familial breast-cancer clusters; its role in the pathogenesis of sporadic breast cancer is less clear. We have evaluated immunohistochemical expression of BRCA2 protein and allelic loss of markers at the BRCA2 locus in tissue derived both from sporadic and from familial cases of prostate cancer. Immunohistochemical analysis was performed in 167 paraffin-embedded archival specimens. Normal prostate and 75% (120/160) of prostate-cancer tissue did not express BRCA2 protein. However, 25% (40/160) of cancer cases did express patchy staining; of these, 17% (2711 60) expressed positive nuclear staining in normal glandular tissue adjacent to tumour (either in addition to, or, independent of tumour). Allelic loss is the hallmark of a tumour-suppressor gene. Markers flanking (D13S267, D13S260) and within (D13S171) the BRCA2 gene indicated allelic loss in at least one locus in 23% (17/73) of tumours analyzed. There was no difference in the rates of allelic loss between sporadic and familial tumours, nor was there any association between immunohistochemical staining and allelic loss. Although immunohistochemical staining provided no useful prognostic information, allelic loss at BRCA2 was shown in univariate analysis to be associated with poorer survival (log-rank test, p = 0.046).

BRCA2 Protein↗
PubMed1998

Allelic imbalance in familial and sporadic prostate cancer at the putative human prostate cancer susceptibility locus, HPC1. CRC/BPG UK Familial Prostate Cancer Study Collaborators. Cancer Research Campaign/British Prostate Group.

A recent report has provided strong evidence for a major prostate cancer susceptibility locus (HPC1) on chromosome 1q24-25 (Smith et al, 1996). Most inherited cancer susceptibility genes function as tumour-suppressor genes (TSGs). Allelic loss or imbalance in tumour tissue is often the hallmark of a TSG. Studies of allelic loss have not previously implicated the chromosomal region 1q24-25 in prostate cancer. However, analysis of tumour DNA from cases in prostate cancer families has not been reported. In this study, we have evaluated DNA from tissue obtained from small families [3-5 affected members (n = 17)], sibling pairs (n = 15) and sporadic (n = 40) prostate tumours using the three markers from Smith et al (1996) that defined the maximum multipoint linkage lod score. Although widely spaced (12-50 cM), each marker showed evidence of allelic imbalance in only approximately 7.5% of informative tumours. There was no difference between the familial and sporadic cases. We conclude that the incidence of allelic imbalance at HPC1 is low in both sporadic tumours and small prostate cancer families. In this group of patients, HPC1 is unlikely to be acting as a TSG in the development of prostate cancer.

Aged↗
PubMed1998

Body size and the risk of colon cancer in a large case-control study.

OBJECTIVE: To investigate the risks of height, weight and body fat distribution associated with colon cancer in subcategories of gender, age and site in the colon. Interaction with family history of colorectal cancer is also examined. DESIGN: Case-control study of diet, anthropometry and colon cancer risk. SUBJECTS: Nineteen hundred and eighty-three colon cancer cases (age 30-79 y) and 2400 age and gender matched population controls. MEASUREMENTS: Height, weight and waist and hip circumferences were obtained by trained interviewers. Body Mass Index (BMI) and Waist-Hip Ratio (WHR) were calculated. RESULTS: Of all anthropometric measurements examined, only BMI was consistently associated with an increased risk of colon cancer. The test for trend for BMI was significant for men and women overall and for the majority of subgroups examined. In younger persons those with a family history of colorectal cancer had a greater risk of colon cancer associated with BMI (Men odds ratio (OR) = 7.76, 95% confidence interval (CI) 2.60, 23.1; Women OR = 4.85, 95% CI 2.33, 10.12) comparing the third tertile to the first, than those with no family history (Men OR = 1.70, 95% CI 1.25, 2.32; Women OR = 1.53, 95% CI 1.22, 1.92). WHR, after controlling for BMI was not associated with colon cancer in men, and was associated with a slight increase in women (primarily in those with distal tumors). CONCLUSION: This study contributes to mounting evidence that excess weight is associated with an increased risk of colon cancer.

Adult↗
PubMed1998

The Sports Inventory for Pain: a confirmatory factor analysis.

This investigation was designed to assess the factorial validity of the Sports Inventory for Pain (SIP) which was completed by 182 undergraduate students. Responses were subjected to a confirmatory factor analysis designed to test the hypothesized underlying factor structure. Of five proposed subscales, only the items for the Cognitive and Coping subscales reasonably fit the hypothesized structure. To improve the fit of the model, factors were allowed to correlate, and the worst fitting item from each of the subscales was removed. The modified model also failed to adequately fit the data. Lastly, the items corresponding to the worst fitting subscale were dropped from the analysis. Again, the modified model failed to fit the data. Discussion suggests a possible respecification of the SIP.

Adaptation, Psychological↗
PubMed1997

No germline mutations in the dimerization domain of MXI1 in prostate cancer clusters. The CRC/BPG UK Familial Prostate Cancer Study Collaborators. Cancer Research Campaign/British Prostate Group.

There is evidence that predisposition to cancer has a genetic component. Genetic models have suggested that there is at least one highly penetrant gene predisposing to this disease. The oncogene MXI1 on chromosome band 10q24-25 is mutated in a proportion of prostate tumours and loss of heterozygosity occurs at this site, suggesting the location of a tumour suppressor in this region. To investigate the possibility that MXI1 may be involved in inherited susceptibility to prostate cancer, we have sequenced the HLH and ZIP regions of the gene in 38 families with either three cases of prostate cancer or two affected siblings both diagnosed below the age of 67 years. These are the areas within which mutations have been described in some sporadic prostate cancers. No mutations were found in these two important coding regions and we therefore conclude that MXI1 does not make a major contribution to prostate cancer susceptibility.

Adult↗
PubMed1997

Hprt- mutation spectrum in a closely related pair of human bladder tumour cell lines after gamma-irradiation at different dose-rates.

The spectrum of deletion sizes in mutants of two human bladder carcinoma cell lines has been examined. The cell lines were MGH-U1 and a radiation-sensitive subline (U1-S40b) that has been developed in this laboratory. Three groups, each of 20-30 mutants at the hprt locus were investigated: arising spontaneously, or induced after exposure to 10 Gy gamma-radiation either at high dose-rate (2 Gy/min) or low dose-rate (0.01 Gy/min). Data on the mutation frequency of the two cell lines at low dose-rate were obtained to supplement previously published data at high dose-rate. The mutation frequency was lower in U1-S40b than in MGH-U1 both for high and low dose-rate irradiation. The presence of intact copies of each of the nine hprt exons was examined using multiplex PCR, supplemented by single-exon PCR. The incidence of small hprt mutations (i.e. leading to no change in the size of the PCR products) was the same for spontaneous mutations in the two cell lines; for radiation-induced mutants it was higher in U1-S40b. The incidence of total deletions (i.e. no positive exon amplification) was lower in U1-S40b both for high and low dose-rate irradiation. The results are consistent with the hypothesis that large deletions tend to lead to the loss of adjacent essential genes and thereby to the death of potential mutants.

Carcinoma↗
PubMed1997

Hyperdynamic therapy: the nurse's role in the treatment of cerebral vasospasm.

The onset of subtle diffuse ischemic neurological deficits often associated with cerebral vasospasm is a major cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage. The exact etiology of cerebral vasospasm is unclear. Increasing intravascular volume, decreasing blood viscosity and inducing hypertension may help prevent or diminish neurological deficits from cerebral vasospasm by improving cerebral blood flow. An intensive multidisciplinary approach is necessary with the role of the neuroscience nurse being pivotal. An understanding of the subtle neurological changes suggestive of cerebral vasospasm and its effects leads to early recognition, and allows for rapid institution of therapy.

Adult↗
PubMed1995

Cytotoxic and clastogenic effects of benzyl isothiocyanate towards cultured mammalian cells.

Benzyl isothiocyanate (BITC), a compound found in cruciferous vegetables present in the human diet, has previously been shown to induce chromosome aberrations in an Indian muntjac cell line. The results of this study show that it also induces both chromosome aberrations and sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells in the absence of an exogenous metabolic activation system and induces DNA strand breaks as measured by the single-cell gel electrophoresis assay. However, whereas it increased the number of aberrations four-fold, it was not able to raise SCE levels by more than 50% and there was a levelling-off in the dose-response curve. Whereas the survival curve of CHO cells exposed to BITC was linear in shape, that of the human colorectal adenocarcinoma cell line HT29 was found to fit the exponential model (with an alpha equivalent of 0.28 and a beta equivalent of 2.80, where the concentration of BITC is measured in micrograms/ml). This pattern of clastogenic and cytotoxic activities is reminiscent of that generated by ionizing radiation and certain radiomimetic chemotherapeutic agents.

Adenocarcinoma↗
PubMed1994

Quantitative in vitro assessment of phototoxicity using a human skin model, Skin2.

The ability to accurately predict the phototoxic potential of personal and skin care products remains a key element in assessing the safety of premarketed products. To find a reliable in vitro alternative test for photoirritancy, the European Commission and the European Cosmetic Association are conducting a 3-year, European validation study. Based on the results of this study, an in vitro photoirritancy method will be selected for incorporation into new international guidelines for photoirritancy testing. As a part of this study, Skin2, a cultured human skin system, was used to evaluate the phototoxic potential of chemicals with known photoirritative properties. The Skin2 ZK1351, a 3-dimensional co-culture system, consists of dermal fibroblasts and a multilayered epidermis comprising differentiated keratinocytes. This product line has previously been used to evaluate the irritative potential of topically applied ingredients and products. In this study, various concentrations of the test chemicals were applied to the epidermal side of the Skin2 tissue for contact times of 1 h or 24 h and then the tissue was exposed to 2.9 J/cm2 of ultraviolet A (UVA) radiation. Treated but nonirradiated tissues were also assayed to predict the cytotoxic potential of the test chemicals, which could mask the phototoxic reaction. After exposure, the tissue substrates were rinsed free of test chemicals and allowed to recover for 24 h. Following this incubation, the MTT reduction assay was used to assess cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzophenones↗
PubMed1993

Mutation induction by ionizing radiation in three human bladder tumour cell lines.

Mutation induction at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus has been studied in three human bladder tumour cell lines of varying radiosensitivity. U1-S40b, a radiosensitive mutant clone of MGH-U1, has been previously reported to show no difference in split-dose recovery or low dose-rate sparing, but to have an impaired repair fidelity when compared to its parent line. In this paper we have shown that U1-S40b is less mutable at the hprt locus at a similar level of survival. This may represent an increased incidence of severe or non-repairable lesions, making hprt- mutants poorly recoverable in U1-S40b when compared to MGH-U1. No difference was seen in mutation induction between MGH-U1 and RT112, another human bladder tumour cell line of similar radiosensitivity to MGH-U1.

Carcinoma, Transitional Cell↗
PubMed1992

A DNA repair defect in a radiation-sensitive clone of a human bladder carcinoma cell line.

DNA repair was measured in an ionising radiation-sensitive mutant of a human bladder carcinoma cell line. No difference in the rate or extent of double-strand break rejoining was found using the techniques of neutral filter elution and pulsed-field gel electrophoresis. In contrast, significant differences in repair fidelity, measured by plasmid reconstitution, were found. The parent line had a repair fidelity of 84.7% compared with 58.9% for S40b (P = 0.0003). It is suggested that repair fidelity can be an important determinant of radiosensitivity in human tumour cells.

Carcinoma↗
PubMed1992

The intrinsic alpha/beta ratio for human tumour cells: is it a constant?

The radiation response of 15 mammalian cell lines comprising 11 human tumour, two human fibroblast and two murine lymphoma cell lines, has been analysed using the linear-quadratic equation. As well as using conventional analysis of acute dose-survival curves to derive values for alpha and beta (termed alpha ac and beta ac), low dose-rate and split-dose experiments have been used to derive independent values of alpha and beta (alpha 1dr and beta RR), respectively. alpha 1dr provides a measure of irrecoverable damage, the magnitude of which agreed well with the initial slope of the acute survival curve for most cell lines. beta RR derived from split-dose experiments represents a unique measure of recovery for each cell line. Large differences were found between individual values of beta ac and beta RR, especially in the radiosensitive cell lines. Since beta RR is a functional measure of recovery we suggest that this is the more relevant parameter in studies of dose sparing. The most striking result of this analysis was found in considering the alpha/beta ratios. No relationship was observed between alpha ac and beta ac resulting in values of alpha ac/beta ac ranging from 1 to 175. In contrast a positive correlation was observed between alpha 1dr beta RR in the 11 tumour cell lines, giving an alpha/beta ratio of 9.4 +/- 1.8 Gy. This observation of the relative constancy of the ratio for human tumour cells leads to an hypothesis about the role of initial damage as a determinant of radiosensitivity.

Animals↗
PubMed1989

The repair of identified large DNA adducts induced by 4-nitroquinoline-1-oxide in normal or xeroderma pigmentosum group A human fibroblasts, and the role of DNA polymerases alpha or delta.

4-Nitroquinoline-1-oxide (4NQO) reacts with DNA primarily at the N2 and C8 of guanosine, with a small percent of reaction at the N6 of adenosine. In human cells it has been unclear whether or not all 4NQO-induced adducts are removed by a nucleotide excision repair mechanism. In this paper we demonstrate that the inhibitor of DNA polymerases alpha and delta, aphidicolin, blocks the repair of all 4NQO adducts. Hence excision repair must operate on all of these lesions. After 4NQO the residual excision repair seen in a xeroderma pigmentosum group A cell line virtually totally defective in UV repair was 40-60% of that in normal cells. Therefore there must be some differences between the excision repair operating on UV as opposed to 4NQO-induced DNA damage.

4-Nitroquinoline-1-oxide↗
PubMed1988

Induction and rejoining of DNA double-strand breaks in human cervix carcinoma cell lines of differing radiosensitivity.

Five recently established cell lines of human carcinoma of the cervix of varying radiosensitivity have been used to determine whether the induction or rejoining of DNA double-strand breaks (dsb) shows any correlation with radiosensitivity or radiation recovery capacity. Double-strand DNA breaks have been measured using neutral filter elution at pH 9.6. The number of breaks induced immediately after irradiation with doses of 10 to 40 Gy 60Co gamma rays appeared to show some correlation with radiosensitivity particularly after 10 Gy; the two more radiosensitive lines incurred more breaks than the more radioresistant lines. In addition, the shape of the induction curve with dose was linear for the two sensitive lines but curvilinear for the resistant lines. Despite the dose scales being different, this mirrored their respective cell survival curve shapes. After 30 or 50 Gy irradiation, rejoining of breaks appeared to be rapid and almost complete within 60 min at 37 degrees C for the three resistant lines. However, for the sensitive lines, one line (HX160c) in particular exhibited a reduced rate of dsb rejoining. In addition, a residual level of dsb was present in this line even after allowing rejoining for 3 h. While induction and rejoining of DNA dsb therefore appears to be a factor in determining radiosensitivity, at doses relevant to cellular survival (up to 10 Gy), the greater induction of DNA dsb in radiosensitive lines may play a significant role in determining the cellular response to ionizing radiation.

Cell Line↗
PubMed1987

Bone and gallium scan findings in malignant fibrous histiocytoma. Case report with radiographic and pathologic correlation.

Malignant fibrous histiocytoma (MFH) is the most common soft tissue malignancy in adults. The Ga-67 citrate scan findings of an extremity-located MFH, the most common location of this neoplasm, have never been published in English language journals to the best of the authors' knowledge. Ga-67 citrate and Tc-99m MDP scans of the thigh mass accurately depicted the tumor's local extent, including the presence of central ischemic necrosis within the tumor, and the absence of adjacent osseous involvement and distant metastases, as correlated with computed tomography, angiography, and pathologic examinations.

Femur↗