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G D Wilson

Publications and source records attributed to G D Wilson.

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

Reporting basal cell carcinoma: a survey of the attitudes of histopathologists.

AIMS: To investigate the histopathological reporting of basal cell carcinoma. METHODS: Methods of classification and attitudes to excision margins were ascertained from histopathologists in 130 centres; 82 replies were obtained (63% response rate). RESULTS: 24% of those replying did not use any classification system for basal cell carcinoma. The remainder (76%) used a wide variety of different classification systems. A small number (9%) of those questioned felt reporting on completeness of excision was not important. The majority of histopathologists considered the excision margin was worth reporting but there were differences in methods of processing and reporting biopsies. CONCLUSIONS: There is considerable variation in histopathological reporting of basal cell carcinoma. There is a need for uniformity of histopathological reporting to allow both improved management decisions and comparative audit of this extremely common skin cancer.

Attitude of Health Personnel↗
PubMed1999

A novel human stress response-related gene with a potential role in induced radioresistance.

We have isolated a novel gene, DIR1, from L132 cells that is transiently repressed after exposure to low radiation doses and has a potential role in induced radioresistance. Molecular and cellular characterization of this gene reveals that it is unique but has similarities to a family of heat-shock-related proteins known as immunophilins. These have been implicated in various cellular functions including general stress responses and control of the cell cycle. Antisense strategies have demonstrated that the DIR1 gene also appears to have some involvement in the control of the cell cycle. Furthermore, there appears be a potential role for this gene product in the phenomenon of induced radioresistance through a mechanism that increases the rate of DNA repair in cells exposed to X rays and subsequently increases the cells' resistance to radiation. This is the first description of an immunophilin-like gene that has a possible role in adaptive/inducible responses to X rays in mammalian cells.

Amino Acid Sequence↗
PubMed1998

Comparison of flow and laser scanning cytometry for the assay of cell proliferation in human solid tumors.

The introduction of the laser scanning cytometer offers new capabilities in cell proliferation research, through its capacity for validation of each and every cell event through direct visualization on the microscope slide. In this study, we report a direct comparison of proliferation data derived from flow and laser scanning cytometry of human tumor nuclei labeled in vivo with bromodeoxyuridine (BrdUrd). Nuclear suspensions from 19 invasive ductal breast carcinomas and 12 gastric adenocarcinomas were prepared and analysed for BrdUrd uptake and DNA content. Specimens were analysed using a FACScan and then prepared on cytocentrifuge preparations for laser scanning cytometry. DNA index, labeling index (LI), duration of S-phase (Ts) and potential doubling time (Tpot) were calculated using standard procedures. There was an excellent correlation between the two techniques in the calculation of DNA index (R = 0.983, P > 0.0001) and LI (R = 0.924, P > 0.0001). The Ts proved more problematical (R = 0.448, P = 0.0115) but the Tpot showed closer agreement (R = 0.851, P > 0.0001) as the LI was the dominant determinant of Tpot. No single parameter could be identified as the major source of variation between the two techniques. We conclude that the laser scanning cytometer produces data equivalent to that obtained by flow cytometry.

Adenocarcinoma↗
PubMed1998

Cell cycle distribution of hypoxia and progression of hypoxic tumour cells in vivo.

Hypoxia was assessed in three murine tumour models in vivo by measuring the incorporation of 7-(4'-(2-nitroimidazole-1-yl)-butyl)-theophylline (NITP), an immunologically identifiable hypoxia marker that binds bioreductively to cells under low-oxygen conditions. Proliferating cells were labelled in the same tumours by administering the thymidine analogue bromodeoxyuridine (BrdUrd). The relative hypoxia in each cell cycle phase of cells isolated from tumours was assessed by addition of propidium iodide with analysis by flow cytometry. There was no relationship between tumour volume and hypoxia in either the anaplastic sarcoma SaF or the poorly differentiated carcinoma CaNT and only a slight negative correlation in moderately well-differentiated carcinoma Rh. The G1/G0 phase contained the greatest number of aneuploid hypoxic cells (aneuploid hypoxia ranging from less than 1% up to 40%, 38% and 71% in SaF, CaNT and Rh respectively), although there were significant amounts of hypoxia present in S- and G2/M phases for all three tumours examined. However, the highest proportion of hypoxia occurred in the G2/M phase, in which up to 60% of the cells were hypoxic. Simultaneous measurement of hypoxia, proliferation and DNA content using a novel triple-staining flow cytometry method showed that hypoxic cells could actively participate in the cell cycle. In addition, the cell cycle distribution of NITP and BrdUrd labelling showed that hypoxic cells could progress through the cell cycle, although their rate of progression was slower than that of better oxygenated cells.

Adenocarcinoma↗
PubMed1998

Expression of c-myc oncoprotein represents a new prognostic marker in cutaneous melanoma.

BACKGROUND: Overexpression of the c-myc oncoprotein has been observed to be of prognostic significance in several human cancers. This study was undertaken to establish whether c-myc has any prognostic significance in melanoma. METHODS: Expression of c-myc oncoprotein was studied in a prospective series of primary and secondary malignant melanomas. Ethanol-fixed tissue was digested into nuclei and stained for flow cytometric analysis using a pan-myc antibody. RESULTS: Overexpression of the c-myc oncoprotein was prevalent in both disease stages. In primary disease, overexpression was associated with tumour thickness and with the presence of ulceration, age and reduced disease-free interval. Of most importance, high expression of c-myc predicted poor outcome in both primary and metastatic disease. In addition, c-myc was able to discriminate prognosis in melanomas uniformly stratified as thick (greater than 3 mm) lesions. CONCLUSION: These results indicate an important role for c-myc in melanoma which may lead to better prognostic information and identification of new therapeutic strategies.

Adult↗
PubMed1998

Cellular proliferation characteristics do not account for the behaviour of horrifying basal cell carcinoma. A comparison of the growth fraction of horrifying and non horrifying tumours.

This study compared the clinical features, histological subtype, growth fraction (by Ki67 immunohistochemistry) and proliferation pattern of 22 clinically defined horrifying basal cell carcinoma compared to 81 non horrifying lesions. Late presentation was associated with half of the horrifying tumours. The other half developed horrifying tumours despite early intervention. The horrifying tumours exhibited a variety of histological growth patterns. A total of 50% were infiltrative, 23% nodular and 18% micronodular. There was no difference in the growth fraction or proliferation pattern between horrifying and non horrifying tumours of similar growth pattern (P = ns), although infiltrative tumours in either group exhibited a significantly higher growth fraction than nodular tumours (P < 0.01). This suggests that there is no intrinsic biological difference between horrifying and non horrifying tumours to account for their behaviour. We conclude that late presentation, failed or inadequate early management especially of infiltrative tumours (and other subtypes) determines the development of horrifying tumours.

Adult↗
PubMed1998

The clinical significance of c-myc oncogene expression in melanomas of the scalp.

Melanomas of the scalp are rare and have a poorer prognosis than melanomas arising at other cutaneous sites. In order to study the biology of this disease, the activity of the c-myc oncogene was studied in tumours from 25 patients with scalp melanoma using the technique of flow cytometry. Survival analysis revealed that stratification of patients according to oncogene activity provided a prognostic marker with shorter overall survival (log rank test, chi 2 = 3.9, P = 0.05) in tumours with high nuclear c-myc oncoprotein positivity. These results support our previous studies of the prognostic value of c-myc expression in melanoma and suggest that estimation of c-myc oncoprotein may be of clinical significance in identifying high risk patients.

Adult↗
PubMed1998

The prognostic significance of c-myc oncogene expression in uveal melanoma.

The role of the c-myc oncogene has been little investigated in uveal melanoma. In this study an analysis of c-myc oncoprotein expression was undertaken using flow cytometry in 71 patients with posterior uveal melanoma. Nuclear c-myc oncoprotein was detected in all of the tumours, and survival analysis revealed a significant association between high oncoprotein positivity and improved survival (log rank test: chi2 = 6.47, P = 0.01). Multifactorial analysis using Cox's proportional hazards model revealed nuclear c-myc oncoprotein to be an independent prognostic marker more accurate than other clinicopathological parameters (log rank test: chi2 = 6.61, P = 0.01). However, this result of high oncoprotein expression correlating with improved outcome is surprising and in contrast to our previous studies using the same method on cutaneous melanoma, where high levels of nuclear c-myc expression have been found to correlate with poor outcome both in primary and secondary disease. This study suggests that the pattern of oncogene expression in uveal melanoma is distinct from cutaneous melanoma and that the underlying biology of these tumours is different.

Adolescent↗
PubMed1998

An analysis of p16 protein expression in sporadic malignant melanoma.

Inactivation of p16 tumour suppressor gene has been reported frequently in melanoma cell lines, and mutations have been detected in familial melanoma kindreds. The aim of this study was to assess the role of p16 inactivation in melanocytic progression by measuring the level of p16 protein in a range of sporadic, benign and malignant melanocytic lesions. Using dual parameter flow cytometry, p16 protein expression was measured in 30 benign melanocytic naevi, 38 primary and 51 metastatic melanomas. A high level of p16 expression was demonstrated in benign melanocytic naevi (96% median nuclear positivity), with a significant reduction in primary melanomas (69%, P < 0.001). The median nuclear positivity of primary melanomas was significantly higher (P < 0.03) than the level of expression in metastatic lesions (median positivity 37%). A progressive loss of p16 expression was demonstrated from benign melanocytic naevi through to primary and metastatic lesions. These data suggest that loss of p16 protein expression is not only associated with the early transformation of benign lesions, but also with the later stages of malignant progression.

Adolescent↗
PubMed1997

Predictive assays of radiation response in patients with head and neck squamous cell carcinoma: a review of the Institute Gustave Roussy experience.

PURPOSE: The aim of the study was to present the updated Institut Gustave Roussy experience of the predictive value of three biological parameters in patients with squamous cell carcinoma of the Head and Neck (HNSCC) treated with radiation therapy. METHODS AND MATERIALS: Three parameters have been investigated independently: tumor cell kinetics (TS, Tpot and LI), oxygen tension measurements (PO2) and intrinsic radiosensitivity (SF2Gy). RESULTS: No relationship has been found between local-regional control and Tpot or LI in a series of 74 patients. Our data also support that the surviving fraction at 2 Gy, (SF2) was unlikely to predict the clinical outcome in a series of 92 patients. Differences in PO2 measurements have been observed between tumors, and tumor oxygenation was lower than that of normal tissue for the majority of patients. However PO2 measurements did not predict clinical outcome, but further investigations are needed to draw definitive conclusions, given the limited number of patients entered in our study (35 patients). In addition, we were able to measure the three parameters in 10 patients showing no correlation between PO2, SF2 and Tpot. CONCLUSIONS: The method used to evaluate Tpot and SF2 did not provide clinically relevant predictive parameters for this type of cancer. Further investigations are needed to assess the predictive value of PO2 measurements and of new biological parameters in a multiparametric approach, taking into account other possible clinical and biological confounding factors.

Adult↗
PubMed1997

Predictive value of potential doubling time in head and neck cancer patients treated by conventional radiotherapy.

PURPOSE: The goal of this study was to investigate the clinical utility of pretreatment measurements of tumor cell kinetics to predict the outcome of patients with squamous cell carcinoma of the head and neck receiving conventional radiotherapy. METHODS AND MATERIALS: All patients received between 64 and 70 Gy as 2 Gy fractions, five fractions per week. Cell kinetics were assayed rapidly and quantitatively using flow cytometric evaluation of iododeoxyuridine (IdUrd) incorporation, in vivo, from a biopsy removed several hours after the administration of the DNA precursor to the patient prior to the start of treatment. RESULTS: The measured proliferation parameters were not related to the clinicopathological features of the tumors, emphasizing the independent nature of these parameters. In univariate analysis, nodal involvement was the most important clinical feature of the tumors related to local control followed by Tpot, DNA aneuploidy, and attainment of complete regression at 6 weeks. Of these only Tpot and nodal status maintained significance in multivariate analysis, with respect to loco-regional control. In subgroup analysis, Tpot was able to stratify patients into high or low rate of loco-regional control in node negative patients, in aneuploid tumors and in patients who did achieve complete regression at 6 weeks. For cause specific survival, N-stage was the only parameter that significantly discriminated the prognosis in these patients. CONCLUSIONS: The conclusion of this study is that Tpot provides clinically important information that can predict patients with a low probability of achieving long-term local control with conventional fractionation. Further improvements to the methodology to address the shortcomings of analyzing diploid tumors may increase the predictive power of the measurement.

Adult↗
PubMed1997

The clinical significance of oncogene expression in subungual melanoma.

Subungual melanoma is a particularly aggressive tumour. However, biological investigations of its behaviour are presently lacking due to its comparative rarity. In order to study the biology of this disease, the activity of the c-myc oncogene was studied in tumours from 24 patients with subungual melanoma using the technique of flow cytometry. High levels of oncoprotein were found in all tumours and exceeded that documented in other varieties of cutaneous melanoma. Survival analysis revealed that stratification of patients according to oncogene activity provided a useful prognostic marker with shorter disease free interval (log rank test, chi 2 = 6.6, P = 0.01) and overall survival (log rank test, chi 2 = 3.6, P = 0.07) in tumours with high oncoprotein levels. This is the first study to investigate oncogene expression in subungual disease and supports its potential application as a prognostic marker.

Adult↗
PubMed1997

Measurement of c-myc oncoprotein provides an independent prognostic marker for regional metastatic melanoma.

Patients with melanoma who develop nodal metastatic disease represent a group with heterogeneous clinical outcome. Nodal positivity remains the most accurate prognostic marker for regional melanoma although it fails to predict outcome in a significant number of patients. Recent studies have illustrated the prognostic potential of c-myc oncogene expression in melanoma. The aim of this study was to measure c-myc oncoprotein in a series of regional metastatic specimens from 48 patients, and evaluate its use as a marker of clinical outcome. Oncoprotein expression was detected in 46 (96%) of the tumours with a median positivity of 68% (range 0-98%). Survival analysis revealed a significant association between oncoprotein positivity and survival (Long-Rank test, chi 2 = 15.2, P < 0.001). Multivariate analysis of outcome showed c-myc oncoprotein to be an independent prognostic marker more accurate than all other clinicopathological parameters including nodal positivity (chi 2 = 8.34, P = 0.003). Estimation of c-myc oncoprotein is therefore recommended as a powerful prognostic marker for regional metastatic melanoma.

Aged↗
PubMed1997

Cellular proliferation characteristics of basal cell carcinoma: relationship to clinical subtype and histopathology.

This study investigates the proliferation characteristics of 81 primary basal cell carcinomas (BCC) using detection of the Ki-67 antigen by immunohistochemistry. The tumours were classified into distinct sub-types based on their histological growth pattern and differentiation status. The mean Ki-67 growth fraction was 0.293 and this was found to vary between the different growth patterns, with morpheic, infiltrating and superficial tumours showing the highest levels of proliferation at 0.373, 0.351 and 0.335, respectively; the nodular and micronodular growth patterns were significantly lower at 0.248 and 0.232, respectively. No overall association was seen between proliferation and differentiation status although certain histological growth patterns such as nodular showed a greater propensity to differentiate. Proliferation was related to tumour size, with larger lesions exhibiting higher growth fractions although this may have also been related to tumour subtype as infiltrating and morpheic tumours tended to present with larger tumour diameters. The spatial distribution of proliferating cells by Ki-67 labelling was not related to tumour subtype, differentiation or growth fraction. These studies have shown BCC to possess proliferative characteristics akin to other solid tumours commonly regarded as more rapidly dividing. There was an association between growth fraction and tumour subtype consistent with higher proliferation in the lesions considered to be more aggressive.

Basal Cell Carcinoma↗
PubMed1997

Hindi translation of the Gray-Wilson Personality Questionnaire: a cross-cultural replication of sex differences.

The Gray-Wilson Personality Questionnaire (GWPQ) was translated into Hindi and administered to 246 male and 191 female university students. It measures six animal-learning paradigms corresponding to Gray's (1987) three-emotion systems model of personality. Sex differences previously reported from the United Kingdom and Japan were replicated: Women scored significantly higher on the Active Avoidance and Flight subscales, men on the Approach subscale. In the Indian sample, women scored higher than men on the Extinction subscale; this difference, although in the same direction, was not significant in the United Kingdom and Japan. In India, as in Japan and the United Kingdom, women were relatively punishment sensitive, and men were relatively reward sensitive. Consistent with Gray's model, scores on Fight and Flight subscales were positively correlated, as were Passive Avoidance and Extinction subscale scores; however, contrary to the model were the negative correlation between subscale scores for Approach and Active Avoidance and the positive correlation between subscale scores for Approach and Passive Avoidance, also observed previously in the United Kingdom and Japan.

Adolescent↗