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Biomedical subjects

Gareth Evans

Publications and source records attributed to Gareth Evans.

28 records · Page 2Linked to original sources
PubMed2004

Preservation and evaluation of semen for artificial insemination.

Many years of research have been devoted to improving the fertility of preserved semen of small ruminants. There have been few significant advances in preservation in recent times, but considerable knowledge has been gained on the effect of preservation on the structure and function of spermatozoa. It has become evident that preservation greatly affects many sperm attributes, such as motility, respiratory activity, membrane status and DNA quality. Consequently, viability is reduced, transport in the female reproductive tract is inhibited, the timing of fertilisation is altered and embryo development is affected following insemination of preserved, compared to fresh spermatozoa. A greater understanding of their functional condition may lead to the development of methods of preventing these alterations or to improved methods of using the preserved spermatozoa for artificial insemination in their altered state.

Animals↗
PubMed2003

Bayesian evaluation of breast cancer screening using data from two studies.

The mean sojourn time (the duration of the period during which a cancer is symptom free but potentially detectable by screening) and the screening sensitivity (the probability that a screen applied to a cancer in the preclinical screen detectable period will result in a positive diagnosis) are two important features of a cancer screening programme. Little data from any single study are available on the potential effectiveness of mammographic screening for breast cancer in women with a family history of the disease, despite this being an important public health issue. We develop a method of estimation, from two separate studies, of the two parameters, assuming that transition from no disease to preclinical screen detectable disease, and from preclinical disease to clinical disease, are Poisson processes. Estimation is performed by a Markov chain Monte Carlo algorithm. The method is applied to the synthesis of two studies of mammographic screening in women with a family history of breast cancer, one in Manchester and one in Kopparberg, Sweden.

Adult↗
PubMed2003

Melanoma invasion in reconstructed human skin is influenced by skin cells--investigation of the role of proteolytic enzymes.

Melanoma invasion is a complex multi stage process involving changes to the cell/extracellular matrix (ECM) and cell/cell interactions. We have previously shown using an in vitro model of reconstructed human skin (consisting of human dermis with a basement membrane [BM] and populated with human skin cells) that some melanoma cells (HBL cell line) invade more actively in the presence of adjacent normal skin cells. The aim of the present study was to further investigate the relationship between melanoma cells, skin cells and ECM proteins during melanoma cell invasion through reconstructed skin, extending this to a study of three melanoma cell lines. We also examined whether such cell/cell induced invasion is due to increased expression and activation of matrix-metalloproteinase-2 (MMP-2) and MMP-9, or due to increases in general protease activity for keratinocytes, fibroblasts or melanoma lines. Addition of skin cells dramatically altered the invasive behaviour of the three metastatic melanoma cell lines (HBL, C8161 and A375SM) used; they increased the invasive ability of HBLs which were unable to invade on their own; they potentiated the invasion of C8161 cells which were invasive in their own right, but reduced the invasion of A375-SM cells which were aggressive invaders in the absence of skin cells. Latent forms of MMP-2, and MMP-9, were clearly expressed by the normal skin cells whereas all three melanoma lines weakly expressed these proteases. Fibroblast and keratinocyte MMPs were activated specifically by culture on type I collagen and on dermis which retained an intact basement membrane. These findings demonstrate that while there is an active communication between melanoma cells and adjacent skin cells, the invasive process is dictated by the melanoma cells and not the skin cells. However, activation of skin cell derived MMPs may play an important role in facilitating invasion by particular melanoma phenotypes.

Cell Communication↗
PubMed2003

Do women understand the odds? Risk perceptions and recall of risk information in women with a family history of breast cancer.

OBJECTIVES: To describe and compare women's risk perceptions and recall of breast cancer risk information in a cohort of first-time attendees at a family history clinic. METHODS: We conducted a 1-year prospective study of 158 women aged 18-45 years with a confirmed lifetime risk of breast cancer of 1 in 6 or greater. Risk perception and recall were assessed using a self-report questionnaire, completed pre-counselling and 3, 6, 9 and 12 months post-counselling, and through interviews conducted at 3 and 12 months. RESULTS: The proportion of women with accurate personal risk perceptions based on 'gambling' odds ('1 chance in x') significantly improved after risk counselling from 12% pre-counselling to 67% 3 months post-counselling (p < 0.001), which was maintained for 1 year. This was the method of reporting perceived risk associated with the best level of risk accuracy and the women's preferred format for describing risk, but the concept of lifetime risk was understood by only 44% of women. Qualitative risk categories ('high', moderate' or 'low') correlated significantly with women's self-reported odds values, but each category comprised a wide range of women's perceived numeric risks. Describing risk as the 'likelihood of breast cancer' resulted in a broad and somewhat inaccurate reporting of risk, compared with numeric ratings made at the same time. There was an increase of up to 4-fold in the proportion of women who failed to recall their risk value over time, and women were unable to accurately put the breast cancer risk in context compared with other health threats. CONCLUSIONS: All methods of describing risk have limitations, but the results of the present study provide good support for women's accurate recall of numeric risk values and their preference for use of these 'gambling' odds. This may have been influenced by consistency of the use of this method both in risk communication and in personal summary letters. Descriptive risk formats reflected higher levels of perceived vulnerability to breast cancer, and genetic counsellors need to be aware of these different perceptions.

Adolescent↗
PubMed2003

High-resolution profiling of an 11 Mb segment of human chromosome 22 in sporadic schwannoma using array-CGH.

Previous low-resolution schwannoma studies have reported diverse frequencies (30-80%) of 22q deletions, involving the neurofibromatosis-2 tumor suppressor (NF2) gene. We constructed an array spanning 11 million base pairs of 22q encompassing the NF2 gene, with 100% coverage and an average resolution of 58 kb. Moreover, the 220 kb genomic sequence encompassing the NF2 gene was covered by 13 cosmids to further enhance the resolution of analysis. The rationale of this array-CGH study was to map and size 22q deletions around the NF2 gene in sporadic schwannoma using a reliable method with maximal resolution. We studied tumor and constitutional DNA from 47 patients and detected heterozygous deletions in 21 (45%) tumors, which could be classified into three profiles. The predominant profile (12/21) was a continuous deletion of the 11 Mb segment, consistent with monosomy 22. The second profile, comprising five schwannomas, was also in agreement with a continuous 11 Mb heterozygous deletion. However, these displayed a distinctly different level of deletion when compared to the first profile, suggesting a considerable amount of normal tissue in the tumor samples. This is the first report demonstrating the sensitivity of array-CGH to discriminate such samples. The third profile was composed of four cases displaying interstitial deletions of various sizes. Two of these did not encompass the NF2 locus, which further emphasize the importance of other loci in schwannoma development. This is the first high-resolution study performed on a large series of tumors, using an array continuously covering 1/3 of a human chromosome. Our findings warrant further studies of an extended tumor series on a full 22q genomic array, to better define additional, putative 22q-located loci important for schwannoma development. Our array also provides a new diagnostic tool for analysis of NF2 gene deletions in patients affected with neurofibromatosis-2.

Adult↗
PubMed2002

Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.

BACKGROUND: Oral contraceptive use has been associated with an increase in the risk of breast cancer in young women. We examined whether this association is seen in women at high risk of breast cancer because they carry a mutation in one of two breast cancer susceptibility genes, BRCA1 and BRCA2. METHODS: We performed a matched case-control study on 1311 pairs of women with known deleterious BRCA1 and/or BRCA2 mutations recruited from 52 centers in 11 countries. Women who had been diagnosed with breast cancer were matched to control subjects by year of birth, country of residence, mutation (BRCA1 or BRCA2), and history of ovarian cancer. All study subjects completed a questionnaire about oral contraceptive use. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. All statistical tests were two-sided. RESULTS: Among BRCA2 mutation carriers, ever use of oral contraceptives was not associated with an increased risk of breast cancer (OR = 0.94, 95% CI = 0.72 to 1.24). For BRCA1 mutation carriers, ever use of oral contraceptives was associated with a modestly increased risk of breast cancer (OR = 1.20, 95% CI = 1.02 to 1.40). However, compared with BRCA1 mutation carriers who never used oral contraceptives, those who used oral contraceptives for at least 5 years had an increased risk of breast cancer (OR = 1.33, 95% CI = 1.11 to 1.60), as did those who used oral contraceptives before age 30 (OR = 1.29, 95% CI = 1.09 to 1.52), those who were diagnosed with breast cancer before age 40 (OR = 1.38, 95% CI = 1.11 to 1.72), and those who first used oral contraceptives before 1975 (OR = 1.42, 95% CI = 1.17 to 1.75). CONCLUSIONS: Among BRCA1 mutation carriers, women who first used oral contraceptives before 1975, who used them before age 30, or who used them for 5 or more years may have an increased risk of early-onset breast cancer. Oral contraceptives do not appear to be associated with risk of breast cancer in BRCA2 carriers, but data for BRCA2 carriers are limited.

Adolescent↗
PubMed2002

Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations.

BACKGROUND: Data concerning the efficacy of bilateral prophylactic oophorectomy for reducing the risk of gynecologic cancer in women with BRCA1 or BRCA2 mutations are limited. We investigated whether this procedure reduces the risk of cancers of the coelomic epithelium and breast in women who carry such mutations. METHODS: A total of 551 women with disease-associated germ-line BRCA1 or BRCA2 mutations were identified from registries and studied for the occurrence of ovarian and breast cancer. We determined the incidence of ovarian cancer in 259 women who had undergone bilateral prophylactic oophorectomy and in 292 matched controls who had not undergone the procedure. In a subgroup of 241 women with no history of breast cancer or prophylactic mastectomy, the incidence of breast cancer was determined in 99 women who had undergone bilateral prophylactic oophorectomy and in 142 matched controls. The length of postoperative follow-up for both groups was at least eight years. RESULTS: Six women who underwent prophylactic oophorectomy (2.3 percent) received a diagnosis of stage I ovarian cancer at the time of the procedure; two women (0.8 percent) received a diagnosis of papillary serous peritoneal carcinoma 3.8 and 8.6 years after bilateral prophylactic oophorectomy. Among the controls, 58 women (19.9 percent) received a diagnosis of ovarian cancer, after a mean follow-up of 8.8 years. With the exclusion of the six women whose cancer was diagnosed at surgery, prophylactic oophorectomy significantly reduced the risk of coelomic epithelial cancer (hazard ratio, 0.04; 95 percent confidence interval, 0.01 to 0.16). Of 99 women who underwent bilateral prophylactic oophorectomy and who were studied to determine the risk of breast cancer, breast cancer developed in 21 (21.2 percent), as compared with 60 (42.3 percent) in the control group (hazard ratio, 0.47; 95 percent confidence interval, 0.29 to 0.77). CONCLUSIONS: Bilateral prophylactic oophorectomy reduces the risk of coelomic epithelial cancer and breast cancer in women with BRCA1 or BRCA2 mutations.

Adult↗
PubMed2002

Germline mutation of ARF in a melanoma kindred.

Familial melanoma predisposition is associated with germline mutations at the CDKN2A/ARF locus in up to 40% of families. The exact role of the two proteins encoded by this complex locus in this predisposition is unclear. Most mutations affect either CDKN2A only or products of both genes. Recently a deletion affecting ARF-specific exon 1beta was reported in a family with melanoma and neural tumours. However, the possibility of this deletion also altering the CDKN2A transcript could not be excluded. More convincingly, a 16 base pair insertion in exon 1beta has been reported in an individual with multiple melanomas suggesting a direct role for ARF in melanoma predisposition. We report here a splice mutation in exon 1beta in a family with melanoma that results in ARF haploinsufficiency. The mutation was observed in a mother and daughter with melanoma. A sibling of the mother with breast cancer also had this mutation. Analysis of the melanoma from one individual revealed a 62 bp deletion in exon 3 of the wildtype allele and loss of the mutant allele; these somatic changes would affect both CDKN2A and ARF. These somatic events suggest that concomitant inactivation of both ARF and CDKN2A may be necessary for melanoma development and that mutations in ARF and CDKN2A possibly confer different levels of susceptibility to melanoma, with the former associated with lesser predisposition. In this situation, the events follow a 'three-hit' model as observed in tumours from FAP patients with an attenuated phenotype. Overall, the data suggest a direct role for ARF haploinsufficiency in melanoma predisposition and co-operation between ARF and CDKN2A in tumour formation, consistent with recent observations in Cdkn2a-specific knockout mice.

Adult↗
PubMedDate not supplied

Panel discussion.

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Adolescent↗