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Biomedical subjects

S Troup

Publications and source records attributed to S Troup.

10 recordsLinked to original sources
PubMed2006

Potential role of estrogen receptor alpha (ERalpha) phosphorylated at Serine118 in human breast cancer in vivo.

Post-translational modifications of proteins are known to be important in protein activity and ERalpha is known to be phosphorylated at multiple sites within the protein. The exact function of site-specific phosphorylation in ERalpha is unknown, although several hypotheses have been developed using site-directed mutagenesis and cell culture models. Targeting the ERalpha at the level of such post-translational modification pathways would be a new and exciting approach to endocrine therapy in breast cancer, but adequate knowledge is lacking with regard to the relevance of site-specific phosphorylation in ERalpha in human breast cancer in vivo. Recently, antibodies to P-Serine(118)-ERalpha and P-Serine(167)-ERalpha, two major sites of phosphorylation in ERalpha, have become available and some in vivo data are now available to complement studies in cells in culture. However, the in vivo data are somewhat contradictory and limited by the small cohorts used and the lack of standard well-characterized reagents and protocols.

Breast Neoplasms↗
PubMed2004

The steroid receptor RNA activator is the first functional RNA encoding a protein.

The steroid receptor RNA activator (SRA) has previously been characterized as belonging to the growing family of functional non-coding RNAs. However, we recently reported the Western blot detection of a putative endogenous SRA protein (SRAP) in breast cancer cells. Herein, we successfully suppressed the expression of this protein through specific RNA interference assay, unequivocally confirming its existence. Moreover, using database searches and Western blot analysis, we also showed that SRAP is highly conserved among chordata. Overall, our results suggest that SRA is the first example of a new class of functional RNAs also able to encode a protein.

Amino Acid Sequence↗
PubMed2003

Current practice in the management of vasectomy reversal and unobstructive azoospermia in Merseyside & North Wales: a questionnaire-based survey.

OBJECTIVE: To investigate the current incidence of vasectomy reversal procedures, the techniques used and which practitioners use them. PATIENTS AND METHODS: Using a questionnaire, 130 general surgeons and urologists practising in Merseyside and North Wales were surveyed. RESULTS: The response rate was 74%, with 24 urological surgeons and 14 general surgeons undertaking vasectomy reversal. Annually, urological surgeons carried out significantly more procedures than did general surgeons, at 8.5 and 5.3 (P = 0.029), respectively. They were also more likely to use double-layer closure and microsurgical techniques, whilst significantly less likely to use stents. Urologists reported significantly greater patency rates, at 76% and 52% (P = 0.017), respectively, with no significant differences in subsequent pregnancy rates (30% vs 25%). Only one practitioner checked tubal patency in the female partner before vasectomy reversal. CONCLUSIONS: The use of vasectomy reversal is a cost-effective treatment for men wanting paternity after vasectomy. The technique used by the clinician and proper audit of the results require close attention; it would also appear to be obvious that all the partners of men seeking a vasectomy reversal should have their fertility status established before reversal, something that is clearly not done at present.

Attitude of Health Personnel↗
PubMed2002

Surgical sperm retrieval after previous vasectomy and failed reversal: clinical implications for in vitro fertilization.

OBJECTIVE: To investigate the effect of the interval between previous vasectomy reversal on retrieval rates of epididymal and testicular spermatozoa using percutaneous epididymal sperm aspiration (PESA), or testicular sperm extraction (TESE), and the subsequent reproductive potential of these gametes in intracytoplasmic sperm injection (ICSI) cycles. PATIENTS AND METHODS: Sixty-six consecutive sperm retrievals were considered in patients who were azoospermic after previous vasectomy, of whom 54 had had a previous failed reversal, the remainder deciding against a reversal. PESA and TESE retrieval rates were noted, as were the time since vasectomy and the interval between vasectomy and unsuccessful reversal. The presence of palpable epididymal cysts was noted, with their effect on sperm retrieval rates. Fertilization and pregnancy rates were analysed in subsequent ICSI cycles using freshly retrieved spermatozoa or frozen-thawed cryopreserved spermatozoa. RESULTS: All 66 patients had sperm retrieved successfully; the success rates for PESA were not significantly affected by previous failed reversal when compared with patients who had not had a reversal, at 14 of 54 (26%) vs five of 12 (P=0.3). The interval since vasectomy did not affect PESA retrieval rates but there was a significantly poorer retrieval rate for PESA in the presence of palpable epididymal cysts, at seven of 35 (20%) vs 12 of 23 (52%) (P=0.012). Fertilization rates were significantly lower using cryopreserved spermatozoa retrieved from either the epididymis or testis (50% vs 70%, P=0.007), although subsequent implantation and pregnancy rates were not significantly different. CONCLUSION: Surgical sperm retrieval is successful in all cases of azoospermia secondary to vasectomy, either by PESA or TESE. There are no clinical markers to indicate which patients will have successful PESA after vasectomy, although the presence of epididymal cysts is associated with significantly lower retrieval rates. The reduction in fertilising ability of cryopreserved spermatozoa does not affect clinical pregnancy rates in ICSI cycles.

Adult↗
PubMed2000

Altered expression of estrogen receptor coregulators during human breast tumorigenesis.

The hypothesis that altered expression of specific coactivators/repressors of the estrogen receptor occurs during human breast tumorigenesis in vivo is examined in this study. Using in situ hybridization and reverse transcription-PCR assays, the expression of two coactivators (SRA and AIB1) and one repressor (REA) of the estrogen receptor was compared between matched breast tumors and adjacent normal human breast tissue. The levels of SRA and AIB1 mRNA were increased in tumors compared with normal tissues (n = 19; Wilcoxon matched pairs test; P < 0.01). In contrast, the expression of REA mRNA was not different between tumors and normal tissues (n = 19; Wilcoxon; P = 0.110). The ratios of AIB1:REA and SRA:REA were higher (Wilcoxon; P < 0.05) in tumors compared with normal tissues. Furthermore, SRA:AIB1 was higher (Wilcoxon; P = 0.0058) in tumors compared with normal tissues. Although our study is small, these data are consistent with the above hypothesis and suggest that such alterations may have a role in the altered estrogen action occurring during breast tumorigenesis.

Breast↗
PubMed2000

Expression of a repressor of estrogen receptor activity in human breast tumors: relationship to some known prognostic markers.

The expression of a specific repressor of estrogen receptor activity (REA) was investigated by a semiquantitative reverse transcription-PCR assay in 40 human breast tumor biopsy samples with respect to steroid hormone receptor status and other known prognostic variables. The data showed that REA expression was positively correlated with estrogen receptor (ER) levels as defined by ligand-binding assays (Spearman r = 03231; P = 0.042) and that the median level of REA mRNA was significantly (Mann-Whitney two-tailed test, P = 0.0424) higher in ER+ tumors (median = 94.5; n = 30) compared with ER- tumors (median = 645; n = 10), with no significant differences (P = 0.4988) associated with progesterone receptor status alone. In addition, REA expression was inversely correlated with tumor grade (Spearman r = -0.4375; P = 0.0054). When the tumors were divided into two groups based on grade, REA expression was significantly (Mann-Whitney two-tailed test, P = 0.0024) higher in low-grade (median = 97; n = 16) compared with high-grade (median = 76; n = 23) tumors. These results provide preliminary data suggesting that the expression of REA varies among breast tumors and is correlated with known treatment response markers and inversely correlated with a marker of breast cancer progression. REA together with ER status may be an improved marker of endocrine therapy responsiveness in human breast cancer.

Biomarkers, Tumor↗
PubMed2000

Lumican and decorin are differentially expressed in human breast carcinoma.

Previous studies have shown that lumican is expressed and increased in the stroma of breast tumours. Lumican expression has now been examined relative to other members of the small leucine-rich proteoglycan gene family in normal and neoplastic breast tissues, to begin to determine its role in breast tumour progression. Western blot study showed that lumican protein is highly abundant relative to decorin, while biglycan and fibromodulin are only detected occasionally in breast tissues (n=15 cases). Further analysis of lumican and decorin expression performed in matched normal and tumour tissues by in situ hybridization showed that both mRNAs were expressed by similar fibroblast-like cells adjacent to epithelium. However, lumican mRNA expression was significantly increased in tumours (n=34, p<0.0001), while decorin mRNA was decreased (p=0.0002) in neoplastic relative to adjacent normal stroma. This was accompanied by a significant increase in lumican protein (n=12, p=0.0122), but not decorin. Further evidence of altered lumican expression in breast cancer was manifested by discordance between lumican mRNA and protein localization in some regions of tumours but not in adjacent morphologically normal tissues. It is concluded that lumican is the most abundant of these proteoglycans in breast tumours and that lumican and decorin are inversely regulated in association with breast tumourigenesis.

Adult↗
PubMed1999

Mammaglobin, a potential marker of breast cancer nodal metastasis.

The Mammaglobin gene, a breast-specific member of the uteroglobin gene family, has been previously identified as being overexpressed in some breast tumours, but the cellular origin and relationship to tumour progression are unknown. Using a subtractive hybridization approach, mammaglobin mRNA has also been found to be overexpressed in the in situ compared to the invasive element within an individual breast tumour. Further study by in situ hybridization performed in 13 breast tumours, selected to include normal, in situ, and invasive primary tumour elements, and in most cases axillary lymph node metastases, revealed that mammaglobin expression occurs in all elements, is restricted to epithelial cells, and is significantly increased in tumour cells compared with normal cells ( p< 0.04). Analysis of mammaglobin expression within 20 independent primary breast tumours and their corresponding axillary lymph nodes revealed that all 13 lymph nodes positive and none of the seven nodes negative for metastatic breast carcinoma by histology were mammaglobin-positive by reverse transcription-polymerase chain reaction (RT-PCR) ( p=0.0001). These results suggest that mammaglobin could be a marker of axillary lymph node breast metastases.

Adult↗