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Biomedical subjects

M J Kerin

Publications and source records attributed to M J Kerin.

At least 19 recordsLinked to original sources
PubMed2006

Molecular profiling techniques and bioinformatics in cancer research.

AIMS: Our aim was to describe the commonly used molecular profiling techniques in cancer research, to examine their limitations and to discuss the challenges of bioinformatics. METHODS: A literature search was performed using the PubMed database to identify publications relevant to this review. Citations from these articles were also examined to yield further relevant publications. RESULTS: We describe the use of DNA microarrays, comparative genomic hybridisation, tissue microarrays and digital differential display. The limitations of these technologies, their contribution to cancer research and the challenges of bioinformatics are also discussed. CONCLUSIONS: Although these high throughput technologies each have their own limitations they are rapidly developing and contributing significantly to our understanding of cancer genetics. They have also led to the emergence of bioinformatics as a rapidly developing and vital field.

Biomarkers, Tumor↗
PubMed2006

Roles for the calcium sensing receptor in primary and metastatic cancer.

AIM: To review the role of the calcium sensing receptor (CASR) in colorectal, breast and parathyroid cancers and related cell lines, and to discuss the effects of CASR in the setting of bone metastases from breast cancer. METHODS: We performed a literature search of the PubMed database of the National Library of Medicine (NLM) to identify articles concerning the CASR's involvement in different cancers. Further relevant papers were obtained from the references of those identified in the original search. RESULTS: Loss of CASR expression is understood to be associated with abnormal differentiation and progression of colorectal carcinoma. It is expressed in both normal and malignant breast tissues and has been implicated in the vicious cycle of bone metastases through its interactions with the parathyroid hormone related peptide (PTHrP). In parathyroid tissue, CASR expression has been linked to proliferation of both parathyroid adenomas and carcinomas. CONCLUSION: Apart from its role in calcium homeostasis, the CASR has many diverse functions in a variety of tissue types throughout the body, and is involved in various signalling pathways relating to cell proliferation and differentiation. CASR has been shown to be involved in the progression and spread of a variety of cancers such as colorectal, breast and parathyroid, and is likely to be the focus of much research to further elucidate its precise role.

Bone Neoplasms↗
PubMed2005

The role of sentinel lymph node biopsy in ductal carcinoma in situ.

AIM: To review the role of sentinel lymph node (SLN) biopsy in the surgical management of patients with ductal carcinoma in situ (DCIS). METHODS: A search was conducted of Medline and the National Library of Medicine to identify key articles concerning DCIS, SLN biopsy (SLNB) and axillary dissection. Further relevant articles were obtained from the references cited in the literature. RESULTS: Up to 20% of patients with a core biopsy diagnosis of DCIS will be later up-staged based on an invasive component identified on the excision specimen. Quality assurance in breast screening programmes requires minimally invasive pre-operative diagnosis and also axillary sampling in the case of documented invasive disease. As an effective and validated procedure, SLNB represents a paradigm shift in the surgical management of the axilla for patients with invasive breast cancer. It remains undefined which, if any, subgroups of patients with DCIS should undergo SLNB. CONCLUSION: Axillary lymphadenectomy is an overtreatment for patients with DCIS. Performing a SLNB during the initial procedure may avoid a second operation in some DCIS patients who are diagnosed with occult invasive disease at their definitive operation. When predictors of hidden invasive disease are clarified by further study, SLNB may be used in the management of selected high-risk DCIS patients.

Axilla↗
PubMed2005

Inhibition of the stress response to breast cancer surgery by regional anesthesia and analgesia does not affect vascular endothelial growth factor and prostaglandin E2.

Angiogenesis is essential for breast cancer metastases formation and is mediated by vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2). We hypothesized that serum levels of VEGF and PGE2 are increased by the stress response to breast cancer surgery and attenuated by paravertebral anesthesia and analgesia (PVAA). Thirty women undergoing mastectomy were enrolled in this prospective, randomized study, to receive general anesthesia (GA) and postoperative opioid analgesia (morphine 0.1 mg/kg bolus and patient-controlled infusion) or GA and PVAA (72-h infusion). All patients received rectal diclofenac. Venous blood samples were taken preoperatively and at 4 and 24 h postoperatively for serum glucose, cortisol, C-reactive protein, VEGF, and PGE2. PVAA inhibited the surgical stress response, as indicated by significantly less plasma glucose, cortisol, and C-reactive protein. VEGF and PGE2 values did not differ significantly between the groups. Mean (SD) percentage change in VEGF at 4 and 24 h respectively were 3% +/- 44% versus 9% +/- 80%, P=0.29 and 5% +/- 43% versus -10% +/- 63%, P=0.41 for patients with combined general and PVAA and GA alone, respectively. Mean percentage change in postoperative PGE2 at 4 and 24 h respectively was 10% +/- 17% versus 11% +/- 69%, P=0.29 and 34% +/- 19% versus 47% +/- 18%, P=0.15. We conclude that despite inhibiting the surgical stress response, PVAA had no effect on serum levels of putative breast cancer angiogenic factors, VEGF and PGE2.

Adult↗
PubMed2004

Minimally invasive parathyroidectomy with operative ultrasound localization of the adenoma.

BACKGROUND: Minimally invasive parathyroidectomy is the procedure of choice for primary hyperparathyroidism due to parathyroid adenoma. Adequate perioperative adenoma localization is essential for this operation. We describe a technique using ultrasound to perform minimally invasive parathyroidectomy. METHODS: 99mTc sestamibi scanning was performed on patients with primary hyperparathyroidism to localize parathyroid adenomas; no intraoperative gamma probe was used. We also performed pre- and intraoperative ultrasound scanning to localize these adenomas. RESULTS: All patients underwent successful localization and removal of their parathyroid adenomas. At follow-up, all patients were well, with calcium within normal limits. CONCLUSION: The use of intraoperative ultrasound facilitates minimally invasive parathyroidectomy and may obviate the need for intraoperative 99mTc sestamibi scanning.

Adenoma↗
PubMed2004

Estrogen receptor alpha and beta profiling in human breast cancer.

BACKGROUND: The identification of a second estrogen receptor (ER-beta) has significant implications for therapeutic strategy in breast cancer management arising from the potential agonist effect of Tamoxifen at estrogen receptor sites and as such, antiestrogen therapy may be inappropriate in patients with a dominance of ER-beta. METHODS: To determine the proportion of breast cancer patients who may be so at risk, we developed a novel multiplexed RT-PCR technique to establish the relative ER-alpha and ER-beta levels in 53 primary breast cancers, 11 normal breast tissues and six cell lines. We further assessed the prognostic significance of receptor status relative to the Nottingham prognostic index (NPI). The ER-alpha and ER-beta status was also determined by immunohistochemistry using previously published and 'in-house' scoring systems. RESULTS: Using RT-PCR analysis, 46 tumours were hormone receptor positive (ER+) with 42 displaying ER-alpha predominance. Comparison with immunohistochemistry demonstrated 44/53 (ER-alpha) and 27/50 (ER-beta) concordance rates. There was no significant difference in the NPI between ER-alpha and ER-beta predominant cohorts or between ER+ and ER- cohorts. CONCLUSION: This study identifies the existence of a subgroup of ER+ patients in whom Tamoxifen therapy may be inappropriate and has significant implications for adjuvant therapy of primary breast cancer.

Adult↗
PubMed2004

Estrogen receptor beta and breast cancer.

A second estrogen receptor, estrogen receptor-beta, was identified in 1996 and has led to an intensive re-evaluation of the role of estrogens in normal physiological and disease processes. While much has been learnt about this new receptor, there remain many outstanding questions, particularly regarding its prognostic significance and therapeutic implications.

Breast Neoplasms↗
PubMed2002

Breast reconstruction in the United Kingdom and Ireland.

BACKGROUND: Although it is becoming more common, previous surveys have identified concerns regarding the safety of immediate reconstruction following mastectomy. The aims of this study were to define current practice of breast reconstruction in the UK and Ireland, and to identify the characteristics of surgeons who use immediate breast reconstruction. METHODS: : A postal questionnaire survey of 498 consultant breast surgeons in the UK and Ireland was performed in January 2000. RESULTS: There were 376 responses (response rate 76 per cent). Eighty-eight per cent of surgeons 'always' or 'usually' discuss reconstruction with patients due to undergo mastectomy; clinicians with a heavy caseload were significantly more likely to discuss it (odds ratio (OR) 18.45 (95 per cent confidence interval 1.99 to 171.07)). The majority of respondents (57 per cent) preferred delayed to immediate breast reconstruction; 70 per cent believed that immediate reconstruction has disadvantages, most commonly that it interferes with adjuvant therapy (56 per cent). Older surgeons were significantly less likely to perform immediate reconstruction (OR 5.18 (2.21 to 12.11)), and were significantly more likely to believe that immediate breast reconstruction has disadvantages (OR 2.02 (1.01 to 4.05)). Surgeons from Ireland were less likely to discuss and perform breast reconstruction (OR 0.20 (0.10 to 0.43) and 0.27 (0.12 to 0.60) respectively), or to have access to a plastic surgeon (OR 0.22 (0.11 to 0.44)). CONCLUSION: : Significant variation exists in the delivery of breast reconstruction after mastectomy in the UK and Ireland. The age, workload and personal characteristics of the surgeon are important in determining reconstructive practice.

Adult↗
PubMed2001

Evaluation of response to neoadjuvant chemoradiotherapy for locally advanced breast cancer with dynamic contrast-enhanced MRI of the breast.

AIMS: This study aimed to examine the feasibility of utilizing dynamic contrast-enhanced MRI (DCE-MRI) of the breast for the planning of surgical intervention following neoadjuvant therapy for locally advanced breast cancer (LABC). METHODS: Following their neoadjuvant therapy, women with LABC were followed-up by DCE-MRI in addition to clinical examination and mammography. If any modality suggested residual disease, surgery was carried out--initially salvage mastectomy and then breast-conserving surgery where appropriate. RESULTS: Seventeen women were recruited: stage III (n=16), stage IV (n=1) mean age 55 (range 34-74). Following neoadjuvant therapy, 10 mastectomies and two local excisions were performed for 10 histologically confirmed residual cancers. Median follow-up for those women not undergoing surgery is 3.24 (IQR 2.8-3.5) years. DCE-MRI proved 100% accurate for the delineation of residual disease and facilitated the planning of the local excisions. Clinical examination and mammography proved inaccurate (PPV 83% and 75% and NPV 55% and 80%, respectively). CONCLUSIONS: DCE-MRI is a potentially accurate method of delineating residual tumour following neoadjuvant therapy for LABC and may be used to plan appropriate operative intervention where required.

Adult↗
PubMed2001

Serum vascular endothelial growth factor in breast cancer: its relation with cancer type and estrogen receptor status.

PURPOSE: Angiogenesis is essential for tumor growth. Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic cytokines. In breast cancer, tumor VEGF has been shown to have a good correlation with relapse-free survival. The aim of this study was to determine the relation of serum VEGF levels to the various indices of breast cancer and known tumor markers carcinoembryonic antigen and CA15.3. EXPERIMENTAL DESIGN: Preoperative serum VEGF levels were determined in 200 women with breast cancer and compared with serum VEGF levels in 88 healthy female controls. RESULTS: The serum VEGF levels of the cancer patients as a group were significantly elevated compared with those of the controls (P < 0.0005). VEGF levels were elevated in patients with invasive cancer of ductal/no specific type, ductal carcinoma in situ, and estrogen receptor (ER)-positive tumors. Patients with lobular carcinoma and ER-negative tumors had serum VEGF levels comparable with those in the controls. VEGF was more sensitive than CA15.3 and carcinoembryonic antigen in detecting breast cancer. CONCLUSIONS: Preoperative serum VEGF detects breast cancer with a sensitivity of 62.1%. The relationship to cancer type and ER status may have future therapeutic implications. Additional long-term studies are required to determine the prognostic significance of serum VEGF.

Breast Neoplasms↗
PubMed2000

Genetic changes in breast cancer detected by comparative genomic hybridisation.

Breast cancer is characterised by a number of genetic aberrations. Our purpose was to use comparative genomic hybridisation (CGH) to screen breast carcinomas for copy number changes: 44 ductal and 8 lobular carcinomas were studied and a large number of genetic aberrations identified. Many of these showed similarity to previous CGH results, however, a number of loci not previously shown to have undergone frequent change were identified. This included copy number gains affecting chromosomes 1p, 4q, 5q, 6q and 13q. Furthermore, we have identified 2 regions of copy number change, the gain on 5p and deletion of 16q, which correlated with lobular carcinomas. Our results highlight several areas of the genome that may be important in the molecular genetics of breast cancer.

Adult↗
PubMed2000

Prognostic significance of oestrogen receptor beta in breast cancer.

BACKGROUND: Endocrine therapy for breast cancer is now well established and with the identification of a second oestrogen receptor, ERbeta, 3 years ago it is timely to review the possible significance of this receptor in breast cancer management. METHODS: An up-to-date review of the current literature concerning the role and possible implications of ERbeta in human breast cancer was undertaken. RESULTS: Wild-type and variant ERbeta are expressed in human breast tumours. Expression of ERbeta correlates with accepted prognostic indicators including lymph node status and tumour grade. Furthermore, levels of ERbeta messenger RNA alter during carcinogenesis and are upregulated in breast tumours that develop antioestrogen resistance. CONCLUSION: ERbeta has potential as a novel clinical prognostic marker in breast cancer, particularly in determining tumours that are resistant to tamoxifen.

Alternative Splicing↗
PubMed2000

Direct activation of oestrogen receptor-alpha by interleukin-6 in primary cultures of breast cancer epithelial cells.

Interleukin 6 (IL-6) is secreted by breast tumours and shows synergistic activity with 17beta-oestradiol (E2), leading to increases in reductive 17beta-hydroxysteroid dehydrogenase activity in breast cancer epithelial cells. However, the mechanisms involved are poorly understood. Using short-term epithelial cultures established from primary breast tumours, we have examined whether IL-6 could directly affect transcriptional activity of oestrogen reception alpha (ERalpha). Tumour epithelial cultures were established from 15 breast tumours, grown to 70% confluence and transiently transfected with a plasmid reporter containing the vitellogenin oestrogen response element and the luciferase coding sequence (ERE-TK-LUC). Following transfection, cells were incubated with E2, IL-6, the pure anti-oestrogen ZM 182780 or combinations of these substances for 48 h. Luciferase activity was then measured in cell lysates. E2 caused a dose-dependent increase in luciferase expression, causing a maximum threefold stimulation at 100 pM. In the presence of IL-6, transcriptional activity was increased by up to 2.5-fold in ERalpha+ cultures (11/15). In combination with E2, synergistic effects were observed with increases in luciferase activity of up to sixfold over controls. This effect could be blocked by treatment with ZM 182780. Pre-incubation of cells with an antibody directed against the signalling component of IL-6, gp130, was ineffective in blocking the E2 response. This antibody reduced, but did not completely block the effect of IL-6 either alone or in combination with E2, suggesting cross-talk between the two signalling pathways. In conclusion, these results provide evidence for direct transcriptional activation of ERalpha by IL-6.

Breast Neoplasms↗
PubMed2000

Gilmore's groin repair in athletes.

Incapacitating groin pain is a frequent problem among athletes and its etiology may be multifactorial. A specific clinical syndrome relating to injury to the lower abdominal wall has been described and successfully treated by O. J. Gilmore. This paper presents our results of 100 consecutive groin repairs in 85 young athletes using a diagnostic and therapeutic strategy similar to Gilmore's. Ninety-six percent of our patients returned to competitive sport within 15 weeks; we suggest that this is an appropriate therapeutic intervention for athletes who develop chronic incapacitating groin pain.

Adolescent↗
PubMed1999

Increased expression of estrogen receptor beta mRNA in tamoxifen-resistant breast cancer patients.

Tamoxifen is currently the first-line therapy for treatment of hormone-dependent breast cancer. However, despite initial benefits, most patients eventually relapse. Two groups of patients were identified: (a) a tamoxifen-sensitive group (n = 8); and (b) a tamoxifen-resistant group (n = 9). Using reverse transcription-PCR, the relative expression of mRNA for both estrogen receptor (ER) beta and transforming growth factor beta1 was determined in each patient group and quantified against a known reference standard. ER-beta mRNA was significantly up-regulated in the tamoxifen-resistant group as compared with the tamoxifen-sensitive group (P = 0.001 by Fisher's exact test), and, consistent with previous findings, transforming growth factor beta1 was also up-regulated in the tamoxifen-resistant cohort (P = 0.02). The importance of ER-beta in tamoxifen resistance was validated using tamoxifen-sensitive and -resistant cell lines, in which it was demonstrated that ER-beta mRNA was significantly up-regulated in the resistant cells. These results lend further support to a role for ER-beta as a poor prognostic factor in breast cancer.

Aged↗