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Biomedical subjects

K Mokbel

Publications and source records attributed to K Mokbel.

At least 37 records · Page 2Linked to original sources
PubMed2003

The evolving role of sentinel lymph node biopsy for breast cancer.

Recent studies have demonstrated that the sentinal node biopsy (SNB), which utilizes a simple principle, is a reliable and minimally invasive method for determining the status of the regional lymph nodes in patients with clinically node-negative breast cancer. The technique has been widely used in the management of patients with early breast cancer despite the lack of long-term data from randomised controlled trials which are currently in progress. The present article reviews the role of the SNB in the context of axillary node sampling and determines the requirements for its safe clinical application. It also highlights the need for further research to clarify the role of the SNB in high risk DCIS, the value of preoperative lymphascintigraphy, and the clinical relevance of internal mammary node dissection and focused examination of the sentinal node by immunohistochemistry and polymerase chain reaction.

Axilla↗
PubMed2003

hTERT expression in human breast cancer and non-cancerous breast tissue: correlation with tumour stage and c-Myc expression.

Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal length and stability thus leading to cellular immortalisation. hTERT (human telomerase reverse transcriptase) gene is the rate-limiting determinant of telomerase reactivation. The present study aims to quantitatively measure the expression of hTERT mRNA in human breast cancer, adjacent non-cancerous tissue (ANCT) and benign breast lesions, examine the association between hTERT and the clinicopathological characteristics of the cancer specimens and to explore the relationship between c-Myc and hTERT expressions. RNA was extracted from 49 breast carcinomas, 46 matched ANCT, and eight fibroadenomas. hTERT and c-Myc mRNA expressions were estimated by reverse transcriptase-PCR (RT-PCR) and Taqman methodology. hTERT mRNA was present in all of the cancerous and most of ANCT specimens with levels being much higher in the cancerous tissue than in ANCT. The ratio of hTERT mRNA in tumour to that in ANCT was 2011 (95% confidence interval 373-10,853, P < 0.0001). There was no significant association between tumour hTERT expression and patient's age, tumour size, grade, nodal metastasis, estrogen receptor (ER) positivity, lymphovascular (LVI) or c-Myc expression. However, there was a weak but significant negative correlation between hTERT expression and progesterone receptor (PR) status (p = 0.04) in tumours. hTERT mRNA expression was also significantly higher in carcinomas (median = 2.61 x 10(6)) than in fibroadenomas (median = 424).We conclude that hTERT mRNA expression is significantly higher in human breast cancer than in non-cancerous breast tissue suggesting that hTERT has a potential role in breast cancer diagnosis. The hTERT mRNA levels in tumour do not seem to be associated with the patient's age or advanced tumour stage. Furthermore, hTERT mRNA expression does not correlate with c-Myc mRNA expression in breast cancer.

Breast↗
PubMed2003

hTERT mRNA expression correlates with telomerase activity in human breast cancer.

AIMS: Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal length and stability thus leading to cellular immortalisation. hTERT (human telomerase reverse transcriptase) gene seems to be the rate-limiting determinant of telomerase reactivation. hTERT mRNA expression was reported to correlate with telomerase activity in cell lines and some human tumours. However the correlation between telomerase activity and hTERT mRNA expression has not been previously examined in human breast cancer. The present study aims to quantitatively measure the expression of hTERT mRNA and telomerase activity in human breast cancer and examine the relationship between these parameters. Furthermore the associations with other parameters including estrogen receptor (ER) and progesterone receptor (PgR) status, DNA ploidy, and S-phase fraction (SPF) are also examined. METHODS: RNA was extracted from 18 breast carcinomas and hTERT mRNA expressions were estimated by reverse transcriptase-PCR (RT-PCR) and Taqman methodology. These tumours had already been analysed for ER and PgR status using ligand-binding assays and had had their DNA ploidy and S-phase fractions measured by flow cytometry. Telomerase activity had already been determined by using a modified telomeric repeat and amplification protocol (TRAP) assay. RESULTS: The expression of hTERT mRNA in the breast tumours ranged between 1.3 and 2.7 x 10(7) copy numbers per micro g of cellular RNA (the median value was 2.7x10(5) and the mean was 3.1 x 10(6)). Telomerase activity was between 0 and 246 units of Total Protein Generated (TPG), where one unit of TPG was equal to 600 molecules, of telomerase substrate primers extended by at least three telomeric repeats. The median level of TPG was 60 units and the mean level was 81 units). Telomerase activity was found to significantly correlate with hTERT expression (r(s)=0.51112, P=0.0302). There was no significant correlation between hTERT and other parameters. CONCLUSION: hTERT mRNA expression significantly correlates with telomerase activity in human breast cancer. This is consistent with the hypothesis that hTERT is the catalytic and rate-limiting determinant subunit of the enzyme.

Adult↗
PubMed2003

Abdominal ganglioneuromas in adults.

Ganglioneuromas are rare tumours of the parasympathetic nervous system. Their definitive diagnosis is made on histological examination. When they arise from the adrenal medulla, their assessment and management are the same as those of other adrenal tumours. We here report 3 cases of ganglioneuromas highlighting important points regarding the radiological assessment, management, decision making and surgical approaches.

Adrenal Gland Neoplasms↗
PubMed2003

Cyclo-oxygenase-2 (COX-2) mRNA expression correlates with progesterone receptor positivity in human breast cancer.

BACKGROUND: We previously presented evidence showing that cyclo-oxygenase 2 (COX-2) plays an important role in mammary carcinogenesis and angiogenesis in human breast cancer. The present study aims to compare COX-2 mRNA expression with hormone receptor status, S-phase fraction, telomerase activity, and DNA ploidy in human breast cancer. METHODS: Total cellular RNA was extracted from frozen breast tissue samples according to standard methodology. The mRNA copy numbers for COX-2 were determined in 18 infiltrating carcinomas using quantitative RT-PCR and TaqMan methodology. The oestrogen receptor (ER) and progesterone receptor (PgR) status was determined using the ligand-binding technique (ER+ = > 3 fmol/mg, PgR+ = > 5 fmol/mg). We also determined DNA ploidy status (diploid or aneuploid), S-phase fraction (< 6% = low, 6-10% = intermediate, > 10% = high), and telomerase activity (total protein generated by TRAP assay). RESULTS: The median COX-2 mRNA copy number per micro g of RNA was 126 713 (range = 15 717-2 022 050). COX-2 expression was significantly associated with PgR positivity (p = 0.013). The association between COX-2 and DNA diploidy failed to reach a statistical significance (p = 0.085). No significant association was detected between COX-2 and S-phase fraction, ER status, or telomerase activity. CONCLUSIONS: COX-2 mRNA expression is associated with PgR positivity in human breast cancer. This observation is consistent with the hypothesis that COX-2 upregulates aromatase activity.

Breast Neoplasms↗
PubMed2003

British women's choice between sentinel node biopsy and axillary node clearance for breast cancer.

BACKGROUND: Recent studies have demonstrated that the sentinel node biopsy (SNB), which utilises a simple principle, is a reliable and minimally invasive method for determining the status of the regional lymph nodes in patients with clinically node-negative breast cancer. The technique is increasingly being used in the management of patients with early breast cancer despite the lack of long-term data from randomised controlled trials which are currently in progress. However, increasing numbers of breast cancer patients are specifically requesting SNB in order to avoid axillary nodal clearance (ANC) if the sentinel node is negative for malignancy. The aim of this study is to determine the proportion of female patients attending a breast unit who would choose the SNB in preference to ANC. METHODS: A detailed questionnaire, based on a utility analysis and containing clear and precise information on arm morbidity associated with ANC (1 in 10) versus a potential reduction in the 5-year-survival rate with SNB (1 in 1000) was distributed to 200 female patients attending the Princess Grace Hospital Breast Unit (London, UK) during January 2003. The questionnaire consisted of two possible treatment scenarios (ANC or SNB) for early-stage breast cancer with their associated risks and benefits, and participants were asked to choose one of the two options. RESULTS: A total of 200 completed questionnaires were received. Out of the 200 women, 99 (49.5%) chose the SNB option and 101 (50.5%) chose the ANC option. There is no significant relationship between the option made with a woman's age (mean age: 53.4 vs 54), family history of breast cancer (p = 0.118), personal history of breast cancer (p = 0.85), or employment status (p = 0.96). CONCLUSION: This study demonstrates that a high level of acceptance exists among women for SNB as an alternative to ANC as the preferred treatment of early breast cancer, despite the risk involved. As this exciting technique continues to evolve and improve, it is hoped that more women will be given the choice to opt for this treatment and that eventually SNB may completely replace ANC as the standard treatment for early breast cancer.

Adult↗
PubMed2003

Focus on anastrozole and breast cancer.

This commentary article provides an overview of recent clinical research trials involving anastrozole and its evolving role in the management of breast cancer. Anti-aromatase agents inhibit the cytochrome P-450 component of the aromatase enzyme complex responsible for the final step of estrogen biosynthesis in peripheral tissues which are the main source of estrogen in postmenopausal women. Anastrozole is a third-generation non-steroidal aromatase inhibitor. It has been shown to be superior to megestrol acetate, in terms of survival and adverse effects, as a second-line therapy in postmenopausal women with estrogen receptor (ER)- and/or progesterone receptor (PgR)-positive advanced breast cancer. Phase III clinical trials have also demonstrated that anastrozole significantly prolongs the time to tumour progression compared with tamoxifen as a first-line therapy for ER- and/or PgR-positive advanced breast cancer in postmenopausal women. Furthermore, the preliminary results of the Arimidex, Tamoxifen, Alone and in Combination (ATAC) study have shown that adjuvant anastrozole is superior to tamoxifen in terms of disease-free survival (DFS), non-musculoskeletal adverse effects and prevention of contralateral breast cancer in postmenopausal women with early, ER-positive breast cancer. Although longer follow-up is required to assess the long-term effects of anastrozole on bone mineral density, cognitive function and overall survival, the drug has been recently approved for adjuvant use in postmenopausal women with early, ER-positive breast cancer who are unable to tolerate tamoxifen or at an increased risk of developing thromboembolism or endometrial cancer. The potential role of anastrozole in the neoadjuvant setting, the management of DCIS, premenopausal breast cancer and breast cancer prevention is currently being investigated.

Anastrozole↗
PubMed2002

Current concepts in cyclooxygenase inhibition in breast cancer.

The prospect that simple medications such as non-steroidal anti-inflammatory drugs (NSAIDs) could be recruited into the physician's armamentarium of anticancer drugs is intriguing, especially in the context of breast cancer, one of the leading causes of mortality in the Western world. There has consequently been a wider exploration of the role of cyclooxygenase (COX) in breast cancer, and we now accept that COX-2, one of its isoenzymes, is clearly implicated in the pathogenesis of the disease. This would seem to translate into a viable role for cyclooxygenase inhibitors in the treatment and prevention of breast cancer, but also raises issues regarding safety and tolerability of these drugs. In this article we discuss the theoretical consequences of cyclooxygenase inhibition, the significance of findings from experimental studies, large scale epidermiological investigations, and the relevance of large population studies of COX-2 inhibitors such as CLASS and VIGOR.

Breast Neoplasms↗
PubMed2002

Telomerase activity and Bcl-2 expression in human breast cancer.

AIMS: Telomerase is a ribonucleoprotein that synthesizes telomeres and plays an important role in cellular immortalization. Bcl-2 gene encodes for a mitochondrial protein thought to prevent apoptosis of normal cells. We previously reported telomerase activity in 74% of human invasive breast cancers and detected a significant association between telomerase activity and prognostic parameters such as nodal status, tumour size and cellular proliferation. We hypothesized that telomerase reactivation in human breast cancer was associated with increased immunohistochemical expression of Bcl-2. METHODS: Bcl-2 immunohistochemical expression was determined in 25 infiltrating breast carcinomas with known telomerase activity (17 telomerase-positive and 8 telomerase-negative). The percentage of strongly and moderately stained tumour cells for Bcl-2 was determined by a breast pathologist who was blinded to telomerase data. Fisher's exact test was used to examine the association between telomerase activity and Bcl-2 expression. RESULTS: The median percentage of strongly stained tumour cells was 50% for telomerase-positive tumours (range, 0--100%) and 45% for telomerase-negative tumours (range, 0--100%). Twelve (70%) of 17 telomerase-positive tumours expressed strong or moderate Bcl-2 staining in >50% of tumour cells compared with six (75%) of eight telomerase-negative tumours (P=1.0). CONCLUSION: Telomerase reactivation seems to be independent of Bcl-2 protein expression in human breast cancer.

Adult↗
PubMed2002

The role of cyclooxygenase-2 (COX-2) in breast cancer, and implications of COX-2 inhibition.

The cyclooxygenase (COX) enzyme system is composed of two isoenzymes, COX-1 and COX-2. Recent sources of experimental and epidemiological evidence suggest a significant role for the COX enzymes, particularly COX-2, in the pathogenesis of breast cancer. This has important implications for treatment of the disease. This article reviews the evidence for a relationship between the COX enzyme system and mammary carcinogenesis, and discusses the likely therapeutic roles and potential pitfalls of COX inhibition.

Animals↗
PubMed2002

Recent advances in breast cancer (the Twenty-fourth San Antonio Breast Cancer Symposium, December, 2001).

This paper reviews the Twenty-fourth Annual San Antonio Breast Cancer Symposium. The preliminary results of the ATAC study have shown that Arimidex is superior to tamoxifen in postmenopausal women with ER-positive early breast cancer in terms of DFS, adverse effects and prevention of contralateral breast cancer. However, longer follow up is required to assess the drug safety regarding bone mineral density and cognitive function. Letrozole seems to be superior to tamoxifen as a first-line therapy in ER-positive advanced breast cancer in postmenopausal women. Although the incidence of acute myeloid leukaemia is significantly increased (cumulative incidence at 5 years = 1.1%) in breast cancer patients receiving cyclophosphamide and anthracyclines, the risk of this complication is easily outweighed by the benefits of chemotherapy. Adjuvant clodronate was found to be associated with a significant reduction in the incidence of bone metastases during the treatment period. A randomised trial comparing axillary dissection and axillary radiotherapy (RT) for early breast cancer reported no significant difference in survival at 15 years. However, axillary recurrence was significantly increased in the RT group. hTERT protein expression by IHC was found to correlate significantly with breast cancer-specific survival. There is no evidence to support the use of IHC of the sentinel node in routine clinical practice. LCIS is currently considered as a non-obligate precursor to breast cancer rather than just a risk factor.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Breast cancer chemoprevention--an update.

This article reviews the recent findings of the IBIS-1 and ATAC trials regarding the role of tamoxifen and anastrozole in the chemoprevention of breast cancer. It also emphasises the need to individualise chemoprevention strategies, and to identify high-risk women who are most likely to develop oestrogen receptor (ER)-positive breast cancer. The prevention of ER-negative disease requires further research, and is likely to be challenging.

Adult↗
PubMed2002

Advances in breast oncology: the 2002 ASCO meeting.

At this year's American Society of Clinical Oncology (ASCO) meeting, a number of important advances in breast cancer diagnosis, treatment and prevention were reported. In this article, we review these current developments, focusing particularly on the ASCO technology assessment report--which discussed the adjuvant use of aromatase inhibitors in breast cancer--and other significant studies which were presented or updated: the role of taxanes in neoadjuvant and adjuvant therapy; current concepts regarding the timing of hormonal therapy during adjuvant chemotherapy; and cyclooxygenase-2 (COX-2) as a target for disruption in breast cancer treatment and prevention. With regards to advances in surgery, we review studies which were presented concerning the evolving role of sentinel lymph node biopsy in the management of the axilla in breast cancer, and review the latest meta-analysis on this subject presented at the meeting.

Anastrozole↗
PubMed2002

Infiltrating fibromatosis of the breast: a potential pitfall.

Mammary fibromatosis is a rare condition. It presents a big dilemma for the clinician, because it mimics breast cancer clinically, radiologically and sometimes cytologically. We report a case of fibromatosis of the breast and highlight the diagnostic difficulties and management.

Biopsy↗