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Search Results: 1 - 10 of 43 matches for " Kefah Mokbel "
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Skin-Sparing Mastectomy: An Update for Clinical Practice  [PDF]
Kelly Lambert, Kefah Mokbel
Surgical Science (SS) , 2013, DOI: 10.4236/ss.2013.41010
Abstract:

Aim: To review the oncological safety and aesthetic advantage of skin-sparing mastectomy (SSM) for invasive breast cancer (IBC) and ductal carcinoma in-situ (DCIS). Controversies including the impact of radiotherapy (RT) on immediate breast reconstruction (IBR), preservation of the nipple-areola complex (NAC) and the role of endoscopic mastectomy are also considered. Methods: Literature review using Medline and PubMed. Results: SSM is safe in selected cases; including IBC < 5 cm, multi-centric tumours, DCIS and for risk-reduction surgery. Inflammatory breast cancers and tumours with extensive involvement of the skin represent contra-indications to SSM due to an unacceptable risk of local recurrence. SSM can facilitate IBR and is associated with an excellent aesthetic result. Prior breast irradiation or the need for post-mastectomy radiotherapy (PMRT) do not preclude SSM, however the cosmetic outcome may be adversely affected. Nipple/areola preservation is safe for peripherally located node negative tumours. A frozen section protocol for the retro-areolar tissue should be considered in these cases. The advent of acellular tissue matrix systems has widened the applicability of implant-based immediate reconstruction following SSM. Data on endoscopic mastectomy is limited and superiority over conventional SSM has not been demonstrated. Conclusion: SSM is safe in selected cases and is associated with advantages over simple mastectomy, including a superior aesthetic outcome and a potential reduction in the number of reconstructive procedures per patient.

Current Treatment of DCIS  [PDF]
Christina Choy, Kefah Mokbel
Journal of Cancer Therapy (JCT) , 2014, DOI: 10.4236/jct.2014.52022
Abstract:

Abstract: Ductal carcinoma in-situ DCIS is a heterogeneous entity in breast neoplasm with unpredictable biological behavior. This poses challenge in the management of DCIS. Various trials on DCIS have shown good outcome with integral treatment of adequate surgery, radiotherapy and hormonal therapy. Identification of subgroup of DCIS for radiotherapy and hormonal therapy could improve recurrence rate, contralateral tumours incidence and perhaps overall survival. Various risk score calculations could help to direct radiotherapy and hormonal treatment verses surgery alone and to avoid over treatment. Oncotype DX assay could be a new way of risk calculation to direct types of DCIS treatment. The recent increased use of MRI could increase the detection of DCIS and a more accurate extent of disease estimation. This article is a summary of major literatures and major trials result for DCIS.

Skin-Sparing Mastectomy and Breast Reconstruction: An Update for Clinical Practice  [PDF]
Abdul Kasem, Christina Choy, Kefah Mokbel
Journal of Cancer Therapy (JCT) , 2014, DOI: 10.4236/jct.2014.53034
Abstract:

Aim: To provide an up-to-date review of the literature on skin-sparing mastectomy (SSM) for breast cancer (BC). The article also reviews the oncological safety, effects of radiotherapy (RT) on immediate breast reconstruction (IBR), the indications for preserving the nipple-areola complex (NAC) and the emerging role of allogenic grafts as adjuncts to implant in IBR. Methods: Review of the English literature from 1965 to 2013 was carried out using Medline and PubMed research engines. Results: SSM is oncologically safe in appropriately selected cases of invasive breast cancer (IBC) and ductal carcinoma in-situ (DCIS) including IBC < 5 cm, multi-centric tumours, DCIS and for risk-reduction surgery. Inflammatory breast cancer and tumours with extensive skin involvement represent contra-indications to SSM due to an unacceptable risk of local recurrence. Prior breast irradiation or the need for post-mastectomy radiotherapy (PMRT) do not preclude SSM with IBR, however the aesthetic outcome may be compromised by radiation. Preservation of the nipple-areola complex (NAC) has aesthetic and psychological benefits and is safe for peripherally located node negative unifocal

Ductal Carcinoma In Situ: Recent Advances and Future Prospects
Kelly Lambert,Neill Patani,Kefah Mokbel
International Journal of Surgical Oncology , 2012, DOI: 10.1155/2012/347385
Abstract: Introduction. This article reviews current management strategies for DCIS in the context of recent randomised trials, including the role of sentinel lymph node biopsy (SLNB), adjuvant radiotherapy (RT) and endocrine treatment. Methods. Literature review facilitated by Medline, PubMed, Embase and Cochrane databases. Results. DCIS should be managed in the context of a multidisciplinary team. Local control depends upon clear surgical margins (at least 2?mm is generally acceptable). SLNB is not routine, but can be considered in patients undergoing mastectomy (Mx) with risk factors for occult invasion. RT following BCS significantly reduces local recurrence (LR), particularly in those at high-risk. There remains a lack of level-1 evidence supporting omission of adjuvant RT in selected low-risk cases. Large, multi-centric or recurrent lesions should be treated by Mx and immediate reconstruction should be discussed. Adjuvant hormonal treatment may reduce the risk of LR in selected cases with hormone sensitive disease. Conclusion. Further research is required to determine the role of new RT regimes and endocrine therapies. Biological profiling and molecular analysis represent an opportunity to improve our understanding of tumour biology in DCIS to rationalise treatment. Reliable identification of low-risk lesions could allow treatment to be less radical. 1. Introduction 1.1. Diagnosis The introduction of national mammographic screening programmes and the increasing use of digital mammography and MRI have dramatically changed the clinical presentation of DCIS. Prior to this, DCIS made up a small proportion of all breast malignancy and was only diagnosed in patients presenting with a palpable mass, pathological nipple discharge, or occasionally found as an incidental biopsy finding [1, 2]. In contrast, it is now most frequently identified in asymptomatic women with screen-detected micro calcifications [3] and makes up a larger proportion of breast malignancy. Approximately one fifth of all screen-detected breast cancers are now DCIS [4]. Although the rates of all breast malignancy have increased with time, between 1980 and 1995, Western countries have experienced a four-fold “increase” in the incidence of DCIS specifically, particularly in women of screening age [5]. Data from a systematic review of 374 studies reported the pooled incidence of DCIS in the early 1970s as 5.8/100000 and this had risen to 32.5/100000 in 2004 [6]. A higher proportion of the cases post screening were non comedo DCIS, which is considered less aggressive. Screening and cancer registry
Risk-reducing strategies for women carrying brca1/2 mutations with a focus on prophylactic surgery
Mohamed Salhab, Selina Bismohun, Kefah Mokbel
BMC Women's Health , 2010, DOI: 10.1186/1472-6874-10-28
Abstract: The literature review is facilitated by Medline and PubMed databases. The cross-referencing of the obtained articles was used to identify other relevant studies.Prophylactic surgery (bilateral mastectomy, bilateral salpingo-oophorectomy or a combination of both procedures) has proved to be the most effective risk-reducing strategy. There are no randomised controlled trials able to demonstrate the potential benefits or harms of prophylactic surgery; therefore, the evidence has been derived from retrospective and short follow-up prospective studies, in addition to hypothetical mathematical models.Based on the current knowledge, it is reasonable to recommend prophylactic oophorectomy for BRCA1 or BRCA2 mutation carriers when childbearing is completed in order to reduce the risk of developing breast and ovarian cancer. In addition, women should be offered the options of rigorous breast surveillance, chemoprevention with anti-oestrogens--especially for carriers of BRCA2--or bilateral prophylactic mastectomy.The selection of the most appropriate risk-reducing strategy is not a straightforward task. The impact of risk-reducing strategies on cancer risk, survival, and overall quality of life are the key criteria considered for decision-making. Notably, various other factors should be taken into consideration when evaluating individual mutation carriers' individual circumstances, namely woman's age, morbidity, type of mutation, and individual preferences and expectations.Although prospective randomised controlled trials concerned with examining the various interventions in relation to the woman's age and type of mutation are needed, randomisation is extremely difficult and rather deemed unethical given the current available evidence from retrospective studies.Breast cancer remains the leading cause of death in women aged 40-55 years[1]. Sporadic breast cancer accounts for 70-80% of all cases [2]. It is estimated that 5-10% of all breast cancers and 25%-40% of breast cancers
Brain-derived neurotrophic factor expression predicts adverse pathological & clinical outcomes in human breast cancer
Neill Patani, Wen G Jiang, Kefah Mokbel
Cancer Cell International , 2011, DOI: 10.1186/1475-2867-11-23
Abstract: BC tissues (n = 127) and normal tissues (n = 33) underwent RNA extraction and reverse transcription, BDNF transcript levels were determined using real-time quantitative PCR. BDNF protein expression in mammary tissues was assessed with standard immuno-histochemical methodology. Expression levels were analyzed against tumour size, grade, nodal involvement, TNM stage, Nottingham Prognostic Index (NPI) and clinical outcome over a 10 year follow-up period.Immuno-histochemical staining revealed substantially greater BDNF expression within neoplastic cells, compared to normal mammary epithelial cells. Significantly higher mRNA transcript levels were found in the BC specimens compared to background tissues (p = 0.007). The expression of BDNF mRNA was demonstrated to increase with increasing NPI; NPI-1 vs. NPI-2 (p = 0.009). Increased BDNF transcript levels were found to be significantly associated with nodal positivity (p = 0.047). Compared to patients who remained disease free, higher BDNF expression was significantly associated with local recurrence (LR) (p = 0.0014), death from BC (p = 0.018) and poor prognosis overall (p = 0.013). After a median follow up of 10 years, higher BDNF expression levels were significantly associated with reduced overall survival (OS) (106 vs. 136 months, p = 0.006). BDNF emerged as an independent prognostic variable in multivariate analysis for disease free survival (DFS) (p = 0.026) and approached significance for OS (p = 0.055).BDNF expression was found to be significantly higher in BC specimens compared to normal tissue. Higher transcript levels were significantly associated with unfavourable pathological parameters including nodal positivity and increasing NPI; and adverse clinical outcomes including LR, death from BC, poor prognosis, reduced DFS and OS. BDNF offers utility as a prognostic marker and potential for targeted therapeutic strategies.Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin (NT) superfamily of polyp
The Role of Suppressors of Cytokine Signalling in Human Neoplasms
Walid Sasi,Anup K. Sharma,Kefah Mokbel
Molecular Biology International , 2014, DOI: 10.1155/2014/630797
Abstract: Suppressors of cytokine signalling 1–7 (SOCS1–7) and cytokine-inducible SH2-containing protein (CIS) are a group of intracellular proteins that are well known as JAK-STAT and several other signalling pathways negative feedback regulators. More recently several members have been identified as tumour suppressors and dysregulation of their biological roles in controlling cytokine and growth factor signalling may contribute to the development of many solid organ and haematological malignancies. This review explores their biological functions and their possible tumour suppressing role in human neoplasms. 1. Cytokines and Their Signalling Pathways Cytokines are a large family of secreted soluble glycoproteins that regulate cellular growth and differentiation which are part of fundamental biological processes including embryonic development, immunity, wound healing, and haematopoiesis. Cytokines carry information about the biological status to target cells by interacting with receptors on the cell surface. Cellular responses to cytokine stimulation depend on the type of cytokine and the nature of the target cell and include proliferation, differentiation, effector function, and survival [1, 2]. Cytokines activate multiple intracellular signalling pathways in order to produce their physiological effects. One of the most studied pathways is that involving the receptor-associated janus kinases (JAKs) and the latent cytoplasmic transcription factors signal transducers and activators of transcription (STATs) [3, 4]. Genetic deletion experiments in mice have demonstrated that this pathway is critical for the actions of specific cytokines. For example, STAT1 is absolutely required for the actions of interferons, STAT4 is absolutely necessary for the actions of interleukin-12 (IL-12), STAT6 is required for the actions of interleukin-4 (IL-4), and JAK3 is required for the actions of cytokines that use the common γ receptor [5]. This cascade requires strict cellular control and loss of regulation can promote tumorigenesis and chronic inflammation. The threshold, magnitude, and specific responses elicited by cytokine stimulation are regulated by numerous mechanisms including tyrosine phosphatases, receptor internalisation, proteasomal degradation of signalling adaptor molecules, soluble receptor antagonists, and specific inhibitors, including the protein inhibitors of activated STATs (PIAS) and suppressor of cytokine signalling (SOCS) proteins. The expression of SOCS proteins can be induced by cytokine stimulation, and they not only serve to interfere with signalling
Evidence for Tumour Suppressor Function of DOK7 in Human Breast Cancer  [PDF]
James Bracken, Tamara Ghanem, Abdul Kasem, Wen G. Jiang, Kefah Mokbel
Journal of Cancer Therapy (JCT) , 2014, DOI: 10.4236/jct.2014.51009
Abstract:

Introduction: Downstream of tyrosine kinase 7 (DOK-7) is a member of the DOK family, which has been associated with the development and progression of various humancancers. Previously, identification of CpG hypermethylation in DOK-7 promoter was identified in breast cancer. Method: DOK-7 mRNA extraction and reverse transcription were performed on fresh frozen breast cancer tissue samples and normal background breast tissue. Transcript levels of expression were analyzed against TNM stage, tumour grade and clinical outcome over a 10-year follow-up period. Results: Levels of DOK-7 expression decreased significantly with increasing TNM stage. Higher DOK-7 expression was correlated with longer disease free and overall survival times. Conclusion: To our knowledge, this is the first study to investigate DOK-7 expression in human breast cancer. We identify a potential DOK-7 tumour suppressor role. DOK-7 as a prognostic biomarker in human breast cancer should be included in future validation studies.

Higher expression levels of SOCS 1,3,4,7 are associated with earlier tumour stage and better clinical outcome in human breast cancer
Walid Sasi, Wen G Jiang, Anup Sharma, Kefah Mokbel
BMC Cancer , 2010, DOI: 10.1186/1471-2407-10-178
Abstract: SOCS1-7 mRNA extraction and reverse transcription were performed on fresh frozen breast cancer tissue samples (n = 127) and normal background breast tissue (n = 31). Transcript levels of expression were determined using real-time PCR and analyzed against TNM stage, tumour grade and clinical outcome over a 10 year follow-up period.SOCS1,4,5,6 and 7 expression decreased with increased TNM stage (TNM1 vs. TNM3 p = 0.039, TNM1 vs. TNM4 p = 0.016, TNM2 vs. TNM4 p = 0.025, TNM1 vs. TNM3 p = 0.012, and TNM1 vs. TNM3 p = 0.044 respectively). SOCS2 and 3 expression decreased with increased Nottingham Prognostic Index (NPI) (NPI1 vs. NPI3 p = 0.033, and NPI2 vs. NPI3 p = 0.041 respectively). SOCS7 expression decreased with higher tumour grade (Grade 3 vs. Grade 2 p = 0.037). After a median follow up period of 10 years, we found higher levels of SOCS1,2 and 7 expression among those patients who remained disease-free compared to those who developed local recurrence (p = 0.0073, p = 0.021, and p = 0.039 respectively). Similarly, we found higher levels of SOCS 2,4, and 7 expression in those who remained disease-free compared to those who developed distant recurrence (p = 0.022, p = 0.024, and p = 0.033 respectively). Patients who remained disease-free had higher levels of SOCS1 and 2 expression compared to those who died from breast cancer (p = 0.02 and p = 0.033 respectively). The disease free survival (DFS) and overall survival (OS) curves showed that higher levels of SOCS1, 3 and 7 were significant predictors of higher DFS (p = 0.015, p = 0.024 and 0.03 respectively) and OS (p = 0.005, p = 0.013 and p = 0.035 respectively). Higher levels of SOCS 4 were significant in predicting better OS (p = 0.007) but not DFS. Immunohistochemical staining of representative samples showed a correlation between SOCS1, 3, 7 protein staining and the SOCS1, 3, 7 mRNA expression.Higher mRNA expression levels of SOCS1, 3, 4 and 7 are significantly associated with earlier tumour stage and better cli
The mRNA expression of SATB1 and SATB2 in human breast cancer
Neill Patani, Wen Jiang, Robert Mansel, Robert Newbold, Kefah Mokbel
Cancer Cell International , 2009, DOI: 10.1186/1475-2867-9-18
Abstract: Breast cancer tissues (n = 115) and normal background tissues (n = 31) were collected immediately after excision during surgery. Following RNA extraction, reverse transcription was carried out and transcript levels were determined using real-time quantitative PCR and normalized against β-actin expression. Transcript levels within the breast cancer specimens were compared to the normal background tissues and analyzed against TNM stage, nodal involvement, tumour grade and clinical outcome over a 10 year follow-up period.The levels of SATB1 were higher in malignant compared with normal breast tissue (p = 0.0167). SATB1 expression increased with increasing TNM stage (TNM1 vs. TNM2 p = 0.0264), increasing tumour grade (grade1 vs. grade 3 p = 0.017; grade 2 vs. grade 3 p = 0.0437; grade 1 vs. grade 2&3 p = 0.021) and Nottingham Prognostic Index (NPI) (NPI-1 vs. NPI-3 p = 0.0614; NPI-2 vs. NPI-3 p = 0.0495). Transcript levels were associated with oestrogen receptor (ER) positivity (ER(-) vs. ER(+) p = 0.046). SABT1 expression was also significantly correlated with downstream regulated genes IL-4 and MAF-1 (Pearson's correlation coefficient r = 0.21 and r = 0.162) and SATB2 (r = 0.506). After a median follow up of 10 years, there was a trend for higher SATB1 expression to be associated with shorter overall survival (OS). Higher levels of SATB2 were also found in malignant compared to background tissue (p = 0.049). SATB2 expression increased with increasing tumour grade (grade 1 vs. grade 3 p = 0.035). SATB2 was associated with ER positivity (ER(-) vs. ER(+) p = 0.0283) within ductal carcinomas. Higher transcript levels showed a significant association with poorer OS (p = 0.0433).SATB1 mRNA expression is significantly associated with poor prognostic parameters in breast cancer, including increasing tumour grade, TNM stage and NPI. SATB2 mRNA expression is significantly associated with increasing tumour grade and poorer OS. These results are consistent with the notion that SA
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