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Androgen signalling in normal and malignant breast epithelial cells.Peters, Amelia Alice January 2008 (has links)
The growth and survival of normal breast epithelial cells and breast cancer cells is promoted by estrogens. In contrast, androgens inhibit the proliferation of normal and malignant breast epithelial cells. While this effect of androgens on breast cells appears to be androgen receptor (AR) dependent, the precise mechanism of inhibition and its functional significance are unknown. The aims of this thesis were to investigate the effect of androgen signalling on growth of normal and malignant breast epithelial cells, and to assess the interactions between androgen and estrogen signalling in the breast. To investigate the role of androgen signalling in the growth and development of the normal mammary gland, female mice were treated with either the native androgen 5α- dihydrotestosterone (DHT) or the antiandrogen, flutamide. Analysis of the mammary glands at the end of the treatment period demonstrated that DHT reduced ductal branching and mammary epithelial cell proliferation when treatment commenced mid-puberty. Conversely, flutamide treatment that commenced post-puberty significantly increased ductal branching and proliferation of mammary epithelial cells. This data demonstrates that androgen signalling inhibits proliferation in the normal mammary gland, and may therefore oppose to the growth stimulatory effects of estrogen signalling to regulate breast growth and development. The antiproliferative effects of androgens on breast epithelial cells may be due in part to direct AR-mediated activation of androgen regulated genes, or alternatively, androgens could act indirectly through AR to inhibit estrogen receptor alpha (ERα) activity. Expression of fulllength AR or a truncated, constitutively active AR (AR-T707) significantly inhibited the activity of ectopically expressed ERα in MDA-MB-231 breast cancer cells (ERα- and ARnegative), in a dose-dependent manner. The functional consequences of inhibition of estrogen signalling by overexpressing AR were investigated in the T-47D breast cancer cell line (ERα- and AR-positive). Expression of AR-T707 in T-47D cells resulted in inhibition of both basal and estradiol-induced cell proliferation and a marked reduction in the steady-state protein levels of the estrogen regulated gene, PR. The final chapter investigated the mechanism by which AR inhibits ERα activity. A coimmunoprecipitation assay demonstrated an interaction between ectopically expressed AR and ERα in COS-1 cells, but not endogenous AR and ERα in a breast cancer cell line. To delineate the regions of AR required for inhibition of ERα signalling, various functional domains of the AR were mutated or deleted. Reporter gene assays showed that the inhibitory effects of AR were abrogated by deletion or mutation of the DNA binding domain (DBD). Furthermore, overexpression of the AR-DBD alone was sufficient to inhibit ERα activity. Consistent with a requirement for the DBD of AR to inhibit ERα activity, mobility shift assays demonstrated binding of AR to the Xenopus vitellogenin A2 consensus estrogen response element (cERE); however AR/ERα heterodimers were not detected on a cERE. Consistent with these findings, molecular modelling demonstrated that it is feasible for the DBD of AR to bind to a cERE and that it is unlikely that AR/ERα heterodimers could bind. Chromatin immunoprecipitation demonstrated recruitment of AR to the promoters of endogenous estrogen regulated genes. The findings suggest that the inhibitory effect of AR on ERα activity may occur either via formation of non-functional AR/ERα heterodimers that are unable to bind to EREs, or AR homodimers competing effectively for binding to EREs, in ERα target genes. The results in this thesis demonstrate an inhibitory effect of androgen signalling on growth of normal and malignant breast epithelial cells. Additionally, the inhibition of breast epithelial cell proliferation by androgen signalling can be attributed, at least in part, to inhibition of ERα activity. These studies have provided insight into androgen action in the breast, and support a model whereby androgens balance the stimulatory effects of estrogen signalling in normal and malignant breast epithelial cells. / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2008
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The narrative construction of breast cancer a comparative case study of the Susan G. Komen Foundation and National Breast Cancer Coalitions' campaign strategies, messages, and effects /Olson, Amanda M. January 2005 (has links)
Thesis (Ph.D.)--Ohio University, August, 2005. / Title from PDF t.p. Includes bibliographical references (p. 188-196)
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Reconstrução mamária imediata utilizando retalho miocutâneo transverso de reto abdominal : influência na recorrência de câncer de mama em pacientes mastectomizadasZucatto, Ângela Erguy January 2009 (has links)
Introdução: O câncer de mama é a neoplasia maligna mais prevalente em mulheres. Em decorrência do diagnóstico tardio, a mastectomia radical modificada (MRM) permanece como tratamento cirúrgico de escolha para a maioria das pacientes portadoras da doença. Em pacientes mastectomizadas, a reconstrução mamária com retalhos miocutâneos é a técnica que apresenta melhor resultado a longo prazo. Material e métodos: O estudo compara as taxas de recorrência local e sistêmica e a sobrevida livre de doença em pacientes submetidas à MRM, associada ou não à reconstrução mamária imediata com retalho miocutâneo transverso do reto abdominal (TRAM). Resultados: O grupo submetido à TRAM apresentou recorrência local de 11,8% e sistêmica de 35,7%, e o grupo da MRM, 4,4 e 26,1%, respectivamente. A sobrevida livre de doença (tempo decorrido entre a cirurgia e a primeira recorrência) foi, em média, de 105,4 meses (IC95% 97,0-113,72) no grupo MRM e de 95,4 meses (IC95% 80,7-110,0) no grupo TRAM, não havendo diferença estatisticamente significativa entre os grupos (P = 0,147). Conclusões: Em pacientes portadoras de câncer de mama, a reconstrução mamária imediata com retalho miocutâneo transverso do reto abdominal não influencia o prognóstico da doença, devendo ser oferecida às pacientes que não apresentam contraindicação clínica ao procedimento. / Introduction: Breast cancer is the most prevalent malignant neoplasia among women. In cases of late diagnoses, modified radical mastectomy (MRM) remains the surgical treatment of choice for most women with this disease, and breast reconstruction with myocutaneous flaps is the technique with the best long-term results. Material and methods: Local and systemic recurrence rates were compared, as well as diseasefree survival of patients who underwent MRM with or without immediate breast reconstruction using transverse rectus abdominis myocutaneous flap (TRAM). Results: The TRAM group had a local recurrence rate of 11.8% and a systemic recurrence rate of 35.7%; for the MRM group, these rates were 4.4 and 26.1%, respectively. Disease-free survival time (from surgery to first recurrence) was 95.4 months (95%CI 80.7-110.0) in the TRAM group and 105.4 (95%CI 97.0-113.72) in the MRM group, but the difference was not statistically significant (P = 0.147). In patients with breast cancer, immediate breast reconstruction with TRAM did not affect disease prognosis, and may be indicated to all patients who undergo MRM, except those with any clinical contraindications to the procedure.
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Micro computed tomography assessment of tumor size in breast cancer compared to histopathological examinationSarraj, Wafa Mowafak 12 March 2016 (has links)
PURPOSE: The purpose of this study was to assess the ability of Micro Computed Tomography (Micro CT) to measure primary tumor size in breast lumpectomy specimens, as compared to the histopathological measurement.
METHODS: This was a diagnostic study involving women who were scheduled to have breast lumpectomy surgery at the Massachusetts General Hospital (MGH) Department of surgery from June 2011 - September 2011. Those who met the study eligibility criteria were recruited to participate in the study. The study was approved by the MGH Institutional Review Board (IRB). All the participants provided consent prior to their participation in the study. The lumpectomy specimens of 45 subjects were scanned by Micro CT scan for no longer than 15 minutes, they were then delivered to the gross pathology lab for processing via the standard pathological protocol. Later on, the maximum dimension of the invasive breast tumor was obtained from the Micro CT image and was compared to the corresponding pathology report for each subject.
RESULTS: We found that Micro CT tends to overestimate the breast malignant tumor size. However, there were few differences in T-stage classification between Micro CT and pathology. Overall, Micro CT demonstrated good agreement with pathological tumor size and staging. For Invasive ductal carcinoma, Micro CT showed a substantial agreement with pathological tumor size and staging. However, Micro CT showed no agreement with pathological tumor size and staging for invasive lobular carcinoma.
CONCLUSIONS: Micro CT is a promising modality in measuring and staging the invasive ductal carcinoma.
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Reconstrução mamária imediata utilizando retalho miocutâneo transverso de reto abdominal : influência na recorrência de câncer de mama em pacientes mastectomizadasZucatto, Ângela Erguy January 2009 (has links)
Introdução: O câncer de mama é a neoplasia maligna mais prevalente em mulheres. Em decorrência do diagnóstico tardio, a mastectomia radical modificada (MRM) permanece como tratamento cirúrgico de escolha para a maioria das pacientes portadoras da doença. Em pacientes mastectomizadas, a reconstrução mamária com retalhos miocutâneos é a técnica que apresenta melhor resultado a longo prazo. Material e métodos: O estudo compara as taxas de recorrência local e sistêmica e a sobrevida livre de doença em pacientes submetidas à MRM, associada ou não à reconstrução mamária imediata com retalho miocutâneo transverso do reto abdominal (TRAM). Resultados: O grupo submetido à TRAM apresentou recorrência local de 11,8% e sistêmica de 35,7%, e o grupo da MRM, 4,4 e 26,1%, respectivamente. A sobrevida livre de doença (tempo decorrido entre a cirurgia e a primeira recorrência) foi, em média, de 105,4 meses (IC95% 97,0-113,72) no grupo MRM e de 95,4 meses (IC95% 80,7-110,0) no grupo TRAM, não havendo diferença estatisticamente significativa entre os grupos (P = 0,147). Conclusões: Em pacientes portadoras de câncer de mama, a reconstrução mamária imediata com retalho miocutâneo transverso do reto abdominal não influencia o prognóstico da doença, devendo ser oferecida às pacientes que não apresentam contraindicação clínica ao procedimento. / Introduction: Breast cancer is the most prevalent malignant neoplasia among women. In cases of late diagnoses, modified radical mastectomy (MRM) remains the surgical treatment of choice for most women with this disease, and breast reconstruction with myocutaneous flaps is the technique with the best long-term results. Material and methods: Local and systemic recurrence rates were compared, as well as diseasefree survival of patients who underwent MRM with or without immediate breast reconstruction using transverse rectus abdominis myocutaneous flap (TRAM). Results: The TRAM group had a local recurrence rate of 11.8% and a systemic recurrence rate of 35.7%; for the MRM group, these rates were 4.4 and 26.1%, respectively. Disease-free survival time (from surgery to first recurrence) was 95.4 months (95%CI 80.7-110.0) in the TRAM group and 105.4 (95%CI 97.0-113.72) in the MRM group, but the difference was not statistically significant (P = 0.147). In patients with breast cancer, immediate breast reconstruction with TRAM did not affect disease prognosis, and may be indicated to all patients who undergo MRM, except those with any clinical contraindications to the procedure.
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AvaliaÃÃo do Tratamento Adjuvante com Tamoxifeno em Mulheres com CÃncer de Mama. / Evaluation of the Adjuvant Treatment with Tamoxifen in Women with Breast Cancer.Victor Hugo Medeiros Alencar 04 April 2006 (has links)
nÃo hà / O cÃncer de mama foi descrito hà muitos anos e documentado, pela primeira vez, por Imhotep, mÃdico, astrÃlogo e arquiteto egÃpcio, nascido em 2.650 antes de Cristo (a.C.) que recomendava Ãquela Ãpoca, como tratamento, a cauterizaÃÃo do tecido doente. Tamoxifeno à o fÃrmaco mais prescrito no tratamento do cÃncer de mama. Sua utilizaÃÃo à principalmente na modalidade adjuvante, em pacientes prà ou pÃs menopausadas, receptor de estrÃgeno e/ou progesterona positivos. à tambÃm utilizado no tratamento da doenÃa localmente avanÃada e metastÃtica e em menor proporÃÃo nas pacientes com contra-indicaÃÃo formal de cirurgia ou que se recusam a se submeter a esta modalidade de tratamento. Na neo-adjuvÃncia à utilizada apenas em ensaios clÃnicos. O tamoxifeno tambÃm diminui, na adjuvÃncia por cinco anos, a probabilidade de recidiva em 47% e de morte por cÃncer de mama em 26% e os dois principais efeitos colaterais, apesar de raros, sÃo aumento da prevalÃncia de cÃncer de endomÃtrio e de fenÃmenos tromboembÃlicos. Este estudo teve como objetivo principal avaliar as pacientes portadoras de cÃncer de mama, no Instituto do CÃncer do CearÃ, tratadas com tamoxifeno de forma adjuvante, no perÃodo de janeiro de 1993 a 1996, com relaÃÃo aos principais benefÃcios e efeitos colaterais, bem como anÃlise de sobrevivÃncia. ProntuÃrios de setecentos e quarenta e duas pacientes foram analisados no que diz respeito aos dados sÃcio- demogrÃficos, idade, status menopausal, estadiamento clÃnico e patolÃgico, dosagem de receptores de estrÃgeno e progesterona, casos de cÃncer de endomÃtrio, principais sÃtios de metÃstases, modalidade de tratamento cirÃrgico, radioterÃpico e quimioterÃpico, causas de Ãbito, tipo histolÃgico, status dos linfonodos axilares e anÃlise de sobrevivÃncia de acordo com o estadiamento. Concluiu-se que a maioria dos dados estÃo de acordo com a literatura e que o prejuÃzo da anÃlise foi resultante da qualidade dos registros realizados nos prontuÃrios, devendo cada vez mais os mÃdicos serem estimulados a documentar, de forma clara e legÃvel, o maior nÃmero de informaÃÃes possÃveis, nÃo apenas as positivas, mas todas aquelas que, mais freqÃentemente, possam ter relaÃÃo com a utilizaÃÃo de qualquer medicamento prescrito. / O cÃncer de mama foi descrito hà muitos anos e documentado, pela primeira vez, por Imhotep, mÃdico, astrÃlogo e arquiteto egÃpcio, nascido em 2.650 antes de Cristo (a.C.) que recomendava Ãquela Ãpoca, como tratamento, a cauterizaÃÃo do tecido doente. Tamoxifeno à o fÃrmaco mais prescrito no tratamento do cÃncer de mama. Sua utilizaÃÃo à principalmente na modalidade adjuvante, em pacientes prà ou pÃs menopausadas, receptor de estrÃgeno e/ou progesterona positivos. à tambÃm utilizado no tratamento da doenÃa localmente avanÃada e metastÃtica e em menor proporÃÃo nas pacientes com contra-indicaÃÃo formal de cirurgia ou que se recusam a se submeter a esta modalidade de tratamento. Na neo-adjuvÃncia à utilizada apenas em ensaios clÃnicos. O tamoxifeno tambÃm diminui, na adjuvÃncia por cinco anos, a probabilidade de recidiva em 47% e de morte por cÃncer de mama em 26% e os dois principais efeitos colaterais, apesar de raros, sÃo aumento da prevalÃncia de cÃncer de endomÃtrio e de fenÃmenos tromboembÃlicos. Este estudo teve como objetivo principal avaliar as pacientes portadoras de cÃncer de mama, no Instituto do CÃncer do CearÃ, tratadas com tamoxifeno de forma adjuvante, no perÃodo de janeiro de 1993 a 1996, com relaÃÃo aos principais benefÃcios e efeitos colaterais, bem como anÃlise de sobrevivÃncia. ProntuÃrios de setecentos e quarenta e duas pacientes foram analisados no que diz respeito aos dados sÃcio- demogrÃficos, idade, status menopausal, estadiamento clÃnico e patolÃgico, dosagem de receptores de estrÃgeno e progesterona, casos de cÃncer de endomÃtrio, principais sÃtios de metÃstases, modalidade de tratamento cirÃrgico, radioterÃpico e quimioterÃpico, causas de Ãbito, tipo histolÃgico, status dos linfonodos axilares e anÃlise de sobrevivÃncia de acordo com o estadiamento. Concluiu-se que a maioria dos dados estÃo de acordo com a literatura e que o prejuÃzo da anÃlise foi resultante da qualidade dos registros realizados nos prontuÃrios, devendo cada vez mais os mÃdicos serem estimulados a documentar, de forma clara e legÃvel, o maior nÃmero de informaÃÃes possÃveis, nÃo apenas as positivas, mas todas aquelas que, mais freqÃentemente, possam ter relaÃÃo com a utilizaÃÃo de qualquer medicamento prescrito. / Breast cancer is a disease that was described many years ago and has been documented, for the first time, by Imhotep, physician, astrologer and Egyptian architect, born in 2.650 before Christ (b.C.), who recommended, at that time, as a way of treatment, cauterization of the diseased tissue. Tamoxifen is the drug more prescribed in the treatment of breast cancer. Itâs use is mainly in the adjuvant modality, in pre or post menopaused patients positive estrogen and/or progesteron receptors. Itâs used in the treatment of locally advanced and metastatic disease and in smaller proportion in patients with formal contraindication of surgery or that refuse to submit this treatment modality. In the neoadjuvancy it is just used in clinical research. The tamoxifen also reduces in the adjuvant modality during five years, the probability of recurrence in 47% and deaths caused by breast cancer in 26% and the two main side effects, in spite of rare, are the increase of the prevalence of endometrial cancer and of thromboembolic phenomenas. This study had as main objective to evaluate the patients, breast cancer bearers, in the Institute of Cancer of CearÃ, treated with tamoxifen in the adjuvant form in the period of 1993 to 1996 regarding the main benefits and side effects, as well as survival analysis. Seven hundred forty-two patientsâprontuaries were analyzed in respect to the demographic datas, age, menopausal status, clinical and pathological staging, dosage of estrogen and/or progesterone receptors, cases of endometrial cancer, main local metastasis, modality of surgical treatment, radiotherapy and chemotherapy, death causes, histological type, status of the axillary lymph nodes and survival analysis in agreement with the staging. We concluded that most of the data is in agreement with the literature and that the demage of the analysis was resulting from the quality accomplished found in the prontuaries. Also, doctors should be more and more stimulated to document, in a clear and readable way, the largest number of possible information, not just the positive ones, but all those that more frequently can have relationships with the use of any prescribed medicine. / Breast cancer is a disease that was described many years ago and has been documented, for the first time, by Imhotep, physician, astrologer and Egyptian architect, born in 2.650 before Christ (b.C.), who recommended, at that time, as a way of treatment, cauterization of the diseased tissue. Tamoxifen is the drug more prescribed in the treatment of breast cancer. Itâs use is mainly in the adjuvant modality, in pre or post menopaused patients positive estrogen and/or progesteron receptors. Itâs used in the treatment of locally advanced and metastatic disease and in smaller proportion in patients with formal contraindication of surgery or that refuse to submit this treatment modality. In the neoadjuvancy it is just used in clinical research. The tamoxifen also reduces in the adjuvant modality during five years, the probability of recurrence in 47% and deaths caused by breast cancer in 26% and the two main side effects, in spite of rare, are the increase of the prevalence of endometrial cancer and of thromboembolic phenomenas. This study had as main objective to evaluate the patients, breast cancer bearers, in the Institute of Cancer of CearÃ, treated with tamoxifen in the adjuvant form in the period of 1993 to 1996 regarding the main benefits and side effects, as well as survival analysis. Seven hundred forty-two patientsâprontuaries were analyzed in respect to the demographic datas, age, menopausal status, clinical and pathological staging, dosage of estrogen and/or progesterone receptors, cases of endometrial cancer, main local metastasis, modality of surgical treatment, radiotherapy and chemotherapy, death causes, histological type, status of the axillary lymph nodes and survival analysis in agreement with the staging. We concluded that most of the data is in agreement with the literature and that the demage of the analysis was resulting from the quality accomplished found in the prontuaries. Also, doctors should be more and more stimulated to document, in a clear and readable way, the largest number of possible information, not just the positive ones, but all those that more frequently can have relationships with the use of any prescribed medicine.
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Fysisk aktivitet vid fatigue : En litteraturöversikt om fysisk aktivitet och dess påverkan på fatigue hos kvinnor med bröstcancer / Physical activity on fatigue : A literature review about physical activity and its impact on fatigue in women with breast cancerAcin, Helin, Jonasson, Hanna January 2017 (has links)
Bakgrund: Bröstcancer är den vanligaste cancerformen att drabbas av som kvinna. Många kvinnor upplever biverkningar från bröstcancerbehandlingen. En av de vanligaste biverkningarna är fatigue som kan upplevas i olika dimensioner. Sjuksköterskan har en viktig roll att informera, stödja och motivera patienten till att utföra egenvård före, under och efter bröstcancerbehandling. Syfte: Belysa olika former av fysisk aktivitet och dess påverkan på fatigue hos kvinnor vid behandling av bröstcancer. Metod: En litteraturöversikt genomfördes där elva kvantitativa studier valdes ut. Databaserna som användes var PubMed, MEDLINE with Full Text och ProQuest Nursing & Allied Health Database. Artiklarna har granskats, diskuterats och sammanfattats för att sedan kunnat urskilja likheter och skillnader. Resultat: Det framkom att utförandet av fysisk aktivitet i olika former hade en påverkbar effekt för att minska fatigue hos kvinnor vid behandling av bröstcancer. Resultatet ledde fram till en huvudrubrik: Fysisk aktivitet som bidrar till minskad fatigue med tre underrubriker: Aerob fysisk aktivitet, Kombination av aerob och muskelstärkande fysisk aktivitet samt Promenader som fysisk aktivitet. Diskussion: Utgår från fyra rubriker: Den fysiska aktivitetens upplägg och struktur, Hinder för att utföra fysisk aktivitet, Känslan av att utföra fysisk aktivitet och Sjuksköterskans stödjande funktion. Innehållet har diskuterats tillsammans med Dorothea E. Orems teori om egenvård, samt ny tillförd kvalitativ data. / Background: Breast cancer is the most common form of cancer that affects women. Many women experience side effects from breast cancer treatments. One of the most common side effects is fatigue that can be perceived in different dimensions. The nurse has an important role by informing, supporting and motivating the patient to perform self-care activities before, during and after breast cancer treatment. Aim: Illustrate different forms of physical activity and its effect on fatigue in women undergoing breast cancer treatment. Method: A literature review has been conducted where eleven quantitative studies were selected. The databases used were PubMed, MEDLINE with Full Text and ProQuest Nursing & Allied Health Database. The articles have been reviewed, discussed and summarized in order to distinguish between similarities and differences. Results: It was found that physical activity, in various forms, had an effect to reduce fatigue. The result led to a main heading: Physical activity’s effect on fatigue with three subheadings: Aerobic physical activity, Combination of aerobic and muscle strengthening physical activity and Walking as physical activity. Discussion: Four parts emerged from the result: The physical activity’s planning and structure, Barriers to perform physical activity, Positive experiences of physical activity and Nurse’s supportive function. The content has been discussed in conjunction with Dorothea E. Orem’s self-care theory and new applied qualitative data.
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The psychological experience of breast cancer and its recurrence : from quantification to interactionFalkson, Annette 22 May 2008 (has links)
Please read the abstract (Summary) in the section, 00front, of this document / Thesis (PhD (Psychology))--University of Pretoria, 2008. / Psychology / PhD / unrestricted
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Evaluation of ricinus communis semi-purified extracts' potential as anti-metastatic agents using metastatic breast cancer (MCF-7) cancer cellsMabasa, Rixile Forever January 2017 (has links)
Thesis (MSc. (Biochemistry)) -- University of Limpopo, 2017 / The malignancy of cancer cells is responsible for the high death rate in patients diagnosed with metastatic cancers. Medicinal plants represent a reservoir of bioactive compounds that can be useful in the management of cancer. In this study, semi-purified extracts of Ricinus communis leaves were evaluated for their potential to serve as an anti-metastatic agent by using in vitro assays that tested their effects on a number of processes related to metastasis. The exhaustive extraction procedure was employed to generate the crude acetone extracts of R. communis leaves. The crude extracts were then subjected to solvent-solvent fractionation to yield six semi-purified extracts (n-butanol, Chloroform, Ethyl-acetate, n-hexane, Methanol + H2O and H2O). Thin layer chromatography (TLC) was done to determine the phytochemical composition of the semi-purified extracts as well as their antioxidant potential. Non-polar fractions showed to have a diverse mixture of phytochemicals with, however, very limited antioxidant activity. On the other hand, polar fractions showed to have phytochemical compounds with strong antioxidant potential. TLC guided the selection of n-hexane and n-butanol as fractions of great phytochemical diversity and antioxidant activity, respectively. The selected fractions were then assessed for their effect on the viability of normal fibroblasts (BUD-8) and breast (MCF-7) cancer cells using the MTT assay. The n-butanol fraction was shown to significantly decrease the viability of BUD-8 at concentrations above 200 µg/ml. The n-hexane fraction, however, showed to significantly affect the viability of the cells even at lower concentrations. On the positive side, the reduced viability of BUD-8 cells after exposure to both fractions was followed by an increase in cell proliferation after 24 hours suggesting that the extracts exhibited cytostatic rather than cytotoxic effects. Treatment of MCF-7 cells with different concentrations (100-500 µg/ml) of the fractions showed a dose- and time-dependant decrease in cell viability. Hoechst stain also confirmed the non-toxicity of the fractions to MCF-7 cells at 100 and 200 µg/ml. The fractions also showed to possess free radical scavenging activities by reducing the amount of intracellular ROS as demonstrated by the DCFH-DA fluorescent assay. Fluorescence intensity was strongly reduced in cells treated with the fractions and elevated in H2O2-treated and untreated MCF-7 cells. The effect of the fractions on metastasis was assessed by determining their effects on MCF-7 cell migration, attachment and invasiveness using wound healing assay, adhesion assay and Boyden chamber invasion assay, respectively. The wound healing assay showed the fractions to have strong inhibitory activities on the migration of MCF-7 cells. The
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ability of the cells to attach to cell culture treated plates was also greatly reduced in cells treated with the fractions. The n-butanol fraction was demonstrated to exhibit a time- and dose-dependent inhibition on MCF-7 cell invasion by reducing the cells’ capability to penetrate through the matrigel matrix to the bottom of the porous membrane. Gelatin-zymography was done to assess the effect of the n-butanol fraction on activity of MMP-2 and MMP-9. The fraction showed to completely inhibit the gelatinolytic activity of MMP-2 and no band corresponding to the molecular weight of MMP-9 was observed, suggesting that MCF-7 cells produce undetectable levels of MMP-9. The n-butanol fraction further showed to down-regulate the expression of a range of proteins such as MMP-9, uPA, VEGF, TGF-β1 implicated in metastasis and angiogenesis determined using the human angiogenesis antibody array kit. This study demonstrated that the fractions of R. communis extracts have the ability to inhibit major processes of the metastatic cascade by down-regulating the expression of proteins relevant to metastasis. Thus, the fractions can be considered as potential anti-metastatic agents functional in the regulation and/or treatment of malignant of cancers. / National Research Foundation (NRF)
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Bi-rads final assessment categories in breast cancer patientsDaniels, Tasneem January 2019 (has links)
Thesis (MSc (Radiography))--Cape Peninsula University of Technology, 2019 / INTRODUCTION: The Breast Imaging Reporting and Data System (BI-RADS) was developed by the American College of Radiology (ACR). The BI-RADS is an internationally accepted method of assessing and reporting on mammograms and breast ultrasound images. The BI-RADS consists of a lexicon (descriptors) and assessment categories. The ACR aimed to standardise mammography reporting and placing the findings in the appropriate assessment category. The aim of this study was to establish the accuracy of the BI-RADS assessment categories for mammography and breast ultrasound images in women diagnosed with breast cancer. METHOD: Data were retrieved from 77 patients who were diagnosed with breast cancer from 1 January 2013 to 31 December 2014. Seven did not meet the inclusion criteria and were excluded. The study sample size was 70 (n=70) patients. All mammography reports included a BI-RADS assessment category of all patients diagnosed with breast cancer within the study period. These reports were analysed and compared with histopathology results. The BI-RADS assessment category and descriptors were collected from the mammogram reports; the histopathology report indicated the type of breast cancer. All reports were obtained from the patients' folders at the research site. In addition, questionnaires were distributed among radiologists to assess whether their experience and training had an influence on the accuracy of reporting in the BI-RADS assessment categories. Descriptive and inferential statistical analysis was used for data analysis. RESULTS: The most common malignancy diagnosed was invasive ductal carcinoma with a total of 70% (n=54), followed by ductal carcinoma in situ with 10.4% (n=8) and invasive lobular carcinoma with 9.1% (n=7). The histology results confirmed breast cancer for all BI-RADS 4 and 5 assessment categories. The mammogram was able to detect 93.5% of abnormalities and breast ultrasound 84.4% of abnormalities in this study sample. Breast ultrasound was used as an adjunct to mammography and hence an overall combined diagnostic rate was 100%. Mammography descriptors: The more common malignancy findings were spiculated mass margin, 35.1% (n=27). Ultrasound descriptors: The more common malignancy findings were hypoechoic echo pattern, 55.8% (n=43). There was no significant association (p=0.152) between the radiologists' years of experience and BI-RADS 3, 4 and 5 assessment category reporting. Of the 15 responses, 67% agreed that the BI-RADS standardises breast imaging reporting and reduces confusion, 33% agreed that the BI-RADS allows better communication between radiologists and referring physicians, and 40% agreed that the BI-RADS clarifies further management for patients by helping to stratify risk management. CONCLUSION: The outcome of this study indicated that the use of BI-RADS assessment categories is useful for predicting the likelihood of malignancy when used correctly. The outcome of BI-RADS 4 and BI-RADS 5 had a positive predictive value of 100%, which corresponded well with histology results. The descriptor findings suggested that spiculated mass margins, irregular-shaped masses, hypoechoic echo pattern and posterior shadowing were high predictors of malignancy and warranted a placement in the BI-RADS 5 assessment category.
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