Cytotoxic activity of Fagonia cretica against human breast cancer cells

In many parts of the world, plants are directly utilised for their medicinal properties. Traditional medicine from Pakistan, India and the Far East is well documented and its history is embedded in folklore. It has been documented that an aqueous extract of the desert shrub, Fagonia cretica, is a popular treatment for breast cancer in Pakistan. The administration of an aqueous extract of Fagonia cretica is reported effective at reducing tumour size and improving the quality of life of breast cancer patients, is well tolerated and does not exhibit adverse effects like vomiting, diarrhoea or alopecia which are common side effects of standard cytotoxic therapy. In the past, many pharmacologically active and chemotherapeutic compounds have been isolated from plants which subsequently have proven to be successful in clinical trials and been used as primary compounds in therapeutic regimes. Fagonia cretica has historical use as a treatment for breast cancer, yet there is little scientific evidence which shows chemotherapeutic potential towards breast tumours. Preparation and analysis of an aqueous extract of Fagonia cretica may reveal novel chemotherapeutic agents that can be used to effectively target cancer cells. An understanding of the mechanism of any activity may improve our understanding of cancer cell biology and reveal novel therapeutic targets. This thesis describes for the first time that an aqueous extract of Fagonia cretica shows potent in vitro cytotoxic activity towards breast cancer epithelial cell lines which was not seen towards normal mammary epithelial cells. Elucidation and characterisation of the cytotoxic mechanism was undertaken by analysing DNA damage, cell cycle status, apoptosis, metabolic state and expression of transcription factors and their targets. Finally, methods for the isolation and identification of active compound(s) were developed using various chromatographic techniques. An aqueous extract of Fagonia cretica was able to reduce cell viability significantly in two phenotypically different breast cancer cell lines (MCF-7 and MDA-MB-231). This activity was markedly reduced in normal mammary epithelial cells (HMEpC). Further investigation into the mode of action revealed that extract treatment induced cell cycle arrest and apoptosis in both MCF-7 and MDA-MB-231 cell lines. This coincided with the formation of DNA double stranded breaks and the DNA repair marker ?-H2AX. In MCF-7 cells, ATM/ATR activation resulted in increased p53 expression and of its transcriptional targets p21 and bax, suggesting a role for a p53-mediated response. Furthermore, inhibition of extract-induced p53 expression with siRNA reduced the cytotoxic effect against MCF-7 cells. Extract treatment was also associated with increased FOXO3a expression in MCF-7 and MDA-MB-231 cells. In the absence of functional p53, siRNA knockdown of extract-induced FOXO3a expression was completely abrogated, suggesting that FOXO3a plays a vital role in extract-induced cytotoxicity. Isolation and characterisation of the active compound(s) within the extract was attempted using liquid chromatography and mass spectrometry in conjunction with a cell viability assay. Multiple fractionations generated an active fraction that contained four major compounds as detected by mass spectrometry. However, none of these compounds were identified structurally or chemically due to constraints within the methodology.

A prosztatarák gazdasági terhe nagy betegregiszterek alapján (The economic burden of prostate cancer. A systematic literature overview of registry-based studies)

INTRODUCTION: Prostate cancer, the most frequent malignant disease in males in Europe, accounts for a great proportion of health expenditures. AIM: A systematic review of registry-based studies about the cost-of-illness and related factors of prostate cancer, published in the last 10 years. METHOD: A MEDLINE-based literature review was carried out between January 1, 2003 and October 1, 2013. RESULTS: Fifteen peer-reviewed articles met the criteria of interest. In developed countries radiotherapy, surgical treatment and hormone therapy account for the greatest per capita costs. In Europe early stage tumours (4-7000 €, 2006), while in the USA metastatic prostate cancer (19 900-25 500 $, 2004) was associated with highest per capita expenses. In Europe the greatest costs incurred within the initial treatment (6400 €/6 months, 2008), while in the USA within the end-of-life care (depending on age: 62 200-93 400 $, 2010). CONCLUSIONS: Despite public health importance of prostate cancer, the cost-of-illness literature from Europe is relatively small.

The epidemiology of prostate cancer among multiethnic men

The research goal was to document differences in the epidemiology of prostate cancer among multicultural men [non-Hispanic White (NHW), Hispanic (H), non-Hispanic Black (NHB)], and Black subgroups, particularly among NHB subgroups [US-born (USB) and Caribbean-born (CBB)]. Study findings will be useful in supporting further research into Black subgroups. Aim 1 explored changes over time in reported prostate cancer prevalence, by race/ethnicity and by birthplace (within the Black subgroups). Aim 2 investigated relationships between observed and latent variables. The analytical approaches included confirmatory factor analysis (CFA for measurement models) and structural equation modeling (SEM for regression models). National Center for Health Statistics, National Health Interview Survey (NHIS) data from 1999–2008 were used. The study sample included men aged 18 and older, grouped by race/ethnicity. Among the CBB group, survey respondents were limited to the English-speaking Caribbean. Prostate cancer prevalence, by race showed a higher trend among NHB men than NHW men overall, however differences over time were not significant. CBB men reported a higher proportion of prostate cancer among cancers diagnosed than USB men overall. Due to small sample sizes, stable prostate cancer prevalence trends could not be assessed over time nor could trends in the receipt of a PSA exam among NHB men when stratified by birthplace. USB and CBB men differ significantly in their screening behavior. The effect of SES on PSA screening adjusted for risk factors was statistically significant while latent variable lifestyle was not. Among risk factors, family history of cancer exhibited a consistent positive effect on PSA screening for both USB and CBB men. Among the CBB men, the number of years lived in the US did not significantly affect PSA screening behavior. When NHB men are stratified by birthplace, CBB men had a higher overall prevalence of prostate cancer diagnoses than USB men although not statistically significant. USB men were 2 to 3 times more likely to have had a PSA exam compared to CBB men, but among CBB men birthplace did not make a significant difference in screening behavior. Latent variable SES, but not lifestyle, significantly affected the likelihood of a PSA exam.

The effects of age, ethnicity, sexual dysfunction, urinary incontinence, masculinity, and relationship with the partner on the quality of life of men with prostate cancer

Prostate cancer, the leading cause of cancer in men, has positive survival rates and constitutes a challenge to men with its side effects. Studies have addressed the bivaritate relationships between prostate cancer treatment side effects masculinity, partner relationship, and quality of life (QOL). However, few studies have highlighted the relationships among prostate cancer treatment side effects (i.e., sexual dysfunction, urinary incontinence), masculinity, and relationship with the partner together on QOL in men. Most studies were conducted with predominately Caucasian sample of men. Miami is a unique multiethnic setting that hosts Cuban, Columbian, Venezuelan, Haitian, other Latin American and Caribbean communities that were not represented in previous literature. The purpose of this study was to examine relative contributions of age, ethnicity, sexual dysfunction, urinary incontinence, masculinity, and perception of the relationship with the partner on the quality of life in men diagnosed with prostate cancer. Data were collected using self administered questionnaires measuring demographic variables, sexual and urinary functioning (UCLA PCI), masculinity (CMNI), partner relationship (DAS), and QOL (SF-36). A total of 117 partnered heterosexual men diagnosed with prostate cancer were recruited from four urology clinics in Miami, Florida. Men were 67.47 (SD = 8.42) years old and identified themselves to be of Hispanic origin (54.3 %, n = 63). Findings demonstrated that there was a significant moderate negative relationship between urinary and sexual functioning of men. There was a significant strong negative association between men's perceived relationship with partner and masculinity. There was a weak negative relationship between the partner relationship and QOL. Hierarchal multiple regression showed that the partner relationship (β = -.25, t (91) = -2.28, p = .03) significantly contributed overall to QOL. These findings highlight the importance of the relationship satisfaction in the QOL of men with prostate cancer. Nursing interventions to enhance QOL for these men should consider strengthening the relationship and involving the female partner as an active participant.^

Regulation of Pygopus (hPygo2) expression in prostate cancer by E74-Like factor 1 (Elf-1) transcription factor

Prostate cancer is a worldwide health concern. Pygopus2 (hPygo2) protein is required for growth in breast, ovarian, cervical and prostate cancer. hPygo2 expression is regulated by the Rb protein via the ETS factor Elf-1 in cervical and breast cancer. Additionally, the ETS family has confirmed roles in carcinogenesis and proliferation. The mechanism of hPygo2 expression has not been elucidated in prostate cancer. My hypothesis proposes that hPygo2 expression is regulated by Elf-1 bound to its promoter region. Prostate cancer cell lines were used to show protein levels of hPygo2, Elf-1 and ETS. ChIP assays confirmed varying binding capability of Elf-1 and ETS factors to the proximal promoter region between cell lines. Elf-1 knockdown experiments were performed, results show no change in hPygo2 protein levels but show reduction in 22Rv1 mRNA levels. These results suggest that Elf-1 might not be exclusively involved in the activation of Pygopus expression in prostate cancer.

Role of Hormonal Treatment in Prostate Cancer Patients with Nonmetastatic Disease Recurrence After Local Curative Treatment : A Systematic Review

Peer reviewed

Targeting androgen receptor activation function-1 with EPI to overcome resistance mechanisms in castration-resistant prostate cancer

Financial support: This research was supported by grants to MDS from the NCI (2R01CA105304), the Canadian Institutes of Health Research (MOP79308) and the US Army Medical Research and Materiel Command Prostate Cancer Research Program (E81XWH-11-1-0551). Research by IJM’s group was supported by the Chief Scientist’s Office of the Scottish Government (ETM-258 and -382). We are grateful to Country Meadows Senior Men’s Golf Charity Classic for financial support of this research.

EPI-001, a compound active against castration-resistant prostate cancer, targets transactivation unit 5 of the androgen receptor

ACKNOWLEDGEMENTS We thank J. M. Valverde (IRB) as well as the NMR facilities of the University of Barcelona (CCiT UB) and the Instituto de Química Física Rocasolano (IQFR, CSIC) for their assistance in, respectively, protein production and NMR. This work was supported by IRB, ICREA (X.S.), Obra Social “la Caixa” (Fellowship to E.D.M. and CancerTec grants to X.S.) MICINN (CTQ2009-08850 to X.S.), MINECO (BIO2012-31043 to X.S.; CTQ2014-56361-P to A.R), Marató de TV3 (102030 to X.S. and 102031 to E.E.P) the COFUND programme of the European Commission (C.T.W.P., A. R. and X.S.), the European Research Council (CONCERT, contract number 648201, to X.S.), the Ramón y Cajal program of MICINN (RYC-2011-07873 to C.W.B.) the Serra Hunter Programme (E.E.P.) and AGAUR (SGR-2014-56RR14 to E.E.P). IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO (Government of Spain)

Predictors of adaptation in wives during the initial psychosocial phase of prostate cancer

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Fatty acid metabolism and modulation of human breast cancer cell survival

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Prostate cancer screening

Universal screening for prostate cancer (Pca) using prostate-specific antigen-based testing is not recommended, as the potential harms of screening (overdiagnosis and overtreatment) outweigh potential benefits. The case for Pca screening requires a paradigm shift, which emphasizes the risks of screening over the risks of undetected cancer. Physicians are encouraged to use shared decision making with patients who express an interest in Pca screening, taking into account both the patient's screening preferences and individual risk profile. New models of care informed by the Patient Protection and Affordable Care Act are intended to assist clinicians in providing recommended preventive services. © 2014 Elsevier Inc.