Findings from this pioneer study demonstrate that CF, which is unique to rice bran oil, is capable of triggering apoptosis in CRC cells at early stages of carcinogenesis. Furthermore, CF enhances TRAIL-induced apoptosis in metastatic CRC cells. This study provides clear evidence that the health-beneficial properties of whole grain consumption are not only limited by the presence of dietary fiber but also other molecules that can either act as a chemopreventive agent to directly induce tumor regression or a sensitizer to enhance TRAIL-induced apoptosis in metastatic cancer cells. / High intake of whole grain food has been suggested as an important factor for reducing the risk of colon cancer, owing to the abundance of indigestible fiber. Rice bran, which is a component of raw rice after removal of starchy endosperm in milling process, has been shown to be a rich source of some health-beneficial compounds for preventing cancer, hyperlipidaemia, fatty liver, hypercalciuria, kidney stones, and heart disease (Jariwalla, 2001). In the present study, proliferation-inhibitory effects of some rice bran polyphenolic compounds were investigated on a panel of human colorectal cancer (CRC) cell lines, including SW480 (stage B), SW620 (stage C) and Colo-201 (stage D) with increasing metastatic potential according to the Dukes' classification system. / Results from the MTT study revealed that, among the polyphenolic compounds tested, cycloartenyl ferulate (CF) showed the most prominent proliferation inhibition on the CRC cells. CF is one of the typical ferulic acid esters of triterpene alcohols present in rice bran oil. The cancer cell proliferation was reduced by 62, 31 and 21% of their control levels after 72 h of 200 muM CF treatment, respectively. CF seemed to possess higher ability to control proliferation of tumor cells at early stages of cancer development. In meanwhile, results from Toxilight study showed that CF had low toxicity on normal colon CCD-18-Co cells. The anticancer activity of CF was further illustrated by its ability to induce significant regression of SW480 xenograft in nude mice. CF was found to induce apoptosis in SW480 cells in vitro. DNA flow cytometric studies demonstrated that CF elevated dose- and time-dependently the sub G1 or apoptotic cells with fragmented DNA. The pro-apoptotic effect of CF was further confirmed using immunoblotting study showing cleavage of poly(ADP-ribose) polymerase (PARP), which is a hallmark feature of apoptosis. Besides, the executioner procaspase-3, -6 and -7 were found to be processed and activated. On the other hand, administration of pan-caspase inhibitor Z-VAD-FMK completely rescued the cells from PARP cleavage, indicating that CF elicited solely caspase-dependent apoptosis. Elevation of death receptors DR4 and DR5 with the CF treatment seems to originate the upstream activation of the initiator procaspase-8 and -10 of the extrinsic apoptosis pathway. Flow cytometric JC-1 studies further demonstrated that CF significantly altered the mitochondrial membrane potential in a dose-dependent manner together with cytochrome c and smac/DIABLO but not AIF release from mitochondria into the cytosol, as well as the activation of procaspase-9 of the intrinsic apoptosis pathway. Depletion of anti-apoptotic Bcl-2 and elevation of pro-apoptotic Bak were observed; meanwhile, Bid was found to be cleaved by caspase-8, so that the death receptor pathway might be exaggerated by the mitochondrial apoptosis pathway. / Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a promising candidate for cancer therapeutics due to its ability to induce apoptosis selectively in cancer cells (Gura, 1997). Result from MTT study illustrated that SW620 was more resistant than SW480 to TRAIL treatment. It is recognized that SW620 is the metastatic form of SW480 derived from the same patient at a later time, so it is important to develop agents that are able to sensitize the cancer cells to TRAIL, or to recover TRAIL sensitivity. We show for the first time that CF sensitizes SW620 cells to TRAIL-induced apoptosis and the mechanisms involved at least elevation of DR4, enhanced activation of caspase-8 and -3, as well as increase in DNA fragmentation. / Kong, Ka Lai. / Adviser: Wong Yum Shing. / Source: Dissertation Abstracts International, Volume: 73-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 119-136). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.

In western societies, skin cancer incidence has increased dramatically over recent decades, due predominantly to increased sun exposure habits. Ultraviolet (UV) light exposure and individual light sensitivity of the skin constitute two important factors affecting the risk for skin cancer development. Individuals with a heightened propensity to get sunburnt have a higher risk for skin malignancies, and need to protect themselves more systematically from the sun. Individual UVlight sensitivity can be determined either by self-estimation of tendency to burn and tan, as in the Fitzpatrick’s classification, or by use of a phototest. Although phototesting constitutes a considerably more objective method, it is only sparsely used, chiefly due to financial and resource related factors, and is mainly limited to investigation of photodermatoses or dose-management in photo therapy. The general aim of this thesis was to develop and improve aspects of the phototest procedure in rder to broaden the utilisation of phototesting within the fields of research, clinical practice and skin cancer prevention. As a first step, a new phototesting technique, using a divergent UVB beam was evaluated. The principle of the method is to provoke a circular UVB-erythema in the skin, the diameter of which is related to the administered dose and thus the Minimal Erythema Dose (MED). In a test group of healthy subjects, naked eye reading by a trained observer resulted in a more exact, estimation of UVB-sensitivity, compared to traditional phototesting. Since the diffuse border of the provoked erythema was challenging for the untrained observer to read, the need for an objective, bio-engineering technique for test reading was clear. In this thesis, Laser Doppler perfusion imaging (LDPI) has been used. This data also enabled an objective description of doseresponse for the reaction, an outcome not possible in traditional testing. The divergent beam method was also shown to be useful as a model for evaluation of the effect of topically applied substances. In order to broaden the utilisation of phototests in general, a test procedure built on patient performed self-reading of skin tests (a traditional phototest and an irritant patch test) was evaluated. The reliability of these self-readings was shown to be substantial when compared to the control readings of a trained observer. Using the self-reporting procedure, phototesting was evaluated as a tool in primary prevention of skin cancer. The study focussed on sun habits and sun protection behaviour, and also on investigating the impact of different forms of presentation of the preventive information. Results showed significantly higher impact for a personally mediated preventive message than by letterform. For individuals with heightened UV-sensitivity the performance of a phototest led to a greater tendency to adopt sun protection behaviour than for subjects with a lower UV-sensitivity, suggesting that phototesting is a useful way to improve the outcome in terms of preventive behaviours for this group of susceptible, at-risk individuals. Divergent beam phototesting, patient-performed self-reading, and the application of phototesting in skin cancer prevention emerge as three novel, previously little investigated, aspects of phototesting, for which promising results could be demonstrated. / Under de senaste årtiondena har insjuknandet i hudcancer ökat dramatiskt i västvärlden, detta till stor del beroende på förändrade solvanor. Exponering för solens ultravioletta strålning (UVstrålning) samt den individuella ljuskänsligheten i huden utgör två viktiga faktorer av betydelse för uppkomsten av hudcancer. Individer med ökad benägenhet att bli rödbrända i solen löper också ökad risk för hudcancer av solexponering, och behöver således vara extra noga med att skydda sig mot solen. Hur känslig man är mot solljuset kan bedömas antingen genom självskattning (klassificering enligt Fitzpatrick), eller genom att använda ett ljustest. Det sistnämnda är en betydligt mer objektiv metod, men används ändå relativt sparsamt, sannolikt ofta beroende på brist på resurser, tid eller klinisk rutin. Det övergripande syftet med avhandlingen var att utveckla och förbättra aspekter på ljustestningsförfarandet med inriktning på att kunna bredda användningen av ljustest inom forskning, klinisk verksamhet och hudcancerprevention. Som ett första steg undersöktes och utvärderades en ny ljustestteknik, baserad på en divergent (spridd) UV-stråle. Genom att belysa huden med ett cirkulärt UV-ljusfält framkallas en cirkulär rodnad (erytem), där diametern på rodnaden står i relation till den individuella ljuskänsligheten i huden. I jämförelse med traditionell ljustestningsmetodik visade sig metoden resultera i en noggrannare uppskattning av ljuskänslighet, samt möjligheten att beskriva ett dos-responsförhållande inom det rodnade hudområdet. Eftersom kanten på den framkallade rodnaden tenderade att bli ganska diffust avgränsad framkom dock, med undantag för speciellt tränade avläsare, svårigheter att läsa av testet med enbart ögats hjälp. Av den anledningen krävdes mer objektiv, hudfysiologisk mätmetodik. I de genomförda studierna användes så kallad Laser Doppler perfusion imaging (LDPI) för detta. Förutom uppskattning av ljuskänsligheten testades den divergenta UV-strålen också som modell för skattning av anti-inflammatorisk effekt av ämnen som appliceras på huden, exempelvis cortison, och visade sig användbar för detta. I syfte att öka förutsättningarna för bredare användning av ljustest, genomfördes en studie där försökspersonerna själva fick avläsa ett traditionellt ljustest och rapportera in testresultatet. Resultaten jämfördes med avläsningar utförda av en kunnig avläsare, och visade på god tillförlitlighet. Slutligen, med hjälp av den beskrivna självavläsningsproceduren, undersöktes i en primärvårdspopulation, om ljustestning kan vara användbart för att förebygga hudcancer, med inriktning på att påverka individers solvanor, solskyddsbeteende och attityder gentemot solning. I studien jämfördes även olika modeller för att presentera ett preventionsbudskap, och där ett muntligt sådant, förmedlat vid ett läkarbesök, hade ett betydligt bättre genomslag än motsvarande, enbart skriftlig, information. För individer med hög ljuskänslighet bidrog ljustestet till ökat solskyddsbeteende, vilket indikerar att ljustest skulle kunna vara ett användbart verktyg i eftersträvan att förebygga hudcancer speciellt i denna grupp av individer med förhöjd hudcancerrisk. Sammanfattningsvis utgör ljustestning med divergent UV-stråle, självavläsning av ljustest samt användning av ljustest vid hudcancerprevention tre nya, tidigare sparsamt undersökta aspekter på ljustestning, för vilka den här avhandlingen visar lovande resultat.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Cervical cancer is the most common malignancy after breast cancer in women worldwide. It accounts for 83% of all new cases and 85% cancer death in developing countries. In South Africa, cervical cancer is the common cancer in women with an annual crude incidence rate of 30.2 per 100,000 women and the highest rate were found to be in women between the ages of 66-69 years. Approximately 6800 women in S.A face new case of cervical cancer while accounting for 3700 cancer death annually. Because of unequal access to the health facilities, socio-economic differences, HPV and HIV infection, the rate of cervical cancer in black women is higher (42.1%) compared to the low rate in white women. Because of the name “cancer bush’ given to Sutherlandia Frutescence(S.F) plant by the traditional healers as well as Xhosas, Zulu, Sotho and cape Dutch for its anti-cancer activity, the plant was in this study to confirm its cytotoxic effect on the cervical cancer cell lines. Aim of the study: to evaluate the methanolic extracts of Sutherlandia Frutescens on cervical cancer cell lines. Materials and Methods: The MTT assay was performed to evaluate SiHa cell lines treated with methanolic extract of S.F (50μg/ml, 100μg/ml, 150μg/ml and 200μg/ml). The three compounds (Canavanine, GABA and Pinitol) were also evaluated for its anti-tumour activity. The cell growth was then showed in real time using Xcilligence. Flow cytometry was employed to determine the mode of action. Caspase 3/7 assay was performed to confirm if cell death was via caspase-dependent or independent and ATP was done to assess the ATP level in S.F treated cells. Results: MTT shows a significant decline in cells treated with 50μg/ml, 100μg/ml and 200μg/ml of the extract and 50μg/ml was concluded to be the concentration at which 50% of the cells die. The ATP results are inconsistent with MTT result; the ATP level increased in S.F treated cells. Cell index which represents the quantitative measure of cell growth in real time decline upon treatment with 50μg/ml. Flow cytometry showed cells are dying by apoptosis and the cell cycle arrest is mostly in the S phase. The cell death was caspase-dependent as it shows an increased luminescence which is proportional to the number of caspase. The concentrations of the compounds used, Canavanine (1000μM, 1500μM and 2500μM), GABA (100μM, 300μM and 500μM) and Pinitol (30μM, 90μM and 120μM) induce cell death and cell death shows to decrease after the maximum concentration. Conclusion: Sutherlandia Frutescence has proven with number of research that it induces cell death via apoptosis. After evaluating its cytotoxicity, the plant shows to be a promising anti-tumor agent that needs to be clinically proven. / Life Sciences / M. Sc. (Life Science)

O rastreamento para o cÃncer do colo uterino e o planejamento familiar sÃo prÃticas preventivas de relevÃncia em saÃde da mulher em idade fÃrtil. A atenÃÃo bÃsica ainda privilegia o ciclo gravÃdico-puerperal e a prevenÃÃo da neoplasia maligna do colo, ficando o planejamento familiar em segundo plano. Contudo, a despeito da melhor cobertura na realizaÃÃo da citologia cervicovaginal, as taxas de mortalidade pela neoplasia persistem elevadas. Persistem, tambÃm, taxas altas de gestaÃÃo na adolescÃncia, de abortamentos e iniquidades em saÃde. O objetivo do projeto foi caracterizar a situaÃÃo de saÃde reprodutiva de mulheres em idade fÃrtil de uma comunidade urbana de baixa renda em Fortaleza, priorizando a realizaÃÃo da citologia e o uso de mÃtodos contraceptivos. Tratou-se de estudo transversal por entrevistas domiciliares com 244 mulheres de 13 a 52 anos. A anÃlise exploratÃria inicial permitiu estabelecer correlaÃÃes atravÃs do teste do qui-quadrado de Pearson para as variÃveis nominais e ANOVA para mÃdias e desvios padrÃes. Para expressar a magnitude das associaÃÃes foram calculadas razÃes de chance (odds ratio) como expressÃes das razÃes de prevalÃncia utilizando regressÃo logÃstica simples e mÃltipla. Dentre as entrevistadas com atividade sexual e 25 anos ou mais, 90,3% realizaram citologia no mÃximo a cada trÃs anos, 59,3% anualmente. Correlacionaram-se positivamente à periodicidade anual o trabalho remunerado (OR=2,63; IC95%: 1,49-4,64) e a condiÃÃo de ter tido no mÃximo uma gestaÃÃo (OR=2,60; IC95%: 1,11-6,08). Quanto ao planejamento familiar, pouco mais da metade das mulheres (51,9%) usava algum mÃtodo e 39,5% delas nÃo foram orientadas por mÃdico ou enfermeiro. Predominou utilizaÃÃo de anticoncepcionais orais (40,4%) e condom (28,7%). A renda familiar de R$ 800,00 ou superior associou-se à maior chance de contracepÃÃo orientada por profissional adequado (OR=3,3, IC95%: 1,28-8,54), contrariamente à histÃria de abortamento (OR=0,32, IC95%: 0,13-0,82). Observou-se alta frequÃncia de realizaÃÃo da citologia cervicovaginal, inclusive anualmente e fora da faixa etÃria recomendada pelo MinistÃrio da SaÃde. Houve baixa prevalÃncia de anticoncepÃÃo, oferta insuficiente quanto à variedade e elevada proporÃÃo de mulheres que nÃo recebeu orientaÃÃo adequada para o uso de mÃtodos contraceptivos. Renda familiar e abortamento prÃvio foram fatores associados ao planejamento familiar orientado por profissional adequado, enquanto o trabalho remunerado e o fato de ter tido no mÃximo uma gestaÃÃo foram associados à coleta anual de citologia para prevenÃÃo do cÃncer do colo uterino. / Cervical cancer screening and family planning are relevant preventive health practices for women of childbearing age. Primary care still privileges gestational period and cervical neoplasia prevention over family planning. Nevertheless, despite improvements on the coverage for cervicovaginal cytology, cervical neoplasia mortality rates show only slight decrease. High rates of teenage pregnancy, abortions and health iniquities persist. The project aimed to portrait the reproductive health situation of childbearing aged women from a low income urban community in Fortaleza, prioritizing cytology procedures and the use of contraceptive methods. This was a cross-sectional study carried out through home interviews with 244 women from the age of 13 to 52 years old. The initial exploratory analysis allowed establishing correlations through the chi-square test for nominal variables and ANOVA for means and standard deviations. Odds ratios as expressions of prevalence ratios were obtained to express the magnitude of the associations using simple and multiple logistic regression. Amongst sexually active women and aged 25 years or more, 90.3% underwent cytology at least every 3 years, and 59.3% did it annually. Cytology annual frequency positively correlated to remunerated employment (OR=2.63; IC95%: 1.49-4.64) and to the condition of having had the maximum of one pregnancy (OR=2.60; IC95%: 1.11-6.08). Regarding family planning, just over half of women (51.9%) used any contraception and 39.5% of them were not guided by doctors or nurses. Oral contraceptives (40.4%) and condom (28.7%) predominated as current contraceptive methods. Family income of R$ 800.00 or above positively correlated with contraception guided by an appropriate professional (OR=3.3, IC95%: 1.28-8.54) and negatively correlated to a history of previous abortion (OR=0.32, IC95%: 0.13-0.82). High rates of cervicovaginal cytology were observed, even annually and out of the age group suggested by the Health Ministry. There was a low rate of contraception, insufficient offer as to methods variety and a high proportion of women who did not received adequate guidance on the use of contraceptive methods. Family income and previous abortion were associated to family planning guided by a qualified professional, whilst remunerated employment and having had the maximum of one pregnancy were associated to annual cytology screening to prevent cervix neoplasia.

Please read the abstract in the section 00front of this document Please cite as follows: Opperman JA, 2002, Die emosionele belewenis van 'n beenmurgoorplanting : 'n Maatskaplike Werk perspektief, MA dissertation, University of Pretoria, Pretoria, viewed yymmdd < http://upetd.up.ac.za/thesis/available/etd- 07252005-110248/ > / Dissertation (MA (Social Work))--University of Pretoria, 2002. / Social Work and Criminology / MA (Social Work) / unrestricted

Breast cancer is the most common cancer and the second most common cause of cancer death in women. In 2008 there were 182,460 women diagnosed with breast cancer, and 40,480 women died of this disease. Breast cancer can be prevented by medical (tamoxifen or raloxifene) or surgical approaches (bilateral mastectomy or oophorectomy). Prevention is only recommended for women at high risk for developing breast cancer; therefore, proper risk calculation is essential in identifying women that may benefit from prevention measures. There is an easy-to-use and easily accessible risk calculation tool for determining a woman's risk of developing breast cancer and need for referral for counseling, gene testing, and possibly preventive therapy. This article reviews the components of risk assessment, the most frequently used risk calculation tool, and approaches to breast cancer risk reduction including medical and surgical therapies. The use of these therapies results in a risk reduction of 50-90%.

This thesis concerns a melanoma-derived growth regulatory factor that inhibited proliferation of several malignant human cell lines, and, in particular, a line designated UCT-BR-1, which was derived from a human breast cancer metastasis. The work is presented in four chapters. Chapter 1 provides a review of the relevant literature at the time of writing; Chapters 2 and 3 describe the experimental work that was done; and in Chapter 4 I discuss the implications of my results for current and future work in growth factors. Experimental results are presented as Charts (which may be Figures or Tables) and the methods and experimental protocols that I used are described in the Chart legends and not in the main text of the thesis. The Appendix contains details of the tissue culture techniques and descriptions of the cell lines that were used. Sources of the various laboratory materials as well as the methods that were employed for the more routine procedures are also described in the appendix.

In Swaziland, cases of cervical cancer among Human Immunodeficiency Virus (HIV)-positive adolescent girls and young women (AGYW) are increasing, but there is low uptake of cervical cancer screening. This study was conducted using the systems thinking theory to explore the relationships between the uptake of cervical cancer screening among HIV-positive AGYW in Swaziland and the availability of trained health providers, cervical screening services, and the provision of referrals for cervical screening. The study also investigated any differences in uptake of cervical screening based on age group. For this quantitative cross-sectional study, secondary HIV program data that were collected routinely between January 2016 and March 2018 were accessed. Data were described with univariate analysis while relationships were tested using bivariate analysis and logistic regression. Most facilities (97%) had staff who had been trained; facilities with greater numbers of trained staff were more likely to have a higher uptake (OR: 30.3, p = 0.000). Facilities with cervical screening services were also more likely to have a higher uptake (x2 = 16.94, p = 0.000), and facilities with all the core components for screening had the highest uptake (p = 0.002). AGYW who had a positive screen were referred equally but the referral rate was low (20.45%). There was no difference in uptake by age group. The results of the study can increase knowledge of the institutional factors that contribute to the low uptake of cervical cancer screening among HIV-positive AGYW and has implications for social change by informing interventions for improving cervical cancer screening uptake in HIV-positive AGYW in similar settings, ultimately reducing the high costs, morbidity, and mortality related to cervical cancer in this population.

The project is a proposal of a new Center of prevention located in the Masaryk’s Oncology Institute in Brno. It includes the oncology center prevention itself, inpatient department for patients who attend radiation therapy and a proton therapy center. It is also supplemented by administration and rentable premises.