University of Macau / Institute of Chinese Medical Sciences

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Although clinical outcomes of some cancer have been greatly improved by advancements made in surgery, chemo or radiotherapy and development of novel strategies such as molecular targeted therapy, Traditional Chinese Medicine (TCM) is particularly appreciated for cancer therapy in China based on its 5,000-year-old history, well established theoretical system and numerous exciting case reports. However, due to lack of quality assurance, laboratory evidences and well-designed clinical trials, TCM always encounters much skepticism and pessimism by the West. The study aims to identify the bioactive compounds in a Chinese herb Spatholobus suberectus (SS, 雞血藤) by targeting on lactate dehydrogenase A (LDH-A) in breast cancer. Glycolysis inhibition has been considered as important strategy to block cancer energy metabolism and therefore suppressing cancer growth. LDH-A has been demonstrated to be up-regulated in various cancer cells. In our study, 46 breast cancer specimens were collected to study the relation between LDH-A expression and clinicopathological characteristics including menopause, tumor size, node involvement, differentiation and pathological subtypes classified by estrogen receptor (ER), progesterone receptor (PR) and Her-2. LDH-A expression was found to be correlated significantly with breast cancer size and independent with other clinicopathological factors. LDH-A silencing in breast cancer cell lines MDA-MB-231 and MCF-7 resulted in an inhibited breast cancer cell proliferation, elevated intracellular oxidative stress, induction of mitochondiral pathway apoptosis and limited tumorigenic ability, indicating that LDH-A inhibition might offer a promising therapeutic strategy for breast cancer. SS is historically recommended to invigorate blood circulation and has been prescribed to treat diseases relating to blood stasis syndromes including menstrual abnormalities, anemia, numbness of the limbs, arthritis and cancer, etc. Our following study revealed that SS aqueous extracts could significantly inhibited breast cancer LDH-A expression and activity in both in vitro and in vivo models built by MDA-MB-231 and MCF-7 cell lines. Bioactivity guided fractionation based on LDH-A activity, apoptosis and LDH-A expression further identified epigallocatechin (EGC) as the key compound responsible for the inhibited LDH-A expression. Mechanistic studies found that the inhibitory effect of EGC on LDH-A expression was mainly through promoting Hypoxia inducible factor-1α (HIF-1α) proteasome degradation rather than inhibiting transcription activity, which might be correlated with decreased binding between HIF-1α and Hsp90. Consistent with in vitro findings, EGC was also demonstrated effecitve in suppressing breast cancer growth in vivo correlating to down-regulation of LDH-A, HIF-1α and triggerment of apoptosis. This study provides preliminary laboratory evidences for applying SS in breast cancer therapy. However, further research is needed to evaluate its metabolism, the synergistic effects with chemotherapeutic agents and clinical efficiency. / published_or_final_version / Chinese Medicine / Doctoral / Doctor of Philosophy

As breast cancer incidence and survival rates increase, there is an urgent need to make appropriate psychosocial support available to all women with breast cancer. In this qualitative study, narrative inquiry was used to examine how women with breast cancer used visual creative expression (art therapy and/or independent art making) to address psychosocial needs that arose for them after their diagnoses. Seventeen women, aged 37-82, participated in this investigation. Data analysis of in-depth interviews with these women focused on narratives they constructed about why they turned to art therapy and/or independent art making and how it helped to be involved in these activities. Particular attention was given to the issue of meaning making. Four storylines emerged from the analysis. "Art and art therapy as a haven" came from narratives about using art making or art therapy for comfort and affirmation. The narratives that comprised "getting a clearer view" were about using visual creative expression to create a clear picture of emotional experience. "Clearing the way emotionally" came from narratives about self-expression and about processing difficult emotions. The narratives that yielded "expanding and enlivening the self were about the women fortifying and energizing themselves through visual creative expression. Two minor themes related to the role of the art therapist and negative experiences with art therapy also emerged. In their narratives, the women portrayed visual creative expression as flexible, compelling, and powerful means of addressing multiple psychosocial needs simultaneously. Above all, the storylines show that the women valued visual creative expression as a way to reduce the feeling of threat to existence, to affirm present existence, and to promote the ongoing existence of both their psyches and their bodies. The results of this study contribute to the field of psycho-oncology by extending understandings of meaning making in relation to breast cancer, supplying detailed explanations from the perspectives of women with breast cancer of how visual creative expression can be helpful, and providing valuable insight into how psychosocial support services based on visual creative expression might meet needs of women with breast cancer that would not be met through other types of services.

There is considerable evidence that delays in diagnosing and treating breast cancer reduce long-term survival. The purpose of this study was to assess the waiting time between diagnosis and treatment for Alberta women with breast cancer and to examine the influence of age, cancer stage, Regional Health Authority (RHA), community size, and year of diagnosis on this time interval. The data were obtained from the Alberta Cancer Board. The information included approximately all Alberta women with breast cancer between 1997 and 2000. The overall median waiting time was 17 days. The mean and median delay increased by an average of two days each year. Only 43.8% of cases were treated within the recommended 14 days. The delay was significantly longer for women younger than 70, with stage 1 disease and from Northern RHAs. Efforts must be made to decrease delay and ensure that all women receive equal access to health services. / xii, 106 leaves : ill. ; 28 cm.

In the treatment of early stage breast cancer, both mastectomy and lumpectomy followed by radiation therapy have been recognized as having similar survival rates. Increasingly, women are being given the opportunity to choose which of these surgical treatment options they wish to pursue. Decisions tend to be made rather quickly, and some women may later regret their treatment choice. In this study, an instrument (Breast Cancer Treatment Inventory (BCTI)) was developed that identified five primary sources of influence that affect women's breast cancer treatment decisions: cosmetic outcome, preparedness, physician's choice, short-term effects, and long-term effects. Items were generated and refined by oncology professionals and breast cancer survivors, followed by a pilot study conducted with members of a breast cancer support group. The resulting 28-item scale was completed by 139 early stage breast cancer patients. A series of oblique factor analyses yielded a five-factor solution with reliabilities ranging from .66 - .87. Content validity was enhanced by involving oncology experts and women with breast cancer in the item generation procedures. Use of the BCTI may assist women through a methodical and effective decision-making process. The BCTI may also be appropriate for research studiesinvolving the process and prediction of treatment selection since it meets requirements for ease of administration, brevity, reliability, and validity. / Department of Counseling Psychology and Guidance Services

Syftet med denna studie var att beskriva unga kvinnors upplevelser av förtidig menopausefter cytostatika- och/eller hormonbehandling. Ett ytterligare syfte var att beskriva hursexualiteten upplevdes efter dessa behandlingar. Undersökningen genomfördes i två etapper med fenomenologisk metod. Öppna individuella intervjuer valdes i delstudie 1. I delstudie 2 användes fokusgrupp. Sammanlagt deltog nio kvinnor i studien. Dessa kvinnor var yngre än 45 år vid diagnosen och hade slutat att menstruera pga. behandling. Essensen befanns vara: Att inte känna igen sig själv, med delkomponenterna den fertila sexuella kroppen, den åldrande kroppen, sårbarhet och bekräftelse. I fokugruppsintervjun utvecklades essensen: Utanförskap med delkomponenterna att inte vara hemma i sin egen ålder, stigma, sexuell lust och intima relationer, existentiell oro samtbekräftelse. Slutsatsen som dras är att man inom sjukvården bör utveckla samtalsformer som riktar uppmärksamhet mot dessa kvinnors upplevelser av identitetsförvirring och utanförskap. Vissa data tydde på att kunskap omsexualitet samt kroppskännedom mildrade de upplevda svårigheterna. / The purpose of this study was to describe young women’s experiences of premature menopause after chemotherapy and/or treatment of hormones. A further purpose was to describe the women’s experiences of sexuality due to these treatments. The study was conducted in two steps with phenomenological method. Unstructured individual interviews were chosen in part 1. In part 2 focus group interviews were used. Nine women in all participated in the study. These women were younger than 45 years at time of diagnoses and had stopped menstruate due to treatment. The essence that emerged: Not recognizing oneself consisting of the following components: the fertile body, the aging body, vulnerability and confirmation. In the focus group the essence turned out to be: feeling marginalized consisting of the following components: not being at home in your own age, stigma, desire and intimate relationships, existential anxiety and confirmation. The conclusion was that health care services should provide room for the women to discuss feelings of identity confusion and marginalization. Some data indicated that beeing knowledgable about sexuality and the functioning of one’s own body helped in coping with the difficulties caused by drug-induced menopaus / <p>ISBN 91-7997-104-0</p>

Thesis (MTech (Biomedical Technology))--Cape Peninsula University of Technology, 2015. / Cancer is the leading cause of death in both developed and developing countries. In particular, breast cancer is regarded as the most common neoplastic disease in females and accounts for the high mortality rates in women. Increased mortality rates could be attributed to ineffective current cancer treatment modalities that have been implicated to cause multidrug resistance, high toxicity and induction of several side effects. In addition, oxidative stress appears to play a role in the development of breast cancer. Therefore, current cancer research aims to search for plant based anticancer compounds with less side effects and toxicity towards the human body. An example of such a plant is Hibiscus sabdariffa also known as roselle and is reported to have bioactive compounds that exhibit anticancer and antioxidant effects. However, the effects of Hibiscus sabdariffa on breast cancer in relation to oxidative stress and apoptosis have not been investigated. In this research study, the aim was to evaluate the cytotoxic and antioxidant effects of water and methanolic extracts of Hibiscus sabdariffa (HS) on cancerous MCF7 and non-cancerous MCF12A breast cell lines with special reference to oxidative stress and apoptosis. This was done based on the fact that HS has been documented for its traditional use against cancer and other ailments.

Magister Scientiae (Medical Bioscience) - MSc(MBS) / Despite the advances in therapies such as chemotherapy and radiotherapy, tumours have been shown to be resistant to the treatments. Gold nanoparticles (AuNPs) have been recognized as effective radiosensitizers of low energy (e.g. 200–500 kV) X-rays, leading to the emission of Auger electrons that cause highly localised ionizing damage to cells. Spherical AuNPs were synthesised via the reduction of the chloroaurate ions by sodium citrate. Characterisation of AuNPs involved UV-visible spectrophotometry, zeta (Z) potential, dynamic light scattering (DLS) and polydispersity index (PDI) measurements for determination of surface plasmon resonance (SPR), surface charge and stability, as well as transmission electron microscopy (TEM) for hydrodynamic core sizes, size distribution width and shape of AuNPs. Both the 5 and 10 nm AuNPs were found to be anionic with λmax absorbance of 525 nm and uniform size distribution. DLS measurement at 38.12 nm and 48.50 nm, respectively for 5 nm and 10 nm AuNPs, points to aggregation of the AuNPs. However, TEM measurements confirmed the core size of the 10 nm AuNPs. Non-malignant Chinese hamster ovary (CHO-K1), brain endothelial (BEnd5), breast (MCF-10A), isolated human lymphocytes and malignant breast (MCF-7) cell lines were treated with 50 μg/ml of AuNPs, and irradiated with either 1, 2 or 4 Gy X-rays or 1 or 2 Gy p(66)/Be neutron radiation. The γ-H2AX foci assay, cytokinesis-block micronucleus assay, MTT assay and fluorescence-activated cell sorting (FACS) was used to determine that amount of double stranded breaks (DSBs) in isolated lymphocytes, the presence and number of micronuclei (MNi) within binucleated cells (BNCs), cell viability and cell cycle progression, respectively. Preliminary experiments that established the reliability of the study regarding the induction of DNA damage after the bombardment of AuNPs by scattered low kV X-rays, were carried out on lymphocytes. Combined treatment (AuNPs and radiation) resulted in more endogenous foci in comparison to lymphocytes that were treated with AuNPs only. The CHO-K1 and MCF-7 cells showed higher MNi frequencies after the combination treatment of AuNPs and radiation compared to the number of MNi in samples exposed to AuNPs and radiation separately. The AuNPs alone influenced the cellular kinetics of all cell types. Interaction indices, which is the enhancement factor of AuNPs in combination with radiation, for AuNPs and 6 MV 2 Gy X-rays of 1.6 to 1.7 and 1.3 to 1.4 have respectively been determined for CHO-K1 and MCF-7 cells, whilst that for the other cell types used in the study were not different from Unity. As expected, the interaction indices between AuNPs and p(66)/Be neutrons was lower than the interaction indices after 2 Gy X-rays, as p(66)/Be neutrons interact only with the nuclei of the AuNP's atoms and the X-ray photons interact with the orbital electrons of the atoms of the AuNPs leading to Auger electron emission. The cell viability assay showed that 50 μg/ml of AuNPs had an inhibitory effect on cellular proliferation, in all four cell linnes whereas the lower concentrations (2.5, 5 and 10 μg/ml) had no effect. Results in this study, revealed an increase in the accumulation of CHO-K1 an MCF-7 cells in the G₂/M phase of the cell cycle after being treated with AuNPs followed by X-ray radiation, suggesting that the cells have possibly been sensitised to the damaging effects of radiation. Further studies are required to quantify internalised AuNPs and to then link the possible concentration differences of the AuNPs to differences in radiation damage effects observed for the different cell types.

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 &amp; 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 &amp; 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.