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Ovarian cancers often develop resistance mechanisms against the standard platinum and taxane chemotherapy, which indicates the need for novel therapeutics to improve patient outcome. In vitro assays were performed to assess the effects and mechanism of action of a novel peptide, GAP-107B8, on ovarian cancer cell viability. Xenograft models were used to determine GAP-107B8’s effects on tumour burden in immune-incompetent mice. GAP-107B8 significantly reduced cell viability in ovarian cancer cell lines, although no synergistic effects with carboplatin were observed. This reduction in cell viability was due in part to apoptosis and may involve mechanisms leading to decreased pAKT, but without any change in pPKC levels. In vivo, GAP-107B8 had no effect on ovarian tumour burden, but significantly reduced ascites volume. The findings suggest that GAP-107B8 can reduce some malignant characteristics of cancer cells in vitro and in vivo and should be evaluated further as a potential therapeutic for ovarian cancer.

No description available.

Selective breeding of chickens for high growth rate and other production traits has led to the modern commercial broiler, a bird that has the genetic potential for reaching an average body weight of 2.7kg within 6 weeks of hatch. However, the breeding stock for modern broilers has to be feed controlled in order to lay large numbers of viable hatching eggs. Broiler breeders, when fed ad libitum, have a propensity to produce internal ovulations, double-yolked, misshapen or shell-less eggs. This is due to the release of multiple ova at ovulation, which results in a significant loss of production. Feed control has been shown to mitigate this effect but welfare concerns have been raised as to the side-effects for the birds. The main objective of this research was to determine the genetic basis for the regulation of ovarian follicle selection and its dysfunction in ad libitum-fed broiler breeders, and how this might be addressed by genetic selection to limit the impact on the management and welfare of future broiler breeders. A multi-layered statistical, expression profiling and cluster analysis of ovarian gene expression data from a microarray study was carried out to identify candidate genes for further study.Key stages of development were investigated for feed restricted and ad libitum-fed broiler breeders. Several gene candidate genes were validated by qPCR in a comparison of different ovarian tissues in layer type hens for subsequent analysis in broiler breeders. Sequencing of the founders of an Advanced Intercross Line (AIL) of commercial broiler breeders and White Leghorn layers was performed covering 3 regions of each of the primary candidate genes in order to identify genetic variation that could account for differences in follicle number between broilers and layers. Expression data from a microarray study highlighted a number of potential candidate genes for regulation of follicle development. One of these genes, Platelet Derived Growth Factor Receptor Like (PDGFRL), shares significant sequence homology with the active domains of Platelet Derived Growth Factor Receptor β. Expression profiling in layers showed peak PDGFRL expression in 5-6 mm follicles and the F2 follicle (P <0.001). PDGFRL was also up-regulated in response to ad libitum feeding in broiler breeders in 6-8 mm follicles (P<0.016), the point at which follicle selection and recruitment is considered to occur. In addition to this, while PDGFRL expression remains relatively constant between tissues under ad libitum conditions, it shows a clear reduction in expression (P <0.001) in prehierarchical follicles relative to the stroma and the F1 follicle under feed restriction. This observation is consistent with results from the original microarray study. Sequencing of the AIL Founders highlighted several SNPs in the broiler that have the potential to be used as markers for incorporation into commercial selection programs. EST alignment in preparation for targeted sequencing of PDGFRL also highlighted three potential forms of the protein, each with a different 5’ starting sequence. Initial investigation has shown all three to be expressed in ovarian follicles. QPCR in a panel of 13 tissues shows marked differences between the 3 variants, implying different and perhaps specialised roles for each. The PDGFR family has a potential role in steroidogenesis, and the expression profiling, combined with the clear effect on expression from ad libitum feeding in broiler breeders, suggest that PDGFRL is a strong candidate for involvement in the regulation of follicle development GDF9, shown to be associated with multiple ovulation in sheep, and FSH receptor, a mediator of neuroendocrine signalling to the ovary, were also investigated. They behaved as expected in layer type birds but both showed significant differential expression (P = 0.005 and 0.018 respectively) as a result of ad libitum feeding in broiler breeders. Though these two genes have been extensively investigated, these are previously unobserved effects. SNPs have also been identified in these genes which have the potential to be used as markers for incorporation into commercial selection programs. To fully exploit these results, additional investigation is recommended to confirm these results in commercial populations and to determine how they can be employed to best effect.

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M.A. / In this study an attempt is made to understand the phenomenological experience of women in spontaneous premature menopause. There is very little literature available about spontaneous premature menopause and even less about the experiences of women in spontaneous premature menopause. Spontaneous premature menopause is viewed as a negative experience in the woman’s life and medical staff recommend that she should receive treatment for spontaneous premature menopause. In this study the woman, herself, was asked how she feels about spontaneous premature menopause and how it affects her life. Phenomenological research procedures are used in this study. Interviews were conducted with three participants. They were asked to tell the researcher about their experience of spontaneous premature menopause and how it affected their lives. Hermeneutic phenomenology is used to analyse the participants’ experience of spontaneous premature menopause. Themes and categories that stood out during analyses are discussed and interpreted. Results of the study show that spontaneous premature menopause can cause bodily changes in women; it can lead to several different menopausal symptoms and it can have a negative effect on her relationship with her family, friends and other people. Bodily changes that can occur, because of spontaneous premature menopause include weight gain, changes in the breasts, changes to the vagina, skin changes, bladder changes, itchy skin, heart palpitations and changes to the pelvic floor. Symptoms that can occur during spontaneous premature menopause include hot flushes, night sweats, headaches, sleep difficulties, tiredness, depression, forgetfulness, mixed emotions and pain in different areas of the body. Participants felt that their bodies, their doctors and their family and friends failed them. They had no one to turn to, because significant people in their lives did not believe that they are in spontaneous premature menopause. They were told that it must be something else like depression. The participants had shock reactions due to feelings of loss. They no longer had the body of a young woman. They had lost their youthful appearance, their sexuality, their abilty to bear children and to function satisfactorily in their daily duties. These women had to come to grips with the fact that their youthful days were over and that they were aging before their time. It is suggested that cross-cultural research be done in the future to establish how women in other cultures experience spontaneous premature menopause. Comparisions can be made and if there are any differences efforts can be made to establish what causes these differences. Cultures where spontaneous premature menopause is viewed as a positive event in a woman’s life can be researched to establish how this experience can be turned into a positive experience in cultures where it is viewed negatively.