LQB184 Assessment Item 1

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Annotated  Bibliography  Can the appetite hormone ghrelin stimulate the molecular pathways

that lead to prostate cancer?

(1) Yeh, A. H., Jeffery, P. L., Duncan, R. P., Herington, A. C. and Chopin, L. K., 2005, ‘Ghrelin and a novel preproghrelin isoform are highly expressed in prostate cancer and ghrelin activates mitogen-activated protein kinase in prostate cancer’, Clinical Cancer Research, vol 11, no. 23, pp. 8295-8303. (2) In this article Yeh et al. review evidence that the appetite hormone ghrelin has a proliferative effect on prostate cancer cells. (3) To investigate how this process is triggered, assays were performed on LNCaP prostate cancer cell lines and western blotting was performed on LNCaP and PC3 cells. (4) The authors focussed on evaluating the role ghrelin played in cell proliferation and apoptosis and tested whether ghrelin activates the mitogen-activated protein kinase (MAPK) pathway through a process known as immunoblotting. (5) This article is useful to my research topic because it is one of the only studies that acknowledges the MAPK signalling pathway. (6) The main limitation within this study is that it lacks a substantial sample size within its experiment and so the precision of its findings are questionable. (7) Hence, the authors have stated that further research in vivo and in vitro must be pursued in able to understand the extent ghrelin has in activating the MAPK cascade which, as a result, increases cell proliferation within prostate cancer cells. (8) It should be noted that other articles studying the association between ghrelin and prostate cancer are known to popularly cite this article. This is for good reason since Yeh et al. presents a very well-articulated report with findings that are still relevant to this research topic. Therefore this article will be a good starting point to lay out the foundations to the research question.

(1) Jeffery, P. L., Herington, A. C. and Chopin, L. K., 2002, ‘Expression and action of the growth hormone releasing peptide ghrelin and its receptor in prostate cancer cell lines’, Journal of Endocrinology, vol 172, no. 3, pp. R7-R11. (2) This article was the first of its kind to discover a ghrelin induced pathway that increased growth within prostate cancer cell lines. (3) Jeffery et al. performed assays on PC3 cell lines by treating these cells with ghrelin concentrations ranging from 0-20nM in each well of a 96-multiwell plate in which these were incubated over a 3 day period. (4) The focus of the experiment involved examining the proliferation numbers within the PC3 prostate cancer cell line. (5) This article is able to describe some details of the mechanisms that underpin cell proliferation in prostate cancer cell lines and thus is proven to be a useful source. (6) However, this study did not use a variety of prostate cell lines and only the PC3 cell line was used to test the effects of ghrelin. By disregarding other cell lines such as DU145 this study is subject to questioning in the accuracy of its data. Furthermore, this is a relatively dated article and thus lacks more specific and detailed findings compared to more recent articles concerning this research topic. (7) The authors conclude that this study was the first to

LQB184 Assessment Item 1

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discover the effect of ghrelin in PC3 proliferation. Results illustrated a bell-shaped response in a histogram format and that samples were still above the control despite the concentration of ghrelin in each sample. (8) Overall this is a good article to begin with, but will not play a large bearing on my research.

(1) Cassoni, P., Ghe´, C., Marrocco, T., Tarabra, E., Allia, E., Catapano, F., (…) Muccioli, G., 2004, ‘Expression of ghrelin and biological activity of specific receptors for ghrelin and des-acyl ghrelin in human prostate neoplasms and related cell lines’, European Journal of Endocrinology, vol 150, no. 2, pp. 173-184. (2) In this article, Cassoni et al. investigates the evidence that ghrelin stimulates prostate cancer cell division. (3) Data was obtained by testing three forms of prostate cancer cell lines – PC3, DU145 and LNCaP. Assays were conducted on each of these cell lines where triplicates of a 48-multiwell plate were made thereby increasing the chance of a more uniform sample and thus reliability; different concentrations (0.1nM - 1 µM) of ghrelin were treated in each cell line. (4) The findings of the experiment were examined by interpreting the results into growth curves where cell proliferation was assessed. (5) This well-designed experiment was able to provide a range of results associated to a wider array of prostate cancer cell lines. (6) The only limitation identified is that this study fails to provide a better insight into the mechanisms that ghrelin is associated with, despite these new findings. (7) The authors conclude that different concentrations of ghrelin affected different prostate cancer cell lines differently. These discrepancies may be attributed to the concentration of ghrelin since it was a much larger range, compared to previous studies where ghrelin concentrations were lower. (8) These discrepancies have not been supported with any other studies thus far and hence will not form the basis of my research but will however be used for supplementary research.

(1) Ławnicka, H., Mełeń-Mucha, G., Motylewska, E., Mucha, S. and Stępień, H., 2012, ‘Modulation of ghrelin axis influences the growth of colonic and prostatic cancer cells in vitro’, Pharmacological Reports, vol 64, no. 4, pp. 951-959. (2) In this article, Ławnicka et al. hypothesised that ghrelin plays a likely role in the progression of human prostate carcinogenesis. (3) The authors of this article aimed to examine the direct effects ghrelin has on the growth of prostate cancer. DU145 prostate cell lines were cultured over a period of 72 hours where the colorimetric Mosmann method was utilised to obtain results. (4) Cell proliferation and apoptosis were assessed to determine the role ghrelin has in stimulating molecular pathways in prostate cancer. (5) This article is useful to my research topic because it presents opposing results compared to earlier studies. (6) Its main limitation however is that experimentation was only tested on one type of cell line DU145, hence its precision is questionable. Moreover, this article is not exactly the most informative report since it also focuses on other research topics. (7) The authors conclude that ghrelin can have an inhibiting effect on cell proliferation in prostate cancer cell lines and supports these findings with previous notable studies. (8) Overall, the experimental design does not seem well planned and the article comes off as biased. Further testing is required in

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order to confirm the validity of its findings. Consequently, this article will not form the base of my research but in instances where its findings are supported with previously recognised studies, this report will prove to be valuable.

(1) Díaz-Lezama, N., Hernández-Elvira, M.,Sandoval, A., Monroy, A. and Felix, R.,Monjaraz, E., 2010, Ghrelin inhibits proliferation and increases T-type Ca 2+ channel expression in PC-3 human prostate carcinoma cells, vol 403, no. 1, pp. 24-29. (2) The authors of this article investigate ghrelin’s involvement in prostate cancer proliferation; by doing so it can potentially lead better treatments and therapies. (3) The aim was to collect data that reflected ghrelin inducing signalling pathways in prostate carcinoma cells. This was achieved by performing assays on the PC3 prostate cancer cell line where they were treated with different concentrations of ghrelin (10 – 50nM) over a period of 72 hours. (4) The authors evaluated cell proliferation and apoptosis to determine the relationship between ghrelin and prostate cancer. (5) This article is particularly relevant to my research because it is able to provide in depth report and attempts to explain the mechanisms behind ghrelin and prostate cancer cells. (6) The experiment was limited to only PC3 cell lines and thus loses some reliability because it lacks variety in cell lines. (7) The study revealed that ghrelin expressed an antiproliferative effect on PC3 cell lines and thus induced apoptosis. (8) Because this article is so comprehensive in presenting a potential molecular pathway involving ghrelin, my research topic will be largely based on this study.

(1) Lanfranco, F., Baldi, M., Cassoni, P.,Bosco, M., Ghé, C. and Muccioli, G., 2007, Ghrelin and Prostate Cancer, Vitamins and Hormones, vol 77, no. 13, pp. 301-324. (2) In this article, Lanfranco et al. analyses ghrelin and its capabilities towards prostate cancer cells. (3) This review aims to provide a source of detailed information and remains unbiased throughout the course of its report by exploring a variety of findings. The authors achieved this by gathering material from primary literature and presented it in its review article format. (4) This article examines cell proliferation stimulated by ghrelin and the ERK1/2 MAPK pathway it activates to do so. (5) This report is particularly useful to my research topic because it is able to summarise and evaluate key details from previous experiments performed on prostate cancer cell lines with ghrelin. (6) The main limitation within this report is that the majority of cited sources restrict their research to only one cell line type and thus comparison of results cannot be achieved properly. (7) The authors of this article summarise in the conclusion that cell proliferation is promoted when ghrelin concentrations typically found in the bloodstream of humans are relatively low, while higher concentrations of ghrelin exhibit an antiproliferative effect in cell proliferation. (8) This review article is an excellent source of literature and will form a large majority for the base of my research. Key: (1) Citation, (2) Introduction, (3) Aims & Research methods, (4) Scope, (5) Usefulness, (6) Limitations, (7) Conclusions, (8) Reflection