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Oesophageal Adenocarcinoma is on the rise globally affecting more than 450,000 people worldwide (Pennathur, Gibson et al. 2013). Once diagnosed overall 5-year survival ranges from 15 % to 25 %, with the best outcomes being associated diagnosis in the early stages of cancer development (Pennathur, Gibson et al. 2013). Oesophageal Adenocarcinoma (OAC) arises from a pre malignant condition known as Barrett’s Oesophagus (BO). BO is associated with an increased risk of developing OAC compared to normal age matched controls. Barrett’s Oesophagus Barrett’s oesophagus (BO) occurs when the normal squamous epithelium of the oesophagus is replaced by …

Protein kinase B or AKT (PKB) is a serine/threonine kinase. In mammals it is comprised of 3 highly homologous isoforms PKBα (Akt1), PKBβ (Akt2), and PKBγ (Akt3) (Manning and Cantley 2007). AKT signalling is activated in response to a variety of hormones, growth factors and extracellular matrix (ECM) components. The serine/threonine kinase AKT is involved in the regulation of a number of cellular processes including cell growth, proliferation, metabolism and cell survival. AKT Signalling Activation AKTs are activated by receptor tyrosine kinases (RTKs). RTKs activate phosphatidylinositol 3-kinase (PI3K) through tyrosine phosphorylation of adaptor proteins …

HMGB1 Functional Overview High mobility group box 1 ( HMGB1), a member of the high-mobility group (HMG) family, was first identified in the thymus in 1973 and is classified as a non-histone DNA-binding protein (Goodwin et al., 1973). HMGB1, a 215 amino-acid protein, is structurally composed of two HMG-box domains, which are DNA-binding, and C-terminal tail which facilitates protein-protein interactions (Park et al., 2004; Stros et al., 2010). Nuclear HMGB1 acts as a DNA chaperone and contributes to several regulatory processes in the nucleus such as transcriptional stability, nucleosome assembly and DNA replication (Agresti et al., 2003; Reeves et a …

Thanks to the great intuitions of brilliant scientists like Louis Pasteur, Edward Jenner, Robert Koch, Emil von Behring, Gaston Leon Ramon, Albert Sabin, Jonas Salk in the past century, the world has gotten to know the super power inside every individual: THE IMMUNE SYSTEM. “Find a pathogen, isolate it, kill it and inject it in the host…… the rest is left to our immune system”. Thanks to that concept, microorganisms like Yersinia pestis, Spanish flu and many others responsible of devastating society provoking millions of deaths were finally facing the end of their days thanks to a very simple, yet new concept developed by the greatest minds of the past century“ Vaccination”. Thi …

Pancreatic cancer survival rates Despite recent advances in our understanding of this disease, pancreatic cancer is one of the world’s most lethal malignancies. Although the disease accounts for only about 3% of all cancers, it is regarded as the 7th leading cause of cancer related deaths worldwide (Siegel, R et al., 2019). Worryingly, the overall 5-year survival rate for pancreatic cancer is less than 6%; where most patients die within 3 to 8 months after diagnosis and can be regarded as the ultimate death penalty. Chemoresistance and radioresistance are leading to tumour recurrence and metastatic lesions with enhanced aggressiveness, and …

By Dr. Lisa Dwane, Postdoctoral Researcher, Royal College of Surgeons in Ireland The first link between estrogen and breast cancer was made in the late 1800s, when physician George Beatson, who correctly suspected a link between the endocrine system and breast cell proliferation, removed the ovaries of a 33-year old woman with advanced breast cancer and controlled the growth of her tumours (Clarke, 1998). The young mother astonishingly lived for four years following this surgery; an unheard miracle in an era that offered toxic chemotherapy and debilitating surgical procedures as the only options for advanced cancer. Over a century later our …

By Rachel Bleach, PhD Student, RCSI By the age of 79 years, 1 in 14 women will develop breast cancer (Global Burden of Disease Cancer 2017). Beatson reported on the utility of removing the ovaries in the treatment of advanced breast cancer in 1896, leading to the observation that estrogen is one of the driving factors in breast cancer. This discovery revolutionised the field for breast cancer treatments and since then, there has been a firm focus on estrogen ablation as a therapy (Love and Philips 2002). Initially therapies such as selective estrogen receptor modulators/degraders were developed to target the estrogen receptor (ER) protein. More rece …

LATS kinases belong to a family of proteins that, in mammals, are comprised of two isoforms, LATS1 and LATS2. Originally identified in Drosophila melanogaster as Warts kinase, LATS1 and LATS2 serine/threonine kinases have been shown to be tumour suppressors (Edwards and Munger 2004). The original homologue of LATS was described as the dlats/warts tumour suppressor in two independent screens in Drosophila (Justice et al. 1995, Xu et al. 1995). Dlats and warts encoded the same gene so in this thesis the original homologue of LATS is warts (wts). Homozygous loss of the warts gene in Drosophila formed greatly overgrown somatic cells which lead to the hypothesis that warts is a tumour suppr …

Cancer DevelopmentCancer is a group of diseases that involves abnormal cell growth resulting in malignant tumours/ malignant neoplasms. Cancer is a leading cause of morbidity, with 14 million new cases diagnosed and 8.2 million people dying from cancer in 2012 (World Health Organisation 2015). The different types of cancers are classified by the cell type they originate from. The most common cancers are breast, colorectum, lung, cervix, and stomach cancer. There are a number of risk factors that lead to cancer development such as smoking tobacco, an unbalanced diet, being overweight, alcohol use and lack of physical activity (World Health Organisation 2015) Cancer development results i …

A wide variety of cell surface receptors activate Ras GTPase, including the tyrosine receptor linked to the epidermal growth factor receptor (EGFR) (Wells 1999). Upon receptor stimulation, son of sevenless (SOS) stimulates Ras to change from GDP to GTP resulting in Ras activation (Geyer and Wittinghofer 1997).Ras GTPaseRas GTPase shuttles between inactive GDP-bound and active GTP-bound conformation (Colicelli 2004). The best characterised isoforms of Ras GTPase are K-Ras, H-Ras and N-Ras, which are demonstrated to be mutated in 30% of human tumours (Repasky et al. 2004). Activated Ras phosphorylates and activates the Ser/Thr kinase Raf. The three isoforms of Raf are B-Raf, Raf-1 and A- …

Unregulated cell growthCancer, although heterogeneous by its very nature, can be broadly defined as a set of diseases characterised by unregulated cell growth leading to invasion of surrounding tissues and spread (metastasis) to other parts of the body (King et al., 2006). Inhibiting cell division therefore represents a key therapeutic target for cancer.Characteristics of cancer cellsIn their seminal review, Hanahan and Weinberg identified 6 key characteristics of cancer cells, namely: autostimulation; angiogenesis; metastasis; insensitivity to antiproliferative signals; resistance to apoptosis; and limitless replicative potential (Hanahan et al., 2000). This list was recently expande …

By Catríona Dowling, Post-Doc, RCSI I want you to come on a journey with me where we are going to the botanic gardens. You will pick a section of the garden that is yours: yours to treasure and nourish. If a weed started to grow in that garden, would you chose to ignore the weed or would you try to remove it? And if you did leave it there, would you expect it to grow and spread or just stay as it is? I am no Diarmuid Gavin but what I am is a cancer researcher and I am here to try and explain the benefits of cancer prevention and early diagnosis. Did you know that 50% of all cancers are preventable with 30% preventable by lifestyle changes alone? Cancer is like the weed in our bod …

ELISA Genie is delighted to announce the date of our next Cancer Research Club which will be taking place on the 31st of March at TTMI, Trinity College Dublin. This event will focus on the role of the mucosal immunity & genetic pathology of the colon. Genetic Pathology & Mucosal Immunity Date: 31/03/2020 Time: 1:30 pm - 5 pm Trinity Translational Medicine Institute, St James's Hospital window.SHOGUN_IMAGE_ELEMENTS = window.SHOGUN_IMAGE_ELEMENTS || …

Hepatocellular carcinoma (HCC) is one of the most frequently occurring cancers and there are 630,000 new cases diagnosed every year worldwide (De Minicis et al. 2013). HCC develops frequently from chronic hepatitis or cirrhosis of the liver (Thorgeirsson and Grisham 2002). These conditions result in hepatocyte destruction and promotion of immune cell invasion of the liver tissue, which in turn results in changes of the matrix and micro-environment of the liver (Bosch et al. 1999). Hepatitis B virus About 80% of HCC develops from hepatitis B virus (HBV), hepatitis C virus (HCV) and aflatoxin B1 (AFB) (Bosch et al. 1999). The development of HCC can take nea …

By Charlotte O’Donnell PhD Cancer Carcinogenesis is a multi-step process that develops through epigenetic changes and mutation of multiple genes, including loss of function of tumour suppressor genes and gain of function of oncogenes. These genetic changes in normal cells can each contribute a growth advantage, leading to the transformation of cells into cancer cells [1]. In 2000, Hanahan and Weinberg described a series of 6 biological capabilities or ‘hallmarks’ acquired by most types of cancers during the multi-step development of cancer (Figure 1). They are as follows; ‘sustaining proliferative signalling’, …

Nanosilver is the most commercialised nanoparticle routinely used for its antibacterial purposes in food preservation, cosmetic and health products such as medical devices and wound treatment products (Vance et al., 2015). Interestingly, research on nanosilver has now progressed beyond antibacterial use to application as anticancer owing to some studies that have demonstrated the anticancer properties of nanosilver (Zhang et al., 2014, Zhang et al., 2016). Unfortunately, the wide antibacterial application of nanosilver coupled with the very high amounts of the nanoparticles in these commercialised and every day consumable products with the new anticancer application portends a seri …

By Charlotte O'Donnell PhD …

By Charlotte O’Donnell PhD Inflammation and Cancer The link between inflammation and cancer is well established, with inflammation highlighted as one of the enabling characteristics in cancer development [1]. As early as 1863, Virchow indicated that cancer tended to occur at sites of chronic inflammation. Indeed many cancers are associated with chronic inflammation. Patients with chronic hepatitis caused by Hepatitis B and C infection are at increased risk of developing hepatocellular carcinoma, while infection with human papilloma virus (HPV) is linked to the development of cervical cancer [2]. In the colon, infla …