Essay Example on Restricted options for treatment Hepatocellular carcinoma HCC

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Due to increasing rates of incidents often late diagnosis and restricted options for treatment Hepatocellular carcinoma HCC is a major concern for public health It is known that Transforming growth factor beta TGF β provides cytostatic signals in both the primary phases of liver damage and in regeneration However TGF β also deploys tumour promoting effects throughout the progression of liver cancer and during onset In this study changes in mRNA levels of E cadherin and Vimentin were measured using quantitative reverse transcriptase PCR qRT PCR to assess the impact of TGF β on human hepatocellular carcinoma cells Results showed significant variation in E cadherin and vimentin expression One sample treated with TGF β stimulated downregulation of E cadherin whereas the other sample that was treated stimulated up regulation of vimentin Introduction The third most significant cause of cancer related mortality worldwide is Hepatocellular carcinoma HCC Parkin et al 2005 The prognosis for many HCC patients remains bleak despite scientific advances This is due to intrahepatic and extrahepatic metastasis and recurrence of cancer post surgery Contributing to the lack of reliable therapy for advanced 



HCC is the fact that the pathological process of HCC development and metastasis is unclear Acloque et al 2009 Mounting evidence suggests that the epithelial to mesenchymal transition EMT of epithelial cancers is related to aggressive tumours in patients suffering with HCC EMT signifies epithelial cells that are stationary polarized and organized in stratum changing to become single fibroblastoid cells capable of locomotion Acloque et al 2009 Initially defined for its role during embryonic development EMT is now hypothesized to impact on metastatic cancers An example is the correlation between the up regulation of Twist a transcription factor that drives EMT and HCC cell invasion and metastasis Matsuo et al 2009 In addition the core protein in the hepatitis C virus is capable of shifting the transforming growth factor β TGF β response from tumour suppression to EMT This potentially contributes to metastasis in HCC Battaglia et al 2009 EMT is categorised by a reduction in cell adhesion which is accompanied by the down regulation of the epithelial adhesion protein E cadherin Kalluri and Weinberg 2009 It is characteristic for cells undergoing EMT to display down regulation of E cadherin and increase expression of the mesenchymal markers N cadherin vimentin and fibronectin Moreno Bueno et al 2009 EMT is regulated by several transcription factors including Snail Slug Zeb1 Zeb2 Twist1 2 and E12 E47 Each of these bind the E cadherin promoter and suppress transcription A number of signalling pathways including TGF β and hepatocyte growth factor HGF are involved in the start and continuation of EMT Kalluri and Weinberg 2009 One of the key molecules involved in cell cell adhesion in epithelial tissues is E cadherin 



This molecule is located on the surface of epithelial cells in regions known as adherens junctions where cadherin receptors connect adjacent plasma membranes E cadherin is a vital molecule involved in the construction and preservation of the epithelia Gumbiner 1996 Further to the role it plays in normal cells this highly conserved gene is capable of majorly impacting the transformation of malignant cells particularly in the growth and progression of tumours Suppressing the expression of E cadherin is considered to be one of the crucial molecular occurrences responsible for dysfunctional cell cell adhesion Most tumours have irregular cellular structures and this loss of tissue integrity can result in local invasion Therefore increased invasiveness and metastasis of tumours is correlated to the loss of function of E cadherin tumour suppressor proteins This results in the loss being referred to as the suppressor of the invasion gene Vleminckx et al 1991 Expressed in mesenchymal cells Vimentin is a type III intermediate filament IF protein and these proteins are found in all metazoan cells Eriksson et al 2009 The cytoskeleton is comprised of IF and tubulin based microtubules and actin based microfilaments Vimentin is the main component of the cytoskeleton in mesenchymal cells All IF proteins are expressed in a highly developmentally regulated manner which consequently means that vimentin is frequently used as a marker throughout normal development and metastatic progression of mesenchymal cells or cells undergoing an epithelial to mesenchymal transition EMT Eriksson et al 2009 Result 



The quantity of RNA extracted was measured from two samples treated and untreated using a spectrophotometer The ratios of OD260 280 and OD260 230 in the untreated sample were 2 0 and 1 34 respectively Figure 2 1 whereas the treated sample were 2 04 and 1 37 respectively Figure 2 2 With regards to agarose gel electrophoresis both samples appeared to lack the typical band pattern expected for RNA Figure 2 3 The quantitative reverse transcriptase PCR QRT PCR was used to measure the level of expression of E cadherin and Vimentin in the untreated sample and TGF B treated sample with 10ng ml for 24hours along with housekeeping gene GAPDH The results revealed that the untreated sample for both E cadherin and Vimentin gave a 1 fold change while the samples treated with TGF B for E cadherin gave a value of 0 012 Figure 2 4 and those for Vimentin gave a 49 69 fold change Figure 2 5


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