Abouda, G.F.; Pohler, E.; Dillon, J.F.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA57
Academic Journal
Background: Oesophageal cancer is a disease with a dreadful prognosis and a rapidly rising incidence. New therapies For treatment of this cancer need to be evaluated and in this area gene therapy may have a role to play. Aims: Using liposomes as a transfer agent, to assess the expression of the p53 gene (human and mouse wild type and mutants) in oesophageal cancer cell lines, estimating the degree of apoptosis in these cell lines. In addition, to determine the effect the mouse Scottin gene, a p53 inducible pro-apoptotic gene, on cell survival. Method: Two squamous cell carcinoma cell lines (OE21 and KYSE30), and two adenocarcinoma cell lines (OE33 and OE19) were transfected with human and mouse wild type p53 constructs. Following 48 hours incubation, cells were analysed by Western blotting (to examine expression of p53) and FACScan (to detect apoptosis). Cells were also transfected with mutant forms of both the human and mouse p53 genes, and the effects of these on the cell survival compared to the wild types. Finally, cells were transfected with the mouse Scottin gene and the consequences of its expression determined. Results: p53 expression was found to be higher in OE33 and OE21 cells by Western blotting than in KYSE30 and OE19. FACScan analysis revealed high levels of apoptosis were achieved in OE21 and OE 33 cells following wild type p53 expression. Apoptosis was also observed in KYSE30 cells but to a lesser degree. In all three of these cell lines, this effect was more pronounced using the mouse p53 gene compared to the human p53. The levels of apoptosis observed were increased further in OE21, OF33 and KYSF30 cells following expression of the mutant forms of both human and mouse p53. However, highest degrees of apoptosis were obtained in these cell lines with expression of the Scottin gene. No apoptosis was seen following expression of any of the constructs in OE19 cells. Conclusion: We have succeeded in inducing apoptosis in three different oesophageal...


Related Articles

  • Selective gene expression using a DF3/MUC1 promoter in a human esophageal adenocarcinoma model. Gupta, V K; Park, J O; Kurihara, T; Koons, A; Mauceri, H J; Jaskowiak, N T; Kufe, D W; Weichselbaum, R R; Posner, M C // Gene Therapy;Feb2003, Vol. 10 Issue 3, p206 

    The efficacy of replication-deficient adenoviral vectors in gene therapy is confined to the number of tumor cells the vector infects. To focus and enhance the therapeutic efficacy, we employed a conditionally replication-competent adenoviral vector with a tissue-specific promoter, DF3/MUC1, in a...

  • P53 gene therapy for esophageal cancer. Shimada, Hideaki; Matsubara, Hisahiro; Ochiai, Takenori // Journal of Gastroenterology;2002 Supplement 14, Vol. 37 Issue 11, p87 

    Despite improvement of surgical treatment and application of multimodality therapies to advanced esophageal cancer, the prognosis is extremely poor for patients with unresectable tumors. Based on the genetic background of esophageal cancer, we have developed various gene therapy strategies...

  • Enhanced growth suppression in esophageal carcinoma cells using adenovirus-mediated fusion gene transfer (uracil phosphoribosyl transferase and herpes simplex virus thymidine kinase). Shimizu, Takanori; Shimada, Hideaki; Ochiai, Takenori; Hamada, Hirofumi // Cancer Gene Therapy;Jul2001, Vol. 8 Issue 7, p512 

    Advanced esophageal cancers are highly malignant and frequently resistant to 5-fluorouracil (5-FU). Escherichia coli uracil phosphoribosyltransferase (UP) is a pyrimidine salvage enzyme that alters 5-FU metabolism and sensitivity. A recombinant adenovirus encoding the UP gene (AxCA.UP) has been...

  • Symptom clusters predicted poor outcomes after surgery for esophageal cancer.  // Hem/Onc Today;1/25/2014, Vol. 15 Issue 2, p16 

    The article discusses a study led by Anna Wikman, published in a 2013 issue of the journal "Cancer," suggesting that symptoms clustering in certain patients after surgery for esophageal cancer appear to have a strong prognostic value.

  • Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma. Kawakami, Kazuyuki; Brabender, Jan; Kawakami, K; Brabender, J; Lord, R V; Groshen, S; Greenwald, B D; Krasna, M J; Yin, J; Fleisher, A S; Abraham, J M; Beer, D G; Sidransky, D; Huss, H T; Demeester, T R; Eads, C; Laird, P W; Ilson, D H; Kelsen, D P; Harpole, D // JNCI: Journal of the National Cancer Institute;11/15/2000, Vol. 92 Issue 22, p1805 

    Background: The adenomatous polyposis coli (APC) locus on chromosome 5q21-22 shows frequent loss of heterozygosity (LOH) in esophageal carcinomas. However, the prevalence of truncating mutations in the APC gene in esophageal carcinomas is low. Because hypermethylation of promoter...

  • Cytotoxicity of adenoviruses expressing the wild-type p53 gene to esophageal carcinoma cells is linked with the CAR expression level and indirectly with the endogenous p53 status. Ma, G.; Kawamura, K.; Li, Q.; Suzuki, N.; Liang, M.; Namba, M.; Shimada, H.; Tagawa, M. // Cancer Gene Therapy;Nov2009, Vol. 16 Issue 11, p832 

    We examined cytotoxic effects of adenoviruses (Ad) expressing the p53 gene (Ad-p53) in nine human esophageal carcinoma cell lines with respect to the Ad receptor expression and the endogenous p53 gene status. Ad-p53-mediated cytotoxicity was related with an expression level of the coxsackievirus...

  • Identification of New Candidate Genes and Chemicals Related to Esophageal Cancer Using a Hybrid Interaction Network of Chemicals and Proteins. Gao, Yu-Fei; Yuan, Fei; Liu, Junbao; Li, Li-Peng; He, Yi-Chun; Gao, Ru-Jian; Cai, Yu-Dong; Jiang, Yang // PLoS ONE;Jun2015, Vol. 10 Issue 6, p1 

    Cancer is a serious disease responsible for many deaths every year in both developed and developing countries. One reason is that the mechanisms underlying most types of cancer are still mysterious, creating a great block for the design of effective treatments. In this study, we attempted to...

  • A nomogram to predict prognostic values of various inflammatory biomarkers in patients with esophageal squamous cell carcinoma. Jin-Shi Liu; Ying Huang; Xun Yang; Ji-Feng Feng // American Journal of Cancer Research;2015, Vol. 5 Issue 7, p2180 

    Background: Inflammation plays an important role in cancer progression and prognosis. However, the prognostic values of inflammatory biomarkers in esophageal cancer (EC) were not established. In the present study, therefore, we initially used a nomogram to predict prognostic values of various...

  • LC3B globular structures correlate with survival in esophageal adenocarcinoma. El-Mashed, Shereen; O'Donovan, Tracey R.; Kay, Elaine W.; Abdallah, Ayat R.; Cathcart, Mary-Clare; O'Sullivan, Jacintha; O'Grady, Anthony; Reynolds, John; O'Reilly, Seamus; O'Sullivan, Gerald C.; McKenna, Sharon L. // BMC Cancer;Aug2015, Vol. 15 Issue 1, p1 

    Background: Esophageal adenocarcinoma has the fastest growing incidence of any solid tumor in the Western world. Prognosis remains poor with overall five-year survival rates under 25%. Only a limited number of patients benefit from chemotherapy and there are no biomarkers that can predict...


Read the Article


Sign out of this library

Other Topics