Abstract The epigenetic alterations marked by DNA methylation contribute to the malignant transformation of cells by silencing critical genes responsible for the regulation of growth. The potent DNA methylation inhibitor 5-aza-2’-deoxycytidine (decitabine; DAC) has shown effectiveness in patients with myeloid malignancies. However, the responses are of short duration. The effectiveness of the DAC therapy may be limited by its incapacity to reactivate enough tumor suppressor genes. Other epigenetic mechanisms, such as the histone modification of target genes, may also hinder gene reactivation by DAC. The dose limiting toxicity of DAC is myelosuppression, which limits the duration of this therapy for clinical use. The clinical effectiveness of DAC may be enhanced by its use in combination with other agents that have diverse mechanisms of action. In this literature review, we summarize the results of preclinical and recent clinical trials of DAC used in combination with other agents to treat cancer. This review was conducted by searching online databases to analyze the available evidence regarding this area of interest. We looked at the combination of DAC with other epigenetic agents, cytotoxic agents, tyrosine kinase inhibitors, biochemical modulators and non-toxic agents. The data compiled suggests that combination epigenetic therapy is feasible, moderately toxic and has promising clinical potential. Preclinical studies showed that some combinations of DAC have additive to synergistic antineoplastic action as compared to DAC alone. The data indicate that combination chemotherapy with DAC merits further investigation. This review may be helpful for the future design of clinical trials using DAC in combination for cancer therapy.
Keywords: decitabine; 5-aza-2’-deoxycytdine; epigenetics; acute myeloid leukemia; cancer; combination chemotherapy; DNA methylation; epigenetic agents; histone deacetylase inhibitors; tyrosine kinase inhibitors; non-toxic agents

Abstract Neuroendocrine tumours of the digestive system (GEP-NET) are relatively rare. Nevertheless, their diagnoses is rising as seen from studies in the US and elsewhere. Gastric neuroendocrine tumours (Gastric NETs) vary through a wide clinical spectrum, from asymptomatic cases to functioning tumours. Gastrointestinal specialists need to be aware and pursue these lesions as they are indolent with a malignant variant and a potential for metastasis. A computerised search through our pathology laboratory data base, using codes for gastric, carcinoid and neuroendocrine tumour/ hyperplasia, was used to identify cases from January 2008 to September 2014. Medical charts were retrieved, examined. Eleven cases were identified and re-examined by one consultant pathologist. There were 5 females - mean age of 50 years (39-59) and 6 males - mean age of 57 years (41-73). Mean follow up period was 4.5 years (1- 9). Gastric NETs fall into Type I, II and III (WHO Classification). Our series showed eight cases of Type I managed by biopsy/ endoscopic mucosal resection (EMR). No Type II cases were identified and one case of Type III had a subtotal gastrectomy and lymphadenectomy. Two neuroendocrine hyperplasia cases were managed by biopsy only. Cases were followed up (except one who refused) with regular upper endoscopy and imaging as indicated. A literature review of managing Gastric NETs was discussed. We aim to alert gastrointestinal specialists by presenting a retrospective study of Gastric NETs from a single teaching institution.
Keywords: gastric; neuroendocrine tumour; hyperplasia; incidence; management of gastric