Epigenetic silencing is considered to be a major mechanism for loss of activity in tumor suppressors. Reversal of epigenetic silencing by using inhibitors of DNA methyltransferase (DNMT) or histone deacetylases (HDACs) such as 5-Aza-CdR and FK228 has shown to enhance cytotoxic activities of several anticancer agents. This study aims to assess the combinatorial effects of gene-silencing reversal agents (5-Aza-CdR and FK228) and oxaliplatin in gastric cancer cells, i.e., Epstein-Barr virus (EBV)-negative SNU-638 and EBV-positive SNU-719 cells. The doublet combinatorial treatment of 5-Aza-CdR and FK228 exhibited synergistic effects in both cell lines, and this was further corroborated by Zta expression induction in SNU-719 cells. Three drug combinations as 5-Aza-CdR/FK228 followed by oxaliplatin, however, resulted in antagonistic effects in both cell lines. Simultaneous treatment with FK228 and oxaliplatin induced synergistic and additive effects in SNU-638 and SNU-719 cells, respectively. Three drug combinations as 5-Aza-CdR prior to FK228/oxaliplatin, however, again resulted in antagonistic effects in both cell lines. This work demonstrated that efficacy of doublet synergistic combination using DNMT or HDACs inhibitors can be compromised by adding the third drug in pre- or post-treatment approach in gastric cancer cells. This implies that the development of clinical trial protocols for triplet combinations using gene-silencing reversal agents should be carefully evaluated in light of their potential antagonistic effects.
Antineoplastic Agents ; Cell Line ; DNA ; Drug Combinations ; Epigenomics* ; Herpesvirus 4, Human ; Histone Deacetylases ; Humans* ; Stomach Neoplasms* ; Triplets

INTRODUCTIONThe revised Human Organ Transplant Act (HOTA) was implemented in Singapore in July 2004. We aim to evaluate expanding the potential donor pool for liver transplant in Singapore with the inclusion of marginal donors.

MATERIALS AND METHODSAll donor referrals between July 2004 and June 2007 were studied. All potential deceased liver donors were heart-beating. After being reviewed by the transplant coordinator, potential donors were assessed by a transplant hepatologist and a transplant surgeon for suitability of organ donation strictly based on the programme's donor assessment protocol. Reasons for rejection as potential donors were documented. The clinical characteristics of all donor referrals were retrospectively reviewed, and an independent decision was made as to whether liver retrieval in each rejected case might have been possible.

RESULTSAmong the 128 potential donor referrals, 20 donors (15.6%) underwent liver retrieval. Of the 20 livers retrieved, 16 were implanted and 4 were not implanted (3 unfit recipients, and 1 donor liver with 40% steatosis). Another 10 donor livers were assessed intraoperatively and were rejected because of varying levels of steatosis. Of these livers assessed, 5 donor livers had steatosis <40% and 5 had steatosis >40%. Of the remaining potential donors, 45 were deemed not possible because of prolonged hypotension (9), on-going or unresolved sepsis (13), high-risk behaviour (4), non-actualisation (8), or pre-existing medical conditions (11). Another 53 donors may potentially have been suitable donors but were rejected because of possible sepsis (13), no suitable recipients (12), transient hypotension (10), transient abnormal liver function test (6), history of alcohol ingestion (5), non-actualisation because of consent (4) and other reasons (3). Overall, it was deemed that 61 donors (47.7%) might potentially have been suitable liver donors.

CONCLUSIONSDespite new legislation (HOTA) in Singapore, the utilisation of cadaveric donor livers showed no increase in the last 3 years. By expanding our donor criteria to include marginal donors, we could potentially increase the availability of deceased donor livers to meet our waiting list demands.

Adult ; Female ; Humans ; Liver Transplantation ; Living Donors ; legislation & jurisprudence ; supply & distribution ; Male ; Middle Aged ; Referral and Consultation ; organization & administration ; Retrospective Studies ; Singapore ; Tissue and Organ Procurement ; legislation & jurisprudence ; Waiting Lists

INTRODUCTIONTraditional Chinese medicine (TCM) has been used as an alternative in treating children with atopic dermatitis (AD) but its efficacy and potential side effects are debatable. We recently used a TCM capsule (PentaHerbs) on 9 children and observed significant reductions in clinical scores of disease severity. However, there have been concerns that the therapeutic effects of many forms of TCM are due to the presence of corticosteroids. The purpose of this study was to evaluate if common corticosteroids are present in PentaHerbs capsules.

MATERIALS AND METHODSPentaHerbs powder was analysed with thin-layer chromatography, infra-red spectrophotometry and liquid chromatography mass spectrometry.

RESULTSHydrocortisone, prednisolone, fludrocortisone and dexamethasone were not detected in the PentaHerbs capsules.

CONCLUSIONCorticosteroids are not present in the 5 familiar herbs that were earlier shown to have efficacy on AD.

Child ; Chromatography, Thin Layer ; Dermatitis, Atopic ; drug therapy ; Drug Combinations ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Glucocorticoids ; analysis ; therapeutic use ; Humans ; Mass Spectrometry ; Pilot Projects ; Spectrophotometry, Infrared