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Among hematological malignancies, acute leukemia is the major cause of mortality. Despite improvement of survival with current chemotherapies, some patients still diefrom the disease or the treatment side effects. Thus, new therapeutic agents are needed. Anti-cancer drugs derived from natural products are of interest. Frondoside A is a triterpenoid glycoside form the sea cucumber, Cucumaria frondosa that has shown potent antitumor effects in various cancers. Previous studies in acute leukemia are limited. The current study investigated the effects of frondoside a in acute leukemia cell lines alone and in combination with drugs currently used for this malignancy. This study is the first to attempt comparing the efficacy of this compound to available conventional drugs. The acute leukemia cell lines used were CCRF-CEM, HL-60 and THP-1. Cells were cultured and treated with different concentrations of frondoside A, vincristine sulphate, asparaginase and prednisolone each compound alone and in combination with frondoside A. Experiments were conducted with treatment incubation periods of 24, 48 and 72h. The inhibitory concentration 50 (IC50) for each compound at each time point was determined for the three cell lines using the CellTiter-Glo luminescence assay. Induction of apoptosis was examined using Annexin V test and expression of apoptosis-related genes (low-density expression array) was investigated in two acute leukemia cell lines. The expression of protein products of selected genes was also investigated. The effect of frondoside A combined with NFκB pathway inhibitor, andrographolide in acute leukemia cell lines was also examined. CCRF-CEM cells were very sensitive to frondoside a treatment while HL-60 and THP-1 were less sensitive. Frondoside A markedly enhanced the anticancer effects of all of the conventional drugs in all cell lines. Synergistic effects were seen in some of the combination concentrations. Induction of apopto

Cancer cachexia is responsible for one third of cancer–related deaths and contributes to the death of many others. More than 80% of cancer patients are cachectic towards the end of life. Despite intensive research, the mechanisms of cancer cachexia are still poorly understood. It is our hypothesis that identification of early changes in gene expression in cachexia will lead to an improved understanding of the mechanism that trigger this important problem in cancer patients. Thus, to shed light on the mechanisms involved in the major cachexia target tissues, we investigated the entire transcriptome in muscle and fat to identify altered expression of genes in cancer patients with and without cachexia. Samples of rectus abdominis muscle and visceral fat were collected at surgery from patients exhibiting 5-10% weight loss prior to surgery, compared with stable-weight patients. Analysis of all expressed genes was carried out using next generation sequencing (Illumina HiSeq 2500). Also, selected differentially expressed genes were confirmed using real time RT-PCR. In muscle, 30 genes showed highly significant changes in expression (25 downregulated and 5 upregulated: P In visceral fat, expression of 6 genes were downregulated and 10 upregulated with high statistical significance (P