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The fusion protein, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), results from the chromosome translocation t(2;5)(p23;q25) and is present in 50-70 percent of anaplastic large-cell lymphomas (ALCLs). NPM-ALK is a constitutively activated kinase that transforms cells through stimulating several mitogenic signaling pathways. To examine if the NPM-ALK is a potential therapeutic target in ALCL, we used siRNA to specifically downregulate the expression of the NPM-ALK in ALCL cell lines. In this report, we demonstrated viability loss in t(2;5)-positive ALCL cell lines, SUDHL-1 and Karpas 299 cells, but not in lymphoma cell lines without the chromosome translocation, Jurkat and Granta 519 cells. Further study demonstrated that the downregulation of NPM-ALK resulted in decreased cell proliferation and increased cell apoptosis. When used in combination with chemotherapeutic agents, such as doxorubicin, the inhibition of the NPM-ALK augments the chemosensitivity of the tumor cells. These results revealed the importance of continuous expression of NPM-ALK in maintaining the growth of ALCL cells. Our data also suggested that the repression of the fusion gene might be a potential novel therapeutic strategy for NPM-ALK positive ALCLs. [ABSTRACT FROM AUTHOR]

Seven new pentasaccharides (1–7), rehmaglupentasaccharides A-G, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known verbascose (8) and stachyose (9) were also obtained in the current investigation, and the structure of stachyose was unequivocally defined using X-ray diffraction data. Compounds 1–9 were tested for their cytotoxicity against five human tumor cell lines, influence on dopamine receptor activation, and proliferation effects against Lactobacillus reuteri. [ABSTRACT FROM AUTHOR]

Epigenetic parameters linked to E-cadherin gene were investigated in 5 human colorectal cancer cell lines. Treatment with trichostatin A led to enhanced acetylation of histone H3-K9 with concurrent induction of E-cadherin mRNA in 3 E-cadherin low/negative cell lines that are not DNA methylated. Co-treatment with 5-aza-2'-deoxycytidine and trichostatin A resulted in additive/synergic induction of E-cadherin mRNA in all 5 cell lines with concomitant enhancement of histone H3-K9 acetylation in 4 E-cadherin low/negative cell lines. Our results suggest that histone H3-K9 deacetylation appears to play a crucial role in transcriptional repression of E-cadherin in colorectal cancers. [ABSTRACT FROM AUTHOR]