5-Fluorouracil targets thymidylate synthase in the selective suppression of TH17 cell differentiation

While it is well established that treatment of cancer patients with 5-Fluorouracil (5-FU) can result in immune suppression, the exact function of 5-FU in the modulation of immune cells has not been fully established. We found that low dose 5-FU selectively suppresses TH17 and TH1 cell differentiation without apparent effect on Treg, TH2, and significantly suppresses thymidylate synthase (TS) expression in TH17 and TH1 cells but has a lesser effect in tumor cells and macrophages. Interestingly, the basal expression of TS varies significantly between T helper phenotypes and knockdown of TS significantly impairs TH17 and TH1 cell differentiation without affecting the differentiation of either Treg or TH2 cells. Finally, low dose 5-FU is effective in ameliorating colitis development by suppressing TH17 and TH1 cell development in a T cell transfer colitis model. Taken together, the results highlight the importance of the anti-inflammatory functions of low dose 5-FU by selectively suppressing TH17 and TH1 immune responses

BRD4 Inhibitor Inhibits Colorectal Cancer Growth and Metastasis

Post-translational modifications have been identified to be of great importance in cancers and lysine acetylation, which can attract the multifunctional transcription factor BRD4, has been identified as a potential therapeutic target. In this paper, we identify that BRD4 has an important role in colorectal cancer; and that its inhibition substantially wipes out tumor cells. Treatment with inhibitor MS417 potently affects cancer cells, although such effects were not always outright necrosis or apoptosis. We report that BRD4 inhibition also limits distal metastasis by regulating several key proteins in the progression of epithelial-to-mesenchymal transition (EMT). This effect of BRD4 inhibitor is demonstrated via liver metastasis in animal model as well as migration and invasion experiments in vitro. Together, our results demonstrate a new application of BRD4 inhibitor that may be of clinical use by virtue of its ability to limit metastasis while also being tumorcidal

λ-selection strategy in C+L band 1-Pbit/s (448 WDM/19-core/128 Gbit/s/channel) flex-grid space division multiplexed transmission

In this paper, an inter-core crosstalk based wavelength selection scheme has been proposed for flex-grid super-channels in space division multiplexed transmission. The two λ-selection strategies are categorized as: (a) aligned wavelength super-channels (Aλ-SCs), where all super-channels are placed at same λ in all the cores and (b) interleaved wavelength super-channels (Iλ-SCs), where all super-channels are placed at different λ in all the neighboring cores. It is depicted that system performance is improved for DP-16QAM channels in 1-Pbit/s (448 WDM/19 Core/128 Gbit/s/channel) 60 km fiber link, when Iλ-SCs scheme is implemented