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Dihomo-γ-Linolenic Acid Inhibits Growth of Xenograft Tumors in Mice Bearing Human Pancreatic Cancer Cells (BxPC-3) Transfected with Delta-5-Desaturase shRNA
In this study, we have further investigated the anti-tumor effects of D5D-knockdown and the resulting intensified COX-2-catalyzed DGLA peroxidation in subcutaneous xenograft tumors. Four-week old female nude mice (Jackson Laboratory, J:Nu-007850) were injected with human pancreatic cancer cell line BxPC-3 or its D5D knockdown counterpart (via shRNA), followed by 4-week treatments of: vehicle control, DGLA supplementation (8 mg/mouse, twice a week), gemcitabine (30 mg/kg, twice a week), and a combination of DGLA and gemcitabine. In D5D-knockdown tumors, DGLA supplementation promoted 8-HOA formation to a threshold ...
Source: Redox Biology - October 17, 2018 Category: Biology Source Type: research

Cooperation of Musashi-2, Numb, MDM2, and P53 in drug resistance and malignant biology of pancreatic cancer Research
Our earlier work showed that Musashi (MSI)-2 promoted the development of pancreatic cancer (PC) by down-regulating Numb, which prevented murine double-minute (MDM)-2–mediated p53 ubiquitin degradation. Thus, we investigate the relationship among MSI2, Numb, MDM2, and p53 in PC in vitro and in vivo, an association that has not been reported to our knowledge. MSI2 had no relationship with mutant p53 (mtp53) and wild-type p53 (wtp53) in normal PC cells. However, in response to gemcitabine or cisplatin treatment, MSI2 silencing simultaneously down-regulated MDM2 and up-regulated Numb and wtp53 protein levels. Moreover, t...
Source: FASEB Journal - June 1, 2017 Category: Biology Authors: Sheng, W., Dong, M., Chen, C., Wang, Z., Li, Y., Wang, K., Li, Y., Zhou, J. Tags: Research Source Type: research

The superoxide dismutase 1 (SOD1) 3'UTR maintains High expression of the SOD1 gene in Cancer cells: The involvement of the RNA binding protein AUF1.
In this study, a full-length 3'UTR of the SOD1 transcript was cloned and characterized for its ability to regulate SOD1 gene expression in human cancer cells. Inclusion of the SOD1 3'UTR in the pGL3 reporter construct dramatically enhanced the reporter activity by 10-220-fold in various cell lines. RT-PCR analysis, however, indicated that the reporter gene mRNA levels were only modestly altered by the SOD1 3'UTR, suggesting that SOD1 3'UTR enhances the reporter gene activity not simply by stabilizing the mRNA but primarily through promoting translation of the protein. Bioinformatics analysis showed multiple stem and loop s...
Source: Free Radical Biology and Medicine - April 20, 2015 Category: Biology Authors: Zhang S, Xue J, Zheng J, Wang S, Zhou J, Jiao Y, Geng Y, Wu J, Hannafon BN, Ding WQ Tags: Free Radic Biol Med Source Type: research

Vav1 as a Central Regulator of Invadopodia Assembly.
Abstract Invadopodia are protrusive structures used by tumor cells for degradation of the extracellular matrix to promote invasion [1]. Invadopodia formation and function are regulated by cytoskeletal-remodeling pathways and the oncogenic kinase Src. The guanine nucleotide exchange factor Vav1, which is an activator of Rho family GTPases, is ectopically expressed in many pancreatic cancers, where it promotes tumor cell survival and migration [2, 3]. We have now determined that Vav1 is also a potent regulator of matrix degradation by pancreatic tumor cells as depletion of Vav1 by siRNA-mediated knockdown inhibits t...
Source: Current Biology - December 11, 2013 Category: Biology Authors: Razidlo GL, Schroeder B, Chen J, Billadeau DD, McNiven MA Tags: Curr Biol Source Type: research

Target Inhibition Networks: Predicting Selective Combinations of Druggable Targets to Block Cancer Survival Pathways
by Jing Tang, Leena Karhinen, Tao Xu, Agnieszka Szwajda, Bhagwan Yadav, Krister Wennerberg, Tero Aittokallio A recent trend in drug development is to identify drug combinations or multi-target agents that effectively modify multiple nodes of disease-associated networks. Such polypharmacological effects may reduce the risk of emerging drug resistance by means of attacking the disease networks through synergistic and synthetic lethal interactions. However, due to the exponentially increasing number of potential drug and target combinations, systematic approaches are needed for prioritizing the most potent multi-target alter...
Source: PLoS Computational Biology - September 12, 2013 Category: Biology Authors: Jing Tang et al. Source Type: research