Medicine and Health Sciences Commons^™

Activation Of Amp-Activated Protein Kinase By 3,39-Diindolylmethane (Dim) Is Associated With Human Prostate Cancer Cell Death In Vitro And In Vivo, Di Chen, Sanjeev Banerjee, Qiuzhi C. Cui, Dejuan Kong, Fazlul H. Sarkar, Q. Ping Dou

Oncology Faculty Publications

There is a large body of scientific evidence suggesting that 3,39-Diindolylmethane (DIM), a compound derived from the digestion of indole-3-carbinol, which is abundant in cruciferous vegetables, harbors anti-tumor activity in vitro and in vivo. Accumulating evidence suggests that AMP-activated protein kinase (AMPK) plays an essential role in cellular energy homeostasis and tumor development and that targeting AMPK may be a promising therapeutic option for cancer treatment in the clinic. We previously reported that a formulated DIM (BR-DIM; hereafter referred as B-DIM) with higher bioavailability was able to induce apoptosis and inhibit cell growth, angiogenesis, and invasion of prostate cancer cells. …

Modulation Of Anti-Tumor Immune Response By Tgf-Β-Inducible Early Gene 1 (Tieg1), Andi Cani

Wayne State University Theses

Cancer immunotherapy has had limited clinical efficacy partly because regulatory T cells (Treg) suppress the immune response to tumor-associated antigens. Inducible regulatory T cells (iTreg), which are converted from naïve CD4 T cells by TGF-β, an abundant cytokine in the tumor microenvironment, may contribute to this immune suppression. Induction of Foxp3 by TGF-β is mediated by the transcription factor TIEG1 and abrogation of this protein prevents Foxp3 expression. We are testing the hypothesis that blockade of TIEG1 to prevent iTreg conversion will enhance immune response in DNA vaccination to the tumor associated antigen Her-2. Wild type and TIEG1 knockout mice …

Substance P And The Host Immune Response, Megan Elizabeth Foldenauer

Wayne State University Dissertations

This body of work examined the mechanism by which SP regulates host immunity, specifically, its control of growth factors and TLR expression in the P. aeruginosa-infected cornea. The role of mTOR and VIP in corneal infection and inflammation also was tested.

SP has a dual role in bacterial infection, unexpectedly upregulating growth factor production. This was accompanied by macrophage-specific upregulation of pro-inflammatory cytokines, downregulation of anti-inflammatory cytokines, and upregulation of anti-apoptotic genes, as well as a decrease in arginase-producing macrophages (M2 cells), important in stromal healing in these mice. All of these lead to worsened disease, despite the stimulatory effects …

Vip And Host Immunity, Xiaoyu Jiang

Wayne State University Dissertations

The purpose of the current dissertation was to examine how VIP regulates host immunity and corneal healing, specifically, its control of growth factors and TLR expression in the P. aeruginosa infected cornea. Firstly, VIP treatment increased growth factor expression (EGF, GHF, FGF and VEGF) in infected cornea. Notably, treatment with a mixture of EGF, FGF and HGF prevented corneal perforation, reduced pro-inflammatory cytokines and bacterial plate count, while increasing anti-inflammatory cytokines and antimicrobials such as murine beta-defensin2 and 3.

We also investigated the expression of TLR-signaling pathways in P. aeruginosa infected corneas with or without VIP treatment. PCR array and …