Entity

Time filter

Source Type

Miami, FL, United States

Zhu Y.,Arizona Cancer Center | Zhu Y.,Tissue Technology Inc. | Zhu M.,Arizona Cancer Center | Lance P.,Arizona Cancer Center
Experimental Cell Research | Year: 2012

COX-2 is a major inflammatory mediator implicated in colorectal inflammation and cancer. However, the exact origin and role of COX-2 on colorectal inflammation and carcinogenesis are still not well defined. Recently, we reported that COX-2 and iNOS signalings interact in colonic CCD18Co fibroblasts. In this article, we investigated whether activation of COX-2 signaling by IL1Β in primary colonic fibroblasts obtained from normal and cancer patients play a critical role in regulation of proliferation and invasiveness of human colonic epithelial cancer cells. Our results demonstrated that COX-2 level was significantly higher in cancer associated fibroblasts than that in normal fibroblasts with or without stimulation of IL-1Β, a powerful stimulator of COX-2. Using in vitro assays for estimating proliferative and invasive potential, we discovered that the proliferation and invasiveness of the epithelial cancer cells were much greater when the cells were co-cultured with cancer associated fibroblasts than with normal fibroblasts, with or without stimulation of IL1Β. Further analysis indicated that the major COX-2 product, prostaglandin E2, directly enhanced proliferation and invasiveness of the epithelial cancer cells in the absence of fibroblasts. Moreover, a selective COX-2 inhibitor, NS-398, blocked the proliferative and invasive effect of both normal and cancer associate fibroblasts on the epithelial cancer cells, with or without stimulation of IL-1Β. Those results indicate that activation of COX-2 signaling in the fibroblasts plays a major role in promoting proliferation and invasiveness of the epithelial cancer cells. In this process, PKC is involved in the activation of COX-2 signaling induced by IL-1Β in the fibroblasts. © 2012 Elsevier Inc. Source


Zhu Y.,Arizona Cancer Center | Zhu Y.,Tissue Technology Inc. | Zhu M.,Arizona Cancer Center | Lance P.,Arizona Cancer Center
Experimental Cell Research | Year: 2012

COX-2 and iNOS are two major inflammatory mediators implicated in colorectal inflammation and cancer. Previously, the role of colorectal fibroblasts involved in regulation of COX-2 and iNOS expression was largely ignored. In addition, the combined interaction of COX-2 and iNOS signalings and their significance in the progression of colorectal inflammation and cancer within the fibroblasts have received little investigation. To address those issues, we investigated the role of colonic fibroblasts in the regulation of COX-2 and iNOS gene expression, and explored possible mechanisms of interaction between COX-2 and iNOS signalings using a colonic CCD-18Co fibroblast line and LPS, a potential stimulator of COX-2 and iNOS. Our results clearly demonstrated that LPS activated COX-2 gene expression and enhanced PGE 2 production, stimulated iNOS gene expression and promoted NO production in the fibroblasts. Interestingly, activation of COX-2 signaling by LPS was not involved in activation of iNOS signaling, while activation of iNOS signaling by LPS contributed in part to activation of COX-2 signaling. Further analysis indicated that PKC plays a major role in the activation and interaction of COX-2 and iNOS signalings induced by LPS in the fibroblasts. © 2012 Elsevier Inc. Source


Zhu Y.,Arizona Cancer Center | Zhu Y.,Tissue Technology Inc. | Zhu M.,Arizona Cancer Center | Lance P.,Arizona Cancer Center
Biochemical and Biophysical Research Communications | Year: 2012

COX-2 is a major regulator implicated in colonic cancer. However, how COX-2 signaling affects colonic carcinogenesis at cellular level is not clear. In this article, we investigated whether activation of COX-2 signaling by deoxycholic acid (DCA) in primary human normal and cancer associated fibroblasts play a significant role in regulation of proliferation and invasiveness of colonic epithelial cancer cells. Our results demonstrated while COX-2 signaling can be activated by DCA in both normal and cancer associated fibroblasts, the level of activation of COX-2 signaling is significantly greater in cancer associated fibroblasts than that in normal fibroblasts. In addition, we discovered that the proliferative and invasive potential of colonic epithelial cancer cells were much greater when the cells were co-cultured with cancer associated fibroblasts pre-treated with DCA than with normal fibroblasts pre-treated with DCA. Moreover, COX-2 siRNA attenuated the proliferative and invasive effect of both normal and cancer associate fibroblasts pre-treated with DCA on the colonic cancer cells. Further studies indicated that the activation of COX-2 signaling by DCA is through protein kinase C signaling. We speculate that activation of COX-2 signaling especially in cancer associated fibroblasts promotes progression of colonic cancer. © 2012 Elsevier Inc. Source


Zhu M.,Arizona Cancer Center | Zhu Y.,Arizona Cancer Center | Zhu Y.,Tissue Technology Inc. | Lance P.,Arizona Cancer Center
Cell Proliferation | Year: 2013

Objectives: Up to now it has been unclear whether stromal/epithelial interaction affects progression of colon cancer. This study was designed to examine effects of tumour necrosis factor alpha (TNFα)-activated stromal cyclooxygenase-2 (COX-2) signalling on proliferation and invasiveness of colon cancer epithelial cells. Materials and methods: Cyclooxygenase-2 mRNA and protein were determined by real-time PCR and western blotting and prostaglandin E2 (PGE2) was assayed by radioimmunoassay. Cell proliferation and invasiveness were determined by transwell chamber assays and protein kinase C (PKC) was assayed by Biotrak™ PKC Assay System. Results: Our results indicated that TNFα, a powerful inflammatory cytokine, strongly promoted COX-2 expression and PGE2 production in colon cancer-associated fibroblasts. Using in vitro assays for estimating proliferative and invasive potential, we discovered that activation of stromal COX-2 signalling significantly promoted proliferation and invasiveness of colon cancer epithelial cells. In addition, selective COX-2 inhibitor N-[2-(Cyclohexyloxy)-4-nitrophenyl]methanesulfonamide, blocked such proliferative and invasive effects on the cancer epithelial cells. In this process, PKC was involved in activation of COX-2 signalling in the fibroblasts. Conclusion: We conclude that activation of stromal COX-2 signalling by TNFα played a major role in promoting proliferation and invasiveness of colon cancer epithelial cells. © 2013 John Wiley & Sons Ltd. Source


Tseng S.C.G.,Tissue Technology Inc. | Chen S.-Y.,Tissue Technology Inc. | Shen Y.-C.,National Taiwan University Hospital | Chen W.-L.,National Taiwan University Hospital | Hu F.-R.,National Taiwan University Hospital
Current Molecular Medicine | Year: 2010

The stem cells (SCs) of the corneal epithelium located in the limbal basal layer are the ultimate source to maintain corneal epithelial homeostasis. Like other adult tissue-specfic SCs, self renewal and fate decision of limbal SCs are regulated by a specialized in vivo microenvironment, termed "niche". Loss of limbal SCs or dysfunction of the limbal niche renders corneas with a unique clinical disease labeled limbal stem cell deficiency (LSCD). Besides transplantation of autologous or allogeneic limbal SCs or amniotic membrane, a new strategy of treating LSCD is to transplant a bio-engineered graft by expanding limbal SCs ex vivo. Herein, we conduct a critical appraisal of six protocols that have successfully been practiced in treating human patients with LSCD, and identify issues whether niche regulation has been disrupted or maintained during isolation and expansion. Consequently, we propose a future direction that may circumvent the potential pitfalls existing in these conventional protocols by preserving the interaction between limbal SCs and their native niche cells during isolation and expansion. Such an approach may one day help realize considerable promise held by adult SCs in treating a number of diseases. © 2010 Bentham Science Publishers Ltd. Source

Discover hidden collaborations