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Search Results: 1 - 10 of 4386 matches for " Jesse Roman "
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Activated PPAR Targets Surface and Intracellular Signals That Inhibit the Proliferation of Lung Carcinoma Cells
Shou Wei Han,Jesse Roman
PPAR Research , 2008, DOI: 10.1155/2008/254108
Abstract: Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Their discovery in the 1990s provided insights into the cellular mechanisms involved in the control of energy homeostasis, the regulation of cell differentiation, proliferation, and apoptosis, and the modulation of important biological and pathological processes related to inflammation and cancer biology, among others. Since then, PPARs have become an exciting target for the development of therapies directed at many disorders including cancer. PPARs are expressed in many tumors including lung cancer, and their function has been linked to the process of carcinogenesis. Consequently, intense research is being conducted in this area with the hope of discovering new PPAR-related therapeutic targets for the treatment of lung cancer. This review summarizes the research being conducted in this area, and focuses on the mechanisms by which a member of this family (PPAR) is believed to affect lung tumor cell biology.
PPARs in Lung Biology and Disease
Theodore J. Standiford,Jesse Roman
PPAR Research , 2007, DOI: 10.1155/2007/28765
Abstract:
Anticancer actions of PPARγ ligands: Current state and future perspectives in human lung cancer
Shou Wei Han,Jesse Roman
World Journal of Biological Chemistry , 2010,
Abstract: Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent nuclear transcription factors and members of the nuclear receptor superfamily. Of the three PPARs identified to date (PPARγ, PPARβ/δ, and PPARα), PPARγ has been studied the most, in part because of the availability of PPARγ agonists (also known as PPARγ ligands) and its significant effects on the management of several human diseases including type 2 diabetes, metabolic syndrome, cardiovascular disease and cancers. PPARγ is expressed in many tumors including lung cancer, and its function has been linked to the process of lung cancer development, progression and metastasis. Studies performed in gynogenic and xenograft models of lung cancer showed decreased tumor growth and metastasis in animals treated with PPARγ ligands. Furthermore, data are emerging from retrospective clinical studies that suggest a protective role for PPARγ ligands on the incidence of lung cancer. This review summarizes the research being conducted in this area and focuses on the mechanisms and potential therapeutic effects of PPARγ ligands as a novel anti-lung cancer treatment strategy.
Peroxisome Proliferator-Activated Receptors in Lung Cancer
Venkateshwar G. Keshamouni,ShouWei Han,Jesse Roman
PPAR Research , 2007, DOI: 10.1155/2007/90289
Abstract: Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Their discovery in the 1990s provided insights into the cellular mechanisms involved in the control of energy homeostasis; the regulation of cell differentiation, proliferation, and apoptosis; and the modulation of important biological and pathological processes related to inflammation, among others. Since then, PPARs have become an exciting therapeutic target for several diseases. PPARs are expressed by many tumors including lung carcinoma cells, and their function has been linked to the process of carcinogenesis in lung. Consequently, intense research is being conducted in this area with the hope of discovering new PPAR-related therapeutic targets for the treatment of lung cancer. This review summarizes the research being conducted in this area and focuses on the mechanisms by which PPARs are believed to affect lung tumor cell biology.
Rosiglitazone, an Agonist of PPAR, Inhibits Non-Small Cell Carcinoma Cell Proliferation In Part through Activation of Tumor Sclerosis Complex-2
ShouWei Han,Ying Zheng,Jesse Roman
PPAR Research , 2007, DOI: 10.1155/2007/29632
Abstract: PPARγ ligands inhibit the proliferation of non-small cell lung carcinoma (NSCLC) cells in vitro. The mechanisms responsible for this effect remain incompletely elucidated, but PPARγ ligands appear to inhibit the mammalian target of rapamycin (mTOR) pathway. We set out to test the hypothesis that PPARγ ligands activate tuberous sclerosis complex-2 (TSC2), a tumor suppressor gene that inhibits mTOR signaling. We found that the PPARγ ligand rosiglitazone stimulated the phosphorylation of TSC2 at serine-1254, but not threonine-1462. However, an antagonist of PPARγ and PPARγ siRNA did not inhibit these effects. Rosiglitazone also increased the phosphorylation of p38 MAPK, but inhibitors of p38 MAPK and its downstream signal MK2 had no effect on rosiglitazone-induced activation of TSC2. Activation of TSC2 resulted in downregulation of phosphorylated p70S6K, a downstream target of mTOR. A TSC2 siRNA induced p70S6K phosphorylation at baseline and inhibited p70S6K downregulation by rosiglitazone. When compared to a control siRNA in a thymidine incorporation assay, the TSC2 siRNA reduced the growth inhibitory effect of rosiglitazone by fifty percent. These observations suggest that rosiglitazone inhibits NSCLC growth partially through phosphorylation of TSC2 via PPARγ-independent pathways.
TGF 1 Controls PPAR Expression, Transcriptional Potential, and Activity, in Part, through Smad3 Signaling in Murine Lung Fibroblasts
Allan Ramirez,Erin N. Ballard,Jesse Roman
PPAR Research , 2012, DOI: 10.1155/2012/375876
Abstract: Transforming growth factor β1 (TGFβ1) promotes fibrosis by, among other mechanisms, activating quiescent fibroblasts into myofibroblasts and increasing the expression of extracellular matrices. Recent work suggests that peroxisome proliferator-activated receptor γ (PPARγ) is a negative regulator of TGFβ1-induced fibrotic events. We, however, hypothesized that antifibrotic pathways mediated by PPARγ are influenced by TGFβ1, causing an imbalance towards fibrogenesis. Consistent with this, primary murine primary lung fibroblasts responded to TGFβ1 with a sustained downregulation of PPARγ transcripts. This effect was dampened in lung fibroblasts deficient in Smad3, a transcription factor that mediates many of the effects of TGFβ1. Paradoxically, TGFβ1 stimulated the activation of the PPARγ gene promoter and induced the phosphorylation of PPARγ in primary lung fibroblasts. The ability of TGFβ1 to modulate the transcriptional activity of PPARγ was then tested in NIH/3T3 fibroblasts containing a PPARγ-responsive luciferase reporter. In these cells, stimulation of TGFβ1 signals with a constitutively active TGFβ1 receptor transgene blunted PPARγ-dependent reporter expression induced by troglitazone, a PPARγ activator. Overexpression of PPARγ prevented TGFβ1 repression of troglitazone-induced PPARγ-dependent gene transcription, whereas coexpression of PPARγ and Smad3 transgenes recapitulated the TGFβ1 effects. We conclude that modulation of PPARγ is controlled by TGFβ1, in part through Smad3 signals, involving regulation of PPARγ expression and transcriptional potential. 1. Introduction Transforming growth factor β1 (TGFβ1) is a pleomorphic growth factor with anti-inflammatory and profibrotic properties that has been implicated in many forms of natural and experimental tissue fibrosis [1]. In lung, TGFβ1 is produced by epithelial cells, alveolar and tissue macrophages, and fibroblasts after exposure to injurious agents such as silica, bleomycin, hyperoxia, and paraquat among others [2]. A key role for TGFβ1 in lung fibrosis has been confirmed in studies showing the development of lung fibrosis in animals transfected with TGFβ1-producing adenovirus, and by work demonstrating inhibition of experimental lung fibrosis by interventions targeting TGFβ1 or its downstream signals [3, 4]. The profibrotic effects of TGFβ1 are mostly, but not entirely, mediated by intracellular signals triggered by the transcription factor Smad3 [5]. TGFβ1/Smad3 signaling stimulates connective tissue expression and epithelial-mesenchymal transition, events considered key to the development
Aging promotes pro-fibrotic matrix production and increases fibrocyte recruitment during acute lung injury  [PDF]
Viranuj Sueblinvong, Wendy A. Neveu, David C. Neujahr, Stephen T. Mills, Mauricio Rojas, Jesse Roman, David M. Guidot
Advances in Bioscience and Biotechnology (ABB) , 2014, DOI: 10.4236/abb.2014.51004
Abstract:

Fibrotic lung diseases increase with age. Previously we determined that senescence increases tissue expression of fibronectin EDA (Fn-EDA) and decreases fibroblast expression of Thy-1, and that fibrocytes contribute to fibrosis following bleomycin-induced lung injury in mice. In this study we hypothesized that fibroblasts lacking Thy-1 expression produce an extracellular matrix that promotes fibrocyte retention and myofibroblast transdifferentiation, thereby promoting fibrogenesis. Young and old mice were treated with bleomycin intratracheally; fibrocytes in the bone marrow, blood, and lungs were quantified, and lung fibroblast Thy-1 expression was assessed. Bone marrowderived fibrocytes were cultured on matrices derived from Thy-1(+) or Thy-1(?) fibroblasts ± the pro-fibrotic cytokine TGFβ1. Older mice had more fibrocytes in their bone marrows at baseline and more fibrocytes in their lungs following bleomycin treatment. In parallel, lung fibroblasts in older mice had lower expression of Thy-1 at baseline that increased transiently 7 days after bleomycin treatment but then rapidly waned such that 14 days after bleomycin treatment Thy-1 expression was again markedly lower. Fibrocytes cultured on matrices derived from Thy-1(?) fibroblasts + TGFβ1 had increased gene expression for collagen type 1, fibronectin, Fn-EDA, and α-smooth muscle actin. In parallel, whereas the matrices derived from Thy-1(?) fibroblasts stimulated phosphorylation of Akt in cultured fibrocytes, the matrices derived from Thy-1(+) fibroblasts induced apoptosis. These findings suggest that senescence increases fibrocyte recruitment to the lung following injury and that loss of Thy-1 expression by lung fibroblasts promotes fibrocyte retention and myofibroblast transdifferentiation that renders the “aging lung” susceptible to fibrosis.

Activation of Tissue Remodeling Precedes Obliterative Bronchiolitis in Lung Transplant Recipients
Allan M. Ramirez,David R. Nunley,Mauricio Rojas,Jesse Roman
Biomarker Insights , 2008,
Abstract: Obliterative bronchiolitis (OB) and Bronchiolitis Obliterans Syndrome (BOS) are frequent complications in the lung transplant recipient, and are the leading cause of mortality after transplantation. The mechanisms responsible for OB remain elusive, but inflammatory and tissue remodeling responses are implicated. We hypothesized that alterations in markers of tissue remodeling in BALF of lung transplant recipients could predict development of OB. To test this, we identified 13 lung transplant recipients who developed both BOS and histologic OB (OB group) at median post-operative day (POD) 485 (range 73–2070). Bronchoalveolar lavage fluid (BALF) was obtained at median POD 387 (range 45–2205), which preceded the onset of OB and BOS by a median of 140 days (range 60–365). As a control, BALF was also obtained from a group of 21 stable recipients without OB (non-OB group) at median POD 335 (range 270–395). BALF was examined for gelatinolytic activity, fibronectin gene transcription, and transforming growth factor-β1 (TGF-β1) expression. Gelatin zymography of BALF from the OB group showed increased matrix metalloproteinase-9 (MMP-9) activity over that of the non-OB group (p < 0.005). Similarly, BALF from the OB group induced greater fibronectin expression in fibroblasts com- pared to the non-OB group (p < 0.03). The induction of fibronectin also correlated with the amount of TGF-β1 protein in BALF (r = 0.71) from the OB group. We conclude that activation of tissue remodeling precedes the onset of OB, and analysis of gelatinolytic and/or fibronectin-inducing activity in BALF can serve as an early, pre-clinical marker for OB.
PPARs: Regulators and Translational Targets in the Lung
Raju C. Reddy,Virender K. Rehan,Jesse Roman,Patricia J. Sime
PPAR Research , 2012, DOI: 10.1155/2012/342924
Abstract:
PPARs: Regulators and Translational Targets in the Lung
Raju C. Reddy,Virender K. Rehan,Jesse Roman,Patricia J. Sime
PPAR Research , 2012, DOI: 10.1155/2012/342924
Abstract:
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