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1.  AP2β nucleolar localization predicts poor survival after stage I non–small cell lung cancer resection 
The Annals of Thoracic Surgery  2011;92(3):1044-1050.
Background
Activating enhancer-binding protein-2β (AP2β) is a transcription factor involved in apoptosis. The purpose of the current study was to assess the cellular location and level of AP2β in Non-Small Cell Lung Cancer (NSCLC) and normal lung tissue and investigate whether the level and localization of AP2β expression is predictive of overall survival in patients with stage I NSCLC.
Methods
We performed immunohistochemical analysis of tissue microarrays (TMAs) prepared from stage I NSCLC specimens with adjacent normal lung tissue from two independent sets of patients who underwent lung resection with curative intent at our institution. AP2β intensity was assessed in TMAs, and AP2β staining patterns were classified as either diffuseor nucleolar in the TMAs. AP2β intensity and localization were analyzed for correlation with patients' survival.
Results
Immunohistochemical analysis of TMAs showed that the intensity of AP2β immunohistochemical staining did not correlate with overall survival. When location of AP2β was analyzed in TMAs, all of the normal lung tissue had diffuse pattern of AP2β. In the first set of NSCLC, patients with nucleolar pattern had a significantly lower 5-year survival rate than patients with diffuse pattern (67% vs. 100%; P = 0.004); this finding was confirmed in the second set (64% vs. 91%; P = 0.02). Multivariate analysis revealed that nucleolar pattern was an independent predictor of poor overall survival in both sets.
Conclusions
The AP2β which is located in the nucleoplasm in normal lung tissue is found in either nucleoplasm or nucleoli in NSCLC. The patients with AP2β in the nucleoli had poor survival compared to patients with AP2β in the cytoplasm.
doi:10.1016/j.athoracsur.2011.04.029
PMCID: PMC3272351  PMID: 21871297
Lung cancer biology; survival analysis
2.  Acute Shingles after Resection of Thoracic Schwannoma 
Texas Heart Institute Journal  2012;39(2):265-267.
Herpes zoster is relatively uncommon after surgery in immunocompetent patients. To our knowledge, there have been no reports of herpes zoster after the resection of a thoracic schwannoma. We report the case of a 48-year-old woman in whom acute shingles developed after the video-assisted thoracic surgical resection of a posterior mediastinal schwannoma adjacent to the 4th thoracic vertebral body. The patient recovered after receiving timely antiviral therapy.
Rash and pain are common in patients who have wound infections and contact dermatitis after surgery, so the possible reactivation of varicella virus might not be prominent in the surgeon's mind. This case serves as a reminder that viral infections such as shingles should be considered in the differential diagnosis of postoperative erythema and pain.
PMCID: PMC3384061  PMID: 22740749
Diagnosis, differential; herpes zoster/diagnosis/epidemiology/etiology; postoperative complications; skin diseases, viral/diagnosis/drug therapy; thoracic surgery, video-assisted; virus activation
3.  Chlamydia pneumoniae Enhances Cytokine-Stimulated Human Monocyte Matrix Metalloproteinases through a Prostaglandin E2-Dependent Mechanism  
Infection and Immunity  2005;73(1):632-634.
Exposure of human monocytes to Chlamydia pneumoniae resulted in a significant enhancement of matrix metalloproteinase (MMP) 1 and 9 production following stimulation with tumor necrosis factor alpha and granulocyte monocyte-colony stimulating factor. The effect of C. pneumoniae on monocyte MMPs was mediated through the induction of prostaglandin E2. These findings may have implications for atherosclerotic plaque rupture.
doi:10.1128/IAI.73.1.632-634.2005
PMCID: PMC538927  PMID: 15618206
4.  Fibulin-2 Is a Driver of Malignant Progression in Lung Adenocarcinoma 
PLoS ONE  2013;8(6):e67054.
The extracellular matrix of epithelial tumors undergoes structural remodeling during periods of uncontrolled growth, creating regional heterogeneity and torsional stress. How matrix integrity is maintained in the face of dynamic biophysical forces is largely undefined. Here we investigated the role of fibulin-2, a matrix glycoprotein that functions biomechanically as an inter-molecular clasp and thereby facilitates supra-molecular assembly. Fibulin-2 was abundant in the extracellular matrix of human lung adenocarcinomas and was highly expressed in tumor cell lines derived from mice that develop metastatic lung adenocarcinoma from co-expression of mutant K-ras and p53. Loss-of-function experiments in tumor cells revealed that fibulin-2 was required for tumor cells to grow and metastasize in syngeneic mice, a surprising finding given that other intra-tumoral cell types are known to secrete fibulin-2. However, tumor cells grew and metastasized equally well in Fbln2-null and -wild-type littermates, implying that malignant progression was dependent specifically upon tumor cell-derived fibulin-2, which could not be offset by other cellular sources of fibulin-2. Fibulin-2 deficiency impaired the ability of tumor cells to migrate and invade in Boyden chambers, to create a stiff extracellular matrix in mice, to cross-link secreted collagen, and to adhere to collagen. We conclude that fibulin-2 is a driver of malignant progression in lung adenocarcinoma and plays an unexpected role in collagen cross-linking and tumor cell adherence to collagen.
doi:10.1371/journal.pone.0067054
PMCID: PMC3677922  PMID: 23785517
5.  Human Lung Cancer Cells Grown in an Ex Vivo 3D Lung Model Produce Matrix Metalloproteinases Not Produced in 2D Culture 
PLoS ONE  2012;7(9):e45308.
We compared the growth of human lung cancer cells in an ex vivo three-dimensional (3D) lung model and 2D culture to determine which better mimics lung cancer growth in patients. A549 cells were grown in an ex vivo 3D lung model and in 2D culture for 15 days. We measured the size and formation of tumor nodules and counted the cells after 15 days. We also stained the tissue/cells for Ki-67, and Caspase-3. We measured matrix metalloproteinase (MMP) levels in the conditioned media and in blood plasma from patients with adenocarcinoma of the lung. Organized tumor nodules with intact vascular space formed in the ex vivo 3D lung model but not in 2D culture. Proliferation and apoptosis were greater in the ex vivo 3D lung model compared to the 2D culture. After 15 days, there were significantly more cells in the 2D culture than the 3D model. MMP-1, MMP-9, and MMP-10 production were significantly greater in the ex vivo 3D lung model. There was no production of MMP-9 in the 2D culture. The patient samples contained MMP-1, MMP-2, MMP-9, and MMP-10. The human lung cancer cells grown on ex vivo 3D model form perfusable nodules that grow over time. It also produced MMPs that were not produced in 2D culture but seen in human lung cancer patients. The ex vivo 3D lung model may more closely mimic the biology of human lung cancer development than the 2D culture.
doi:10.1371/journal.pone.0045308
PMCID: PMC3444466  PMID: 23028922

Results 1-5 (5)