The role of Dickkopf-3 overexpression in esophageal adenocarcinoma

Slides:

Advertisements

Similar presentations

Aldehyde Dehydrogenase 1A1 Possesses Stem-Like Properties and Predicts Lung Cancer Patient Outcome Xiao Li, MD, Liyan Wan, MD, Jian Geng, MD, Chin-Lee.

Advertisements

Overexpression of CRM1: A Characteristic Feature in a Transformed Phenotype of Lung Carcinogenesis and a Molecular Target for Lung Cancer Adjuvant Therapy

Vascular endothelial growth factor expression in non-small-cell lung cancer: Prognostic significance in squamous cell carcinoma Hideyuki Imoto, MD, Toshihiro.

Manuel J. Antunes, MD, PhD, DSc

INHBA Overexpression Promotes Cell Proliferation and May Be Epigenetically Regulated in Esophageal Adenocarcinoma Christopher W. Seder, MD, Wibisono.

Stephen R. Broderick, MD, MPHS

Selective decrease in the DNA base excision repair pathway in squamous cell cancer of the esophagus Pramod Bonde, MD, MS, FRCS, Daqing Gao, PhD, Lei.

Modulation of growth in human esophageal adenocarcinoma cells by group IIa secretory phospholipase A2 David Mauchley, MD, Xianzhong Meng, MD, PhD, Thomas.

Heat shock protein 27: Induction by gastroduodenal reflux in vivo and augmentation of human esophageal mucosal cell growth in vitro David Mauchley, MD,

Volume 15, Issue 6, Pages (June 2009)

Group IIa secretory phospholipase expression correlates with group IIa secretory phospholipase inhibition–mediated cell death in K-ras mutant lung cancer.

Phosphorylated mammalian target of rapamycin expression is associated with the response to chemoradiotherapy in patients with esophageal squamous cell.

Knockdown of secretory phospholipase A2 IIa reduces lung cancer growth in vitro and in vivo Jessica A. Yu, MD, David Mauchley, MD, Howard Li, MD, Xianzhong.

AZGP1 Autoantibody Predicts Survival and Histone Deacetylase Inhibitors Increase Expression in Lung Adenocarcinoma Daniel L. Albertus, BS, Christopher.

INHBA Overexpression Promotes Cell Proliferation and May Be Epigenetically Regulated in Esophageal Adenocarcinoma Christopher W. Seder, MD, Wibisono.

Characterization of microRNA transcriptome in tumor, adjacent, and normal tissues of lung squamous cell carcinoma Jun Wang, MD, PhD, Zhi Li, MD, PhD,

Gastroesophageal tumor embolization to the popliteal arteries

TGM2: A Cell Surface Marker in Esophageal Adenocarcinomas

Justin D. Blasberg, MD, Chandra M. Goparaju, PhD, Harvey I

Aldehyde Dehydrogenase 1A1 Possesses Stem-Like Properties and Predicts Lung Cancer Patient Outcome Xiao Li, MD, Liyan Wan, MD, Jian Geng, MD, Chin-Lee.

Changfa Guo, MD, Husnain Kh. Haider, PhD, Winston S. N

Oncogenic Potential of CYP24A1 in Lung Adenocarcinoma

Cytogenetic characterization and gene expression profiling in the rat reflux-induced esophageal tumor model Pramod Bonde, MD, MS, FRCS, Guoping Sui,

Combining the Multitargeted Tyrosine Kinase Inhibitor Vandetanib with the Antiestrogen Fulvestrant Enhances Its Antitumor Effect in Non-small Cell Lung.

Chandra Goparaju, PhD, Jessica S

Co-Overexpression of Cyclooxygenase-2 and Microsomal Prostaglandin E Synthase-1 Adversely Affects the Postoperative Survival in Non-small Cell Lung Cancer

A novel biomarker for the detection of esophageal adenocarcinoma

A novel vascularized patch enhances cell survival and modifies ventricular remodeling in a rat myocardial infarction model Qi Zhou, MD, PhD, Jian-Ye.

Intrinsic cardiac stem cells are essential for regeneration

Abracadabra I, II…HeartMate 3?

Victor van Berkel, MD, PhD

How should we treat air leaks?

A high-fat diet is associated with altered adipokine production and a more aggressive esophageal adenocarcinoma phenotype in vivo Aaron J. Fowler, BS,

MicroRNA expression profiles of esophageal cancer

Lung cancer cell invasion and expression of intercellular adhesion molecule-1 (ICAM-1) are attenuated by secretory phospholipase A2 inhibition Jessica.

Interstitial tumor-associated macrophages combined with tumor-derived colony- stimulating factor-1 and interleukin-6, a novel prognostic biomarker in non–small.

Dasatinib, a small molecule inhibitor of the Src kinase, reduces the growth and activates apoptosis in pre-neoplastic Barrett's esophagus cell lines:

The lord of the rings Antonio Miceli, MD, PhD

Gastric conduit revision after esophagectomy: The raising of Lazarus

Loss of CRNN expression is associated with advanced tumor stage and poor survival in patients with esophageal squamous cell carcinoma Po-Kuei Hsu, MD,

The tissue-engineered vascular graft using bone marrow without culture

Identification and characterization of stemlike cells in human esophageal adenocarcinoma and normal epithelial cell lines Ronghua Zhao, MD, PhD, Luca.

The assessment of cost effectiveness and the effectiveness of cost assessment in cardiothoracic surgery Vinay Badhwar, MD The Journal of Thoracic and.

It's not “just a shunt” but sometimes it should be…

Jules Lin, MD The Journal of Thoracic and Cardiovascular Surgery

Stephen R. Broderick, MD, MPHS

Get it right the first time

Choice of second pericardial drainage tube for posterior placement

Resection of primary lung cancer with incidental pleural seeding: Seeds of change or reap what you sow? Jules Lin, MD The Journal of Thoracic and Cardiovascular.

Fenton H. McCarthy, MD, MS, Nimesh D. Desai, MD, PhD

Niv Ad, MD, Lawrence M. Wei, MD

Frozen elephant trunk technique: Ready to get back to the future?

Attachment disorder in thoracoabdominal surgery

Case reporter's notebook: The who, what, when, where, how, and why of extraction of a benign intracaval tumor Verdi J. DiSesa, MD, MBA The Journal of.

Pathologic correlates of heparin-free donation after cardiac death in lung transplantation Chase R. Brown, BS, Alexis E. Shafii, MD, Carol F. Farver,

Passing the torch The Journal of Thoracic and Cardiovascular Surgery

The origins of open heart surgery at the University of Minnesota 1951 to 1956 Richard A. DeWall, MD The Journal of Thoracic and Cardiovascular Surgery

The Journal of Thoracic and Cardiovascular Surgery

Discussion The Journal of Thoracic and Cardiovascular Surgery

Tissue valve, nitinol stent, or storage solution

The future of cardiac surgery training: A survival guide

Ralph E. Delius, MD The Journal of Thoracic and Cardiovascular Surgery

The Robin Hood principle in the treatment of congenital heart disease: Taking technologic developments intended for adults and using it in kids Paul.

“The more things change…”: The challenges ahead

Why arch curvature affects arch resistance

Kiran H. Lagisetty, David G. Beer, Andrew C. Chang

Apples remain apples NO matter what

Of mice and men… The Journal of Thoracic and Cardiovascular Surgery

Samuel Kim, MD The Journal of Thoracic and Cardiovascular Surgery

Overexpression of CRM1: A Characteristic Feature in a Transformed Phenotype of Lung Carcinogenesis and a Molecular Target for Lung Cancer Adjuvant Therapy

Presentation transcript:

The role of Dickkopf-3 overexpression in esophageal adenocarcinoma Zhuwen Wang, MS, Lin Lin, MD, PhD, Dafydd G. Thomas, MD, Ernest Nadal, MD, Andrew C. Chang, MD, David G. Beer, PhD, Jules Lin, MD The Journal of Thoracic and Cardiovascular Surgery Volume 150, Issue 2, Pages 377-385.e2 (August 2015) DOI: 10.1016/j.jtcvs.2015.05.006 Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Representative sections from a tissue microarray showing low (A) and high (B) cytoplasmic DKK3 staining in 2 EACs. Moderate to high expression (2-3+) was found in 46.8% (29/62) of EACs. Low (C) and high (D) SMAD4 staining correlated with DKK3 in the same tumors. Original magnifications are all 100×. DKK3, Dickkopf-3. The Journal of Thoracic and Cardiovascular Surgery 2015 150, 377-385.e2DOI: (10.1016/j.jtcvs.2015.05.006) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 A, OE33/DKK3 had significantly increased Matrigel (BD Biosciences, San Jose, Calif) invasion compared with controls (∗∗P < .001). Du145 prostate cancer cells served as a positive control. B, All assays were performed in duplicate. DKK3, Dickkopf-3. The Journal of Thoracic and Cardiovascular Surgery 2015 150, 377-385.e2DOI: (10.1016/j.jtcvs.2015.05.006) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 A. SMAD4 was significantly increased on Western blot in OE33/DKK3 after treatment with 1 or 100 ng/mL of activin compared with native and vector controls (C, carrier control). B and C, Treatment of OE33/DKK3 cells with siSMAD4 resulted in significantly less Matrigel invasion compared with a nontargeting control (**P < .001). DKK3, Dickkopf-3. The Journal of Thoracic and Cardiovascular Surgery 2015 150, 377-385.e2DOI: (10.1016/j.jtcvs.2015.05.006) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 The presence of stably transfected OE33 (OE33/DKK3 + Endo) increased endothelial tube formation similar to the tube formation seen after adding VEGF to endothelial cells (Endo + VEGF) and to OE33/Vector (OE33/Vector + Endo + VEGF). Endothelial, native OE33, and vector controls showed minimal tube formation. OE33 and endothelial cells were labeled green and red, respectively. Original magnifications were 200×. VEGF, Vascular endothelial growth factor. The Journal of Thoracic and Cardiovascular Surgery 2015 150, 377-385.e2DOI: (10.1016/j.jtcvs.2015.05.006) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 A, OE33/DKK3 were significantly more resistant to 5-FU and cisplatin compared with treatment with vehicle control for 48 hours (*P < .05). B, DKK3 expression was significantly higher on RT-PCR in chemoresistant (n = 21) compared with chemonaive EACs (n = 95) (**P < .005). VC, Vector control; 5FU, 5-fluorouracil; CDDP, cis-diamminedichloroplatinum(II) (cisplatin); DKK3, Dickkopf-3. The Journal of Thoracic and Cardiovascular Surgery 2015 150, 377-385.e2DOI: (10.1016/j.jtcvs.2015.05.006) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

OE33/DKK3 had significantly increased Matrigel (BD Biosciences, San Jose, Calif) invasion compared with controls (P < .001). The Journal of Thoracic and Cardiovascular Surgery 2015 150, 377-385.e2DOI: (10.1016/j.jtcvs.2015.05.006) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure E1 A, RT-PCR analysis of 95 EAC samples showed 2-fold overexpression of DKK3 in 72/95 (75.8%) EACs relative to BM. B, A total of 40 esophageal samples including 14 EACs showed significant overexpression in EAC in the progression from BM (*P < .05). BL, Barrett's/low-grade dysplasia; BM, Barrett's metaplasia; EAC, esophageal adenocarcinoma; LGD, low-grade dysplasia; HGD, high-grade dysplasia. The Journal of Thoracic and Cardiovascular Surgery 2015 150, 377-385.e2DOI: (10.1016/j.jtcvs.2015.05.006) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions

Figure E2 NOD/SCIDγ mice were injected in the flank with 1 × 106 cells. A, Only 1 of 8 OE33/Vector tumor sites produced a tumor (2 mm). B, All (8/8) tumor sites injected with OE33/DKK3 cells resulted in tumors (4-5 mm) after 5 weeks (3/4 mice are shown). C, Three OE33/DKK3 tumors are shown after explant. DKK3 overexpression in the OE33/DKK3 tumors was confirmed on RT-PCR and Western blot. The Journal of Thoracic and Cardiovascular Surgery 2015 150, 377-385.e2DOI: (10.1016/j.jtcvs.2015.05.006) Copyright © 2015 The American Association for Thoracic Surgery Terms and Conditions