Jeffrey S. Scehnet

University of Southern California

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Parkash S. Gill

Rutgers, The State University of New Jersey

Valery Krasnoperov

VasGene Therapeutics (United States)

Eric J. Ley

Cedars-Sinai Medical Center

Fred A. Weaver

University of Southern California

J. B. Singh

Panjab University

Debra Hawes

University of Southern California

Parmeet K. Manchanda

The Ohio State University

Robert D. Ladner

Queen's University Belfast

Robert W. Beart

Creighton University

Michaël Kahn

Beckman Research Institute

Cooperative Institutions

University of Southern California

Southern California University for Professional Studies

University of Utah

USC Norris Comprehensive Cancer Center

VA Salt Lake City Healthcare System

Keck Hospital of USC

University of Lisbon

Health Services Research & Development

Children's Hospital of Los Angeles

Vanderbilt University Medical Center

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Preferential Induction of EphB4 over EphB2 and Its Implication in Colorectal Cancer Progression

Cancer Research (2009)

Sunil Kumar Jeffrey S. Scehnet Eric J. Ley J. B. Singh Valery Krasnoperov

Abstract The receptor tyrosine kinase EphB2 is expressed by colon progenitor cells; however, only 39% of colorectal tumors express EphB2 and expression levels decline with disease progression. Conversely, EphB4 is absent in normal colon but is expressed in all 102 colorectal cancer specimens analyzed, and its expression level correlates with higher tumor stage and grade. Both EphB4 and EphB2 are regulated by the Wnt pathway, the activation of which is critically required for the progression of colorectal cancer. Differential usage of transcriptional coactivator cyclic AMP-responsive element binding protein–binding protein (CBP) over p300 by the Wnt/β-catenin pathway is known to suppress differentiation and increase proliferation. We show that the β-catenin-CBP complex induces EphB4 and represses EphB2, in contrast to the β-catenin-p300 complex. Gain of EphB4 provides survival advantage to tumor cells and resistance to innate tumor necrosis factor-related apoptosis-inducing ligand–mediated cell death. Knockdown of EphB4 inhibits tumor growth and metastases. Our work is the first to show that EphB4 is preferentially induced in colorectal cancer, in contrast to EphB2, whereby tumor cells acquire a survival advantage. [Cancer Res 2009;69(9):3736–45]

Tumor progression

Tumor M2-PK

10.1158/0008-5472.can-08-3232

Cite

Citations (124)

The receptor tyrosine kinase EphB4 is overexpressed in ovarian cancer, provides survival signals and predicts poor outcome

British Journal of Cancer (2007)

S. Ram Kumar R. Masood Whitney A. Spannuth J. B. Singh Jeffrey S. Scehnet

EphB4 is a member of the largest family of transmembrane receptor tyrosine kinases and plays critical roles in axonal pathfinding and blood vessel maturation. We wanted to determine the biological role of EphB4 in ovarian cancer. We studied the expression of EphB4 in seven normal ovarian specimens and 85 invasive ovarian carcinomas by immunohistochemistry. EphB4 expression was largely absent in normal ovarian surface epithelium, but was expressed in 86% of ovarian cancers. EphB4 expression was significantly associated with advanced stage of disease and the presence of ascites. Overexpression of EphB4 predicted poor survival in both univariate and multivariate analyses. We also studied the biological significance of EphB4 expression in ovarian tumour cells lines in vitro and in vivo. All five malignant ovarian tumour cell lines tested expressed higher levels of EphB4 compared with the two benign cell lines. Treatment of malignant, but not benign, ovarian tumour cell lines with progesterone, but not oestrogen, led to a 90% reduction in EphB4 levels that was associated with 50% reduction in cell survival. Inhibition of EphB4 expression by specific siRNA or antisense oligonucleotides significantly inhibited tumour cell viability by inducing apoptosis via activation of caspase-8, and also inhibited tumour cell invasion and migration. Furthermore, EphB4 antisense significantly inhibited growth of ovarian tumour xenografts and tumour microvasculature in vivo. Inhibition of EphB4 may hence have prognostic and therapeutic utility in ovarian carcinoma.

Ovarian tumor

10.1038/sj.bjc.6603642

Cite

Citations (97)

Evo-Devo of amniote integuments and appendages.

The International Journal of Developmental Biology (2004)

Ping Wu Lianhai Hou Maksim V. Plikus Michael W. Hughes Jeffrey S. Scehnet

Integuments form the boundary between an organism and the environment. The evolution of novel developmental mechanisms in integuments and appendages allows animals to live in diverse ecological environments. Here we focus on amniotes. The major achievement for reptile skin is an adaptation to the land with the formation of a successful barrier. The stratum corneum enables this barrier to prevent water loss from the skin and allowed amphibian / reptile ancestors to go onto the land. Overlapping scales and production of beta-keratins provide strong protection. Epidermal invagination led to the formation of avian feather and mammalian hair follicles in the dermis. Both adopted a proximal - distal growth mode which maintains endothermy. Feathers form hierarchical branches which produce the vane that makes flight possible. Recent discoveries of feathered dinosaurs in China inspire new thinking on the origin of feathers. In the laboratory, epithelial - mesenchymal recombinations and molecular mis-expressions were carried out to test the plasticity of epithelial organ formation. We review the work on the transformation of scales into feathers, conversion between barbs and rachis and the production of

Appendage

Amniote

Tetrapod (structure)

10.1387/ijdb.15272390

Cite

Citations (195)

Supplementary Figures 1-11 from Preferential Induction of EphB4 over EphB2 and Its Implication in Colorectal Cancer Progression

S. Ram Kumar Jeffrey S. Scehnet Eric J. Ley J. B. Singh Valery Krasnoperov

Supplementary Figures 1-11 from Preferential Induction of EphB4 over EphB2 and Its Implication in Colorectal Cancer Progression

10.1158/0008-5472.22381299.v1

Cite

Citations (0)

Data from Preferential Induction of EphB4 over EphB2 and Its Implication in Colorectal Cancer Progression

S. Ram Kumar Jeffrey S. Scehnet Eric J. Ley J. B. Singh Valery Krasnoperov

<div>Abstract<p>The receptor tyrosine kinase EphB2 is expressed by colon progenitor cells; however, only 39% of colorectal tumors express EphB2 and expression levels decline with disease progression. Conversely, EphB4 is absent in normal colon but is expressed in all 102 colorectal cancer specimens analyzed, and its expression level correlates with higher tumor stage and grade. Both EphB4 and EphB2 are regulated by the Wnt pathway, the activation of which is critically required for the progression of colorectal cancer. Differential usage of transcriptional coactivator cyclic AMP-responsive element binding protein–binding protein (CBP) over p300 by the Wnt/β-catenin pathway is known to suppress differentiation and increase proliferation. We show that the β-catenin-CBP complex induces EphB4 and represses EphB2, in contrast to the β-catenin-p300 complex. Gain of EphB4 provides survival advantage to tumor cells and resistance to innate tumor necrosis factor-related apoptosis-inducing ligand–mediated cell death. Knockdown of EphB4 inhibits tumor growth and metastases. Our work is the first to show that EphB4 is preferentially induced in colorectal cancer, in contrast to EphB2, whereby tumor cells acquire a survival advantage. [Cancer Res 2009;69(9):3736–45]</p></div>

Tumor progression

Tumor M2-PK

10.1158/0008-5472.c.6499827.v1

Cite

Citations (0)

Novel EphB4 Monoclonal Antibodies Modulate Angiogenesis and Inhibit Tumor Growth

American Journal Of Pathology (2010)

Valery Krasnoperov Sunil Kumar Eric J. Ley Xiu‐Qing Li Jeffrey S. Scehnet

10.2353/ajpath.2010.090755

Cite

Citations (82)

KSHV-induced notch components render endothelial and mural cell characteristics and cell survival