ZhongrenZhouMDPhD

PubMed

• 1 citations
  Infection and inflammation stimulate expansion of a CD74Paneth cell subset to regulate disease progression.
  Iyshwarya Balasubramanian, Sheila Bandyopadhyay, Juan Flores, Jared Bianchi-Smak, Xiang Lin, Haoran Liu, Shengxiang Sun, Natasha B Golovchenko, Yue Liu, Dahui Wang, Ra...> ;The EMBO Journal. 2023 Nov 2
• 2 citations
  NR4A3 fluorescence in situ hybridization analysis in cytologic and surgical specimens of acinic cell carcinoma.
  Qiuying Shi, Bin Zhang, Caroline Bsirini, Liqiong Li, Ellen J Giampoli, Kelly R Magliocca, Michelle Reid, Zhongren Zhou> ;Human Pathology. 2022 Sep 1
• Renal Cell Carcinoma with Cardiac Metastases: A Case Report and Review of the Literature.
  Ellen M Cahill, Alexandra Tabakin, Brian Shinder, Mark Bramwit, Biren Saraiya, Cristo G Salazar, Zhongren Zhou, Eric A Singer, Xu, X.> ;Journal of Kidney Cancer and VHL. 2022 Jan 1
• 3 citations
  Comparison of programmed death ligand 1 immunostaining for pancreatic ductal adenocarcinoma between paired cytological and surgical samples
  Michael Muggilli, Donna Russell, Zhongren Zhou> ;Cytojournal. 2021 Nov 3
• Phosphomannose Isomerase High Expression Associated with Better Prognosis in Pancreatic Ductal Adenocarcinoma.
  Zahra Alipour, Diana Agostini-Vulaj, Jennifer J. Findeis-Hosey, Lei Liu, Raul S. Gonzalez, Michael G. Drage, Hannah R. Krigman, Zhongren Zhou> ;Clinical and Experimental Gastroenterology. 2021 Sep 1
• 6 citations
  Pilot Study of the Performance of 19-G Needle in Endobronchial Ultrasound-guided Transbronchial Aspiration for the Diagnosis and Testing of Molecular Markers in Lung C...
  Momen M. Wahidi, Kevin Davidson, Scott Shofer, Kamran Mahmood, George Cheng, Coral X. Giovacchini, Claudia Jones, Rachel Jug, Elizabeth N. Pavlisko, Xiaofei Wang, Lin ...> ;Journal of Bronchology & Interventional Pulmonology. 2021 Jul 1
• 8 citations
  FILIP1L Loss Is a Driver of Aggressive Mucinous Colorectal Adenocarcinoma and Mediates Cytokinesis Defects through PFDN1.
  Mijung Kwon, Genesaret Rubio, Nicholas Nolan, Peter Auteri, Jean Arly Volmar, Asha Adem, Parisa Javidian, Zhongren Zhou, Michael P. Verzi, Sharon R. Pine, Steven K. Li...> ;Cancer Research. 2021 Jan 1
• 5 citations
  DNA methylation markers in esophageal cancer: an emerging tool for cancer surveillance and treatment.
  He Wang, Samuel M DeFina, Manisha Bajpai, Qin Yan, Lei Yang, Zhongren Zhou> ;American Journal of Cancer Research. 2021 Jan 1
• 32 citations
  Detection of Circulating Tumor DNA in Plasma: A Potential Biomarker for Esophageal Adenocarcinoma.
  Matthew Egyud, Mohamedtaki Abdulaziz Tejani, Arjun Pennathur, James D. Luketich, Praveen Sridhar, Emiko Yamada, Anders Ståhlberg, Stefan Filges, Paul M. Krzyzanowski, ...> ;The Annals of Thoracic Surgery. 2019 Aug 1
• 1 citations
  Hepatic sclerosing cavernous haemangioma can mimic the nodular elastosis stage of segmental atrophy.
  Jennifer J. Findeis-Hosey, Zhongren Zhou, Raul S. Gonzalez> ;Histopathology. 2019 Jul 29
• 1 citations
  Expression of GCRG213p, LINE-1 endonuclease variant, significantly different in gastric complete and incomplete intestinal metaplasia.
  Xiaojian Duan, Hongwei Lian, Jie Li, Ben-Yan Wu, Weihua Wang, Tao Wu, Changzheng Wang, Yan Dou, Zhongren Zhou, Bingzhi Wang, Liyan Xue, Gang-Shi Wang> ;Diagnostic Pathology. 2019 Jun 21
• 9 citations
  Combined EsophaCap cytology and MUC2 immunohistochemistry for screening of intestinal metaplasia, dysplasia and carcinoma
  Zhongren Zhou, Irina Kalatskaya, Donna Russell, Norman E. Marcon, Maria Cirocco, Paul M. Krzyzanowski, Cathy Streutker, Hua Liang, Virginia R. Litle, Tony E. Godfrey, ...> ;Clinical and Experimental Gastroenterology. 2019 May 15
• 8 citations
  Incidence and Significance of GATA3 Positivity in Pancreatic Ductal Adenocarcinoma and Cholangiocarcinoma.
  Diana Agostini-Vulaj, Laura Bratton, Richard F. Dunne, Justin M M Cates, Zhongren Zhou, Jennifer J. Findeis-Hosey, Qi Yang, Mira K Ramesh, Raul S. Gonzalez> ;Applied Immunohistochemistry & Molecular Morphology. 2020 Jul 1
• 25 citations
  PD-L1 expression and its clinicopathological correlation in advanced esophageal squamous cell carcinoma in a Chinese population
  Lulu Rong, Yong Liu, Zhouguang Hui, Zitong Zhao, Yueming Zhang, Bingzhi Wang, Yanling Yuan, Wenbin Li, Lei Guo, Jianming Ying, Yongmei Song, Luhua Wang, Zhongren Zhou,...> ;Diagnostic Pathology. 2019 Jan 26
• 17 citations
  Pharmacological targeting of p38 MAP-Kinase 6 (MAP2K6) inhibits the growth of esophageal adenocarcinoma.
  Sijie Lin, Kuancan Liu, Yongchun Zhang, Ming Jiang, Rong Lu, Christopher J. Folts, Xia Gao, Mark Noble, Tingting Zhao, Zhongren Zhou, Xiaopeng Lan, Jianwen Que> ;Cellular Signalling. 2018 Nov 1
• 6 citations
  Unexpectedly High Prevalence of Cystoisospora belli Infection in Acalculous Gallbladders of Immunocompetent Patients.
  Mushal Noor, Philip J. Katzman, Aaron R Huber, Jennifer J. Findeis-Hosey, Christa L. Whitney-Miller, Raul S. Gonzalez, Zhongren Zhou, Henriette D N’kodia, Kathryn Skon...> ;American Journal of Clinical Pathology. 2018 Oct 4
• 18 citations
  Comparison of programmed death-ligand 1 (PD-L1) immunostain for nonsmall cell lung carcinoma between paired cytological and surgical specimens.
  Huihong Xu, Laura Bratton, Michael Nead, Donna Russell, Zhongren Zhou> ;Cytojournal. 2018 Jan 1
• Endophenotypes: A conceptual link between anorexia nervosa and autism spectrum disorder.
  Zhou, Z. C.,McAdam, D. B.,Donnelly, D. R.> ;Res Dev Disabil. 2017 Dec 15
• 150 citations
  Transitional basal cells at the squamous–columnar junction generate Barrett’s oesophagus
  Ming Jiang, Haiyan Li, Yongchun Zhang, Ying Yang, Rong Lu, Kuancan Liu, Sijie Lin, Xiaopeng Lan, Haikun Wang, Han Wu, Jian Zhu, Zhongren Zhou, Jianming Xu, Dong Kee Le...> ;Nature. 2017 Oct 26
• 14 citations
  Bile salt receptor TGR5 is highly expressed in esophageal adenocarcinoma and precancerous lesions with significantly worse overall survival and gender differences.
  Chunhong Pang, Amy LaLonde, Tony E. Godfrey, Jianwen Que, Jun Sun, Tong Tong Wu, Zhongren Zhou> ;Clinical and Experimental Gastroenterology. 2017 Feb 7
• 22 citations
  High expression of Claudin-2 in esophageal carcinoma and precancerous lesions is significantly associated with the bile salt receptors VDR and TGR5.
  Sohaib Abu-Farsakh, Tong Tong Wu, Amy LaLonde, Jun Sun, Zhongren Zhou> ;BMC Gastroenterology. 2017 Feb 17
• 56 citations
  MCM4 and MCM7, potential novel proliferation markers, significantly correlated with Ki-67, Bmi1, and cyclin E expression in esophageal adenocarcinoma, squamous cell ca...
  Bonnie Choy, Amy LaLonde, Jianwen Que, Tong Tong Wu, Zhongren Zhou> ;Human Pathology. 2016 Nov 1
• 58 citations
  Salmonella Protein AvrA Activates the STAT3 Signaling Pathway in Colon Cancer
  Rong Lu, Shaoping Wu, Yong Guo Zhang, Yinglin Xia, Zhongren Zhou, Ikuko Kato, Hui Dong, Marc Bissonnette, Jun Sun> ;Neoplasia. 2016 May 1
• 5 citations
  Bile Salts at Low pH Cause Dilation of Intercellular Spaces in In Vitro Stratified Primary Esophageal Cells, Possibly by Modulating Wnt Signaling.
  Sayak Ghatak, Marie Reveiller, Liana Toia, Andrei I. Ivanov, Zhongren Zhou, Eileen M. Redmond, Tony E. Godfrey, Jeffrey H. Peters> ;Journal of Gastrointestinal Surgery. 2016 Mar 1
• 6 citations
  Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of pancreatic cysts by combined cytopathology and cystic content analysis.
  Amanda K Martin, Zhongren Zhou> ;World Journal of Gastrointestinal Endoscopy. 2015 Oct 25
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Journal Articles

• Clinical Impact of Tumor-infiltrating Inflammatory Cells in Primary Small Cell Esophageal Carcinoma  
  Y. Zhang, H. Ren, Z. Ning, Y. Zhuang, J. Gan, L. Wang, S. Chen, Z. Zhou, H. Zhu, D. Tan, H. Zhang, International Journal of Molecular Sciences, 1/1/2014
• Enteric Bacterial Protein AvrA Promotes Colonic Tumorigenesis and Activates Colonic Beta-catenin Signaling Pathway  
  J. Sun, R. Lu, S. Wu, Y. Zhang, Y. Xia, X. Liu, Y. Zheng, H. Chen, KL Schaefer, Z. Zhou, M. Bissonnette, and L. Li, Oncogene, 1/1/2014
• Case Report: Different Metastatic Components from Anaplastic Thyroid Carcinoma in Mediastinal and Neck Lymph Nodes Simultaneously Diagnosed by FNA  
  Costaldi M, Z Zhou, Diagnostic Cytopathology, 6/1/2013
• Clinicopathologic Conference: Floor of Mouth Mass  
  Fernando HR, LD Pollan, Z Zhou, Oral Surg Oral Med Oral Pathol Oral Radiol, 1/1/2013
• Exome and Whole-genome Sequencing of Esophageal Adenocarcinoma Identifies Recurrent Driver Events and Mutational Complexity  
  Dulak A, P Stojanov, S Peng, MS Lawrence, C Fox, C Stewart, S Bandla, Y Imamura1, SE Schumacher, E Shefler, A McKenna, K Cibulskis, A Sivachenko, SL Carter, G Saksena,..., Nature Genetics, 1/1/2013
• False-negative Rate of Endoscopic Ultrasound-guided Fine-needle Aspiration for Pancreatic Solid and Cystic Lesions with Matched Surgical Resections as the Gold Standar...  
  Woolf K, H. Liang, Z Sletten, D Russell, T Bonfiglio, Z Zhou, Cancer Cytopathology, 1/1/2013
• Bile Exposure Inhibits Expression of Squamous Differentiation Genes in Human Esophageal Epithelial Cells  
  Reveiller M, S Ghatak, L Toia, I Kalatskaya, L Stein, M D'Souza, Z Zhou, S Bandla, WE Gooding, TE. Godfrey and J Peters, Annals of Surgery, 1/1/2012
• Clinicopathological Characteristics of Amplification and over Expression of Bmi1 in Esophageal Adenocarcinoma and Squamous Cell Carcinoma  
  Choy B, S. Bandla, Y. Xia, D. Tan, T. Godfrey, J. Sun, Z Zhou, BMC Gastroenterology, 1/1/2012
• Wingless Homolog Wnt 11 Suppresses Bacterial Invasion and Inflammation in Intestinal Epithelial Cells  
  Liu X, S Wu, Y Xia, X Li, Z Zhou, J Sun, Am J Physiol Gastrointest Liver Physiol, 12/1/2011
• HER-2/Neu Over expression and Amplification in Esophageal Adenocarcinoma and High Grade Dysplasia  
  Hu Y. S Bandla, TE Godfrey, D Tan, JD Luketich, A Pennathur, X Qiu, DG Hicks, J Peters, Z Zhou, Modern Pathology, 1/1/2011
• Expression of Insulin-like Growth Factor II mRNA-binding Protein 3 in Human Esophageal Adenocarcinoma and Its Precursor Lesions  
  Feng W., Zhou, Z., J. Peters, T. Khoury; Q. Zhai, Q Wei, C. Truong, S. W. Song, D. Tan, Arch Pathol Lab Med, 1/1/2011
• Early G1 Cyclin-dependent Kinases as Prognostic Markers and Potential Therapeutic Targets in Esophageal Adenocarcinoma  
  Ismail A, Bandla S, Reveiller M, Toia L, Zhou Z, Gooding WE, Kalatskaya I, Stein L, D'Souza M, Litle VR, Peters JH, Pennathur A, Luketich JD, Godfrey TE, Clin Cancer Res, 1/1/2011
• Clinicopathologic Significance of Putative Stem Cell Markers, CD44 and Nestin, in Gastric Adenocarcinoma  
  Dhingra S, Feng W, Brown RE, Zhou Z, Khoury T, Zhang R, Tan D, Int J Clin Exp Pathol, 1/1/2011
• Are Endoscopic Therapies Appropriate for Superficial Submucosal Esophageal Adenocarcinoma? An Analysis of Esophagectomy Specimens  
  Sepesi B, Watson TJ, Zhou Z, Polomsky M, Litle VR, Jones CE, Raymond DP, Hu R, Qiu X, Peters JH, J Am Coll Surg, 4/1/2010
• Neutrophil VCS Parameters Are Superior Indicators for Acute Infection  
  Bagdasaryan, R, Zhou, Z; Tierno B, Dara Rosenman, and Xu DS, Laboratory Hematology, 1/1/2007
• Endothlin-1 Selectively Enhances the Activation Gating of Tetrodotoxin-resistant Sodium Currents in Rat Sensory Neurons: A Mechanism for the Algogenic Actions of ET-1  
  Zhou Z., Gudarz Davar, G.R. Strichartz, J Neuroscience, 1/1/2002
• NMDA Receptor Activity in Utero Averts Respiratory Depression and Anomalous Long-term Depression in Newborn Mice  
  Poon C.-S, Z. Zhou, Y. J. Champagnat, J Neurosci, 5/1/2000
• Field Potential Analysis of Synaptic Transmission in Spiking Neurons in a Sparse and Irregular Neuronal Structure in Vitro  
  Zhou Z., C.-S. Poon, J Neurosci Methods, 1/15/2000
• Distribution of the Cell Bodies and Dendrites of Motoneurons Innervating the Bulbocavernosus in Male Rat  
  Zhi Y, Wu J, Zhou Z, Chinese Journal of Neuroanatomy, 1/1/1999
• Distribution and Quantitative Study of Dendrites and Cell Bodies of Motoneurons Innervating the External Anal Sphincter in Rat  
  Zhi Y, Lu H, Zhou Z, Li S, Chinese Journal of Anatomy, 1/1/1998
• Phasic and Long-term Depression in Brainstem NTS Neurons: Differing Roles of AMPA Receptor Desensitization  
  Zhou Z., J. Champagnat and C.-S. Poon, J Neurosci, 1/1/1997
• Colocalization of Serotonin and Fos-like Protein in the Rat CNS after Electoacupuncture and Pain Stimulation  
  Zhou J.X. and Zhou Z, Acta Academia Medicinae Shanghai, 1/1/1993
• Co-localization of Fos-like Protein and NA in Pons and Medulla Neurons following Electric Acupuncture of "Quan-liao" and Electric Stimulation of the Rat-tail  
  Zhou Z. and Zhou J.X., Chin. J. Histochem. Cytochem, 1/1/1993
• Expression of C-fos Protein in CNS following Electro Acupuncture of "Quanliao" and Electrostimulation of the Rat Tail  
  Zhou Z., He L. and Zhou J.X., Acupuncture Res, 1/1/1993
• Distribution of the Somatostatin-like Peptide and the Dendrites of the Motoneurons Innervating the External Anal Sphincter of the Rat Investigated by Combined CB-HRP R...  
  Zhou Z. and Li S.F., J. North China Coal Medical College, 1/1/1989
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Books/Book Chapters

• Therapeutic Concentrations of Local Anesthetics Unveil the Potential Role of Sodium Channels in Neuropathic Pain 
  Strichartz G., Z. Zhou, C. Sinnott and A. KhodorovaJohn Wiley & Sons Ltd., Baffins Lane, Chichester, West Sussex2001

Abstracts/Posters

• Squamous Cell Carcinoma Arising In a Peri-coccygeal Epithelial Inclusion Cyst with Adjacent Benign Notochordal Cell Tumor: First Case Report
  Lopez L., MD, Schoeninger L., Z. Zhou, CAP Annual Meeting, San Diego, 10/1/2012
• Does Immunohistochemical Subtyping of Non-small Cell Lung Carcinoma in Fine Needle Aspiration Play a Similar Role as in Surgical Resection Tissue?
  Brooke RK, Zachary JS, Donna KR, Thomas AB, Haodong X, Zhou Z, American Society of Cytopathology, 59th Annual Scientific Meeting, Baltimore, MD, 1/1/2011
• Cyclin E Amplification and over Expression in Esophageal Carcinoma and Dysplasia by SNP Microarray and Immunohistochemisty Studies
  Ye J, S. Bandla, Y. Xia, D. Tan, J. Peters, T. Godfrey, Zhou, Z, USCAP Annual Meeting, San Antonio, 1/1/2011
• False Positive and Negative Rates of Pancreatic EUS-guided FNA Diagnosis by Fine Needle Aspiration and Bile Duct Brushing: One Institution's Experience
  Woolf K, Z Sletten, D Russell, T Bonfiglio, Z Zhou, USCAP Annual Meeting, San Antonio, 1/1/2011
• Gastroesophageal Junction microRNA
  Bandla S, Feber, A, Pennathur A, Luketich JD, Zhou Z, Godfrey T, Litle V, ISEC, Kagoshima, Japan, 1/1/2010
• Is CDK6 the Target of Amplification at 7q21 in Esophageal Adenocarcinoma?
  Ismail A, Z Zhou, L Toia, M Reveiller, S Bandla, A Pennathur, J Luketich and T Godfrey, AACR, Washington DC, 1/1/2010
• Stem Cell Markers CD44 and Nestin in Human Esophageal Adenocarcinoma and Its Precursor Lesions
  Feng W, Z Zhou, D Tan, USCAP Annual Meeting, Washington DC, 1/1/2010
• Expression of S100p in Human Esophageal Adenocarcinoma and Its Precursor Lesions
  Feng W, Z Zhou, D Tan, USCAP Annual Meeting, Washington DC, 1/1/2010
• Expression of Insulin-Like Growth Factor II mRNA-Binding Protein 3 (IMP3) in Human Esophageal Adenocarcinoma and Its Precursor Lesions
  Feng W, CD Truong, J Zhai, Z Zhou, D Tan, USCAP Annual Meeting, Boston MA, 1/1/2009
• Therapeutic Concentrations of Local Anesthetics Unveil the Potential Role of Sodium Channels in Neuropathic Pain
  Strichartz G., Z. Zhou, C. Sinnott and A. Khodorova, Sodium Channels and Neuronal Hyperexcitability. Novartis Foundation Symposium, UK, 1/1/2001
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Lectures

• Biomarkers of Esophageal Adenocarcinoma and Precancerous Lesion, Grand Round 
  Department of Pathology and Laboratory Medicine, University of Rochester - 4/1/2014
• Carbonic Anhydrase IX is Not a Prognostic Marker in Esophageal Adenocarcinoma, Instead it is a Unique Marker to Differentiate Squamous Cell Carcinoma from Adenocarcinoma 
  3/1/2014
• Electromagnetic Navigation Bronchoscopy and the Diagnostic Yield of Cytology and Concurrent Surgical Pathology Specimens 
  11/1/2013
• BIOMED-2 Is A Reliable Test For Lymphoma In Cytopathogical Samples 
  11/1/2013
• Lung FNA: Interesting Cases 
  Shanxi, China - 7/1/2013
• Diagnosis of Esophageal Adenocarcinoma and Precancerous Lesion 
  Shanxi, China - 7/1/2013
• Molecular Biomarkers of Esophageal Adenocarcinoma and Precancerous Lesion 
  China-Japan Friendship Hospital - 7/1/2013
• Biomarkers of Esophageal Adenocarcinoma and Precancerous Lesion-new Diagnosis Tool 
  Temple University Medical Center, Philadelphia, PA - 5/1/2013
• Analysis of Columnar Lined Esophagus Reveals Less Frequent Mutations in Non-goblet Cell Metaplasia than Intestinal Metaplasia 
  3/1/2013
• ALK Status in Esophageal Adenocarcinoma and Squamous Carcinoma Studied by DNA Microarray, FISH and Immunohistochemistry 
  3/1/2013
• ALK Protein Expression in Lung Adenocarcinomas Correlates with ALK Rearrangement, but Not Increased ALK Copy Numbers 
  3/1/2013
• Clinicopathological Characteristics of Amplification and over Expression of Bmi1 in Esophageal Adenocarcinoma and Squamous Cell Carcinoma 
  Boston - 11/1/2012
• The Role of Double Immunostaining for Desmoglein 3+napsin a in Subtyping Non-small Cell Lung Carcinoma in Fine Needle Aspiration Cytology: A Quality Control Study Comp... 
  Las Vegas - 11/1/2012
• The Role of Double Immunostaining for Cytokeratin 5 and TTF-1 in Subtyping Non-small Cell Lung Carcinoma in Fine Needle Aspiration Cytology: A Quality Control Study Co... 
  Las Vegas - 11/1/2012
• Using Flow Cytometry for the Diagnosis of Small Cell Lung Carcinoma by Endobronchial Ultrasound Fine Needle Aspiration 
  Las Vegas - 11/1/2012
• Esophageal Adenocarcinoma and Precancerous Lesion-New Concepts 
  Beijing, China - 7/1/2012
• Lung FNA: Morphology, Classification and Molecular Test 
  Beijing, China - 7/1/2012
• Clinical Diagnosis and Biomarkers of Esophageal Adenocarcinoma and Precancerous Lesion 
  Beijing Hospital, Beijing, China - 7/1/2012
• Biomarkers of Esophageal Adenocarcinoma and Precancerous Lesion 
  Department of Pathology and Laboratory Medicine Tufts University Medical Center - 3/1/2012
• Analysis of Genetic Alterations in Esophageal Metaplasia: Are Goblet Cells Required for Neoplastic Risk? 
  Vancouver, Canada - 1/1/2012
• Cyclin E Amplification and over Expression in Esophageal Carcinoma 
  James P. Wilmot Cancer Center - 6/1/2011
• Esophagus and G-E Junction 
  Histology and Pathology, Dept of Surgery; URMC - 8/1/2010
• HER-2/Neu Overexpression and Amplification in Esophageal Adenocarcinoma and High Grade Dysplasia 
  Washington DC - 1/1/2010
• Endoscopic Resection of Submucosal Esophageal Adenocarcinoma - A Word of Caution 
  Chicago, IL - 10/1/2009
• Comparison of the Neutrophil Volume with Manual Band Count, C-Reactive Protein and Absolute Neutrophil Count for Predicting Acute Infection 
  Las Vegas - 1/1/2006
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Other

• Comparison of Cancer-associated Genetic Abnormalities in Columnar-lined Esophagus Tissues with and without Goblet Cells 
  S. Bandla, JH Peters, D. Ruff, S-M Chen, C-Y Li, K Song, K Thoms, VR. Litle, T Watson, N Chapurin, M Lada, A Pennathur, JD. Luketich, D Peterson, A Dulak, L Lin, A Bas..., Annals Surgery Online
  1/1/2014
• HER2 Amplification or Over expression on Solid Tumor with Clinical Diagnosis and Treatment 
  Zhou Z. and D. Hicks, Oncogene
  http://www.intechopen.com/books/oncogene-and-cancer-from-bench-to-clinic/her2-amplification-or-overexpression-in-upper-gi-tract-and-breast-cancer-with-clinical-diagnosis-and