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McCall, Shannon Jones

Overview:

As an anatomic pathologist, I am involved in numerous translational cancer research projects that rely on the study of human biological samples.  I direct the Duke Biospecimen Repository and Processing Core Laboratory for the School of Medicine and the Duke Cancer Institute.  My own area of research interest is gastrointestinal tract metaplasias and their relationship to carcinogenesis.

Positions:

Associate Professor of Pathology

Pathology
School of Medicine

Assistant Professor in Surgery

Surgery, Surgical Sciences
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 1996

B.S. — North Carolina State University

M.D. 2000

M.D. — Duke University

Resident, Pathology

Duke University

News:

Grants:

Mutation analysis of pap smear samples and associated tissues for ovarian cancer diagnostics

Administered By
Pathology
AwardedBy
Genendeavor LLC
Role
Principal Investigator
Start Date
October 12, 2017
End Date
October 11, 2022

Characterization of Tumor Immunobiological Factors that Promote Lymphovascular Invasion and Dissemination in Locally Advanced Breast Cancer

Administered By
Surgery, Surgical Sciences
AwardedBy
Department of Defense
Role
Co Investigator
Start Date
August 15, 2017
End Date
August 14, 2020

Targeting differential apoptosis regulation in triple negative breast cancer

Administered By
Pharmacology & Cancer Biology
AwardedBy
Department of Defense
Role
Collaborator
Start Date
September 30, 2016
End Date
September 29, 2019

Lung Squamous Cell Carcinoma: Validation of Molecular Signatures of Prognosis

Administered By
Surgery, Cardiovascular and Thoracic Surgery
AwardedBy
University of Colorado - Denver
Role
Pathologist
Start Date
July 09, 2012
End Date
May 30, 2017

The genetics of hepatosplenic T cell lymphoma

Administered By
Medicine, Hematological Malignancies
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
April 01, 2015
End Date
March 31, 2017

Preoperative Breast Radiotherapy: A Tool to Provide Individualized and Biologically-Based Radiation Therapy

Administered By
Radiation Oncology
AwardedBy
Gateway for Cancer Research
Role
Pathologist
Start Date
July 01, 2015
End Date
June 30, 2016

The effect of pre-analytical variables on the ability to detect PD-L1 by immunohistochemical staining of placental tissu

Administered By
Pathology
AwardedBy
Merck
Role
Principal Investigator
Start Date
November 05, 2014
End Date
January 18, 2015

TCGA Contract

Administered By
Pathology
AwardedBy
SAIC-Frederick, Inc.
Role
Principal Investigator
Start Date
December 03, 2013
End Date
December 31, 2014
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Awards:

Fellowship, Duke Clinical Leadership Program. Chancellor of Duke Medicine.

Type
School
Awarded By
Chancellor of Duke Medicine
Date
January 01, 2016

Bernard Fetter Faculty Teaching Award. Department of Pathology.

Type
Department
Awarded By
Department of Pathology
Date
January 01, 2015

William D. Bradford Resident Teaching Award. Department of Pathology.

Type
Department
Awarded By
Department of Pathology
Date
January 01, 2005

Alpha Omega Alpha, Medical Honor Society Induction. Alpha Omega Alpha.

Type
National
Awarded By
Alpha Omega Alpha
Date
January 01, 2004

Young Leader Award. College of American Pathologists.

Type
National
Awarded By
College of American Pathologists
Date
January 01, 2004

Tau Beta Pi Engineering Honor Society Induction. Tau Beta Pi.

Type
National
Awarded By
Tau Beta Pi
Date
January 01, 1994

Publications:

Porcine Esophageal Submucosal Gland Culture Model Shows Capacity for Proliferation and Differentiation.

Although cells comprising esophageal submucosal glands (ESMGs) represent a potential progenitor cell niche, new models are needed to understand their capacity to proliferate and differentiate. By histologic appearance, ESMGs have been associated with both overlying normal squamous epithelium and columnar epithelium. Our aim was to assess ESMG proliferation and differentiation in a 3-dimensional culture model.We evaluated proliferation in human ESMGs from normal and diseased tissue by proliferating cell nuclear antigen immunohistochemistry. Next, we compared 5-ethynyl-2'-deoxyuridine labeling in porcine ESMGs in vivo before and after esophageal injury with a novel in vitro porcine organoid ESMG model. Microarray analysis of ESMGs in culture was compared with squamous epithelium and fresh ESMGs.Marked proliferation was observed in human ESMGs of diseased tissue. This activated ESMG state was recapitulated after esophageal injury in an in vivo porcine model, ESMGs assumed a ductal appearance with increased proliferation compared with control. Isolated and cultured porcine ESMGs produced buds with actively cycling cells and passaged to form epidermal growth factor-dependent spheroids. These spheroids were highly proliferative and were passaged multiple times. Two phenotypes of spheroids were identified: solid squamous (P63+) and hollow/ductal (cytokeratin 7+). Microarray analysis showed spheroids to be distinct from parent ESMGs and enriched for columnar transcripts.Our results suggest that the activated ESMG state, seen in both human disease and our porcine model, may provide a source of cells to repopulate damaged epithelium in a normal manner (squamous) or abnormally (columnar epithelium). This culture model will allow the evaluation of factors that drive ESMGs in the regeneration of injured epithelium. The raw microarray data have been uploaded to the National Center for Biotechnology Information Gene Expression Omnibus (accession number: GSE100543).

Authors
von Furstenberg, RJ; Li, J; Stolarchuk, C; Feder, R; Campbell, A; Kruger, L; Gonzalez, LM; Blikslager, AT; Cardona, DM; McCall, SJ; Henning, SJ; Garman, KS
MLA Citation
von Furstenberg, RJ, Li, J, Stolarchuk, C, Feder, R, Campbell, A, Kruger, L, Gonzalez, LM, Blikslager, AT, Cardona, DM, McCall, SJ, Henning, SJ, and Garman, KS. "Porcine Esophageal Submucosal Gland Culture Model Shows Capacity for Proliferation and Differentiation. (Accepted)" Cellular and molecular gastroenterology and hepatology 4.3 (November 2017): 385-404.
PMID
28936470
Source
epmc
Published In
Cellular and molecular gastroenterology and hepatology
Volume
4
Issue
3
Publish Date
2017
Start Page
385
End Page
404
DOI
10.1016/j.jcmgh.2017.07.005

Immune Activation in Early Stage Non-Small Cell Lung Cancer Patients Receiving Neoadjuvant Chemotherapy Plus Ipilimumab.

To determine the immunologic effects of neoadjuvant chemotherapy plus ipilimumab in early stage non-small cell lung cancer (NSCLC) patients.This is a single-arm chemotherapy plus phased ipilimumab Phase II study of 24 treatment-naïve patients with Stage IB-IIIA NSCLC. Patients received neoadjuvant therapy consisting of 3 cycles of paclitaxel with either cisplatin or carboplatin and ipilimumab included in the last 2 cycles.Chemotherapy alone had little effect on immune parameters in PBMCs. Profound CD28 dependent activation of both CD4 and CD8 cells was observed following ipilimumab. Significant increases in the frequencies of CD4+ cells expressing activation markers ICOS, HLA-DR, CTLA-4, and PD-1 were apparent. Likewise, increased frequencies of CD8+ cells expressing the same activation markers, with the exception of PD-1, were observed. We also examined 7 resected tumors and found higher frequencies of activated TILs than those observed in PBMCs. Surprisingly, we found 4 cases of pre-existing tumor-associated antigens (TAA) responses against survivin, PRAME, or MAGE-A3 present in PBMC at baseline, but neither increased frequencies nor the appearance of newly detectable responses following ipilimumab therapy. Ipilimumab had little effect on the frequencies of circulating Tregs and MDSCs.This study did not meet the primary endpoint of detecting an increase in blood based tumor associated antigen T cell responses after ipilimumab. Collectively, these results highlight the immune activating properties of ipilimumab in early stage NSCLC. The immune profiling data for ipilimumab alone can contribute to the interpretation of immunological data from combined immune checkpoint blockade immunotherapies.

Authors
Yi, JS; Ready, N; Healy, P; Dumbauld, C; Osborne, R; Berry, M; Shoemaker, D; Clarke, J; Crawford, J; Tong, BC; Harpole, D; D'Amico, TA; McSherry, F; Dunphy, F; McCall, SJ; Christensen, JD; Wang, X; Weinhold, KJ
MLA Citation
Yi, JS, Ready, N, Healy, P, Dumbauld, C, Osborne, R, Berry, M, Shoemaker, D, Clarke, J, Crawford, J, Tong, BC, Harpole, D, D'Amico, TA, McSherry, F, Dunphy, F, McCall, SJ, Christensen, JD, Wang, X, and Weinhold, KJ. "Immune Activation in Early Stage Non-Small Cell Lung Cancer Patients Receiving Neoadjuvant Chemotherapy Plus Ipilimumab." Clinical cancer research : an official journal of the American Association for Cancer Research (September 26, 2017).
PMID
28951518
Source
epmc
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Publish Date
2017
DOI
10.1158/1078-0432.ccr-17-2005

Ductular and proliferative response of esophageal submucosal glands in a porcine model of esophageal injury and repair.

Esophageal injury is a risk factor for diseases such as Barrett's esophagus (BE) and esophageal adenocarcinoma. To improve understanding of signaling pathways associated with both normal and abnormal repair, animal models are needed. Traditional rodent models of esophageal repair are limited by the absence of esophageal submucosal glands (ESMGs), which are present in the human esophagus. Previously, we identified acinar ductal metaplasia in human ESMGs in association with both esophageal injury and cancer. In addition, the SOX9 transcription factor has been associated with generation of columnar epithelium and the pathogenesis of BE and is present in ESMGs. To test our hypothesis that ESMGs activate after esophageal injury with an increase in proliferation, generation of a ductal phenotype, and expression of SOX9, we developed a porcine model of esophageal injury and repair using radiofrequency ablation (RFA). The porcine esophagus contains ESMGs, and RFA produces a consistent and reproducible mucosal injury in the esophagus. Here we present a temporal assessment of this model of esophageal repair. Porcine esophagus was evaluated at 0, 6, 18, 24, 48, and 72 h and 5 and 7 days following RFA and compared with control uninjured esophagus. Following RFA, ESMGs demonstrated an increase in ductal phenotype, echoing our prior studies in humans. Proliferation increased in both squamous epithelium and ESMGs postinjury with a prominent population of SOX9-positive cells in ESMGs postinjury. This model promises to be useful in future experiments evaluating mechanisms of esophageal repair.NEW & NOTEWORTHY A novel porcine model of injury and repair using radiofrequency ablation has been developed, allowing for reproducible injury to the esophagus to study repair in an animal model with esophageal submucosal glands, a key anatomical feature and missing in rodent models but possibly harboring progenitor cells. There is a strong translational component to this porcine model given the anatomical and physiological similarities between pigs and humans.

Authors
Krüger, L; Gonzalez, LM; Pridgen, TA; McCall, SJ; von Furstenberg, RJ; Harnden, I; Carnighan, GE; Cox, AM; Blikslager, AT; Garman, KS
MLA Citation
Krüger, L, Gonzalez, LM, Pridgen, TA, McCall, SJ, von Furstenberg, RJ, Harnden, I, Carnighan, GE, Cox, AM, Blikslager, AT, and Garman, KS. "Ductular and proliferative response of esophageal submucosal glands in a porcine model of esophageal injury and repair." American journal of physiology. Gastrointestinal and liver physiology 313.3 (September 2017): G180-G191.
PMID
28572084
Source
epmc
Published In
American journal of physiology. Gastrointestinal and liver physiology
Volume
313
Issue
3
Publish Date
2017
Start Page
G180
End Page
G191
DOI
10.1152/ajpgi.00036.2017

A Landscape of Therapeutic Cooperativity in KRAS Mutant Cancers Reveals Principles for Controlling Tumor Evolution.

Combinatorial inhibition of effector and feedback pathways is a promising treatment strategy for KRAS mutant cancers. However, the particular pathways that should be targeted to optimize therapeutic responses are unclear. Using CRISPR/Cas9, we systematically mapped the pathways whose inhibition cooperates with drugs targeting the KRAS effectors MEK, ERK, and PI3K. By performing 70 screens in models of KRAS mutant colorectal, lung, ovarian, and pancreas cancers, we uncovered universal and tissue-specific sensitizing combinations involving inhibitors of cell cycle, metabolism, growth signaling, chromatin regulation, and transcription. Furthermore, these screens revealed secondary genetic modifiers of sensitivity, yielding a SRC inhibitor-based combination therapy for KRAS/PIK3CA double-mutant colorectal cancers (CRCs) with clinical potential. Surprisingly, acquired resistance to combinations of growth signaling pathway inhibitors develops rapidly following treatment, but by targeting signaling feedback or apoptotic priming, it is possible to construct three-drug combinations that greatly delay its emergence.

Authors
Anderson, GR; Winter, PS; Lin, KH; Nussbaum, DP; Cakir, M; Stein, EM; Soderquist, RS; Crawford, L; Leeds, JC; Newcomb, R; Stepp, P; Yip, C; Wardell, SE; Tingley, JP; Ali, M; Xu, M; Ryan, M; McCall, SJ; McRee, AJ; Counter, CM; Der, CJ; Wood, KC
MLA Citation
Anderson, GR, Winter, PS, Lin, KH, Nussbaum, DP, Cakir, M, Stein, EM, Soderquist, RS, Crawford, L, Leeds, JC, Newcomb, R, Stepp, P, Yip, C, Wardell, SE, Tingley, JP, Ali, M, Xu, M, Ryan, M, McCall, SJ, McRee, AJ, Counter, CM, Der, CJ, and Wood, KC. "A Landscape of Therapeutic Cooperativity in KRAS Mutant Cancers Reveals Principles for Controlling Tumor Evolution." Cell reports 20.4 (July 2017): 999-1015.
PMID
28746882
Source
epmc
Published In
Cell Reports
Volume
20
Issue
4
Publish Date
2017
Start Page
999
End Page
1015
DOI
10.1016/j.celrep.2017.07.006

Professional Practice Evaluation for Pathologists: The Development, Life, and Death of the Evalumetrics Program.

- In 2008, the Joint Commission (JC) implemented a standard mandating formal monitoring of physician professional performance as part of the process of granting and maintaining practice privileges.- To create a pathology-specific management tool to aid pathologists in constructing a professional practice-monitoring program, thereby meeting the JC mandate.- A total of 105 College of American Pathologists (CAP)-defined metrics were created. Metrics were based on the job descriptions of pathologists' duties in the laboratory, and metric development was aided by experience from the Q-Probes and Q-Tracks programs. The program was offered in a Web-based format, allowing secure data entry, customization of metrics, and central data collection for future benchmarking.- The program was live for 3 years, with 347 pathologists subscribed from 61 practices (median, 4 per institution; range, 1-35). Subscribers used 93 of the CAP-defined metrics and created 109 custom metrics. The median number of CAP-defined metrics used per pathologist was 5 (range, 1-43), and the median custom-defined metrics per pathologist was 2 (range, 1-5). Most frequently, 1 to 3 metrics were monitored (42.7%), with 20% each following 4 to 6 metrics, 5 to 9 metrics, or greater than 10 metrics. Anatomic pathology metrics were used more commonly than clinical pathology metrics. Owing to low registration, the program was discontinued in 2016.- Through careful vetting of metrics it was possible to develop a pathologist-specific management tool to address the JC mandate. While this initial product failed, valuable metrics were developed and implementation knowledge was gained that may be used to address new regulatory requirements for emerging value-based payment systems.

Authors
Volmar, KE; McCall, SJ; Schifman, RB; Talbert, ML; Tworek, JA; Hulkower, KI; Guidi, AJ; Nakhleh, RE; Souers, RJ; Bashleben, CP; Blond, BJ
MLA Citation
Volmar, KE, McCall, SJ, Schifman, RB, Talbert, ML, Tworek, JA, Hulkower, KI, Guidi, AJ, Nakhleh, RE, Souers, RJ, Bashleben, CP, and Blond, BJ. "Professional Practice Evaluation for Pathologists: The Development, Life, and Death of the Evalumetrics Program." Archives of pathology & laboratory medicine 141.4 (April 2017): 551-558.
PMID
28353384
Source
epmc
Published In
Archives of Pathology and Laboratory Medicine
Volume
141
Issue
4
Publish Date
2017
Start Page
551
End Page
558
DOI
10.5858/arpa.2016-0275-cp

Serum Amyloid A (SAA) and C-Reactive Protein (CRP) Are Commonly Positive in Hepatocellular Carcinoma and Expression Levels Stratify According to Etiology and the Absence of Cirrhosis

Authors
Shaar, M; Suzuki, A; Poster, C; de Ridder, G; Zhang, X; Cronin, MK; McCall, S; Cardona, D; Abdelmalek, M; Pizzo, S; Jiang, XS; Lefaivre, M; Guy, C
MLA Citation
Shaar, M, Suzuki, A, Poster, C, de Ridder, G, Zhang, X, Cronin, MK, McCall, S, Cardona, D, Abdelmalek, M, Pizzo, S, Jiang, XS, Lefaivre, M, and Guy, C. "Serum Amyloid A (SAA) and C-Reactive Protein (CRP) Are Commonly Positive in Hepatocellular Carcinoma and Expression Levels Stratify According to Etiology and the Absence of Cirrhosis." February 2017.
Source
wos-lite
Published In
Laboratory Investigation
Volume
97
Publish Date
2017
Start Page
424A
End Page
425A

Metastatic Renal Cell Carcinoma Presenting as a Solitary Subcentimeter Gastroesophageal Mucosal Polyp: Report of 5 Cases

Authors
Sham, M; Guy, C; McCall, S; Cardona, D; Zhang, X
MLA Citation
Sham, M, Guy, C, McCall, S, Cardona, D, and Zhang, X. "Metastatic Renal Cell Carcinoma Presenting as a Solitary Subcentimeter Gastroesophageal Mucosal Polyp: Report of 5 Cases." February 2017.
Source
wos-lite
Published In
Laboratory Investigation
Volume
97
Publish Date
2017
Start Page
258A
End Page
258A

TFE3 and SOX11 as Novel Diagnostic Markers for Solid Pseudopapillary Neoplasms

Authors
Harrison, G; Hemmerich, A; Cardona, D; Guy, C; McCall, S; Zhang, X
MLA Citation
Harrison, G, Hemmerich, A, Cardona, D, Guy, C, McCall, S, and Zhang, X. "TFE3 and SOX11 as Novel Diagnostic Markers for Solid Pseudopapillary Neoplasms." February 2017.
Source
wos-lite
Published In
Laboratory Investigation
Volume
97
Publish Date
2017
Start Page
174A
End Page
174A

TFE3 and SOX11 as Novel Diagnostic Markers for Solid Pseudopapillary Neoplasms

Authors
Harrison, G; Hemmerich, A; Cardona, D; Guy, C; McCall, S; Zhang, X
MLA Citation
Harrison, G, Hemmerich, A, Cardona, D, Guy, C, McCall, S, and Zhang, X. "TFE3 and SOX11 as Novel Diagnostic Markers for Solid Pseudopapillary Neoplasms." February 2017.
Source
wos-lite
Published In
Modern Pathology
Volume
30
Publish Date
2017
Start Page
174A
End Page
174A

Serum Amyloid A (SAA) and C-Reactive Protein (CRP) Are Commonly Positive in Hepatocellular Carcinoma and Expression Levels Stratify According to Etiology and the Absence of Cirrhosis

Authors
Shaar, M; Suzuki, A; Poster, C; de Ridder, G; Zhang, X; Cronin, MK; McCall, S; Cardona, D; Abdelmalek, M; Pizzo, S; Jiang, XS; Lefaivre, M; Guy, C
MLA Citation
Shaar, M, Suzuki, A, Poster, C, de Ridder, G, Zhang, X, Cronin, MK, McCall, S, Cardona, D, Abdelmalek, M, Pizzo, S, Jiang, XS, Lefaivre, M, and Guy, C. "Serum Amyloid A (SAA) and C-Reactive Protein (CRP) Are Commonly Positive in Hepatocellular Carcinoma and Expression Levels Stratify According to Etiology and the Absence of Cirrhosis." February 2017.
Source
wos-lite
Published In
Modern Pathology
Volume
30
Publish Date
2017
Start Page
424A
End Page
425A

Metastatic Renal Cell Carcinoma Presenting as a Solitary Subcentimeter Gastroesophageal Mucosal Polyp: Report of 5 Cases

Authors
Shaar, M; Guy, C; McCall, S; Cardona, D; Zhang, X
MLA Citation
Shaar, M, Guy, C, McCall, S, Cardona, D, and Zhang, X. "Metastatic Renal Cell Carcinoma Presenting as a Solitary Subcentimeter Gastroesophageal Mucosal Polyp: Report of 5 Cases." February 2017.
Source
wos-lite
Published In
Modern Pathology
Volume
30
Publish Date
2017
Start Page
258A
End Page
258A

Coded aperture coherent scatter spectral imaging for assessment of breast cancers: An ex-vivo demonstration

© 2017 SPIE. A Coded Aperture Coherent Scatter Spectral Imaging (CACSSI) system was developed in our group to differentiate cancer and healthy tissue in the breast. The utility of the experimental system was previously demonstrated using anthropomorphic breast phantoms and breast biopsy specimens. Here we demonstrate CACSSI utility in identifying tumor margins in real time using breast lumpectomy specimens. Fresh lumpectomy specimens were obtained from Surgical Pathology with the suspected cancerous area designated on the specimen. The specimens were scanned using CACSSI to obtain spectral scatter signatures at multiple locations within the tumor and surrounding tissue. The spectral reconstructions were matched with literature form-factors to classify the tissue as cancerous or non-cancerous. The findings were then compared against pathology reports to confirm the presence and location of the tumor. The system was found to be capable of consistently differentiating cancerous and healthy regions in the breast with spatial resolution of 5 mm. Tissue classification results from the scanned specimens could be correlated with pathology results. We now aim to develop CACSSI as a clinical imaging tool to aid breast cancer assessment and other diagnostic purposes.

Authors
Spencer, JR; Carter, JE; Leung, CK; McCall, SJ; Greenberg, JA; Kapadia, AJ
MLA Citation
Spencer, JR, Carter, JE, Leung, CK, McCall, SJ, Greenberg, JA, and Kapadia, AJ. "Coded aperture coherent scatter spectral imaging for assessment of breast cancers: An ex-vivo demonstration." January 1, 2017.
Source
scopus
Published In
Proceedings of SPIE
Volume
10132
Publish Date
2017
DOI
10.1117/12.2253975

Biobanking-Budgets and the Role of Pathology Biobanks in Precision Medicine.

Biobanks have become an important component of the routine practice of pathology. At the 2016 meeting of the Association of Pathology Chairs, a series of presentations covered several important aspects of biobanking. An often overlooked aspect of biobanking is the fiscal considerations. A biobank budget must address the costs of consenting, procuring, processing, and preserving high-quality biospecimens. Multiple revenue streams will frequently be necessary to create a sustainable biobank; partnering with other key stakeholders has been shown to be successful at academic institutions which may serve as a model. Biobanking needs to be a deeply science-driven and innovating process so that specimens help transform patient-centered clinical and basic research (ie, fulfill the promise of precision medicine). Pathology's role must be at the center of the biobanking process. This ensures that optimal research samples are collected while guaranteeing that clinical diagnostics are never impaired. Biobanks will continue to grow as important components in the mission of pathology, especially in the era of precision medicine.

Authors
Andry, C; Duffy, E; Moskaluk, CA; McCall, S; Roehrl, MHA; Remick, D
MLA Citation
Andry, C, Duffy, E, Moskaluk, CA, McCall, S, Roehrl, MHA, and Remick, D. "Biobanking-Budgets and the Role of Pathology Biobanks in Precision Medicine." Academic pathology 4 (January 2017): 2374289517702924-.
PMID
28725790
Source
epmc
Published In
Academic Pathology
Volume
4
Publish Date
2017
Start Page
2374289517702924
DOI
10.1177/2374289517702924

Radiographic and endoscopic regression of metastatic gastric cancer to the colon in the setting of 5-aminosalicylic acid use.

Colonic metastases from gastric cancer are a rare phenomenon and sparsely reported in the literature. We report a case of a 59-year-old woman who presented with vague abdominal symptoms and initial computer tomography (CT) imaging suggestive of a colonic apple-core lesion with serial colonoscopic biopsies diagnostic of metastatic signet ring cell gastric adenocarcinoma. This case is unique given the evolving CT and endoscopic findings that suggested a regression in colonic wall thickening in the setting of 5-aminosalicylic acid (5-ASA) use prior to histologic diagnosis.

Authors
Patel, YA; McCall, SJ; Zhang, X; Jaffe, T; Shimpi, RA
MLA Citation
Patel, YA, McCall, SJ, Zhang, X, Jaffe, T, and Shimpi, RA. "Radiographic and endoscopic regression of metastatic gastric cancer to the colon in the setting of 5-aminosalicylic acid use." Journal of gastrointestinal oncology 7.6 (December 2016): E88-E92.
PMID
28078130
Source
epmc
Published In
Journal of Gastrointestinal Oncology
Volume
7
Issue
6
Publish Date
2016
Start Page
E88
End Page
E92
DOI
10.21037/jgo.2016.05.02

PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation.

Therapies that efficiently induce apoptosis are likely to be required for durable clinical responses in patients with solid tumors. Using a pharmacological screening approach, we discovered that combined inhibition of B cell lymphoma-extra large (BCL-XL) and the mammalian target of rapamycin (mTOR)/4E-BP axis results in selective and synergistic induction of apoptosis in cellular and animal models of PIK3CA mutant breast cancers, including triple-negative tumors. Mechanistically, inhibition of mTOR/4E-BP suppresses myeloid cell leukemia-1 (MCL-1) protein translation only in PIK3CA mutant tumors, creating a synthetic dependence on BCL-XL This dual dependence on BCL-XL and MCL-1, but not on BCL-2, appears to be a fundamental property of diverse breast cancer cell lines, xenografts, and patient-derived tumors that is independent of the molecular subtype or PIK3CA mutational status. Furthermore, this dependence distinguishes breast cancers from normal breast epithelial cells, which are neither primed for apoptosis nor dependent on BCL-XL/MCL-1, suggesting a potential therapeutic window. By tilting the balance of pro- to antiapoptotic signals in the mitochondria, dual inhibition of MCL-1 and BCL-XL also sensitizes breast cancer cells to standard-of-care cytotoxic and targeted chemotherapies. Together, these results suggest that patients with PIK3CA mutant breast cancers may benefit from combined treatment with inhibitors of BCL-XL and the mTOR/4E-BP axis, whereas alternative methods of inhibiting MCL-1 and BCL-XL may be effective in tumors lacking PIK3CA mutations.

Authors
Anderson, GR; Wardell, SE; Cakir, M; Crawford, L; Leeds, JC; Nussbaum, DP; Shankar, PS; Soderquist, RS; Stein, EM; Tingley, JP; Winter, PS; Zieser-Misenheimer, EK; Alley, HM; Yllanes, A; Haney, V; Blackwell, KL; McCall, SJ; McDonnell, DP; Wood, KC
MLA Citation
Anderson, GR, Wardell, SE, Cakir, M, Crawford, L, Leeds, JC, Nussbaum, DP, Shankar, PS, Soderquist, RS, Stein, EM, Tingley, JP, Winter, PS, Zieser-Misenheimer, EK, Alley, HM, Yllanes, A, Haney, V, Blackwell, KL, McCall, SJ, McDonnell, DP, and Wood, KC. "PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation." Science translational medicine 8.369 (December 2016): 369ra175-.
Website
http://hdl.handle.net/10161/13335
PMID
27974663
Source
epmc
Published In
Science Translational Medicine
Volume
8
Issue
369
Publish Date
2016
Start Page
369ra175
DOI
10.1126/scitranslmed.aae0348

TGF-β-induced stromal CYR61 promotes resistance to gemcitabine in pancreatic ductal adenocarcinoma through downregulation of the nucleoside transporters hENT1 and hCNT3.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer in part due to inherent resistance to chemotherapy, including the first-line drug gemcitabine. Although low expression of the nucleoside transporters hENT1 and hCNT3 that mediate cellular uptake of gemcitabine has been linked to gemcitabine resistance, the mechanisms regulating their expression in the PDAC tumor microenvironment are largely unknown. Here, we report that the matricellular protein cysteine-rich angiogenic inducer 61 (CYR61) negatively regulates the nucleoside transporters hENT1 and hCNT3. CRISPR/Cas9-mediated knockout of CYR61 increased expression of hENT1 and hCNT3, increased cellular uptake of gemcitabine and sensitized PDAC cells to gemcitabine-induced apoptosis. In PDAC patient samples, expression of hENT1 and hCNT3 negatively correlates with expression of CYR61 . We demonstrate that stromal pancreatic stellate cells (PSCs) are a source of CYR61 within the PDAC tumor microenvironment. Transforming growth factor-β (TGF-β) induces the expression of CYR61 in PSCs through canonical TGF-β-ALK5-Smad2/3 signaling. Activation of TGF-β signaling or expression of CYR61 in PSCs promotes resistance to gemcitabine in PDAC cells in an in vitro co-culture assay. Our results identify CYR61 as a TGF-β-induced stromal-derived factor that regulates gemcitabine sensitivity in PDAC and suggest that targeting CYR61 may improve chemotherapy response in PDAC patients.

Authors
Hesler, RA; Huang, JJ; Starr, MD; Treboschi, VM; Bernanke, AG; Nixon, AB; McCall, SJ; White, RR; Blobe, GC
MLA Citation
Hesler, RA, Huang, JJ, Starr, MD, Treboschi, VM, Bernanke, AG, Nixon, AB, McCall, SJ, White, RR, and Blobe, GC. "TGF-β-induced stromal CYR61 promotes resistance to gemcitabine in pancreatic ductal adenocarcinoma through downregulation of the nucleoside transporters hENT1 and hCNT3." Carcinogenesis 37.11 (November 2016): 1041-1051.
PMID
27604902
Source
epmc
Published In
Carcinogenesis
Volume
37
Issue
11
Publish Date
2016
Start Page
1041
End Page
1051
DOI
10.1093/carcin/bgw093

Physician Satisfaction With Clinical Laboratory Services: A College of American Pathologists Q-Probes Study of 81 Institutions.

-Assessment of customer satisfaction is a vital component of the laboratory quality improvement program.-To survey the level of physician satisfaction with hospital clinical laboratory services.-Participating institutions provided demographic information and survey results of physician satisfaction, with specific features of clinical laboratory services individually rated on a scale of 5 (excellent) to 1 (poor).-Eighty-one institutions submitted 2425 surveys. The median overall satisfaction score was 4.2 (10th percentile, 3.6; 90th percentile, 4.6). Of the 16 surveyed areas receiving the highest percentage of excellent/good ratings (combined scores of 4 and 5), quality of results was highest along with test menu adequacy, staff courtesy, and overall satisfaction. Of the 4 categories receiving the lowest percentage values of excellent/good ratings, 3 were related to turnaround time for inpatient "STAT" (tests performed immediately), outpatient STAT, and esoteric tests. The fourth was a new category presented in this survey: ease of electronic order entry. Here, 11.4% (241 of 2121) of physicians assigned below-average (2) or poor (1) scores. The 5 categories deemed most important to physicians included quality of results, turnaround times for inpatient STAT, routine, and outpatient STAT tests, and clinical report format. Overall satisfaction as measured by physician willingness to recommend their laboratory to another physician remains high at 94.5% (2160 of 2286 respondents).-There is a continued trend of high physician satisfaction and loyalty with clinical laboratory services. Physician dissatisfaction with ease of electronic order entry represents a new challenge. Test turnaround times are persistent areas of dissatisfaction, representing areas for improvement.

Authors
McCall, SJ; Souers, RJ; Blond, B; Massie, L
MLA Citation
McCall, SJ, Souers, RJ, Blond, B, and Massie, L. "Physician Satisfaction With Clinical Laboratory Services: A College of American Pathologists Q-Probes Study of 81 Institutions." Archives of pathology & laboratory medicine 140.10 (October 2016): 1098-1103.
PMID
27684982
Source
epmc
Published In
Archives of Pathology and Laboratory Medicine
Volume
140
Issue
10
Publish Date
2016
Start Page
1098
End Page
1103
DOI
10.5858/arpa.2015-0486-cp

Identification and Therapeutic Inhibition of Pathways Driving Resistance to Targeted Breast Cancer Therapies

Authors
Wood, KC; Anderson, GR; Wardell, SE; Jasper, JS; Stein, EM; Martz, CA; Alley, HM; Haney, V; Yllanes, A; Blackwell, KL; McCall, SJ; McDonnell, DP
MLA Citation
Wood, KC, Anderson, GR, Wardell, SE, Jasper, JS, Stein, EM, Martz, CA, Alley, HM, Haney, V, Yllanes, A, Blackwell, KL, McCall, SJ, and McDonnell, DP. "Identification and Therapeutic Inhibition of Pathways Driving Resistance to Targeted Breast Cancer Therapies." JOURNAL OF WOMENS HEALTH 25.9 (September 2016): 976-976.
Source
wos-lite
Published In
Journal of Women's Health
Volume
25
Issue
9
Publish Date
2016
Start Page
976
End Page
976

TH-AB-209-10: Breast Cancer Identification Through X-Ray Coherent Scatter Spectral Imaging.

We have previously described the development and testing of a coherent-scatter spectral imaging system for identification of cancer. Our prior evaluations were performed using either tissue surrogate phantoms or formalin-fixed tissue obtained from pathology. Here we present the first results from a scatter imaging study using fresh breast tumor tissues obtained through surgical excision.A coherent-scatter imaging system was built using a clinical X-ray tube, photon counting detectors, and custom-designed coded-apertures. System performance was characterized using calibration phantoms of biological materials. Fresh breast tumors were obtained from patients undergoing mastectomy and lumpectomy surgeries for breast cancer. Each specimen was vacuum-sealed, scanned using the scatter imaging system, and then sent to pathology for histological workup. Scatter images were generated separately for each tissue specimen and analyzed to identify voxels containing malignant tissue. The images were compared against histological analysis (H&E + pathologist identification of tumors) to assess the match between scatter-based and histological diagnosis.In all specimens scanned, the scatter images showed the location of cancerous regions within the specimen. The detection and classification was performed through automated spectral matching without the need for manual intervention. The scatter spectra corresponding to cancer tissue were found to be in agreement with those reported in literature. Inter-patient variability was found to be within limits reported in literature. The scatter images showed agreement with pathologist-identified regions of cancer. Spatial resolution for this configuration of the scanner was determined to be 2-3 mm, and the total scan time for each specimen was under 15 minutes.This work demonstrates the utility of coherent scatter imaging in identifying cancer based on the scatter properties of the tissue. It presents the first results from coherent scatter imaging of fresh (unfixed) breast tissue using our coded-aperture scatter imaging approach for cancer identification.

Authors
Kapadia, A; Morris, R; Albanese, K; Spencer, J; McCall, S; Greenberg, J
MLA Citation
Kapadia, A, Morris, R, Albanese, K, Spencer, J, McCall, S, and Greenberg, J. "TH-AB-209-10: Breast Cancer Identification Through X-Ray Coherent Scatter Spectral Imaging." Medical physics 43.6 (June 2016): 3865-.
PMID
28047602
Source
epmc
Published In
Medical physics
Volume
43
Issue
6
Publish Date
2016
Start Page
3865
DOI
10.1118/1.4958101

Mixed Adenoneuroendocrine Carcinoma, Amphicrine Type, of the Small Bowel.

Amphicrine-type mixed adenoneuroendocrine carcinomas are exceedingly rare lesions of the gastrointestinal tract, comprising tumor cells simultaneously demonstrating both neuroendocrine and exocrine features. To date, only 14 cases of amphicrine carcinoma have been reported; here we report the first definitive case of amphicrine carcinoma in the small bowel.A 72-year-old woman who sought treatment for nonspecific abdominal complaints was found to have a duodenojejunal junction tumor and underwent radical surgical resection.Morphologically, the tumor consisted of areas of moderately differentiated adenocarcinoma intermingled with areas characteristic of neuroendocrine tumor. The entire tumor showed strong, diffuse immunoreactivity for synaptophysin. Coexpression of exocrine and neuroendocrine features by neoplastic cells indicates bivalent differentiation, and therefore the tumor was classified as an amphicrine carcinoma of the small bowel.Demonstration of amphicrine carcinoma in the small bowel carries implications with regard to the common origin of exocrine and neuroendocrine cells in the gastrointestinal tract.

Authors
Ludmir, EB; McCall, SJ; Cardona, DM; Perkinson, KR; Guy, CD; Zhang, X
MLA Citation
Ludmir, EB, McCall, SJ, Cardona, DM, Perkinson, KR, Guy, CD, and Zhang, X. "Mixed Adenoneuroendocrine Carcinoma, Amphicrine Type, of the Small Bowel." American journal of clinical pathology 145.5 (May 2016): 703-709.
PMID
27124941
Source
epmc
Published In
American Journal of Clinical Pathology
Volume
145
Issue
5
Publish Date
2016
Start Page
703
End Page
709
DOI
10.1093/ajcp/aqw028

Primary high-grade neuroendocrine carcinoma emerging from an adenomatous polyp in the setting of familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is a rare inherited syndrome that is characterised by innumerable adenomas of the colon and rectum, a high risk of colorectal cancer and a variety of extracolonic manifestations. FAP presents as hundreds to thousands of colonic adenomas beginning in adolescence. The syndrome is associated with less than 1% of all colorectal cancer cases, but there is a nearly 100% lifetime risk of colorectal cancer in individuals with FAP. This case demonstrates a 60-year-old man with FAP who developed high-grade neuroendocrine carcinoma with glandular and squamous differentiation, and regional lymph node and liver metastases. Early diagnosis of FAP is of the utmost importance to start screening colonoscopies to assess disease burden, perform polypectomies and to make management decisions. Neuroendocrine carcinomas rarely occur in patients with FAP, and awareness of this association among general medical physicians and pathologists is essential for the diagnosis and care of these patients.

Authors
Detweiler, CJ; Cardona, DM; Hsu, DS; McCall, SJ
MLA Citation
Detweiler, CJ, Cardona, DM, Hsu, DS, and McCall, SJ. "Primary high-grade neuroendocrine carcinoma emerging from an adenomatous polyp in the setting of familial adenomatous polyposis." BMJ case reports 2016 (February 16, 2016).
PMID
26884076
Source
epmc
Published In
BMJ Case Reports
Volume
2016
Publish Date
2016
DOI
10.1136/bcr-2015-214206

Transcription Factor E3 as a Novel Diagnostic Marker for Solid Pseudopapillary Neoplasm

Authors
Harrison, G; Hemmerich, A; Guy, C; McCall, SJ; Cardona, DM; Zhang, X
MLA Citation
Harrison, G, Hemmerich, A, Guy, C, McCall, SJ, Cardona, DM, and Zhang, X. "Transcription Factor E3 as a Novel Diagnostic Marker for Solid Pseudopapillary Neoplasm." February 2016.
Source
wos-lite
Published In
Laboratory Investigation
Volume
96
Publish Date
2016
Start Page
174A
End Page
174A

Transcription Factor E3 as a Novel Diagnostic Marker for Solid Pseudopapillary Neoplasm

Authors
Harrison, G; Hemmerich, A; Guy, C; McCall, SJ; Cardona, DM; Zhang, X
MLA Citation
Harrison, G, Hemmerich, A, Guy, C, McCall, SJ, Cardona, DM, and Zhang, X. "Transcription Factor E3 as a Novel Diagnostic Marker for Solid Pseudopapillary Neoplasm." February 2016.
Source
wos-lite
Published In
Modern Pathology
Volume
29
Publish Date
2016
Start Page
174A
End Page
174A

Validation of coded aperture coherent scatter spectral imaging for normal and neoplastic breast tissues via surgical pathology

© 2016 SPIE. This study intends to validate the sensitivity and specificity of coded aperture coherent scatter spectral imaging (CACSSI) by comparison to standard histological preparation and pathologic analysis methods used to differentiate normal and neoplastic breast tissues. A composite overlay of the CACSSI rendered image and pathologist interpreted stained sections validate the ability of CACSSI to differentiate normal and neoplastic breast structures ex-vivo. Via comparison to pathologist annotated slides, the CACSSI system may be further optimized to maximize sensitivity and specificity for differentiation of breast carcinomas.

Authors
Morris, RE; Albanese, KE; Lakshmanan, MN; McCall, SJ; Greenberg, JA; Kapadia, AJ
MLA Citation
Morris, RE, Albanese, KE, Lakshmanan, MN, McCall, SJ, Greenberg, JA, and Kapadia, AJ. "Validation of coded aperture coherent scatter spectral imaging for normal and neoplastic breast tissues via surgical pathology." January 1, 2016.
Source
scopus
Published In
Proceedings of SPIE
Volume
9783
Publish Date
2016
DOI
10.1117/12.2216974

Ductal metaplasia in oesophageal submucosal glands is associated with inflammation and oesophageal adenocarcinoma.

Recent studies have suggested that oesophageal submucosal gland (ESMG) ducts harbour progenitor cells that may contribute to oesophageal metaplasia. Our objective was to determine whether histological differences exist between the ESMGs of individuals with and without oesophageal adenocarcinoma (EAC).We performed histological assessment of 343 unique ESMGs from 30 control patients, 24 patients with treatment-naïve high-grade columnar dysplasia (HGD) or EAC, and 23 non-EAC oesophagectomy cases. A gastrointestinal pathologist assessed haematoxylin and eosin-stained ESMG images by using a scoring system that assigns individual ESMG acini to five histological types (mucous, serous, oncocytic, dilated, or ductal metaplastic). In our model, ductal metaplastic acini were more common in patients with HGD/EAC (12.7%) than in controls (3.5%) (P = 0.006). We also identified greater proportions of acini with dilation (21.9%, P < 0.001) and, to a lesser extent, ductal metaplasia (4.3%, P = 0.001) in non-EAC oesophagectomy cases than in controls. Ductal metaplasia tended to occur in areas of mucosal ulceration or tumour.We found a clear association between ductal metaplastic ESMG acini and HGD/EAC. Non-EAC cases had dilated acini and some ductal dilation. Because ESMGs and ducts harbour putative progenitor cells, these associations could have significance for understanding the pathogenesis of EAC.

Authors
Garman, KS; Kruger, L; Thomas, S; Swiderska-Syn, M; Moser, BK; Diehl, AM; McCall, SJ
MLA Citation
Garman, KS, Kruger, L, Thomas, S, Swiderska-Syn, M, Moser, BK, Diehl, AM, and McCall, SJ. "Ductal metaplasia in oesophageal submucosal glands is associated with inflammation and oesophageal adenocarcinoma." Histopathology 67.6 (December 2015): 771-782.
PMID
25847432
Source
epmc
Published In
Histopathology
Volume
67
Issue
6
Publish Date
2015
Start Page
771
End Page
782
DOI
10.1111/his.12707

The Molecular Taxonomy of Primary Prostate Cancer.

There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects.

Authors
Cancer Genome Atlas Research Network,
MLA Citation
Cancer Genome Atlas Research Network, . "The Molecular Taxonomy of Primary Prostate Cancer." Cell 163.4 (November 2015): 1011-1025.
PMID
26544944
Source
epmc
Published In
Cell
Volume
163
Issue
4
Publish Date
2015
Start Page
1011
End Page
1025
DOI
10.1016/j.cell.2015.10.025

Metastatic gallbladder cancer masquerading as primary colon malignancy.

Authors
Sun, Z; Galeotti, J; McCall, SJ; Mantyh, C
MLA Citation
Sun, Z, Galeotti, J, McCall, SJ, and Mantyh, C. "Metastatic gallbladder cancer masquerading as primary colon malignancy." Clinical Medicine Review Case Reports 2 (June 1, 2015): 1-3.
Source
manual
Published In
Clinical Medicine Review Case Reports
Volume
2
Publish Date
2015
Start Page
1
End Page
3

Error Reduction and Prevention in Surgical Pathology

Diagnostic musculoskeletal surgical pathology. Philadelphia: Elsevier; 2004. pp. 1–18. Suriawinata AA, Antonio LB, Thung SN. Liver tissue processing and normal histology. In: Odze RD, Goldblum JR, editors. Surgical pathology of the GI tract, ...

Authors
Nakhleh, RE
MLA Citation
Nakhleh, RE. "Error Reduction and Prevention in Surgical Pathology." Springer, March 3, 2015.
Source
google-books
Publish Date
2015

Mismatch repair gone awry: Management of Lynch syndrome.

The hallmark of Lynch syndrome involves germline mutations of genes important in DNA mismatch repair. Affected family kindreds will have multiple associated malignancies, the most common of which is colorectal adenocarcinoma. Recently, evidence has shown that clinical diagnostic criteria provided by the Amsterdam Criteria and the Bethesda Guidelines must be linked with microsatellite instability testing to correctly diagnose Lynch syndrome. We present a case of metachronous colorectal adenocarcinomas in a patient less than 50 years of age, followed by a discussion of Lynch syndrome, with an emphasis on surveillance and prevention of malignancies.

Authors
Zhang, T; Boswell, EL; McCall, SJ; Hsu, DS
MLA Citation
Zhang, T, Boswell, EL, McCall, SJ, and Hsu, DS. "Mismatch repair gone awry: Management of Lynch syndrome." Critical reviews in oncology/hematology 93.3 (March 2015): 170-179. (Review)
PMID
25459670
Source
epmc
Published In
Critical Reviews in Oncology/Hematology
Volume
93
Issue
3
Publish Date
2015
Start Page
170
End Page
179
DOI
10.1016/j.critrevonc.2014.10.005

Endogenous elevation of plasma cholecystokinin does not prevent gallstones.

Regular gall bladder contraction reduces bile stasis and prevents gallstone formation. Intraduodenal administration of exogenous pancreatic secretory trypsin inhibitor-I (PSTI-I, also known as monitor peptide) causes cholecystokinin (CCK) secretion.We proposed that stimulation of CCK release by PSTI would produce gall bladder contraction and prevent gallstones in mice fed a lithogenic diet. Therefore, we tested the effect of overexpression of rat PSTI-I in pancreatic acinar cells on plasma CCK levels and gall bladder function in a transgenic mouse line (TgN[Psti1]; known hereafter as PSTI-I tg).Importantly, PSTI tg mice had elevated fasting and fed plasma CCK levels compared to wild-type (WT) mice. Only mice fed the lithogenic diet developed gallstones. Both fasting and stimulated plasma CCK levels were substantially reduced in both WT and PSTI-I tg mice on the lithogenic diet. Moreover, despite higher CCK levels PSTI-I tg animals developed more gallstones than WT animals.Together with the previously observed decrease in CCK-stimulated gall bladder emptying in mice fed a lithogenic diet, our findings suggest that a lithogenic diet causes gallstone formation by impaired CCK secretion in addition to reduced gall bladder sensitivity to CCK.

Authors
Shahid, RA; Wang, DQ-H; Fee, BE; McCall, SJ; Romac, JM-J; Vigna, SR; Liddle, RA
MLA Citation
Shahid, RA, Wang, DQ-H, Fee, BE, McCall, SJ, Romac, JM-J, Vigna, SR, and Liddle, RA. "Endogenous elevation of plasma cholecystokinin does not prevent gallstones." European journal of clinical investigation 45.3 (March 2015): 237-246.
PMID
25641074
Source
epmc
Published In
European Journal of Clinical Investigation
Volume
45
Issue
3
Publish Date
2015
Start Page
237
End Page
246
DOI
10.1111/eci.12400

Diagnosing Hepatocellular Carcinoma With Immunohistochemistry: Quantitative Assessment of Performance Characteristics for gamma-H2AX, Glypican-3, Clathrin Heavy Chain, and Glutamine Synthetase

Authors
Poster, C; Gustafson, K; Furth, E; McCall, S; Cardona, D; Zhang, X; Lagoo, A; Lefaivre, M; Guy, C
MLA Citation
Poster, C, Gustafson, K, Furth, E, McCall, S, Cardona, D, Zhang, X, Lagoo, A, Lefaivre, M, and Guy, C. "Diagnosing Hepatocellular Carcinoma With Immunohistochemistry: Quantitative Assessment of Performance Characteristics for gamma-H2AX, Glypican-3, Clathrin Heavy Chain, and Glutamine Synthetase." February 2015.
Source
wos-lite
Published In
Laboratory Investigation
Volume
95
Publish Date
2015
Start Page
421A
End Page
421A

Diagnosing Hepatocellular Carcinoma With Immunohistochemistry: Quantitative Assessment of Performance Characteristics for gamma-H2AX, Glypican-3, Clathrin Heavy Chain, and Glutamine Synthetase

Authors
Poster, C; Gustafson, K; Furth, E; McCall, S; Cardona, D; Zhang, X; Lagoo, A; Lefaivre, M; Guy, C
MLA Citation
Poster, C, Gustafson, K, Furth, E, McCall, S, Cardona, D, Zhang, X, Lagoo, A, Lefaivre, M, and Guy, C. "Diagnosing Hepatocellular Carcinoma With Immunohistochemistry: Quantitative Assessment of Performance Characteristics for gamma-H2AX, Glypican-3, Clathrin Heavy Chain, and Glutamine Synthetase." February 2015.
Source
wos-lite
Published In
Modern Pathology
Volume
28
Publish Date
2015
Start Page
421A
End Page
421A

Patterns of failure for stage I ampulla of Vater adenocarcinoma: a single institutional experience.

Ampullary adenocarcinoma is a rare malignancy associated with a relatively favorable prognosis. Given high survival rates in stage I patients reported in small series with surgery alone, adjuvant chemoradiotherapy (CRT) has traditionally been recommended only for patients with high risk disease. Recent population-based data have demonstrated inferior outcomes to previous series. We examined disease-related outcomes for stage I tumors treated with pancreaticoduodenectomy, with and without CRT.All patients with stage I ampullary adenocarcinoma treated from 1976 to 2011 at Duke University were reviewed. Disease-related endpoints including local control (LC), metastasis-free survival (MFS), disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method.Forty-four patients were included in this study. Thirty-one patients underwent surgery alone, while 13 also received adjuvant CRT. Five-year LC, MFS, DFS and OS for patients treated with surgery only and surgery with CRT were 56% and 83% (P=0.13), 67% and 83% (P=0.31), 56% and 83% (P=0.13), and 53% and 68% (P=0.09), respectively.The prognosis for patients diagnosed with stage I ampullary adenocarcinoma may not be as favorable as previously described. Our data suggests a possible benefit of adjuvant CRT delivery.

Authors
Zhong, J; Palta, M; Willett, CG; McCall, SJ; McSherry, F; Tyler, DS; Uronis, HE; Czito, BG
MLA Citation
Zhong, J, Palta, M, Willett, CG, McCall, SJ, McSherry, F, Tyler, DS, Uronis, HE, and Czito, BG. "Patterns of failure for stage I ampulla of Vater adenocarcinoma: a single institutional experience." Journal of gastrointestinal oncology 5.6 (December 2014): 421-427.
PMID
25436120
Source
epmc
Published In
Journal of Gastrointestinal Oncology
Volume
5
Issue
6
Publish Date
2014
Start Page
421
End Page
427
DOI
10.3978/j.issn.2078-6891.2014.084

Q-Probes studies in anatomic pathology: quality improvement through targeted benchmarking.

CONTEXT: The Q-Probes program is a peer-comparison quality assurance service offered by the College of American Pathologists that was created in 1989. OBJECTIVE: To establish national benchmarks around a specific quality metric at a specific point in time in anatomic pathology (AP). DESIGN: Q-Probes are based on a voluntary subscription for an individual study. Hospital-based laboratories in the United States, Canada, and 16 other countries have participated. Approximately one-third of all Q-Probes studies address AP metrics. Each Q-Probes study has a primary quality indicator and additional minor indicators. RESULTS: There have been 52 AP Q-Probes studies addressing process-, outcome-, and structure-related quality assurance issues. These Q-Probes studies often represented the first standardized national benchmark for specific metrics in the disciplines of cytopathology, surgical pathology, and autopsy pathology, and as such have been cited more than 1700 times in peer-reviewed literature. The AP Q-Probes studies that have been repeated over time demonstrate improvement in laboratory performance across an international spectrum. CONCLUSIONS: The Q-Probes program has produced important national benchmarks in AP, addressing preanalytic, analytic, and postanalytic factors in the disciplines of cytopathology, surgical pathology, and autopsy pathology. Q-Probes study data have been published, cited, and used in the creation of laboratory accreditation standards and other national guidelines.

Authors
Tworek, JA; Volmar, KE; McCall, SJ; Bashleben, CP; Howanitz, PJ
MLA Citation
Tworek, JA, Volmar, KE, McCall, SJ, Bashleben, CP, and Howanitz, PJ. "Q-Probes studies in anatomic pathology: quality improvement through targeted benchmarking." Archives of pathology & laboratory medicine 138.9 (September 2014): 1156-1166.
PMID
25171698
Source
epmc
Published In
Archives of Pathology and Laboratory Medicine
Volume
138
Issue
9
Publish Date
2014
Start Page
1156
End Page
1166
DOI
10.5858/arpa.2014-0149-oa

Comprehensive molecular characterization of gastric adenocarcinoma.

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein-Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies.

Authors
Cancer Genome Atlas Research Network,
MLA Citation
Cancer Genome Atlas Research Network, . "Comprehensive molecular characterization of gastric adenocarcinoma." Nature 513.7517 (September 2014): 202-209.
PMID
25079317
Source
epmc
Published In
Nature
Volume
513
Issue
7517
Publish Date
2014
Start Page
202
End Page
209
DOI
10.1038/nature13480

Identification and validation of actionable mutations in solid tumors

Authors
Zessin, AS; Randall, A; McCall, S; Datto, MB; Hsu, SD
MLA Citation
Zessin, AS, Randall, A, McCall, S, Datto, MB, and Hsu, SD. "Identification and validation of actionable mutations in solid tumors." May 20, 2014.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
32
Issue
15
Publish Date
2014

Phase I study of dasatinib in combination with capecitabine, oxaliplatin and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer.

PURPOSE: Dasatinib inhibits src family kinases and has anti-angiogenic properties. We conducted a phase I study of dasatinib, capecitabine, oxaliplatin, and bevacizumab (CapeOx/bevacizumab), with an expansion cohort in metastatic colorectal cancer (CRC). METHODS: Patients were enrolled in a dose escalation cohort to establish the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D). Using a "3 + 3" design, twelve patients with advanced solid tumors received dasatinib (50 mg twice daily or 70 mg daily), capecitabine (850 mg/m(2) twice daily, days 1-14), oxaliplatin (130 mg/m(2) on day 1) and bevacizumab (7.5 mg/kg on day1), every 3 weeks. Ten patients with previously untreated metastatic CRC were then enrolled in an expansion cohort. Activated src (src(act)) expression was measured by immunohistochemistry, using an antibody that selectively recognizes the active conformation of src (clone 28). RESULTS: Twenty-two patients were enrolled between June 2009 and May 2011. Two DLTs were observed in the 50 mg bid dasatinib cohort, and one DLT was observed in the 70 mg daily dasatinib cohort. The MTD and RP2D for dasatinib was 70 mg daily. The most common treatment-related adverse events were fatigue (20; 91 %) and diarrhea (18; 82 %). Biomarker analysis of src(act) expression demonstrated that the overall response rate (ORR) was 75 % (6/8) for patients with high src(act) expression (IHC ≥ 2), compared to 0 % (0/8) for patients with low srcact expression (IHC 0 or 1); (p = 0.007). CONCLUSIONS: The RP2D of dasatinib is 70 mg daily in combination with CapeOx/bevacizumab. High levels of srcact expression may predict those patients most likely to benefit from dasatinib.

Authors
Strickler, JH; McCall, S; Nixon, AB; Brady, JC; Pang, H; Rushing, C; Cohn, A; Starodub, A; Arrowood, C; Haley, S; Meadows, KL; Morse, MA; Uronis, HE; Blobe, GC; Hsu, SD; Zafar, SY; Hurwitz, HI
MLA Citation
Strickler, JH, McCall, S, Nixon, AB, Brady, JC, Pang, H, Rushing, C, Cohn, A, Starodub, A, Arrowood, C, Haley, S, Meadows, KL, Morse, MA, Uronis, HE, Blobe, GC, Hsu, SD, Zafar, SY, and Hurwitz, HI. "Phase I study of dasatinib in combination with capecitabine, oxaliplatin and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer." Invest New Drugs 32.2 (April 2014): 330-339.
PMID
24173967
Source
pubmed
Published In
Investigational New Drugs
Volume
32
Issue
2
Publish Date
2014
Start Page
330
End Page
339
DOI
10.1007/s10637-013-0042-9

TTF-1 Is Expressed in a Subset of Esophageal Adenocarcinomas

Authors
Layne, AC; Cummings, TJ; Guy, CD; Cardona, DM; Bentley, RC; Shealy, MJ; Zhang, X; McCall, SJ
MLA Citation
Layne, AC, Cummings, TJ, Guy, CD, Cardona, DM, Bentley, RC, Shealy, MJ, Zhang, X, and McCall, SJ. "TTF-1 Is Expressed in a Subset of Esophageal Adenocarcinomas." February 2014.
Source
wos-lite
Published In
Modern Pathology
Volume
27
Publish Date
2014
Start Page
188A
End Page
188A

TTF-1 Is Expressed in a Subset of Esophageal Adenocarcinomas

Authors
Layne, AC; Cummings, TJ; Guy, CD; Cardona, DM; Bentley, RC; Shealy, MJ; Zhang, X; McCall, SJ
MLA Citation
Layne, AC, Cummings, TJ, Guy, CD, Cardona, DM, Bentley, RC, Shealy, MJ, Zhang, X, and McCall, SJ. "TTF-1 Is Expressed in a Subset of Esophageal Adenocarcinomas." February 2014.
Source
wos-lite
Published In
Laboratory Investigation
Volume
94
Publish Date
2014
Start Page
188A
End Page
188A

Delayed Specimen Collection May Artifactually Damage the Mucosal Surface in Barrett's EMR Specimens

Authors
Zhang, X; Zhao, L; Guy, CD; McCall, SJ; Cardona, DM; Burbridge, RA; Garman, KS; Branch, MS; Siddiqui, U; Xiao, S-Y; Waxman, I; Hart, J
MLA Citation
Zhang, X, Zhao, L, Guy, CD, McCall, SJ, Cardona, DM, Burbridge, RA, Garman, KS, Branch, MS, Siddiqui, U, Xiao, S-Y, Waxman, I, and Hart, J. "Delayed Specimen Collection May Artifactually Damage the Mucosal Surface in Barrett's EMR Specimens." February 2014.
Source
wos-lite
Published In
Laboratory Investigation
Volume
94
Publish Date
2014
Start Page
211A
End Page
211A

Delayed Specimen Collection May Artifactually Damage the Mucosal Surface in Barrett's EMR Specimens

Authors
Zhang, X; Zhao, L; Guy, CD; McCall, SJ; Cardona, DM; Burbridge, RA; Garman, KS; Branch, MS; Siddiqui, U; Xiao, S-Y; Waxman, I; Hart, J
MLA Citation
Zhang, X, Zhao, L, Guy, CD, McCall, SJ, Cardona, DM, Burbridge, RA, Garman, KS, Branch, MS, Siddiqui, U, Xiao, S-Y, Waxman, I, and Hart, J. "Delayed Specimen Collection May Artifactually Damage the Mucosal Surface in Barrett's EMR Specimens." February 2014.
Source
wos-lite
Published In
Modern Pathology
Volume
27
Publish Date
2014
Start Page
211A
End Page
211A

The Role of Eosinophils and Neuroendocrine Cell Nests in the Assessment of Gastrointestinal Biopsies in Bone Marrow Transplant Patients

Authors
Shealy, MJ; de Ridder, GG; McCall, SJ; Guy, CD; Zhang, X; Cardona, DM
MLA Citation
Shealy, MJ, de Ridder, GG, McCall, SJ, Guy, CD, Zhang, X, and Cardona, DM. "The Role of Eosinophils and Neuroendocrine Cell Nests in the Assessment of Gastrointestinal Biopsies in Bone Marrow Transplant Patients." February 2014.
Source
wos-lite
Published In
Laboratory Investigation
Volume
94
Publish Date
2014
Start Page
203A
End Page
203A

The Role of Eosinophils and Neuroendocrine Cell Nests in the Assessment of Gastrointestinal Biopsies in Bone Marrow Transplant Patients

Authors
Shealy, MJ; de Ridder, GG; McCall, SJ; Guy, CD; Zhang, X; Cardona, DM
MLA Citation
Shealy, MJ, de Ridder, GG, McCall, SJ, Guy, CD, Zhang, X, and Cardona, DM. "The Role of Eosinophils and Neuroendocrine Cell Nests in the Assessment of Gastrointestinal Biopsies in Bone Marrow Transplant Patients." February 2014.
Source
wos-lite
Published In
Modern Pathology
Volume
27
Publish Date
2014
Start Page
203A
End Page
203A

Phase i study of dasatinib in combination with capecitabine, oxaliplatin and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer

Purpose Dasatinib inhibits src family kinases and has anti-angiogenic properties. We conducted a phase I study of dasatinib, capecitabine, oxaliplatin, and bevacizumab (CapeOx/bevacizumab), with an expansion cohort in metastatic colorectal cancer (CRC). Methods Patients were enrolled in a dose escalation cohort to establish the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D). Using a "3 + 3" design, twelve patients with advanced solid tumors received dasatinib (50 mg twice daily or 70 mg daily), capecitabine (850 mg/m 2 twice daily, days 1-14), oxaliplatin (130 mg/m 2 on day 1) and bevacizumab (7.5 mg/kg on day1), every 3 weeks. Ten patients with previously untreated metastatic CRC were then enrolled in an expansion cohort. Activated src (src act ) expression was measured by immunohistochemistry, using an antibody that selectively recognizes the active conformation of src (clone 28). Results Twenty-two patients were enrolled between June 2009 and May 2011. Two DLTs were observed in the 50 mg bid dasatinib cohort, and one DLT was observed in the 70 mg daily dasatinib cohort. The MTD and RP2D for dasatinib was 70 mg daily. The most common treatment-related adverse events were fatigue (20; 91 %) and diarrhea (18; 82 %). Biomarker analysis of src act expression demonstrated that the overall response rate (ORR) was 75 % (6/8) for patients with high src act expression (IHC ≥ 2), compared to 0 % (0/8) for patients with low src act expression (IHC 0 or 1); (p = 0.007). Conclusions The RP2D of dasatinib is 70 mg daily in combination with CapeOx/bevacizumab. High levels of src act expression may predict those patients most likely to benefit from dasatinib. © 2013 Springer Science+Business Media New York.

Authors
Strickler, JH; McCall, S; Nixon, AB; Brady, JC; Pang, H; Rushing, C; Cohn, A; Starodub, A; Arrowood, C; Haley, S; Meadows, KL; Morse, MA; Uronis, HE; Blobe, GC; Hsu, SD; Zafar, SY; Hurwitz, HI
MLA Citation
Strickler, JH, McCall, S, Nixon, AB, Brady, JC, Pang, H, Rushing, C, Cohn, A, Starodub, A, Arrowood, C, Haley, S, Meadows, KL, Morse, MA, Uronis, HE, Blobe, GC, Hsu, SD, Zafar, SY, and Hurwitz, HI. "Phase i study of dasatinib in combination with capecitabine, oxaliplatin and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer." Investigational New Drugs 32.2 (January 1, 2014): 330-339.
Source
scopus
Published In
Investigational New Drugs
Volume
32
Issue
2
Publish Date
2014
Start Page
330
End Page
339
DOI
10.1007/s10637-013-0042-9

Radiosensitive orbital metastasis as presentation of occult colonic adenocarcinoma.

An 82-year-old man presented with progressive right frontal headaches. The patient's history was significant for benign polyps on surveillance colonoscopy 2 years prior, without high-grade dysplasia or carcinoma. MRI revealed an enhancing lesion arising within the superomedial aspect of the right orbit. Lesion biopsy demonstrated histological appearance and immunophenotype suggestive of colonic adenocarcinoma. Staging positron emission tomography/CT showed visceral metastases and diffuse activity in the posterior rectosigmoid, consistent with metastatic colon cancer. Treatment of the orbital lesion with external beam radiotherapy to 30 Gy resulted in significant palliation of the patient's headaches. The patient expired 2 months following treatment completion due to disease progression. Orbital metastasis as the initial presentation of an occult colorectal primary lesion is exceedingly rare, and occurred in this patient despite surveillance colonoscopy. Radiotherapy remains an efficacious modality for treatment of orbital metastases.

Authors
Ludmir, EB; McCall, SJ; Czito, BG; Palta, M
MLA Citation
Ludmir, EB, McCall, SJ, Czito, BG, and Palta, M. "Radiosensitive orbital metastasis as presentation of occult colonic adenocarcinoma." BMJ case reports 2014 (January 2014).
PMID
25240005
Source
epmc
Published In
BMJ Case Reports
Volume
2014
Publish Date
2014
DOI
10.1136/bcr-2014-206407

Patterns of Failure for Stage I Ampulla of Vater Adenocarcinoma: A Single Institutional Experience

Authors
Zhong, J; Palta, M; Willett, CG; McCall, SJ; McSherry, F; Uronis, HE; Tyler, DS; Czito, BG
MLA Citation
Zhong, J, Palta, M, Willett, CG, McCall, SJ, McSherry, F, Uronis, HE, Tyler, DS, and Czito, BG. "Patterns of Failure for Stage I Ampulla of Vater Adenocarcinoma: A Single Institutional Experience." October 1, 2013.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
87
Issue
2
Publish Date
2013
Start Page
S317
End Page
S317

Correlation of Src activation with response to dasatinib, capecitabine, oxaliplatin, and bevacizumab in advanced solid tumors

Authors
Strickler, JH; McCall, S; Nixon, AB; Pang, H; Rushing, C; Arrowood, C; Haley, S; Meadows, K; Hurwitz, H
MLA Citation
Strickler, JH, McCall, S, Nixon, AB, Pang, H, Rushing, C, Arrowood, C, Haley, S, Meadows, K, and Hurwitz, H. "Correlation of Src activation with response to dasatinib, capecitabine, oxaliplatin, and bevacizumab in advanced solid tumors." May 20, 2013.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
31
Issue
15
Publish Date
2013

The role of local excision in invasive adenocarcinoma of the ampulla of Vater.

BACKGROUND: Ampulla of Vater carcinomas are rare malignancies that have been traditionally treated with radical surgical resection. Given the mortality associated with pancreaticoduodenectomy, some patients may benefit from local resection. A single-institution outcomes analysis was performed to define the role of local resection. METHODS: Patients undergoing local resection (ampullectomy) for ampullary carcinomas at Duke University between 1976 and 2010 were analyzed retrospectively. Time-to-event analysis was conducted analyzing all patients undergoing surgery, with and without adjuvant chemoradiation therapy (CRT). Overall survival (OS), local control (LC), metastases-free survival (MFS), and disease-free survival (DFS) were studied using Kaplan-Meier analysis. RESULTS: A total of 17 patients with invasive carcinoma underwent ampullectomy. The 3-and 5-year LC, MFS, DFS and OS rates were 36% and 24%, 68% and 54%, 31% and 21%, and 35% and 21%, respectively. Patients receiving adjuvant CRT did not appear to have improved outcomes compared with surgery alone, although this group tended to have poorer histological grade, more advanced tumor staging and involved surgical margins. CONCLUSIONS: Ampullectomy for invasive ampullary adenocarcinomas is a safe procedure but does not offer satisfactory long-term results, mostly due to high local failure rates. Adjuvant CRT therapy does not appear to offer increased local control or survival benefit following ampullectomy, although these results may suffer from selection bias and small sample size. Local resection should be limited to benign ampullary lesions or patients with very small, early tumors with favorable histologic features where radical resection is not feasible.

Authors
Zhong, J; Palta, M; Willett, CG; McCall, SJ; Bulusu, A; Tyler, DS; White, RR; Uronis, HE; Pappas, TN; Czito, BG
MLA Citation
Zhong, J, Palta, M, Willett, CG, McCall, SJ, Bulusu, A, Tyler, DS, White, RR, Uronis, HE, Pappas, TN, and Czito, BG. "The role of local excision in invasive adenocarcinoma of the ampulla of Vater." J Gastrointest Oncol 4.1 (March 2013): 8-13.
PMID
23450004
Source
pubmed
Published In
Journal of Gastrointestinal Oncology
Volume
4
Issue
1
Publish Date
2013
Start Page
8
End Page
13
DOI
10.3978/j.issn.2078-6891.2012.055

Costaining for keratins 8/18 plus ubiquitin improves detection of hepatocyte injury in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease is a global health dilemma. The gold standard for diagnosis is liver biopsy. Ballooned hepatocytes are histologic manifestations of hepatocellular injury and are characteristic of steatohepatitis, the more severe form of nonalcoholic fatty liver disease. Definitive histologic identification of ballooned hepatocytes on routine stains, however, can be difficult. Immunohistochemical evidence for loss of the normal hepatocytic keratin 8/18 can serve as an objective marker of ballooned hepatocytes. We sought to explore the utility of a keratin 8/18 plus ubiquitin double immunohistochemical stain for the histologic evaluation of adult nonalcoholic fatty liver disease. Double immunohistochemical staining for keratin 8/18 and ubiquitin was analyzed using 40 adult human nonalcoholic fatty liver disease core liver biopsies. Ballooned hepatocytes lack keratin 8/18 staining as previously shown by others, but normal-size hepatocytes with keratin loss are approximately 5 times greater in number than keratin-negative ballooned hepatocytes. Keratin-negative ballooned hepatocytes, normal-size hepatocytes with keratin loss, and ubiquitin deposits show a zonal distribution, are positively associated with each other, and are frequently found adjacent to or intermixed with fibrous matrix. All 3 lesions correlate with fibrosis stage and the hematoxylin and eosin diagnosis of steatohepatitis (all P < .05). Compared with hematoxylin and eosin staining, immunohistochemical staining improves the receiver operating characteristics curve for advanced fibrosis (0.77 versus 0.83, 0.89, and 0.89 for keratin-negative ballooned hepatocytes, normal-size hepatocytes with keratin loss, and ubiquitin, respectively) because immunohistochemistry is more sensitive and specific for fibrogenic hepatocellular injury than hematoxylin and eosin staining. Keratin 8/18 plus ubiquitin double immunohistochemical stain improves detection of hepatocyte injury in nonalcoholic fatty liver disease. Thus, it may help differentiate nonalcoholic steatohepatitis from nonalcoholic fatty liver.

Authors
Guy, CD; Suzuki, A; Burchette, JL; Brunt, EM; Abdelmalek, MF; Cardona, D; McCall, SJ; Ünalp, A; Belt, P; Ferrell, LD; Diehl, AM; Nonalcoholic Steatohepatitis Clinical Research Network,
MLA Citation
Guy, CD, Suzuki, A, Burchette, JL, Brunt, EM, Abdelmalek, MF, Cardona, D, McCall, SJ, Ünalp, A, Belt, P, Ferrell, LD, Diehl, AM, and Nonalcoholic Steatohepatitis Clinical Research Network, . "Costaining for keratins 8/18 plus ubiquitin improves detection of hepatocyte injury in nonalcoholic fatty liver disease." Hum Pathol 43.6 (June 2012): 790-800.
PMID
22036053
Source
pubmed
Published In
Human Pathology
Volume
43
Issue
6
Publish Date
2012
Start Page
790
End Page
800
DOI
10.1016/j.humpath.2011.07.007

A phase I/II study of capecitabine (Cape), oxaliplatin (Ox), panitumumab (Pmab), and external beam radiation therapy (RT) for patients with esophagogastric carcinoma (EC).

68 Background: EC is commonly managed with concurrent chemoradiotherapy, with or without surgical resection. The optimal combination and dose of agents is the subject of continued investigation. This study examines chemotherapeutic agents with known efficacy in EC in combination with the EGFR inhibitor panitumumab.Eligible pts received RT (1.8 Gy qd to 50.4 Gy) combined with concurrent chemotherapy. Dose-level (DL) 1 was cape (625 mg/m2/bid RT days), ox (40 mg/m2 weekly X 6 weeks), and pmab (3.6 mg/kg, weeks 1, 3 and 5). Chemotherapy doses were escalated barring dose limiting toxicity (DLT). The primary endpoint was defining the maximally tolerated dose with this combination. Secondary endpoints included toxicity and radiographic/pathologic response rates.Twenty-nine pts were enrolled. Twenty-five had adenocarcinoma, 24 (83%) were cN+ and 9 (31%) had M1a/b disease. DLT was not encountered in DL 1. Two of 6 patients at DL 2 (cape 825 mg/m2/bid RT days, ox 50 mg/m2 weekly, pmab 4.8 mg/kg, weeks 1, 3 and 5) developed DLT (one hospitalization due to dehydration; one with drug reaction requiring hospitalization). Twenty additional pts were enrolled at DL1. Primary toxicities were EGFR-rash, esophagitis, nausea/vomiting and fatigue. On repeat endoscopy, 16 (55%) had CR, 10 (35%) PR and 2 (7%) SD. Using PERCIST criteria, 12 (41%), 11 (38%), 2 (7%) and 3 (10%) had CR, PR, SD and PD response on restaging PET, respectively. Twenty pts underwent esophagectomy, revealing Gr 0 response (no residual disease) in 9 (45%), Gr 1 (single/microscopic cells) in 3 (15%), Gr 2 (fibrosis > gross disease) in 4 (20%) and Gr 3 (gross residual > fibrosis or no evident response) in 4 (20%). Seven pts (35%) experienced anastomotic leak (2 requiring reoperation and 3 stent placement).Concurrent chemoradiotherapy utilizing capecitabine, oxaliplatin, panitumumab is reasonably well-tolerated and associated with high rates of radiographic, endoscopic and pathologic response. Postoperative anastomotic leak rates were higher than expected. Further study of this regimen in the operative and nonoperative settings is warranted.

Authors
Czito, BG; Willett, C; Palta, M; McCall, S; Gee, N; Hurwitz, H; Coleman, RE; Zafar, Y; Kennedy-Newton, P; Uronis, H
MLA Citation
Czito, BG, Willett, C, Palta, M, McCall, S, Gee, N, Hurwitz, H, Coleman, RE, Zafar, Y, Kennedy-Newton, P, and Uronis, H. "A phase I/II study of capecitabine (Cape), oxaliplatin (Ox), panitumumab (Pmab), and external beam radiation therapy (RT) for patients with esophagogastric carcinoma (EC)." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 30.4_suppl (February 2012): 68-.
PMID
27982872
Source
epmc
Published In
Journal of Clinical Oncology
Volume
30
Issue
4_suppl
Publish Date
2012
Start Page
68

A phase I/II study of capecitabine (Cape), oxaliplatin (Ox), panitumumab (Pmab), and external beam radiation therapy (RT) for patients with esophagogastric carcinoma (EC).

Authors
Czito, BG; Willett, C; Palta, M; McCall, S; Gee, N; Hurwitz, H; Coleman, RE; Zafar, Y; Kennedy-Newton, P; Uronis, H
MLA Citation
Czito, BG, Willett, C, Palta, M, McCall, S, Gee, N, Hurwitz, H, Coleman, RE, Zafar, Y, Kennedy-Newton, P, and Uronis, H. "A phase I/II study of capecitabine (Cape), oxaliplatin (Ox), panitumumab (Pmab), and external beam radiation therapy (RT) for patients with esophagogastric carcinoma (EC)." February 2012.
Source
crossref
Published In
Journal of Clinical Oncology
Volume
30
Issue
4_suppl
Publish Date
2012
Start Page
68
End Page
68
DOI
10.1200/jco.2012.30.4_suppl.68

Histological and molecular evaluation of patient-derived colorectal cancer explants.

Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies. While genetically engineered and carcinogen-induced mouse models have provided important information with regard to the mechanisms underlying the oncogenic process, tumor xenograft models remain the standard for the evaluation of new chemotherapy and targeted drug treatments for clinical use. However, it remains unclear to what extent explanted colorectal tumor tissues retain inherent pathological features over time. In this study, we have generated a panel of 27 patient-derived colorectal cancer explants (PDCCEs) by direct transplantation of human colorectal cancer tissues into NOD-SCID mice. Using this panel, we performed a comparison of histology, gene expression and mutation status between PDCCEs and the original human tissues from which they were derived. Our findings demonstrate that PDCCEs maintain key histological features, basic gene expression patterns and KRAS/BRAF mutation status through multiple passages. Altogether, these findings suggest that PDCCEs maintain similarity to the patient tumor from which they are derived and may have the potential to serve as a reliable preclinical model that can be incorporated into future strategies to optimize individual therapy for patients with colorectal cancer.

Authors
Uronis, JM; Osada, T; McCall, S; Yang, XY; Mantyh, C; Morse, MA; Lyerly, HK; Clary, BM; Hsu, DS
MLA Citation
Uronis, JM, Osada, T, McCall, S, Yang, XY, Mantyh, C, Morse, MA, Lyerly, HK, Clary, BM, and Hsu, DS. "Histological and molecular evaluation of patient-derived colorectal cancer explants." PLoS One 7.6 (2012): e38422-.
PMID
22675560
Source
pubmed
Published In
PloS one
Volume
7
Issue
6
Publish Date
2012
Start Page
e38422
DOI
10.1371/journal.pone.0038422

Hedgehog activity, epithelial-mesenchymal transitions, and biliary dysmorphogenesis in biliary atresia.

UNLABELLED: Biliary atresia (BA) is notable for marked ductular reaction and rapid development of fibrosis. Activation of the Hedgehog (Hh) pathway promotes the expansion of populations of immature epithelial cells that coexpress mesenchymal markers and may be profibrogenic. We examined the hypothesis that in BA excessive Hh activation impedes ductular morphogenesis and enhances fibrogenesis by promoting accumulation of immature ductular cells with a mesenchymal phenotype. Livers and remnant extrahepatic ducts from BA patients were evaluated by quantitative reverse-transcription polymerase chain reaction (QRT-PCR) and immunostaining for Hh ligands, target genes, and markers of mesenchymal cells or ductular progenitors. Findings were compared to children with genetic cholestatic disease, age-matched deceased donor controls, and adult controls. Ductular cells isolated from adult rats with and without bile duct ligation were incubated with Hh ligand-enriched medium ± Hh-neutralizing antibody to determine direct effects of Hh ligands on epithelial to mesenchymal transition (EMT) marker expression. Livers from pediatric controls showed greater innate Hh activation than adult controls. In children with BA, both intra- and extrahepatic ductular cells demonstrated striking up-regulation of Hh ligand production and increased expression of Hh target genes. Excessive accumulation of Hh-producing cells and Hh-responsive cells also occurred in other infantile cholestatic diseases. Further analysis of the BA samples demonstrated that immature ductular cells with a mesenchymal phenotype were Hh-responsive. Treating immature ductular cells with Hh ligand-enriched medium induced mesenchymal genes; neutralizing Hh ligands inhibited this. CONCLUSION: BA is characterized by excessive Hh pathway activity, which stimulates biliary EMT and may contribute to biliary dysmorphogenesis. Other cholestatic diseases show similar activation, suggesting that this is a common response to cholestatic injury in infancy.

Authors
Omenetti, A; Bass, LM; Anders, RA; Clemente, MG; Francis, H; Guy, CD; McCall, S; Choi, SS; Alpini, G; Schwarz, KB; Diehl, AM; Whitington, PF
MLA Citation
Omenetti, A, Bass, LM, Anders, RA, Clemente, MG, Francis, H, Guy, CD, McCall, S, Choi, SS, Alpini, G, Schwarz, KB, Diehl, AM, and Whitington, PF. "Hedgehog activity, epithelial-mesenchymal transitions, and biliary dysmorphogenesis in biliary atresia." Hepatology 53.4 (April 2011): 1246-1258.
PMID
21480329
Source
pubmed
Published In
Hepatology
Volume
53
Issue
4
Publish Date
2011
Start Page
1246
End Page
1258
DOI
10.1002/hep.24156

A Novel Immunohiostochemical Staining Pattern for Keratin 8/18 Plus Ubiquitin in Nonalcoholic Fatty Liver Disease Is Associated with Increased Disease Severity and Advanced Fibrosis

Authors
Guy, CD; Suzuki, A; Burchette, JL; Brunt, EM; Abelmalek, MF; Cardona, D; McCall, SJ; Unlap, A; Belt, P; Wilson, L; Ferrell, LD; Diehl, AM
MLA Citation
Guy, CD, Suzuki, A, Burchette, JL, Brunt, EM, Abelmalek, MF, Cardona, D, McCall, SJ, Unlap, A, Belt, P, Wilson, L, Ferrell, LD, and Diehl, AM. "A Novel Immunohiostochemical Staining Pattern for Keratin 8/18 Plus Ubiquitin in Nonalcoholic Fatty Liver Disease Is Associated with Increased Disease Severity and Advanced Fibrosis." February 2011.
Source
wos-lite
Published In
Laboratory Investigation
Volume
91
Publish Date
2011
Start Page
361A
End Page
361A

A Novel Immunohiostochemical Staining Pattern for Keratin 8/18 Plus Ubiquitin in Nonalcoholic Fatty Liver Disease Is Associated with Increased Disease Severity and Advanced Fibrosis

Authors
Guy, CD; Suzuki, A; Burchette, JL; Brunt, EM; Abelmalek, MF; Cardona, D; McCall, SJ; Unlap, A; Belt, P; Wilson, L; Ferrell, LD; Diehl, AM
MLA Citation
Guy, CD, Suzuki, A, Burchette, JL, Brunt, EM, Abelmalek, MF, Cardona, D, McCall, SJ, Unlap, A, Belt, P, Wilson, L, Ferrell, LD, and Diehl, AM. "A Novel Immunohiostochemical Staining Pattern for Keratin 8/18 Plus Ubiquitin in Nonalcoholic Fatty Liver Disease Is Associated with Increased Disease Severity and Advanced Fibrosis." February 2011.
Source
wos-lite
Published In
Modern Pathology
Volume
24
Publish Date
2011
Start Page
361A
End Page
361A

Rho GTPase activity modulates Wnt3a/beta-catenin signaling.

Wnt proteins constitute a family of secreted signaling molecules that regulate highly conserved pathways essential for development and, when aberrantly activated, drive oncogenesis in a number of human cancers. A key feature of the most widely studied Wnt signaling cascade is the stabilization of cytosolic beta-catenin, resulting in beta-catenin nuclear translocation and transcriptional activation of multiple target genes. In addition to this canonical, beta-catenin-dependent pathway, Wnt3A has also been shown to stimulate RhoA GTPase. While the importance of activated Rho to non-canonical Wnt signaling is well appreciated, the potential contribution of Wnt3A-stimulated RhoA to canonical beta-catenin-dependent transcription has not been examined and is the focus of this study. We find that activated Rho is required for Wnt3A-stimulated osteoblastic differentiation in C3H10T1/2 mesenchymal stem cells, a biological phenomenon mediated by stabilized beta-catenin. Using expression microarrays and real-time RT-PCR analysis, we show that Wnt3A-stimulated transcription of a subset of target genes is Rho-dependent, indicating that full induction of these Wnt targets requires both beta-catenin and Rho activation. Significantly, neither beta-catenin stabilization nor nuclear translocation stimulated by Wnt3A is affected by inhibition or activation of RhoA. These findings identify Rho activation as a critical element of the canonical Wnt3A-stimulated, beta-catenin-dependent transcriptional program.

Authors
Rossol-Allison, J; Stemmle, LN; Swenson-Fields, KI; Kelly, P; Fields, PE; McCall, SJ; Casey, PJ; Fields, TA
MLA Citation
Rossol-Allison, J, Stemmle, LN, Swenson-Fields, KI, Kelly, P, Fields, PE, McCall, SJ, Casey, PJ, and Fields, TA. "Rho GTPase activity modulates Wnt3a/beta-catenin signaling." Cell Signal 21.11 (November 2009): 1559-1568.
PMID
19482078
Source
pubmed
Published In
Cellular Signalling
Volume
21
Issue
11
Publish Date
2009
Start Page
1559
End Page
1568
DOI
10.1016/j.cellsig.2009.05.010

Analysis of Hepatic Progenitor Populations in Methyl Deficient Liver Injury

Authors
Sicklick, JK; Huang, J; McCall, SJ; Torbenson, MS; Diehl, AM
MLA Citation
Sicklick, JK, Huang, J, McCall, SJ, Torbenson, MS, and Diehl, AM. "Analysis of Hepatic Progenitor Populations in Methyl Deficient Liver Injury." ANNALS OF SURGICAL ONCOLOGY 16 (February 2009): 33-33.
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
16
Publish Date
2009
Start Page
33
End Page
33

Fructose consumption as a risk factor for non-alcoholic fatty liver disease.

BACKGROUND/AIMS: While the rise in non-alcoholic fatty liver disease (NAFLD) parallels the increase in obesity and diabetes, a significant increase in dietary fructose consumption in industrialized countries has also occurred. The increased consumption of high fructose corn syrup, primarily in the form of soft drinks, is linked with complications of the insulin resistance syndrome. Furthermore, the hepatic metabolism of fructose favors de novo lipogenesis and ATP depletion. We hypothesize that increased fructose consumption contributes to the development of NAFLD. METHODS: A dietary history and paired serum and liver tissue were obtained from patients with evidence of biopsy-proven NAFLD (n=49) without cirrhosis and controls (n=24) matched for gender, age (+/-5 years), and body mass index (+/-3 points). RESULTS: Consumption of fructose in patients with NAFLD was nearly 2- to 3-fold higher than controls [365 kcal vs 170 kcal (p<0.05)]. In patients with NAFLD (n=6), hepatic mRNA expression of fructokinase (KHK), an important enzyme for fructose metabolism, and fatty acid synthase, an important enzyme for lipogenesis were increased (p=0.04 and p=0.02, respectively). In an AML hepatocyte cell line, fructose resulted in dose-dependent increase in KHK protein and activity. CONCLUSIONS: The pathogenic mechanism underlying the development of NAFLD may be associated with excessive dietary fructose consumption.

Authors
Ouyang, X; Cirillo, P; Sautin, Y; McCall, S; Bruchette, JL; Diehl, AM; Johnson, RJ; Abdelmalek, MF
MLA Citation
Ouyang, X, Cirillo, P, Sautin, Y, McCall, S, Bruchette, JL, Diehl, AM, Johnson, RJ, and Abdelmalek, MF. "Fructose consumption as a risk factor for non-alcoholic fatty liver disease." J Hepatol 48.6 (June 2008): 993-999.
PMID
18395287
Source
pubmed
Published In
Journal of Hepatology
Volume
48
Issue
6
Publish Date
2008
Start Page
993
End Page
999
DOI
10.1016/j.jhep.2008.02.011

Pharmacologic disruption of TRPV1-expressing primary sensory neurons but not genetic deletion of TRPV1 protects mice against pancreatitis.

OBJECTIVES: Transient receptor potential subtype vanilloid 1 (TRPV1) is an ion channel that is primarily expressed by primary sensory neurons where it mediates pain and heat sensation and participates in neurogenic inflammation. In this study, we examined the role of TRPV1 during neurogenic activation of pancreatic inflammation using a secretagogue-induced model in mice. METHODS: A supramaximal dose of caerulein (50 microg/kg) was injected hourly for 12 hours. Mice lacking TRPV1 were compared to wild-type animals. RESULTS: All the parameters: serum amylase, pancreatic myeloperoxidase activity, histological scoring, pancreatic wet weight/body weight ratio, and quantification of neurokinin-1 receptor internalization indicated that null mice were not protected from acute pancreatitis. However, when primary sensory neurons were ablated by injection of the neurotoxin and TRPV1 agonist, resiniferatoxin, pancreatitis was ameliorated in wild-type mice but not in null mice, indicating that nerves bearing TRPV1 are part of the inflammatory pathway in acute pancreatitis because disappearance significantly reduced the inflammatory response. CONCLUSIONS: Nerves expressing TRPV1 participate in the neurogenic inflammation during acute pancreatitis. The lack of protection in TRPV1 null mice suggests that an alternate pathway to TRPV1 coexists in the same neurons.

Authors
Romac, JMJ; McCall, SJ; Humphrey, JE; Heo, J; Liddle, RA
MLA Citation
Romac, JMJ, McCall, SJ, Humphrey, JE, Heo, J, and Liddle, RA. "Pharmacologic disruption of TRPV1-expressing primary sensory neurons but not genetic deletion of TRPV1 protects mice against pancreatitis." Pancreas 36.4 (May 2008): 394-401.
PMID
18437086
Source
pubmed
Published In
Pancreas
Volume
36
Issue
4
Publish Date
2008
Start Page
394
End Page
401
DOI
10.1097/MPA.0b013e318160222a

Diacylglycerol acyltranferase 1 anti-sense oligonucleotides reduce hepatic fibrosis in mice with nonalcoholic steatohepatitis.

UNLABELLED: Retinyl ester (RE) stores decrease during hepatic stellate cell (HSC) activation and liver fibrosis. Although retinol esterification is mostly catalyzed by lecithin:retinol acyltransferase (LRAT), diacylglycerol acyltransferase (DGAT)1 also does this. In previous reports, LRAT(-/-) mice had reduced hepatic RE but neither excessive HSC activation nor liver fibrosis, and DGAT1(-/-) mice had increased liver levels of RE and retinol. We sought to clarify the role of DGAT1 in liver fibrosis. Expression of DGAT1/2 was compared by real time PCR in freshly isolated, primary mouse HSCs and hepatocytes. To induce nonalcoholic steatohepatitis (NASH) and liver fibrosis, adult male db/db mice were fed methionine choline-deficient (MCD) diets. Half were treated with DGAT1 antisense oligonucleotide (ASO); the rest were injected with saline. Results were compared with chow-fed controls. Inhibition of DGAT1 in liver had no effect on hepatic triglyceride content or liver necroinflammation but reduced HSC activation and liver fibrosis in mice with NASH. To evaluate the role of DGAT1 in HSC activation, HSC were isolated from healthy rats treated with DGAT1 ASO or saline. DGAT1 was expressed at relatively high levels in HSCs. HSC isolated from DGAT1 ASO-treated rats had reduced DGAT1 expression and increased messenger RNA (mRNA) levels of LRAT and cellular retinol binding protein-1. During culture, they retained more vitamin A, had repressed collagen a2 (I) transcriptional activity, and expressed less collagen a1 (I) and a2 (I) mRNA. CONCLUSION: DGAT1 may be a therapeutic target in NASH because inhibiting DGAT1 favorably altered. HSC retinoid homeostasis and inhibited hepatic fibrosis in mice with NASH.

Authors
Yamaguchi, K; Yang, L; McCall, S; Huang, J; Yu, XX; Pandey, SK; Bhanot, S; Monia, BP; Li, Y-X; Diehl, AM
MLA Citation
Yamaguchi, K, Yang, L, McCall, S, Huang, J, Yu, XX, Pandey, SK, Bhanot, S, Monia, BP, Li, Y-X, and Diehl, AM. "Diacylglycerol acyltranferase 1 anti-sense oligonucleotides reduce hepatic fibrosis in mice with nonalcoholic steatohepatitis." Hepatology 47.2 (February 2008): 625-635.
PMID
18000880
Source
pubmed
Published In
Hepatology
Volume
47
Issue
2
Publish Date
2008
Start Page
625
End Page
635
DOI
10.1002/hep.21988

Effectiveness of Glycerol Mono-oleate as a Biosealant.

BACKGROUND: The number of femoral artery catheterizations will increase over the next decade to more than 9 million worldwide. Accordingly, a new era of access site management with vascular closure techniques utilizing biologics are being developed and implemented. Glycerol mono-oleate (GMO) is one such biologic - a biodegradable compound that changes from a solid phase to a bioadhesive swollen semisolid phase when exposed to aqueous solutions and heat. We assessed whether GMO would: 1) achieve hemostasis more effectively than control when injected into a swine liver biopsy tract; and 2) inhibit common percutaneous procedure pathogens. METHODS: During the hemostasis experiment, seven swine anticoagulated with heparin (ACT > 250) underwent 10 open-liver biopsies with a 14 gauge cutting needle; 5 injected with GMO (treatment) and 5 injected with nothing (control). Thirty seconds, 2 minutes, 5 minutes and 10 minutes after the procedure, bleeding was objectively graded; 0 = no bleeding (success) and 1 = bleeding (failure). During the bacteria experiment, GMO was injected into plates containing culture media for 4 common percutaneous pathogens (Enteroccocis faecalis, Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae). When injected, GMO converted to a semisolid phase with definitive margins in the culture media. Each bacterium was then coated over their respective media and GMO. RESULTS: The results showed a significant treatment effect (p < 0.017) on each success/failure bleeding outcome at 30 seconds (p < 0.0001), 2 minutes (p < 0.0001) and 5 minutes (p = 0.0038) based on a multiple logistic regression analysis controlling for initial bleeding, pig and side-of-liver biopsy (medial or lateral lobe). At 10 minutes, the bleeding results were not significant (p = 0.0917), likely explained by a pig's innate ability to clot at this time period. For the bacteria experiment, there was no growth of bacteria on the GMO for any of the plates. Specifically, the Staphylococcus aureus plate displayed a 200 micron halo containing no bacterial growth surrounding the GMO. CONCLUSION: In conclusion, these results illustrate a significant hemostatic effect post liver biopsy at multiple time points using GMO. Furthermore, GMO displays bacterial deterrent properties.

Authors
Adams, GL; Manson, RJ; Giangiacomo, DM; Fronheiser, L; McCall, S; Nightingale, R; Hasselblad, V; Shaw, LK; Milton, L; Lawson, JH
MLA Citation
Adams, GL, Manson, RJ, Giangiacomo, DM, Fronheiser, L, McCall, S, Nightingale, R, Hasselblad, V, Shaw, LK, Milton, L, and Lawson, JH. "Effectiveness of Glycerol Mono-oleate as a Biosealant." J Invasive Cardiol 20.1 (January 2008): 29-34.
PMID
18174616
Source
pubmed
Published In
Journal of Invasive Cardiology
Volume
20
Issue
1
Publish Date
2008
Start Page
29
End Page
34

Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis.

UNLABELLED: In the early stages of nonalcoholic fatty liver disease (NAFLD), triglycerides accumulate in hepatocytes. Diacylglycerol acyltransferase 2 (DGAT2) catalyzes the final step in hepatocyte triglyceride biosynthesis. DGAT2 antisense oligonucleotide (ASO) treatment improved hepatic steatosis dramatically in a previous study of obese mice. According to the 2-hit hypothesis for progression of NAFLD, hepatic steatosis is a risk factor for nonalcoholic steatohepatitis (NASH) and fibrosis. To evaluate this hypothesis, we inhibited DGAT2 in a mouse model of NASH induced by a diet deficient in methionine and choline (MCD). Six-week-old genetically obese and diabetic male db/db mice were fed either the control or the MCD diet for 4 or 8 weeks. The MCD diet group was treated with either 25 mg/kg DGAT2 ASO or saline intraperitoneally twice weekly. Hepatic steatosis, injury, fibrosis, markers of lipid peroxidation/oxidant stress, and systemic insulin sensitivity were evaluated. Hepatic steatosis, necroinflammation, and fibrosis were increased in saline-treated MCD diet-fed mice compared to controls. Treating MCD diet-fed mice with DGAT2 ASO for 4 and 8 weeks decreased hepatic steatosis, but increased hepatic free fatty acids, cytochrome P4502E1, markers of lipid peroxidation/oxidant stress, lobular necroinflammation, and fibrosis. Progression of liver damage occurred despite reduced hepatic expression of tumor necrosis factor alpha, increased serum adiponectin, and striking improvement in systemic insulin sensitivity. CONCLUSION: Results from this mouse model would suggest accumulation of triglycerides may be a protective mechanism to prevent progressive liver damage in NAFLD.

Authors
Yamaguchi, K; Yang, L; McCall, S; Huang, J; Yu, XX; Pandey, SK; Bhanot, S; Monia, BP; Li, Y-X; Diehl, AM
MLA Citation
Yamaguchi, K, Yang, L, McCall, S, Huang, J, Yu, XX, Pandey, SK, Bhanot, S, Monia, BP, Li, Y-X, and Diehl, AM. "Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis." Hepatology 45.6 (June 2007): 1366-1374.
PMID
17476695
Source
pubmed
Published In
Hepatology
Volume
45
Issue
6
Publish Date
2007
Start Page
1366
End Page
1374
DOI
10.1002/hep.21655

Hedgehog-mediated mesenchymal-epithelial interactions modulate hepatic response to bile duct ligation.

In bile duct-ligated (BDL) rodents, as in humans with chronic cholangiopathies, biliary obstruction triggers proliferation of bile ductular cells that are surrounded by fibrosis produced by adjacent myofibroblastic cells in the hepatic mesenchyme. The proximity of the myofibroblasts and cholangiocytes suggests that mesenchymal-epithelial crosstalk promotes the fibroproliferative response to cholestatic liver injury. Studying BDL mice, we found that bile duct obstruction induces activity of the Hedgehog (Hh) pathway, a system that regulates the viability and differentiation of various progenitors during embryogenesis. After BDL, many bile ductular cells and fibroblastic-appearing cells in the portal stroma express Hh ligands, receptor and/or target genes. Transwell cocultures of an immature cholangiocyte line that expresses the Hh receptor, Patched (Ptc), with liver myofibroblastic cells demonstrated that both cell types produced Hh ligands that enhanced each other's viability and proliferation. Further support for the concept that Hh signaling modulates the response to BDL was generated by studying PtcLacZ mice, which have an impaired ability to constrain Hh signaling due to a heterozygous deficiency of Ptc. After BDL, PtcLacZ mice upregulated fibrosis gene expression earlier than wild-type controls and manifested an unusually intense ductular reaction, more expanded fibrotic portal areas, and a greater number of lobular necrotic foci. Our findings reveal that adult livers resurrect developmental signaling systems, such as the Hh pathway, to guide remodeling of the biliary epithelia and stroma after cholestatic injury.

Authors
Omenetti, A; Yang, L; Li, Y-X; McCall, SJ; Jung, Y; Sicklick, JK; Huang, J; Choi, S; Suzuki, A; Diehl, AM
MLA Citation
Omenetti, A, Yang, L, Li, Y-X, McCall, SJ, Jung, Y, Sicklick, JK, Huang, J, Choi, S, Suzuki, A, and Diehl, AM. "Hedgehog-mediated mesenchymal-epithelial interactions modulate hepatic response to bile duct ligation." Lab Invest 87.5 (May 2007): 499-514.
PMID
17334411
Source
pubmed
Published In
Laboratory Investigation
Volume
87
Issue
5
Publish Date
2007
Start Page
499
End Page
514
DOI
10.1038/labinvest.3700537

Bile ductules and stromal cells express hedgehog ligands and/or hedgehog target genes in primary biliary cirrhosis.

UNLABELLED: Indian Hedgehog (Ihh) regulates tissue morphogenesis. Hedgehog (Hh) activity has been demonstrated in human cholangiocarcinoma and hepatocellular carcinoma lines, and in myofibroblasts and progenitors from adult rodent livers. We evaluated Hh pathway involvement in the response to biliary injury in primary biliary cirrhosis (PBC). Liver sections from 3 PBC patients and 3 controls without liver disease were studied. Immunohistochemistry was used to determine if cells that accumulate in PBC livers express Ihh or Hh-target genes including the Hh-receptor, Patched (Ptc), and the Hh-transcriptional activator glioblastoma (Gli) 2. Positive cells were further identified by costaining for cytokeratin (CK) 19, a biliary marker, or OV6, a hepatic progenitor marker. In all subjects, Gli2 and Ptc expression localized in portal areas. The numbers of Gli2- or Ptc-expressing cells/portal triad were each 10-fold greater in patients with PBC than in controls (P<0.05). In PBC livers, some CK19+ cells coexpressed Gli2 or Ptc. Many stromal fibroblastic cells were also Gli2+. Strong Ihh expression was detected in most bile ductular cells. Scattered stromal cells also expressed Ihh. The number of Ihh+ cells/portal triad was 6-fold greater in PBC livers than controls (P<0.05). OV6+ progenitors increased significantly in PBC livers, and some of these cells coexpressed Ihh, Ptc, and/or Gli2. CONCLUSION: This is the first direct evidence that noncancerous, adult human livers harbor several types of cells that produce and/or respond to Hh ligands. Such Hh-responsive cells accumulate during the fibroproliferative response to chronic cholestatic liver injury, suggesting a role for Hh signaling in this process.

Authors
Jung, Y; McCall, SJ; Li, Y-X; Diehl, AM
MLA Citation
Jung, Y, McCall, SJ, Li, Y-X, and Diehl, AM. "Bile ductules and stromal cells express hedgehog ligands and/or hedgehog target genes in primary biliary cirrhosis." Hepatology 45.5 (May 2007): 1091-1096.
PMID
17464985
Source
pubmed
Published In
Hepatology
Volume
45
Issue
5
Publish Date
2007
Start Page
1091
End Page
1096
DOI
10.1002/hep.21660

Qualitative and quantitative differences in response to liver injury in OB/OB mice

Authors
Fleig, SV; Yang, L; Huang, J; Mccall, SJ; Jung, Y; Vandongen, HM; Omenetti, A; Sicklick, JK; Li, Y-X; Diehl, AM
MLA Citation
Fleig, SV, Yang, L, Huang, J, Mccall, SJ, Jung, Y, Vandongen, HM, Omenetti, A, Sicklick, JK, Li, Y-X, and Diehl, AM. "Qualitative and quantitative differences in response to liver injury in OB/OB mice." April 2007.
Source
wos-lite
Published In
Gastroenterology
Volume
132
Issue
4
Publish Date
2007
Start Page
A818
End Page
A818

Aminoaciduria and altered renal expression of luminal amino acid transporters in mice lacking novel gene collectrin.

Defects in renal proximal tubule transport manifest in a number of human diseases. Although variable in clinical presentation, disorders such as Hartnup disease, Dent's disease, and Fanconi syndrome are characterized by wasting of solutes commonly recovered by the proximal tubule. One common feature of these disorders is aminoaciduria. There are distinct classes of amino acid transporters located in the apical and basal membranes of the proximal tubules that reabsorb >95% of filtered amino acids, yet few details are known about their regulation. We present our physiological characterization of a mouse line with targeted deletion of the gene collectrin that is highly expressed in the kidney. Collectrin-deficient mice display a reduced urinary concentrating capacity due to enhanced solute clearance resulting from profound aminoaciduria. The aminoaciduria is generalized, characterized by loss of nearly every amino acid, and results in marked crystalluria. Furthermore, in the kidney, collectrin-deficient mice have decreased plasma membrane populations of amino acid transporter subtypes B(0)AT1, rBAT, and b(0,+)AT, as well as altered cellular distribution of EAAC1. Our data suggest that collectrin is a novel mediator of renal amino acid transport and may provide further insight into the pathogenesis of a number of human disease correlates.

Authors
Malakauskas, SM; Quan, H; Fields, TA; McCall, SJ; Yu, MJ; Kourany, WM; Frey, CW; Le, TH
MLA Citation
Malakauskas, SM, Quan, H, Fields, TA, McCall, SJ, Yu, MJ, Kourany, WM, Frey, CW, and Le, TH. "Aminoaciduria and altered renal expression of luminal amino acid transporters in mice lacking novel gene collectrin." American journal of physiology. Renal physiology 292.2 (February 2007): F533-F544. (Academic Article)
PMID
16985211
Source
manual
Published In
American journal of physiology. Renal physiology
Volume
292
Issue
2
Publish Date
2007
Start Page
F533
End Page
F544

Evidence for epithelial-mesenchymal transitions in adult liver cells.

Both myofibroblastic hepatic stellate cells (HSC) and hepatic epithelial progenitors accumulate in damaged livers. In some injured organs, the ability to distinguish between fibroblastic and epithelial cells is sometimes difficult because cells undergo epithelial-mesenchymal transitions (EMT). During EMT, cells coexpress epithelial and mesenchymal cell markers. To determine whether EMT occurs in adult liver cells, we analyzed the expression profile of primary HSC, two HSC lines, and hepatic epithelial progenitors. As expected, all HSC expressed HSC markers. Surprisingly, these markers were also expressed by epithelial progenitors. In addition, one HSC line expressed typical epithelial progenitor mRNAs, and these epithelial markers were inducible in the second HSC line. In normal and damaged livers, small ductular-type cells stained positive for an HSC marker. In conclusion, HSC and hepatic epithelial progenitors both coexpress epithelial and mesenchymal markers, providing evidence that EMT occurs in adult liver cells.

Authors
Sicklick, JK; Choi, SS; Bustamante, M; McCall, SJ; Pérez, EH; Huang, J; Li, Y-X; Rojkind, M; Diehl, AM
MLA Citation
Sicklick, JK, Choi, SS, Bustamante, M, McCall, SJ, Pérez, EH, Huang, J, Li, Y-X, Rojkind, M, and Diehl, AM. "Evidence for epithelial-mesenchymal transitions in adult liver cells." Am J Physiol Gastrointest Liver Physiol 291.4 (October 2006): G575-G583.
PMID
16710052
Source
pubmed
Published In
American journal of physiology. Gastrointestinal and liver physiology
Volume
291
Issue
4
Publish Date
2006
Start Page
G575
End Page
G583
DOI
10.1152/ajpgi.00102.2006

DGAT2 aso treatment improves hepatic steatosis, but not fibrosis in DB/DB mice fed methionine choline deficient diets

Authors
Yamaguchi, K; Yang, L; McCall, S; Huang, J; Yu, XX; Pandey, SK; Hanot, S; Monia, BP; Li, Y-X; Diehl, AM
MLA Citation
Yamaguchi, K, Yang, L, McCall, S, Huang, J, Yu, XX, Pandey, SK, Hanot, S, Monia, BP, Li, Y-X, and Diehl, AM. "DGAT2 aso treatment improves hepatic steatosis, but not fibrosis in DB/DB mice fed methionine choline deficient diets." October 2006.
Source
wos-lite
Published In
Hepatology
Volume
44
Issue
4
Publish Date
2006
Start Page
665A
End Page
665A

DGAT1 ASO treatment reduces hepatic fibrosis without improving hepatic steatosis in DB/DB mice fed methionine choline deficient diets

Authors
Yamaguchi, K; Yang, L; McCall, S; Huang, J; Yu, XX; Pandey, SK; Bhanot, S; Monia, BP; Li, Y-X; Diehl, AM
MLA Citation
Yamaguchi, K, Yang, L, McCall, S, Huang, J, Yu, XX, Pandey, SK, Bhanot, S, Monia, BP, Li, Y-X, and Diehl, AM. "DGAT1 ASO treatment reduces hepatic fibrosis without improving hepatic steatosis in DB/DB mice fed methionine choline deficient diets." October 2006.
Source
wos-lite
Published In
Hepatology
Volume
44
Issue
4
Publish Date
2006
Start Page
663A
End Page
663A

Development and cardiac contractility: cardiac troponin T isoforms and cytosolic calcium in rabbit.

Cardiac contractility depends on calcium sensitivity of the myofilaments and cytosolic free calcium concentration ([Ca(2+)](i)) during activation. During development, the cardiac troponin T isoform cTnT(1) is replaced by shorter cTnT isoforms, including cTnT(4), and changes occur in other myofibrillar proteins and in calcium regulation. We expressed rabbit recombinant (r)cTnT(1) and rcTnT(4) in Spodoptera frugiperda cells and determined their effect on calcium binding to TnC in solution and on the calcium sensitivity of myofilaments in skinned rabbit ventricular fibers in vitro. We measured [Ca(2+)](i) and L-type calcium current (I(Ca)) in ventricular myocytes from 3-wk-old and adult rabbits. The dissociation constant (K(d)) of Ca-Tn(cTnT1) in solution was smaller than that of Ca-Tn(cTnT4) (mean +/- SE: 0.52 +/- 0.08 mumol/L versus 0.83 +/- 0.09 mumol/L). The Ca(2+) sensitivity of force development was greater in fibers reconstituted with rcTnT(1) (pCa(50) 6.07 +/- 0.04) than those reconstituted with rcTnT(4) (pCa(50) 5.75 +/- 0.07). Systolic [Ca](i) was lower in 3-wk-old than adult cells (443 +/- 35 nmol/L versus 882 +/- 88 nmol/L) as was I(Ca) (5.8 +/- 0.9 pA/pF versus 14.2 +/- 1.6 pA/pF). The higher calcium sensitivity of Tn-Ca binding and of force development conferred by rcTnT(1) suggest that higher neonatal cTnT(1) expression may partially compensate for the lower systolic [Ca(2+)](i).

Authors
McCall, SJ; Nassar, R; Malouf, NN; Saunders, AJ; Oakeley, AE; Henderson, PM; Solaro, RJ; Pielak, GJ; Alexander, KA; Anderson, PAW
MLA Citation
McCall, SJ, Nassar, R, Malouf, NN, Saunders, AJ, Oakeley, AE, Henderson, PM, Solaro, RJ, Pielak, GJ, Alexander, KA, and Anderson, PAW. "Development and cardiac contractility: cardiac troponin T isoforms and cytosolic calcium in rabbit." Pediatr Res 60.3 (September 2006): 276-281.
PMID
16857772
Source
pubmed
Published In
Pediatric Research
Volume
60
Issue
3
Publish Date
2006
Start Page
276
End Page
281
DOI
10.1203/01.pdr.0000233004.95404.1f

Interleukin-15 increases hepatic regenerative activity.

BACKGROUND/AIMS: Interleukin-15 (IL-15) is expressed in many organs. It generally inhibits apoptosis and increases cellular proliferation and differentiation. However, IL-15's roles in liver are unknown. We aimed to determine if IL-15 influences hepatic integrity and regenerative activity. METHODS: Expression of IL-15 and its receptors was evaluated in several liver injury models, primary hepatocytes, and two liver cell lines. Effects of IL-15 on viability, proliferation, and apoptosis were assessed in cultured liver cells, and also in the livers of healthy mice. RESULTS: IL-15 and its receptors are expressed constitutively in healthy livers, and ligand expression is induced in injured livers. Cultured primary hepatocytes and liver cell lines express IL-15 and its receptors. Administration of IL-15 has minimal effects on cultured liver cells, but significantly up-regulates oval cell accumulation, cyclin mRNA expression, and mature hepatocyte replication in healthy mice. These effects are associated with focal hepatic inflammation and increased expression of TNF-alpha and IFN-gamma, but not with increased cell death or aminotransferase release. CONCLUSIONS: IL-15 expression increases during liver injury and IL-15 treatment induces a wound healing-type response in healthy adult mice. These findings suggest that IL-15 may contribute to regenerative activity in damaged liver.

Authors
Suzuki, A; McCall, S; Choi, SS; Sicklick, JK; Huang, J; Qi, Y; Zdanowicz, M; Camp, T; Li, Y-X; Diehl, AM
MLA Citation
Suzuki, A, McCall, S, Choi, SS, Sicklick, JK, Huang, J, Qi, Y, Zdanowicz, M, Camp, T, Li, Y-X, and Diehl, AM. "Interleukin-15 increases hepatic regenerative activity." J Hepatol 45.3 (September 2006): 410-418.
PMID
16781000
Source
pubmed
Published In
Journal of Hepatology
Volume
45
Issue
3
Publish Date
2006
Start Page
410
End Page
418
DOI
10.1016/j.jhep.2006.04.008

Loss of heterozygosity of M6P/IGF2R gene is an early event in the development of prostate cancer.

BACKGROUND: The genetic events leading to initiation and/or progression of prostate cancer are not well characterized. The gene coding for the mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) has recently been identified as a tumor suppressor in several types of cancer. The purpose of the present study is to determine whether the M6P/IGF2R gene is inactivated in human prostate cancer, and if so, whether this is an early or late transformational event. METHODS: In total, 43 patients with prostate cancer treated by radical prostatectomy, with archival material available for analysis, were assessed for loss of heterozygosity (LOH) in the M6P/IGF2R gene using six different gene-specific nucleotide polymorphisms. Regions of tumor, normal prostate and premalignant high-grade prostate intraepithelial neoplasia (PIN) were identified and cells were excised by laser capture microdissection (LCM). DNA segments were amplified using polymerase chain reaction (PCR). RESULTS: The M6P/IGF2R gene was polymorphic in 83.7% (36/43) of patients, and 41.7% (15/36) of these informative patients had LOH in the tumor tissue. In 11/15 patients with LOH in malignant tissue, high-grade PIN could be identified, and 63.6% (7/11) also had LOH in this premalignant tissue. CONCLUSIONS: This study is the first to find that the M6P/IGF2R gene is inactivated in prostate cancer. LOH in premalignant tissue as well suggests that mutation in the M6P/IGF2R gene is an early event in the development of prostate cancer, supporting the conclusion that it functions as a tumor suppressor gene in this disease.

Authors
Hu, CK; McCall, S; Madden, J; Huang, H; Clough, R; Jirtle, RL; Anscher, MS
MLA Citation
Hu, CK, McCall, S, Madden, J, Huang, H, Clough, R, Jirtle, RL, and Anscher, MS. "Loss of heterozygosity of M6P/IGF2R gene is an early event in the development of prostate cancer." Prostate Cancer Prostatic Dis 9.1 (2006): 62-67.
PMID
16304558
Source
pubmed
Published In
Prostate Cancer and Prostatic Diseases
Volume
9
Issue
1
Publish Date
2006
Start Page
62
End Page
67
DOI
10.1038/sj.pcan.4500842

IL-15 increases regenerative activity in the livers

Authors
Suzuki, A; McCall, S; Huang, JW; Qi, Y; Zdanowicz, M; Sicklick, J; Camp, T; Li, YX; Diehl, AME
MLA Citation
Suzuki, A, McCall, S, Huang, JW, Qi, Y, Zdanowicz, M, Sicklick, J, Camp, T, Li, YX, and Diehl, AME. "IL-15 increases regenerative activity in the livers." October 2005.
Source
wos-lite
Published In
Hepatology
Volume
42
Issue
4
Publish Date
2005
Start Page
572A
End Page
572A

Pulmonary embolization of microcrystalline cellulose in a lung transplant recipient.

Intravenous injection of drugs that contain insoluble foreign material can lead to pulmonary embolization of the material and can have devastating results, including pulmonary hypertension and death. Most cases are detected after the onset of extensive, irreversible damage, precluding potentially life-saving intervention, or are detected at autopsy. We report here a case of microcrystalline cellulose embolization in a lung transplant recipient detected at routine transbronchial biopsy, and we describe the circumstances associated with the development of this condition and its clinical outcome.

Authors
Fields, TA; McCall, SJ; Reams, BD; Roggli, VL; Palmer, SM; Howell, DN
MLA Citation
Fields, TA, McCall, SJ, Reams, BD, Roggli, VL, Palmer, SM, and Howell, DN. "Pulmonary embolization of microcrystalline cellulose in a lung transplant recipient." J Heart Lung Transplant 24.5 (May 2005): 624-627.
PMID
15896764
Source
pubmed
Published In
The Journal of Heart and Lung Transplantation
Volume
24
Issue
5
Publish Date
2005
Start Page
624
End Page
627
DOI
10.1016/j.healun.2004.01.023

Loss of heterozygosity in the M6P/IFG2R gene is an early event in the development of prostate cancer

Authors
HU, C; MCCALL, S; MADDEN, J; HUANG, H; CLOUGH, R; RABBANI, Z; JIRTLE, R; ANSCHER, M
MLA Citation
HU, C, MCCALL, S, MADDEN, J, HUANG, H, CLOUGH, R, RABBANI, Z, JIRTLE, R, and ANSCHER, M. "Loss of heterozygosity in the M6P/IFG2R gene is an early event in the development of prostate cancer." September 2004.
Source
crossref
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
60
Publish Date
2004
Start Page
S460
End Page
S460
DOI
10.1016/S0360-3016(04)01675-X

Prognostic significance of microvascular thrombosis in donor kidney allograft biopsies.

BACKGROUND: With a continuing demand for donor kidneys for organ transplantation, it is important to understand the significance of pathologic findings in the donor organ before transplantation. Microvascular thrombosis is sometimes encountered in association with disseminated intravascular coagulation in the donor, and it is unclear whether this finding may affect immediate allograft function and long-term graft survival. To further elucidate this question, we examined our experience with microvascular thrombosis in donor biopsies in the kidney transplant program at our institution. METHODS: Donor kidney biopsies showing microvascular thrombosis were identified from consecutive donor biopsies in the Duke University Medical Center transplant file database between January 1, 1995 and December 31, 2000. These biopsies and all other kidney biopsies and specimens from the recipients of these kidneys thus identified were reviewed. Sections were stained using a variety of methods, including hematoxylin-eosin, periodic acid-Schiff, methenamine silver, and Masson trichrome methods. Clinical records of the transplant recipients of these kidneys were also reviewed to assess allograft performance and survival. RESULTS: From 230 consecutive donor kidney biopsies, we identified eight cases exhibiting donor-microvascular thrombosis. Mean follow-up times were 27.5 months for the thrombi group and 35 months for the non-thrombi group. Recipients of grafts with donor thrombi were more likely to exhibit delayed graft function, but graft function at 1 and 2 years and graft survival were similar between the two groups. Subsequent posttransplantation biopsies in five of eight cases showed no evidence of residual thrombosis. CONCLUSIONS: These data suggest that the presence of donor microvascular thrombosis does not portend poor outcome in renal transplantation.

Authors
McCall, SJ; Tuttle-Newhall, JE; Howell, DN; Fields, TA
MLA Citation
McCall, SJ, Tuttle-Newhall, JE, Howell, DN, and Fields, TA. "Prognostic significance of microvascular thrombosis in donor kidney allograft biopsies." Transplantation 75.11 (June 15, 2003): 1847-1852.
PMID
12811244
Source
pubmed
Published In
Transplantation
Volume
75
Issue
11
Publish Date
2003
Start Page
1847
End Page
1852
DOI
10.1097/01.TP.0000063126.88887.68

Hepatic veno-occlusive disease in primary humoral immunodeficiency

Authors
McCall, SJ; Myers, LA; Treem, WR; Patel, DD; Gottfried, MR
MLA Citation
McCall, SJ, Myers, LA, Treem, WR, Patel, DD, and Gottfried, MR. "Hepatic veno-occlusive disease in primary humoral immunodeficiency." January 2003.
Source
wos-lite
Published In
Laboratory Investigation
Volume
83
Issue
1
Publish Date
2003
Start Page
281A
End Page
281A

Hepatic veno-occlusive disease in primary humoral immunodeficiency

Authors
McCall, SJ; Myers, LA; Treem, WR; Patel, DD; Gottfried, MR
MLA Citation
McCall, SJ, Myers, LA, Treem, WR, Patel, DD, and Gottfried, MR. "Hepatic veno-occlusive disease in primary humoral immunodeficiency." January 2003.
Source
wos-lite
Published In
Modern Pathology
Volume
16
Issue
1
Publish Date
2003
Start Page
281A
End Page
281A
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Research Areas:

  • Ampulla of Vater
  • Apoptosis
  • Bevacizumab
  • Bile Ducts
  • Biological Markers
  • Biopsy
  • Biopsy, Needle
  • Cell Differentiation
  • Cell Line
  • Cell Nucleus
  • Cell Proliferation
  • Cell Survival
  • Cells, Cultured
  • Colorectal Neoplasms
  • Colorectal Neoplasms, Hereditary Nonpolyposis
  • Cytochrome P-450 CYP2E1
  • Endocytosis
  • Epithelial Cells
  • Epithelial-Mesenchymal Transition
  • Gene Deletion
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease
  • Hedgehog Proteins
  • Homeodomain Proteins
  • Humans
  • Hydroxyproline
  • Immunohistochemistry
  • Kruppel-Like Transcription Factors
  • Lasers
  • Mesenchymal Stromal Cells
  • Mesoderm
  • Microdissection
  • Mutation
  • Nuclear Proteins
  • Oligonucleotides, Antisense
  • Oligoribonucleotides, Antisense
  • Oncogenes
  • Organoplatinum Compounds
  • Pancreaticoduodenectomy
  • Pancreatitis
  • Pilot Projects
  • Prognosis
  • Protein Isoforms
  • Proteome
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins B-raf
  • Pyrimidines
  • RNA, Messenger
  • Receptors, Cell Surface
  • Recombinant Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Stromal Cells
  • Thiazoles
  • Tissue Donors
  • Tumor Markers, Biological
  • Tumor Necrosis Factor-alpha
  • Wnt Proteins
  • Xenograft Model Antitumor Assays
  • ras Proteins