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Dive into the research topics where James P. Stewart is active.

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Featured researches published by James P. Stewart.


British Journal of Haematology | 2004

Correlation of TACC3, FGFR3, MMSET and p21 expression with the t(4;14)(p16.3;q32) in multiple myeloma.

James P. Stewart; Alexander Thompson; Madhumita Santra; Bart Barlogie; Terence Lappin; John D. Shaughnessy

The t(4;14)(p16;q32) translocation seen in c. 18% of newly diagnosed multiple myeloma (MM) cases, results in FGFR3 activation and creation of an IGH/MMSET fusion transcript. We have recently shown that FGFR3 is activated in only 75% of t(4;14)+ cases, suggesting that alternative genes near the breakpoint may be involved in the transforming event. The gene, TACC3, located just 50 kb telomeric of FGFR3, with transforming capacity, therefore represented a candidate gene. Using a real‐time quantitative polymerase chain reaction‐based approach on a cohort of 54 patients, we found a statistically significant, twofold increase in TACC3 expression in t(4;14)+ cases. TACC3, MMSET and p21 values were positively correlated in all cases and, of particular interest, six patient samples [three t(4;14)−, three t(4;14)+] samples showed a joint up‐regulation of TACC3, MMSET and p21. Although a poor prognosis is linked with elevated MMSET expression, an extended follow‐up period will be required to evaluate the significance of elevated TACC3 and p21 expression in this subgroup of MM.


Journal of Cellular Biochemistry | 2006

Role of osteoblast suppression in multiple myeloma.

James P. Stewart; John D. Shaughnessy

Multiple myeloma is the most common form of plasma cell dyscrasia and virtually all cases of myeloma exhibit osteolytic lesions, which result in bone pain, pathological fractures, spinal cord compression, and hypercalcaemia. Malignant plasma cells disrupt the delicate balance between bone formation and bone resorption, which ultimately leads to the debilitating osteolytic lesions. This review focuses principally on mechanisms of osteoblast inhibition by malignant plasma cells with emphasis placed on our experimental findings, which support a model for abnormal Wnt signaling in osteoblast suppression. We describe how excessive amounts of soluble Wnt inhibitors secreted by malignant plasma cells in multiple myeloma could promote osteolytic lesions, tumor growth, suppress hematopoiesis, prevent proper engraftment, and expansion of transplanted stem cells. Finally, we detail current therapies shown to disrupt the interaction between the myeloma cell and the microenvironment, leading to activation of osteoblasts. J. Cell. Biochem. 98: 1–13, 2006.


Blood | 2014

CYR61/CCN1 overexpression in the myeloma microenvironment is associated with superior survival and reduced bone disease

Sarah K. Johnson; James P. Stewart; Rakesh Bam; Pingping Qu; Bart Barlogie; Frits van Rhee; John D. Shaughnessy; Joshua Epstein; Shmuel Yaccoby

Secreted protein CCN1, encoded by CYR61, is involved in wound healing, angiogenesis, and osteoblast differentiation. We identified CCN1 as a microenvironmental factor produced by mesenchymal cells and overexpressed in bones of a subset of patients with monoclonal gammopathy of undetermined significance (MGUS), asymptomatic myeloma (AMM), and multiple myeloma (MM). Our analysis showed that overexpression of CYR61 was independently associated with superior overall survival of MM patients enrolled in our Total Therapy 3 protocol. Moreover, elevated CCN1 was associated with a longer time for MGUS/AMM to progress to overt MM. During remission from MM, high levels of CCN1 were associated with superior progression-free and overall survival and stratified patients with molecularly defined high-risk MM. Recombinant CCN1 directly inhibited in vitro growth of MM cells, and overexpression of CYR61 in MM cells reduced tumor growth and prevented bone destruction in vivo in severe combined immunodeficiency-hu mice. Signaling through αvβ3 was required for CCN1 prevention of bone disease. CYR61 expression may signify early perturbation of the microenvironment before conversion to overt MM and may be a compensatory mechanism to control MM progression. Therapeutics that upregulate CYR61 should be investigated for treating MM bone disease.


Biochimica et Biophysica Acta | 2017

Standardising RNA profiling based biomarker application in cancer - the need for robust control of technical variables

James P. Stewart; Susan Richman; Tim Maughan; Mark Lawler; Philip D. Dunne; Manuel Salto-Tellez

Histopathology-based staging of colorectal cancer (CRC) has utility in assessing the prognosis of patient subtypes, but as yet cannot accurately predict individual patients treatment response. Transcriptomics approaches, using array based or next generation sequencing (NGS) platforms, of formalin fixed paraffin embedded tissue can be harnessed to develop multi-gene biomarkers for predicting both prognosis and treatment response, leading to stratification of treatment. While transcriptomics can shape future biomarker development, currently <1% of published biomarkers become clinically validated tests, often due to poor study design or lack of independent validation. In this review of a large number of CRC transcriptional studies, we identify recurrent sources of technical variability that encompass collection, preservation and storage of malignant tissue, nucleic acid extraction, methods to quantitate RNA transcripts and data analysis pipelines. We propose a series of defined steps for removal of these confounding issues, to ultimately aid in the development of more robust clinical biomarkers.


The Journal of Pathology | 2018

Prospective patient stratification into robust cancer-cell intrinsic subtypes from colorectal cancer biopsies

Matthew Alderdice; Susan Richman; Simon Gollins; James P. Stewart; Chris Nicholas Hurt; Richard Adams; Amy M.B. McCorry; Aideen Roddy; Dale Vimalachandran; Claudio Isella; Enzo Medico; Tim Maughan; Darragh G. McArt; Mark Lawler; Philip D. Dunne

Colorectal cancer (CRC) biopsies underpin accurate diagnosis, but are also relevant for patient stratification in molecularly‐guided clinical trials. The consensus molecular subtypes (CMSs) and colorectal cancer intrinsic subtypes (CRISs) transcriptional signatures have potential clinical utility for improving prognostic/predictive patient assignment. However, their ability to provide robust classification, particularly in pretreatment biopsies from multiple regions or at different time points, remains untested. In this study, we undertook a comprehensive assessment of the robustness of CRC transcriptional signatures, including CRIS and CMS, using a range of tumour sampling methodologies currently employed in clinical and translational research. These include analyses using (i) laser‐capture microdissected CRC tissue, (ii) eight publically available rectal cancer biopsy data sets (n = 543), (iii) serial biopsies (from AXEBeam trial, NCT00828672; n = 10), (iv) multi‐regional biopsies from colon tumours (n = 29 biopsies, n = 7 tumours), and (v) pretreatment biopsies from the phase II rectal cancer trial COPERNCIUS (NCT01263171; n = 44). Compared to previous results obtained using CRC resection material, we demonstrate that CMS classification in biopsy tissue is significantly less capable of reliably classifying patient subtype (43% unknown in biopsy versus 13% unknown in resections, p = 0.0001). In contrast, there was no significant difference in classification rate between biopsies and resections when using the CRIS classifier. Additionally, we demonstrated that CRIS provides significantly better spatially‐ and temporally‐ robust classification of molecular subtypes in CRC primary tumour tissue compared to CMS (p = 0.003 and p = 0.02, respectively). These findings have potential to inform ongoing biopsy‐based patient stratification in CRC, enabling robust and stable assignment of patients into clinically‐informative arms of prospective multi‐arm, multi‐stage clinical trials.


Blood | 2006

The molecular classification of multiple myeloma

Fenghuang Zhan; Yongsheng Huang; Simona Colla; James P. Stewart; Ichiro Hanamura; Sushil Gupta; Joshua Epstein; Shmuel Yaccoby; Jeffrey R. Sawyer; Bart Burington; Elias Anaissie; Klaus Hollmig; Mauricio Pineda-Roman; Guido Tricot; Frits van Rhee; Ronald Walker; Maurizio Zangari; John Crowley; Bart Barlogie; John D. Shaughnessy


Blood | 2007

A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1

John D. Shaughnessy; Fenghuang Zhan; Bart Burington; Yongsheng Huang; Simona Colla; Ichiro Hanamura; James P. Stewart; Bob Kordsmeier; Christopher Randolph; David R. Williams; Yan Xiao; Hongwei Xu; Joshua Epstein; Elias Anaissie; Somashekar G. Krishna; Michele Cottler-Fox; Klaus Hollmig; Abid Mohiuddin; Mauricio Pineda-Roman; Guido Tricot; Frits van Rhee; Jeffrey R. Sawyer; Yazan Alsayed; Ronald Walker; Maurizio Zangari; John Crowley; Bart Barlogie


Cancer Cell | 2006

High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients

Daniel R. Carrasco; Giovanni Tonon; Yongsheng Huang; Yunyu Zhang; Raktim Sinha; Bin Feng; James P. Stewart; Fenghuang Zhan; Deepak Khatry; Marina Protopopova; Alexei Protopopov; Kumar Sukhdeo; Ichiro Hanamura; Owen Stephens; Bart Barlogie; Kenneth C. Anderson; Lynda Chin; John D. Shaughnessy; Cameron Brennan; Ronald A. DePinho


Blood | 2006

Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation

Ichiro Hanamura; James P. Stewart; Yongsheng Huang; Fenghuang Zhan; Madhumita Santra; Jeffrey R. Sawyer; Klaus Hollmig; Maurizio Zangarri; Mauricio Pineda-Roman; Frits van Rhee; Federica Cavallo; Bart Burington; John Crowley; Guido Tricot; Bart Barlogie; John D. Shaughnessy


Blood | 2007

CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms

Fenghuang Zhan; Simona Colla; Xiaosong Wu; Bangzheng Chen; James P. Stewart; W. Michael Kuehl; Bart Barlogie; John D. Shaughnessy

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Bart Barlogie

University of Arkansas for Medical Sciences

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John D. Shaughnessy

University of Arkansas for Medical Sciences

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Fenghuang Zhan

University of Arkansas for Medical Sciences

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Yongsheng Huang

University of Arkansas for Medical Sciences

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Frits van Rhee

University of Arkansas for Medical Sciences

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Simona Colla

University of Arkansas for Medical Sciences

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Guido Tricot

University of Arkansas for Medical Sciences

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Joshua Epstein

University of Arkansas for Medical Sciences

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Klaus Hollmig

University of Arkansas for Medical Sciences

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