Life Sciences Commons^™

The Dose-Response Effect Of Aerobic Exercise On Inflammation In Colon Cancer Survivors, Justin C. Brown, Stephanie L.E. Compton, Jeffrey A. Meyerhardt, Guillaume Spielmann, Shengping Yang

School of Medicine Faculty Publications

Background; Physical activity after surgical resection for colon cancer is associated with significantly longer disease-free survival. Inflammation is hypothesized to mediate the association between physical activity and disease-free survival in colon cancer. Methods; In this exploratory analysis of a randomized dose-response trial, 39 colon cancer survivors who completed standard therapy were stratified by cancer stage and randomized in a 1;1;1 ratio to one of three treatment groups for 24 weeks of usual-care control, 150 min/wk of moderate-intensity aerobic exercise (low-dose), or 300 min/wk of moderate-intensity aerobic exercise (high-dose). Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL6), and soluble tumor …

The Use Of Prognostic Markers To Predict Disease Progression And Clinical Outcome In Monoclonal Gammopathy Of Undetermined Significance, Smouldering Multiple Myeloma And Multiple Myeloma., Róisín C. Mcmonagle

International Undergraduate Journal of Health Sciences

Multiple Myeloma (MM) is an incurable plasma cell malignancy with a complex and incompletely understood molecular pathogenesis. Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smouldering Multiple Myeloma (SMM) precede MM, with variable risks and rates of disease progression. The continuing high relapse and death rate in MM cases has prompted research into more accurate prognostic markers to predict progression from MGUS and SMM to MM, as well as identify MM cases with aggressive disease, in order to begin early, targeted and effective therapeutic intervention. Many studies have focused on utilising current markers more effectively, including M-protein, serum-free light chain ratio, …

Antioxidant Biomarkers And Nutraceutical Therapeutics In Neurodegeneration And Neurotrauma, Lilia A. Koza

Electronic Theses and Dissertations

Mild traumatic brain injury (mTBI), yielding a Glascow Coma Scale of 13-15, is the most commonly occurring severity of TBI. Pathology from mTBI consists of blood brain barrier disruption, neuroinflammation, oxidative stress, excitotoxicity, mitochondrial dysfunction, protein aggregation, axonal degeneration, and resulting neuronal death. These processes deplete the body’s endogenous antioxidant system. We report a retrospective analysis of antioxidant blood biomarkers in patients with a history of mTBI from a local sports medicine clinic, Resilience Code. We found persistent sex-specific antioxidant depletions in mTBI patients associated with worsened symptomology.

Certain populations, such as athletes, are at high risk for repetitive mTBI …

Bile Acid Profiling Reveals Distinct Signatures In Undernourished Children With Environmental Enteric Dysfunction, Xueheng Zhao, Kenneth D R. Setchell, Rong Huang, Indika Mallawaarachchi, Lubaina Ehsan, Edward Dobrzykowski Iii, Junfang Zhao, Sana Syed, Najeeha Talat Iqbal, Junaid Iqbal, Kamran Sadiq, Sheraz Ahmed, Syed Asad Ali

Department of Paediatrics and Child Health

Background: Intestinal inflammation and malabsorption in environmental enteric dysfunction (EED) are associated with early childhood growth faltering in impoverished settings worldwide.
Objectives: The goal of this study was to identify candidate biomarkers associated with inflammation, EED histology, and as predictors of later growth outcomes by focusing on the liver-gut axis by investigating the bile acid metabolome.
Methods: Undernourished rural Pakistani infants (n = 365) with weight-for-height Z score (WHZ) < -2 were followed up to the age of 24 mo and monitored for growth, infections, and EED. Well-nourished local children (n = 51) were controls, based on consistent WHZ > 0 and height-for-age Z score (HAZ) > -1 on 2 consecutive visits at 3 and 6 mo. Serum bile acid (sBA) profiles were measured by tandem MS at the ages of 3-6 …

Developing Methods To Detect And Diagnose Chronic Traumatic Encephalopathy During Life: Rationale, Design, And Methodology For The Diagnose Cte Research Project, Jeffrey Cummings, Numerous Authors, See Full List Below

School of Medicine Faculty Publications

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been neuropathologically diagnosed in brain donors exposed to repetitive head impacts, including boxers and American football, soccer, ice hockey, and rugby players. CTE cannot yet be diagnosed during life. In December 2015, the National Institute of Neurological Disorders and Stroke awarded a seven-year grant (U01NS093334) to fund the “Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project.” The objectives of this multicenter project are to: develop in vivo fluid and neuroimaging biomarkers for CTE; characterize its clinical presentation; refine …

The Context-Dependent Impact Of Integrin-Associated Cd151 And Other Tetraspanins On Cancer Development And Progression: A Class Of Versatile Mediators Of Cellular Function And Signaling, Tumorigenesis And Metastasis, Sonia F. Erfani, Hui Hua, Yueyin Pan, Binhua P. Zhou, Xiuwei H. Yang

Molecular and Cellular Biochemistry Faculty Publications

As a family of integral membrane proteins, tetraspanins have been functionally linked to a wide spectrum of human cancers, ranging from breast, colon, lung, ovarian, prostate, and skin carcinomas to glioblastoma. CD151 is one such prominent member of the tetraspanin family recently suggested to mediate tumor development, growth, and progression in oncogenic context- and cell lineage-dependent manners. In the current review, we summarize recent advances in mechanistic understanding of the function and signaling of integrin-associated CD151 and other tetraspanins in multiple cancer types. We also highlight emerging genetic and epigenetic evidence on the intrinsic links between tetraspanins, the epithelial-mesenchymal transition …

Real World Clinicopathologic Observations Of Patients With Metastatic Solid Tumors Receiving Immune Checkpoint Inhibitor Therapy: Analysis From Kentucky Cancer Registry, Aasems Jacob, Jianrong Wu, Jill M. Kolesar, Eric B. Durbin, Aju Mathew, Susanne Arnold, Aman Chauhan

Biostatistics Faculty Publications

The state of Kentucky has the highest cancer incidence and mortality in the United States. High‐risk populations such as this are often underrepresented in clinical trials. The study aims to do a comprehensive analysis of molecular landscape of metastatic cancers among these patients with detailed evaluation of factors affecting response and outcomes to immune checkpoint inhibitor (ICI) therapy. We performed a retrospective analysis of metastatic solid tumor patients who received ICI and underwent molecular profiling at our institution.

Sixty nine patients with metastatic solid tumors who received ICI were included in the study. Prevalence of smoking and secondhand tobacco exposure …

Isolation And Characterization Of Α-Gal-Containing Extracellular Vesicles (Evs) From Three Major Genotypes Of Trypanosoma Cruzi: Potential Biomarkers Of Chagas Disease, Nasim Karimi Hosseini

Open Access Theses & Dissertations

Chagas disease (ChD) is a neglected tropical disease (NTD) caused by the protozoan parasite, Trypanosoma cruzi. It is transmitted by the insect-vector triatomine (popular known as kissing bug), blood transfusion, organ transplantation, congenitally, and contaminated foods and juices. T. cruzi has evolved several strategies to invade the host cells, including the release extracellular vesicles (EVs), which assist pathogen survival and its replication within the host. T. cruzi is covered with highly glycosylated surface molecules such as glycoproteins and glycolipids, which are shown to be involved in the interaction with host immune cells. These molecules are highly immunogenic and reactive with …

Acetaminophen Protein Adducts In Hospitalized Children Receiving Multiple Doses Of Acetaminophen., Sibo Jiang, Valvanera Vozmediano, Susan M. Abdel-Rahman, Stephan Schmidt, Laura P. James

Manuscripts, Articles, Book Chapters and Other Papers

Previous reports have questioned the safety of multiple doses of acetaminophen administered to ill children. Acetaminophen protein adducts (adducts) are a biomarker of acetaminophen-induced liver injury and reflect the oxidative metabolism of acetaminophen, a known mechanism in acetaminophen toxicity. In this prospective observational study, we analyzed adduct concentrations in 1034 blood samples obtained from 181 hospitalized children (1 to 18 years inclusive) who received 2 or more doses of acetaminophen. Linear regression analysis showed that serum adduct concentrations increased as a function of the cumulative acetaminophen dose, which could be attributed, in part, to a long half-life of adducts (2.17 …

Trypanosoma Cruzi Trypomastigote Glycosylphosphatidylinositol-Anchored Mucins And A Synthetic Alpha-Gal-Containing Neoglycoprotein As Potential Biomarkers And Vaccines For Chagas Disease, Igor Leandro Estevao

Open Access Theses & Dissertations

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a neglected tropical disease that kills or permanently disable thousands of people annually. About 6-8 million people are estimated to be infected worldwide. Although many efforts have been made for the development of an effective immunotherapy, currently there is no vaccine to prevent or treat CD in humans. Despite their toxicity, the two current drugs for CD, benznidazole (BZN) and nifurtimox (NFX), have medium-to-high efficacy in the chronic stage of the disease and could save or improve the lives of thousands of patients. However, negative seroconversion in treated patients, as …

Antibodies In The Diagnosis, Prognosis, And Prediction Of Psychotic Disorders., Thomas A Pollak, Jonathan P Rogers, Robert G Nagele, Mark Peakman, James M Stone, Anthony S David, Philip Mcguire

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Blood-based biomarker discovery for psychotic disorders has yet to impact upon routine clinical practice. In physical disorders antibodies have established roles as diagnostic, prognostic and predictive (theranostic) biomarkers, particularly in disorders thought to have a substantial autoimmune or infective aetiology. Two approaches to antibody biomarker identification are distinguished: a "top-down" approach, in which antibodies to specific antigens are sought based on the known function of the antigen and its putative role in the disorder, and emerging "bottom-up" or "omics" approaches that are agnostic as to the significance of any one antigen, using high-throughput arrays to identify distinctive components of the …

Analysis Of The Immunological Biomarker Profile During Acute Zika Virus Infection Reveals The Overexpression Of Cxcl10, A Chemokine Linked To Neuronal Damage., Felipe Gomes Naveca, Gemilson Soares Pontes, Aileen Yu-Hen Chang, George Allan Villarouco Da Silva, Valdinete Alves Do Nascimento, Dana Cristina Da Silva Monteiro, +Several Additional Authors

Medicine Faculty Publications

BACKGROUND: Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis.

OBJECTIVES: To define the immunologic biomarkers that correlate with acute ZIKV infection.

METHODS: We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining.

FINDINGS: ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite …

Bilateral Carotid Artery Stenosis Causes Unexpected Early Changes In Brain Extracellular Matrix And Blood-Brain Barrier Integrity In Mice, Jill M. Roberts, Michael E. Maniskas, Gregory J. Bix

Neuroscience Faculty Publications

Bilateral carotid artery stenosis (BCAS) is one experimental model of vascular dementia thought to preferentially impact brain white matter. Indeed, few studies report hippocampal and cortical pathology prior to 30 days post-stenosis; though it is unclear whether those studies examined regions outside the white matter. Since changes in the blood-brain barrier (BBB) permeability precede more overt brain pathology in various diseases, we hypothesized that changes within the BBB and/or BBB-associated extracellular matrix (ECM) could occur earlier after BCAS in the hippocampus, cortex and striatum and be a precursor of longer term pathology. Here, C57Bl/6 mice underwent BCAS or sham surgeries …

Extracellular Vesicles Released By Cardiomyocytes In A Doxorubicin-Induced Cardiac Injury Mouse Model Contain Protein Biomarkers Of Early Cardiac Injury, Chontida Yarana, Dustin W. Carroll, Jing Chen, Luksana Chaiswing, Yanming Zhao, Teresa Noel, Michael Alstott, Younsoo Bae, Emily V. Dressler, Jeffrey A. Moscow, D. Allan Butterfield, Haining Zhu, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Purpose—Cardiac injury is a major cause of death in cancer survivors, and biomarkers for it are detectable only after tissue injury has occurred. Extracellular vesicles (EV) remove toxic biomolecules from tissues and can be detected in the blood. Here, we evaluate the potential of using circulating EVs as early diagnostic markers for long-term cardiac injury.

Experimental Design—Using a mouse model of doxorubicin (DOX)-induced cardiac injury, we quantified serum EVs, analyzed proteomes, measured oxidized protein levels in serum EVs released after DOX treatment, and investigated the alteration of EV content.

Results—Treatment with DOX caused a significant increase in …

Identification Of Prognostic Cancer Biomarkers Through The Application Of Rna-Seq Technologies And Bioinformatics, Nathan Wong

McKelvey School of Engineering Theses & Dissertations

MicroRNAs (miRNAs) are short single-stranded RNAs that function as the guide sequence of the post-transcriptional regulatory process known as the RNA-induced silencing complex (RISC), which targets mRNA sequences for degradation through complementary binding to the guide miRNA. Changes in miRNA expression have been reported as correlated with numerous biological processes, including embryonic development, cellular differentiation, and disease manifestation. In the latter case, dysregulation has been observed in response to infection by human papillomavirus (HPV), which has also been established as both oncogenic in cervical cancers and oropharyngeal cancers and favorable for overall patient survival after tumor formation. The identification of …

A Customized Quantitative Pcr Microrna Panel Provides A Technically Robust Context For Studying Neurodegenerative Disease Biomarkers And Indicates A High Correlation Between Cerebrospinal Fluid And Choroid Plexus Microrna Expression, Wang-Xia Wang, David W. Fardo, Gregory A. Jicha, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNA (miRNA) expression varies in association with different tissue types and in diseases. Having been found in body fluids including blood and cerebrospinal fluid (CSF), miRNAs constitute potential biomarkers. CSF miRNAs have been proposed as biomarkers for neurodegenerative diseases; however, there is a lack of consensus about the best candidate miRNA biomarkers and there has been variability in results from different research centers, perhaps due to technical factors. Here, we sought to optimize technical parameters for CSF miRNA studies. We examined different RNA isolation methods and performed miRNA expression profiling with TaqMan® miRNA Arrays. More specifically, we developed a customized …

Moonlighting Newborn Screening Markers: The Incidental Discovery Of A Second-Tier Test For Pompe Disease, Silvia Tortorelli, Jason S. Eckerman, Joseph J. Orsini, Colleen Stevens, Jeremy Hart, Patricia L. Hall, John J. Alexander, Dimitar Gavrilov, Devin Oglesbee, Kimiyo Raymond, Dietrich Matern, Piero Rinaldo

Pathology and Laboratory Medicine Faculty Publications

Purpose: To describe a novel biochemical marker in dried blood spots suitable to improve the specificity of newborn screening for Pompe disease.

Methods: The new marker is a ratio calculated between the creatine/creatinine (Cre/Crn) ratio as the numerator and the activity of acid α-glucosidase (GAA) as the denominator. Using Collaborative Laboratory Integrated Reports (CLIR), the new marker was incorporated in a dual scatter plot that can achieve almost complete segregation between Pompe disease and false-positive cases.

Results: The (Cre/Crn)/GAA ratio was measured in residual dried blood spots of five Pompe cases and was found to be elevated (range 4.41–13.26; 99%ile …

Autoantibodies As Diagnostic Biomarkers For The Detection And Subtyping Of Multiple Sclerosis, Cassandra Demarshall, Eric Goldwaser, Abhirup Sarkar, George Godsey, Nimish Acharya, Umashanger Thayasivam, Benjamin Belinka, Robert Nagele

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

The goal of this preliminary proof-of-concept study was to use human protein microarrays to identify blood-based autoantibody biomarkers capable of diagnosing multiple sclerosis (MS). Using sera from 112 subjects, including 51 MS subjects, autoantibody biomarkers effectively differentiated MS subjects from age- and gender-matched normal and breast cancer controls with 95.0% and 100% overall accuracy, but not from subjects with Parkinson's disease. Autoantibody biomarkers were also useful in distinguishing subjects with the relapsing-remitting form of MS from those with the secondary progressive subtype. These results demonstrate that autoantibodies can be used as noninvasive blood-based biomarkers for the detection and subtyping of …

Hepatitis C Virus-Induced Monocyte Differentiation Into Polarized M2 Macrophages Promotes Stellate Cell Activation Via Tgf-Beta, Banishree Saha, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND and AIMS: Monocyte and macrophage (MPhi) activation contributes to the pathogenesis of chronic hepatitis C virus (HCV) infection. Disease pathogenesis is regulated by both liver-resident MPhis and monocytes recruited as precursors of MPhis into the damaged liver. Monocytes differentiate into M1 (classic/proinflammatory) or M2 (alternative/anti-inflammatory) polarized MPhis in response to tissue microenvironment. We hypothesized that HCV-infected hepatoma cells (infected with Japanese fulminant hepatitis-1 [Huh7.5/JFH-1]) induce monocyte differentiation into polarized MPhis. METHODS: Healthy human monocytes were co-cultured with Huh7.5/JFH-1 cells or cell-free virus for 7 days and analyzed for MPhi markers and cytokine levels. A similar analysis was performed on …

Csf Protein Changes Associated With Hippocampal Sclerosis Risk Gene Variants Highlight Impact Of Grn/Pgrn, David W. Fardo, Yuriko Katsumata, John S. K. Kauwe, Yuetiva Deming, Oscar Harari, Carlos Cruchaga, Alzheimer’S Disease Neuroimaging Initiative, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Objective—Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults. We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs).

Methods—Alzheimer’s Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454). For controls, non-HS-Aging SNPs in APOE (rs429358/rs7412) and MAPT (rs8070723) were also analyzed against Aβ1-42 and total tau CSF analytes.

Results—The GRN risk …

Protein Calorie Malnutrition, Nutritional Intervention And Personalized Cancer Care, Anju Gangadharan, Sung-Eun Choi, Ahmed Hassan, Nehad M. Ayoub, Gina Durante, Sakshi Balwani, Young Hee Kim, Andrew Pecora, Andre Goy, K. Stephen Suh

Publications and Research

Cancer patients often experience weight loss caused by protein calorie malnutrition (PCM) during the course of the disease or treatment. PCM is expressed as severe if the patient has two or more of the following characteristics: obvious significant muscle wasting, loss of subcutaneous fat; nutritional intake of <50% of recommended intake for 2 weeks or more; bedridden or otherwise significantly reduced functional capacity; weight loss of >2% in 1 week, 5% in 1 month, or 7.5% in 3 months. Cancer anorexiacachexia syndrome (CACS) is a multifactorial condition of advanced PCM associated with underlying illness (in this case cancer) and is characterized by loss of muscle with or without loss of fat mass. Cachexia is defined as weight loss of …

Nicotinamide Adenine Dinucleotide Phosphate Oxidase 2 Regulates Lps-Induced Inflammation And Alveolar Remodeling In The Developing Lung., Heather Menden, Sheng Xia, Sherry M. Mabry, Angels Navarro, Michael F. Nyp, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

In premature infants, sepsis is associated with alveolar simplification manifesting as bronchopulmonary dysplasia. The redox-dependent mechanisms underlying sepsis-induced inflammation and alveolar remodeling in the immature lung remain unclear. We developed a neonatal mouse model of sepsis-induced lung injury to investigate whether nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) regulates Toll-like receptor (TLR)-mediated inflammation and alveolar remodeling. Six-day-old NOX2

Utilization Of The Clinical Laboratory For The Implementation Of Concussion Biomarkers In Collegiate Football And The Necessity Of Personalized And Predictive Athlete Specific Reference Intervals, Stefanie Podlog (Nee Schulte), Natalie N. Rasmussen, Joseph W. Mcbeth, Patrick Q. Richards, Eric Yochem, David J. Petron, Frederick G. Strathmann

Athletic Training Collection

Background: A continued interest in concussion biomarkers makes the eventual implementation of identified biomarkers into routine concussion assessment an eventual reality. We sought to develop and test an interdisciplinary approach that could be used to integrate blood-based biomarkers into the established concussion management program for a collegiate football team.

Methods: We used a CLIA-certified laboratory for all testing and chose biomarkers where clinically validated testing was available as would be required for results used in clinical decision making. We summarized the existing methods and results for concussion assessment across an entire season to identify and demonstrate the challenges with the …

Chronic Systemic Immune Dysfunction In African-Americans With Small Vessel-Type Ischemic Stroke, Candice M. Brown, Cheryl D. Bushnell, Gregory P. Samsa, Larry B. Goldstein, Carol A. Colton

Neurology Faculty Publications

The incidence of small vessel-type (lacunar) ischemic strokes is greater in African-Americans compared to whites. The chronic inflammatory changes that result from lacunar stroke are poorly understood. To elucidate these changes, we measured serum inflammatory and thrombotic biomarkers in African-Americans at least 6 weeks post-stroke compared to control individuals. Cases were African-Americans with lacunar stroke (n = 30), and controls were age-matched African-Americans with no history of stroke or other major neurologic disease (n = 37). Blood was obtained > 6 weeks post-stroke and was analyzed for inflammatory biomarkers. Freshly isolated peripheral blood mononuclear cells were stimulated with lipopolysaccharide …

Meta-Analysis Of Dna Methylation And Expression In Liver Cancer Patients, Daniele Todorov, Barbara Stefanska, Katarzyna Lubecka-Pietruszewska

The Summer Undergraduate Research Fellowship (SURF) Symposium

Hepatocellular carcinoma (HCC), the most common liver cancer, is the second leading cause of cancer-related death worldwide. HCC is often diagnosed at late stages, for which there are no effective chemotherapies. Biomarkers unique to HCC patients could be used to detect HCC early and improve treatment. In the present project, we have performed a meta-analysis to compare the gene-specific DNA methylation and gene expression patterns of HCC patients as reported by four independent studies. Our goal was to discover the strongest changes that distinguish HCC from normal tissue. The relationship between methylation and expression in HCC was examined and genes …

Investigation Of Rice Bran Derived Anti-Cancer Pentapeptide For Mechanistic Potency In Breast Cancer Cell Models, Ruiqi Li

Graduate Theses and Dissertations

Bioactive peptides derived from food sources with anti-proliferative properties against cancer have drawn more attention in recent years. A pentapeptide derived from rice bran has shown anti-proliferative propertiesagainst human breast cancer cells. The objective of this study was to investigate the mechanistic action of the pentapeptide-induced apoptosis in breast cancer cell models (MCF-7 and MDA-MB-231). The growth inhibition activity of the pentapeptide was

evaluated by MTS[3-(4,5-dimethylthiazol-2-yl)-5-(3- arboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assayand trypan blue assay in a dose- and time-dependent manner.

The apoptotic properties of pentapeptide-induced apoptosis on cancerous breast cells were evaluated by morphological changes, DNA fragmentation, and caspases-3/7, -8,and -9 …

Maldi Mass Spectrometry Imaging For The Discovery Of Prostate Carcinoma Biomarkers, Lisa Harris Cazares

Theses and Dissertations in Biomedical Sciences

The elucidation of new biological markers of prostate cancer (PCa) should aid in the detection, and prognosis of this disease. Diagnostic decision making by pathologists in prostate cancer is highly dependent on tissue morphology. The ability to localize disease-specific molecular changes in tissue would help improve this critical pathology decision making process. Direct profiling of proteins in tissue sections using MALDI imaging mass spectrometry (MALDI-IMS) has the power to link molecular detail to morphological and pathological changes, enhancing the ability to identify candidates for new specific biomarkers. However, critical questions remain regarding the integration of this technique with clinical decision …