Medicine and Health Sciences Commons^™

Partner Influence In Diet And Exercise Behaviors: Testing Behavior Modeling, Social Control, And Normative Body Size, Brea Perry, Gabriele Ciciurkaite, Christy Freadreacea Brady, Justin Garcia

Sociology Faculty Publications

Previous research has documented social contagion in obesity and related health behaviors, but less is known about the social processes underlying these patterns. Focusing on married or cohabitating couples, we simultaneously explore three potential social mechanisms influencing obesity: normative body size, social control, and behavior modeling. We analyze the association between partner characteristics and the obesity-related health behaviors of focal respondents, comparing the effects of partners’ body type, partners’ attempts to manage respondents’ eating behaviors, and partners’ own health behaviors on respondents’ health behaviors (physical activity, fruit and vegetable consumption, and fast food consumption). Data on 215 partners are extracted …

Alcohol Use And Strenuous Physical Activity In College Students: A Longitudinal Test Of 2 Explanatory Models Of Health Behavior, Heather A. Davis, Elizabeth N. Riley, Gregory T. Smith, Richard S. Milich, Jessica L. Burris

Psychology Faculty Publications

Objective: To help clarify the effect of gender on the bidirectional relationship between alcohol use and strenuous physical activity in college students. Participants: Five hundred twenty-four (52% female) college students recruited in August 2008 and 2009 and followed up in April 2009 and April 2011, respectively. Methods: Participants reported their alcohol use and strenuous physical activity on 2 occasions (baseline and follow-up) spaced approximately 1 or 2 years apart. Results: For females, alcohol use quantity at baseline was associated with increased strenuous physical activity at 1- and 2-year follow-ups, and alcohol use frequency at baseline was …

The Carrot And The Stick? Strategies To Improve Compliance With College Campus Tobacco Policies, Amanda Fallin-Bennett, Maria Roditis, Stanton A. Glantz

Nursing Faculty Publications

Objective: Tobacco-free policies are being rapidly adopted nationwide, yet compliance with these policies remains a challenge. This study explored college campus key informants' experiences with tobacco policies, and their perceived benefits, drawbacks, and outcomes. Participants: The sample for this study was 68 key informants representing 16 different California universities with varying tobacco policies (no smoking indoors and within 20 feet of entrances, designated smoking areas, 100% smoke-free, and 100% tobacco-free). Methods: Qualitative, descriptive study. Semistructured interviews were transcribed verbatim and analyzed using content analysis. Results: Strategies to improve compliance ranged from a social approach to a …

Dna Methylation Signatures Of Chronic Low-Grade Inflammation Are Associated With Complex Diseases, Symen Ligthart, Carola Marzi, Stella Aslibekyan, Michael M. Mendelson, Karen N. Conneely, Toshiko Tanaka, Elena Colicino, Lindsay L. Waite, Roby Joehanes, Weihua Guan, Jennifer A. Brody, Cathy Elks, Riccardo Marioni, Min A. Jhun, Golareh Agha, Jan Bressler, Cavin K. Ward-Caviness, Brian H. Chen, Tianxiao Huan, Kelly Bakulski, Elias L. Salfati, Whi-Empc Investigators, Giovanni Fiorito, Charge Epigenetics Of Coronary Heart Disease, Simone Wahl, Katharina Schramm, Jin Sha, Dena G. Hernandez, Allan C. Just, Jennifer A. Smith, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation.

Results: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P < 1.15 × 10^–7) in the discovery panel …

Self-Reported Sleep Apnea And Dementia Risk: Findings From The Prevention Of Alzheimer's Disease With Vitamin E And Selenium Trial, Xiuhua Ding, Richard J. Kryscio, Joshua Turner, Gregory A. Jicha, Gregory E. Cooper, Allison M. Caban-Holt, Frederick A. Schmitt, Erin L. Abner

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVES: To investigate the association between baseline sleep apnea and risk of incident dementia in the Prevention of Alzheimer's Disease with Vitamin E and Selenium (PREADViSE) study and to explore whether the association depends on apolipoprotein E (APOE) ɛ4 allele status.

DESIGN: Secondary analysis based on data collected during PREADViSE.

SETTING: Participants were assessed at 128 local clinical study sites during the clinical trial phase and later were followed by telephone from a centralized location.

PARTICIPANTS: Men enrolled in PREADViSE (without dementia or other active neurological conditions that affect cognition such as major psychiatric disorders, including depression; N = …

Farm Work Injuries Among A Cohort Of Children In Kentucky, Usa, Steven R. Browning, Susan C. Westneat, Deborah B. Reed

Epidemiology and Environmental Health Faculty Publications

Children residing on farms with livestock may be at an increased risk for work-related injuries, compared to children who work on other commodity farms. This study characterizes children's work tasks on Kentucky farms and assesses whether children who work on beef cattle farms are at an increased risk for farm work injuries. The results of a cohort study of children aged 5-18 years (N=999 at baseline) working on family farms in Kentucky, followed for two consecutive years after an initial enumeration five years previously, found that 70% of the children were involved in animal-related chores. Across all age groups, children …

Analysis Of Rna Expression Of Normal And Cancer Tissues Reveals High Correlation Of Cop9 Gene Expression With Respiratory Chain Complex Components, Christina A. Wicker, Tadahide Izumi

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: The COP9 signalosome, composed of eight subunits, is implicated in cancer genetics with its deneddylase activity to modulate cellular concentration of oncogenic proteins such as IkB and TGFβ. However, its function in the normal cell physiology remains elusive. Primarily focusing on gene expression data of the normal tissues of the head and neck, the cancer genome atlas (TCGA) database was used to identify groups of genes that were expressed synergistically with the COP9 genes, particularly with the COPS5 (CSN5), which possesses the catalytic activity of COP9.

RESULTS: Expressions of seven of the COP9 genes (COPS2, COPS3, COPS4, COPS5, COPS6, …

Genomics And Csf Analyses Implicate Thyroid Hormone In Hippocampal Sclerosis Of Aging, Peter T. Nelson, Yuriko Katsumata, Kwangsik Nho, Sergey C. Artiushin, Gregory A. Jicha, Wang-Xia Wang, Erin L. Abner, Andrew J. Saykin, Walter A. Kukull, Alzheimer’S Disease Neuroimaging Initiative (Adni), David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

We report evidence of a novel pathogenetic mechanism in which thyroid hormone dysregulation contributes to dementia in elderly persons. Two single nucleotide polymorphisms (SNPs) on chromosome 12p12 were the initial foci of our study: rs704180 and rs73069071. These SNPs were identified by separate research groups as risk alleles for non-Alzheimer’s neurodegeneration. We found that the rs73069071 risk genotype was associated with hippocampal sclerosis (HS) pathology among people with the rs704180 risk genotype (National Alzheimer’s Coordinating Center/Alzheimer’s Disease Genetic Consortium data; n = 2113, including 241 autopsy-confirmed HS cases). Furthermore, both rs704180 and rs73069071 risk genotypes were associated with widespread brain …

Correlates Of Sexual-Risk Behaviors Among Young Black Msm: Implications For Clinic-Based Counseling Programs, Richard A. Crosby, Leandro Mena, Janelle M. Ricks

Health, Behavior & Society Faculty Publications

This study applied an 8-item index of recent sexual-risk behaviors to young Black men who have sex with men (YBMSM) and evaluated the distribution for normality. The distribution was tested for associations with possible antecedents of sexual risk. YBMSM (N = 600), aged 16–29 years, were recruited from a sexually transmitted infection clinic, located in the southern US. Men completed an extensive audio computer-assisted self-interview. Thirteen possible antecedents of sexual risk, as assessed by the index, were selected for analyses. The 8-item index formed a normal distribution with a mean of 4.77 (SD = 1.77). In adjusted analyses, not …

Subjective Report Of Side Effects Of Prescribed And Nonprescribed Psychostimulant Use In Young Adults, Tess E. Smith, Michelle M. Martel, Alan D. Desantis

Psychology Faculty Publications

Background: Side effects of prescribed and nonprescribed psychostimulant use are understudied. Objectives: The study examined side effects of prescribed and nonprescribed psychostimulant use in a college sample with attention to possible gender differences. Methods: 2716 undergraduates (1448 male) between the ages of 17 and 57 years (M = 19.43 years, SD = 1.7 years) completed an online survey that included questions about the subjective side effects of prescribed and nonprescribed psychostimulant use. Results: Results suggested that prescribed users more frequently reported side effects, compared to nonprescribed users. For prescribed users, females more frequently reported appetite, somatic, and anxiety-related side …

Administration Of Electroconvulsive Therapy For Depression Associated With Deep Brain Stimulation In A Patient With Post-Traumatic Parkinson's Disease: A Case Study, Miles G. Cunningham, Golnaz Yadollahikhales, Gordana Vitaliano, Craig Van Horne

Neurosurgery Faculty Publications

Background: Deep brain stimulation (DBS) has been shown to be effective for parkinsonian symptoms poorly responsive to medications. DBS is typically well-tolerated, as are the maintenance battery changes. Here we describe an adverse event during a battery replacement procedure that caused rapid onset of severe depression.

Case Presentation: The patient is a 58-year-old woman who was in a serious motor vehicle accident and sustained a concussion with loss of consciousness. Within weeks of the accident she began developing parkinsonian symptoms that progressively worsened over the subsequent 10 years. Responding poorly to medications, she received DBS, which controlled her movement symptoms. …

Circumcision Status Is Not Associated With Condom Use And Prevalence Of Sexually Transmitted Infections Among Young Black Msm, Richard A. Crosby, Cynthia A. Graham, Leandro Mena, William L. Yarber, Stephanie A. Sanders, Robin R. Milhausen, Angelica Geter

Health, Behavior & Society Faculty Publications

This study investigated whether intact young Black MSM differed from their circumcised counterparts regarding condom use behaviors and perceptions and HIV/Chlamydia/gonorrhea. Young Black MSM completed a self-interview, including a pictorial item assessing circumcision status and measures of condom use. Twenty-seven percent of 388 participants reported not being circumcised. With one exception, no associations tested approached significance. The mean frequency of unprotected insertive anal sex for circumcised men was about twice as high compared to those intact (P = .04). Intact young Black MSM did not differ from circumcised men relative to prevalence of STIs (including HIV) or condom use behaviors …

Accuracy Of Name And Age Data Provided About Network Members In A Social Network Study Of People Who Use Drugs: Implications For Constructing Sociometric Networks, April M. Young, Abby E. Rudolph, Amanda E. Su, Lee King, Susan Jent, Jennifer R. Havens

Epidemiology and Environmental Health Faculty Publications

Purpose—Network analysis has become increasingly popular in epidemiologic research, but the accuracy of data key to constructing risk networks is largely unknown. Using network data from people who use drugs (PWUD), the study examined how accurately PWUD reported their network members’ (i.e., alters’) names and ages.

Methods—Data were collected from 2008 to 2010 from 503 PWUD residing in rural Appalachia. Network ties (n=897) involved recent (past 6 months) sex, drug co-usage, and/or social support. Participants provided alters’ names, ages, and relationship-level characteristics; these data were cross-referenced to that of other participants to identify participant-participant relationships and to determine …

Effects Of Target-Controlled Infusion Of High-Dose Naloxone On Pain And Hyperalgesia In A Human Thermal Injury Model: A Study Protocol, Anders D. Springborg, Elisabeth K. Jensen, Bradley K. Taylor, Mads U. Werner

Physiology Faculty Publications

Mu-opioid-receptor antagonists have been extensively studied in experimental research as pharmacological tools uncovering mechanisms of pain modulation by the endogenous opioid system. In rodents, administration of high doses of mu-opioid-receptor antagonists after the resolution of an inflammatory injury has demonstrated reinstatement of nociceptive hypersensitivity indicating unmasking of latent sensitization. In a recent human study, pain hypersensitivity assessed as secondary hyperalgesia area (SHA), was reinstated 7 days after a mild thermal injury, in 4 out of 12 subjects after a naloxone infusion.

The aims of the present study are first, to replicate our previous findings in a larger-sized study; second, to …

New Findings, Classification And Long-Term Follow-Up Study Based On Mri Characterization Of Brainstem Encephalitis Induced By Enterovirus 71, Hongwu Zeng, Feiqiu Wen, Wenxian Huang, Yungen Gan, Weibin Zeng, Ranran Chen, Yanxia He, Yonker Wang, Zaiyi Liu, Changhong Liang, Kelvin K. L. Wong

Radiology Faculty Publications

Background To report the diversity of MRI features of brainstem encephalitis (BE) induced by Enterovirus 71. This is supported by implementation and testing of our new classification scheme in order to improve the diagnostic level on this specific disease.

Methods Neuroimaging of 91 pediatric patients who got EV71 related BE were hospitalized between March, 2010 to October, 2012, were analyzed retrospectively. All patients underwent pre- and post-contrast MRI scan. Thereafter, 31 patients were randomly called back for follow-up MRI study during December 2013 to August 2014. The MRI signal patterns of BE primary lesion were analyzed and classified according to …

P70s6k1 (S6k1)-Mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I Γ Degradation And Cell Invasion, Naser Jafari, Qiaodan Zheng, Liqing Li, Wei Li, Lei Qi, Jianyong Xiao, Tianyan Gao, Cai Huang

Markey Cancer Center Faculty Publications

Phosphatidylinositol 4-phosphate 5-kinase type I γ (PIPKIγ90) ubiquitination and subsequent degradation regulate focal adhesion assembly, cell migration, and invasion. However, it is unknown how upstream signals control PIPKIγ90 ubiquitination or degradation. Here we show that p70S6K1 (S6K1), a downstream target of mechanistic target of rapamycin (mTOR), phosphorylates PIPKIγ90 at Thr-553 and Ser-555 and that S6K1-mediated PIPKIγ90 phosphorylation is essential for cell migration and invasion. Moreover, PIPKIγ90 phosphorylation is required for the development of focal adhesions and invadopodia, key machineries for cell migration and invasion. Surprisingly, substitution of Thr-553 and Ser-555 …

Plant Expression Of Cocaine Hydrolase-Fc Fusion Protein For Treatment Of Cocaine Abuse, Guojun Wang, Ting Zhang, Haifeng Huang, Shurong Hou, Xiabin Chen, Fang Zheng, Chang-Guo Zhan

Molecular Modeling and Biopharmaceutical Center Faculty Publications

BACKGROUND: A recently reported cocaine hydrolase (CocH3) fused with fragment crystallizable (Fc) region of human immunoglobulin G1, denoted as CocH3-Fc, is known as a promising therapeutic candidate for the treatment of cocaine overdose and addiction. A challenge for practical therapeutic use of this enzyme exists in the large-scale protein production and, therefore, it is interesting to identify a low-cost and feasible, sustainable source of CocH3-Fc production.

RESULTS: CocH3-Fc was transiently expressed in plant Nicotiana benthamiana leaves. The plant-expressed protein, denoted as pCocH3-Fc, was as active as that expressed in mammalian cells both in vitro and in vivo. However, compared to …

Pleckstrin Homology (Ph) Domain Leucine-Rich Repeat Protein Phosphatase Controls Cell Polarity By Negatively Regulating The Activity Of Atypical Protein Kinase C, Xiaopeng Xiong, Xin Li, Yang-An Wen, Tianyan Gao

Markey Cancer Center Faculty Publications

The proper establishment of epithelial polarity allows cells to sense and respond to signals that arise from the microenvironment in a spatiotemporally controlled manner. Atypical PKCs (aPKCs) are implicated as key regulators of epithelial polarity. However, the molecular mechanism underlying the negative regulation of aPKCs remains largely unknown. In this study, we demonstrated that PH domain leucine-rich repeat protein phosphatase (PHLPP), a novel family of Ser/Thr protein phosphatases, plays an important role in regulating epithelial polarity by controlling the phosphorylation of both aPKC isoforms. Altered expression of PHLPP1 or PHLPP2 disrupted polarization of Caco2 cells grown in 3D cell cultures …

Sphingosine 1-Phosphate Activation Of Egfr As A Novel Target For Meningitic Escherichia Coli Penetration Of The Blood-Brain Barrier, Xiangru Wang, Ravi Maruvada, Andrew J. Morris, Jun O. Liu, Michael J. Wolfgang, Dong Jae Baek, Robert Bittman, Kwang Sik Kim

Internal Medicine Faculty Publications

Central nervous system (CNS) infection continues to be an important cause of mortality and morbidity, necessitating new approaches for investigating its pathogenesis, prevention and therapy. Escherichia coli is the most common Gram-negative bacillary organism causing meningitis, which develops following penetration of the blood–brain barrier (BBB). By chemical library screening, we identified epidermal growth factor receptor (EGFR) as a contributor to E. coli invasion of the BBB in vitro. Here, we obtained the direct evidence that CNS-infecting E. coli exploited sphingosine 1-phosphate (S1P) for EGFR activation in penetration of the BBB in vitro and in vivo. We …

Defining And Targeting Health Disparities In Chronic Obstructive Pulmonary Disease, Roy A. Pleasants, Isaretta L. Riley, David M. Mannino

Preventive Medicine and Environmental Health Faculty Publications

The global burden of chronic obstructive pulmonary disease (COPD) continues to grow in part due to better outcomes in other major diseases and in part because a substantial portion of the worldwide population continues to be exposed to inhalant toxins. However, a disproportionate burden of COPD occurs in people of low socioeconomic status (SES) due to differences in health behaviors, sociopolitical factors, and social and structural environmental exposures. Tobacco use, occupations with exposure to inhalant toxins, and indoor biomass fuel (BF) exposure are more common in low SES populations. Not only does SES affect the risk of developing COPD and …

Tgf-Β Signaling: New Insights Into Aortic Aneurysms, Sean E. Thatcher

Pharmacology and Nutritional Sciences Faculty Publications

No abstract provided.

Talin2-Mediated Traction Force Drives Matrix Degradation And Cell Invasion, Lei Qi, Naser Jafari, Xiang Li, Zaozao Chen, Liqing Li, Vesa P. Hytönen, Benjamin T. Goult, Chang-Guo Zhan, Cai Huang

Markey Cancer Center Faculty Publications

Talin binds to β-integrin tails to activate integrins, regulating cell migration, invasion and metastasis. There are two talin genes, TLN1 and TLN2, encoding talin1 and talin2, respectively. Talin1 regulates focal adhesion dynamics, cell migration and invasion, whereas the biological function of talin2 is not clear and, indeed, talin2 has been presumed to function redundantly with talin1. Here, we show that talin2 has a much stronger binding to β-integrin tails than talin1. Replacement of talin2 Ser339 with Cys significantly decreased its binding to β1-integrin tails to a level comparable to that of talin1. Talin2 localizes at invadopodia and is indispensable …

Walking Performance Is Positively Correlated To Calf Muscle Fiber Size In Peripheral Artery Disease Subjects, But Fibers Show Aberrant Mitophagy: An Observational Study, Sarah H. White, Mary M. Mcdermott, Robert L. Sufit, Kate Kosmac, Alex W. Bugg, Marta Gonzalez-Freire, Luigi Ferrucci, Lu Tian, Lihui Zhao, Ying Gao, Melina R. Kibbe, Michael H. Criqui, Christiaan Leeuwenburgh, Charlotte A. Peterson

Physical Therapy Faculty Publications

Background: Patients with lower extremity peripheral artery disease (PAD) have decreased mobility, which is not fully explained by impaired blood supply to the lower limb. Additionally, reports are conflicted regarding fiber type distribution patterns in PAD, but agree that skeletal muscle mitochondrial respiration is impaired.

Methods: To test the hypothesis that reduced muscle fiber oxidative activity and type I distribution are negatively associated with walking performance in PAD, calf muscle biopsies from non-PAD (n = 7) and PAD participants (n = 26) were analyzed immunohistochemically for fiber type and size, oxidative activity, markers of autophagy, and capillary density. Data were …

Reduced Efficacy Of Anti-AΒ Immunotherapy In A Mouse Model Of Amyloid Deposition And Vascular Cognitive Impairment Comorbidity, Erica M. Weekman, Tiffany L. Sudduth, Carly N. Caverly, Timothy J. Kopper, Oliver W. Phillips, David K. Powell, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Vascular cognitive impairment and dementia (VCID) is the second most common form of dementia behind Alzheimer's disease (AD). It is estimated that 40% of AD patients also have some form of VCID. One promising therapeutic for AD is anti-Aβ immunotherapy, which uses antibodies against Aβ to clear it from the brain. While successful in clearing Aβ and improving cognition in mice, anti-Aβ immunotherapy failed to reach primary cognitive outcomes in several different clinical trials. We hypothesized that one potential reason the anti-Aβ immunotherapy clinical trials were unsuccessful was due to this high percentage of VCID …

Airway Secretory Micrornaome Changes During Rhinovirus Infection In Early Childhood, Maria J. Gutierrez, Jose L. Gomez, Geovanny F. Perez, Krishna Pancham, Stephanie Val, Dinesh K. Pillai, Mamta Giri, Sarah Ferrante, Robert Freishtat, Mary C. Rose, Diego Preciado, Gustavo Nino

Pediatrics Faculty Publications

Background Innate immune responses are fine-tuned by small noncoding RNA molecules termed microRNAs (miRs) that modify gene expression in response to the environment. During acute infections, miRs can be secreted in extracellular vesicles (EV) to facilitate cell-to-cell genetic communication. The purpose of this study was to characterize the baseline population of miRs secreted in EVs in the airways of young children (airway secretory microRNAome) and examine the changes during rhinovirus (RV) infection, the most common cause of asthma exacerbations and the most important early risk factor for the development of asthma beyond childhood.

Methods Nasal airway secretions were obtained from …

Increasing Incidence Within Pubmed Of The Use Of The Misspelling "Pruritis" (Sic) Instead Of "Pruritus" For Itch, Alan B. Fleischer Jr.

Surgery Faculty Publications

Writers generally benefit from word processing technology, and the use of other forms of formal writing such as typewriters is archaic. The first stand-alone spell checker programs originated in the early 1980s, and by 1995 they were embedded within word processing programs such as Word 95 (1). With the ubiquity of such software, spelling errors in the medical literature should be extinct. Yet, as a reader of the medical literature with an interest in itch, this author is impressed with the numbers of misspellings of the word «pruritus.» The word pruritus is derived from the Latin pruritus, past participle …

Putting Parity Into Practice – Integrating Opioid-Use Disorder Treatment Into The Hospital Setting, Laura Fanucchi, Michelle R. Lofwall

Center for Health Services Research Faculty Publications

No abstract provided.

Living With Traumatic Brain Injury In A Rural Setting: Supports And Barriers Across The Continuum Of Care, Anne L. Harrison, Elizabeth G. Hunter, Heather Thomas, Paige Bordy, Erin Stokes, Patrick H. Kitzman

Physical Therapy Faculty Publications

Purpose: Traumatic brain injury (TBI) is prevalent in Kentucky and comes with a high cost in care and quality of life for individuals and caregivers affected. Many people living with the condition of TBI have unmet needs. Research among people living with TBI in rural areas is limited. The purposes of this study were to (1) increase understanding of the lived experience of people with TBI and caregivers in rural regions of Kentucky across the continuum of their care and (2) provide their perspectives on barriers and facilitators of optimal function and well-being.

Methods: A qualitative descriptive interview study was …

Integrated Molecular Pathway Analysis Informs A Synergistic Combination Therapy Targeting Pten/Pi3k And Egfr Pathways For Basal-Like Breast Cancer, Qing-Bai She, Sofia K. Gruvberger-Saal, Matthew Maurer, Yilun Chen, Mervi Jumppanen, Tao Su, Meaghan Dendy, Ying-Ka Ingar Lau, Lorenzo Memeo, Hugo M. Horlings, Marc J. Van De Vijver, Jorma Isola, Hanina Hibshoosh, Neal Rosen, Ramon Parsons, Lao H. Saal

Markey Cancer Center Faculty Publications

Background: The basal-like breast cancer (BLBC) subtype is characterized by positive staining for basal mammary epithelial cytokeratin markers, lack of hormone receptor and HER2 expression, and poor prognosis with currently no approved molecularly-targeted therapies. The oncogenic signaling pathways driving basal-like tumorigenesis are not fully elucidated.

Methods: One hundred sixteen unselected breast tumors were subjected to integrated analysis of phosphoinositide 3-kinase (PI3K) pathway related molecular aberrations by immunohistochemistry, mutation analysis, and gene expression profiling. Incidence and relationships between molecular biomarkers were characterized. Findings for select biomarkers were validated in an independent series. Synergistic cell killing in vitro and in vivo tumor …

Elevated Integrin Α6Β4 Expression Is Associated With Venous Invasion And Decreased Overall Survival In Non-Small Cell Lung Cancer, Rachel L. Stewart, Dava West, Chi Wang, Heidi L. Weiss, Tamas S. Gal, Eric B. Durbin, William O'Connor, Min Chen, Kathleen L. O'Connor

Pathology and Laboratory Medicine Faculty Publications

Lung cancer carries a poor prognosis and is the most common cause of cancer-related death worldwide. The integrin α6β4, a laminin receptor, promotes carcinoma progression in part by cooperating with various growth factor receptors to facilitate invasion and metastasis. In carcinoma cells with mutant TP53, the integrin α6β4 promotes cell survival. TP53 mutations and integrin α6β4 overexpression co-occur in many aggressive malignancies. Because of the high frequency of TP53 mutations in lung squamous cell carcinoma (SCC), we sought to investigate the association of integrin β4 expression with clinicopathologic features and survival in non–small cell lung cancer (NSCLC). We constructed …