Pharmacy and Pharmaceutical Sciences Commons^™

Impact Of Medicare Reimbursement Policy Change On The Utilization, Risks, And Costs Associated With Erythropoiesis-Stimulating Agents In Cancer Patients With Chemotherapy-Induced Anemia, Minghui Li

Theses and Dissertations

Background: Erythropoiesis-stimulating agents (ESAs) are biological drugs used to stimulate the production of red blood cells. ESAs are commonly prescribed for cancer patients with chemotherapy-induced anemia and chronic kidney disease (CKD) patients with low levels of hemoglobin. Due to the increasing safety concerns, Centers for Medicare and Medicaid Services (CMS) issued a Medicare reimbursement policy change for ESAs in cancer patients to regulate the utilization of ESAs. For chemotherapy-induced anemia, when patients had solid tumors, multiple myeloma, lymphoma, or lymphocytic leukemia, ESA treatment is reimbursable by CMS only when the hemoglobin level is < 10g/dL.

Objectives: The objectives of this study were …

Chlor-Amidine, A Novel Pad Inhibitor, As An Effective Drug For The Treatment Of Ulcerative Colitis And Prevention Of Colorectal Cancer, Erin Witalison

Theses and Dissertations

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that affects the quality of life of millions of patients worldwide. This disease is associated with inflammation and ulceration of the colonic epithelium, leading to an increased risk for the development of UC-associated colorectal cancer (CRC). Current UC medications are designed to manage the symptoms and induce remission; however, several challenges are faced with current treatment options. 5-aminosalicyclic acid and corticosteroids have few side effects, but have limited efficacy and often the disease becomes refractory. Biologics are introduced after initial treatments fail, but serious side effects are often associated with these …

The Effect Of Depression And Antidepressants On Cost, Survival And Adherence To Hormone Therapy In Breast Cancer, Virginia Noxon

Theses and Dissertations

Introduction: Breast cancer patients with a depression diagnosis before or after cancer diagnosis have increased cost, shorter survival time and reduced adherence to hormone therapy. Treating depression in these patients should improve these outcomes; however, there is scarce literature on this topic. Currently, no study has determined the association of concurrent depression while adjusting for a history of depression or treating depression with antidepressants with cost, survival and adherence to hormone therapy. This study has two objectives: 1) to determine the association of concurrent depression with cost, survival and adherence to hormone therapy adjusting for a history of depression 2) …

Prediction Of Fluoroquinolone Resistance In Gram-Negative Bacteria Causing Bloodstream Infections, Seejil Dan, Ansal Shah, Julie Ann Justo, P Brandon Bookstaver, Joseph Kohn, Helmut Albrecht, Majdi N. Al-Hasan

Faculty Publications

Increasing rates of fluoroquinolone resistance (FQ-R) have limited empirical treatment options for Gram-negative infections, particularly in patients with severe beta-lactam allergy. This case-control study aims to develop a clinical risk score to predict the probability of FQ-R in Gram-negative bloodstream isolates. Adult patients with Gram-negative bloodstream infections (BSI) hospitalized at Palmetto Health System in Columbia, South Carolina, from 2010 to 2013 were identified. Multivariate logistic regression was used to identify independent risk factors for FQ-R. Point allocation in the fluoroquinolone resistance score (FQRS) was based on regression coefficients. Model discrimination was assessed by the area under receiver operating characteristic curve …

Multifunctional Nanocarriers For Cancer Therapy, Bei Cheng

Theses and Dissertations

Cancer is one of the leading causes of human mortality and mortality in all diseases. There has been a boost in developing nanocarrier-based therapies for treating cancer or other diseases during the past decade. One of the major advantages about nanocarrier (with the size range from 1-1000 nm) lies in its ability to specifically target tumor and maximize drug accumulation in tumor foci through the enhanced permeability and retention effect. Advancement in nanotechnology has opened a new paradigm in pharmaceutical field. But new challenges have to be overcome in order to fully exploit the technology and improve safety in clinical …

Selectivity Targeting Polo-Like Kinase 1 (Plk1) Using Novel Inhibitors Of The Polo-Box Domain, Merissa Lynnea Baxter

Theses and Dissertations

Polo-like Kinse 1 (PLK1) is a serine/threonine protein kinase that is expressed in dividing cells. It is a widely studied protein that plays an important role in regulating mitotic progression. PLK1 is over-expressed in several tumor types, and studies have shown that down-regulating PLK1 expression inhibits cancer cell proliferation, validating PLK1 as an oncotarget. Efforts to target this protein therapeutically has led to the development of several ATP-based inhibitors, although these are not exclusively specific. Because other PLK family members are tumor suppressors, it is important that PLK1 inhibitors selectively bind to PLK1 and not the other PLKs, particularly PLK3. …

Stimuli Responsive Nanoparticle For Cancer Targeted Therapy, Huacheng He

Theses and Dissertations

Nanoparticle is the particle with a size in the range from several nanometers to hundreds of nanometers. It has been extensively used for cancer diagnosis and therapy. However, it is still a great challenge to fabricate nanoparticles with spatiotemporally controllable delivery of anticancer drugs to tumors and with high therapeutic efficacy. This thesis mainly focuses on the development of stimuli responsive nanoparticles for cancer targeted therapy. These nanoparticles either response to internal stimuli such as pH and redox potential or external stimuli like temperature and light could effectively target tumors and control the release of anticancer drugs there to improve …

High-Throughput Sequencing-Based Approaches For The Identification And Development Of Molecular Targets For Cancer Therapy, David Joel Oliver

Theses and Dissertations

Effective cancer treatment depends on the development of therapeutics that efficiently eliminate the disease without significant reduction to quality of life. Targeted therapeutics achieve these goals, but their long-term efficacy is limited by the ability of cancers to become resistant to these therapies over time. The identification of new therapeutic targets is crucial for the future of cancer treatment. In this work we present functional identification and characterization of novel targets for cancer therapy.

Loss-of-function screens are a well-founded approach for the functional identification of new therapeutic targets, and, in combination with high-throughput sequencing technology, can now be performed at …

Identification Of Novel Genes That Regulate Androgen Receptor Signaling And Growth Of Androgen-Deprived Prostate Cancer Cells, Elina Levina, Hao Ji, Mengqiang Chen, Mirza Baig, David Oliver, Patrice Ohouo, Chang-Uk Lim, Garry Schools, Steven Carmack, Ye Ding, Eugenia Broude, Igor Roninson, Ralph Buttyan, Michael Shtutman

Faculty Publications

Prostate cancer progression to castration refractory disease is associated with anomalous transcriptional activity of the androgen receptor (AR) in an androgen-depleted milieu. To identify novel gene products whose downregulation transactivates AR in prostate cancer cells, we performed a screen of enzymatically-generated shRNA lenti-libraries selecting for transduced LNCaP cells with elevated expression of a fluorescent reporter gene under the control of an AR-responsive promoter. The shRNAs present in selected populations were analyzed using high-throughput sequencing to identify target genes. Highly enriched gene targets were then validated with siRNAs against selected genes, testing first for increased expression of luciferase from an AR-responsive …

Stratification Of The Impact Of Inappropriate Empirical Antimicrobial Therapy For Gram-Negative Bloodstream Infections By Predicted Prognosis, Sarah E. Cain, Joseph Kohn, P. Brandon Bookstaver, Helmut Albrecht, Majdi N. Al-Hasan

Faculty Publications

The bloodstream infection mortality risk score (BSIMRS) predicts the outcome of patients with Gram-negative bloodstream infections (BSI) with high discrimination. This retrospective cohort study examined the impact of inappropriate antimicrobial therapy on mortality in adult patients with Gram-negative BSI admitted to Palmetto Health Hospitals in Columbia, SC, USA, from 1 January 2011 to 31 December 2012 after stratification by predicted prognosis at initial presentation using BSIMRS. A multivariate Cox regression model was used to identify independent risk factors for 28-day mortality overall and within each predefined BSIMRS category (<5, 5 to 9, and ≥10). Relative risk reduction (RRR), absolute risk reduction (ARR), and number needed to treat (NNT) were calculated from a predictive logistic regression model of mortality. Overall, 390 unique patients with first episodes of Gram-negative BSI were identified. The median age was 66 years, and 229 (59%) were women. There was significant association between inappropriate antimicrobial therapy and mortality in patients with BSIMRS of 5 to 9 (adjusted hazard ratio [aHR], 3.55; 95% confidence intervals [CI], 1.22 to 8.31; P = 0.02) and BSIMRS of ≥10 (aHR, 4.99; 95% CI, 1.09 to 22.87; P = 0.04) but not in those with BSIMRS of <5 (aHR, 3.34; 95% CI, 0.17 to 22.77; P = 0.34). RRR, ARR, and NNT were 0.25, 0.02, and 63 for BSIMRS of <5; 0.56, 0.32, and 3 for BSIMRS of 5 to 9; and 0.39, 0.39, and 3 for BSIMRS of ≥10, respectively. There is a significant benefit from appropriate antimicrobial therapy in patients with Gram-negative BSI with guarded (BSIMRS of 5 to 9) and poor (BSIMRS of ≥10) predicted prognosis. Survival difference remains unclear among those with good predicted prognosis (BSIMRS of <5) at initial presentation.

Molecular Mechanisms Underlying Environmental Enrichment-Induced Neuroprotection In Vulnerability To Nicotine Addiction, Adrian Michael Gomez

Theses and Dissertations

Tobacco use is the number one preventable cause of death in the world. Nicotine is the principal, addictive component in tobacco responsible for its reinforcing properties that drive the behavioral manifestations of nicotine addiction. Environment is becoming increasingly implicated in nicotine susceptibility. However, the molecular mechanisms that underlie susceptibility to nicotine addiction remain unknown. An ideal animal model that addresses environmental factors uses rats raised in an enriched condition (EC), a standard condition (SC), and an impoverished condition (IC); which differ in novelty, social cohorts, handling, and physical activity. EC rats exhibit a neuroprotective-like phenotype in the behavioral resistance to …

Design And Development Of A Novel Class Of Cell Cycle Cdk Inhibitors Targeting The Cyclin Binding Groove Utilizing The Replace Strategy, Padmavathy Nandha Premnath

Theses and Dissertations

Inhibition of CDK2 activity in G1 and S phases of the cell cycle can promote selective apoptosis of cancer cells through the E2F1 pathway. Currently available CDK inhibitors target the ATP binding pocket and result in lack of specificity for the cell cycle vs. the transcriptional CDKs. It has been shown that a peptide HAKRRLIF derived from the tumor suppressor p21 binds to the cyclin binding groove (CBG) and selectively inhibits cell cycle CDKs (CDK2/Cyclin A, CDK2/Cyclin E and CDK4/Cyclin D). The CBG is unique to cell cycle CDKs hence targeting this site avoids the inhibition of transcriptional CDKs can …

Musculoskeletal Safety Outcomes Of Patients Receiving Daptomycin With Hmg-Coa Reductase Inhibitors, Christopher M. Bland, P Brandon Bookstaver, Z Kevin Lu, Brianne L. Dunn, Kathey Fulton Rumley

Faculty Publications

Daptomycin, a cyclic lipopeptide antibiotic, and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are commonly administered in the inpatient setting and are associated with creatine phosphokinase (CPK) elevations, myalgias, and muscle weakness. Safety data for coadministration of daptomycin with statins are limited. To determine the safety of coadministration of daptomycin with statin therapy, a multicenter, retrospective, observational study was performed at 13 institutions in the Southeastern United States. Forty-nine adult patients receiving statins concurrently with daptomycin were compared with 171 patients receiving daptomycin without statin therapy. Detailed information, including treatment indication and duration, infecting pathogen, baseline and subsequent CPK levels, and …

Six1 Overexpression Promotes Epithelial– Mesenchymal Transition And Malignant Progression In Models Of Cervical And Colon Cancer, Hanwen Xu

Theses and Dissertations

Inappropriate expression of embryonic genes, particularly homeodomain transcription factors, contributes to tumorigenesis and tumor progression. The overexpression of Six1, a member of the Six family of homeodomain transcription factors, has been found in various human cancers, and is associated with tumor progression and metastasis. We have previously determined that the expression of SIX1 mRNA increased during in vitro progression of human papillomavirus type 16 (HPV16)- immortalized human keratinocytes (HKc/HPV16) toward a differentiation-resistant (HKc/DR) phenotype. However, the mechanism(s) of how Six1 promotes HPV16- mediated transformation remain unknown. In this study, we explored the role of Six1 at early stages and late …

Investigation Of The Response And Repair Of Replication, Kathryn Brady

Theses and Dissertations

When a mammalian cell suffers DNA damage, DNA damage signaling responses and repair pathways are invoked. The phosphorylation of histone variant H2AX (γH2AX) and of replication protein A (pRPA) are two well-documented damage signals, marking double strand breaks and stalled replication forks, respectively. Inhibitors of thymidylate synthase (TS) and ribonucleotide reductase (RNR) are chemotherapeutics that act by depriving cells of the deoxynucleotides necessary for DNA synthesis, which causes damage. The response and repair pathways activated by these chemotherapeutics have been studied for a number of years but there remain unanswered questions as to how cancer cells perceive this damage, the …

Effects Of Hiv-1 Tat Protein On Structure, Function And Trafficking Of The Dopamine Transporter, Narasimha Murty Midde

Theses and Dissertations

The alarming rise in HIV-1 associated neurocognitive disorder (HAND) is, at least in part, associated with HIV-1 viral proteins shed from infected macrophages, including transactivator of transcription (Tat) despite the success of anti-retroviral therapies. The dopamine (DA) system is greatly involved in the progression of HAND and is influenced by psychostimulants like cocaine. The DA transporter (DAT), a key regulator of neurocognitive functions, is a major molecular target for both Tat and cocaine. Our lab previously reported that exposure to Tat decreases DA uptake through allosteric regulation and alters cocaine binding sites in DAT.

In this research project the hypothesis …

Antibiotic Lock Therapy: Review Of Technique And Logistical Challenges, Julie Ann Justo, P Brandon Bookstaver

Faculty Publications

Antibiotic lock therapy (ALT) for the prevention and treatment of catheter-related bloodstream infections is a simple strategy in theory, yet its real-world application may be delayed or avoided due to technical questions and/or logistical challenges. This review focuses on these latter aspects of ALT, including preparation information for a variety of antibiotic lock solutions (ie, aminoglycosides, beta-lactams, fluoroquinolones, folate antagonists, glycopeptides, glycylcyclines, lipopeptides, oxazolidinones, polymyxins, and tetracyclines) and common clinical issues surrounding ALT administration. Detailed data regarding concentrations, additives, stability/compatibility, and dwell times are summarized. Logistical challenges such as lock preparation procedures, use of additives (eg, heparin, citrate, or ethylenediaminetetraacetic …

Role Of Micro Rna 148/152 Family In Cancer Progression, Anusha Chaparala

Theses and Dissertations

Micro RNA are small single stranded RNA that regulate the expression of various genes. MiRNA guide the mRNA disintegrating RISC complex to the complimentary sequence in the target mRNA. Each micro RNA has multiple targets and can play a different biological role depending on the population of targets at the particular stage of the cell or a physiological state. Several miRNA show elevated or decreased levels of expression in various cancers because of their role in tumor initiation and progression. MiRNA belonging to mir148/152 family are examples of such MicroRNA. This family includes miR148a, miR148b and miR152. MiR148a and miR152 …

Effects Of Dna Damage And Cdk Inhibitors On The Nucleoli, Vineet Garg

Theses and Dissertations

The nucleolus is the primary site of ribogenesis and consists of three compartments, namely, fibrillar center (FC), dense fibrillar component (DFC) and granular component (GC). Recent studies have observed a novel structure distinct from these three compartments which forms in the nucleolus upon DNA damage called Intranucleolar body (INoB). Previous studies in our laboratory have found INoBs forming in HT1080 fibrosarcoma cell lines after ectopic overexpression of damage-inducible cell cycle inhibitor p21. This INoB formation has been observed to be decreased by Senexin A which is an inhibitor of transcription regulating kinases CDK8/CDK19.

Here we show that INoB formation correlates …

A Novel Approach To The Design Of Selective Inhibitors For Cell Cycle Cyclin Dependent Kinases, Tracy Perkins

Theses and Dissertations

CDK2/cyclin A and CDK4/cyclin D1 are proven targets for cancer drug discovery. The development of novel CDK inhibitors, with high selectivity, are being investigated by targeting the cyclin binding groove (CBG) located on the cyclin, the regulatory subunit of CDK. The CBG is a shallow area that is involved in signaling and the inhibition of cell cycle CDKs via endogenous tumor suppressors. Currently, non-peptidic inhibitors are being developed based on the recognition amino acid sequence, HAKRRLIF, of the C-terminal peptide sequence of the CDK inhibitor p21WAF1. Computational design and the utilization of non-natural amino acids are being proposed to identify …

K+ Channels And Beta3 Adrenergic Receptors As New Pharmacological Targets For Overactive Bladder Treatment, Serge Amani Yao Afeli

Theses and Dissertations

Overactive bladder (OAB) is a pathophysiological condition which is characterized by the urinary bladder's failure to achieve proper storage of urine. OAB has a tremendous impact on the patient's quality of life by disturbing his sleep, work, and sexual activity. About 17% of Americans are affected with this disease and most patients experience symptoms of urgency, frequent urination, and abnormally elevated detrusor smooth muscle (DSM) contractility. Despite, numerous attempts to treat the disorder in the past with antimuscarinics and now with beta3 adrenergic receptors (beta3-AR agonists), OAB still remains a serious public health issue because the long term efficacy of …

Bioassay Guided Fractionation Of American Ginseng. A Hexane Fraction Of American Ginseng Suppresses Colitis And Associated Colon Cancer. Mechanism Of Action., Deepak Poudyal

Theses and Dissertations

Inflammatory Bowel Disease (IBD) [Ulcerative colitis (UC) and Crohn's Disease (CD)] is a group of chronic disorders of unknown etiology characterized by inflammation in the gastrointestinal tract associated with a high colon cancer risk. UC is characterized by periods of active disease ("flare-ups"), followed by periods when the disease is inactive ("remission"). The end result is an abnormal immune response with repeated episodes of colonic inflammation. Conventional treatment of UC by aminosalicylates, TNFα inhibitors, and steroids have modest effects, and come with a high risk of side effects including dyspeptic symptoms, gastric ulceration and sometimes hospitalization and deaths. Because of …

Role Of Raltegravir In Hiv-1 Management, Kristina E. Rokas, P Brandon Bookstaver, Caitlin L. Shamroe, S Scott Sutton, Vanessa E. Millisor, Jacquelyn E. Bryant, Sharon B. Weissman

Faculty Publications

OBJECTIVE: To review the literature concerning the role of raltegravir in the treatment of HIV-1 in antiretroviral (ARV)-experienced and ARV-naïve patients. DATA SOURCES: A PubMed search was conducted for published data through March 2012 using the search terms raltegravir, MK-0518, and integrase strand transfer inhibitor. An additional search of International Pharmaceutical Abstracts for unpublished data, including data from the Infectious Diseases Society of America, the Conference on Retroviruses and Opportunistic Infections, the International AIDS Society, and the Interscience Conference on Antimicrobial Agents and Chemotherapy, was conducted using similar search terms. STUDY SELECTION AND DATA EXTRACTION: In vitro and in vivo …

Reactive Oxygen Species And Mitochondrial Sensitivity To Oxidative Stress Determine Induction Of Cancer Cell Death By P21, Ionica Masgras, Samantha Carrera, Petra J. De Verdier, Paul Brennan, Aneela Majid, Wan Makhtar, Eugene Tulchinsky, George D. Jones, Igor Roninson, Salvador Macip

Faculty Publications

p21(Waf1/Cip1/Sdi1) is a cyclin-dependent kinase inhibitor that mediates cell cycle arrest. Prolonged p21 up-regulation induces a senescent phenotype in normal and cancer cells, accompanied by an increase in intracellular reactive oxygen species (ROS). However, it has been shown recently that p21 expression can also lead to cell death in certain models. The mechanisms involved in this process are not fully understood. Here, we describe an induction of apoptosis by p21 in sarcoma cell lines that is p53-independent and can be ameliorated with antioxidants. Similar levels of p21 and ROS caused senescence in the absence of significant death in other cancer …

Tp53 Codon 72 Polymorphism Affects Accumulation Of Mtdna Damage In Human Cells, Serena Altilia, Aurelia Santoro, Davide Malagoli, Catia Lanzarini, Josué Adolfo Ballesteros Álvarez, Gianluca Galazzo, Donald Carl Porter, Paolina Crocco, Giuseppina Rose, Giuseppe Passarino, Igor Roninson, Claudio Franceschi, Stefano Salvioli

Faculty Publications

Human TP53 gene is characterised by a polymorphism at codon 72 leading to an Arginine-to-Proline (R/P) substitution. The two resulting p53 isoforms have a different subcellular localisation after stress (more nuclear or more mitochondrial for the P or R isoform, respectively). p53P72 variant is more efficient than p53R72 in inducing the expression of genes involved in nuclear DNA repair. Since p53 is involved also in mitochondrial DNA (mtDNA) maintenance, we wondered whether these p53 isoforms are associated with different accumulation of mtDNA damage. We observed that cells bearing p53R72 accumulate lower amount of mtDNA damage upon rotenone stress with respect …

Relationship Between Vancomycin Trough Concentrations And Nephrotoxicity: A Prospective Multicenter Trial, John A. Bosso, Jean Nappi, Celeste Rudisill, Marlea Wellein, P Brandon Bookstaver, Jenna Swindler, Patrick D. Mauldin

Faculty Publications

Several single-center studies have suggested that higher doses of vancomycin, aimed at producing trough concentrations of >15 mg/liter, are associated with increased risk of nephrotoxicity. We prospectively assessed the relative incidence of nephrotoxicity in relation to trough concentration in patients with documented methicillin-resistant Staphylococcus aureus (MRSA) infections at seven hospitals throughout South Carolina. Adult patients receiving vancomycin for at least 72 h with at least one vancomycin trough concentration determined under steady-state conditions were prospectively studied. The relationship between vancomycin trough concentrations of >15 mg/ml and the occurrence of nephrotoxicity was assessed using univariate and multivariate analyses, controlling for age, …

Effects Of Androgen Receptor And Androgen On Gene Expression In Prostate Stromal Fibroblasts And Paracrine Signaling To Prostate Cancer Cells, Matthew J. Tanner, R. Charles Welliver, Mengqian Chen, Michael Shtutman, Alejandro Godoy, Gary Smith, Badar M. Mian, Ralph Buttyan

Faculty Publications

The androgen receptor (AR) is expressed in a subset of prostate stromal cells and functional stromal cell AR is required for normal prostate developmental and influences the growth of prostate tumors. Although we are broadly aware of the specifics of the genomic actions of AR in prostate cancer cells, relatively little is known regarding the gene targets of functional AR in prostate stromal cells. Here, we describe a novel human prostate stromal cell model that enabled us to study the effects of AR on gene expression in these cells. The model involves a genetically manipulated variant of immortalized human WPMY-1 …

Topiramate: Safety And Efficacy Of Its Use In The Prevention And Treatment Of Migraine, Ginger C. Minton, April D. Miller, P Brandon Bookstaver, Bryan L. Love

Faculty Publications

Migraine headaches are typically episodic in nature and may affect nearly 10% of the population. In addition to treatment, prevention of subsequent episodes or progression to a chronic migraine state is an important therapeutic area. Topiramate is a centrally acting medication approved for both the prevention of seizures and migraine headache. At this time, the exact mechanism of how topiramate assists in migraine prevention is unknown. Several large randomized, controlled trials have aided in establishing topiramate's role in migraine prevention. Despite a favorable pharmacokinetic and adverse effect profile established in clinical trials, several additional studies, case reports and toxicology reports …

Intravenous Ibuprofen: The First Injectable Product For The Treatment Of Pain And Fever, P Brandon Bookstaver, April D. Miller, Celeste N. Rudisill, Leann B. Norris

Faculty Publications

This paper reviews the current data on the use of the first approved intravenous ibuprofen product for the management of post-operative pain and fever in the United States. The management of acute and post-operative pain and fever with nonsteroidal anti-inflammatory agents (NSAIDs) is well documented. A search in Medline and International Pharmaceutical Abstracts of articles until the end of November 2009 and references of all citations were conducted. Available manufacturer data on file were also analyzed for this report. Several randomized controlled studies have demonstrated the opioid-sparing and analgesic effects of 400 and 800 mg doses of intravenous ibuprofen in …

Hedgehog/Gli Supports Androgen Signaling In Androgen Deprived And Androgen Independent Prostate Cancer Cells, Mengqian Chen, Michael A. Feuerstein, Elina Levina, Prateek S. Baghel, Richard D. Carkner, Matthew J. Tanner, Michael Shtutman, Francis Vacherot, Stéphane Terry, Alexandre De La Taille, Ralph Buttyan

Faculty Publications

Background: Castration resistant prostate cancer (CRPC) develops as a consequence of hormone therapies used to deplete androgens in advanced prostate cancer patients. CRPC cells are able to grow in a low androgen environment and this is associated with anomalous activity of their endogenous androgen receptor (AR) despite the low systemic androgen levels in the patients. Therefore, the reactivated tumor cell androgen signaling pathway is thought to provide a target for control of CRPC. Previously, we reported that Hedgehog (Hh) signaling was conditionally activated by androgen deprivation in androgen sensitive prostate cancer cells and here we studied the potential for cross-talk …