Digital Commons Network^™

Regulation Of The Bioavailability Of Thioredoxin In The Lens By A Specific Thioredoxin-Binding Protein (Tbp-2), Namal P.M. Liyanage, M. Rohan Fernando, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Thioredoxin (TRx) is known to control redox homeostasis in cells. In recent years, a specific TRx binding protein called thioredoxin binding protein-2 (TBP-2) was found in other cell types and it appeared to negatively regulate TRx bioavailability and thereby control TRx biological function. In view of the sensitivity of lens transparency to redox status, proper regulation of TRx bioavailability is of the utmost importance. This study was conducted to examine the presence and function of TBP-2 in human lens epithelial cells (HLE B3). We cloned human lens TBP-2 from a human cDNA library (GenBank accession number AY 594328) and showed …

Bilateral Claudication Results In Alterations In The Gait Biomechanics At The Hip And Ankle Joints, Shing-Jye Chen, Iraklis Pipinos, Jason Johanning, Matija Radovic, Jessie M. Huisinga, Sara A. Myers, Nikolaos Stergiou

Health and Kinesiology Faculty Publications

Claudication is the most common symptomatic manifestation of peripheral arterial disease (PAD), producing significant ambulatory compromise. The purpose of this study was to use advanced biomechanical gait analysis to determine the gait alterations occurring in claudicating patients both before and after onset of claudication pain in their legs. Hip, knee, and ankle joint moments were measured in claudicating patients (age: 64.46±8.47 years; body mass: 80.70±12.64 kg; body height: 1.72±0.08 m) and were compared to gender–age–body mass–height-matched healthy controls (age 66.27±9.22 years; body mass: 77.89±10.65 kg; body height: 1.74±0.08 m). The claudicating patients were evaluated both before (pain-free (PF) condition) and …

Blunted Cystine–Glutamate Antiporter Function In The Nucleus Accumbens Promotes Cocaine-Induced Drug Seeking, Kristen S. Kau, Aric Madayag, John R. Mantsch, Mark D. Grier, Omer Abdulhameed, David A. Baker

Biomedical Sciences Faculty Research and Publications

Repeated cocaine alters glutamate neurotransmission, in part, by reducing cystine–glutamate exchange via system x_c−, which maintains glutamate levels and receptor stimulation in the extrasynaptic compartment. In the present study, we undertook two approaches to determine the significance of plasticity involving system x_c−. First, we examined whether the cysteine prodrug N-acetylcysteine attenuates cocaine-primed reinstatement by targeting system x_c−. Rats were trained to self-administer cocaine (1 mg/kg/200 μl, i.v.) under extended access conditions (6 h/day). After extinction training, cocaine (10 mg/kg, i.p.) primed reinstatement was assessed in rats pretreated with N-acetylcysteine (0–60 mg/kg, i.p.) in the …

Pegylated Interferon 2a And 2b In Combination With Ribavirin For The Treatment Of Chronic Hepatitis C In Hiv Infected Patients., Ravinder Dhillon, Simona Rossi, Steven K Herrine

Department of Medicine Faculty Papers

Coinfection with hepatitis C virus (HCV) and HIV is an increasingly recognized clinical dilemma, particularly since the advent of highly active antiretroviral therapy. Several studies of this population have demonstrated both more rapid progression of liver disease and poorer overall prognosis compared to HCV monoinfected patients. Consensus guidelines, based primarily on the results of 4 major randomized trials, recommend treatment with peginterferon and ribavirin for 48 weeks in coinfected patients. However, this current standard of care is associated with lower response rates to therapy than those seen in monoinfected patients. Important predictors of response include HCV genotype, pretreatment HCV RNA …

The Aryl Hydrocarbon Receptor Binds To E2f1 And Inhibits E2f1-Induced Apoptosis., Jennifer L Marlowe, Yunxia Fan, Xiaoqing Chang, Li Peng, Erik S Knudsen, Ying Xia, Alvaro Puga

Kimmel Cancer Center Faculty Papers

Cellular stress by DNA damage induces checkpoint kinase-2 (CHK2)-mediated phosphorylation and stabilization of the E2F1 transcription factor, leading to induction of apoptosis by activation of a subset of proapoptotic E2F1 target genes, including Apaf1 and p73. This report characterizes an interaction between the aryl hydrocarbon (Ah) receptor (AHR), a ligand-activated transcription factor, and E2F1 that results in the attenuation of E2F1-mediated apoptosis. In Ahr(-/-) fibroblasts stably transfected with a doxycycline-regulated AHR expression vector, inhibition of AHR expression causes a significant elevation of oxidative stress, gammaH2A.X histone phosphorylation, and E2F1-dependent apoptosis, which can be blocked by small interfering RNA-mediated knockdown of …

Bh3-Only Protein Mimetic Obatoclax Sensitizes Cholangiocarcinoma Cells To Apo2l/Trail-Induced Apoptosis., Justin L. Mott, Steve F. Bronk, Ruben A. Mesa, Scott H. Kaufmann, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

Human cholangiocarcinomas evade apoptosis by overexpression of Mcl-1. The drug obatoclax (GX15-070) inhibits antiapoptotic members of the Bcl-2 family including Mcl-1. The purpose of this study is to determine if obatoclax sensitizes human cholangiocarcinoma cells to apoptosis. The human cholangiocarcinoma cell lines, KMCH, KMBC, and TFK, were employed for these studies. Protein expression was assessed by immunoblot and protein-protein interactions detected by coprecipitation of the polypeptide of interest with S-tagged Mcl-1. Activation of Bak and Bax was observed by immunocytochemistry with conformation-specific antisera. Obatoclax induced minimal apoptosis alone; however, it increased apoptosis 3- to 13-fold in all three cancer cell …

Neutralization Of Botulinum Neurotoxin By A Human Monoclonal Antibody Specific For The Catalytic Light Chain., Sharad P Adekar, Tsuyoshi Takahashi, R Mark Jones, Fetweh H Al-Saleem, Denise M Ancharski, Michael J Root, B P Kapadnis, Lance L Simpson, Scott K Dessain

Department of Biochemistry and Molecular Biology Faculty Papers

BACKGROUND: Botulinum neurotoxins (BoNT) are a family of category A select bioterror agents and the most potent biological toxins known. Cloned antibody therapeutics hold considerable promise as BoNT therapeutics, but the therapeutic utility of antibodies that bind the BoNT light chain domain (LC), a metalloprotease that functions in the cytosol of cholinergic neurons, has not been thoroughly explored.

METHODS AND FINDINGS: We used an optimized hybridoma method to clone a fully human antibody specific for the LC of serotype A BoNT (BoNT/A). The 4LCA antibody demonstrated potent in vivo neutralization when administered alone and collaborated with an antibody specific for …

Transcriptional Regulation Network Analysis Of The Hypertension-Perturbed Nucleus Tractus Solitarius, Gregory E. Gonye, Rajanikanth Vadigepalli, Haiping Hao, James S. Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Poster Presentation.

Multi-Scale Modeling Of Angiotensin Ii Induced Neuronal Regulatory Mechanisms In The Brain, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Poster Presentation.

Murine Monoclonal Anti-Idiotype Antibody 11d10 And Methods Of Use Thereof, Malaya Chatterjee, Kenneth A. Foon, Sunil K. Chatterjee

Microbiology, Immunology and Molecular Genetics Faculty Patents

The present invention provides a monoclonal anti-Idiotype antibody 11D10 that elicits an immune response against a specific epitope of a high molecular weight mucin of human milk fat globule (HMFG) and a hybridoma that produces 11D10. The hybridoma that produces 11D10 was selected by specific procedures. 11D10 induces an immunological response to HMFG in mice, rabbits, monkeys and patients with advanced HMFG-associated tumors. This invention provides compositions derived from polynucleotide sequences encoding the variable light and/or variable heavy regions of monoclonal anti-idiotype antibody 11D10, as well as polypeptides encoded thereby. The invention also provides compositions which can be used in …

Promotion Of Tumor Cell Death Through The Induction Of, Tuyen Nguyen

Theses and Dissertations

Microtubule poisons have proven to be effective in the treatment of a variety of malignancies. Although taxol-based derivatives promote microtubule stabilization, there is continuing interest in compounds that, like colchicines, act as microtubule destabilizing agents. Previous work from this laboratory showed that the novel microtubule poison, JG- 03-14, was active against breast tumor cells, promoting autophagic cell death. In the current work, we studied the influence of JG-03-14 on p53 wild type HCT116 colon carcinoma cells. A crystal violet sensitivity assay indicated that JG-03-14 induced growth inhibition, with 75% suppression of growth evident at a concentration of 500 nM. Time …

Surface Charge Effects Involved In The Control Of Stability Of Sols Comprising Uniform Cholesterol Particles, Vuk Uskoković

Pharmacy Faculty Articles and Research

The reported is a method for the preparation of stable dispersions of narrowly dispersed cholesterol crystals, which may provide an excellent model for the aggregation studies thereof. The effects of experimental parameters that include concentration, pH, ionic strength, temperature, and aging on the resulting morphologies are acknowledged. Regardless of the cause of destabilization, the multilayered aggregates of cholesterol particles are formed by “face-to-face” stacking of the original platelets, as promoted by higher surface charge density on particle sides comparing to their faces. In accordance with the crucial involvement of surface charge effects in stabilization of cholesterol dispersions produced hereby, aggregation …

Three-Dimensional Arm Movements At Constant Equi-Affine Speed, Frank E. Pollick, Uri Maoz, Amir A. Handzel, Peter J. Giblin, Guillermo Sapiro, Tamar Flash

Psychology Faculty Articles and Research

It has long been acknowledged that planar hand drawing movements conform to a relationship between movement speed and shape, such that movement speed is inversely proportional to the curvature to the power of one-third. Previous literature has detailed potential explanations for the power-law’s existence as well as systematic deviations from it. However, the case of speed-shape relations for three-dimensional (3D) drawing movements has remained largely unstudied. In this paper we first derive a generalization of the planar power law to 3D movements, which is based on the principle that this power law implies motion at constant equi-affine speed. This generalization …

Beta3 Integrin Haplotype Influences Gene Regulation And Plasma Von Willebrand Factor Activity, Katie E. Payne, Paul F. Bray, Peter J. Grant, Angela M. Carter

Department of Medicine Faculty Papers

The Leu33Pro polymorphism of the gene encoding beta(3) integrin (ITGB3) is associated with acute coronary syndromes and influences platelet aggregation. Three common promoter polymorphisms have also been identified. The aims of this study were to (1) investigate the influence of the ITGB3 -400C/A, -425A/C and -468G/A promoter polymorphisms on reporter gene expression and nuclear protein binding and (2) determine genotype and haplotype associations with platelet alpha(IIb)beta(3) receptor density. Promoter haplotypes were introduced into an ITGB3 promoter-pGL3 construct by site directed mutagenesis and luciferase reporter gene expression analysed in HEL and HMEC-1 cells. Binding of nuclear proteins was assessed by electrophoretic …

Investigating The Complexity Of Respiratory Patterns During The Laryngeal Chemoreflex, Andrei Dragomir, Yasemin Akay, Aidan K. Curran, Metin Akay

Dartmouth Scholarship

The laryngeal chemoreflex exists in infants as a primary sensory mechanism for defending the airway from the aspiration of liquids. Previous studies have hypothesized that prolonged apnea associated with this reflex may be life threatening and might be a cause of sudden infant death syndrome. In this study we quantified the output of the respiratory neural network, the diaphragm EMG signal, during the laryngeal chemoreflex and eupnea in early postnatal (3–10 days) piglets. We tested the hypothesis that diaphragm EMG activity corresponding to reflex-related events involved in clearance (restorative) mechanisms such as cough and swallow exhibit lower complexity, suggesting that …

Enterotoxin Preconditioning Restores Calcium-Sensing Receptor-Mediated Cytostasis In Colon Cancer Cells, Giovanni Mario Pitari, Jieru E. Lin, Fawad J. Shah, Wilhelm J. Lubbe, David Zuzga, Peng Li, Stephanie Schulz, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Guanylyl cyclase C (GCC), the receptor for diarrheagenic bacterial heat-stable enterotoxins (STs), inhibits colorectal cancer cell proliferation by co-opting Ca(2+) as the intracellular messenger. Similarly, extracellular Ca(2+) (Ca(2+)(o)) opposes proliferation and induces terminal differentiation in intestinal epithelial cells. In that context, human colon cancer cells develop a phenotype characterized by insensitivity to cytostasis imposed by Ca(2+)(o). Here, preconditioning with ST, mediated by GCC signaling through cyclic nucleotide-gated channels, restored Ca(2+)(o)-dependent cytostasis, reflecting posttranscriptional regulation of calcium-sensing receptors (CaRs). ST-induced GCC signaling deployed CaRs to the surface of human colon cancer cells, whereas elimination of GCC signaling in mice nearly abolished …

Critical Involvement Of The Atm-Dependent Dna Damage Response In The Apoptotic Demise Of Hiv-1-Elicited Syncytia, Jean-Luc Perfettini, Roberta Nardacci, Mehdi Bourouba, Frederic Subra, Laurent Gros, Claire Séror, Gwenola Manic, Filippo Rosselli, Alessandra Amendola, Peggy Masdehors, Luciana Chessa, Giuseppe Novelli, David M. Ojcius, Jan Konrad Siwicki, Magdalena Chechlinska, Christian Auclair, Jose R. Regueiro, Hughes De Thé, Marie-Lise Gougeon, Mauro Piacentini, Guido Kroemer

All Dugoni School of Dentistry Faculty Articles

DNA damage can activate the oncosuppressor protein ataxia telangiectasia mutated (ATM), which phosphorylates the histone H2AX within characteristic DNA damage foci. Here, we show that ATM undergoes an activating phosphorylation in syncytia elicited by the envelope glycoprotein complex (Env) of human immunodeficiency virus-1 (HIV-1) in vitro. This was accompanied by aggregation of ATM in discrete nuclear foci that also contained phospho-histone H2AX. DNA damage foci containing phosphorylated ATM and H2AX were detectable in syncytia present in the brain or lymph nodes from patients with HIV-1 infection, as well as in a fraction of blood leukocytes, correlating with viral status. Knockdown …

Radiotherapy Optimal Design: An Academic Radiotherapy Treatment Design System, R Acosta, W Brick, A Hanna, Allen Holder, D Lara, G Mcquillen, D Nevin, P Uhlig, B Salter

Mathematical Sciences Technical Reports (MSTR)

Optimally designing radiotherapy and radiosurgery treatments to increase the likelihood of a successful recovery from cancer is an important application of operations research. Researchers have been hindered by the lack of academic software that supports head-to-head comparisons of different techniques, and this article addresses the inherent difficulties of designing and implementing an academic treatment planning system. In particular, this article details the algorithms and the software design of Radiotherapy optimAl Design (RAD).

The Role Of Extracellular Matrix And Matrix-Degrading Proteases In Neonatal Hypoxic-Ischemic Injury, Christopher C. Leonardo

USF Tampa Graduate Theses and Dissertations

Improvements in medical care over recent decades have increased the number of premature and low birth weight infants that survive hypoxic-ischemic (H-I) insults. Because there is a rising incidence in diseases associated with these events, it is critical to develop effective therapies to treat the various resulting neuropathies. Extracellular matrix constitutes the majority of brain parenchyma. Lecticans and matrix-degrading proteases including ADAMTSs (a disintegrin and metalloproteinase with thrombospondin repeats) and matrix metalloproteinases (MMPs) exert effects on cell viability and may be associated with either protective or destructive processes after H-I. Both ADAMTSs (Cross et al. 2006; Tian et al. 2007) …

Response Of Endothelial Cells To Stressors: The Impact Of Aging And Diabetes, Katie Mclellan

Loma Linda University Electronic Theses, Dissertations & Projects

Preliminary research indicates there is some impairment of the endothelial cells to respond to single stressors such as local heat, shear stress, and global heat in older people and people who have diabetes. The response of the skin blood flow to local heat is an indicator of the endothelial cells ability to cope with stress. In addition, factors such as thicker subcutaneous fat and skin moisture may impair the skin’s ability to dissipate heat. For older people and people with diabetes, this endothelial dysfunction may cause an even more diminished response to multiple stressors. However, no studies have examined the …

Novel Binding Domains Mediate Binding Of Hpv 16 E6 To Fadd And Procaspase 8, Sandy S. Tungteakkhun

Loma Linda University Electronic Theses, Dissertations & Projects

To evade the host response to infection, viruses have developed means to survive and propagate. HPV 16, a causative agent of cervical cancer and of some cases of oropharyngeal cancers, is one example. We have reported that the early viral protein E6 binds to proteins necessary for propagation of the apoptotic signal following receptor/ligand interactions, such as those mediated by FADD DED and procaspase 8 DED. E6 expression leads to the dose-dependent accelerated degradation of FADD and the protection of E6-expressing cells from Fas-induced apoptosis. Surprisingly, the splice isoforms of E6, E6_large and E6*, affect the stability of procaspase …

Mechanisms Of T Helper Cell Modulation In A Simulated Space Radiation Environment, Asma Rizvi

Loma Linda University Electronic Theses, Dissertations & Projects

Exposure to solar particle events (SPEs) poses the most serious threat to astronaut health. Due to this radiation environment, exploration of the solar system beyond Earth’s orbit entails many risks for the crew on these deep space missions. Depression or dysfunction of the immune system is a major concern due to its high radio-sensitivity; potential consequences include overwhelming infection, development of cancer, fibrosis, and poor wound healing. Astronauts are also exposed to low dose/low dose rate (LDR) radiation. A three month stay at the international space station exposes them to ~ 0.05 Gy of radiation.

C57BL/6 mice received LDR gamma-radiation …

Supracutaneous Vibrotactile Perception Threshold At Various Non-Glabrous Body Loci, Miriam Bikah, M. Susan Hallbeck, John H. Flowers

Department of Psychology: Faculty Publications

Researchers at the University of Nebraska–Lincoln are currently designing a wearable/portable neutron detector. As an alerting mechanism, the device will transmit vibration to the wearer’s skin in the presence of hazardous levels of neutron radiation. The present study was designed to help in the ergonomically correct body placement of the neutron detection device while providing numerical values for vibratory thresholds at the surface of various non-glabrous body loci. The aim of the study was to investigate the underlying effects of locus stimulated, amount of subcutaneous fat around a specific body site and gender on low frequency vibration thresholds. Thirty-six participants, …

Demyelinating And Nondemyelinating Strains Of Mouse Hepatitis Virus Differ In Their Neural Cell Tropism., Jayasri Das Sarma, Kathryn Iacono, Lilli Gard, Ryan Marek, Lawrence C. Kenyon, Michael Koval, Susan R. Weiss

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Some strains of mouse hepatitis virus (MHV) can induce chronic inflammatory demyelination in mice that mimics certain pathological features of multiple sclerosis. We have examined neural cell tropism of demyelinating and nondemyelinating strains of MHV in order to determine whether central nervous system (CNS) cell tropism plays a role in demyelination. Previous studies demonstrated that recombinant MHV strains, isogenic other than for the spike gene, differ in the extent of neurovirulence and the ability to induce demyelination. Here we demonstrate that these strains also differ in their abilities to infect a particular cell type(s) in the brain. Furthermore, there is …

A New Model For Hemoglobin Ingestion And Transport By The Human Malaria Parasite Plasmodium Falciparum., Michelle D Lazarus, Timothy G Schneider, Theodore F Taraschi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The current model for hemoglobin ingestion and transport by intraerythrocytic Plasmodium falciparum malaria parasites shares similarities with endocytosis. However, the model is largely hypothetical, and the mechanisms responsible for the ingestion and transport of host cell hemoglobin to the lysosome-like food vacuole (FV) of the parasite are poorly understood. Because actin dynamics play key roles in vesicle formation and transport in endocytosis, we used the actin-perturbing agents jasplakinolide and cytochalasin D to investigate the role of parasite actin in hemoglobin ingestion and transport to the FV. In addition, we tested the current hemoglobin trafficking model through extensive analysis of serial …

Muc4 And Muc5ac Are Highly Specific Tumour-Associated Mucins In Biliary Tract Cancer., W. R. Matull, F. Andreola, A. Loh, Z. Adiguzel, M. Deheragoda, U. Qureshi, Surinder K. Batra, D. M. Swallow, S. P. Pereira

Journal Articles: Biochemistry & Molecular Biology

Alterations in epithelial mucin expression are associated with carcinogenesis, but there are few data in biliary tract cancer (BTC). In pancreatic malignancy, MUC4 is a diagnostic and prognostic tumour marker, whereas MUC5AC has been proposed as a sensitive serological marker for BTC. We assessed MUC4 and MUC5AC expression in (i) prospectively collected bile and serum specimens from 72 patients with biliary obstruction (39 BTC) by real-time reverse transcriptase-PCR (qPCR) and western blot analysis, and (ii) 79 archived biliary tissues (69 BTC) by immunohistochemistry. In bile, MUC4 protein was detected in 27% of BTC and 29% of primary sclerosing cholangitis (PSC) …

The Synthetic Triterpenoid Cddo-Methyl Ester Modulates Microglial Activities, Inhibits Tnf Production, And Provides Dopaminergic Neuroprotection, Thi A. Tran, Melissa K. Mccoy, Michael B. Sporn, Malú G. Tansey

Dartmouth Scholarship

Recent animal and human studies implicate chronic activation of microglia in the progressive loss of CNS neurons. The inflammatory mechanisms that have neurotoxic effects and contribute to neurodegeneration need to be elucidated and specifically targeted without interfering with the neuroprotective effects of glial activities. Synthetic triterpenoid analogs of oleanolic acid, such as methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me, RTA 402) have potent anti-proliferative and differentiating effects on tumor cells, and anti-inflammatory activities on activated macrophages. We hypothesized that CDDO-Me may be able to suppress neurotoxic microglial activities while enhancing those that promote neuronal survival. Therefore, the aims of our study were to identify specific …

Early Diagnosis Of Pancreatic Cancer: Neutrophil Gelatinase-Associated Lipocalin As A Marker Of Pancreatic Intraepithelial Neoplasia., N. Moniaux, S. Chakraborty, M. Yalniz, J. Gonzalez, Valerie K. Shostrom, J. Standop, Subodh M. Lele, Michel M. Ouellette, Parviz M. Pour, Aaron Sasson, R. E. Brand, Michael A. Hollingsworth, Maneesh Jain, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Pancreatic cancer is a highly lethal malignancy with a dismal 5-year survival of less than 5%. The scarcity of early biomarkers has considerably hindered our ability to launch preventive measures for this malignancy in a timely manner. Neutrophil gelatinase-associated lipocalin (NGAL), a 24-kDa glycoprotein, was reported to be upregulated nearly 27-fold in pancreatic cancer cells compared to normal ductal cells in a microarray analysis. Given the need for biomarkers in the early diagnosis of pancreatic cancer, we investigated the expression of NGAL in tissues with the objective of examining if NGAL immunostaining could be used to identify foci of pancreatic …

Cif Is Negatively Regulated By The Tetr Family Repressor Cifr, Daniel P. Maceachran, Bruce A. Stanton, George A. O'Toole

Dartmouth Scholarship

We previously reported that the novel Pseudomonas aeruginosa toxin Cif is capable of decreasing apical membrane expression of the cystic fibrosis transmembrane conductance regulator (CFTR). We further demonstrated that Cif is capable of degrading the synthetic epoxide hydrolase (EH) substrate S-NEPC [(2S,3S)-trans-3-phenyl-2-oxiranylmethyl 4-nitrophenol carbonate], suggesting that Cif may be reducing apical membrane expression of CFTR via its EH activity. Here we report that Cif is capable of degrading the xenobiotic epoxide epibromohydrin (EBH) to its vicinal diol 3-bromo-1,2-propanediol. We also demonstrate that this epoxide is a potent inducer of cif gene expression. We show that the predicted TetR family transcriptional …

Factors Influencing Topotecan Cns Penetration In Mouse Models, Jun Shen

Theses and Dissertations (ETD)

Camptothecin analogs such as topotecan are currently tested in clinical trials for brain tumors. However the clinical outcome is far below the expectations, which are derived from the promising preclinical studies. This discrepancy could be partially attributed to the presence of two barrier systems in the brain, the blood brain barrier (BBB) and blood cerebrospinal fluid (CSF) barrier (BCB). Further investigations have demonstrated multiple ATP-binding cassette (ABC) transporters are present at the two barriers. Camptothecin analogs are well known substrates for several of the transporters. This work defined the role of two ABC transporters, Bcrp1 and P-gp in determination of …