Digital Commons Network^™

Gene Expression Profiling Revealed Novel Mechanism Of Action Of Taxotere And Furtulon In Prostate Cancer Cells, Yiwei Li, Maha Hussain, Sarah H. Sarkar, James Eliason, Ran Li, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Both Taxotere and Capecitabine have shown anti-cancer activity against various cancers including prostate cancer. In combination, Taxotere plus Capecitabine has demonstrated higher anti-cancer activity in advanced breast cancers. However, the molecular mechanisms of action of Taxotere and Capecitabine have not been fully elucidated in prostate cancer.

Methods

The total RNA from PC3 and LNCaP prostate cells untreated and treated with 2 nM Taxotere, 110 μM Furtulon (active metabolite of Capecitabine), or 1 nM Taxotere plus 50 μM Furtulon for 6, 36, and 72 hours, was subjected to Affymetrix Human Genome U133A Array analysis. Real-time PCR and Western Blot …

Life Style Related Risk Factors For Cardiovascular Disease Among Patients At A Teaching Hospital In Karachi, Waris Qidwai, Ar Mangi, R Bux

Department of Family Medicine

BACKGROUND: Cardiovascular disease is a leading cause for morbidity and mortality all over the world. It is important to study life style related, modifiable cardiovascular risk factors among patients, in order to devise preventive strategies.
METHODS: We surveyed family practice patients visiting the out-patient clinics of Aga Khan University Hospital, Karachi. The interview was questionnaire-based and recorded the demographic profile of the patients, in addition to information on life style related cardiovascular risk factors. The ethical requirements for the study were met. SPSS computer software was used for data management. RESULTS: Fifty patients were surveyed and included …

Primaquine-Induced Hemolytic Anemia: Hemotoxicity Of 5-Hydroxyprimaquine (5-Hpq), Zachary Scott Bowman

MUSC Theses and Dissertations

Primaquine is an important antimalarial agent because of its activity against exoerythrocytic forms of Plasmodium sp. Methemoglobinemia and hemolytic anemia, however, are dose-limiting side effects of primaquine therapy. These hemotoxic effects are believed to be mediated by metabolites, though the identity of the toxic specie(s) and the mechanism underlying hemotoxicity have remained unclear. Previous studies showed that an N-hydroxylated metabolite of primaquine, 6-methoxy-8- hydroxylaminoquinoline, was capable of mediating primaquine-induced hemotoxicity. The present studies were undertaken to investigate the hemolytic mechanism of 5-hydroxyprimaquine (5-HPQ), a phenolic metabolite that has been detected in experimental animals. 5-HPQ was synthesized, isolated by flash chromatography …

Palm Is Expressed In Both Developing And Adult Mouse Lens And Retina., Meryl Castellini, Louise V Wolf, Bharesh K Chauhan, Deni S Galileo, Manfred W Kilimann, Ales Cvekl, Melinda K Duncan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Paralemmin (Palm) is a prenyl-palmitoyl anchored membrane protein that can drive membrane and process formation in neurons. Earlier studies have shown brain preferred Palm expression, although this protein is a major water insoluble protein in chicken lens fiber cells and the Palm gene may be regulated by Pax6. METHODS: The expression profile of Palm protein in the embryonic, newborn and adult mouse eye as well as dissociated retinal neurons was determined by confocal immunofluorescence. The relative mRNA levels of Palm, Palmdelphin (PalmD) and paralemmin2 (Palm2) in the lens and retina were determined by real time rt-PCR. RESULTS: In the …

Referred Cutaneous Allodynia In A Migraine Patient Without Simultaneous Headache, Avi Ashkenazi, Carla Lopinto, William B. Young

Department of Neurology Faculty Papers

Cutaneous allodynia is defined as the perception of pain when a non-noxious stimulus is applied to normal skin. This phenomenon has been demonstrated in migraine patients during an acute attack. It is thought to result from central sensitization of neurons in the trigemino-vascular system and may spread to areas beyond that of the referred head pain.

In a recent study, migraine patients demonstrated increased temporal summation to painful mechanical stimuli in their referred head pain area between attacks. This suggests that changes in physiologic properties of nociceptive neurons may occur in migraine patients between attacks.

We describe a migraine patient …

Global Gene Expression Profiling Of Cells Overexpressing Smc3., Giancarlo Ghiselli, Chang-Gong Liu

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: The Structural Maintenance of Chromosome 3 protein (SMC3) plays an essential role during the sister chromatid separation, is involved in DNA repair and recombination and participates in microtubule-mediated intracellular transport. SMC3 is frequently elevated in human colon carcinoma and overexpression of the protein transforms murine NIH3T3 fibroblasts. In order to gain insight into the mechanism of SMC3-mediated tumorigenesis a gene expression profiling was performed on human 293 cells line stably overexpressing SMC3. RESULTS: Biotinylated complementary RNA (cRNA) was used for hybridization of a cDNAmicroarray chip harboring 18,861 65-mer oligos derived from the published dEST sequences. After filtering, the hybridization …

Antigenicity And Immunogenicity Of A Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein, Feng Gao, Eric A. Weaver, Zhongjing Lu, Yingying Li, Hua-Xin Liao, Benjiang Ma, S. Munir Alam, Richard M. Scearce, Laura L. Sutherland, Jae-Sung Yu, Julie M. Decker, George M. Shaw, David C. Montefiori, Bette T. Korber, Beatrice H. Hahn, Barton F. Haynes

Nebraska Center for Virology: Faculty Publications

Genetic variation of human immunodeficiency virus (HIV-1) represents a major obstacle for AIDS vaccine development. To decrease the genetic distances between candidate immunogens and field virus strains, we have designed and synthesized an artificial group M consensus env gene (CON6 gene) to be equidistant from contemporary HIV-1 subtypes and recombinants. This novel envelope gene expresses a glycoprotein that binds soluble CD4, utilizes CCR5 but not CXCR4 as a coreceptor, and mediates HIV-1 entry. Key linear, conformational, and glycan-dependent monoclonal antibody epitopes are preserved in CON6, and the glycoprotein is recognized equally well by sera from individuals infected with different HIV-1 …

Antigenicity And Immunogenicity Of A Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein, Feng Gao, Eric A. Weaver, Zhongjing Lu, Yingying Li, Hua-Xin Liao, Benjiang Ma, S. Munir Alam, Richard M. Scearce, Laura L. Sutherland, Jae-Sung Yu, Julie M. Decker, George M. Shaw, David C. Montefiori, Bette T. Korber, Beatrice H. Hahn, Barton F. Haynes

Nebraska Center for Virology: Faculty Publications

Genetic variation of human immunodeficiency virus (HIV-1) represents a major obstacle for AIDS vaccine development. To decrease the genetic distances between candidate immunogens and field virus strains, we have designed and synthesized an artificial group M consensus env gene (CON6 gene) to be equidistant from contemporary HIV-1 subtypes and recombinants. This novel envelope gene expresses a glycoprotein that binds soluble CD4, utilizes CCR5 but not CXCR4 as a coreceptor, and mediates HIV-1 entry. Key linear, conformational, and glycan-dependent monoclonal antibody epitopes are preserved in CON6, and the glycoprotein is recognized equally well by sera from individuals infected with different HIV-1 …

Potential Roles Of Follicular Dendritic Cell–Associated Osteopontin In Lymphoid Follicle Pathology And Repair And In B Cell Regulation In Hiv-1 And Siv Infection, Qingsheng Li, Jeffrey D. Lifson, Lijie Duan, Timothy Schacker, Cavan Reilly, John V. Carlis, Jacob D. Estes, Ashley T. Haase

Qingsheng Li Publications

Osteopontin is a multifunctional protein with known roles in bone remodeling, wound healing, and normal and pathological immune responses. We showed in microarray studies that osteopontin gene expression is increased in human immunodeficiency virus type 1 (HIV-1)–infected lymphatic tissues after treatment, and we undertook mapping experiments to study osteopontin’s possible functions in this context. We discovered species-specific colocalization of osteopontin with the follicular dendritic cell (FDC) network in lymphatic tissues in HIV-1 and simian immunodeficiency virus infections, and we found that changes in FDC-associated osteopontin covary with changes in lymphoid follicles during acute and late stages of infection and in …

Interleukin-17/Interleukin-17 Receptor-Mediated Signaling Is Important For Generation Of An Optimal Polymorphonuclear Response Against Toxoplasma Gondii Infection, Michelle N. Kelly, Jay K. Kolls, Kyle Happel, Joseph D. Schwartzman

Dartmouth Scholarship

We investigated the role of interleukin-17 (IL-17)/IL-17 receptor (IL-17R)-mediated signaling in the protective immunity against Toxoplasma gondii. IL-17R−/− mice developed a normal adaptive immunity against the parasite. However, increased mortality in the knockout animals can be attributed to a defect in the migration of polymorphonuclear leukocytes to infected sites during early infection.

Epileptogenesis Causes Long-Term Plasticity Changes In Calbindin D-28k In The Rat Pilocarpine Model Of Acquired Epilepsy, Anne Johnston Harrison

Theses and Dissertations

Epilepsy is one of the most common neurological disorders, affecting more than 2% of children and 1% of adults in the U.S. Emerging research has demonstrated that calcium, as a major second messenger system, underlies many of these injury-induced plasticity changes associated with the development of epilepsy. Recent evidence has suggested that long term elevations in neuronal resting calcium levels play a role in initiating and maintaining epileptogenesis (the development of epilepsy). Collaborations between our lab and others have produced microarray data that suggests that a major calcium-binding protein, calbindin D-28k, mRNA levels are decreased in epileptic rats even up …

Evidence For Absence Of Latchbridge Formation In Phasic Saphenous Artery, Shaojie Han

Theses and Dissertations

Tonic arterial smooth muscle can produce strong contractions indefinitely by formation of slowly cycling crossbridges (latchbridges) that maintain force at a high energy economy. To fully understand the uniqueness of mechanisms regulating tonic arterial contraction, comparisons have been made to phasic visceral smooth muscles that do not sustain high forces. This study explored mechanisms of force maintenance in a phasic artery by comparing KCl-induced contractions in the tonic, femoral artery (FA) and its primary branch, the phasic saphenous artery (SA). KCl rapidly (5 N/m2) and [ca2+]i (250 nM) in FA and SA. By 10 min, [ca2+]i declined to 175 nM …

Genetic Networks Controlling Retinal Injury, Felix R Vazquez-Chona, Amna N Khan, Chun K Chan, Anthony N Moore, Pramod K Dash, M Rosario Hernandez, Lu Lu, Elissa J Chesler, Kenneth F Manly, Robert W Williams, Eldon E Geisert

Faculty, Staff and Student Publications

PURPOSE: The present study defines genomic loci underlying coordinate changes in gene expression following retinal injury.

METHODS: A group of acute phase genes expressed in diverse nervous system tissues was defined by combining microarray results from injury studies from rat retina, brain, and spinal cord. Genomic loci regulating the brain expression of acute phase genes were identified using a panel of BXD recombinant inbred (RI) mouse strains. Candidate upstream regulators within a locus were defined using single nucleotide polymorphism databases and promoter motif databases.

RESULTS: The acute phase response of rat retina, brain, and spinal cord was dominated by transcription …

Regulatory Role Of Glycogen Synthase Kinase 3 For Transcriptional Activity Of Add1/Srebp1c, Kang Ho Kim, Min Jeong Song, Eung Jae Yoo, Sung Sik Choe, Sang Dai Park, Jae Bum Kim

Faculty, Staff and Student Publications

Adipocyte determination- and differentiation-dependent factor 1 (ADD1) plays important roles in lipid metabolism and insulin-dependent gene expression. Because insulin stimulates carbohydrate and lipid synthesis, it would be important to decipher how the transcriptional activity of ADD1/SREBP1c is regulated in the insulin signaling pathway. In this study, we demonstrated that glycogen synthase kinase (GSK)-3 negatively regulates the transcriptional activity of ADD1/SREBP1c. GSK3 inhibitors enhanced a transcriptional activity of ADD1/SREBP1c and expression of ADD1/SREBP1c target genes including fatty acid synthase (FAS), acetyl-CoA carboxylase 1 (ACC1), and steroyl-CoA desaturase 1 (SCD1) in adipocytes and hepatocytes. In contrast, overexpression of GSK3beta down-regulated the transcriptional …

Chloride Equilibrium Potential In Salamander Cones., Wallace B. Thoreson, Eric J. Bryson

Journal Articles: Ophthalmology

BACKGROUND: GABAergic inhibition and effects of intracellular chloride ions on calcium channel activity have been proposed to regulate neurotransmission from photoreceptors. To assess the impact of these and other chloride-dependent mechanisms on release from cones, the chloride equilibrium potential (ECl) was determined in red-sensitive, large single cones from the tiger salamander retinal slice.

RESULTS: Whole cell recordings were done using gramicidin perforated patch techniques to maintain endogenous Cl- levels. Membrane potentials were corrected for liquid junction potentials. Cone resting potentials were found to average -46 mV. To measure ECl, we applied long depolarizing steps to activate the calcium-activated chloride current …

Methods And Apparatus For In Vivo Identification And Characterization Of Vulnerable Atherosclerotic Plaques, Pedro Moreno, Robert A. Lodder, William O'Connor, James E. Muller

Internal Medicine Faculty Patents

Methods and apparatus for analyzing the chemical composition of vulnerable plaques with an intravascular catheter having a near-infrared light source, a fiber-optic probe, a mechanism for directing the light from the light source into a blood vessel, and detectors for detecting light reflected or scattered by the tissue. The light source may be a tunable laser, and may transmit an incident beam having a wavelength ranging from 1400 to 4100 nm. A computer may be included to receive and process the spectral data in the analysis of the vulnerable plaques. A catheter system may be configured to provide near-IR spectrometric …

Rgs14 Is A Mitotic Spindle Protein Essential From The First Division Of The Mammalian Zygote., Luke Martin-Mccaffrey, Francis S Willard, Antonio J Oliveira-Dos-Santos, David R C Natale, Bryan E Snow, Randall J Kimple, Agnieszka Pajak, Andrew J Watson, Lina Dagnino, Josef M Penninger, David P Siderovski, Sudhir J A D'Souza

Obstetrics & Gynaecology Publications

Heterotrimeric G protein alpha subunits, RGS proteins, and GoLoco motif proteins have been recently implicated in the control of mitotic spindle dynamics in C. elegans and D. melanogaster. Here we show that "regulator of G protein signaling-14" (RGS14) is expressed by the mouse embryonic genome immediately prior to the first mitosis, where it colocalizes with the anastral mitotic apparatus of the mouse zygote. Loss of Rgs14 expression in the mouse zygote results in cytofragmentation and failure to progress to the 2-cell stage. RGS14 is found in all tissues and segregates to the nucleus in interphase and to the mitotic spindle …

A Study Of Pediatric Heart Transplant Patients In Relationship To Post Transplant Coronary Artery Disease, Mark Randall

Loma Linda University Electronic Theses, Dissertations & Projects

Post transplant coronary artery disease influences short and long-term survival of pediatric heart transplant recipients. Associated cardiovascular disease risk factors among non-heart transplant adult and pediatric heart populations for development of coronary artery disease have been documented. Little is known about these typical cardiovascular disease risk factors as well as other possible risk factors in the development of post transplant coronary artery disease. Objective: The purpose of this research was to examine children/adolescents (n=194), 5-18 years old, at least one-year post heart transplant. This study also investigated if there were physiological and psychological/behavioral differences between recipients with (n = 28) …

Sensory Hypoinnervation In Club Foot, M Ahmed, N Ahmed, K. M. Khan, Masood Umer, H. Rashid,, Pervaiz Hashmi

Department of Surgery Docs

Abstract

We have compared the density of nerve fibres in the synovium in club foot with that of specimens obtained from the synovium of the hip at operations for developmental dysplasia. The study focused on the sensory neuropeptides substance P; calcitonin gene-related peptide; protein gene product 9.5, a general marker for mature peripheral nerve fibres; and growth associated protein 43, a neuronal marker for new or regenerating nerve fibres. In order to establish whether there might be any inherent difference we analysed the density of calcitonin gene-related peptide-positive nerve fibres in the hip and ankle joints in young rats. Semi-quantitative …

Relationship Of Serum Prolactin With Severity Of Drug Use And Treatment Outcome In Cocaine Dependence., Ashwin A. Patkar, Paolo Mannelli, Kenneth M. Certa, Kathleen Peindl, Heather Murray, Michael J. Vergare, Wade H. Berrettini

Department of Psychiatry and Human Behavior Faculty Papers

RATIONALE: Alteration in serum prolactin (PRL) levels may reflect changes in central dopamine activity, which modulates the behavioral effects of cocaine. Therefore, serum PRL may have a potential role as a biological marker of drug severity and treatment outcome in cocaine dependence.

OBJECTIVE: We investigated whether serum PRL levels differed between cocaine-dependent (CD) subjects and controls, and whether PRL levels were associated with severity of drug use and treatment outcome in CD subjects.

METHODS: Basal PRL concentrations were assayed in 141 African-American (AA) CD patients attending an outpatient treatment program and 60 AA controls. Severity of drug use was assessed …

A Vibrio Cholerae Classical Tcpa Amino Acid Sequence Induces Protective Antibody That Binds An Area Hypothesized To Be Important For Toxin-Coregulated Pilus Structure, Ronald K. Taylor, Thomas J. Kirn, Michael D. Meeks, Terri K. Wade, William F. Wade

Dartmouth Scholarship

Vibrio cholerae is a gram-negative bacterium that has been associated with cholera pandemics since the early 1800s. Whole-cell, killed, and live-attenuated oral cholera vaccines are in use. We and others have focused on the development of a subunit cholera vaccine that features standardized epitopes from various V. cholerae macromolecules that are known to induce protective antibody responses. TcpA protein is assembled into toxin-coregulated pilus (TCP), a type IVb pilus required for V. cholerae colonization, and thus is a strong candidate for a cholera subunit vaccine. Polypeptides (24 to 26 amino acids) in TcpA that can induce protective antibody responses have …

Occipital Nerve Block Rapidly Eliminates Allodynia Far From The Site Of Headache: A Case Report, William B. Young, Valentin Mateos, Avi Ashkenazi

Department of Neurology Faculty Papers

Seventy to 80% of persons with migraine develop allodynia during the course of a severe attack. During a migraine attack, allodynia spreads topographically to extratrigeminal territory. Dynamic mechanical allodynia, otherwise known as brush allodynia (BA), is a subtype of allodynia that is easily tested. Ashkenazi & Young recently reported on the immediate benefits of greater occipital nerve (GON) block on brush allodynia and pain in migraine and in cluster headache. In these studies, testing was performed at fixed sites in the trigeminal and cervical distributions. Allodynia in thoracic dermatomes was not studied.

Headache Management For The Pain Specialist, Avi Ashkenazi, Stephen Silberstein

Department of Neurology Faculty Papers

Headache is a common symptom caused by a wide variety of diseases. Primary headaches include migraine, cluster headache, tension-type headache and other less common diseases. It is important to differentiate these headaches from secondary headaches caused by vascular, neoplastic, infectious, metabolic and toxic disorders. Most primary headaches have a genetic basis, with environmental factors acting as triggers. Recent advances in basic research resulted in the development of more specific and effective therapies. Medication overuse headache is a very common cause of chronic daily headache. Detoxification from the offending drug is essential for headache improvement. Cervicogenic headache is common and needs …

Oncolog, Volume 49, Number 12, December 2004, David Galloway, Katie Prout Matias, Diane Witter, Paul Mathew Md

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Advances in Prostate Cancer Treatment
• Everyday Drugs Show New Promise for Cancer
• Are COX-2 Inhibitors Safe?
• House Call: Myths & Facts about Cancer Prevention
• DiaLog: Neoadjuvant Trials in Prostate Cancer, by Paul Mathew, MD, Assistant Professor, Department of Genitourinary Medical Oncology

Long-Term Correction Of Ornithine Transcarbamylase Deficiency By Wpre-Mediated Overexpression Using A Helper-Dependent Adenovirus, Asad Mian, W. Michael Mccormack Jr, Viraj Mane, Soledad Kleppe, Philip Ng, Milton Finegold, William E. O'Brien, John R. Rodgers, Arthur L. Beaude, Brendan Lee

Department of Emergency Medicine

The urea cycle disorders (UCDs) are important models for developing gene replacement therapy for liver diseases. Long-term correction of the most common UCD, ornithine transcarbamylase (OTC) deficiency, has yet to be achieved in clinical or preclinical settings. The single human clinical trial using early-generation adenovirus (Ad) failed to show any biochemical correction. In adult OTC-deficient mice, an E1/E2-deleted Ad vector expressing the mouse OTC gene, but not the human, was only transiently therapeutic. By using post-transcriptional overexpression in the context of the less immunogenic helper-dependent adenoviral vector, we achieved metabolic correction of adult OTC-deficient mice for >6 months. Demonstrating this …

Infant Heart Transplant: Perioperative Indicators Of Neurocognitive Development, Joy Michelle Gardner

Loma Linda University Electronic Theses, Dissertations & Projects

Approximately five to eight births per 1000 in the United States are born with a congenital heart defect (Limperopoulos et al, 1999), the primary defect in 57% is hypoplastic left heart syndrome (Johnston, 1991). A fatal disease twenty years ago, survival has jumped from less than 5% to 91% of infants surviving their one-month birthday due to advances in palliative and transplant procedures (Razzouk et al, 1996). Unfortunately, the decrease in mortality has been unmatched by a decrease in morbidity, which continues to be a major risk factor when undergoing deep hypothermia (du Plessis, 2000). While neurodevelopmental and cognitive dysfunction …

Impact Of Antibiotic Usage On Resistance In Microorganisms; Urinary Tract Infections With E-Coli As A Case In Point, N Sabir, Erum Khan, L Sheikh, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objectives:
In this study, we sought to establish a correlation between consumption of flouoroquinolones in our hospital and the emergence of ofloxacin resistant strains of E. coli in the urinary specimens. Data of all urinary samples, received at Aga Khan University Hospital between January 1995 and December 2002, was retrieved and analyzed. Specimens yielding E-coli as an isolate were included in this study.
Methods:
E. coli Isolates showing >103 colonies were identified using standard microbiological techniques. Antibiotic susceptibility of E. coli was tested using Kirby Bauer disc diffusion method. Antimicrobial usage data, obtained through hospital Pharmacy as unit utilized per …

Method Of Inhibiting Alu Rna And Therapeutic Uses Thereof, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

The presently-disclosed subject matter includes methods of identifying an Alu RNA inhibitor, and methods and compo sitions for inhibiting Alu RNA. Methods and compositions can be used for the treatment of geographic atrophy and other conditions of interest.

Il-5 Links Adaptive And Natural Immunity In Reducing Atherosclerotic Disease, Alan Daugherty, Debra L. Rateri, Victoria L. King

Gill Heart & Vascular Institute Faculty Publications

Oxidized LDL induces changes in several facets of the immune system, although the relationships between these facets and their contributions to atherogenesis have yet to be fully elucidated. A report in this issue of the JCI provides a novel demonstration of the adaptive immune system influencing the production of natural antibodies. The results demonstrate that injection of malondialdehyde-modified LDL promotes a Th2 response that in turn increases the titers of the natural antibody T15/EO6, which recognizes the oxidized phospholipid POVPC. Atherosclerotic lesion size in LDL receptor–deficient mice is reduced as a consequence of the increase in natural antibody titers, and …

Gitr Activation Induces An Opposite Effect On Alloreactive Cd4(+) And Cd8(+) T Cells In Graft-Versus-Host Disease., Stephanie J Muriglan, Teresa Ramirez-Montagut, Onder Alpdogan, Thomas W Van Huystee, Jeffrey M Eng, Vanessa M Hubbard, Adam A Kochman, Kartono H Tjoe, Carlo Riccardi, Pier Paolo Pandolfi, Shimon Sakaguchi, Alan N Houghton, Marcel R M Van Den Brink

Department of Medical Oncology Faculty Papers

Glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) is a member of the tumor necrosis factor receptor (TNFR) family that is expressed at low levels on unstimulated T cells, B cells, and macrophages. Upon activation, CD4(+) and CD8(+) T cells up-regulate GITR expression, whereas immunoregulatory T cells constitutively express high levels of GITR. Here, we show that GITR may regulate alloreactive responses during graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). Using a BMT model with major histocompatibility complex class I and class II disparity, we demonstrate that GITR stimulation in vitro and in vivo enhances alloreactive CD8(+)CD25(-) T …