Medical Sciences Commons^™

Il-7 Enhances Peripheral T Cell Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation., Onder Alpdogan, Stephanie J Muriglan, Jeffrey M Eng, Lucy M Willis, Andrew S Greenberg, Barry J Kappel, Marcel R M Van Den Brink

Department of Medical Oncology Faculty Papers

We used clinically relevant murine allogeneic bone marrow transplantation (BMT) models to study the mechanisms by which IL-7 administration can improve posttransplant peripheral T cell reconstitution. After transplant we could distinguish two populations of mature donor T cells: (a) alloreactive T cells with decreased expression of CD127 (IL-7 receptor alpha chain) and (b) nonalloreactive T cells, which express CD127 and undergo homeostatic proliferation. IL-7 administration increased the homeostatic proliferation of nonalloreactive T cells, but had no effect on alloreactive T cells and the development of graft-versus-host disease. Allogeneic transplant of purified hematopoietic stem cells and adoptive transfer of thymocytes into …

Genetic Polymorphisms Of The Interleukin-1 Gene And Early Marginal Bone Loss Around Endosseous Dental Implants, Hitomi Shimpuku, Yasuhiro Nosaka, Tatsuya Kawamura, Yoichi Tachi, Mitsuko Shinohara, Kiyoshi Ohura

Faculty, Staff and Student Publications

Dental implant surgery commonly proceeds in two stages. It is generally accepted that bone loss around implants does not occur at stage-II surgery because implants do not receive mechanical loading. However, early marginal bone loss around implants occasionally does occur during the healing period. Genetic polymorphisms in the interleukin-1 (IL-1) gene have been reported to be important for bone homeostasis and susceptibility to bone disease. We therefore investigated whether the idiopathic early marginal bone loss around implants is related to polymorphisms in the IL-1 gene. We performed a case-control study. Patients demonstrating marginal bone loss around implants at stage-II surgery …

Expression Of Glutathione-S-Transferase Mu 1 (Gstm1) And Glutathione-S-Transferase Theta 1 (Gstt1) In Patients With Aplastic Anemia And Myelodysplastic Syndromes, Aaron Conrad Spivey

Theses and Dissertations in Biomedical Sciences

Aplastic Anemia is a disorder of the hematopoietic bone marrow stem cells that is frequently associated with drug or chemical exposures. Reduced ability to detoxify drugs or chemicals may result in an increased risk of disease. Glutathione S-transferases are Phase II enzymes, which help detoxify xenobiotics. Many patients who have developed aplastic anemia and myelodysplastic syndrome have the null genotype for GSTMI and/or GSTTI. For patients with GSTMI and GSTTI positive genotypes, non-expression of these enzymes may cause an increased risk in developing aplastic anemia or myelodysplastic syndrome. To test whether genotype positive patients have GSTMI or GSTTI null …

High Dietary Level Of Synthetic Vitamin E On Lipid Peroxidation, Membrane Fatty Acid Composition And Cytotoxicity In Breast Cancer Xenograft And In Mouse Host Tissue, Ivan L. Cameron, Jesus Munoz, Christopher J. Barnes, W. Elaine Hardman

Biochemistry and Microbiology

Background

d-α-tocopherol is a naturally occurring form of vitamin E not previously known to have antitumor activity. Synthetic vitamin E (sE) is a commonly used dietary supplement consisting of a mixture of d-α-tocopherol and 7 equimolar stereoisomers. To test for antilipid peroxidation and for antitumor activity of sE supplementation, two groups of nude mice bearing a MDA-MB 231 human breast cancer tumor were fed an AIN-76 diet, one with and one without an additional 2000 IU/kg dry food (equivalent to 900 mg of all-rac-α-tocopherol or sE). This provided an intake of about 200 mg/kg body weight per day. The mice …

Analysis Of Gene × Environment Interactions In Sibships Using Mixed Models, Jill S. Barnholtz-Sloan, Laila M. Poisson, Steven W. Coon, Gary A. Chase, Benjamin A. Rybicki

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Gene × environment models are widely used to assess genetic and environmental risks and their association with a phenotype of interest for many complex diseases. Mixed generalized linear models were used to assess gene × environment interactions with respect to systolic blood pressure on sibships adjusting for repeated measures and hierarchical nesting structures. A data set containing 410 sibships from the Framingham Heart Study offspring cohort (part of the Genetic Analysis Workshop 13 data) was used for all analyses. Three mixed gene × environment models, all adjusting for repeated measurement and varying levels of nesting, were compared for …

The Role Of Ap-1 Transcription Complex In Retinoic Acid-Dependent B16 Melanoma Cell Growth Arrest And Differentiation, Ying Huang

Theses, Dissertations and Capstones

Our laboratory has been studying the effects of all-trans retinoic acid (atRA) on the growth and differentiation of the B16 mouse melanoma cells. RA inhibits both anchorage-dependent and –independent growth and stimulates melanin production in B16 cells, which are accompanied by an increase in AP-1 activity. To further investigate the RA-induced AP-1 activity, I established clones of B16 stably expressing an AP-1-luciferase reporter gene. Treatment of these clones with phorbol dibutyrate (PDB), a known activator of AP-1, rapidly increased AP-1 activity which reached its maximum level at 2-4 h and returned to baseline level by 24 h. In contrast, RA …

Regulation Of Retinoic Acid Receptor Α By Protein Kinase C In B16 Mouse Melanoma Cells, Goran Boskovic, Dinakar Desai, Richard M. Niles

Biochemistry and Microbiology

We have previously found that retinoic acid stimulates the expression of protein kinase Cα (PKC) in B16 mouse melanoma cells. Because it has been reported that PKC can phosphorylate retinoic acid receptor (RAR) and alter its function, we determined whether changes in the level and/or activity of PKC could affect the expression or function of the RAR in B16 melanoma. Using in vivophosphorylation and band shift techniques, we could not demonstrate that altering PKC activity and/or protein level changed thein vivo phosphorylation of RARα. However activation of PKC resulted in increased RARα protein. Increased receptor protein correlated with …

Role Of Lipid Peroxidation And Antioxidant Enzymes In Omega 3 Fatty Acids Induced Suppression Of Breast Cancer Xenograft Growth In Mice, W. Elaine Hardman, Jesus Munoz Jr., Ivan L. Cameron

Biochemistry and Microbiology

Background:

Supplementing mice with high levels of dietary n-3 polyunsaturated fatty acids (PUFAs) increases the n-3 PUFAs in cell membranes, increases the susceptibility of the cells for lipid peroxidation (LPO) and decreases the growth rate of mammary and other tumors. However, the results of an earlier study indicated that a factor in addition to LPO was involved in the reduction in tumor growth in n-3 PUFAs fed mice. Athymic mice bearing MDA-MB-231 human breast carcinoma xenografts, were fed fish oil concentrate (FOC) or control diets, with and without supplemental Vitamin E (2000 IU /kg diet) and were sacrificed both before …

Siva-1 Binds To And Inhibits Bcl-Xl-Mediated Protection Against Uv Radiation-Induced Apoptosis, Li Xue, Fei Chu, Yuan Cheng, Xiangjie Sun, Alip Borthakur, Manjunath Ramarao, Pramod Pandey, Mei Wu, Stuart F. Schlossman, Kanteti V. S. Prasad

Clinical & Translational Sciences

We previously cloned Siva-1 by using the cytoplasmic tail of CD27, a member of the tumor necrosis factor receptor family, as the bait in the yeast two-hybrid system. The Siva gene is organized into four exons that code for the predominant full-length Siva-1 transcript, whereas its alternate splice form, Siva-2, lacks exon 2 coding sequence. Various groups have demonstrated a role for Siva-1 in several apoptotic pathways. Interestingly, the proapoptotic properties of Siva-1 are lacking in Siva-2. The fact that Siva-1 is partly localized to mitochondria despite the absence of any mitochondrial targeting signal, it harbors a 20-aa-long putative amphipathic …

The Role Of Diet And Physical Activity For Ovarian Cancer Results From The Adventist Health Study, Fatemeh Kiani

Loma Linda University Electronic Theses, Dissertations & Projects

A few aspects of the epidemiology of ovarian cancer are well understood, such as the inverse relationship with parity and oral contraceptive (OC) use. The role of other factors such as the potential influence of diet or physical activity is far from being established. A few studies, however, have been able to identify dietary risk factors for ovarian cancer. In this dissertation, I have conducted two studies that investigate the relationship between dietary factors and physical activity and the three endpoints: 1) nonfatal ovarian cancer (1976-1982; time to diagnosis), 2) fatal ovarian cancer (1976-1988; time to death), and 3) total …

Therapeutic Electromagnetic Field Effects On Angiogenesis And Tumor Growth, C. Douglas Williams, Marko S. Markov, W. Elaine Hardman, Ivan L. Cameron

Biochemistry and Microbiology

Background: A new approach to cancer therapy based on the application of therapeutic electromagnetic fields (TEMF) has been developed by EMF Therapeutics, Inc., Chattanooga, TN, USA. This study was designed to assess the effect of TEMF on tumor vascularization and growth of murine 16/C mammmary adenocarcinoma cells in C3H/HeJ mice.

Materials and Methods: Implanted tumors were allowed to grow for seven days until the tumor volume reached 100 mm3 before treatment was started. Mice (20 per control, 10 per EMF exposed group) received treatment (10 minutes per day with 0, 10 mT, 15 mT or 20 mT) with a 120 …

Department Of Radiation Oncology And Kimmel Cancer Center, Thomas Jefferson University, The Intronic G13964c Variant In P53 Is Not A High-Risk Mutation In Familial Breast Cancer In Australia., Anna Marsh, Amanda B Spurdle, Bruce C Turner, Sian Fereday, Heather Thorne, Gulietta M Pupo, Graham J Mann, John L Hopper, Joseph F Sambrook, Georgia Chenevix-Trench

Department of Radiation Oncology Faculty Papers

BACKGROUND: Mutations in BRCA1 and BRCA2 account for approximately 50% of breast cancer families with more than four affected cases, whereas exonic mutations in p53, PTEN, CHK2 and ATM may account for a very small proportion. It was recently reported that an intronic variant of p53--G13964C--occurred in three out of 42 (7.1%) 'hereditary' breast cancer patients, but not in any of 171 'sporadic' breast cancer control individuals (P = 0.0003). If this relatively frequent occurrence of G13964C in familial breast cancer and absence in control individuals were confirmed, then this would suggest that the G13964C variant plays a role in …

Epstein-Barr Virus Serology In The Diagnosis Of Nasopharyngeal Carcinoma From Sarawak, Madeline Wong Mei Fong

Student Works (2000-2009)

The Epstein-Barr virus (EBV) is closely associated with nasopharyngcal carcinoma (NPC). The role(s) of EBV in NPC remains unclear but antibodies to two EBV proteins namely the viral capsid antigen (VCA) and early antigen (EA), are clinically useful diagnostic markers of NPC. The NPC scenario in Malaysia has been based on studies done on West Malaysian patients but not much has been described for NPC in Sarawak, East Malaysia. In this study, 164 NPC sera from newly histologically confirmed NPC patients were collected from the Radiotherapy Unit of Kuching General Hospital, Sarawak prior to radiotherapy. One hundred and forty seven …

Vitamin A And Cancer, Richard M. Niles

Biochemistry and Microbiology

Vitamin A, its physiological metabolites and synthetic derivatives (retinoids) have been shown to have protective effects against the development of certain types of cancer. In addition, pharmacological amounts of retinoids have been used with some success in the treatment of a few human tumors. The chemoprevention effect of retinoids is most likely exerted at the tumor promotion phase of carcinogenesis. Retinoids block tumor promotion by either inhibiting proliferation, inducing apoptosis, inducing differentiation, or a combination of these actions. Clinically, isotretinoin (13-cis-retinoic acid) significantly decreases the incidence of second primary tumors in patients with head and neck cancer and also reduces …

Effect Of Receptor-Selective Retinoids On Growth And Differentiation Pathways In Mouse Melanoma Cells, Sejal H. Desai, Goran Boskovic, Linda L. Eastham, Marcia Dawson, Richard M. Niles

Biochemistry and Microbiology

Treatment of B16 mouse melanoma cells with all-trans-retinoic acid (ATRA) results in inhibition of cell proliferation and induction of differentiation. Accompanying these events is an induction of retinoic acid receptor β (RARβ) expression, an increase in protein kinase Cα (PKCα) expression, and enhanced activator protein-1 (AP-1) transcriptional activity. These cells express nuclear RARα and RARγ and nuclear retinoid X receptors (RXR) α and β constitutively. We tested the ability of receptor-selective retinoids to induce the biochemical changes found in ATRA-treated melanoma cells and also tested their effectiveness in decreasing anchorage-dependent and -independent growth. The RXR-selective ligand (2E,4E)-6-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)-3,7-dimethyl-2,4,6-octatrienoic acid (SR11246) was …

Dietary Fish Oil Sensitizes A549 Lung Xenografts To Doxorubicin Chemotherapy, W. Elaine Hardman, Mary Pat Moyer, Ivan L. Cameron

Biochemistry and Microbiology

A549 xenografts were allowed to grow in nude mice to about 5 mm in diameter, then diets were changed to modified AIN-76 diets containing 19% wt/wt. fish oil (FO) or 20% wt./wt. com oil (CO). Ten days later dietary ferric citrate (0.3% wt./dry wt.) was added and doxoribicin (DOX) treatment (3.6 mg/kg i.v. each of the 5 days for 18 days) commenced. Treatment with DOX halted the growth of tumors in the CO fed mice. However, in those mice, which consumed FO or FO with ferric citrate, treatment with DOX caused significant tumor regression.

Uwomj Volume 69, No 2, Spring 1999, Western University

University of Western Ontario Medical Journal

An interdisciplinary medical science publication; established 1930.

Soft Tissue Sarcomas: Pattern Diagnosis Or Entity, Naasha Talati, Shahid Pervez

Department of Pathology and Laboratory Medicine

Soft tissue sarcomas (STS) are a diverse and heterogeneous group of tumours The sub-classification of these tumours is of importance for both prognosis and treatment. Classically, sub- categorization is based purely on histomorphological grounds, but as new techniques evolve, a more, conclusive and accurate diagnosis can be made. This study describes the prevalence of soft tissue sarcomas in adults diagnosed at The Aga Khan University Hospital (AKUH) and the impact of immunohistochemistry(IHC) on the precise sub-categorization of these tumours. The study included 364 adults (age 16+) who were diagnosed as soft tissue sarcoma in the past six years (May 1991 …

Reaction-Diffusion Models Of Cancer Dispersion, Kim Yvette Ward

Mathematics & Statistics Theses & Dissertations

The phenomenological modeling of the spatial distribution and temporal evolution of one-dimensional models of cancer dispersion are studied. The models discussed pertain primarily to the transition of a tumor from an initial neoplasm to the dormant avascular state, i.e. just prior to the vascular state, whenever that may occur. Initiating the study is the mathematical analysis of a reaction-diffusion model describing the interaction between cancer cells, normal cells and growth inhibitor. The model leads to several predictions, some of which are supported by experimental data and clinical observations $\lbrack25\rbrack$. We will examine the effects of additional terms on these characteristics. …

Phosphorylation Of Elongation Factor 1 And Ribosomal Protein S6 By Multipotential S6 Kinase And Insulin Stimulation Of Translational Elongation, Y W Chang, J A Traugh

Faculty, Staff and Student Publications

Stimulation of protein synthesis in response to insulin is concomitant with increased phosphorylation of initiation factors 4B and 4G and ribosomal protein S6 (Morley, S. J., and Traugh, J. A. (1993) Biochimie 75, 985-989) and is due at least in part to multipotential S6 kinase. When elongation factor 1 (EF-1) from rabbit reticulocytes was examined as substrate for multipotential S6 kinase, up to 1 mol/mol of phosphate was incorporated into the alpha, beta, and delta subunits. Phosphorylation of EF-1 resulted in a 2-2. 6-fold stimulation of EF-1 activity, as measured by poly(U)-directed polyphenylalanine synthesis. The rate of elongation was also …

Molecular And Cellular Biology Of Prostate Cancer, El-Nasir Lalani, Marc Elie Laniado, Paul David Abel

Department of Pathology and Laboratory Medicine

Prostate cancer is an enigmatic disease. Although prostatic-intraepithelial neoplasia appears as early as the third decade and as many as 80% of 80 year old men have epithelial cells in their prostate that fit the morphological criteria for cancer, only about 10% of men will ever have the clinical disease and less than 3% will die from it. There have been no significant proven interventions which have altered the natural history of the disease since hormone down regulation was introduced in the 1940s and new research has been poorly supported. There is however an urgent need to develop new criteria …

Biochemical And Molecular Characterization Of The Prostate-Specific Membrane Antigen (Psma), John Karl Troyer

Theses and Dissertations in Biomedical Sciences

Prostate cancer is the most common malignancy and the second leading cause of cancer death in males in the United States. Additionally, the number of deaths attributed to prostate cancer is increasing at a rate of approximately 8% a year. Development of new diagnostic and therapy strategies are needed in order to improve the life expectancy of patients with this disease. One tool which may allow for improvements in prostate cancer diagnosis and therapy is the monoclonal antibody (MAb) 7E11-C5.3 which was first described in 1987. Since then, the antigen recognized by MAb 7E11-C5.3 has been named the prostate specific …

Identification Of An Idiotypic Peptide Recognized By Autoantibodies In Human Immunodeficiency Virus-1-Infected Individuals, Q. L. Wang, H.-T. Wang, Edwin Blalock, Sybille Müller, Heinz Köhler

Markey Cancer Center Faculty Publications

Antibodies against HIV-1 proteins in HIV-1-infected individuals share a cross-reactive idiotype defined by the monoclonal antiidiotypic antibody 1F7 (5). Using a computer algorithm based on the molecular recognition theory, regions of inverse hydropathy between the variable sequence of 1F7 and human monoclonal anti-HIV-1 antibodies were identified, which are assumed to be involved in idiotype-antiidiotype contacts. A peptide was designed from the proposed contact in the variable heavy chain framework 3-complementarity determining region 3 (FR3-CDR3) of human antibodies and was synthesized. This peptide is recognized by the antiidiotype 1F7 and inhibits the binding of 1F7 to human anti-HIV-1 antibodies which express …

Immune Response To The Carcinoembryonic Antigen In Patients Treated With An Anti-Idiotype Antibody Vaccine, Kenneth A. Foon, Mala Chakraborty, William J. John, Amanda Sherratt, Heinz Köhler, Malaya Bhattacharya-Chatterjee

Markey Cancer Center Faculty Publications

We have generated an IgG1 murine monoclonal anti-idiotype antibody (Ab2) designated 3H1, which mimics a specific epitope on the carcinoembryonic antigen (CEA). Patients with CEA positive tumors are immunologically "tolerant" to CEA. We used 3H1 as a surrogate for CEA for vaccine therapy of 12 patients with advanced colorectal cancer. Each of the patients received a minimum of four intracutaneous injections of aluminum hydroxide precipitated 3H1 at either 1, 2, or 4 mg dosage per injection. 9 of 12 patients demonstrated anti-anti-idiotypic (Ab3) response to 3H1. All nine patients generated specific anti-CEA antibody demonstrated by reactivity with radiolabeled purified CEA; …

Estimation Of The Incidence Of A Rare Genetic Disease Through A Two-Tier Mutation Survey, R Chakraborty, M R Srinivasan, S Raskin

Faculty, Staff and Student Publications

Recent attempts to detect mutations involving single base changes or small deletions that are specific to genetic diseases provide an opportunity to develop a two-tier mutation-screening program through which incidence of rare genetic disorders and gene carriers may be precisely estimated. A two-tier survey consists of mutation screening in a sample of patients with specific genetic disorders and in a second sample of newborns from the same population in which mutation frequency is evaluated. We provide the statistical basis for evaluating the incidence of affected and gene carriers in such two-tier mutation-screening surveys, from which the precision of the estimates …

Can An Anesthesia Machine Flush Valve Provide For Effective Jet Ventilation?, S D Gaughan, J L Benumof, G T Ozaki

Faculty, Staff and Student Publications

Transtracheal jet ventilation (TTJV) using a percutaneously inserted intravenous (IV) catheter for the patient who cannot be ventilated or tracheally intubated or, using a jet stylet for changing endotracheal tubes (ETT) in patients for whom subsequent ventilation and/or tracheal reintubation may be difficult, are extremely valuable therapeutic options. The jet ventilation system must have a sufficiently high pressure-oxygen source to drive oxygen through noncompliant tubing and through relatively small IV catheters and/or jet stylets in order to achieve adequate ventilation and oxygenation. There is no evidence that using the common gas outlet of an anesthesia machine by activating the flush …

Statistical Interpretation Of Dna Typing Data, R Chakraborty

Faculty, Staff and Student Publications

No abstract provided.

Inclusion Of Data On Relatives For Estimation Of Allele Frequencies, R Chakraborty

Faculty, Staff and Student Publications

No abstract provided.

In Vitro Evaluation Of Cancer Patient Immune Responses Following Infusion Of Radiolabeled Murine Monoclonal Antibody, Kelly A. King

Loma Linda University Electronic Theses, Dissertations & Projects

Several monoclonal antibody (MAb) types derived from mice have been developed specifically for the use of targeting human tumors. The specificity of these murine MAb’s for their respective tumor antigens is very high making them potentially good immunotherapeutic agents for cancer treatment and diagnosis. A limiting factor in using these murine MAb’s in patients is the development of human anti-mouse antibody (HAMA). The presence of HAMA may reduce the effectiveness of MAb for tumor targeting. If patient sensitization could be quickly detected following the initial infusion of MAb, then future infusion could be altered or terminated to prevent further sensitization. …

Population Amalgamation And Genetic Variation: Observations On Artificially Agglomerated Tribal Populations Of Central And South America, R Chakraborty, P E Smouse, J V Neel

Faculty, Staff and Student Publications

The interpretation of data on genetic variation with regard to the relative roles of different evolutionary factors that produce and maintain genetic variation depends critically on our assumptions concerning effective population size and the level of migration between neighboring populations. In humans, recent population growth and movements of specific ethnic groups across wide geographic areas mean that any theory based on assumptions of constant population size and absence of substructure is generally untenable. We examine the effects of population subdivision on the pattern of protein genetic variation in a total sample drawn from an artificial agglomerate of 12 tribal populations …