| Multiadaptive Plan (MAP) IMRT to Accommodate Independent Movement of the Prostate and Pelvic Lymph Nodes |
Dec 2012 |
19 pages |
| Authors:
Ping Xia; CLEVELAND CLINIC FOUNDATION OH
|
 | Using our current planning margins to the prostate (6 mm posterior and 8 mm elsewhere) and pelvic lymph nodes (5 mm uniform), we found that aligning daily images to the pelvic bones would require a planning margin of the prostate greater what we used clinically. Aligning to the prostate soft tissue, a planning margin of 5 mm to the pelvic lymph nodes is adequate while the planning margin to the ... |
|
| Complementation of Myelodysplastic Syndrome Clones with Lentivirus Expression Libraries |
Jul 2012 |
10 pages |
| Authors:
Daniel Lindner; CLEVELAND CLINIC FOUNDATION OH
|
| We have successfully prepared sense expression libraries, characterized the size of their inserts which are fused to a green fluorescent protein tag, and packaged these libraries into lentivirus. Four different human MDS bone marrow isolates have been transfected with lentivirus at multiplicity of infection of 0.1. A collection of 252 puromycin resistant clones were isolated, genomic DNA was prepared, and clones were screened for ability to undergo myeloid differentiation in ... |
|
| WAVE3 is a Biomarker for Breast Cancer Progression and Metastasis |
Apr 2012 |
78 pages |
| Authors:
Khalid Sossey-Alaoui; CLEVELAND CLINIC FOUNDATION OH
|
| About one-third of patients with cancer have metastases that are detected at the time their cancer is first diagnosed, and an additional third of patients have metastases that are too small to be detected by usual diagnostic tests. These micrometastases, however, will eventually grow into clinically significant metastases if the patient receives no treatment or local treatment of the primary tumor only. Metastatic breast cancer is a disease with low ... |
|
| Multiadaptive Plan (MAP) IMRT to Accommodate Independent Movement of the Prostate and Pelvic Lymph Nodes |
Dec 2011 |
75 pages |
| Authors:
Ping Xia; CLEVELAND CLINIC FOUNDATION OH
|
| We found that the rotational shifts detected by aligning implanted markers between the planning images and the verification images may not determine the true rotation of the prostate. Ignoring these detected rotational shifts may lead to erroneous errors of localizing the prostate. We found that the prostate rotation can be compensated with corrections made in translational shifts, achieving improved geometric and dosimetric evaluation indices. Furthermore, we found that when the ... |
|
| Neuromimaging of Brain Injuries and Disorders at Cleveland Clinic |
Oct 2011 |
7 pages |
| Authors:
Stephen Rao; CLEVELAND CLINIC FOUNDATION OH
|
| Blast injuries are the leading cause of injury in the Afghanistan and Iraq wars. It is unknown whether the neural and cognitive sequelae of blast-related traumatic brain injury (TBI) differs from those resulting from mechanically-induced TBI commonly observed in civilian accidents. Understanding the potentially unique sequelae of blast-related TBI is critical for accurate diagnosis and designing effective pharmacological and neurorehabilitation interventions. Functional MRI is an imaging method that detects increases ... |
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| Neural and Behavioral Sequelae of Blast-Related Traumatic Brain Injury |
Sep 2011 |
6 pages |
| Authors:
Stephen M Rao; CLEVELAND CLINIC FOUNDATION OH
|
| Traumatic brain injuries (TBI) are a common occurrence from roadside blasts of improvised explosive devices (IEDs). In the proposed cross-sectional study, we aim to apply neurobehavioral testing and advanced MRI techniques [task-activated functional MRI (fMRI) and diffusion tensor imaging (DTI)] to gain a comprehensive understanding of the neural changes underlying blast-related MTBI. We will accomplish this goal by conducting advanced neuroimaging (task-activated fMRI and DTI fiber tracking) and neurobehavioral testing ... |
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| Molecular Basis of Autophagy-Mediated Resistance to Radiation and Apo2L/TRAIL Therapy in Prostate Cancer Cells |
MAY 2011 |
22 pages |
| Authors:
Kamini Singh; CLEVELAND CLINIC FOUNDATION OH
|
| Cell death and survival signaling pathways are important for the cellular response against ionizing radiation (IR) and chemotherapy in prostate cancer (PCa). IR and Apo2L/TRAIL, are widely used as therapeutics for PCa, however cellular resistance developed over the time may hinder their effectiveness. In this study we have investigated the response of Apo2L/TRAIL and IR in PCa cell lines. PC3 cells were more sensitive to Apo2L/TRAIL-mediated cell death as compared ... |
|
| WAVE3 Is a Biomarker for Breast Cancer Progression And Metastasis |
APR 2011 |
27 pages |
| Authors:
Khalid Sossey-Alaoui; CLEVELAND CLINIC FOUNDATION OH
|
| About one-third of patients with cancer have metastases that are detected at the time their cancer is first diagnosed, and an additional third of patients have metastases that are too small to be detected by usual diagnostic tests. These micrometastases, however, will eventually grow into clinically significant metastases if the patient receives no treatment or local treatment of the primary tumor only. Metastatic breast cancer is a disease with low ... |
|
| New Imaging Strategies for Prostate Cancer |
01 OCT 2010 |
50 pages |
| Authors:
Warren Heston; CLEVELAND CLINIC FOUNDATION OH
|
| Imaging prostate cancer could be desirable from the perspective of helping tell where the tumor is, which can also aid the choice of therapeutic approaches and as a means to quantitate the results of therapy. Best would be the availability of low molecular ligands that could be generated with positron containing radionucleotides given their high sensitivity. In this report we describe the development of these new ligands and their improved ... |
|
| Neural and Behavioral Sequelae of Blast-Related Traumatic Brain Injury |
Sep 2010 |
6 pages |
| Authors:
Stephen M Rao; Harvey Levin; CLEVELAND CLINIC FOUNDATION OH
|
| Traumatic brain injuries (TBI) are a common occurrence from roadside blasts of improvised explosive devices (IEDs). In the proposed cross-sectional study, we aim to apply neurobehavioral testing and advanced MRI techniques [task-activated functional MRI (fMRI) and diffusion tensor imaging (DTI)] to gain a comprehensive understanding of the neural changes underlying blast-related MTBI. We will accomplish this goal by conducting advanced neuroimaging (task-activated fMRI and DTI fiber tracking) and neurobehavioral testing ... |
|
| A Systems Biology Approach to Evaluate Ezrin as a Therapeutic Target in Breast Cancer |
Oct 2009 |
16 pages |
| Authors:
Neetu Gupta; CLEVELAND CLINIC FOUNDATION OH
|
| The complexity of breast cancer demands a systems level understanding of aberrant biochemical signaling in order to develop smart therapeutic targets. This study was undertaken to identify the binding partners of the ERM family protein, ezrin, in normal and metastatic breast cancer cells. We report the generation of ezrin constructs that were tagged at the C- and N-terminus to enable tandem affinity purification of ezrin protein complexes. Mutagenesis of ezrin ... |
|
| Deep Brain Stimulation of Treatment of Traumatic Brain Injury |
Oct 2009 |
5 pages |
| Authors:
Imad Najm; CLEVELAND CLINIC FOUNDATION OH
|
| This document explains the change in Principal Investigator for the award as of 13 Jul 2009. The initial Principal Investigator has relocated to another institution, and has relinquished the award back to Cleveland Clinic. Subsequent conversations with TATRC have led to a new project focus, utilizing deep brain stimulation (DBS) for the treatment of traumatic brain injury-related epilepsy. The new Principal Investigator, Dr. Imad Najm, is in the process of ... |
|
| Neural and Behavioral Sequelae of Blast-Related Traumatic Brain Injury |
30 Sep 2009 |
11 pages |
| Authors:
Stephen M Rao; CLEVELAND CLINIC FOUNDATION OH
|
| Traumatic brain injuries (TBI) are a common occurrence from roadside blasts of improvised explosive devices (IEDs). In the proposed cross-sectional study, we aim to apply neurobehavioral testing and advanced MRI techniques [task-activated functional MRI (fMRI) and diffusion tensor imaging (DTI)] to gain a comprehensive understanding of the neural changes underlying blast-related MTBI. We will accomplish this goal by conducting advanced neuroimaging (task-activated fMRI and DTI fiber tracking) and neurobehavioral testing ... |
|
| Allograft Fascia Lata as an Augmentation Device for Musculoskeletal Repairs |
Dec-2008 |
7 pages |
| Authors:
K A Derwin; A Aurora; J P Iannotti; CLEVELAND CLINIC FOUNDATION OH
|
| Musculoskeletal soft tissue injuries during combat are a source of debilitating pain, the treatment and evaluation of which pose a significant challenge to the orthopedic community. Extracellular matrix (ECM) scaffolds derived from various sources and species are being explored for the repair of musculoskeletal tendon injuries. In this paper we demonstrate that amongst these ECM scaffolds, only tensor fascia lata has structural and tensile material properties comparable to tendon, but ... |
|
| Targeting Androgen Receptor Function by MicroRNA in Prostate Cancer |
Jul-2008 |
7 pages |
| Authors:
Girish C Shukla; CLEVELAND CLINIC FOUNDATION OH
|
| Prostate cancer is the most commonly diagnosed and second most deadly cancer in North American men and the blockade of androgen action through the AR has been the cornerstone of systemic therapy of prostate cancer. However, the effectiveness of this therapy is rather transient which inevitably fails and tumor growth resumes despite androgen blockade. The failure of AR receptor antagonists results in higher levels of AR protein which promotes the ... |
|
| Acceleration of Ligament Healing with Cellular Attractants |
Jul 2008 |
67 pages |
| Authors:
Cahir A McDevitt; CLEVELAND CLINIC FOUNDATION OH
|
| Rupture of the anterior cruciate ligament (ACL) with subsequent damage to the menisci and articular cartilage in the knee joint is a major cause of morbidity in the armed forces. type VI collagen is a haptotactic cell attractant. We have shown that type VI collagen with bound heparin/FGF-2 or hyaluronan or fibronectin promotes migration of canine ACL and DET cells. Insertion of type VI collagen into a wound in the ... |
|
| Multi Institutional, Multi National Medical Simulator Validation Studies |
Apr-2008 |
14 pages |
| Authors:
Charles P Steiner; CLEVELAND CLINIC FOUNDATION OH
|
| The use of medical skills simulators for the training and assessment of clinicians is gaining support in the medical teaching facilities around the world. We propose the use and assessment of a medical simulator for the teaching of a set of urological procedures. Clinicians will be enrolled at multiple centers and complete a course of study which may involved the use of a medical simulator training system. At the end ... |
|
| Targeting Androgen Receptor Function by MicroRNA in Prostate Cancer |
JUL 2007 |
6 pages |
| Authors:
Girish C. Shula; CLEVELAND CLINIC FOUNDATION OH
|
| Prostate cancer is the most commonly diagnosed and second most deadly cancer in North American men and the blockade of androgen action through the AR has been the cornerstone of systemic therapy of prostate cancer. However, the effectiveness of this therapy is rather transient which inevitably fails and tumor growth resumes despite androgen blockade. The failure of AR receptor antagonists results in higher levels of AR protein which promotes the ... |
|
| Novel Role of Prostate-Specific Membrane Antigen in Prostate Cancer Invasion and Metastasis |
APR 2007 |
21 pages |
| Authors:
Arundhati Ghosh; CLEVELAND CLINIC FOUNDATION OH
|
| Prostate Specific Membrane Antigen, PSMA is a type II transmembrane glycoprotein, overexpressed in prostate carcinoma (PCa) including androgen sensitive and independent disease, increased in expression with early relapse following therapy. PSMA is a carboxypeptidase with two important enzymatic functions, namely, folate hydrolase and NAALADase. We have used in vitro invasion assays to explore the possible role of PSMA in PCa cells. Androgen dependent PCa lines, which express PSMA endogenously (e.g., ... |
|
| CTLA-4 Blockade-Based Immunotherapy in Prostate Cancer |
Jan 2007 |
8 pages |
| Authors:
Brian I Rini; CLEVELAND CLINIC FOUNDATION OH
|
| This research project investigated immunotherapy for prostate cancer. Specifically, we explored the use of Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) in combination with blockade of a T cell inhibitory molecule called Cytotoxic T-Lymphocyte-Associated Molecule-4 (CTLA-4). We studied repetitive dosing of an anti-CTLA-4 antibody in combination with subcutaneous GM-CSF to determine the safety of this combination. Concomitantly, peripheral blood was being collected from patients to evaluate the immune response generated. The original ... |
|
| Far Forward Battlefield Telemedicine: Ultrasonic Guidance in Diagnosis and Emergency Therapeutics |
Aug 2006 |
16 pages |
| Authors:
James D Thomas; CLEVELAND CLINIC FOUNDATION OH
|
| To improve battlefield assessment of injured personnel we are exploiting several convergent trends in medicine and technology, including ultrasound miniaturization and wireless connectivity. Specific aims include (1) validation of portable ultrasound to diagnose cardiac tamponade, pneumothorax, intraabdominal hemorrhage, etc.; (2) extension of digital echocardiography and local telemedicine to assist remote centers in transesophageal echocardiography; (3) Development of wireless telemedicine systems to relay ultrasonic images and loops to a remote review ... |
|
| Advanced Soft Tissue for Telemedicine and Surgical Simulation |
JUL 2006 |
10 pages |
| Authors:
Ivan Vesely; CLEVELAND CLINIC FOUNDATION OH
|
| The objectives of this project were to develop computer based models of soft tissues that could eventually be integrated into virtual reality-based surgical simulators. To that end, we have developed a number of computer algorithms that span the scales from the microstructural to the phenomenological, and from 1-D to 3-D. For the 1-D case, we have developed a model of fractional order viscoelasticity. For the 3-D case, we have developed ... |
|
| Far Forward Battlefield Telemedicine: Ultrasonic Guidance in Diagnosis and Emergency Therapeutics |
SEP 2005 |
14 pages |
| Authors:
James D. Thomas; CLEVELAND CLINIC FOUNDATION OH
|
| To improve battlefield assessment of injured personnel we are exploiting several convergent trends in medicine and technology, including ultrasound miniaturization and wireless connectivity. Specific aims include (1) validation of portable ultrasound to diagnose cardiac tamponade, pneumothorax, intraabdominal hemorrhage, etc.; (2) extension of digital echocardiography and local telemedicine to assist remote centers in transesophageal echocardiography; (3) Development of wireless telemedicine systems to relay ultrasonic images and loops to a remote review ... |
|
| Neural Mechanism of Chronic Fatigue Syndrome |
Apr 2005 |
5 pages |
| Authors:
Quang H Yue; CLEVELAND CLINIC FOUNDATION OH
|
| Nearly one million Americans suffer from chronic fatigue syndrome (CFS). More than 15% of Gulf War veterans (GWV) were found to have CFS. The disease significantly reduces work production of civilian patients and combat ability/readiness of US military forces. Increasing scientific evidence suggests that CFS is a biological illness involving pathology of the central nervous system (CNS). However, little is known about how the CNS is affected by CFS. This ... |
|
| Rapid Detection of Cellular Response to Biological Agents |
FEB 2005 |
135 pages |
| Authors:
Bryan R. Williams; CLEVELAND CLINIC FOUNDATION OH
|
| Our program objective is to develop simple and rapid methods for detecting at a cellular level, individual responses to environmental stresses elaborated by exposure to infectious agents such as bacteria and viruses. Our methods are based on transcript profiling and post-translational modification of proteins involved in signal transduction. Our hypothesis is that human cells respond to infectious insults to a genetically predetermined extent by stimulating the expression of sets of ... |
|
| Far Forward Battlefield Telemedicine: Ultrasonic Guidance in Diagnosis and Emergency Therapeutic |
SEP 2004 |
16 pages |
| Authors:
James D. Thomas; CLEVELAND CLINIC FOUNDATION OH
|
| To improve battlefield assessment of injured personnel we are exploiting several convergent trends in medicine and technology, including ultrasound miniaturization and wireless connectivity. Specific aims include (1) validation of portable ultrasound to diagnose cardiac tamponade, pneumothorax, intraabdominal hemorrhage, etc.; (2) extension of digital echocardiography and local telemedicine to assist remote centers in transesophageal echocardiography; (3) Development of wireless telemedicine systems to relay ultrasonic images and loops to a remote review ... |
|
| A Novel Role for Integrin Linked Kinase in Breast Cancer |
SEP 2004 |
37 pages |
| Authors:
Pratima Karnik; CLEVELAND CLINIC FOUNDATION OH
|
| Allelic loss at the short arm of chromosome 11 is one of the most common and potent events in the progression and metastasis of breast cancer. Here, we present evidence that the Integrin-Linked Kinase (ILK) gene maps to the commonly deleted chromosome 11p15.5 and suppresses malignant growth of human breast cancer cells both in vitro and in vivo. ILK is expressed iii normal breast tissue but not in metastatic breast ... |
|
| Rapid Detection of Cellular Responses to Biological Agents |
FEB 2004 |
33 pages |
| Authors:
Bryan R. Williams; CLEVELAND CLINIC FOUNDATION OH
|
| Our program objective is to develop simple and rapid methods for detecting, at a cellular level, individual responses to environmental stresses elaborated by exposure to infectious agents such as bacteria and viruses. Our methods are based on transcript profiling and post-translational modification of proteins involved in signal transduction. Our hypothesis is that human cells respond to infectious insults to a genetically predetermined extent by stimulating the expression of sets of ... |
|
| Development of a Biologic Basis for PSMA Targeting in Prostate Cancer |
FEB 2004 |
45 pages |
| Authors:
Warren Heston; CLEVELAND CLINIC FOUNDATION OH
|
| PSMA is a membrane protein that is highly expressed in the prostate and prostate cancers. It is also strongly expressed in the neovasculature of most solid tumors. PSMA is therefore an excellent target for therapy. We have examined the biology of PSMA relative to ;he possibility of it serving as a target for prodrug or targeted small molecule therapeutics. We observe that although PSMA can hydrolyze glutamate from polygammglutamated methotrexate, ... |
|
| Investigation of SNARE-Mediated Membrane Trafficking in Prostate Cancer Cells |
NOV 2003 |
58 pages |
| Authors:
Xin Li; CLEVELAND CLINIC FOUNDATION OH
|
| In order to better understand how polarized membrane trafficking pathways change during the loss of epithelial cell polarity during cancer progression we have studied syntaxins 3 and 4 in prostate cancer. Tumors of different stages from a TRAMP mice, human prostate cancers, and human prostate cancer cell lines were investigated for the expression and subcellular localization of syntaxins 3 and 4 by confocal microscopy and Western blot analysis. Like in ... |
|
| Far Forward Battlefield Telemedicine: Ultrasonic Guidance in Diagnosis and Emergency Therapeutics |
SEP 2003 |
13 pages |
| Authors:
James D. Thomas; CLEVELAND CLINIC FOUNDATION OH
|
| To improve battlefield assessment of injured personnel we are exploiting several convergent trends in medicine and technology, including ultrasound miniaturization and wireless connectivity. Specific aims include (1) validation of portable ultrasound to diagnose cardiac tamponade, pneumothorax, intraabdominal hemorrhage, etc.; (2) extension of digital echocardiography and local telemedicine to assist remote centers in transesophageal echocardiography; (3) Development of wireless telemedicine systems to relay ultrasonic images and loops to a remote review ... |
|
| A Novel Role for Integrin-Linked Kinase in Breast Cancer |
SEP 2003 |
13 pages |
| Authors:
Pratima Karnik; CLEVELAND CLINIC FOUNDATION OH
|
| Allelic loss at the short arm of chromosome 11 is one of the most common and potent events in the progression and metastasis of breast cancer. Here, we present evidence that the Integrin-Linked Kinase (ILK) gene maps to the commonly deleted chromosome 11p15.5 and suppresses malignant growth of human breast cancer cells both in vitro and in vivo. ILK is expressed in normal breast tissue but not in metastatic breast ... |
|
| Neural Mechanisms of Chronic Fatigue Syndrome |
APR 2003 |
4 pages |
| Authors:
Guang H. Yue; CLEVELAND CLINIC FOUNDATION OH
|
| Nearly one million Americans suffer from chronic fatigue syndrome (CFS). More than 15% of Gulf War veterans (GWV) were found to have CFS. The disease significantly reduces work production of civilian patients and combat ability/readiness of US military forces. Increasing scientific evidence suggests that CFS is a biological illness involving pathology of the central nervous system (CNS). However, little is known about how the CNS is affected by CFS. This ... |
|
| Development of a Biologic Basis for PSMA Targeting in Prostate Cancer |
FEB 2003 |
85 pages |
| Authors:
Warren D. Heston; CLEVELAND CLINIC FOUNDATION OH
|
| PSMA is a strongly expressed protein in prostate cancer. It is a type two-membrane protein with a short 19 amino acid terminal piece inside the cell, a membrane-spanning region from amino acids 20 to 43, and the rest of the 750 amino acids residing outside of the cell. We discovered that PSMA has unique hydrolytic activity as a carboxypeptidase in releasing glutamate either from polygammaglutamated folate as a folate hydrolase ... |
|
| Investigation of SNARE-Mediated Membrane Trafficking in Prostate Cancer Cells |
FEB 2003 |
20 pages |
| Authors:
Xin Li; CLEVELAND CLINIC FOUNDATION OH
|
| The specific purposes of this project are to investigate how the expression and localization of membrane SNAREs in prostate carcinomas, and what the relationship to the degree of malignancy and metastasis. 15 transgenic mice of prostate cancer (Tramp) with different stages of carcingensis, and 5 cases of human prostatic carcinomas were used. Paraffin sections were immuno-stained with anti-t-SNARE antibodies, syntaxin 3 and syntaxin 4. The localizations of t- SNAREs were ... |
|
| Rapid Detection of Cellular Responses to Biological Agents |
FEB 2003 |
14 pages |
| Authors:
Bryan R. G. Williams; CLEVELAND CLINIC FOUNDATION OH
|
| Our program objective is to develop simple and rapid methods for detecting, at a cellular level, individual responses to environmental stresses elaborated by exposure to infectious agents such as bacteria and viruses. Our methods are based on transcript profiling and post-translational modification of proteins involved in signal transduction. Our hypothesis is that human cells respond to infectious insults to a genetically predetermined extent by stimulating the expression of sets of ... |
|
| Ultrasound Imaging Initiative |
JAN 2003 |
94 pages |
| Authors:
Raj Shekhar; CLEVELAND CLINIC FOUNDATION OH
|
| This objective of this project was to build a real-time 3D ultrasound imaging system for combat casualty care. The high frame rate necessary for real-time 3D imaging was obtained using a synthetic aperture beamforming technique. The technique uses a fraction of the transmit pulses required by a conventional imaging system and permits very rapid image acquisition with no degradation of image quality. A beamformer capable of generating 650 2D image ... |
|
| Foot and Ankle Injuries in the Military |
OCT 2002 |
17 pages |
| Authors:
Mark D. Grabiner; CLEVELAND CLINIC FOUNDATION OH
|
| More than 80 % of military injuries occur in the lower extremities and the most frequent site of injury is the foot and ankle (Atmeida et al, 1996) . Calcaneal fractures are one of the serious and debilitating injuries, which are difficult to treat and rehabilitate. The severity of the injury is dependent on the type of fracture. The most difficult to manage are the intra-articular fractures which occur in ... |
|
| A Novel Role for Integrin-Linked Kinase in Breast Cancer |
SEP 2002 |
12 pages |
| Authors:
Pratima Karnik; CLEVELAND CLINIC FOUNDATION OH
|
| Allelic loss at the short arm of chromosome 11 is one of the most common and potent events in the progression and metastasis of breast cancer. Here, we present evidence that the Integrin-Linked Kinase (ILK) gene maps to the commonly deleted chromosome 11p15.5 and suppresses malignant growth of human breast cancer cells both in vitro and in vivo. ILK is expressed in normal breast tissue but not in metastatic breast ... |
|
| Tissue Engineering Initiative |
AUG 2002 |
184 pages |
| Authors:
Vincent C. Hascall; CLEVELAND CLINIC FOUNDATION OH
|
| The Cleveland Clinic Foundation Tissue Engineering Initiative was proposed to initiate novel tissue engineering projects as a collaboration between connective tissue biochemists, bioengineers, prototype engineers, and physician researchers from the Department of Biomedical Engineering. The primary focus of these projects was to test applications of hylan gels (divinyl sulfone crosslinked, purified hyaluronan). Gels were formulated in-house, as well as evaluating specimens obtained from the Matrix Biology Institute. During the final ... |
|
| Eosinophils as Mediators of DNA Oxidative Damage in Breast Cancer |
JUL 2002 |
11 pages |
| Authors:
Stanley L. Hazen; CLEVELAND CLINIC FOUNDATION OH
|
| The overall goal of this proposal were to test the hypothesis that eosinophils promote DNA oxidative damage in breast carcinoma. DNA oxidative damage is linked to mutation, transformation and cancer development and eosinophil peroxidase (EPO), a hemoprotein secreted from eosinophils, is present in the majority of breast cancer biopsies. Our initial aim was to determine whether EPO promotes oxidative damage of cellular DNA through formation of mutagenic hydroxyl radical (DN)-generated ... |
|
| Characterization of Prostate-Specific Membrane Antigen (PSMA) for Use in Therapeutic and Diagnostic Strategies Against Prostate Cancer |
JUN 2002 |
55 pages |
| Authors:
Denise S. O'Keefe; Warren D. Heston; CLEVELAND CLINIC FOUNDATION OH
|
| Prostate-Specific Membrane Antigen (PSMA) appears to be an ideal prostate cancer marker and potential therapeutic target, however there have been reports of PSMA expression in non-prostatic tissues, including brain, kidney and liver. Such expression of PSMA could weaken the potential of the gene as a prostate cancer marker or at least produce confusing and conflicting data. Prior to this project, we had demonstrated that there was another human gene, 97% ... |
|
| Development of a Biological Basis for PSMA Targeting in Prostate Cancer |
FEB 2002 |
52 pages |
| Authors:
Warren D. Heston; CLEVELAND CLINIC FOUNDATION OH
|
| PSMA is a strongly expressed protein in prostate cancer, and it is a type-two membrane protein with the bulk of the molecule and enzymatic activity outside of the cell and thus is accessible to therapeutic attack. We discovered that PSMA has activity as a unique folate hydrolase, being a glutamate carboxypeptidase. We also observed that cells expressing PSMA were sensitive to killing by polygammaglutamated methotrexate while non-PSMA expressing cells were ... |
|
| A Novel Role for Integrin Linked Kinase in Breast Cancer |
SEP 2001 |
21 pages |
| Authors:
Pratima Karnik; CLEVELAND CLINIC FOUNDATION OH
|
| Allelic loss at the short arm of chromosome ii is one of the most common and potent events in the progression and metastasis of breast cancer. Here, we present evidence that the Integrin-Linked Kinase (ILK) gene maps to the commonly deleted chromosome 11p15.5 and suppresses malignant growth of human breast cancer cells in vitro. ILK is expressed in normal breast tissue but not in metastatic breast cancer cell lines or ... |
|
| Isolation of Genes from Chromosome Region Ip31 Involved in the Development of Breast Cancer |
SEP 2001 |
5 pages |
| Authors:
John K. Cowell; CLEVELAND CLINIC FOUNDATION OH
|
| The p31 region of chromosome 1 shows frequent (50%) loss of heterozygosity (LOH) in breast tumors. This observation implies the presence of a tumor suppressor gene in this region which, when mutated contributes to tumorigenesis. The maximal common region undergoing LOH extends over approximately 2Mbp. We have constructed a map of overlapping BAC clones spanning this region with only 4 gaps. The total available sequence from this region suggests that ... |
|
| Targeted Therapy of Human Breast Cancer by 2-5A-Antisense Directed Against Telomerase RNA |
SEP 2001 |
5 pages |
| Authors:
John K. Cowell; CLEVELAND CLINIC FOUNDATION OH
|
| Targeting telomerase RNA (hTR) for degradation by RNAseL in breast cancer cells using antisense molecules linked to 2-5A has demonstrated high levels of cytotoxicity in vivo and in vitro. The antisense molecules used in preliminary studies carried a phosphodiester backbone which can be recognized by endogenous nucleases and so make the half-life of these molecules very short. Having demonstrated in vitro that breast cancer cells undergo apoptosis following this treatment, ... |
|
| Isolation of Breast Tumor Suppressor Genes from Chromosome 11p |
SEP 2001 |
43 pages |
| Authors:
Pratima Karnik; CLEVELAND CLINIC FOUNDATION OH
|
| In published studies, we have shown that chromosome 11p15.5 exhibits loss of heterozygosity (LOH) in ^60% of breast tumors, and that there is a significant correlation between lip LOH, lymphatic invasion and aggressive metastatic disease. Our data suggests that chromosome 11p15.5 harbors a tumor/metastasis suppressor gene. An intriguing candidate gene that we have mapped to the tumor/metastasis suppressor locus on chromosome 11p15.5 is Integrin-linked Kinase (ILK). ILK is a newly ... |
|
| Computer Assisted Minimally Invasive Surgery |
AUG 2001 |
16 pages |
| Authors:
Joseph F. Hahn; CLEVELAND CLINIC FOUNDATION OH
|
| The Operating Room of the Future will deliver the optimal surgical environment through the integration of people, equipment, space and process. The Computer Assisted Minimally Invasive Surgery (CAMIS) project has completed the development and deployment of a number of components critical to the achievement of The Operating Room of the Future concept. The first component is a Digital Micro Encoscope (DME). This device provides endoscopic visualization of orthopaedic joint spaces. ... |
|
| Eosinophils as Mediators of DNA Oxidative Damage in Breast Cancer |
JUL 2001 |
33 pages |
| Authors:
Stanley Hazen; CLEVELAND CLINIC FOUNDATION OH
|
| The overall goal of this proposal is to test the hypothesis that eosinophils promote DNA oxidative damage in breast carcinoma. DNA oxidative damage is linked to mutation, transformation and cancer development and eosinophil peroxidase (EPO), a hemoprotein secreted from eosinophils, is present in the majority of breast cancer biopsies. Our initial aim was to determine whether EBO promotes oxidative damage of cellular DNA through formation of mutagenic hydroxyl radical (OH) ... |
|
| Characterization of Prostate-Specific Membrane Antigen (PSMA) for Use in Therapeutic and Diagnostic Strategies Against Prostate Cancer |
JUL 2001 |
63 pages |
| Authors:
Denise S. O'Keefe; Warren D. Heston; CLEVELAND CLINIC FOUNDATION OH
|
| Prostate-Specific Membrane Antigen (PSMA) appears to be an ideal prostate cancer marker and potential therapeutic target, however there have been reports of PSMA expression in non-prostatic tissues, including brain, kidney and liver. Such expression of PSMA could weaken the potential of the gene as a prostate cancer marker or at least produce confusing and conflicting data. Prior to this project, we had demonstrated that there was another human gene, 97% ... |
|
Reports by Corporate Author
