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Histological and fine structural alterations in the aging rat ventral prostate gland

Description: The purpose of this study was to examine the ventral prostate from Sprague-Dawley rats of the ages two, twelve, and twenty-four months to determine the extent of histological and fine structural change. The tissue was processed for routine light and electron microscopy.
Date: August 1982
Creator: Bentley, Evert Randall
Partner: UNT Libraries

Initial results of a positron tomograph for prostate imaging

Description: We present the status and initial images of a positrontomograph for prostate imaging that centers a patient between a pair ofexternal curved detector banks (ellipse: 45 cm minor, 70 cm major axis).The distance between detector banks adjusts to allow patient access andto position the detectors as closely as possible for maximum sensitivitywith patients of various sizes. Each bank is composed of two axial rowsof 20 CTI PET Systems HR+ block detectors for a total of 80 modules inthe camera. Compared to an ECAT HR PET system operating in 3D mode, ourcamera uses about one-quarter the number of detectors and hasapproximately the same sensitivity for a central point source, becauseour detectors are close to the patient. The individual detectors areangled in the plane to point towards the prostate to minimize resolutiondegradation in that region. The detectors are read out by modified CTIdata acquisition electronics. We have completed construction of thegantry and electronics, have developed detector calibration and dataacquisition software, and are taking coincidence data. We demonstratethat we can clearly visualize a "prostate" in a simple phantom.Reconstructed images of two phantoms are shown.
Date: November 29, 2004
Creator: Huber, J. S.; Choong, W. S.; Moses, W. W.; Qi, J.; Hu, J.; Wang, G. C. et al.
Partner: UNT Libraries Government Documents Department

Ursolic Acid Inhibits the Initiation, Progression of Prostate Cancer and Prolongs the Survival of TRAMP Mice by Modulating Pro-Inflammatory Pathways

Description: Article on ursolic acid inhibiting the initiation, progression of prostate cancer and prolonging the survival of TRAMP mice by modulating pro-inflammatory pathways.
Date: March 12, 2012
Creator: Shanmugam, Muthu K.; Ong, Tina H.; Kumar, Alan Prem; Chang, Kai Lun; Ho, Paul C.; Wong, Peter T. H. et al.
Partner: UNT College of Arts and Sciences

Development of New Treatments for Prostate Cancer

Description: The Dean and Betty Gallo Prostate Cancer Center (GPCC) was established with the goal of eradicating prostate cancer and improving the lives of men at risk for the disease through research, treatment, education and prevention. GPCC was founded in the memory of Dean Gallo, a beloved New Jersey Congressman who died tragically of prostate cancer diagnosed at an advanced stage. GPCC unites a team of outstanding researchers and clinicians who are committed to high-quality basic research, translation of innovative research to the clinic, exceptional patient care, and improving public education and awareness of prostate cancer. GPCC is a center of excellence of The Cancer Institute of New Jersey, which is the only NCI-designated comprehensive cancer center in the state. GPCC efforts are now integrated well as part of our Prostate Program at CINJ, in which Dr. Robert DiPaola and Dr. Cory Abate-Shen are co-leaders. The Prostate Program unites 19 investigators from 10 academic departments who have broad and complementary expertise in prostate cancer research. The overall goal and unifying theme is to elucidate basic mechanisms of prostate growth and oncogenesis, with the ultimate goal of promoting new and effective strategies for the eradication of prostate cancer. Members' wide range of research interests collectively optimize the chances of providing new insights into normal prostate biology and unraveling the molecular pathophysiology of prostate cancer. Cell culture and powerful animal models developed by program members recapitulate the various stages of prostate cancer progression, including prostatic intraepithelial neoplasia, adenocarcinoma, androgen-independence, invasion and metastases. These models promise to further strengthen an already robust program of investigator-initiated therapeutic clinical trials, including studies adopted by national cooperative groups. Efforts to translate laboratory results into clinical studies of early detection and chemoprevention are underway. The specific goals of this program are: (1) To investigate the molecular mechanisms underlying ...
Date: February 1, 2005
Creator: DiPaola, R. S.; Abate-Shen, C. & Hait, W. N.
Partner: UNT Libraries Government Documents Department

Characterization of a PET Camera Optimized for ProstateImaging

Description: We present the characterization of a positron emission tomograph for prostate imaging that centers a patient between a pair of external curved detector banks (ellipse: 45 cm minor, 70 cm major axis). The distance between detector banks adjusts to allow patient access and to position the detectors as closely as possible for maximum sensitivity with patients of various sizes. Each bank is composed of two axial rows of 20 HR+ block detectors for a total of 80 detectors in the camera. The individual detectors are angled in the transaxial plane to point towards the prostate to reduce resolution degradation in that region. The detectors are read out by modified HRRT data acquisition electronics. Compared to a standard whole-body PET camera, our dedicated-prostate camera has the same sensitivity and resolution, less background (less randoms and lower scatter fraction) and a lower cost. We have completed construction of the camera. Characterization data and reconstructed images of several phantoms are shown. Sensitivity of a point source in the center is 946 cps/mu Ci. Spatial resolution is 4 mm FWHM in the central region.
Date: November 11, 2005
Creator: Huber, Jennifer S.; Choong, Woon-Seng; Moses, William W.; Qi,Jinyi; Hu, Jicun; Wang, G.C. et al.
Partner: UNT Libraries Government Documents Department

Dual-Modality PET/Ultrasound imaging of the Prostate

Description: Functional imaging with positron emission tomography (PET)will detect malignant tumors in the prostate and/or prostate bed, as well as possibly help determine tumor ''aggressiveness''. However, the relative uptake in a prostate tumor can be so great that few other anatomical landmarks are visible in a PET image. Ultrasound imaging with a transrectal probe provides anatomical detail in the prostate region that can be co-registered with the sensitive functional information from the PET imaging. Imaging the prostate with both PET and transrectal ultrasound (TRUS) will help determine the location of any cancer within the prostate region. This dual-modality imaging should help provide better detection and treatment of prostate cancer. LBNL has built a high performance positron emission tomograph optimized to image the prostate.Compared to a standard whole-body PET camera, our prostate-optimized PET camera has the same sensitivity and resolution, less backgrounds and lower cost. We plan to develop the hardware and software tools needed for a validated dual PET/TRUS prostate imaging system. We also plan to develop dual prostate imaging with PET and external transabdominal ultrasound, in case the TRUS system is too uncomfortable for some patients. We present the design and intended clinical uses for these dual imaging systems.
Date: November 11, 2005
Creator: Huber, Jennifer S.; Moses, William W.; Pouliot, Jean & Hsu, I.C.
Partner: UNT Libraries Government Documents Department

The development of a compact positron tomograph for prostate imaging

Description: We give design details and expected image results of a compact positron tomograph designed for prostate imaging that centers a patient between a pair of external curved detector banks (ellipse: 45 cm minor, 70 cm major axis). The bottom bank is fixed below the patient bed, and the top bank moves upward for patient access and downward for maximum sensitivity. Each bank is composed of two rows (axially) of 20 CTI PET Systems HR+ block detectors, forming two arcs that can be tilted to minimize attenuation. Compared to a conventional PET system, our camera uses about one-quarter the number of detectors and has almost two times higher solid angle coverage for a central point source, because the detectors are close to the patient. The detectors are read out by modified CTI HRRT data acquisition electronics. The individual detectors are angled in the plane to point towards the prostate to minimize reso
Date: December 17, 2002
Creator: Huber, Jennifer S.; Qi, Jinyi; Derenzo, Stephen E.; Moses, William W.; Huesman, Ronald H. & Budinger, Thomas F.
Partner: UNT Libraries Government Documents Department

Designing a Social Marketing Plan to Promote Hispanic Participation at Prostate Cancer Screenings

Description: Prostate cancer is the most commonly occurring cancer and the second leading cause of cancer death for men in the United States. Because early prostate cancer is frequently without symptoms and data on how to prevent prostate cancer is lacking, early detection has the greatest potential for decreasing mortality. Studies have shown Hispanics/Latinos to be less likely than whites or African-Americans to utilize prostate cancer screening exams. The purpose of this descriptive study was to design a social marketing plan which could be used as a model to promote Hispanic/Latino participation at prostate cancer screenings. Information obtained through medical and marketing literature review, the author's experiences serving on the promotion committee of a community-sponsored prostate cancer screening project, and interviews with 51 Hispanic/Latino prostate cancer screening participants is described and incorporated into a guide with recommendations for future program planners.
Date: December 1995
Creator: Zimmerman, Suzanne M. (Suzanne Marie)
Partner: UNT Libraries

Inflammation and Atrophy Precede Prostate Neoplasia in PhIP Induced Rat Model

Description: 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) has been implicated as a major mutagenic heterocyclic amine in the human diet and is carcinogenic in the rat prostate. In order to validate PhIP induced rat prostate neoplasia as a model of human prostate cancer progression, we sought to study the earliest histologic and morphologic changes in the prostate and to follow the progressive changes over time. We fed 67 male Fischer F344 5 week old rats with PhIP (400 PPM) or control diets for 20 weeks, and then sacrificed animals for histomorphologic examination at age 25 weeks, 45 weeks, and 65 weeks. Animals treated with PhIP showed significantly more inflammation (P=.002 (25wk), >.001(45wk), .016(65wk)) and atrophy (P=.003(25wk), >.001(45wk), .006 (65wk)) in their prostate glands relative to controls. Prostatic intraepithelial neoplasia (PIN) occurred only in PhIP treated rats. PIN lesions arose in areas of glandular atrophy, most often in the ventral prostate. Atypical cells in areas of atrophy show loss of glutathione S-transferase pi immunostaining preceding development of PIN. None of the animals in this study developed invasive carcinomas differing from previous reports. Overall, these findings suggest that the pathogenesis of prostatic neoplasia in the PhIP treated rat prostate proceeds from inflammation to post-inflammatory proliferative atrophy to PIN.
Date: June 1, 2006
Creator: Borowsky, A D; Dingley, K; Ubick, E; Turteltaub, K; Cardiff, R D & DeVere-White, R
Partner: UNT Libraries Government Documents Department

Numerical simulations of a diode laser BPH treatment system

Description: Numerical simulations are presented of the laser-tissue interaction of a diode laser system for treating benign prostate hyperplasia. The numerical model includes laser light transport, heat transport, cooling due to blood perfusion, thermal tissue damage, and enthalpy of tissue damage. Comparisons of the simulation results to clinical data are given. We report that a reasonable variation from a standard set of input data produces heating times which match those measured in the clinical trials. A general trend of decreasing damage volume with increasing heating time is described. We suggest that the patient-to- patient variability seen in the data can be explained by differences in fundamental biophysical properties such as the optical coefficients. Further work is identified, including the measurement and input to the model of several specific data parameters such as optical coefficients, blood perfusion cooling rate, and coagulation rates.
Date: February 23, 1999
Creator: Esch, V; London, R A & Papademetriou, S
Partner: UNT Libraries Government Documents Department

Does Prostate Cancer Begin in the Prostate? Key Predictors of Diagnosis

Description: The purpose of this exploratory study was to identify the key predictors of prostate cancer; such study may lead to the development of appropriate interventions and prevention. Previous epidemiological studies have found these following factors to be key predictors for being diagnosed with hormone-associated carcinoma such as prostate cancer: age, ethnicity, physical activity, family history, diet, sleep amount, marital status, and having another form of carcinoma. Many studies have included results only for men over the age of 65, however, prostate cancer is claiming the lives of many African American, Hispanic and White American men over the age of 35, and younger men are more likely to battle it if they are genetically predisposed. The sample population (N =21,646) was selected because men aged 35 or over have the highest prevalence of prostate cancer. Of this sample, 619 reported having prostate cancer, and 1,401 reported having some other type of cancer. This study employs a logistic regression model using SAS® and utilizes the National Health Interview Survey data set and a multivariate analysis of the years 2006, 2007, and 2008. To improve the quality of future research the methods need modification, the subpopulation being studied should be larger, and the studies should be longitudinal. This particular study found the aforementioned factors to be critical in predicting prostate cancer. Maximum sun exposure was found to be also related to having prostate cancer. Key predictors for prostate cancer diagnosis are age, ethnicity, having some other cancer and maximum sun exposure, and education. Though previous studies have found physical activity, sleep amount, and occupation to be beneficial in reducing the risk for prostate cancer, it was not confirmed in this particular study.
Date: August 2011
Creator: Orakpo, W. Nnamdi
Partner: UNT Libraries

Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor

Description: Cellular senescence suppresses cancer by arresting cell proliferation, essentially permanently, in response to oncogenic stimuli, including genotoxic stress. We modified the use of antibody arrays to provide a quantitative assessment of factors secreted by senescent cells. We show that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy. This senescence-associated secretory phenotype (SASP) developed slowly over several days and only after DNA damage of sufficient magnitude to induce senescence. Remarkably similar SASPs developed in normal fibroblasts, normal epithelial cells, and epithelial tumor cells after genotoxic stress in culture, and in epithelial tumor cells in vivo after treatment of prostate cancer patients with DNA-damaging chemotherapy. In cultured premalignant epithelial cells, SASPs induced an epithelial-mesenchyme transition and invasiveness, hallmarks of malignancy, by a paracrine mechanism that depended largely on the SASP factors interleukin (IL)-6 and IL-8. Strikingly, two manipulations markedly amplified, and accelerated development of, the SASPs: oncogenic RAS expression, which causes genotoxic stress and senescence in normal cells, and functional loss of the p53 tumor suppressor protein. Both loss of p53 and gain of oncogenic RAS also exacerbated the promalignant paracrine activities of the SASPs. Our findings define a central feature of genotoxic stress-induced senescence. Moreover, they suggest a cell-nonautonomous mechanism by which p53 can restrain, and oncogenic RAS can promote, the development of age-related cancer by altering the tissue microenvironment.
Date: October 24, 2008
Creator: Coppé, Jean-Philippe; Patil, Christopher; Rodier, Francis; Sun, Yu; Munoz, Denise; Goldstein, Joshua et al.
Partner: UNT Libraries Government Documents Department

PSA-Based Screening Outcomes, Dietary Heterocyclic Amine Exposure, and Prostate Cancer Risk in African Americans: Annual Report (Year 1 of 3)

Description: Prostate cancer (PC) is the second leading cause of male U.S. cancer deaths, with African-Americans having the highest rate of PC mortality worldwide, as well as more abnormal results from screening tests that correlate with current or eventual PC. A 3-year prospective clinic-based study is studying the performance of current (PSA and DRE) vs. (% free PSA) clinical biomarkers of PC risk in 400 African-American men 50 to 70 years of age who undergo PC screening in Oakland, CA (East Bay San Francisco area), as well as possible association of PC screening results for these men with their dietary exposures to the cancer-causing heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) that forms when meat is cooked. This study expands an ongoing NIH-funded study (by the same research team) to add a new %-free-PSA test, results of which will be compared with PSA/DRE results and PhIP exposures estimated by dietary interviews. For 392 men studied under the NIH protocol, an odds ratio (95% CL) of 32 (3.2, 720) for highly elevated PSA ({ge}20 ng/mL) was observed in the highest 15% vs. the lower 50% of estimated daily PhIP intakes. Approximately 100 additional men have completed participation in the expanded NIH/DOD-supported study. This study will help define the potential value of improved screening and dietary/behavioral intervention to reduce PC risk, namely, prevention of PhIP intake by avoiding overcooked meats.
Date: January 18, 2006
Creator: Bogen, K T
Partner: UNT Libraries Government Documents Department

Inhibiting Vimentin or beta 1-integrin Reverts Prostate Tumor Cells in IrECM and Reduces Tumor Growth

Description: Prostate epithelial cells grown embedded in laminin-rich extracellular matrix (lrECM) undergo morphological changes that closely resemble their architecture in vivo. In this study, growth characteristics of three human prostate epithelial sublines derived from the same cellular lineage, but displaying different tumorigenic and metastatic properties in vivo, were assessed in three-dimensional (3D) lrECM gels. M12, a highly tumorigenic and metastatic subline, was derived from the parental prostate epithelial P69 cell line by selection in nude mice and found to contain a deletion of 19p-q13.1. The stable reintroduction of an intact human chromosome 19 into M12 resulted in a poorly tumorigenic subline, designated F6. When embedded in lrECM gels, the nontumorigenic P69 line produced acini with clearly defined lumena. Immunostaining with antibodies to {beta}-catenin, E-cadherin or {alpha}6-, {beta}4- and {beta}1-integrins showed polarization typical of glandular epithelium. In contrast, the metastatic M12 subline produced highly disorganized cells with no evidence of polarization. The F6 subline reverted to acini-like structures exhibiting basal polarity marked with integrins. Reducing either vimentin levels via siRNA interference or {beta}1-integrin expression by the addition of the blocking antibody, AIIB2, reorganized the M12 subline into forming polarized acini. The loss of vimentin significantly reduced M12-Vim tumor growth when assessed by subcutaneous injection in athymic mice. Thus, tumorigenicity in vivo correlated with disorganized growth in 3D lrECM gels. These studies suggest that the levels of vimentin and {beta}1-integrin play a key role in the homeostasis of the normal acini in prostate and that their dysregulation may lead to tumorigenesis.
Date: July 27, 2009
Creator: Zhang, Xueping; Fournier, Marcia V.; Ware, Joy L.; Bissell, Mina J. & Zehner, Zendra E.
Partner: UNT Libraries Government Documents Department

Inhibition of vimentin or B1 integrin reverts morphology of prostate tumor cells grown in laminin-rich extracellular matrix gels and reduces tumor growth in vivo

Description: Prostate epithelial cells grown embedded in laminin-rich extracellular matrix (lrECM) undergo morphologic changes that closely resemble their architecture in vivo. In this study, growth characteristics of three human prostate epithelial sublines derived from the same cellular lineage, but displaying different tumorigenic and metastatic properties in vivo, were assessed in three-dimensional lrECM gels. M12, a highly tumorigenic and metastatic subline, was derived from the immortalized, prostate epithelial P69 cell line by selection in athymic, nude mice and found to contain a deletion of 19p-q13.1. The stable reintroduction of an intact human chromosome 19 into M12 resulted in a poorly tumorigenic subline, designated F6. When embedded in lrECM gels, the parental, nontumorigenic P69 line produced acini with clearly defined lumena. Immunostaining with antibodies to {beta}-catenin, E-cadherin, or {alpha}6 and {beta}1 integrins showed polarization typical of glandular epithelium. In contrast, the metastatic M12 subline produced highly disorganized cells with no evidence of polarization. The F6 subline reverted to acini-like structures exhibiting basal polarity marked with integrins. Reducing either vimentin levels via small interfering RNA interference or the expression of {alpha}6 and {beta}1 integrins by the addition of blocking antibodies, reorganized the M12 subline into forming polarized acini. The loss of vimentin significantly reduced M12-Vim tumor growth when assessed by s.c. injection in athymic mice. Thus, tumorigenicity in vivo correlated with disorganized growth in three-dimensional lrECM gels. These studies suggest that the levels of vimentin and {beta}1 integrin play a key role in the homeostasis of the normal acinus in prostate and that their dysregulation may lead to tumorigenesis. [Mol Cancer Ther 2009;8(3):499-508].
Date: June 12, 2008
Creator: Zhang, Xueping; Fournier, Marcia V; Ware, Joy L; Bissell, Mina J; Yacoub, Adly & Zehner, Zendra E
Partner: UNT Libraries Government Documents Department

Investigations into the Optimization of Multi-Source Strength Brachytherapy Treatment Procedures

Description: The goal of this project is to investigate the use of multi-strength and multi-specie radioactive sources in permanent prostate implant brachytherapy. In order to fulfill the requirement for an optimal dose distribution, the prescribed dose should be delivered to the target in a nearly uniform dose distribution while simultaneously sparing sensitive structures. The treatment plan should use a small number of needles and sources while satisfying the treatment requirements. The hypothesis for the use of multi-strength and/or multi-specie sources is that a better treatment plan using fewer sources and needles could be obtained than by treatment plans using single-strength sources could reduce the overall number of sources used for treatment. We employ a recently developed greedy algorithm based on the adjoint concept as the optimization search engine. The algorithm utilizes and ''adjoint ratio'', which provides a means of ranking source positions, as the pseudo-objective function. It ha s been shown that the greedy algorithm can solve the optimization problem efficiently and arrives at a clinically acceptable solution in less than 10 seconds. Our study was inclusive, that is there was no combination of sources that clearly stood out from the others and could therefore be considered the preferred set of sources for treatment planning. Source strengths of 0.2 mCi (low), 0.4 mCi (medium), and 0.6 mCi (high) of {sup 125}I in four different combinations were used for the multi-strength source study. The combination of high- and medium-strength sources achieved a more uniform target dose distribution due to few source implants whereas the combination of low-and medium-strength sources achieved better sparing of sensitive tissues including that of the single-strength 0.4 mCi base case. {sup 125}I at 0.4 mCi and {sup 192}Ir at 0.12 mCi and 0.25 mCi source strengths were used for the multi-specie source study. This study also proved inconclusive ...
Date: September 30, 2002
Creator: Henderson, D. L.; Yoo, S. & Thomadsen, B.R.
Partner: UNT Libraries Government Documents Department

Costs and Effectiveness of Prostate Cancer Screening in Elderly Men

Description: The background paper summarizes the evidence on the effectiveness and costs of prostate cancer screening and treatment in elderly men and explores the implications for Medicare of offering this preventive technology as a Medicare benefit.
Date: May 1995
Creator: United States. Congress. Office of Technology Assessment.
Partner: UNT Libraries Government Documents Department

Septa design for a prostate specific PET camera

Description: The recent development of new prostate tracers has motivated us to build a low cost PET camera optimized to image the prostate. Coincidence imaging of positron emitters is achieved using a pair of external curved detector banks. The bottom bank is fixed below the patient bed, and the top bank moves upward for patient access and downward for maximum sensitivity. In this paper, we study the design of septa for the prostate camera using Monte Carlo simulations. The system performance is measured by the detectability of a prostate lesion. We have studied 17 septa configurations. The results show that the design of septa has a large impact on the lesion detection at a given activity concentration. Significant differences are also observed between the lesion detectability and the conventional noise equivalent count (NEC) performance, indicating that the NEC is not appropriate for the detection task.
Date: November 15, 2003
Creator: Qi, Jinyi; Huber, Jennifer S.; Huesman, Ronald H.; Moses, William W.; Derenzo, Stephen E. & Budinger, Thomas F.
Partner: UNT Libraries Government Documents Department

Diagnostic and therapeutic applications of diode lasers and solid state lasers in medicine. Progress report

Description: The Texas Medical Center in Houston and the nearby UT Medical Branch at Galveston together constitute a major center of medical research activities. Laser applications in medicine are under development with the engineering assistance of the colloborating engineering centers at Rice University, UT-Austin, and Texas A&M Univ. In addition, this collective is collaborating with the Naval Research Laboratory, where new developments in laser design are underway, in order to transfer promising new laser technology rapidly into the medical environment.
Date: May 1, 1992
Creator: Jacques, S. L.; Welch, A. J.; Motamedi, M.; Rastegar, S.; Tittel, F. & Esterowitz, L.
Partner: UNT Libraries Government Documents Department

BRCA1 loss pre-existing in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood

Description: A recent study concluded that serum prostate specific antigen (PSA)-based screening is beneficial for reducing the lethality of PCa, but was also associated with a high risk of 'overdiagnosis'. Nevertheless, also PCa patients who suffered from organ confined tumors and had negative bone scans succumb to distant metastases after complete tumor resection. It is reasonable to assume that those tumors spread to other organs long before the overt manifestation of metastases. Our current results confirm that prostate tumors are highly heterogeneous. Even a small subpopulation of cells bearing BRCA1 losses can initiate PCa cell regional and distant dissemination indicating those patients which might be at high risk of metastasis. A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances (AI) among circulating tumor cells (CTCs). The present analysis was aimed to elucidate the biological and clinical role of BRCA1 losses on metastatic spread and tumor progression in prostate cancer patients. Experimental Design: To map molecular progression in PCa outgrowth we used FISH analysis of tissue microarrays (TMA), lymph node sections and CTC from peripheral blood. We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by AI of the tumor suppressor gene PTEN and lack of the BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (p < 0.05), invasion to pelvic lymph nodes (LN, p < 0.05) as well as BR (p < 0.01). Their prevalence was twice as high within 62 LN metastases (LNMs) as in primary tumors (27%, p < 0.01). The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between those two sites. ...
Date: March 19, 2010
Creator: Bednarz, Natalia; Eltze, Elke; Semjonow, Axel; Rink, Michael; Andreas, Antje; Mulder, Lennart et al.
Partner: UNT Libraries Government Documents Department

Novel Chemical Strategies for Labeling Small Molecule Ligands for Androgen, Progestin, and Peroxisome Proliferator-Activated Receptors for Imaging Prostate and Breast Cancer and the Heart

Description: Summary of Progress The specific aims of this project can be summarized as follows: • Aim 1: Prepare and evaluate radiolabeled ligands for the peroxisome proliferator-activated receptor  (PPAR), a new nuclear hormone receptor target for tumor imaging and hormone therapy. • Aim 2: Prepare steroids labeled with a cyclopentadienyl tricarbonyl technetium or rhenium unit. • Aim 3: Prepare and evaluate other organometallic systems of novel design as ligand mimics and halogenated ligands for nuclear hormone receptor-based tumor imaging. As is described in detail below, we made excellent progress on all three of these aims; the highlights of our progress are the following: • we have prepared the first fluorine-18 labeled analogs of ligands for the PPAR receptor and used these in tissue distribution studies in rats • we have developed three new methods for the synthesis of cyclopentadienyltricarbonyl rhenium and technetium (CpRe(CO)3 and CpTc(CO)3) systems and we have adapted these to the synthesis of steroids labeled with these metals, as well as ligands for other receptor systems • we have prepared a number of fluorine-18 labeled steroidal and non-steroidal androgens and measured their tissue distribution in rats • we have prepared iodine and bromine-labeled progestins with high progesterone receptor binding affinity • we have prepared inorganic metal tricarbonyl complexes and steroid receptor ligands in which the metal tricarbonyl unit is an integral part off the ligand core.
Date: April 19, 2007
Creator: Katzenellenbogen, John, A.
Partner: UNT Libraries Government Documents Department