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A novel approach to the study of the functional proteome in breast cancer

Description: Factors including intratumoral heterogeneity and variability in tissue handling potentially hamper the application of reverse phase protein arrays (RPPA) to study of the solid tumor functional proteome. To address this, RPPA was applied to quantify protein expression and activation in 233 human breast tumors and 52 breast cancer cell lines. Eighty-two antibodies that recognize kinase and steroid signaling events and their effectors were validated for RPPA because of the importance of these proteins to breast carcinogenesis. Reproducibility in replicate lysates was excellent. Intratumoral protein expression was less variable than intertumoral expression, and prognostic biomarkers retained the ability to accurately predict patient outcomes when analyzed in different tumor sites. Although 21/82 total and phosphoproteins demonstrated time-dependent instability in breast tumors that were placed at room temperature after surgical excision for 24 hours prior to freezing, the functional proteomic 'fingerprint' was robust in most tumors until at least 24 hours before tissue freezing. Correlations between RPPA and immunohistochemistry were statistically significant for assessed proteins but RPPA demonstrated a superior dynamic range and detected, for example, an 866-fold difference in estrogen receptor alpha level across breast tumors. Protein and mRNA levels were concordant (at p {le} 0.05) for 41.3% and 61.1% of assayed targets in breast tumors and cell lines, respectively. Several phosphorylation and cleavage products did not correlate with the corresponding transcript levels. In conclusion, the reproducibility of RPPA, the faithfulness with which proteins and the functional proteomic 'fingerprint' are preserved in different sections derived from primary breast tumors, and the surprising stability of this 'fingerprint' with increasing time to freezing all facilitate the application of RPPA to the accurate study of protein biomarkers in non-microdissected tumor specimens. The lack of correlation between several protein phosphorylation and cleavage products and the corresponding transcripts underlines the importance of study of the functional proteome ...
Date: October 10, 2008
Creator: Hennessy, Bryan; Lu, Yiling; Gonzalez-Angulo, Ana Maria; Carey, Mark; Myhre, Simen; Ju, Zhenlin et al.
Partner: UNT Libraries Government Documents Department

Targeted Radiotherapy of Estrogen Receptor Positive Tumors

Description: The overall objectives of the proposal were to develop estrogen receptor (ER) binding small molecule radiopharmaceuticals for targeted radiotherapy of ER positive (ER+) tumors. In particular, this proposal focused on embedding a {sup 186,188}Re or a {sup 32}P radionuclide into an estrogen steroidal framework by isosteric substitution such that the resulting structure is topologically similar to the estrogen (estrogen mimic). The estrogen mimic molecules expected to bind to the ER and exhibit biodistribution akin to that of native estrogen due to structural mimicry. It is anticipated that the {sup 186,188}Re- or a {sup 32}P-containing estrogen mimics will be useful for targeted molecular radiotherapy of ER+ tumors. It is well established that the in vivo target tissue uptake of estrogen like steroidal molecules is related to the binding of the steroids to sex hormone binding globulin (SHBG). SHBG is important in the uptake of estrogens and testosterone in target tissues by SHBG receptors on the cell surface. However, hitherto the design of estrogen like small molecule radiopharmaceuticals was focused on optimizing ER binding characteristics without emphasis on SHBG binding properties. Consequently, even the molecules with good ER affinity in vitro, performed poorly in biodistribution studies. Based on molecular modeling studies the proposal focused on developing estrogen mimics 1-3 which were topologically similar to native estrogens, and form hydrogen bonds in ER and SHBG in the same manner as those of native estrogens. To this end the technical objectives of the proposal focused on synthesizing the rhenium-estrone and estradiol mimics 1 and 2 respectively, and phosphorous estradiol mimic 3 and to assess their stability and in vitro binding characteristics to ER and SHBG.
Date: August 31, 2006
Creator: Rajagopalan, Raghavan
Partner: UNT Libraries Government Documents Department

A STUDY OF THE EFFECTS OF NUCLEAR RADIATION ON ORGANIC EXPLOSIVES

Description: Samples of 6 explosive compounds (TNT, tetryl, NC, ROX, HMX, and PETN) and 4 explosive mixtures were exposed to the neutron and gamma radiation from a power reactor at integrated flux levels of approximately 10/sup 15/ and 3 x 10/ sup 16/ n/cm/sup 2/. The irradiated samples were subjected to a variety of chemical and physical tests. Only minor effects were noted at the lower exposure level, but extensive deterioration of the aliphatic and and heterocyclic compounds occurred in the 10/sup 16/ run. G-values of 2.9 and 1.4 were obtained for the destruction of ROX and HMX, respectively. An experiment in which samples of 5 explosive compounds and mixtures were exposed to a radiation burst from the Godiva II critical assembly is described. No significant damage to the samples resulted from this exposure. (auth)
Date: January 1, 1960
Creator: Urizar, M.J.; Loughran, E.D. & Smith, L.C.
Partner: UNT Libraries Government Documents Department

Non-carrier-added 186, 188Re labeled 17a-ethynylestradiol : a potential breast cancer imaging and therapy agent

Description: Receptor-targeted radiopharmaceuticals constitute potential agents for the diagnosis and therapy of cancer. Breast cancer is the most prevalent form of diagnosed cancer in women in the United States, and it accounts for the second highest number of cases of cancer fatalities (1). In Approximately two-thirds of the breast tumors, estrogen and progesterone steroid hormone receptors can be found. Such tumors can often be treated successfully with anti-estrogen hormone therapy (2). Hence, the ability to determine the estrogen receptor (ER) contend of the breast tumor is essential for making the most appropriate choice of treatment for the patient. Along with this diagnostic aspect, steroid-based radiopharmaceuticals with high specific activity offer an encouraging prospect for therapeutic applications: {sup 186,188}Re labeled steroids binding to receptors expressed by cancer cells appear to be potential agents for the irradiation of small to medium-sized tumors. {sup 186}Re has been regarded as an ideal radionuclide for radiotherapy due to its appropriate half-live of 90 h and {beta}-energy of 1.07 MeV. Moreover, the {gamma}-emission of 137 keV that allows in vivo imaging while in therapy is an additional bonus. {sup 188}Re is obtained from a {sup 188}W/{sup 188}Re radionuclide generator system, representing an advantage for availability at radiopharmacy laboratory by daily elution. In addition, {sup 188}Re emits high energy beta particles with an average energy of 769 keV, and the emission of the 155 keV allows simultaneous imaging for biodistribution evaluation in vivo. In order to avoid competitive saturation of the binding sites of the ligand receptor, Re labeled steroids with high specific activity are required, and the removal of all excess unlabeled ligands is mandatory. {sup 188}Re is eluted from a {sup 188}W/{sup 188}Re generator produced and provided by Oak Ridge National Laboratory (3). This paper outlines the solid phase-supported preparation of an n.c.a. [{sup 188}Re]Re-imido estradiol ...
Date: January 1, 2001
Creator: Fassbender, M. E. (Michael E.); Phillips, Dennis R.; Peterson, E. J. (Eugene J.); Ott, K. C. (Kevin C.) & Arterburn, J. B. (Jeffrey B.)
Partner: UNT Libraries Government Documents Department

International Convention Against Doping in Sport: Issues for Congress

Description: The International Convention Against Doping in Sport seeks to harmonize anti-doping commitments for non-professional sports at the international level. Issues that may continue to arise as policymakers evaluate the Convention include its relationship to anti-doping regulations in professional sports and the legitimacy and effectiveness of current international anti-doping activities.
Date: August 11, 2008
Creator: Wyler, Liana Sun
Partner: UNT Libraries Government Documents Department

International Convention Against Doping in Sport: Issues for Congress

Description: The International Convention Against Doping in Sport seeks to harmonize anti-doping commitments for non-professional sports at the international level. Issues that could arise as the Senate considers the Convention include its relationship to anti-doping regulations in professional sports, potential consequences that non-ratification could pose to the United States, and the legitimacy and effectiveness of current international anti-doping activities.
Date: June 26, 2008
Creator: Wyler, Liana Sun
Partner: UNT Libraries Government Documents Department

International Convention Against Doping in Sport: Issues for Congress

Description: The International Convention Against Doping in Sport seeks to harmonize anti-doping commitments for non-professional sports at the international level. This Convention was adopted by the United Nations Educational, Scientific, and Cultural Organization (UNESCO) in 2005 and entered in force on February 1, 2007. Issues that could arise as the Senate considers the treaty include its relationship to anti-doping regulations in professional sports, potential consequences that non-ratification could pose to the United States, and the legitimacy and effectiveness of current international anti-doping activities.
Date: May 28, 2008
Creator: Wyler, Liana Sun
Partner: UNT Libraries Government Documents Department

Tissue architecture and breast cancer: the role of extracellular matrix and steroid hormones

Description: The changes in tissue architecture that accompany the development of breast cancer have been the focus of investigations aimed at developing new cancer therapeutics. As we learn more about the normal mammary gland, we have begun to understand the complex signaling pathways underlying the dramatic shifts in the structure and function of breast tissue. Integrin-, growth factor-, and steroid hormone-signaling pathways all play an important part in maintaining tissue architecture; disruption of the delicate balance of signaling results in dramatic changes in the way cells interact with each other and with the extracellular matrix, leading to breast cancer. The extracellular matrix itself plays a central role in coordinating these signaling processes. In this review, we consider the interrelationships between the extracellular matrix, integrins, growth factors, and steroid hormones in mammary gland development and function.
Date: June 1, 2000
Creator: Hansen, R K & Bissell, M J
Partner: UNT Libraries Government Documents Department

SEMIANNUAL REPORT TO THE ATOMIC ENERGY COMMISSION

Description: Progress is reported in the following studies: the degradation of uric acid in man; the effect cf triiodothyronine on the oxidative metabolism of erythrocytes; the biosynthesis of abnormal proteins in multiple myeloma; tracer studies on the methbolism of DLglutamic acid in man; the effect of triiodothyronine on radiosensitivity of rats; the physiologic and clinical significance of erythropoietin; the measurement of isodose distributions from a revolving beam cobalt-60 therapy unit; tracer studies of protein binding and subcellular localization of digitoxin; applications of carbon-14 in methbolic studies; and tracer studies on the methbolism of progesterone. A list of publications during the period is included. (C.H.)
Date: September 1, 1958
Creator: Jacobson, L.O. ed. & Skozen, F.J. comp.
Partner: UNT Libraries Government Documents Department

SOME ATTEMPTS TO MODIFY THE EARLY HEALING PROCESS OF MODERATE SECOND DEGREE BURNS

Description: By the injection of hormones and other agents which have been reported to influence scar formation, attempts were made to interfere with normal wound healing after the production of moderate second degree burns in pigs. It was hoped that some information on the development or prevention of hypertrophic scars and keloids might be gained from this experiment. Systemic administration of Doca, cortisone, and toluidine blue, and local injection of cortisone, histamine, and hyaluronidase neither delayed healing nor altered significantly the histologic processes involved in the restoration of dermal tissues. (auth)
Date: December 4, 1958
Creator: Lerman, B. & Hinshaw, J.R.
Partner: UNT Libraries Government Documents Department

Biomedical Research Group, Health Division annual report 1954

Description: This report covers the activities of the Biomedical Research Group (H-4) of the Health Division during the period January 1 through December 31, 1954. Organizationally, Group H-4 is divided into five sections, namely, Biochemistry, Radiobiology, Radiopathology, Biophysics, and Organic Chemistry. The activities of the Group are summarized under the headings of the various sections. The general nature of each section`s program, publications, documents and reports originating from its members, and abstracts and summaries of the projects pursued during the year are presented.
Date: December 1955
Creator: Langham, W. H. & Storer, J. B.
Partner: UNT Libraries Government Documents Department

Review of Androgenic Anabolic Steroid Use

Description: An area that has been overlooked within personnel security evaluations is employee use of androgenic-anabolic steroids (AAS). Current drug testing within the federal government does not include testing for anabolic steroids, and the difficulties to implement such testing protocols-not to mention the cost involved-make AAS testing highly improbable. The basis of this report is to bring to the forefront the damage that anabolic steroids can cause from both a physical and a psychological standpoint. Most individuals who use AASs do so to increase their muscle mass because they wish to gain some type of competitive edge during athletic competition or they wish to enhance their physical features for self-satisfaction and self-esteem (i.e., body building). Security officers are one group of men who often take high doses of anabolic steroids, according to the Second Report of the Senate Standing Committee (1990). The negative psychological characteristics for AAS use is extensive and includes prominent hostility, aggressiveness, irritability, euphoria, grandiose beliefs, hyperactivity, reckless behavior, increased sexual appetite, unpredictability, poor impulse control, mood fluctuations, and insomnia. The drug may invoke a sense of power and invincibility (Leckman and Scahill, 1990). Depressive symptoms, such as anhedonia, fatigue, impaired concentration, decreased libido, and even suicidality (Pope and Katz, 1992) have been noted with steroid withdrawal. It appears that long-term users of AAS experience similar characteristics as other substance abusers (i.e., craving, dependence, and withdrawal symptoms).
Date: July 31, 2001
Creator: Borges, T.; Eisele, G. & Byrd, C.
Partner: UNT Libraries Government Documents Department

Study of the mechanism of carcinogenesis by carcinogens which are negative in the Ames test. Progress report. [ICE; TUMOR PROMOTERS; PROGESTERONE; QUANTITY RATIO; RATS]

Description: Research progress for 1980 is reported. The role of tRNA methyltransferases in two-1 stage carcinogenesis of mice by phorbol esters has been investigated. The mechanisms of elevation of progesterone levels in the rat by ethionine have also beed studied. (ACR)
Date: unknown
Creator: Borek, E.
Partner: UNT Libraries Government Documents Department