Breast cancer -specific activation of topoisomerase IIalpha and its application in the tumor -targeting gene therapy

To ensure the success of systemic gene therapy, it is critical to enhance the tumor specificity and activity of the promoter. In the current study, we identified the breast cancer-specific activity of the topoisomerase IIα promoter. We further showed that cdk2 and cyclin A activate topoisomerase IIα promoter in a breast cancer-specific manner. An element containing an inverted CCAAT box (ICB) was shown to respond this signaling. When the ICB-harboring topoisomerase IIα minimal promoter was linked with an enhancer sequence from the cytomegalovirus immediate early gene promoter (CMV promoter), this composite promoter, CT90, exhibited activity comparable to or higher than the CMV promoter in breast cancer cells in vitro and in vivo, yet expresses much lower activity in normal cell lines and normal organs than the CMV promoter. A CT90-driven construct expressing BikDD, a potent pro-apoptotic gene, was shown to selectively kill breast cancer cells in vitro and to suppress mammary tumor development in an animal model of intravenously administrated, liposome-delivered gene therapy. Expression of BikDD was readily detectable in the tumors but not in the normal organs of CT90-BikDD-treated animals. Finally, we demonstrated that CT90-BikDD treatment potentially enhanced the sensitivity of breast cancer cells to chemotherapeutic agents, especially doxorubicin and taxol. The results indicate that liposomal CT90-BikDD is a novel and effective systemic breast cancer-targeting gene therapy, and its combination with chemotherapy may further improve the current adjuvant therapy for breast cancer. ^

Molecular mechanism of the relaxin signaling pathways: Activation of cAMP, PI3K, and PKCzeta

Relaxin is a polypeptide hormone that has diverse effects on reproductive and non-reproductive tissues. Relaxin activates the G-protein coupled receptors, LGR7 and LRG8. Early studies described increased cAMP and protein kinase A activity upon relaxin treatment, but cAMP accumulation alone could not account for all of the relaxin-mediated effects. We utilized the human monocyte cell line THP-1 to study the mechanism of relaxin-stimulated CAMP production. ^ Relaxin treatment in THP-1 cells produces a biphasic time course in cAMP accumulation, where the first peak appears as early as 1–2 minutes with a second peak at 10–20 minutes. Selective inhibitors for phosphoinositide 3-kinase (P13K), such as wortmannin and LY294002, show a dose-dependent inhibition of relaxin-stimulated cAMP accumulation, specific for the second peak of the relaxin time course. Neither the effects of relaxin nor the inhibition of relaxin by LY294002 is mediated by the activity of phosphodiesterases. Furthermore, LY294002 blocks upregulation of vascular endothelial growth factor transcript levels by relaxin. ^ To further delineate relaxin signaling pathways, we searched for downstream targets of PI3K that could activate adenylyl cyclase (AC). Protein kinase C ζ (PKCζ) was a prime candidate because it activates types II and V AC. Chelerythrine chloride (a general PKC inhibitor) inhibits relaxin-induced cAMP production to the same degree as LY294002 (∼40%). Relaxin stimulates PKCζ translocation to the plasma membrane in THP-1, MCF-7, PHM1-31, and MMC cells, as shown by immunocytochemistry. PKCζ translocation is P13K-dependent and independent of cAMP production. Antisense PKCζ oligodeoxynucleotides (PKCζ-ODNs) deplete both PKCζ transcript and protein levels in THP-1 cells. PKCζ-ODNs abolish relaxin-mediated PKCζ translocation and inhibit relaxin stimulation of cAMP by 40%, as compared to mock and random ODN controls. Treatment with LY294002 in the presence of PKCζ-ODNs results in little further inhibition. Taken together, we present a novel role for PI3K and PKCζ in relaxin stimulation of cAMP and provide the first example of the PKCζ regulation of AC in an endogenous system. Furthermore, we have identified higher order complexes of AC isoforms and PKA anchoring proteins in attempts to explain the differential coupling of relaxin to cAMP and PI3K-signaling pathways in various cell types. ^

A rural virtual health sciences library project: research findings with implications for next generation library services*

Purpose: The Shared Hospital Electronic Library of Southern Indiana (SHELSI) research project was designed to determine whether access to a virtual health sciences library and training in its use would support medical decision making in rural southern Indiana and achieve the same level of impact seen by targeted information services provided by health sciences librarians in urban hospitals.

Building a retrospective collection in pharmacy: a brief history of the literature with some considerations for U.S. health sciences library professionals

This paper argues that historical works in pharmacy are important tools for the clinician as well as the historian. With this as its operative premise, delineating the tripartite aspects of pharmacy as a business enterprise, a science, and a profession provides a conceptual framework for primary and secondary resource collecting. A brief history and guide to those materials most essential to a historical collection in pharmacy follows. Issues such as availability and cost are discussed and summarized in checklist form. In addition, a glossary of important terms is provided as well as a list of all the major U.S. dispensatories and their various editions. This paper is intended to serve as a resource for those interested in collecting historical materials in pharmacy and pharmaco-therapeutics as well as provide a history that gives context to these classics in the field. This should provide a rationale for selective retrospective collection development in pharmacy.

Health sciences libraries in Kuwait: a study of their resources, facilities, and services

The purpose of this study was to examine the current status of health sciences libraries in Kuwait in terms of their staff, collections, facilities, use of information technology, information services, and cooperation. Seventeen libraries participated in the study. Results show that the majority of health sciences libraries were established during the 1980s. Their collections are relatively small. The majority of their staff is nonprofessional. The majority of libraries provide only basic information services. Cooperation among libraries is limited. Survey results also indicate that a significant number of health sciences libraries are not automated. Some recommendations for the improvement of existing resources, facilities, and services are made.

Providing health information to the general public: a survey of current practices in academic health sciences libraries*

A questionnaire was mailed to 148 publicly and privately supported academic health sciences libraries affiliated with Association of American Medical Colleges (AAMC)–accredited medical schools in the United States and Canada to determine level of access and services provided to the general public. For purposes of this study, “general public” was defined as nonaffiliated students or health care professionals, attorneys and other nonhealth-related professionals, patients from affiliated or other hospitals or clinics, and general consumers. One hundred five (71%) libraries responded. Results showed 98% of publicly supported libraries and 88% of privately supported libraries provided access to some or all of the general public. Publicly supported libraries saw greater numbers of public patrons, often provided more services, and were more likely to circulate materials from their collections than were privately supported libraries. A significant number of academic health sciences libraries housed a collection of consumer-oriented materials and many provided some level of document delivery service, usually for a fee. Most allowed the public to use some or all library computers. Results of this study indicated that academic health sciences libraries played a significant role in serving the information-seeking public and suggested a need to develop written policies or guidelines covering the services that will be provided to minimize the impact of this service on primary clientele.

Monograph use at an academic health sciences library: the first three years of shelf life

Objective: To study the circulation of monographs during the first three years of shelf life at an academic health sciences library.

Frieze -- Health Sciences

Frieze located in front of building. Smith, Hinchman & Grylls, architects. W.B. Wood Co., construction

International comparison of resource allocation in health sciences : an analysis of expenditures on biomedical research in 19 industrialized countries /

Item 507

Spanish-English chemical and medical dictionary; comprising terms employed in medicine, biochemistry, surgery, dentistry, veterinary, biology, pharmacy, allied sciences, and related scientific equipment.

Bibliography: p. 607-609.

English-Spanish chemical and medical dictionary; comprising terms employed in medicine, surgery, dentistry, veterinary, biochemistry, biology, pharmacy, allied sciences and related scientific equipment ...

Mode of access: Internet.

Semiconductor detectors in medicine, March 8-9, 1973, presented by Nuclear Medicine Division, Department of Radiology, University of California School of Medicine and Continuing Education in Health Sciences, University of California, San Francisco, California, supported in part by KeVex Corporation, Burlingame, California [et al.

Mode of access: Internet.

Uniformed Services University of the Health Sciences, F. Edward Hʹebert School of Medicine.

Mode of access: Internet.

Annual report - National Institute of Environmental Health Sciences.

Mode of access: Internet.