ヒト前立腺癌の進行モデルと新しい治療法

著者等はヒト前立腺癌の進展に関した2つの細胞モデルを開発した.LNCaP前立腺癌進展モデルは, 生体内での前立腺又は骨の間質細胞とLNCaP細胞との相互作用に基づいており, これによって腫瘍形成能と転移能を獲得したものである.派生株C4-2は去勢動物で容易に発育し, リンパ節, 精嚢腺, 骨に転移する.次のモデルARCaPは, 癌性腹水由来のヒト前立腺癌細胞で, アンドロゲン及びエストロゲンによって増殖を抑制され, 去勢下で腫瘍を形成した.ARCaPはアンドロゲン受容体及びPSAを低レベルで発現し, 同所移植によって肝, 腎, 骨等に高頻度で転移した.これらのモデルを用いて遺伝子治療の研究を行ったOur laboratory has developed two cellular models of human prostate cancer progression. The LNCaP prostate cancer progression model is based upon the well-known cellular interaction between human prostate or bone stromal cells and LNCaP cells in vivo. The marginally tumorigenic LNCaP cells acquired tumorigenic and metastatic potential upon cellular interaction with either prostate or bone fibroblasts. A subline termed C4-2 was observed to grow readily in castrated animals and acquired metastatic potential spreading from the primary tumor site to the lymph node, the seminal vesicles, and the axial skeleton, resulting in an intense osteoblastic reaction. The second model is ARCaP, where prostate cancer cells derived from the ascites fluid of a man with metastatic disease exhibited an Androgen- and estrogen-Repressed Prostate Cancer cell growth and tumor formation in either a hormone-deficient or a castrated environment. However, the growth of either the tumor cells in vitro or the tumors in vivo was suppressed by both estrogen and androgen. While the tumor cells expressed low levels of androgen receptor and prostate-specific antigen (PSA), they were highly metastatic when inoculated orthotopically. Distant metastases to a number of organs were detected, including the liver, lung, kidney, and bone. We have employed a human prostate cancer progression model as a system to study the efficacy of gene therapy. Results of the study show that whereas universal promoters, such as Cytomegalovirus (CMV) and Rous Sarcoma Virus (RSV) promoter-driven tumor suppressors (e.g. p53, p21, and p16), were effective in inhibiting prostate tumor growth, the advantages of driving the expression of therapeutic toxic genes using a tissue-specific promoter prostate-specific antigen (PSA) and a tumor--but not tissue-specific promoter, osteocalcin (OC), are preferred. In the case of the PSA promoter, we can achieve cell-kill in PSA-producing human prostate cancer cells. To circumvent the supporting role of bone stroma for prostate cancer epithelial growth, we have recently developed a novel concept where the expression of therapeutic toxic genes is driven by a tumor--but not a tissue-specific OC promoter. Osteocalcin-thymidine kinase (OC-TK) was found to efficiently eradicate the growth of osteosarcoma, prostate, and brain tumors both in vitro and in vivo. We observed that androgen-independent human prostate cancer cells lines expressed OC-TK at higher levels than androgen-dependent human prostate cancer cell lines. We have obtained data to suggest that Ad-OC-TK plus a pro-drug acyclovir (ACV) may be used as an effective therapy to treat prostate cancer bone metastasis in models where the growth of androgen-independent PC-3 and C4-2 tumors in the bone has occurred

Lighted Schoolhouse at Daniel E. Morgan Elementary School: Pilot Program Evaluation

The Lighted Schoolhouse pilot project (LSH) at Daniel E. Morgan Elementary School (DEM) in the Hough neighborhood of Cleveland began operation in February 2005. It is a collaborative effort among a number of community organizations, led by the Urban League of Greater Cleveland (ULGC). The pilot LSH was initiated by then-Mayor Jane Campbell as a response to Cleveland’s designation as the poorest large city in the U.S., and was meant to address three community priorities: after-school programming, fuller use of schools, and pathways out of poverty. In June 2005, a team of evaluators from the Levin College of Urban Affairs at Cleveland State University was selected to evaluate the pilot project. The purpose of this evaluation is to: 1) assess the start-up and implementation process and the lessons learned; 2) track program activities and accomplishments; and 3) develop recommendations regarding the sustainability and replication of the pilot program. The Levin College Evaluation Team (LCET) also developed a

UV-Vis/FT-NIR in situ monitoring of visible-light induced polymerization of PEGDA hydrogels initiated by eosin/triethanolamine/O₂

In conjunction with a tertiary amine coinitiator, eosin, a photoreducible dye, has been shown to successfully circumvent oxygen inhibition in radical photopolymerization reactions. However, the role of O₂ in the initiation and polymerization processes remains inconclusive. Here, we employ a UV-Vis/FT-NIR analytical tool for real-time, simultaneous monitoring of chromophore and monomer reactive group concentrations to investigate the eosin-activated photopolymerization of PEGDA-based hydrogels under ambient conditions. First, we address the challenges associated with spectroscopic monitoring of the polymerization of hydrogels using UV-Vis and FT-NIR, proposing metrics for quantifying the extent of signal loss from reflection and scattering, and showing their relation to microgelation and network formation. Second, having established a method for extracting kinetic information by eliminating the effects of changing refractive index and scattering, the coupled UV-Vis/FT-NIR system is applied to the study of eosin-activated photopolymerization of PEGDA in the presence of O₂. Analysis of the inhibition time, rate of polymerization, and rate of eosin consumption under ambient and purged conditions indicates that regeneration of eosin in the presence of oxygen and consumption of oxygen occur via a nonchain process. This suggests that the uniquely high O₂ resilience is due to alternative processes such as energy transfer from photo-activated eosin to oxygen. Uncovering the intricacies of the role of O₂ in eosin-mediated initiation aids the design of O₂ resistant free radical polymerization systems relevant to photonics, optoelectronics, biomaterials, and biosensing.United States. Department of Defense (W81XWH-13-1-0272

Evaluating the sensitivity of hybridization-based epigenotyping using a methyl binding domain protein

Hypermethylation of CpG islands in gene promoter regions has been shown to be a predictive biomarker for certain diseases. Most current methods for methylation profiling are not well-suited for clinical analysis. Here, we report the development of an inexpensive device and an epigenotyping assay with a format conducive to multiplexed analysis.David H. Koch Institute for Integrative Cancer Research at MIT (First-year Graduate Fellowship)National Science Foundation (U.S.). Graduate Research FellowshipBurroughs Wellcome Fund (Career Award at the Scientific Interface)National Institute of Environmental Health Sciences (Grant P30-ES002109)Massachusetts Institute of Technology. James H. Ferry Fund for Innovation in Research Educatio

"It was then that I thought 'whaat? This is not my Dad”: the implications of the ‘still the same person’ narrative for children and young people who have a parent with dementia

This research used auto/biographical interviews to explore the experiences of 19, 8 to 31 year olds who had a parent with dementia. Thematic analysis revealed challenges occasioned by the master narrative that people with dementia are ‘still’ the same person they were prior to the onset of their condition. While this notion is – rightly – at the heart of person-centered care in dementia services, the ‘still’ discourse conflicts with the experiences of young people. Their accounts suggest that the construction of their parent as the same person is not helpful and that, furthermore, expectations that they will behave and feel towards that parent as they did before are a source of distress in what is already a challenging situation. This paper highlights the need to equip young people with support that acknowledges that their parent may well be drastically different to the Mum or Dad they previously ‘knew

Coupled ecological and management connectivity across administrative boundaries in undeveloped landscapes

Human-induced ecological boundaries, or anthropogenic ecotones, may arise where administrative boundaries meet on undeveloped lands. Landscape-level ecological processes related to factors such as fire, invasive species, grazing, resource extraction, wildlife, and water may be affected due to unique management strategies adopted by each administrative unit. Over time, different management can result in discernible ecological differences (e.g., species composition or soil characteristics). Thus, fragmentation in the management landscape can correspond to ecological fragmentation. Different ecological patterns may emerge due to an increase in the number of management units in a region, or due to an increase in the number of different types of management units in the region. Temporal effects and collaboration history can also affect the emergence of ecotones. We use conceptual models to explore the relationship between these aspects of management fragmentation and the anthropogenic ecotones between management parcels. We then use examples of different management challenges to explore how anthropogenic ecotones can disrupt ecological flows. Our models suggest that cross-boundary collaboration that enhances management connectivity is likely essential to ecological connectivity in the face of environmental and social change

Quantifying ecological variation across jurisdictional boundaries in a management mosaic landscape

Context Large landscapes exhibit natural heterogeneity. Land management can impose additional variation, altering ecosystem patterns. Habitat characteristics may reflect these management factors, potentially resulting in habitat differences that manifest along jurisdictional boundaries. Objectives We characterized the patchwork of habitats across a case study landscape, the Grand Canyon Protected Area-Centered Ecosystem. We asked: how do ecological conditions vary across different types of jurisdictional boundaries on public lands? We hypothesized that differences in fire and grazing, because they respond to differences in management over time, contribute to ecological differences by jurisdiction. Methods We collected plot-scale vegetation and soils data along boundaries between public lands units surrounding the Grand Canyon. We compared locations across boundaries of units managed differently, accounting for vegetation type and elevation differences that pre-date management unit designations. We used generalized mixed effects models to evaluate differences in disturbance and ecology across boundaries. Results Jurisdictions varied in evidence of grazing and fire. After accounting for these differences, some measured vegetation and soil properties also differed among jurisdictions. The greatest differences were between US Forest Service wilderness and Bureau of Land Management units. For most measured variables, US Forest Service non-wilderness units and National Park Service units were intermediate. Conclusions In this study, several ecological properties tracked jurisdictional boundaries, forming a predictable patchwork of habitats. These patterns likely reflect site differences that pre-date jurisdictions as well as those resulting from different management histories. Understanding how ecosystem differences manifest at jurisdictional boundaries can inform resource management, conservation, and cross-boundary collaborations

Plug-In Hybrid Electric Vehicle Value Proposition Study: Phase 1, Task 2: Select Value Propositions/Business Model for Further Study

The Plug-In Hybrid Electric Vehicle (PHEV) Value Propositions Workshop held in Washington, D.C. in December 2007 served as the Task 1 Milestone for this study. Feedback from all five Workshop breakout sessions has been documented in a Workshop Summary Report, which can be found at www.sentech.org/phev. In this report, the project team compiled and presented a comprehensive list of potential value propositions that would later serve as a 'grab bag' of business model components in Task 2. After convening with the Guidance and Evaluation Committee and other PHEV stakeholders during the Workshop, several improvements to the technical approach were identified and incorporated into the project plan to present a more realistic and accurate case study and evaluation. The assumptions and modifications that will have the greatest impact on the case study selection process in Task 2 are described in more detail in this deliverable. The objective of Task 2 is to identify the combination of value propositions that is believed to be achievable by 2030 and collectively hold promise for a sustainable PHEV market by 2030. This deliverable outlines what the project team (with input from the Committee) has defined as its primary scenario to be tested in depth for the remainder of Phase 1. Plans for the second and third highest priority/probability business scenarios are also described in this deliverable as proposed follow up case studies in Phase 2. As part of each case study description, the proposed utility system (or subsystem), PHEV market segment, and facilities/buildings are defined

Vibrational Enhancement of the Effective Donor - Acceptor Coupling

The paper deals with a simple three sites model for charge transfer phenomena in an one-dimensional donor (D) - bridge (B) - acceptor (A) system coupled with vibrational dynamics of the B site. It is found that in a certain range of parameters the vibrational coupling leads to an enhancement of the effective donor - acceptor electronic coupling as a result of the formation of the polaron on the B site. This enhancement of the charge transfer efficiency is maximum at the resonance, where the effective energy of the fluctuating B site coincides with the donor (acceptor) energy.Comment: 5 pages, 3 figure

Superconductivity coexisting with phase-separated static magnetic order in (Ba,K)Fe2_{2}As2_{2}, (Sr,Na)Fe2_{2}As2_{2} and CaFe2_{2}As2_{2}

The recent discovery and subsequent developments of FeAs-based superconductors have presented novel challenges and opportunities in the quest for superconducting mechanisms in correlated-electron systems. Central issues of ongoing studies include interplay between superconductivity and magnetism as well as the nature of the pairing symmetry reflected in the superconducting energy gap. In the cuprate and RE(O,F)FeAs (RE = rare earth) systems, the superconducting phase appears without being accompanied by static magnetic order, except for narrow phase-separated regions at the border of phase boundaries. By muon spin relaxation measurements on single crystal specimens, here we show that superconductivity in the AFe$_{2}$As$_{2}$ (A = Ca,Ba,Sr) systems, in both the cases of composition and pressure tunings, coexists with a strong static magnetic order in a partial volume fraction. The superfluid response from the remaining paramagnetic volume fraction of (Ba$_{0.5}$K$_{0.5}$)Fe$_{2}$As$_{2}$ exhibits a nearly linear variation in T at low temperatures, suggesting an anisotropic energy gap with line nodes and/or multi-gap effects.Comment: 14 pages 7 figures (4 for main text and 3 for on-line supplementary documents