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

Conductivity of graphene: How to distinguish between samples with short and long range scatterers

Applying a quasiclassical equation to carriers in graphene we found a way how to distinguish between samples with the domination of short and long range scatterers from the conductivity measurements. The model proposed explains recent transport experiments with chemically doped as well as suspended graphene.Comment: 6 pages, 3 figures, some references have been corrected and revise

The effect of electro-hydrodynamic shockwaves on the quality of striploin and brisket beef muscles during long-term storage

Shockwaves generate instantaneous high pressures, which could affect meat shelf-life or quality. This study assessed microbiological counts, pH, drip, cook and moisture loss and texture of striploin (longissimus lumborum) and brisket (pectoralis profundus) treated with electrical shockwave (25 kV, 8 pulses) and subsequently stored (−0.5 °C) for 0, 4, 8, 12, 16 and 20 weeks. Shockwave did not affect total viable counts (p>0.05), with all samples considered microbiologically acceptable (0.05). Shockwave × storage time increased moisture losses in striploin (p<0.01) and brisket (p<0.01) at week 0 but this decreased over subsequent storage weeks. Shockwave technology did not affect meat shelf-life and has potential for beef tenderisation

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

'It would be easier if she’d died’: young people with parents with dementia articulating inadmissible stories

In the U.K. context where the emphasis is (quite rightly) on living well with dementia, on positivity and enabling approaches, it can be difficult for researchers to investigate and report negative experiences. Failing to re-present perceptions and experiences as they are lived, however, does a serious disservice to the research endeavor and can prevent policy and service development and positive change. In this article, we present some stories told by participants in an Alzheimer’s Society (United Kingdom) Funded project uniquely investigating the perceptions and experiences of children and young people who have a parent with dementia. Sometimes the stories were not easy to hear, especially when they challenged dominant master narratives around dementia. We discuss our view that when the young people we spoke with told us how things were for them, we were ethically bound to respect and disseminate their accounts

Methodological approaches to determining the marine radiocarbon reservoir effect

The marine radiocarbon reservoir effect is an offset in 14C age between contemporaneous organisms from the terrestrial environment and organisms that derive their carbon from the marine environment. Quantification of this effect is of crucial importance for correct calibration of the &lt;sup&gt;14&lt;/sup&gt;C ages of marine-influenced samples to the calendrical timescale. This is fundamental to the construction of archaeological and palaeoenvironmental chronologies when such samples are employed in &lt;sup&gt;14&lt;/sup&gt;C analysis. Quantitative measurements of temporal variations in regional marine reservoir ages also have the potential to be used as a measure of process changes within Earth surface systems, due to their link with climatic and oceanic changes. The various approaches to quantification of the marine radiocarbon reservoir effect are assessed, focusing particularly on the North Atlantic Ocean. Currently, the global average marine reservoir age of surface waters, R(t), is c. 400 radiocarbon years; however, regional values deviate from this as a function of climate and oceanic circulation systems. These local deviations from R(t) are expressed as +R values. Hence, polar waters exhibit greater reservoir ages (&#948;R = c. +400 to +800 &lt;sup&gt;14&lt;/sup&gt;C y) than equatorial waters (&#948;R = c. 0 &lt;sup&gt;14&lt;/sup&gt;C y). Observed temporal variations in &#948;R appear to reflect climatic and oceanographic changes. We assess three approaches to quantification of marine reservoir effects using known age samples (from museum collections), tephra isochrones (present onshore/offshore) and paired marine/terrestrial samples (from the same context in, for example, archaeological sites). The strengths and limitations of these approaches are evaluated using examples from the North Atlantic region. It is proposed that, with a suitable protocol, accelerator mass spectrometry (AMS) measurements on paired, short-lived, single entity marine and terrestrial samples from archaeological deposits is the most promising approach to constraining changes over at least the last 5 ky BP

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

The experience of children with parents diagnosed with young onset dementia: A systematic literature review

Background: Young onset dementia (YOD) may develop rapidly, and affect those who have dependent children. Currently, there remains a lack of understanding of the impact on children living with a parent with YOD. Aim: The aim of this systematic literature review is to explore published literature in order to understand the impact on children living with a parent with YOD. Methods: A systematic search of the following databases: Medline; PsychINFO; CINAHL and Scopus for literature published from 1/1/2013 to 31/12/2018. Results: Three major themes were identified, firstly coping encompassed two sub-themes of avoiding the situation and being empowered. Secondly, change encompassed two sub-themes of change of personality and change of family role, and lastly loss. Conclusion: There remains a need to raise awareness and develop support services for children of parents with YOD. Community nurses are the best place healthcare professionals to identify and support the needs of both the person with YOD and their children

Guidelines of the American Society of Mammalogists for the use of wild mammals in research

Guidelines for use of wild mammal species are updated from the American Society of Mammalogists (ASM) 2007 publication. These revised guidelines cover current professional techniques and regulations involving mammals used in research and teaching. They incorporate additional resources, summaries of procedures, and reporting requirements not contained in earlier publications. Included are details on marking, housing, trapping, and collecting mammals. It is recommended that institutional animal care and use committees (IACUCs), regulatory agencies, and investigators use these guidelines as a resource for protocols involving wild mammals. These guidelines were prepared and approved by the ASM, working with experienced professional veterinarians and IACUCs, whose collective expertise provides a broad and comprehensive understanding of the biology of nondomesticated mammals in their natural environments. The most current version of these guidelines and any subsequent modifications are available at the ASM Animal Care and Use Committee page of the ASM Web site (http://mammalsociety.org/committees/index.asp).American Society of Mammalogist

"From ‘What the hell is going on?’ to the ‘Mushy middle ground’ to ‘getting used to a new normal’: Young people’s biographical narratives around navigating parental dementia"

The number of young people who have a parent with dementia is rising as a result of improvements in diagnosis of young onset variants and demographic shifts. There has, however, been very little research focusing on this group. Accounts elicited as part of the Perceptions and Experiences of Young People With a Parent With Dementia described the period, usually some years, leading up to a diagnosis of a dementia and then the progress of the condition post diagnosis. These narratives were characterised by confusion, uncertainty, trauma and distress as the young people struggled to make sense of the significant and often extreme, behavioural and attitudinal changes that were symptoms of the illness. This paper describes and discusses how the young people experienced and navigated the temporal messiness and consequent biographical disruption arising from parental dementia