Characterization of a novel novobiocin analogue as a putative Cterminal inhibitor of heat shock protein 90 in prostate cancer cells

PURPOSE: Hsp90 is important in the folding, maturation and stabilization of pro-tumorigenic client proteins and represents a viable drug target for the design of chemotherapies. Previously, we reported the development of novobiocin analogues designed to inhibit the C-terminal portion of Hsp90, which demonstrated the ability to decrease client protein expression. We now report the characterization of the novel novobiocin analogue, F-4, which demonstrates improved cytotoxicity in prostate cancer cell lines compared to the N-terminal inhibitor, 17-AAG. MATERIALS AND METHODS: LNCaP and PC-3 cells were treated with 17-AAG or F-4 in anti-proliferative, apoptosis, cell cycle and cytotoxicity assays. Western blot and prostate specific antigen (PSA) ELISAs were used to determine client protein degradation, induction of Hsp90 and to assess the functional status of the androgen receptor (AR) in response to F-4 treatment. Surface Plasmon Resonance (SPR) was also used to determine the binding properties of F-4 to Hsp90. RESULTS: F-4 demonstrated improved potency and efficacy compared to novobiocin in anti-proliferative assays and decreased expression of client proteins. PSA secretion was inhibited in a dose-dependent manner that paralleled a decrease in AR expression. The binding of F-4 to Hsp90 was determined to be saturable with a binding affinity (Kd) of 100 µM. In addition, superior efficacy was demonstrated by F-4 compared to 17-AAG in experiments measuring cytotoxicity and apoptosis. CONCLUSIONS: These data reveal distinct modes of action for N-terminal and C-terminal Hsp90 inhibitors, which may offer unique therapeutic benefits for the treatment of prostate cancer

Recovery of the herbaceous layer in the young silver birch and black alder stands that developed spontaneously after a forest fire

The studies, which were conducted in southern Poland, focused on the recovery of the herb layer in 17-year-old post-fire silver birch and black alder forests. Although both types of stands, which are of the same age, developed spontaneously, the alder stands occupied damper sites (with thicker A horizons that survived the fire) than those in the birch forests. We surveyed the migration rates of 44 woodland species, primarily ancient woodland indicators, into both forests and the potential differences in these rates depending on their moisture regime and the community type represented by unburned forests, which were treated as the source of the woodland species pool. Additionally, the role of local depressions with high humidity that were covered by post-fire alder woods in the colonization process, as well as species survivorship and recolonisation, were estimated. Woodland species showed diverse migration paces among the sites; most of them migrated faster on more fertile sites with a higher humidity. Small patches of post-fire alder woods contributed to the recolonisation process since many woodland species in the herb layer survived the fire due to its high humidity, which inhibited the intensity of the forest fire. The recovery of woodland species in post-fire woods is the combined effect of regeneration, which relies on autochthonic propagules, and secondary succession, which is based on allochthonic propagules. Local depressions, which provide refuges for fire-sensitive, dispersal-limited species, contribute to their survivorship and thus to the successive recovery of herbaceous layers after a fire

Silvicultural and economic aspects of container-grown seedling production subjected to controlled mycorrhization

This study focuses on the variation in the growth and development parameters of seedlings and their survival in plantations in relation to the degree of soil degradation and seedling production method. Seedlings were planted on former agricultural land, industry damaged forest zones II and III, burnt areas, reclaimed sand mine excavations and industrial soils. The material used in the study comprised container−grown seedlings mycorrhized with the fungus Hebeloma crustuliniforme and Laccaria bicolor, seedlings not subjected to controlled mycorrhization and field−grown bare−root seedlings

The search of perspective concept of forest protection

Ochrona lasu już w swej pierwotnej formie dostrzegała powiązania stanu zagrożenia drzewostanu ze stanem środowiska leśnego. Nie znalazła jednak koncepcji uporządkowania metodologicznego tej dyscypliny zgodnie z jej proekologiczną perspektywą. Zasadniczy wpływ na kształt ochrony lasu miała przez dziesiątki lat schwerdfegerowska idea nawiązywania metodologii ochrony lasu do metodologii nauk medycznych, co w Polsce rozwinął Witold Koehler wprowadzając do przestrzeni intelektualnej koncepcję hylopatologii. Następnie dyskutowano nad ochroną lasu jako ochroną ekosystemów leśnych lub hylosozologią wykorzystującą możliwości inżynierii ekologicznej. Były to próby twórcze, ale nie zakończone powszechną akceptacją. Tymczasem zmiana charakteru gospodarki leśnej na proekologiczną i wielofunkcyjną i silne zmiany w środowisku globalnym wykazały niedostatki dotychczasowej klasyfi kacji celów ochrony lasu, możliwości ich osiągania zarówno w zakresie nauki jak i działań praktycznych. Istnieje więc uzasadnienie, by do tej tematyki powrócić poddając ją osądowi zawodowemu jak i z punktu widzenia metodologii naukowej.The search of perspective concept of forest protection. The forest protection just in it’s primeval form notices the link between treats to a forest stands and the state of forest ecosystem. But it has not found a methodological way to order this branch according to ecological perspective yet. The Schwerdfeger idea of forest protection methodology referring to a medical science methodology has signifi cant impact on the forest protection consistence for many decades. This idea was developed in Poland by Witold Koehler who introduced it into intellectual sphere of the hylopathology. Than the forest protection was discussed as a forest ecosystem protection or hylosozology using a potential of the ecological engineering. Those were fruitful approaches but not universally accepted. Meantime the character changes of a forest economy to an ecological and sustainable direction and signifi cant changes in a global environment have demonstrated the imperfection of up to now forest protection tasks classifi cation and the possibility to gain them from the scientific as well as practical point of view. Therefore there is a reason to come back to this issues taking under the consideration professional as well as scientific methodology

Educational program in onco-urology for young urologists: What are their needs?

International audiencePurposeThe emergence of new communication media such as digital contents are progressively replacing more traditional medias in the field of educational programs. Our purpose was to assess urologist in training aspirations regarding urological education.MethodsMembers of a national urologist in training association were sent an anonymous online questionnaire regarding their medical formation in the field of urology. Responders interest for urological sub-specialty or education support (new tools and traditional support) were evaluated through a 5-point Likert scale.ResultsOverall, 109 young urologists (26%) responded to the survey. Most of the respondents worked during their training in an academic hospital (n = 89, 82%). The three favorite tools for training chosen by the responders were: videos, workshop or masterclass, and podcasts (responders very interested were respectively n = 64 (58.7%), n = 50 (45.9%), and n = 49 (45%)). E-mail newsletters were reported as the less useful educational tool by participants (n = 38, 34.9%). Participants were very interested in improving their surgical skills and their radiological knowledge. Responders who were the most attracted by PCa were much more looking to improve their systemic treatment and radiological knowledges.ConclusionsUrologic-oncology was a priority regarding education for urologists in training. A majority of participants expressed a lack in their surgical education, revealing a reduced OR access and underlining utilization of new tools such as simulation. New digital contents such as social media or podcast achieved high interest for the participants, instead of more traditional media. There is a need that educational content evolve and uses new digital media.ButDans la formation médicale, les nouveaux médias de communication tels que les contenus numériques se développent très rapidement et tendent à remplacer les médias plus traditionnels. Notre objectif était d’évaluer les aspirations des urologues en matière de formation en onco-urologie.MatérielLes membres de l’Associations française des urologues en formation ont répondu à un questionnaire en ligne anonyme concernant leur formation en onco-urologie. L’intérêt des participants pour les différents moyens de formation ainsi que pour les spécialités d’organes ont été évalués avec une échelle de Likert à 5-points.RésultatsAu total, 109 urologues en formation ont répondu à l’enquête (26 %). La plupart ont effectué leur formation exclusivement dans un hôpital universitaire (n = 89, 82 %). Les trois outils de formation préférés des participants étaient : les supports vidéo, les ateliers ou masterclass, et les podcast (étaient très intéressés respectivement n = 64 (59 %), n = 50 (46 %) et n = 49 (45 %)). Les newsletters ont été considérées comme l’outil éducatif le moins utile (n = 39, 35 %). Les participants étaient très intéressés par l’amélioration de leurs compétences chirurgicales et de leurs connaissances radiologiques. Les participants qui s’intéressaient le plus au cancer de la prostate cherchaient à consolider leurs connaissances sur les traitements systémiques ainsi qu’en radiologie.ConclusionL’onco-urologie est une priorité pour les urologues en formation. Les nouveaux contenus numériques tels que les réseaux sociaux ou les podcasts ont suscité un grand intérêt chez les participants, supplantant les médias plus traditionnels. Il est nécessaire que le contenu éducatif évolue et se repose sur les nouveaux médias numériques

Residents and patients benefit from surgical simulation on a live porcine model, could we consider it as ethical?

International audienceIntroduction: The objective was to evaluate, by self-questionnaire, the feeling of participants in surgical training sessions on a live porcine model.Methods: A computerized questionnaire (GoogleForm ©) was sent to the members of the French Association of Urologists-in-Training (AFUF) (fellows and residents). Only questionnaires from Urologists-in-training who had participated in surgical training sessions were included. The sessions consisted of performing surgeries such as laparoscopic nephrectomies or laparoscopic cystectomies.Results: Overall, 198 met the inclusion criteria. A total of 36.4% (72/198) of the participants were fellows and 63.6% (126/198) were residents. According to the participants, the main interest of sessions was to be able to train for emergency situations. A total of 79.8% (158/198) of the participants wanted surgical simulation to become compulsory. To their opinion, the main advantage of surgical simulation on a live porcine model was: technical progress in 87.4% (173/198) of cases. A total of 13.1% (26/198) of the participants found it was unethical to perform the first technical procedures on live animal models. A total of 65.7% (130/198) of the participants considered that there is currently no system of substitution.Conclusion: For the participants, surgical training on a live porcine model allows technical progress while training for serious emergency situations. Surgeons and patients could benefit from this risk-free mock surgical scenario.Level of evidence: 3