A V530I Mutation in c-KIT Exon 10 Is Associated to Imatinib Response in Extraabdominal Aggressive Fibromatosis

Aggressive fibromatosis (AF) or desmoid tumor is a rare condition, characterized by deep tissue invasion by a monoclonal fibroblastic neoplasm, developed from musculoaponeurotic structures. Surgery is the treatment of choice, but negative margins can hardly been achieved in large tumors, and can lead to major functional disability. AF medical therapy includes nonsteroids anti-inflammatory drugs, tamoxifen, with inconsistent results. Several reports of imatinib efficacy in AF appear in the literature. Here, we describe for the first time a V530I KIT exon 10 mutant that was associated to a dramatic imatinib response in an extraabdominal aggressive fibromatosis. The previously discovered V530I substitution was characterized in the core binding factor AML, but had never been reported in any other condition, so far. In this paper, we discuss the KIT exon 10 mutations or polymorphisms that have been described in a variety of KIT-related conditions, including acute myelogenous leukemia, mastocytosis, and aggressive fibromatosis

Receptor Tyrosine Kinases in Osteosarcoma: 2019 Update

The primary conclusions of our 2014 contribution to this series were as follows: Multiple receptor tyrosine kinases (RTKs) likely contribute to aggressive phenotypes in osteosarcoma and, therefore, inhibition of multiple RTKs is likely necessary for successful clinical outcomes. Inhibition of multiple RTKs may also be useful to overcome resistance to inhibitors of individual RTKs as well as resistance to conventional chemotherapies. Different combinations of RTKs are likely important in individual patients. AXL, EPHB2, FGFR2, IGF1R, and RET were identified as promising therapeutic targets by our in vitro phosphoproteomic/siRNA screen of 42 RTKs in the highly metastatic LM7 and 143B human osteosarcoma cell lines. This chapter is intended to provide an update on these topics as well as the large number of osteosarcoma clinical studies of inhibitors of multiple tyrosine kinases (multi-TKIs) that were recently published

Fostering mathematical competence through outdoor play for 3-4 years old children

Darba autore: Līga Asmane. Kvalifikācijas darba temats: “3-4 gadīgu bērnu matemātisko prasmju sekmēšana āra rotaļās”. Darba mērķis ir teorētiski un praktiski izzināt 3-4 gadīgu bērnu matemātisko prasmju sekmēšanas iespējas āra rotaļās. Pētījuma objekts ir āra rotaļas pedagoģiskajā procesā pirmsskolā, pētījuma priekšmets ir 3-4 gadīgu bērnu matemātisko prasmju attīstība. Mērķa sasniegšanai tika realizēti sekojoši uzdevumi: 1. Raksturot pirmsskolas vecuma bērnu dažādu prasmju veidošanos un attīstību; 2. Analizēt pedagoģijas un psiholoģijas zinātnieku atziņas par matemātiskām prasmēm; 3. Izzināt matemātisko prasmju sekmēšanas iespējas āra darbībās; 4. Praktiski pētīt matemātisko prasmju sekmēšanu; 5. Apkopot un analizēt pētījumu rezultātus, izstrādāt secinājumus. Kvalifikācijas darbs sastāv no divām daļām – teorētiskās un empīriskās daļas. Kvalifikācijas darbā tika analizētas autoru A. Šponas, V. Golubina, I. Bullas-Bitenieces, I. Krūmiņas, D. Dzintares, I. Stangaines, J. Aunītes, I. Helmanes, R. Andersones un citu autoru atziņas par vecuma īpatnībām, matemātiskām prasmēm un āra rotaļu nozīmi 3-4. gadīgu bērnu prasmju attīstībā. Darba teorētiska daļa sastāv no trīs apakšnodaļām. Pirmajā apakšnodaļā tiek izzināta bērna attīstība, raksturojums un to spējas. Otrajā apakšnodaļā tiek apskatīta matemātisko prasmju attīstība pirmsskolā. Trešajā apakšnodaļā tiek izzinātas āra rotaļas, kā matemātisko prasmju sekmētājas. Darba empīriskā daļa tiek atspoguļota otrajā nodaļā un tā sastāv no četrām apakšnodaļām. Lai noskaidrotu 3-4 gadīgu bērnu matemātisko prasmju sekmēšanas iespējas āra rotaļās, tika izmantota tiešā novērošana. Kvalifikācijas darbā tika izvērtēts bērnu matemātisko prasmju attīstības līmenis pētījuma sākumā un beigās. Bērnu prasmes tika sekmētas ar praktisko darbības palīdzību, bērniem piedāvājot caur āra rotaļām apgūt matemātiskās prasmes. Apkopojot iegūtos rezultātus, tiek veikta analīze un izstrādāti secinājumi. Kvalifikācijas darba apjoms ir 44 lapaspuses., darbā iekļauti 16 attēli un 3 tabulas, izmantoti 47 literatūras un informācijas avoti.Author of qualification assignment: Liga Asmane. The topic of the qualification assignment is fostering mathematical competence through outdoor play for 3-4 years old children. Research's study aim is to theoretically and practically acquire 3-4-year-old children's mathematical competence possibilities of fostering in outdoor play. The subject of study is outdoor play in the pedagogical process for primary school, the object of study - the development of mathematical competence for 3-4- years old children. To accomplish the aims of the research’s study following tasks were implemented: 1. To feature the formation of primary school children's various competencies and development; 2. To analyze pedagogical and psychological scientist realizations about mathematical competencies; 3. To practically research mathematical competencies fostering; 4. To summarize and analyze research results, develop conclusions. Qualification assignment depicts from the theoretical and empirical part, analysing authors A. Šponas, V. Golubina, I. Bullas- Bitenieces, I.Krūmiņas, D. Dzintares, I.Stangaines, J.Aunītes, I.Helmanes, R. Andersones and other authors' realizations about peculiarities of age and mathematical competencies and outdoor play significance for 3-4-years old children competencies development. The assignments theoretical part consists of three subsections. The first subsection explores the child's development, characteristics, and abilities. The second subsection deals with the development of mathematical competencies in primary school. The third subsection explores outdoor games as facilitators of mathematical competence. The empirical part of the assignment is presented in the second chapter and consists of four subsections. Direct observation was used to establish the possibilities to facilitate the mathematical competencies of 3-4-year-old children in outdoor games. The level of development on children's mathematical competencies was assessed at the beginning of the research and at the end. Children's competencies were facilitated with the aid of practical activities, to provide for children to acquire mathematical competencies through outdoor games. Summarizing the obtained results, the analysis is carried out and conclusions are drawn. The Qualification assignment consists of 44 pages including 3 tables, 16 pictures, 47 literature and information sources and appendices

Specific cooperation between stromal microenvironment and constitutively active androgen receptor variants in prostate cancer

Malgré le rôle des variants constitutivement actifs du récepteur des androgènes (RA) et du stroma tumoral dans le cancer de la prostate résistant à la castration (CRPC), leurs relations restent inconnues. Nous rapportons l’impact de l’interleukine-6 (IL-6) sécrétée par les cellules stromales prostatiques (PrSC) sur les cellules épithéliales tumorales prostatiques exprimant les variants autonomes du RA. Le milieu de culture conditionné par les PrSC (CMPrSC) contenait des taux élevés d’IL-6 et induisait une augmentation de l’activité transcriptionnelle de STAT3 dans les LNCaP et C4-2b exprimant le variant RAQ640X, via une activation de pY705-STAT3. Cette activité de STAT3 était inhibée par la neutralisation de l’IL-6. L’analyse par mRNA array et RT-qPCR a mis en évidence un profil transcriptomique spécifique lié à l’expression du RAQ640X et à l’exposition au CMPrSC, impliquant les fonctions de motilité, d’invasion et de migration cellulaires, et l’expression de gènes favorisant la dissémination métastatique. Ainsi, nos résultats illustrent une coopération épithélio-stromale «privilégiée» en présence de variants autonomes du RA, impliquée dans la progression tumorale.Constitutively active androgen receptor (AR) variants and stromal microenvironment are involved in castration resistant prostate cancer (CRPC), but their relationship remains unknown. We describe the effects of interleukin-6 (IL6) secreted from prostate stromal fibroblast cells (PrSC) towards prostate epithelial cancer cells expressing constitutively active AR variants. Conditioned culture medium from PrSC (CMPrSC) contained high levels of IL-6 and led to an increased STAT3 transcriptional activity in LNCaP and C4-2b cells expressing the ARQ640X variant, through pY705-STAT3 activation. This STAT3 activity was significantly diminished with neutralizing antibody anti-IL6. Gene expression analysis using mRNA array and RT-qPCR highlighted a specific transcriptional profile related to ARQ640X expression and PrSC exposure, resulting in cellular motility, invasion and cellular migration, and IL-6 genes expression promoting metastatic dissemination. Overall, our data emphasize a “preferred” epithelio-stromal cooperation when expressing constitutive active RA variants, which contributes to tumor progression

Fostering the acquisition of the field of study of health and physical activities for children, 5-6 years old, through active movement games

Darba autore: Ilga Asmane Kvalifikācijas darba temats: „5 – 6 gadīgu bērnu veselības un fiziskās aktivitātes mācību jomas apguves veicināšana kustību rotaļās”. Pētījuma priekšmets: veselības un fiziskās mācību jomas apguves veicināšana pirmsskolā. Pētījumu objekts: kustību rotaļas pedagoģiskajā procesā pirmsskolā. Pētījuma mērķis: teorētiski izzināt un praktiski pamatot kustību rotaļu izmantošanas iespējas 5 - 6 gadīgu bērnu veselības un fiziskās aktivitātes mācību jomas apguvē. Pētījuma mērķa sasniegšanai, tika īstenoti šādi uzdevumi: 1. analizēt pedagoģisko un psiholoģisko literatūru par veselības un fiziskās mācību jomas saturu, pamatkustībām un to veidiem; 2. izzināt bērna fiziskās attīstības un pamatkustību apguves likumsakarības; 3. praktiski izzināt kustību rotaļu ietekmi uz pamatkustību apguvi bērniem vecākajā pirmsskolas vecumā. Kvalifikācijas darbs sastāv no teorētiskās un empīriskās daļas, darbā tika analizētas autoru Z. Višķeres, I. Stangaines, D.Dzintares, R. Ļesņičija, R. Karlovskas, V. Ripas un citu autoru atziņas par vecuma īpatnībām un kustību rotaļu nozīmi 5-6 gadīgu bērnu attīstībā. Darba autore empīriskajā daļā veica bērnu darbības novērošanu, lai izzinātu pamatkustību apguvi bērniem vecākajā pirmsskolas vecumā. Pamatojoties uz iegūtajiem rezultātiem, tika veikta mērķtiecīga pedagoģiskā procesa izmēģinājuma darbība. Veselības un fiziskās aktivitātes mācību joma tika sekmēta ar kustību rotaļu palīdzību, iekļaujot rotaļas rīta vingrošanā, pastaigās un sporta nodarbībās. Kvalifikācijas darba analīze un secinājumi tika izstrādāti, pamatojoties uz pētījuma sākumā un beigās iegūtajiem rezultātiem, kur uzskatāmi vērojams, ka bērnu veselības un fiziskās aktivitātes mācību jomas apguve tiek sekmēta, ja skolotājs pedagoģiskajā procesā iekļauj kustību rotaļas ar pamatkustību elementiem. Kvalifikācijas darba apjoms ir 56 lapaspuses, darbā iekļauti 23 attēli un divas tabulas, izmantoti 43 literatūras un informācijas avoti.Author of qualification assignment: Ilga Asmane The topic of qualification assignment: “Fostering the acquisition of the field of study of health and physical activities for children, 5-6 years old, through active movement games.” The subject of study: fostering the acquisition of the field of study of health and physical activities in preschool. The object of study: the importance of active motion games in the preschool's pedagogical process. Research's study aim: to theoretically acknowledge and practically substantiate options of using active movement games in the field of study of health and physical activities for children 5-6 years old. Tasks implemented to accomplish the aims of the research’s study: 1.to analyze pedagogical and psychological literature about the context of the study of health and physical activities, basic movements and their types; 2.acknowledge the causal of a child's physical development and acquisition of basic movements; 3.practically study the impact of the child’s basic movement acquisition on active movement games in the elder age of preschool. Qualification assignment depicts from the theoretical and empirical part, analysing authors Z. Višķeres, I. Stangaines, D. Dzintares, R. Ļesņičija, R. Karlovskas, V. Ripas, and other authors realisations about peculiarities of age and importance of active movement games in 5-6 years old children's development. To study basic movement acquisition for older preschoolers, the author of the qualification assignment has carried out observations in the empirical part of the paper. Trial work of purposeful pedagogical process was carried out based on obtained results. With the aid of movement games including morning physical exercises, walks, and sporting activities the field of study of health and physical activities was promoted. The qualification assignment analysis and conclusions are drawn based on the beginning and the end parts of the research obtained results. These results clearly state that the acquisition of the field of children's health and physical activity is fostered if the teacher includes active movement games with elements of basic movements in the pedagogical process. The Qualification assignment consists of 56 pages including 23 pictures, two tables, and 43 literature and information sources

Specific cooperation between stromal microenvironment and constitutively active androgen receptor variants in prostate cancer

Malgré le rôle des variants constitutivement actifs du récepteur des androgènes (RA) et du stroma tumoral dans le cancer de la prostate résistant à la castration (CRPC), leurs relations restent inconnues. Nous rapportons l’impact de l’interleukine-6 (IL-6) sécrétée par les cellules stromales prostatiques (PrSC) sur les cellules épithéliales tumorales prostatiques exprimant les variants autonomes du RA. Le milieu de culture conditionné par les PrSC (CMPrSC) contenait des taux élevés d’IL-6 et induisait une augmentation de l’activité transcriptionnelle de STAT3 dans les LNCaP et C4-2b exprimant le variant RAQ640X, via une activation de pY705-STAT3. Cette activité de STAT3 était inhibée par la neutralisation de l’IL-6. L’analyse par mRNA array et RT-qPCR a mis en évidence un profil transcriptomique spécifique lié à l’expression du RAQ640X et à l’exposition au CMPrSC, impliquant les fonctions de motilité, d’invasion et de migration cellulaires, et l’expression de gènes favorisant la dissémination métastatique. Ainsi, nos résultats illustrent une coopération épithélio-stromale «privilégiée» en présence de variants autonomes du RA, impliquée dans la progression tumorale.Constitutively active androgen receptor (AR) variants and stromal microenvironment are involved in castration resistant prostate cancer (CRPC), but their relationship remains unknown. We describe the effects of interleukin-6 (IL6) secreted from prostate stromal fibroblast cells (PrSC) towards prostate epithelial cancer cells expressing constitutively active AR variants. Conditioned culture medium from PrSC (CMPrSC) contained high levels of IL-6 and led to an increased STAT3 transcriptional activity in LNCaP and C4-2b cells expressing the ARQ640X variant, through pY705-STAT3 activation. This STAT3 activity was significantly diminished with neutralizing antibody anti-IL6. Gene expression analysis using mRNA array and RT-qPCR highlighted a specific transcriptional profile related to ARQ640X expression and PrSC exposure, resulting in cellular motility, invasion and cellular migration, and IL-6 genes expression promoting metastatic dissemination. Overall, our data emphasize a “preferred” epithelio-stromal cooperation when expressing constitutive active RA variants, which contributes to tumor progression

Coopération privilégiée entre le microenvironnement stromal et les variants autonomes du récepteur des androgènes dans le cancer de la prostate

Constitutively active androgen receptor (AR) variants and stromal microenvironment are involved in castration resistant prostate cancer (CRPC), but their relationship remains unknown. We describe the effects of interleukin-6 (IL6) secreted from prostate stromal fibroblast cells (PrSC) towards prostate epithelial cancer cells expressing constitutively active AR variants. Conditioned culture medium from PrSC (CMPrSC) contained high levels of IL-6 and led to an increased STAT3 transcriptional activity in LNCaP and C4-2b cells expressing the ARQ640X variant, through pY705-STAT3 activation. This STAT3 activity was significantly diminished with neutralizing antibody anti-IL6. Gene expression analysis using mRNA array and RT-qPCR highlighted a specific transcriptional profile related to ARQ640X expression and PrSC exposure, resulting in cellular motility, invasion and cellular migration, and IL-6 genes expression promoting metastatic dissemination. Overall, our data emphasize a “preferred” epithelio-stromal cooperation when expressing constitutive active RA variants, which contributes to tumor progression.Malgré le rôle des variants constitutivement actifs du récepteur des androgènes (RA) et du stroma tumoral dans le cancer de la prostate résistant à la castration (CRPC), leurs relations restent inconnues. Nous rapportons l’impact de l’interleukine-6 (IL-6) sécrétée par les cellules stromales prostatiques (PrSC) sur les cellules épithéliales tumorales prostatiques exprimant les variants autonomes du RA. Le milieu de culture conditionné par les PrSC (CMPrSC) contenait des taux élevés d’IL-6 et induisait une augmentation de l’activité transcriptionnelle de STAT3 dans les LNCaP et C4-2b exprimant le variant RAQ640X, via une activation de pY705-STAT3. Cette activité de STAT3 était inhibée par la neutralisation de l’IL-6. L’analyse par mRNA array et RT-qPCR a mis en évidence un profil transcriptomique spécifique lié à l’expression du RAQ640X et à l’exposition au CMPrSC, impliquant les fonctions de motilité, d’invasion et de migration cellulaires, et l’expression de gènes favorisant la dissémination métastatique. Ainsi, nos résultats illustrent une coopération épithélio-stromale «privilégiée» en présence de variants autonomes du RA, impliquée dans la progression tumorale

Les fibromatoses agressives ou tumeurs desmoïdes (recherche de facteurs cliniques, histologiques et moléculaires liés à la rechute et à la sensibilité thérapeutique. A propos d'une série de 77 cas.)

STRASBOURG-Medecine (674822101) / SudocSudocFranceF