Targeting CXCR4 with CTCE-9908 inhibits prostate tumor metastasis

Abstract Background CXCL12/CXCR4 transactivation of epidermal growth factor family receptors in lipid raft membrane microdomains on cell surface is thought to mediate tumor growth and subsequent development of metastatic disease. CTCE-9908 is a known inhibitor of CXCR4. Herein, we tested the efficacy of CTCE-9908 in inhibiting prostate cancer cell growth, invasion, and metastasis. Methods We used a panel of in vitro assays utilizing human prostate cancer cell lines and an in vivo orthotopic prostate cancer model to assess the anti-tumoral activity of CTCE-9908. Results We demonstrated that (a) CTCE-9908 treatment resulted in no significant change in the growth of PC-3 and C4-2B cells; (b) 50 μg/ml of CTCE-9908 inhibited the invasive properties of PC-3 cells; (c) 25 mg/kg of CTCE-9908 did not alter primary tumor growth but it did significantly reduce total tumor burden in the animal including the growth of prostate and soft tissue metastases to lymph node and distant organ tissues. Histological analysis showed that CTCE-9908 treatment resulted in tumor necrosis in primary prostate tumors and no significant change in proliferation of tumor cells as measured by Ki-67 staining; (d) CTCE-9908 inhibited the tumor angiogenesis as measured by CD34 positive vessels in tumors. Conclusions These data suggest that CXCR4 inhibition by CTCE-9908 decreases the invasion potential in vitro, which then translated to a reduction of tumor spread with associated reduction in angiogenesis. Hence, CTCE-9908 may prove to be an efficacious novel agent to prevent and treat the spread of metastatic prostate cancer

Alergia à proteína do leite de vaca, qualidade de vida e estilos parentais

Introduction: Cow’s milk protein allergy requires changes in family habits to maintain children’s health. Objective: This study evaluated the effects of cow’s milk protein allergy on the health of children, the quality of life of parents and children, and the adopted parental styles. Methods: Control case study. The case group consisted of children with cow’s milk protein allergy, from eight months to five years old, and those guardians, and the Control Group, for healthy children of the same age group, and their parents. The quality of life of the child (TNO-AZL Preschool Children Quality of Life) and the caregiver (SF-36) were evaluated; parental style (Parental Beliefs and Care Practices Scale); and socioeconomic and health data of the child. The Mann-Whitney test was used to compare the groups (p <0.05). Results: 76 dyads from the case group and 44 from the control group participated. Children with cow’s milk protein allergy had a lower quality of life in the health dimension, worse nutritional status, followed up with a larger number of health professionals. Those in charge of the case group offered less body stimulation to the children. Those in the control group had a lower quality of emotional life. Conclusions: Cow’s milk protein allergy had an impact on the health and nutritional status of children, on the corporal stimulation received by the children, and on the quality of emotional life of those guardians.Introdução: A alergia à proteína do leite de vaca requer alterações dos hábitos familiares para manutenção das condições de saúde das crianças. Objetivo: Este estudo analisou os efeitos da alergia à proteína do leite de vaca sobre a saúde de crianças, qualidade de vida de responsáveis e crianças e sobre os estilos parentais adotados. Método: Estudo caso controle. O grupo caso foi constituído por crianças com alergia à proteína do leite de vaca, de oito meses a cinco anos de idade, e seus responsáveis, e o Grupo Controle, por crianças saudáveis, de mesma faixa etária, e seus responsáveis. Foram avaliadas a qualidade de vida da criança (TNO-AZL Preschool Children Quality of Life) e do responsável (SF-36); estilo parental (Escala de Crenças Parentais e Práticas de Cuidado); e dados socioeconômicos e de saúde da criança. O teste de Mann-Whitney foi utilizado para comparar os grupos (p <0,05). Resultados: Participaram 26 díades do grupo caso e 44 do grupo controle. Crianças com alergia proteína do leite de vaca apresentaram menor qualidade de vida na dimensão saúde, pior estado nutricional, realizaram acompanhamento com maior número de profissionais da saúde. Os responsáveis do grupo caso ofereceram menor estimulação corporal às crianças. Responsáveis do grupo controle apresentaram menor qualidade de vida emocional. Conclusão: A alergia à proteína do leite de vaca impactou na saúde e no estado nutricional das crianças, na estimulação corporal recebida pelas crianças, e na qualidade de vida emocional dos responsáveis

Важливе історико-географічне дослідження

Рец. на кн. Темушева В.Н. "Гомельская земля в конце XV первой половине XVI в. Территориальные трансформации в пограничном регионе". — М.: "Квадрига", 2009. — 190 с.Review of the book: Temushev V.N. "Gomel Land in the Late 15th — the 1st half of the 16th Centuries. Territorial Transformations in the Frontier Area". — Moscow: "Kvadriga", 2009. — 190 p

Rapid Changes in the Light/Dark Cycle Disrupt Memory of Conditioned Fear in Mice

Background: Circadian rhythms govern many aspects of physiology and behavior including cognitive processes. Components of neural circuits involved in learning and memory, e.g., the amygdala and the hippocampus, exhibit circadian rhythms in gene expression and signaling pathways. The functional significance of these rhythms is still not understood. In the present study, we sought to determine the impact of transiently disrupting the circadian system by shifting the light/ dark (LD) cycle. Such ‘‘jet lag’ ’ treatments alter daily rhythms of gene expression that underlie circadian oscillations as well as disrupt the synchrony between the multiple oscillators found within the body. Methodology/Principal Findings: We subjected adult male C57Bl/6 mice to a contextual fear conditioning protocol either before or after acute phase shifts of the LD cycle. As part of this study, we examined the impact of phase advances and phase delays, and the effects of different magnitudes of phase shifts. Under all conditions tested, we found that recall of fear conditioned behavior was specifically affected by the jet lag. We found that phase shifts potentiated the stress-evoked corticosterone response without altering baseline levels of this hormone. The jet lag treatment did not result in overall sleep deprivation, but altered the temporal distribution of sleep. Finally, we found that prior experience of jet lag helps to compensate for the reduced recall due to acute phase shifts. Conclusions/Significance: Acute changes to the LD cycle affect the recall of fear-conditioned behavior. This suggests that

Samen op weg naar een duurzaam mobiliteitssysteem

Duurzame mobiliteit is een noodzaak én een kans. Aangezien de behoefte aan verplaatsing van mensen en goederen blijft groeien is dé uitdaging voor ons mobiliteitssysteem voor de komende 10 jaar om in die behoefte te voorzien op een betrouwbare, betaalbare, schone, stille en veilige manier. Dat biedt ook kansen voor versterking van economische slagkracht (nieuwe businesskansen en kennisexport) en leefbaarheid in ons land. De publicatie Samen op weg naar een duurzaam mobiliteitssysteem is een inspirerende visie op de toekomst van mobiliteit. Met deze visie leggen TNO en Den Haag Centrum Strategische Studies (HCSS) de inhoudelijke basis voor een transitieprogramma waarin bedrijven, kennisinstellingen en overheden hun initiatieven bundelen om duurzame innovaties in het mobiliteitsdomein te versnellen. In deze studie zijn modellen uit de systeemdynamica gebruikt om goed zicht te krijgen op de beslissende relaties binnen het mobiliteitssysteem, die kunnen zorgen voor duurzame veranderingen in dat systeem: Klassiek leidt economische groei tot een groei in mobiliteit. Dit automatisme is te doorbreken met innovaties als het Nieuwe Werken en produceren op afstand. Het is cruciaal de beschikbare capaciteit op onze infrastructurele netwerken (weg, water en spoor) optimaal te benutten. Door inzet van Intelligente Transport Systemen (ITS) is een betere verdeling van transport over de bestaande infrastructuur en in de tijd mogelijk. Een goed voorbeeld in de logistiek is ‘Synchromodaliteit’ , in personenvervoer is goede multimodale reisinformatie een goed voorbeeld. Meer mobiliteit hoeft niet automatisch te leiden tot meer nadelige effecten voor mens en milieu, mits de voertuigen schoner, stiller en veiliger kunnen voortbewegen. Dit is mogelijk met bijvoorbeeld elektrische voertuigen, maar vereist ook een ander mobiliteitsgedrag. Tenslotte is het nodig de infrastructurele netwerken zelf minder kwetsbaar te maken voor incidenten. Soms dienen de netwerken hiervoor uitgebreid te worden met extra verbindingen zodat een robuust netwerk ontstaat dat alternatieve routes mogelijk maakt

Toxikologische Untersuchungen zur Interaktion von Chlordibrommethan mit anderen Haloformen und Quecksilber

Available from TIB Hannover: F98B330 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman