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1.
Child Dev ; 93(1): 254-268, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34463360

RESUMO

National-level monitoring of quality of early childhood education (ECE) is key to achieving inclusive and equitable education. Most countries report structural quality while process characteristics are rarely observed at the national level. This study examined the associations between ECE and children's development in a middle-income country using data from a nationally representative sample of public centers serving Colombian children (N = 3163; M = 4.3 years, 50% girls; 42% Mestizo, 16% White, 15% Afro-Colombian, 4% Indigenous, 23% not reported). Descriptive findings evidenced low to moderate quality. Multilevel models showed several positive associations between structural and process quality and child outcomes. Results have implications for the existing literature and highlight the feasibility of quality monitoring in low- and middle-income countries.


Assuntos
Desenvolvimento Infantil , Renda , Criança , Pré-Escolar , Colômbia , Escolaridade , Feminino , Humanos , Masculino
2.
Trials ; 22(1): 542, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404454

RESUMO

BACKGROUND: The Sustainable Development Goals (SDGs) highlight the importance of investments in early childhood care and education (ECCE) and youth development. Given Pakistan's large young population, and gender and urban-rural inequalities in access to education, training, and employment, such investments offer opportunities. LEAPS is a youth-led ECCE program that trains female youth, 18-24 years, as Community Youth Leaders (CYLs) to deliver high-quality ECCE for children, 3.5-5.5 years, in rural Sindh, Pakistan. METHODS: We use a stepped wedge cluster-randomized trial to evaluate implementation of LEAPS. Ninety-nine clusters will be randomized to receive the intervention in one of three 7-month steps (33 clusters/step). The primary outcome is children's school readiness (indexed by the total score on the International Development and Early Learning Assessment (IDELA)). Secondary child outcomes are children's IDELA domain scores and executive functions. Data are collected in cross-sectional surveys of 1089 children (11 children/cluster from 99 clusters) aged 4.5-5.5 years at four timepoints (baseline and at the end of each step). Additionally, we will enroll three non-randomized youth participant open cohorts, one per step (33 CYLs: 66 comparison youth per cohort; 99:198 in total). Youth cohorts will be assessed at enrollment and every 7 months thereafter to measure secondary outcomes of youth personal and professional development, depressive symptoms, and executive functions. A non-randomized school cohort of 330 LEAPS students (10 students/cluster from 33 clusters) will also be enrolled and assessed during Step 1 after intervention rollout and at endline. The quality of the learning environment will be assessed in each LEAPS ECCE center and in a comparison center at two timepoints midway following rollout and at endline. A concurrent mixed-methods implementation evaluation will assess program fidelity and quality, and the extent to which a technical support strategy is successful in strengthening systems for program expansion. A cost evaluation will assess cost per beneficiary. Data collection for implementation and cost evaluations will occur in Step 3. DISCUSSION: Youth-led models for ECCE offer a promising approach to support young children and youth. This study will contribute to the evidence as a means to promote sustainable human development across multiple SDG targets. TRIAL REGISTRATION: ClinicalTrials.gov NCT03764436 . Registered on December 5, 2018.


Assuntos
População Rural , Instituições Acadêmicas , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Aprendizagem , Paquistão , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Compr Psychoneuroendocrinol ; 8: 100092, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35757671

RESUMO

Children's environments - especially relationships with caregivers - sculpt not only developing brains but also multiple bio-behavioral systems that influence long-term cognitive and socioemotional outcomes, including the ability to empathize with others and interact in prosocial and peaceful ways. This speaks to the importance of investing resources in effective and timely programs that work to enhance early childhood development (ECD) and, by extension, reach communities at-scale. Given the limited resources currently devoted to ECD services, and the devastating impact of COVID-19 on children and communities, there is a clear need to spur government leaders and policymakers to further invest in ECD and related issues including gender and racial equity. This essay offers concrete examples of scholarly paradigms and leadership efforts that focus on child development to build a peaceful, equitable, just, and sustainable world. As scholars and practitioners, we need to continue to design, implement, assess, and revise high-quality child development programs that generate much-needed evidence for policy and programmatic changes. We must also invest in global partnerships to foster the next generation of scholars, practitioners, and advocates dedicated to advance our understanding of the bio-behavioral systems that underlie love, sociality, and peace across generations. Especially where supported by structural interventions, ECD programs can help create more peaceful, just, and socially equitable societies.

4.
Dev Psychopathol ; 33(2): 409-420, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32935656

RESUMO

This article provides an overview of selected ongoing international efforts that have been inspired by Edward Zigler's vision to improve programs and policies for young children and families in the United States. The efforts presented are in close alignment with three strategies articulated by Edward Zigler: (a) conduct research that will inform policy advocacy; (b) design, implement, and revise quality early childhood development (ECD) programs; and (c) invest in building the next generation of scholars and advocates in child development. The intergenerational legacy left by Edward Zigler has had an impact on young children not only in the United States, but also across the globe. More needs to be done. We need to work together with a full commitment to ensure the optimal development of each child.


Assuntos
Desenvolvimento Infantil , Família , Criança , Pré-Escolar , Humanos , Estados Unidos
5.
New Dir Child Adolesc Dev ; 2020(172): 103-123, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32964646

RESUMO

There is an urgent need to strengthen early childhood development and education in emergencies (ECDEiE) globally. Colombia has faced protracted and acute crises for decades. Also, the country has applied a unique approach to holistic and integrated ECDE policy formulation. We argue that these characteristics offer a valuable country-case to identify barriers and levers to the operationalization of ECDEiE. We applied a sector-wide analysis protocol that harmonized components of the Humanitarian Programme Cycle by the Inter-Agency Standing Committee and of a framework to characterize the governance of ECDE systems. The study outlines how the policy and program characteristics identified may represent levers or barriers to the effective operationalization of ECDEiE in Colombia. We discuss how these attributes could be considered in the trans-sectoral dialogue between ECDE and humanitarian actors with the aim of strengthening ECDEiE systems globally.


Assuntos
Desenvolvimento Infantil , Educação , Emergências , Desenvolvimento de Programas , Criança , Pré-Escolar , Colômbia , Saúde Global , Humanos , Colaboração Intersetorial , Desenvolvimento de Programas/economia
6.
New Dir Child Adolesc Dev ; 2020(172): 135-149, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32960503

RESUMO

Although developmental science has always been evolving, these times of fast-paced and profound social and scientific changes easily lead to disorienting fragmentation rather than coherent scientific advances. What directions should developmental science pursue to meaningfully address real-world problems that impact human development throughout the lifespan? What conceptual or policy shifts are needed to steer the field in these directions? The present manifesto is proposed by a group of scholars from various disciplines and perspectives within developmental science to spark conversations and action plans in response to these questions. After highlighting four critical content domains that merit concentrated and often urgent research efforts, two issues regarding "how" we do developmental science and "what for" are outlined. This manifesto concludes with five proposals, calling for integrative, inclusive, transdisciplinary, transparent, and actionable developmental science. Specific recommendations, prospects, pitfalls, and challenges to reach this goal are discussed.


Assuntos
Ciências Biocomportamentais , Psicologia do Desenvolvimento , Ciências Biocomportamentais/métodos , Ciências Biocomportamentais/normas , Ciências Biocomportamentais/tendências , Humanos , Psicologia do Desenvolvimento/métodos , Psicologia do Desenvolvimento/normas , Psicologia do Desenvolvimento/tendências
8.
PLoS One ; 15(3): e0229670, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32134961

RESUMO

The role of fathers in (co-)parenting their children among refugee and disadvantaged families in low and middle-income countries (LMICs) remains poorly understood. This study sought to examine the associations among mothers' perceptions of their husband's involvement (hereafter referred to as paternal involvement), and her perceptions of her own well-being and a number of other variables, as well as observed mother-child interactions in families living in refugee and disadvantaged communities in Beirut, Lebanon. We analyzed baseline data from 104 mother-child dyads (mean age of children = 4.34 years; range = 2.05 to 7.93 years of age) who participated in a randomized controlled trial aimed at evaluating the impact of the Mother-Child Education Program in Beirut. In addition to the mother's perception of paternal involvement and the videotaped mother-child interactions, data were collected concerning the mother's well-being and her level of social support, as well as her level of stress as a parent and the way her children were disciplined in the family. Mother-child pairs were videotaped while completing a puzzle together and dyadic interactions were coded. Path analysis showed that paternal involvement was significantly associated with a higher level of maternal well-being and lower distress levels. In addition, higher levels of maternal distress were associated with higher levels of harsh discipline and parenting stress. Correlation analysis showed that higher perceptions of paternal involvement were associated with more positive affect displayed by the child, more positive regard for the child, and better mother-child synchrony during the dyadic interactions. Limitations include the cross-sectional design and the modest sample size, which hinder causal inferences and generalizability of the findings. These preliminary findings suggest that higher levels of paternal involvement may have an impact on markers of maternal mental health and positive mother-child interactions in families living in disadvantaged communities or humanitarian settings. Paternal involvement should be considered when designing and implementing parenting programs in LMICs.


Assuntos
Pai/psicologia , Relações Mãe-Filho/psicologia , Mães/psicologia , Refugiados/psicologia , Adulto , Criança , Pré-Escolar , Estudos Transversais , Relações Pai-Filho , Feminino , Humanos , Líbano , Masculino , Saúde Mental , Pessoa de Meia-Idade , Poder Familiar/psicologia , Pais/psicologia , Cônjuges/psicologia , Adulto Jovem
9.
J Am Acad Child Adolesc Psychiatry ; 59(6): 727-738, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32014538

RESUMO

OBJECTIVE: Few randomized controlled trials (RCTs) have explored the implementation and impact of early childhood parenting education programs in very fragile contexts and humanitarian settings. We tested the effects of a group-based intervention, the Mother-Child Education Program (MOCEP), on parenting stress and practices among two refugee communities and one other marginalized community in Beirut, Lebanon. METHOD: A pilot wait-list RCT was conducted to assess the program's impact on maternal, child (average age: 4 years), and dyadic outcomes. A total of 106 mother-child dyads were randomly assigned to either the intervention group (n = 53) or the wait-list control group (n = 53). Analysis was conducted by modified intention-to-treat and supplemental analyses through multiple imputation of missing post-intervention data. RESULTS: Forty families (38%) withdrew early from the study. After completing the program, mothers in the intervention group showed a reduction in their harsh parenting practices, as indexed by the Disciplinary Style Questionnaire (Cohen's d = -0.76, 95% CI = -1.24, -0.27) and in their level of parenting stress, as indexed by the Parenting Stress Index-Short Form (PSI-SF; Cohen's d = -0.90, 95% CI = -1.39, -0.40). Exploratory but underpowered analyses of dyadic interactions revealed reductions in the PSI were associated with a reduction in harsh parenting after the intervention. However, we did not detect any positive impact on behavioral or emotional outcomes among the children. CONCLUSION: Our analyses suggest that MOCEP had a positive impact on disciplinary practices and parenting stress in a context of high fragility, but that broader effects on maternal and child outcomes may be dependent on program attendance and the availability of other services. We discuss implications of this pilot study for practice and research of a largely unexplored area of program evaluation. CLINICAL TRIAL REGISTRATION INFORMATION: Mother and Child Education Program in Palestinian Refugee Camps; https://clinicaltrials.gov; NCT02402556.


Assuntos
Poder Familiar , Refugiados , Criança , Pré-Escolar , Feminino , Humanos , Líbano , Relações Mãe-Filho , Mães , Projetos Piloto
10.
Soc Sci Med ; 239: 112476, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31539783

RESUMO

Grandparents are often a key source of care provision for their grandchildren, yet they are sidelined in caregiving research and policy decisions. We conducted a global, systematic review of the literature to examine the scope and quality of studies to date (PROSPERO database CRD42019133894). We screened 12,699 abstracts across 7 databases, and identified 206 studies that examined how grandparents influence child health and development. Indicators of grandparent involvement were contact, caregiving behaviors, and financial support. Our review focused on two research questions: how do grandparents influence child health and development outcomes, and what range of child outcomes is reported globally? We examined study design, sample characteristics, key findings, and outcomes pertaining to grandchildren's physical health, socio-emotional and behavioral health, and cognitive and educational development.  Our search captured studies featuring grandparent custodial care (n = 35), multigenerational care (n = 154), and both types of care (n = 17). We found substantial heterogeneity in the data provided on co-residence, caregiving roles, resources invested, outcomes, and mechanisms through which "grandparent effects" are manifested. We identified two important issues, related to operationalizing indicators of grandparent involvement and conceptualizing potential mechanisms, leading to gaps in the evidence base. Currently, our understanding of the pathways through which grandparents exert their influence is constrained by limited data on what grandparents actually do and insufficient attention given to interpersonal and structural contexts. We present a conceptual framework to explicitly measure and theorize pathways of care, with a view to inform research design and policy implementation. We underscore the need for more robust data on three indicators of caregiver involvement-contact, behavior, and support-and for careful description of structural and interpersonal contexts in caregiving research.


Assuntos
Cuidadores , Desenvolvimento Infantil , Saúde da Criança , Avós , Relação entre Gerações , Adolescente , Comportamento , Criança , Pré-Escolar , Cognição , Assistência de Custódia , Escolaridade , Saúde Global , Comportamentos Relacionados com a Saúde , Humanos , Renda , Lactente , Fatores Socioeconômicos
11.
New Dir Child Adolesc Dev ; 2019(167): 91-116, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31509332

RESUMO

Despite the knowledge that quality early childhood development programs, including those that target parental knowledge and behaviors, are essential for ameliorating the negative effects of early-life adversity, robust analyses of their implementation and impact in highly vulnerable settings are scarce. To address this knowledge gap, we conducted a pilot wait-list randomized controlled trial (RCT) to assess the impact and the process of implementing and evaluating the Mother-Child Education Program (MOCEP) among refugee families and one low-income community in Beirut, Lebanon. This paper focuses on the analysis of MOCEP's implementation (i.e., key enablers of and barriers to the application and evaluation of the program). Our analysis suggests that, despite multiple challenges, implementation and robust evaluations of early childhood parenting programs in fragile contexts are feasible and urgently needed. This study illustrates how implementation evaluations are a key component of RCTs and crucial to identifying strategies to optimize program uptake and maximize impact.


Assuntos
Educação não Profissionalizante/normas , Relações Mãe-Filho , Avaliação de Processos em Cuidados de Saúde/normas , Avaliação de Programas e Projetos de Saúde/normas , Refugiados , Populações Vulneráveis , Adulto , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Humanos , Ciência da Implementação , Líbano , Projetos Piloto , Desenvolvimento de Programas
12.
PLoS One ; 13(12): e0208335, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30566498

RESUMO

BACKGROUND: The United Nation's Sustainable Development Goals encompass lifelong learning from birth to youth to adulthood (Goal 4) and economic opportunities for young people (Goal 8). The targets include improving access to quality early childhood care and education (ECCE) as well as learning and training opportunities for adolescents and youth. Cross-generational models for young children and youth may offer opportunities to address the interconnections between goals and targets for the next generation. We investigated whether an ECCE programme for young children (3.5-6.5 years) delivered by female youth (18-24 years) in rural Pakistan would be effective on children's school readiness. METHODS: In partnership with the National Commission for Human Development in Pakistan, we implemented the 'Youth Leaders for Early Childhood Assuring Children are Prepared for School' (LEAPS) programme to train female youth to deliver ECCE. The effectiveness of the LEAPS programme on children's school readiness was evaluated in a cluster-randomised controlled trial. We randomly allocated five clusters (villages) to receive the intervention (n = 170 children) and five clusters to control (n = 170 children). Children's school readiness was assessed after nine months of intervention exposure using the International Development and Early Learning Assessment tool. Analyses was by intention-to-treat. The trial is registered with ClinicalTrials.gov, number NCT02645162. FINDINGS: At endline, the intervention group had significantly higher school readiness scores (n = 166, mean percentage score 59.4, 95% CI 52.7 to 66.2) compared with the control group (n = 168, mean percentage score 45.5, 95% CI 38.8 to 52.3). The effect size (Cohen's d) was 0.3. CONCLUSION: Trained female youth delivered an ECCE programme that was effective in benefitting young children's school readiness. The cross-generational model is a promising approach to support early child development; however, further evaluation of the model is needed to assess the specific benefits to youth including their skills and economic development.


Assuntos
Desenvolvimento Infantil , Adolescente , Adulto , Criança , Pré-Escolar , Intervenção Educacional Precoce , Feminino , Humanos , Masculino , Paquistão , População Rural/estatística & dados numéricos , Instituições Acadêmicas/estatística & dados numéricos , Adulto Jovem
13.
New Dir Child Adolesc Dev ; 2018(159): 71-89, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29537185

RESUMO

The international community has set forth global targets that include calls for universal access to high-quality early childhood care and education (ECCE), as indicated in the United Nations' Sustainable Development Goals. One major impediment to achieving this target is the lack of a skilled workforce. In this paper, we argue the case for leveraging youth as an untapped resource for supplying the workforce the ECCE system needs. Youth comprise a large proportion of the global population, and historically, although youth experience higher unemployment rates than their adult counterparts, youth are important agents of social awareness, social transformation, and community mobilization in multiple global contexts. We provide a conceptual model based on developmental theories and program examples to leverage the discourse of youth-led ECCE programs as a viable option to address workforce gaps while benefiting both young children and youth.


Assuntos
Desenvolvimento do Adolescente , Desenvolvimento Infantil , Conservação dos Recursos Naturais , Liderança , Desenvolvimento de Programas , Nações Unidas , Adolescente , Criança , Pré-Escolar , Humanos
14.
J Lat Psychol ; 4(3): 131-141, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28804695

RESUMO

There is a significant burden of hypertension in the United States, which extends to the large and growing Hispanic/Latino population. Previous literature suggests that psychosocial factors are related to hypertension in Hispanics/Latinos. However, cultural factors unique to this population have been largely understudied in this context. The purpose of the current investigation was to examine the association of hypertension prevalence with social support and simpatía, a Hispanic/Latino cultural value emphasizing social harmony. Cross-sectional data from 5,313 adult Hispanics/Latinos, age 18 to 75 years, representing multiple heritage groups were collected as part of the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study. Contrary to predictions, higher social support was related to higher odds of hypertension prevalence across models (OR = 1.11, 95% CI: 1.02, 1.22). In the final main effects logistic regression model, higher simpatía was related to lower odds of hypertension (OR = .83, 95% CI: .77, .90). Sex modified the link between simpatía and hypertension, with significant effects for men but not women. A 1 SD increase in simpatía was associated with 36% lower odds of hypertension in Hispanic/Latino men. The findings suggest that social support was inversely related with hypertension prevalence and that simpatía may be a protective cultural characteristic in relation to hypertension in the Hispanic/Latino population, but only in men. These results contribute to a growing discourse about the role of Hispanic/Latino cultural values in cardiovascular health.

15.
Ann N Y Acad Sci ; 1308: 245-255, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24571220

RESUMO

While there has been substantial growth in early childhood development (ECD) services in low- and middle-income countries (LMICs), there is considerable inequity in their distribution and quality. Evidence-based governance strategies are necessary, but currently they are insufficient for widespread, quality implementation. In particular, there is a limited understanding of the use of systems approaches for the analysis of ECD services as they go to scale. The aim of this paper is to present findings from four countries, using a cross-national case study approach to explore governance mechanisms required to strengthen national systems of ECD services. While different sets of governance strategies and challenges were identified in each country, overarching themes also emerged with implications for systems strengthening. Study results focus on local, mid-level and central governance, with recommendations for effective coordination and the integration of ECD services in LMICs.


Assuntos
Desenvolvimento Infantil , Intervenção Educacional Precoce/organização & administração , Criança , Pré-Escolar , Prestação Integrada de Cuidados de Saúde/organização & administração , Intervenção Médica Precoce/organização & administração , Humanos , Lactente , Recém-Nascido , Programas Nacionais de Saúde
16.
Psychol Assess ; 26(2): 384-94, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24320763

RESUMO

The Interpersonal Support Evaluation List-12 (ISEL-12; Cohen, Mermelstein, Kamarck, & Hoberman, 1985) is broadly employed as a short-form measure of the traditional ISEL, which measures functional (i.e., perceived) social support. The ISEL-12 can be scored by summing the items to create an overall social support score; three subscale scores representing appraisal, belonging, and tangible social support have also been proposed. Despite extensive use, studies of the psychometric properties of ISEL-12 scores have been limited, particularly among Hispanics/Latinos, the largest and fastest growing ethnic group in the United States. The current study investigated the reliability and structural and convergent validity of ISEL-12 scores using data from 5,313 Hispanics/Latinos who participated in the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study. Participants completed measures in English or Spanish and identified their ancestry as Dominican, Central American, Cuban, Mexican, Puerto Rican, or South American. Cronbach's alphas suggested adequate internal consistency for the total score for all languages and ancestry groups; coefficients for the subscale scores were not acceptable. Confirmatory factor analyses revealed that the one-factor and three-factor models fit the data equally well. Results from multigroup confirmatory factor analyses supported a similar one-factor structure with equivalent response patterns and variances between language groups and ancestry groups. Convergent validity analyses suggested that the total social support score related to scores of social network integration, life engagement, perceived stress, and negative affect (depression, anxiety) in the expected directions.


Assuntos
Hispânico ou Latino/psicologia , Relações Interpessoais , Apoio Social , Inquéritos e Questionários/normas , Ansiedade/psicologia , Cultura , Depressão/psicologia , Análise Fatorial , Feminino , Humanos , Idioma , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Fatores de Risco , Fatores Socioeconômicos , Estresse Psicológico/psicologia
17.
J Biol Chem ; 283(30): 20989-1001, 2008 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-18511414

RESUMO

The androgen receptor (AR) is required for prostate cancer development and contributes to tumor progression after remission in response to androgen deprivation therapy. Epidermal growth factor (EGF) increases AR transcriptional activity at low levels of androgen in the CWR-R1 prostate cancer cell line derived from the castration-recurrent CWR22 prostate cancer xenograft. Here we report that knockdown of AR decreases EGF stimulation of prostate cancer cell growth and demonstrate a mechanistic link between EGF and AR signaling. The EGF-induced increase in AR transcriptional activity is dependent on phosphorylation at mitogen-activated protein kinase consensus site Ser-515 in the AR NH(2)-terminal region and at protein kinase C consensus site Ser-578 in the AR DNA binding domain. Phosphorylation at these sites alters the nuclear-cytoplasmic shuttling of AR and AR interaction with the Ku-70/80 regulatory subunits of DNA-dependent protein kinase. Abolishing AR Ser-578 phosphorylation by introducing an S578A mutation eliminates the AR transcriptional response to EGF and increases both AR binding of Ku-70/80 and nuclear retention of AR in association with hyperphosphorylation of AR Ser-515. The results support a model in which AR transcriptional activity increases castration-recurrent prostate cancer cell growth in response to EGF by site-specific serine phosphorylation that regulates nuclear-cytoplasmic shuttling through interactions with the Ku-70/80 regulatory complex.


Assuntos
Fator de Crescimento Epidérmico/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/metabolismo , Serina/química , Animais , Linhagem Celular , Núcleo Celular/metabolismo , Chlorocebus aethiops , Dependovirus/metabolismo , Humanos , Masculino , Transplante de Neoplasias , Fosforilação , Recidiva
18.
Clin Cancer Res ; 11(5): 1704-12, 2005 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-15755991

RESUMO

PURPOSE: The androgen receptor (AR) is a ligand-dependent transcription factor that mediates gene expression and growth of normal and malignant prostate cells. In prostate tumors that recur after androgen withdrawal, the AR is highly expressed and transcriptionally active in the absence of testicular androgens. In these "androgen-independent" tumors, alternative means of AR activation have been invoked, including regulation by growth factors and their receptors in prostate cancer recurrence. EXPERIMENTAL DESIGN AND RESULTS: In this report, we show that HER receptor tyrosine kinases 1 through 4 are expressed in the CWR-R1 recurrent prostate cancer cell line; their stimulation by epidermal growth factor (EGF) and heregulin activates downstream signaling, including mitogen-activated protein kinase and phosphatidylinositol-3 kinase and Akt pathways. We show that heregulin activates HER2 and HER3 and increases androgen-dependent AR transactivation of reporter genes in CWR-R1 cells. Tyrosine phosphorylation of HER2 and HER3, AR transactivation, and cell proliferation induced by heregulin were more potently inhibited by the EGFR/HER2 dual tyrosine kinase inhibitor GW572016 (lapatinib) than the EGFR-specific inhibitor ZD1839 (gefitinib). Basal proliferation in the absence of growth factors was also inhibited by GW572016 to a greater extent than ZD1839, suggesting that low level HER2/HER3 activation perhaps by an autocrine pathway contributes to the proliferation signal. CONCLUSIONS: These data indicate that heregulin signaling through HER2 and HER3 increases AR transactivation and alters growth in a recurrent prostate cancer cell line. Therefore, inhibition of low-level HER2 signaling may be a potential novel therapeutic strategy in prostate cancer.


Assuntos
Neuregulina-1/farmacologia , Neoplasias da Próstata/patologia , Receptor ErbB-2/biossíntese , Receptor ErbB-3/biossíntese , Receptores Androgênicos/biossíntese , Genes Reporter , Genes erbB-2 , Humanos , Masculino , Fosforilação , Receptores Androgênicos/genética , Recidiva , Transdução de Sinais , Ativação Transcricional , Células Tumorais Cultivadas , Tirosina/metabolismo
19.
J Neurobiol ; 60(3): 369-80, 2004 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-15281074

RESUMO

The Lan3-14 and Laz10-1 monoclonal antibodies recognize a 400 kDa antigen that is specifically expressed by all muscle cells in leech. We show that the antigen recognized by both antibodies is a member of the filamin family of actin binding proteins. Leech filamin has two calponin homology domains and 35 filamin/ABP-repeat domains. In addition, we used the Laz10-1 antibody to characterize the development of the segmentally iterated dorsoventral flattener muscles. We demonstrate that the dorsoventral flattener muscle develops as three discrete bundles of myofibers and that CNS axons pioneering the DP nerve extend only along the middle bundle. Interestingly, the middle dorsoventral muscle anlage is associated with only non-neuronal expression of the L1-family cell adhesion molecule Tractin. This expression is transient and occurs at the precise developmental stages when DP nerve formation takes place. Based on these findings we propose that the middle dorsoventral muscle anlagen provides a substrate for early axonal outgrowth and nerve formation and that this function may be associated with differential expression of distinct cell adhesion molecules.


Assuntos
Moléculas de Adesão Celular Neuronais/metabolismo , Sistema Nervoso Central/metabolismo , Proteínas Contráteis/metabolismo , Proteínas dos Microfilamentos/metabolismo , Músculos/metabolismo , Animais , Biomarcadores/análise , Northern Blotting/métodos , Western Blotting/métodos , Moléculas de Adesão Celular Neuronais/genética , Sistema Nervoso Central/embriologia , Sistema Nervoso Central/fisiologia , Clonagem Molecular/métodos , Proteínas Contráteis/genética , Embrião não Mamífero , Filaminas , Humanos , Imuno-Histoquímica/métodos , Sanguessugas , Proteínas dos Microfilamentos/genética , Desenvolvimento Muscular/fisiologia , Músculos/embriologia , Músculos/fisiologia , Filogenia , Estrutura Terciária de Proteína/fisiologia , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Análise de Sequência/métodos , Tubulina (Proteína)/metabolismo
20.
J Biol Chem ; 279(8): 7119-30, 2004 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-14662770

RESUMO

Growth of normal and neoplastic prostate is mediated by the androgen receptor (AR), a ligand-dependent transcription factor activated by high affinity androgen binding. The AR is highly expressed in recurrent prostate cancer cells that proliferate despite reduced circulating androgen. In this report, we show that epidermal growth factor (EGF) increases androgen-dependent AR transactivation in the recurrent prostate cancer cell line CWR-R1 through a mechanism that involves a post-transcriptional increase in the p160 coactivator transcriptional intermediary factor 2/glucocorticoid receptor interacting protein 1 (TIF2/GRIP1). Site-specific mutagenesis and selective MAPK inhibitors linked the EGF-induced increase in AR transactivation to phosphorylation of TIF2/GRIP1. EGF signaling increased the coimmunoprecipitation of TIF2 and AR. AR transactivation and its stimulation by EGF were reduced by small interfering RNA inhibition of TIF2/GRIP1 expression. The data indicate that EGF signaling through MAPK increases TIF2/GRIP1 coactivation of AR transactivation in recurrent prostate cancer.


Assuntos
Fator de Crescimento Epidérmico/metabolismo , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/metabolismo , Animais , Northern Blotting , Células COS , Divisão Celular , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Genes Reporter , Humanos , Immunoblotting , Ligantes , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Nus , Mutagênese Sítio-Dirigida , Mutação , Transplante de Neoplasias , Coativador 2 de Receptor Nuclear , Plasmídeos/metabolismo , Testes de Precipitina , Ligação Proteica , Interferência de RNA , Transdução de Sinais , Fatores de Transcrição/metabolismo , Transcrição Gênica , Ativação Transcricional , Técnicas do Sistema de Duplo-Híbrido
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