Search results for "Development"
showing 10 items of 26949 documents
Dynamiques de développement et inégalités régionales en Chine
2009
Le rapide développement économique de la Chine a généré des inégalités socio-spatiales croissantes, qui se marquent par un décalage croissant entre provinces littorales et intérieures, et entre villes et campagnes. À partir de l’examen des données statistiques officielles chinoises, on peut clairement repérer une aggravation des déséquilibres internes de la Chine, qui sont des facteurs potentiels de déstabilisation sociale, en particulier dans le cas des paysans venus tenter leur chance dans les grandes aires urbaines littorales, ou chassés de leurs terres par l’expansion périmétropolitaine. Cela entraîne aujourd’hui une politique différenciée d’aménagement du territoire chinois visant à co…
Epigenetic siRNA and Chemical Screens Identify SETD8 Inhibition as a Therapeutic Strategy for p53 Activation in High-Risk Neuroblastoma
2017
Given the paucity of druggable mutations in high-risk neuroblastoma (NB), we undertook chromatin-focused small interfering RNA and chemical screens to uncover epigenetic regulators critical for the differentiation block in high-risk NB. High-content Opera imaging identified 53 genes whose loss of expression led to a decrease in NB cell proliferation and 16 also induced differentiation. From these, the secondary chemical screen identified SETD8, the H4K20me1 methyltransferase, as a druggable NB target. Functional studies revealed that SETD8 ablation rescued the pro-apoptotic and cell-cycle arrest functions of p53 by decreasing p53K382me1, leading to activation of the p53 canonical pathway. I…
Genetic profile and immunohistochemical study of clear cell renal carcinoma: Pathological-anatomical correlation and prognosis.
2021
Abstract Introduction Renal cell carcinoma (RCC) accounts for 2–3% of all tumors being the most frequent solid lesion in the kidney. Objective To determine what genetic alterations and immunohistochemical (IHC) of clear cell renal carcinoma (ccRCC) are associated with prognosis and tumor aggressiveness. Patients and Methods Experimental analytical study with 57 patients who underwent radical and partial nephrectomy between 2005 and 2011, all with diagnosis of ccRCC and minimum post-operative follow-up of 36 months. The pathological study included IHC determination of biomarkers associated (CAIX, CAM 5.2, CD10, c-erbB-2, EGFR, HIF-1a, Ki67, MDM2, PAX-2 y 8, p53, survivin and VEGFR 1 and 2). …
Expression of p63, p53 and ki-67 in patients with cervical intraepithelial neoplasia
2017
Objective: Cervical intraepithelial neoplasia (CIN) is a dysplastic process in cervical squamous epithelium and carries a risk of progression to cervical cancer. The aim of this study was to compare expression of three biomarkers named p53, p63 and Ki-67 in patients with various grades of cervical intraepithelial neoplasia and in a control group. Material and Method: 58 patients were enrolled in the study. Each patient underwent a colposcopy-guided biopsy of the cervix. Immunostaining for markers (p53, p63 and Ki-67) was performed on tissue samples of normal cases (n=10), CIN I (n=20), CIN II (n=14), and CIN III (n=14). Results: Our study showed a significant increase of the expression of t…
Endoderm development requires centrioles to restrain p53-mediated apoptosis in the absence of ERK activity
2021
Centrioles comprise the heart of centrosomes, microtubule-organizing centers. To study the function of centrioles in lung and gut development, we genetically disrupted centrioles throughout the mouse endoderm. Surprisingly, removing centrioles from the endoderm did not disrupt intestinal growth or development but blocked lung branching. In the lung, acentriolar SOX2-expressing airway epithelial cells apoptosed. Loss of centrioles activated p53, and removing p53 restored survival of SOX2-expressing cells, lung branching, and mouse viability. To investigate how endodermal p53 activation specifically killed acentriolar SOX2-expressing cells, we assessed ERK, a prosurvival cue. ERK was active t…
Plausible Role of Estrogens in Pathogenesis, Progression and Therapy of Lung Cancer
2021
Malignant neoplasms are among the most common diseases and are responsible for the majority of deaths in the developed world. In contrast to men, available data show a clear upward trend in the incidence of lung cancer in women, making it almost as prevalent as breast cancer. Women might be more susceptible to the carcinogenic effect of tobacco smoke than men. Furthermore, available data indicate a much more frequent mutation of the tumor suppressor gene-p53 in non-small cell lung cancer (NSCLC) female patients compared to males. Another important factor, however, might lie in the female sex hormones, whose mitogenic or carcinogenic effect is well known. Epidemiologic data show a correlatio…
Molecular mechanisms of MYCN-dependent apoptosis and the MDM2-p53 pathway: an Achille’s heel to be exploited for the therapy of MYCN amplified neurob…
2012
The p53 oncosuppressor is very seldom mutated in neuroblastoma, but several mecha- nisms cooperate to its functional inactivation in this tumor. Increased MDM2 levels, due to genetic amplification or constitutive inhibition of p14ARF, significantly contribute to this event highlighting p53 reactivation as an attractive perspective for neuroblastoma treat- ment. In addition to its role in tumorigenesis, MYCN sensitizes untransformed and cancer cells to apoptosis. This is associated to a fine modulation of the MDM2-p53 pathway Indeed MYCN induces p53 and MDM2 transcription, and, by evoking a DNA damage response (DDR), it stabilizes p53 and its proapoptotic kinase Homeodomain Interacting Prote…
Factors Enabling and Hindering Value Co-Creation in Continuous Service Development: A Systematic Literature Review
2022
This paper presents a systematic literature review (SLR) investigating the factors that enable and hinder value co-creation in organizations’ continuous service development processes. Employing the lens of service-dominant (S-D) logic, we classify the identified factors into three interrelated dimensions: institutions, resources, and service exchange. Our systematic findings may inform organizations’ efforts to support the emergence of positive rather than negative value outcomes when implementing continuous practices in their service development. In addition, we outline avenues for further research in this emerging topic area. peerReviewed
Achieving agreement on service needs in child protection : Comparing children’s, mothers’ and practitioners’ views over time and between approaches
2022
Purpose While studies on service users’ participation and their perceptions on the quality of services exist, agreement between family members’ and practitioners’ assessments of the family’s situation has received less interest. The purpose of this paper is to investigate agreement and its effect on outcomes by comparing the viewpoints of three groups of informants (children, mothers and practitioners) in the context of statutory child protection in two study groups – one applying a systemic approach (SPM) and a service-as-usual control group (SAU). Design/methodology/approach A quasi-experimental repeated-measures study design was applied. Outcome data comprised 112 cases (SPM cases n = 5…
Attributions and paradoxes of agency in socially sustainable development : perspectives from small-scale NGOs in Jinja, Uganda
2014
During the past decades, sustainable development has become an important phenomenon in the global development discourse. The concept has been widely used by both large international bodies such as the United Nations as well as small grassroots organization. In the beginning, the interest was mainly in questions of environmental and ecological aspects of the concept but especially since the introduction of the Human Development Approach the importance of social and cultural aspects of sustainable development became more important. In the discussions on Human Development and sustainable development, the people are in the center of the discussion. Both concepts emphasize the importance of agen…