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1.
Palliat Med ; 38(6): 679-688, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38813757

RESUMEN

BACKGROUND: Caring for parents continuing pregnancy after learning about a severe life-limiting condition in their unborn is challenging. Most existing studies focus on affected families, whereas research on the subjective experience of care professionals is scarce. AIM: We aimed to (1) explore experiences and needs of involved care professionals, (2) obtain information about existing care structures, and (3) identify requirements for a structured perinatal palliative care program. DESIGN: Grounded Theory study using theoretical sampling. Data was collected by semi-structured interviews and analyzed following the principles of grounded theory coding and situational analysis. SETTING: A total of 18 professionals from 12 different services in Munich and surroundings participated in the study: 8 physicians, 3 midwives, 2 nurses, 1 each pregnancy counselor, grief counselor, chaplain, clinical psychologist, and undertaker. RESULTS: Several organizations provide support for affected parents, but inter-institutional communication is scarce. Due to the lack of a dedicated perinatal palliative care program, professionals make immense and partly unpaid efforts to support concerned parents. Providers experience "collateral beauty" in their work despite all the suffering and grief. This includes the development of a humble attitude and feelings of gratitude toward life, the feeling of having a meaningful task and professional as well as personal growth. Requirements for a structured perinatal palliative care program include: fostering peer support, ensuring regular supervision, and enhancing interdisciplinary exchange. CONCLUSIONS: Perinatal palliative care demands a high level of personal engagement but is experienced as highly rewarding by care professionals.


Asunto(s)
Teoría Fundamentada , Cuidados Paliativos , Padres , Diagnóstico Prenatal , Humanos , Femenino , Embarazo , Cuidados Paliativos/psicología , Padres/psicología , Adulto , Diagnóstico Prenatal/psicología , Investigación Cualitativa , Masculino , Personal de Salud/psicología , Actitud del Personal de Salud , Persona de Mediana Edad , Pesar
2.
Palliat Med ; 34(3): 300-308, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31985331

RESUMEN

BACKGROUND: Although international guidelines recommend discussions about goals of care and treatment options for children with severe and life-limiting conditions, there are still few structured models of paediatric advance care planning. AIM: The study aimed at identifying key components of paediatric advance care planning through direct discussions with all involved parties. DESIGN: The study had a qualitative design with a participatory approach. Participants constituted an advisory board and took part in two transdisciplinary workshops. Data were collected in discussion and dialogue groups and analysed using content analysis. SETTING/PARTICIPANTS: We included bereaved parents, health care providers and stakeholders of care networks. RESULTS: Key elements were discussions, documentation, implementation, timing and participation of children and adolescents. Parents engage in discussions with facilitators and persons of trust to reach a decision. Documentation constitutes the focus of professionals, who endorse brief recommendations for procedures in case of emergencies, supplemented by larger advance directives. Implementation hindrances include emotional barriers of stakeholders, disagreements between parents and professionals and difficulties with emergency services. Discussion timing should take into account parental readiness. The intervention should be repeated at regular intervals, considering emerging needs and increasing awareness of families over time. Involving children and adolescents in advance care planning remains a challenge. CONCLUSION: A paediatric advance care planning intervention should take into account potential pitfalls and barriers including issues related to timing, potential conflicts between parents and professionals, ambiguity towards written advance directives, the role of non-medical carers for paediatric advance care planning implementation, the need to involve the child and the necessity of an iterative process.


Asunto(s)
Planificación Anticipada de Atención , Personal de Salud/psicología , Padres/psicología , Pediatría , Participación de los Interesados/psicología , Humanos , Investigación Cualitativa
3.
Nucleic Acids Res ; 46(16): 8197-8215, 2018 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-29986055

RESUMEN

A fundamental as yet incompletely understood feature of Notch signal transduction is a transcriptional shift from repression to activation that depends on chromatin regulation mediated by transcription factor RBP-J and associated cofactors. Incorporation of histone variants alter the functional properties of chromatin and are implicated in the regulation of gene expression. Here, we show that depletion of histone variant H2A.Z leads to upregulation of canonical Notch target genes and that the H2A.Z-chaperone TRRAP/p400/Tip60 complex physically associates with RBP-J at Notch-dependent enhancers. When targeted to RBP-J-bound enhancers, the acetyltransferase Tip60 acetylates H2A.Z and upregulates Notch target gene expression. Importantly, the Drosophila homologs of Tip60, p400 and H2A.Z modulate Notch signaling response and growth in vivo. Together, our data reveal that loading and acetylation of H2A.Z are required to assure tight control of canonical Notch activation.


Asunto(s)
Regulación de la Expresión Génica , Histonas/genética , Receptores Notch/genética , Transducción de Señal/genética , Acetilación , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adenosina Trifosfatasas/genética , Adenosina Trifosfatasas/metabolismo , Animales , Línea Celular , Línea Celular Tumoral , Células HEK293 , Células HeLa , Histonas/metabolismo , Humanos , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/genética , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/metabolismo , Lisina Acetiltransferasa 5/genética , Lisina Acetiltransferasa 5/metabolismo , Ratones Noqueados , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Receptores Notch/metabolismo
4.
Palliat Med ; 33(6): 704-711, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30843464

RESUMEN

BACKGROUND: A prenatal diagnosis of a life-limiting disease raises complex ethical, emotional, and medical issues. Studies suggest that 40%-85% of parents decide to continue the pregnancy if given the option of Perinatal Palliative Care. However, structured Perinatal Palliative Care programs are missing in many European countries. In Germany, parents have the right to free psychosocial support from pregnancy counseling services after the prenatal diagnosis of a life-limiting disease. AIM: We aimed to investigate whether German professional pregnancy counselors perceive the need for structured Perinatal Palliative Care and if so, how it should be conceived. DESIGN: This is a qualitative interview study with purposeful sampling. The interviews were analyzed with the coding method of Saldaña. SETTING/PARTICIPANTS: A total of 10 professionals from three different pregnancy counseling services participated in the study. RESULTS: The main topics raised by the professionals were as follows: (1) counseling and parental support during the decision-making process; (2) fragmented or missing support infrastructure for parents; and (3) challenges, hesitations, and barriers, particularly from the different stakeholders, regarding a Perinatal Palliative Care framework. They highlighted the importance of the integration of Perinatal Palliative Care in existing structures, a multi-professional approach, continuous coordination of care and education for all healthcare providers involved. CONCLUSION: A structured Perinatal Palliative Care program is considered as necessary by the pregnancy counselors. Future research should focus on (1) needs reported by concerned parents; (2) attitude and role of all healthcare providers involved; (3) strategies to include stakeholders in the development of Perinatal Palliative Care networks; and (4) outcome parameters for evaluation of Perinatal Palliative Care frameworks.


Asunto(s)
Actitud Frente a la Muerte , Consejo/normas , Pesar , Cuidados Paliativos/normas , Padres/psicología , Atención Perinatal/normas , Guías de Práctica Clínica como Asunto , Diagnóstico Prenatal/psicología , Adulto , Toma de Decisiones , Femenino , Grupos Focales , Alemania , Humanos , Masculino , Persona de Mediana Edad , Cuidados Paliativos/psicología , Embarazo , Relaciones Profesional-Familia , Investigación Cualitativa
5.
Nucleic Acids Res ; 44(10): 4703-20, 2016 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-26912830

RESUMEN

The transcriptional shift from repression to activation of target genes is crucial for the fidelity of Notch responses through incompletely understood mechanisms that likely involve chromatin-based control. To activate silenced genes, repressive chromatin marks are removed and active marks must be acquired. Histone H3 lysine-4 (H3K4) demethylases are key chromatin modifiers that establish the repressive chromatin state at Notch target genes. However, the counteracting histone methyltransferase required for the active chromatin state remained elusive. Here, we show that the RBP-J interacting factor SHARP is not only able to interact with the NCoR corepressor complex, but also with the H3K4 methyltransferase KMT2D coactivator complex. KMT2D and NCoR compete for the C-terminal SPOC-domain of SHARP. We reveal that the SPOC-domain exclusively binds to phosphorylated NCoR. The balance between NCoR and KMT2D binding is shifted upon mutating the phosphorylation sites of NCoR or upon inhibition of the NCoR kinase CK2ß. Furthermore, we show that the homologs of SHARP and KMT2D in Drosophila also physically interact and control Notch-mediated functions in vivo Together, our findings reveal how signaling can fine-tune a committed chromatin state by phosphorylation of a pivotal chromatin-modifier.


Asunto(s)
Cromatina/metabolismo , Proteínas Co-Represoras/metabolismo , Regulación de la Expresión Génica , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Proteínas Nucleares/metabolismo , Receptores Notch/metabolismo , Transcripción Genética , Animales , Quinasa de la Caseína II/metabolismo , Línea Celular , Línea Celular Tumoral , Proteínas de Unión al ADN , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Código de Histonas , N-Metiltransferasa de Histona-Lisina , Proteínas de Homeodominio/química , Proteínas de Homeodominio/metabolismo , Humanos , Ratones , Proteínas Nucleares/química , Fosforilación , Dominios y Motivos de Interacción de Proteínas , Proteínas de Unión al ARN , Xenopus laevis
6.
Children (Basel) ; 9(10)2022 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-36291491

RESUMEN

In Germany, research on experiences and care pathways of parents continuing pregnancy after a life-limiting fetal diagnosis is scarce. There are several recommendations but few structured programs. We aimed to explore experiences and needs of parents, reconstruct their care pathways, and identify requirements for a perinatal palliative care program. We conducted semi-structured interviews with 11 mothers and 9 fathers and analyzed data using the Saldaña's Coding Method. Codes were organized in templates to reconstruct care pathways. Pathways started with a suspicious finding prompting a referral to prenatal diagnostics. Parents experienced severe emotional distress during prenatal diagnostics due to scarce information, insensitiveness, and a perceived pressure towards abortion. As a result, they overlooked referrals to psychosocial counseling, generating a care gap. Most parents reached the decision to continue pregnancy without professional support. They then chose a trusted midwife or gynecologist as main caregiver during pregnancy. There were no regular referrals to palliative care, which mainly became relevant when the child survived. Our data indicate that a perinatal palliative care program requires early and comprehensive information, sensitivity, and a non-directive approach. Already existing support services need to be identified and connected through structured pathways, with a particular focus on midwives.

7.
J Palliat Med ; 25(4): 562-569, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34807732

RESUMEN

Context: Advance care discussions (ACD) between health care professionals (HCPs) and parents of children with a life-limiting disease are a core element of successful pediatric advance care planning (pACP). Yet, they are perceived as a challenging situation for all participants. Objectives: Our goal was to investigate the first step of ACD and identify its challenges and helpful communication strategies to develop a conversation guide for initiating the pACP process and structure the conversational opening. Methods: We performed a participant observation of 11 initial ACD and 24 interviews with 13 HCPs and 20 parents of 11 children cared for by 3 different palliative care teams in southern Germany. Qualitative data collection was supplemented by a questionnaire. Content analysis and conversation analysis were used for evaluation. Results: Parents and HCPs start the process with different expectations, which can lead to misunderstandings and confusion. HCPs gain parental cooperation when they express the purpose of the meeting clearly and early, provide structure and guidance, and give parents time to talk about their experiences and feelings. Addressing dying and death is hard for both sides and requires a sensitive approach. Conclusions: Initiating ACD is extremely challenging for all participants. HCPs and parents should clarify expectations and aims at the beginning of the conversation. Future research should focus on how HCPs can be trained for this task and how the right timing for introducing ACD to families can be identified. Clinical Trial Registration number 049-12.


Asunto(s)
Planificación Anticipada de Atención , Cuidados Paliativos , Niño , Humanos , Padres , Investigación Cualitativa , Encuestas y Cuestionarios
8.
J Pain Symptom Manage ; 63(2): 189-198, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34597758

RESUMEN

CONTEXT: Decision-making in pediatric palliative care concerns mainly children without decision-making capacity. It has to balance the child's best interests, parental responsibility and the impact on the family system. OBJECTIVES: Advance care planning (ACP) supports decision making about future medical care. A consistent pediatric approach is still missing. This study aimed at developing a pediatric ACP program (pedACP) meeting specific needs of children, parents and professionals. METHODS: Bereaved parents of children with life-limiting conditions and professionals involved in pedACP participated. Employing the technique of constellation analysis, they collaboratively assigned content, actors, tools and warning notes about pedACP along a timeline. The researchers analyzed, systematized and translated these results into a pedACP program draft, which was revised by the participants. RESULTS: The participants' overall focus was on the children's quality of life and an individualized interdisciplinary communication process along the disease trajectory. The program was conceptualized in modular design with fixed modules at the beginning (to build a trustful relationship and frame the process) and at the end (to summarize results and prepare implementation). The main discussions are structured in flexible modules (About the child, Emergencies, Disease-specific scenarios and End of life care). General themes cover timing, communication, engaging children and structural issues. The participants appreciated the program's comprehensiveness and flexibility. CONCLUSION: Parents and professionals combined their perspectives on reflecting goals of care and the complexity of pedACP. They perceived the resulting modular program as suitable for meeting the individual needs of patients, families and professional stakeholders.


Asunto(s)
Planificación Anticipada de Atención , Cuidado Terminal , Niño , Humanos , Cuidados Paliativos , Padres , Investigación Cualitativa , Calidad de Vida
9.
Artículo en Inglés | MEDLINE | ID: mdl-33430189

RESUMEN

Targeting dementia prevention, first trials addressing multiple modifiable risk factors showed promising results in at-risk populations. In Germany, AgeWell.de is the first large-scale initiative investigating the effectiveness of a multi-component lifestyle intervention against cognitive decline. We aimed to investigate the recruitment process and baseline characteristics of the AgeWell.de participants to gain an understanding of the at-risk population and who engages in the intervention. General practitioners across five study sites recruited participants (aged 60-77 years, Cardiovascular Risk Factors, Aging, and Incidence of Dementia/CAIDE dementia risk score ≥ 9). Structured face-to-face interviews were conducted with eligible participants, including neuropsychological assessments. We analyzed group differences between (1) eligible vs. non-eligible participants, (2) participants vs. non-participants, and (3) between intervention groups. Of 1176 eligible participants, 146 (12.5%) dropped out before baseline; the study population was thus 1030 individuals. Non-participants did not differ from participants in key sociodemographic factors and dementia risk. Study participants were M = 69.0 (SD = 4.9) years old, and 52.1% were women. The average Montreal Cognitive Assessment/MoCA score was 24.5 (SD = 3.1), indicating a rather mildly cognitively impaired study population; however, 39.4% scored ≥ 26, thus being cognitively unimpaired. The bandwidth of cognitive states bears the interesting potential for differential trial outcome analyses. However, trial conduction is impacted by the COVID-19 pandemic, requiring adjustments to the study protocol with yet unclear methodological consequences.


Asunto(s)
Disfunción Cognitiva/prevención & control , Estilo de Vida , Selección de Paciente , Anciano , Femenino , Alemania , Envejecimiento Saludable , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas
10.
Mol Microbiol ; 74(6): 1412-26, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19889088

RESUMEN

Stress-induced degradation of the Bacillus subtilis anti-sigma factor RsiW results in the induction of genes controlled by the extracytoplasmic function sigma factor sigma(W). RsiW is cleaved by the mechanism of regulated intramembrane proteolysis at site-1 and -2 by PrsW and RasP respectively, and is then further degraded by cytoplasmic Clp peptidases. In a reconstituted Escherichia coli system, PrsW removes 40 amino acids from RsiW by cleaving between Ala168 and Ser169 of the extracytoplasmic domain, thereby generating RsiW-S1. Further trimming of RsiW-S1's C-terminus by the periplasmic tail-specific protease Tsp is crucial for subsequent RasP-catalysed clipping. In B. subtilis, mutation of RsiW at Ala168 severely impairs site-1 processing. RsiW-S1 is undetectable in wild-type B. subtilis and knockout strains lacking various extracytoplasmic proteases. While it can be stabilized by C-terminal tagging, even this fusion protein is still attacked. Thus, several peptidases seem to be involved in trimming of RsiW downstream of PrsW and upstream of RasP in B. subtilis. Overall, the RsiW degradation pathway can be subdivided into two modules each consisting of a site-specific peptidase that prepares RsiW for further degradation by downstream proteases.


Asunto(s)
Bacillus subtilis/fisiología , Proteínas Bacterianas/metabolismo , Membrana Celular/metabolismo , Regulación Bacteriana de la Expresión Génica , Péptido Hidrolasas/metabolismo , Estrés Fisiológico , Secuencia de Aminoácidos , Bacillus subtilis/genética , Proteínas Bacterianas/genética , Secuencia de Bases , Sitios de Unión , Escherichia coli/genética , Modelos Biológicos , Datos de Secuencia Molecular , Mutación Missense
11.
Cell Rep ; 26(4): 845-854.e6, 2019 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-30673607

RESUMEN

Notch is a conserved signaling pathway that is essential for metazoan development and homeostasis; dysregulated signaling underlies the pathophysiology of numerous human diseases. Receptor-ligand interactions result in gene expression changes, which are regulated by the transcription factor RBPJ. RBPJ forms a complex with the intracellular domain of the Notch receptor and the coactivator Mastermind to activate transcription, but it can also function as a repressor by interacting with corepressor proteins. Here, we determine the structure of RBPJ bound to the corepressor SHARP and DNA, revealing its mode of binding to RBPJ. We tested structure-based mutants in biophysical and biochemical-cellular assays to characterize the role of RBPJ as a repressor, clearly demonstrating that RBPJ mutants deficient for SHARP binding are incapable of repressing transcription of genes responsive to Notch signaling in cells. Altogether, our structure-function studies provide significant insights into the repressor function of RBPJ.


Asunto(s)
Proteínas de Unión al ADN , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas , Complejos Multiproteicos , Proteínas de Unión al ARN , Transducción de Señal , Transcripción Genética , Animales , Sitios de Unión , ADN/química , ADN/genética , ADN/metabolismo , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Células HEK293 , Células HeLa , Humanos , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/química , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/genética , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/metabolismo , Ratones , Complejos Multiproteicos/química , Complejos Multiproteicos/genética , Complejos Multiproteicos/metabolismo , Estructura Cuaternaria de Proteína , Proteínas de Unión al ARN/química , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Receptores Notch/química , Receptores Notch/genética , Receptores Notch/metabolismo
12.
J Biotechnol ; 263: 11-20, 2017 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-29017849

RESUMEN

Human-derived CAP-T cell line has been demonstrated to be a powerful platform for high-titer production of HIV virus-like particles (VLPs) by PEI-mediated transient transfection. Scale-up of transfection processes is key to ensure the necessary quantities for pre-clinical and clinical testing. One of the major operational challenges of large-scale transient transfection is the medium replacement step that is often required before transfection. In this work, CAP-T cells were cultured in 1L bioreactor with addition of sodium bicarbonate and surface aeration, which were observed to improve cell state for transfection. Remarkably, the medium replacement step was avoided by culturing the cells in a combination of media (FreeStyleF17+1% of PEM) compatible with cell growth and PEI-mediated transient transfection. In the conditions developed in this work, 0.5×106cells/mL were seeded in 1L bioreactor. Two days later, ∼2×106cells/mL were transfected without medium exchange, using 0.5pg of DNA/cell and 3pg of PEI/cell. Transfection efficiency and VLP production comparable to shake flasks were obtained with a production of 4×1010VLPs/mL. This novel strategy significantly simplifies large-scale transient transfection, while suitable cell growth, transfection efficiency, and high quality VLP production are achieved.


Asunto(s)
Reactores Biológicos , VIH-1/metabolismo , Transfección/métodos , Virión/metabolismo , Cultivo de Virus/métodos , Línea Celular , Supervivencia Celular , Medios de Cultivo , VIH-1/genética , Humanos , Virión/aislamiento & purificación
13.
Sci Signal ; 8(369): ra30, 2015 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-25805888

RESUMEN

Physiologically, Notch signal transduction plays a pivotal role in differentiation; pathologically, Notch signaling contributes to the development of cancer. Transcriptional activation of Notch target genes involves cleavage of the Notch receptor in response to ligand binding, production of the Notch intracellular domain (NICD), and NICD migration into the nucleus and assembly of a coactivator complex. Posttranslational modifications of the NICD are important for its transcriptional activity and protein turnover. Deregulation of Notch signaling and stabilizing mutations of Notch1 have been linked to leukemia development. We found that the methyltransferase CARM1 (coactivator-associated arginine methyltransferase 1; also known as PRMT4) methylated NICD at five conserved arginine residues within the C-terminal transactivation domain. CARM1 physically and functionally interacted with the NICD-coactivator complex and was found at gene enhancers in a Notch-dependent manner. Although a methylation-defective NICD mutant was biochemically more stable, this mutant was biologically less active as measured with Notch assays in embryos of Xenopus laevis and Danio rerio. Mathematical modeling indicated that full but short and transient Notch signaling required methylation of NICD.


Asunto(s)
Arginina/metabolismo , Proteína-Arginina N-Metiltransferasas/metabolismo , Receptor Notch1/metabolismo , Transducción de Señal , Secuencia de Aminoácidos , Animales , Arginina/genética , Sitios de Unión/genética , Western Blotting , Línea Celular Tumoral , Núcleo Celular/genética , Núcleo Celular/metabolismo , Células Cultivadas , Perfilación de la Expresión Génica , Células HEK293 , Células HeLa , Humanos , Metilación , Ratones , Datos de Secuencia Molecular , Mutación , Proteína-Arginina N-Metiltransferasas/genética , Interferencia de ARN , Receptor Notch1/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Aminoácido , Activación Transcripcional , Xenopus laevis/embriología , Xenopus laevis/genética , Xenopus laevis/metabolismo , Pez Cebra/genética , Pez Cebra/metabolismo
14.
Science ; 336(6088): 1549-54, 2012 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-22723415

RESUMEN

Telomerase activity controls telomere length and plays a pivotal role in stem cells, aging, and cancer. Here, we report a molecular link between Wnt/ß-catenin signaling and the expression of the telomerase subunit Tert. ß-Catenin-deficient mouse embryonic stem (ES) cells have short telomeres; conversely, ES cell expressing an activated form of ß-catenin (ß-cat(ΔEx3/+)) have long telomeres. We show that ß-catenin regulates Tert expression through the interaction with Klf4, a core component of the pluripotency transcriptional network. ß-Catenin binds to the Tert promoter in a mouse intestinal tumor model and in human carcinoma cells. We uncover a previously unknown link between the stem cell and oncogenic potential whereby ß-catenin regulates Tert expression, and thereby telomere length, which could be critical in human regenerative therapy and cancer.


Asunto(s)
Células Madre Adultas/metabolismo , Células Madre Embrionarias/metabolismo , Neoplasias/metabolismo , Telomerasa/genética , Vía de Señalización Wnt , beta Catenina/metabolismo , Animales , Línea Celular Tumoral , Células HEK293 , Humanos , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/metabolismo , Ratones , Neoplasias/genética , Regiones Promotoras Genéticas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Telomerasa/metabolismo , Telómero/metabolismo , Telómero/ultraestructura , Homeostasis del Telómero , Sitio de Iniciación de la Transcripción , Proteínas Wnt/metabolismo , beta Catenina/genética
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