Adaptación transcultural al español chileno de las escalas CAP-II y SIR en formato online para padres de niños(as) con audífonos o implantes cocleares / Chilean spanish transcultural adaptation of CAP-II and SIR scales in an online format for parents of children with hearing aids or cochlear implants

La adquisición de lengua oral representa un desafío para niñas/os sordas/os o con pérdida auditiva (NSPA) que utilizan audífonos o implante coclear (CI). Tomar decisiones a tiempo durante el tratamiento con dispositivos es esencial y requiere de evaluaciones adecuadas. Dos instrumentos usados en la toma de decisiones son las escalas "Categories of Auditory Performance Index II" (CAP-II) y "Speech Intelligibility Rating Scale" (SIR). Estas escalas han mostrado ser útiles para la evaluación continua del desarrollo de habilidades auditivas y de la lengua oral en variados idiomas, pero estas no están disponibles para el español chileno. El objetivo de este estudio es crear traducciones en español chileno de las escalas CAP-II y SIR, las que puedan ser usadas como auto-reporte online por padres y cuidadores con el fin de asistir a profesionales en el monitoreo del progreso de niños/as NSPA, considerando las restricciones impuestas por el COVID-19. El método usado en el proceso comienza con la traducción de una propuesta de auto-reporte de las versiones originales en inglés de las escalas CAP-II y SIR. Finalmente, las versiones en español chileno fueron testeadas en 107 padres-cuidadores de niñas/os NSPA con CI. Los resultados sugieren que estos instrumentos serían adecuados para su uso en el contexto chileno.

Spoken language acquisition is challenging for very young deaf or hard-of-hearing children (DHH) who wear hearing aids or cochlear implants (CI). Timely decision-making for treatment is essential for these children and requires suitable assessments. Two such assessments are the Categories of Auditory Performance Index II (CAP-II) and the Speech Intelligibility Rating Scale (SIR). These have been shown to be helpful for the ongoing evaluation of developing speech perception and spoken language skills in various languages, but they are not available in Chilean Spanish. This study aimed to create a Chilean Spanish translation of the CAP-II and SIR, appropriate for online self-administration by parents-caregivers in Chile, to assist professionals in monitoring DHH children's progress, considering the COVID-19 restrictions. The methods used in the process started with translating a self-report proposal from the original English versions of the CAP-II and SIR scales. Finally, the Chilean Spanish versions were tested in 107 Chilean parents-caregivers of DHH children with CIs. The results suggest these instruments are suitable for use in a Chilean context.

Co-regulated gene expression by oestrogen receptor α and liver receptor homolog-1 is a feature of the oestrogen response in breast cancer cells.

Oestrogen receptor α (ERα) is a nuclear receptor that is the driving transcription factor expressed in the majority of breast cancers. Recent studies have demonstrated that the liver receptor homolog-1 (LRH-1), another nuclear receptor, regulates breast cancer cell proliferation and promotes motility and invasion. To determine the mechanisms of LRH-1 action in breast cancer, we performed gene expression microarray analysis following RNA interference for LRH-1. Interestingly, gene ontology (GO) category enrichment analysis of LRH-1-regulated genes identified oestrogen-responsive genes as the most highly enriched GO categories. Remarkably, chromatin immunoprecipitation coupled to massively parallel sequencing (ChIP-seq) to identify genomic targets of LRH-1 showed LRH-1 binding at many ERα binding sites. Analysis of select binding sites confirmed regulation of ERα-regulated genes by LRH-1 through binding to oestrogen response elements, as exemplified by the TFF1/pS2 gene. Finally, LRH-1 overexpression stimulated ERα recruitment, while LRH-1 knockdown reduced ERα recruitment to ERα binding sites. Taken together, our findings establish a key role for LRH-1 in the regulation of ERα target genes in breast cancer cells and identify a mechanism in which co-operative binding of LRH-1 and ERα at oestrogen response elements controls the expression of oestrogen-responsive genes.

Discovery of a new class of liver receptor homolog-1 (LRH-1) antagonists: virtual screening, synthesis and biological evaluation.

Targeting LRH-1: Virtual screening and molecular modeling were used to identify novel antagonists of liver receptor homolog-1 (LRH-1), an emerging therapeutic target for breast cancer. Hit compounds were synthesized and biologically assayed, and the preliminary results suggest that raloxifene-based analogues, substituted at the position C-7 of the benzothiophene ring, might generate an inactive protein conformation through binding and thus antagonize this nuclear receptor.

Transient over-expression of estrogen receptor-α in breast cancer cells promotes cell survival and estrogen-independent growth.

Estrogen receptor-α (ERα) positive breast cancer frequently responds to inhibitors of ERα activity, such as tamoxifen, and/or to aromatase inhibitors that block estrogen biosynthesis. However, many patients become resistant to these agents through mechanisms that remain unclear. Previous studies have shown that expression of ERα in ERα-negative breast cancer cell lines frequently inhibits their growth. In order to determine the consequence of ERα over-expression in ERα-positive breast cancer cells, we over-expressed ERα in the MCF-7 breast cancer cell line using adenovirus gene transduction. ERα over-expression led to ligand-independent expression of the estrogen-regulated genes pS2 and PR and growth in the absence of estrogen. Interestingly, prolonged culturing of these cells in estrogen-free conditions led to the outgrowth of cells capable of growth in cultures from ERα transduced, but not in control cultures. From these cultures a line, MLET5, was established which remained ERα-positive, but grew in an estrogen-independent manner. Moreover, MLET5 cells were inhibited by anti-estrogens showing that ERα remains important for their growth. Gene expression microarray analysis comparing MCF-7 cells with MLET5 highlighted apoptosis as a major functional grouping that is altered in MLET5 cells, such that cell survival would be favoured. This conclusion was further substantiated by the demonstration that MLET5 show resistance to etoposide-induced apoptosis. As the gene expression microarray analysis also shows that the apoptosis gene set differentially expressed in MLET5 is enriched for estrogen-regulated genes, our findings suggest that transient over-expression of ERα could lead to increased cell survival and the development of estrogen-independent growth, thereby contributing to resistance to endocrine therapies in breast cancer patients.

The liver receptor homolog-1 regulates estrogen receptor expression in breast cancer cells.

Estrogen receptor-α (ER) is expressed in the great majority of breast cancers, and the inhibition of ER action is a key part of breast cancer treatment. The inhibition of ER action is achieved using anti-estrogens, primarily tamoxifen, and with aromatase inhibitors that inhibit estrogen biosynthesis, thereby preventing ER activation. However, resistance to these therapies is common. With the aim of identifying new molecular targets for breast cancer therapy, we have identified the liver receptor homolog-1 (LRH-1) as an estrogen-regulated gene. RNA interference and over-expression studies were used to investigate the role of the LRH-1 in regulating breast cancer growth and to identify the targets of an LRH-1 action. Promoter recruitment was determined using reporter gene and chromatin immunoprecipitation (ChIP) assays. We show that LRH-1 regulates breast cancer cell growth by regulating the ER expression. Reporter gene and in vitro DNA-binding assays identified an LRH-1-binding site in the ER gene promoter, and ChIP assays have demonstrated in vivo binding at this site. We also provide evidence for new LRH-1 variants in breast cancer cells arising from the use of alternative promoters. Previous studies have shown that LRH-1 functions in estrogen biosynthesis by regulating aromatase expression. Our findings extend this by highlighting LRH-1 as a key regulator of the estrogen response in breast cancer cells through the regulation of ER expression. Hence, inhibition of LRH-1 could provide a powerful new approach for the treatment of endocrine-resistant breast cancer.

NHL (diffuse large B-cell lymphoma).

INTRODUCTION: Non-Hodgkin's lymphoma (NHL) is the sixth most common cancer in the UK; 9443 new cases were diagnosed in the UK in 2002, and it caused 4418 UK deaths in 2003. Incidence rates show distinct geographical variation, with age-standardised incidence rates ranging from 17 per 100,000 in northern America to 4 per 100,000 in south-central Asia. NHL occurs more commonly in males than in females, and the age-standardised UK incidence increased by 10.3% between 1993 and 2002. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of first-line treatments for aggressive, or for relapsed aggressive, non-Hodgkin's lymphoma (diffuse large B-cell lymphoma)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 26 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: allogeneic stem-cell support, chemotherapy (conventional dose salvage, high-dose plus autologous transplant stem-cell support, conventional dose in people with chemosensitive disease), CHOP 14, CHOP 21, CHOP 21 with radiotherapy, CHOP 21 with rituximab, ACVBP, MACOP-B, m-BACOD, PACEBOM, and ProMACE-CytaBOM.

Targeted therapies in non-small cell lung cancer.

Chemotherapy now has an established role in the treatment of non-small cell lung cancer, with randomised evidence supporting a survival benefit in both advanced disease and the adjuvant setting. The availability of newer cytotoxic agents has not led to further improvement in outcome, and novel approaches a re needed. Growth factor-mediated signalling pathways are frequently subverted in human cancers, so that physiological processes become abnormally regulated by oncogene products such as epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF). Drugs targeting EGFR and VEGF have already demonstrated improved survival compared with standard of care in lung cancer, and the evidence supporting the use of these and related agents is reviewed here. These newer agents are in general cytostatic rather than cytotoxic, so that clinical benefit can be associated with stable disease rather than with disease response alone, and the impact of this on imaging modalities used to assess response in trials and clinical practice is discussed.

NHL (diffuse large B cell lymphoma).

INTRODUCTION: Non-Hodgkin's lymphoma (NHL) is the sixth most common cancer in the UK; 9443 new cases were diagnosed in the UK in 2002, and it caused 4418 UK deaths in 2003. Incidence rates show distinct geographical variation, with age-standardised incidence rates ranging from 17 per 100,000 in Northern America to 4 per 100,000 in south-central Asia. NHL occurs more commonly in males than in females, and the age-standardized UK incidence increased by 10.3% between 1993 and 2002. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of first-line treatments for aggressive, or for relapsed aggressive, non-Hodgkin's lymphoma (diffuse large B cell lymphoma)? We searched: Medline, Embase, The Cochrane Library and other important databases up to April 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 33 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: allogeneic stem cell support, chemotherapy (conventional dose salvage, high-dose plus autologous transplant stem cell support, conventional dose in people with chemosensitive disease), CHOP 14, CHOP 21, CHOP 21 with radiotherapy, CHOP 21 with rituximab, MACOP-B, m-BACOD, PACEBOM, and ProMACE-CytaBOM.