YAP promotes proliferation, chemoresistance, and angiogenesis in human cholangiocarcinoma through TEAD transcription factors.

UNLABELLED: The Yes-associated protein (YAP)/Hippo pathway has been implicated in tissue development, regeneration, and tumorigenesis. However, its role in cholangiocarcinoma (CC) is not established. We show that YAP activation is a common feature in CC patient biopsies and human CC cell lines. Using microarray expression profiling of CC cells with overexpressed or down-regulated YAP, we show that YAP regulates genes involved in proliferation, apoptosis, and angiogenesis. YAP activity promotes CC growth in vitro and in vivo by functionally interacting with TEAD transcription factors (TEADs). YAP activity together with TEADs prevents apoptosis induced by cytotoxic drugs, whereas YAP knockdown sensitizes CC cells to drug-induced apoptosis. We further show that the proangiogenic microfibrillar-associated protein 5 (MFAP5) is a direct transcriptional target of YAP/TEAD in CC cells and that secreted MFAP5 promotes tube formation of human microvascular endothelial cells. High YAP activity in human CC xenografts and clinical samples correlates with increased MFAP5 expression and CD31(+) vasculature. CONCLUSIONS: These findings establish YAP as a key regulator of proliferation and antiapoptotic mechanisms in CC and provide first evidence that YAP promotes angiogenesis by regulating the expression of secreted proangiogenic proteins.

Preliminary results of the effect of music therapy treatment on anxiety, sadness, physical discomfort, mood, and quality of life in hospitalized onco-haematological patients.

BACKGROUND: Physical and psychological distress may occur in patients facing an onco-haematological diagnosis and undergoing complex therapies such as intensive chemotherapy, stem cell transplantation, and immunotherapy. Studies have shown the need for incorporating different therapeutic modalities to respond to patients' physical and psychosocial needs. AIMS: The purpose of this study was to evaluate the effectiveness of music therapy treatment on mood, anxiety, depression, and physical discomfort in hospitalized onco-haematological patients. METHODS: Forty patients were included in this music therapy study from November 2021 to May 2023. Treatment consisted of individual weekly music therapy sessions. Participants completed the following evaluation instruments before and after the intervention: the Hospital Anxiety and Depression Scale (HADS), Profile of Mood States-Short Form A-Version (POMS-A), and European Organization for Research and Treatment of Cancer-Quality of Life Core Questionnaire-30 (EORTC QLQ-C30). A three-item numerical rating scale (NRS) for anxiety, sadness, and physical discomfort was administered at the beginning and end of each session (pre-/postsession). RESULTS: Differences (p < 0.05) were shown in NRS scores for anxiety, sadness, and physical discomfort before and after the music therapy sessions. Quality of life (QoL) was affected in almost all items, and patients could be anxious at a nonclinical level, but they were clinically depressed. EORTC QLQ-C30 scores for insomnia and pain related to the hospitalization process got worse after discharge. CONCLUSIONS: The interim results of our study showed that music therapy sessions can positively change emotional distress and improve the mood of haematological patients after every session. Despite the difficulties and limitations of this study, this preliminary report contributes to a greater understanding of the potential benefits of music therapy in hospitalized onco-haematological patients.

The RSPO-LGR4/5-ZNRF3/RNF43 module controls liver zonation and size.

LGR4/5 receptors and their cognate RSPO ligands potentiate Wnt/ß-catenin signalling and promote proliferation and tissue homeostasis in epithelial stem cell compartments. In the liver, metabolic zonation requires a Wnt/ß-catenin signalling gradient, but the instructive mechanism controlling its spatiotemporal regulation is not known. We have now identified the RSPO-LGR4/5-ZNRF3/RNF43 module as a master regulator of Wnt/ß-catenin-mediated metabolic liver zonation. Liver-specific LGR4/5 loss of function (LOF) or RSPO blockade disrupted hepatic Wnt/ß-catenin signalling and zonation. Conversely, pathway activation in ZNRF3/RNF43 LOF mice or with recombinant RSPO1 protein expanded the hepatic Wnt/ß-catenin signalling gradient in a reversible and LGR4/5-dependent manner. Recombinant RSPO1 protein increased liver size and improved liver regeneration, whereas LGR4/5 LOF caused the opposite effects, resulting in hypoplastic livers. Furthermore, we show that LGR4(+) hepatocytes throughout the lobule contribute to liver homeostasis without zonal dominance. Taken together, our results indicate that the RSPO-LGR4/5-ZNRF3/RNF43 module controls metabolic liver zonation and is a hepatic growth/size rheostat during development, homeostasis and regeneration.

Music therapy with Alzheimer's patients and their family caregivers: a pilot project.

The purpose of this paper is to present the results of a pilot project sponsored by a private foundation in Spain ("Fundació la Caixa"), in order to demonstrate some of the applications of music therapy, and to measure more systematically some of its effects on people with a probable diagnosis of Alzheimer's Disease and Related Disorders (ADRD) in early-moderate stages of the disease, and their family caregivers. Subjects for this project were 14 patients (5 women and 9 men) with a probable diagnosis of Alzheimer's disease, and 14 family caregivers (9 women and 5 men) from a rural area outside of Barcelona. Their age range was 70 to 80 years. Prior to the beginning of the project, a neuropsychologist specialized in gerontology administered a series of standardized tests to the participants. These same tests were administered again 2 days before the end of the project and 2 months later for follow-up purposes. The results of the satisfaction questionnaire showed that the caregivers perceived an improvement in the social and emotional areas of their patients, and statistical tests showed significant differences between pre and posttest scores in the following tests: (a) Dementia Scale (X2 = 12.29, p = .002), (b) NPI (X2 = 17.72, p = .001), (c) the Cohen-Mansfield agitation scale (X2 = 11.45, p = .003), (d) Burden Interview (X2 = 9.19, p = .01), (e) Memory and Behavior Problems Checklist (frequency subscale) (X2 = 11.09, p = .004), (f) STAI-S (X2 = 14.72, p = .001), and (g) Beck's Depression Inventory (X2 = 9.38, p = .009). These results and their implications are discussed extensively.

LIM-homeobox gene 2 promotes tumor growth and metastasis by inducing autocrine and paracrine PDGF-B signaling.

An epithelial-mesenchymal transition (EMT) is a critical process during embryonic development and the progression of epithelial tumors to metastatic cancers. Gene expression profiling has uncovered the transcription factor LIM homeobox gene 2 (Lhx2) with up-regulated expression during TGFß-induced EMT in normal and cancerous breast epithelial cells. Loss and gain of function experiments in transgenic mouse models of breast cancer and of insulinoma in vivo and in breast cancer cells in vitro indicate that Lhx2 plays a critical role in primary tumor growth and metastasis. Notably, the transgenic expression of Lhx2 during breast carcinogenesis promotes vessel maturation, primary tumor growth, tumor cell intravasation and metastasis by directly inducing the expression of platelet-derived growth factor (PDGF)-B in tumor cells and by indirectly increasing the expression of PDGF receptor-ß (PDGFRß) on tumor cells and pericytes. Pharmacological inhibition of PDGF-B/PDGFRß signaling reduces vessel functionality and tumor growth and Lhx2-induced cell migration and cell invasion. The data indicate a dual role of Lhx2 during EMT and tumor progression: by inducing the expression of PDGF-B, Lhx2 provokes an autocrine PDGF-B/PDGFRß loop required for cell migration, invasion and metastatic dissemination and paracrine PDGF-B/PDGFRß signaling to support blood vessel functionality and, thus, primary tumor growth.

Aplicación de la musicoterapia en las demencias / No disponible

No disponible

Musicoterapia / Music therapy

La Musicoterapia se trata de una disciplina que a menudo se incluye dentro del marco de las terapias naturales, complementarias y no farmacológicas. Cabe destacar la importancia del trabajo en equipo y de la comunicación interdisciplinar entre el musicoterapeuta y los otros profesionales

Music therapy is a discipline which often is included in the group of natural, complementary and non-pharmaceutical therapies. In this therapy, the importance of teamwork and interdisciplinary communication between the musical therapist and the other professionals deserve to be highlighted