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RATIONALE: Non-small cell lung cancer (NSCLC) carries a poor survival rate mainly because of metastasis. However, the molecular mechanisms that govern NSCLC metastasis have not been described. Because huntingtin-interacting protein-1 (HIP1) is known to play a role in tumorigenesis, we tested the involvement of HIP1 in NSCLC progression and metastasis. OBJECTIVES: HIP1 expression was measured in human NSCLC tumors, and correlation with survival outcome was evaluated. Furthermore, we investigated the ability of HIP1 to suppress metastasis. The molecular mechanism by which HIP1 contributes to suppress metastasis was investigated. METHODS: We used tissue arrays containing samples from 121 patients with NSCLC to analyze HIP1 expression by immunohistochemistry. To investigate the role of HIP1 expression on metastasis, we evaluated cellular mobility, migration, and invasion using lung adenocarcinoma (AdCA) cells with modified HIP1 expression levels. The human disease mouse models with the same cells were applied to evaluate the HIP1 suppressing metastasis and its mechanism in vivo. MEASUREMENTS AND MAIN RESULTS: HIP1 expression in AdCA progression was found to be an early-stage prognostic biomarker, with low expression correlated to poor prognosis. We also found HIP1 to be a metastatic suppressor in AdCA. HIP1 significantly repressed the mobility of lung cancer cells in vitro and in vivo and regulated the epithelial-mesenchymal transition by repressing AKT/glycogen synthase kinase-3ß/ß-catenin signaling. CONCLUSIONS: HIP1 serves as an early-stage prognostic biomarker and a metastatic suppressor. Reduced expression during AdCA progression can relieve HIP1 suppression of Akt-mediated epithelial-mesenchymal transition and thereby lead to development of late metastases and poor prognosis.
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Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias Pulmonares/genética , Proteínas de Transporte Vesicular/genética , Proteínas Adaptadoras de Transdução de Sinal , Adenocarcinoma de Pulmão , Biomarcadores Tumorais/genética , Feminino , Humanos , Masculino , Proteínas dos Microfilamentos , Pessoa de Meia-Idade , Análise de SobrevidaRESUMO
Deciphering the network of signaling pathways in cancer via protein-protein interactions (PPIs) at the cellular level is a promising approach but remains incomplete. We used an in situ proximity ligation assay to identify and quantify 67 endogenous PPIs among 21 interlinked pathways in two hepatocellular carcinoma (HCC) cells, Huh7 (minimally migratory cells) and Mahlavu (highly migratory cells). We then applied a differential network biology analysis and determined that the novel interaction, CRKL-FLT1, has a high centrality ranking, and the expression of this interaction is strongly correlated with the migratory ability of HCC and other cancer cell lines. Knockdown of CRKL and FLT1 in HCC cells leads to a decrease in cell migration via ERK signaling and the epithelial-mesenchymal transition process. Our immunohistochemical analysis shows high expression levels of the CRKL and CRKL-FLT1 pair that strongly correlate with reduced disease-free and overall survival in HCC patient samples, and a multivariate analysis further established CRKL and the CRKL-FLT1 as novel prognosis markers. This study demonstrated that functional exploration of a disease network with interlinked pathways via PPIs can be used to discover novel biomarkers.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Nucleares/metabolismo , Mapas de Interação de Proteínas , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Intervalo Livre de Doença , Células HEK293 , Células Hep G2 , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Transdução de Sinais , Análise Serial de Tecidos , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adulto JovemRESUMO
BACKGROUND: Pin1 promotes oncogenesis by regulating multiple oncogenic signaling. In this study, we investigated the involvement of Pin1 in tumor progression and in the prognosis of human esophageal squamous cell carcinoma (ESCC). RESULTS: We observed that proliferation, clonogenicity and tumorigenesis of CE81T cells were inhibited by Pin1 knockdown. We next analyzed Pin1 expression in clinical ESCC specimens. When compared to the corresponding non-tumor part, Pin1 protein and mRNA levels in tumor part were higher in 84% and 62% patients, respectively. By immunohistochemistry, we identified that high Pin1 expression was associated with higher primary tumor stage (p = 0.035), higher overall cancer stage (p = 0.047) and poor overall survival (p < 0.001). Furthermore, the association between expression of Pin1 and levels of ß-catenin and cyclin D in cell line and clinical specimens was evaluated. ß-catenin and cyclin D1 were decreased in CE81T cells with Pin1 knockdown. Cyclin D1 level correlated with Pin1 expression in clinical ESCC specimens. CONCLUSIONS: Pin1 upregulation was associated with advanced stage and poor prognosis of ESCC. Pin1 knockdown inhibited aggressiveness of ESCC cells. ß-catenin and cyclin D1 were positively regulated by Pin1. These results indicated that targeting Pin1 pathway could represent a potential modality for treating ESCC.
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Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/mortalidade , Neoplasias Esofágicas/enzimologia , Neoplasias Esofágicas/mortalidade , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/metabolismo , Peptidilprolil Isomerase/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Ciclina D1/genética , Ciclina D1/metabolismo , Intervalo Livre de Doença , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptidilprolil Isomerase de Interação com NIMA , Proteínas de Neoplasias/genética , Peptidilprolil Isomerase/genética , Estudos Retrospectivos , Taxa de Sobrevida , Regulação para Cima , beta Catenina/genética , beta Catenina/metabolismoRESUMO
This study explored the effects of advance care planning interventions on end-of-life treatment decisions among patients with heart failure. The study design was a randomized controlled trial. An intervention involving a motivational video, a cartoon version educational brochure, and a guided discussion was implemented. A total of 82 hospitalized patients with heart failure were recruited. Half of the participants received the intervention, and the other half received routine care. The Life Support Preferences Questionnaire was the primary measurement instrument. Before the advance care planning intervention, a significant difference between the experimental and control groups was observed in the cardiopulmonary resuscitation score but not the total, antibiotics, surgery, and artificial nutrition and hydration scores. In the experimental group but not in the control group, significant differences were observed between pretest and posttest total, antibiotics, cardiopulmonary resuscitation, surgery, and artificial nutrition and hydration scores. Significant differences in mean score changes were observed in total and each treatment score between the experimental and control groups. The advance care planning intervention led participants to select fewer medical treatments. This intervention may be suitable for societies where people are unfamiliar with advance care planning and may feel uncomfortable discussing death.
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Planejamento Antecipado de Cuidados , Insuficiência Cardíaca , Assistência Terminal , Humanos , Insuficiência Cardíaca/terapia , Antibacterianos , MorteRESUMO
Breast cancer (BC) is the most common cancer and the leading cause of cancer-related deaths in women worldwide. The 5-year survival rate is over 90% in BC patients, but once BC cells metastasis into distal organs, it is dramatically decreasing to less than 30%. Especially, triple-negative breast cancer (TNBC) patients usually lead to poor prognosis and survival because of metastasis. Understanding the underline mechanisms of TNBC metastasis is a critical issue. Non-coding RNAs, including of lncRNAs and microRNAs, are non-protein-coding transcripts and have been reported as important regulators in TNBC metastasis. However, the underline mechanisms for non-coding RNAs regulating TNBC metastasis remain largely unclear. Here, we found that lncRNA MIR4500HG003 was highly expressed in highly metastatic MDA-MB-231 TNBC cells and overexpression of MIR4500HG003 enhanced metastasis ability in vitro and in vivo and promoted MMP9 expression. Furthermore, we found MIR4500HG003 physically interacted with miR-483-3p and reporter assay showed miR-483-3p attenuated MMP9 expression. Importantly, endogenous high expressions of MIR4500HG003 were correlated with tumor recurrence in TNBC patients with tumor metastasis. Taken together, our findings suggested that MIR4500HG003 promotes metastasis of TNBC through miR-483-3p-MMP9 signaling axis and may be used as potential prognostic marker for TNBC patients.
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Regulação Neoplásica da Expressão Gênica , Metaloproteinase 9 da Matriz , MicroRNAs , Metástase Neoplásica , RNA Longo não Codificante , Neoplasias de Mama Triplo Negativas , Humanos , MicroRNAs/metabolismo , MicroRNAs/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Feminino , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Linhagem Celular Tumoral , Animais , Camundongos , Camundongos Nus , Movimento Celular/genética , Camundongos Endogâmicos BALB CRESUMO
Loss of RUNX3 expression is frequently observed in gastric cancer and is highly associated with lymph node metastasis and poor prognosis. However, the underlying molecular mechanisms of gastric cancer remain unknown. In this study, we found that the protein levels of RUNX3 and osteopontin (OPN) are inversely correlated in gastric cancer clinical specimens and cell lines. Furthermore, similar inverse trends between RUNX3 and OPN messenger RNA (mRNA) expression were demonstrated in six out of seven normal-tumor-paired gastric cancer clinical specimens. In addition, low RUNX3 and high OPN expression were associated with poor prognosis in gastric cancer patients. Ectopic expression of green fluorescent protein-RUNX3 reduced OPN protein and mRNA expression in the AGS and SCM-1 gastric cancer cell lines. In contrast, knockdown of RUNX3 in GES-1, a normal gastric epithelial cell line, increased OPN expression. Although three RUNX3-binding sequences have been identified in the OPN promoter region, direct binding of RUNX3 to the specific binding site, -142 to -137bp, was demonstrated by chromatin immunoprecipitation assay. The binding of RUNX3 to the OPN promoter significantly decreased OPN promoter activity. The knockdown of OPN or overexpression of RUNX3 inhibited cell migration in AGS and SCM-1 cells; however, the coexpression of RUNX3 and OPN reversed the RUNX3-reduced migration ability in AGS and SCM-1 cells. In contrast, the knockdown of both RUNX3 and OPN inhibited RUNX3-knockdown-induced migration of GES-1 cells. Together, our data demonstrated that RUNX3 is a transcriptional repressor of OPN and that loss of RUNX3 upregulates OPN, which promotes migration in gastric cancer cells.
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Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Movimento Celular , Subunidade alfa 3 de Fator de Ligação ao Core/metabolismo , Osteopontina/metabolismo , Neoplasias Gástricas/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Apoptose , Sequência de Bases , Biomarcadores Tumorais/metabolismo , Western Blotting , Adesão Celular , Proliferação de Células , Imunoprecipitação da Cromatina , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Citometria de Fluxo , Mucosa Gástrica/metabolismo , Perfilação da Expressão Gênica , Humanos , Dados de Sequência Molecular , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Osteopontina/genética , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Taxa de SobrevidaRESUMO
BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths around the world, and a high recurrence rate after complete resection is an important issue reducing the cure rate and survival of patients with early stage NSCLC. Several pathologic biomarkers are associated with recurrence in early stage lung cancer after complete resection. METHODS: We evaluated the expression and prognostic value of the α1 subunit of the nicotinic acetylcholine receptor (CHRNA1) as well as other pathologic features of tumor tissues resected from patients with stage I adenocarcinoma of the lung. RESULTS: A high ratio (173/185) of CHRNA1 expression (93.5 %) was found in stage I lung adenocarcinoma. In the multivariate survival analysis, tumor necrosis, angiolymphatic invasion, perineural invasion, and CHRNA1 expression were independent poor prognostic factors for both recurrence-free and overall survival (OS). Patients expressing CHRNA1 had worse median recurrence-free survival (60.6 vs. 77.9 months, P = 0.03) and OS (65.1 vs. 77.9 months, P = 0.04) compared with CHRNA1-negative patients. CONCLUSIONS: CHRNA1 expression could be directly tested from the tumor after complete resection. In early stage NSCLC, it could be a useful prognostic factor for recurrence and survival.
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Adenocarcinoma/mortalidade , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Recidiva Local de Neoplasia/mortalidade , Receptores Nicotínicos/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
We report a new turning film structure for widening the viewing angle of a vertical-field-switching blue-phase liquid crystal display, which employs a directional backlight. The turning film consists of periodic prismatic structures: each period has three prisms with different base angles so that the output light can be spread to a larger angle. Simulation results show that a full width at half-maximum of ±80° in the horizontal direction and ±45° in the vertical direction can be achieved.
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Asians believe discussing death-related topics is inauspicious and may bring bad luck. It is critical to explore the end-of-life care preferences of the Asian elderly with less-threatening tools. The study examined older adults' preferences regarding end-of-life treatments by applying a cartoon version of the Life Support Preferences Questionnaire (LSPQ). A cross-sectional survey was conducted to understand older adults' preferences for end-of-life treatments. A total of 342 older adults participated in the study, comprising 268 elderly patients from a veterans hospital located in northern Taiwan and 74 elderly family members of the patients. Regardless of scenario, cardiopulmonary resuscitation (CPR) had the lowest score, indicating that older adults considered it a less desirable medical treatment. By contrast, antibiotics and intravenous infusions had the highest scores, indicating that older adults tended to prefer them. End-of-life care preferences were significantly different in genders. CPR and surgical preferences of older adults differed significantly with education level. Different demographic characteristics had different end-of-life treatment preferences, and future research may develop advance care planning programs for different attributes. This cartoon version of the LSPQ can help healthcare professionals to understand older adults' preferences for end-of-life care and warrants further empirical research.
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Antibacterianos , Tomada de Decisões , Humanos , Masculino , Feminino , Idoso , Infusões Intravenosas , Estudos Transversais , Inquéritos e QuestionáriosRESUMO
Currently, the survival rate for breast cancer is more than 90%, but once the cancer cells metastasize to distal organs, the survival rate is dramatically reduced, to less than 30%. Triple-negative breast cancer accounts for 15-20% of all breast cancers. Triple-negative breast cancer (TNBC) is associated with poor prognostic and diagnostic outcomes due to the limiting therapeutic strategies, relative to non-TNBC breast cancers. Therefore, the development of targeted therapy for TNBC metastasis remains an urgent issue. In this study, high Carboxyl-terminal modulator protein (CTMP) is significantly associated with recurrence and disease-free survival rate in TNBC patients. Overexpression of CTMP promotes migration and invasion abilities in BT549 cells. Down-regulating of CTMP expression inhibits migration and invasion abilities in MDA-MB-231 cells. In vivo inoculation of high-CTMP cells enhances distant metastasis in mice. The metastasis incidence rate is decreased in mice injected with CTMP-downregulating MDA-MB-231 cells. Gene expression microarray analysis indicates the Akt-dependent pathway is significantly enhanced in CTMP overexpressing cells compared to the parental cells. Blocking Akt activation via Akt inhibitor treatment or co-expression of the dominant-negative form of Akt proteins successfully abolishes the CTMP mediating invasion in TNBC cells. Our findings suggest that CTMP is a potential diagnostic marker for recurrence and poor disease-free survival in TNBC patients. CTMP promotes TNBC metastasis via the Akt-activation-dependent pathway.
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Neoplasias de Mama Triplo Negativas , Animais , Humanos , Camundongos , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Palmitoil-CoA Hidrolase/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Neoplasias de Mama Triplo Negativas/metabolismo , FemininoRESUMO
Leptomeningeal metastasis (LM) occurs when tumor cells spread to the leptomeningeal space surrounding the brain and the spinal cord, thereby causing poor clinical outcomes. The triple-negative breast cancer (TNBC) has been associated with symptoms of LM and mechanism remained unclear. Through proteomic analysis, we identified high expression of ICAM2 in leptomeningeal metastatic TNBC cells, which promoted the colonization of the spinal cord and resulted in poor survival in vivo. Two-way demonstration indicated that high levels of ICAM2 promoted blood-cerebrospinal fluid barrier (BCB) adhesion, trans-BCB migration, and stemness abilities and determined the specificity of LM in vivo. Furthermore, pull-down and antibody neutralizing assay revealed that ICAM2 determined the specificity of LM through interactions with ICAM1 in the choroid plexus epithelial cells. Therefore, neutralizing ICAM2 can attenuate the progression of LM and prolong survival in vivo. The results suggested that targeting ICAM2 is a potential therapeutic strategy for LM in TNBC.
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Neoplasias Meníngeas , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/patologia , Proteômica , Moléculas de Adesão Celular , Células Epiteliais/metabolismo , Antígenos CDRESUMO
Tumor recurrence is the most common cause of disease failure after surgical resection in early-stage lung adenocarcinoma. Identification of clinically relevant prognostic markers could help to predict patients with high risk of disease recurrence. A meta-analysis of available lung adenocarcinoma microarray datasets revealed that T-LAK cell-originated protein kinase (TOPK), a serine/threonine protein kinase, is overexpressed in lung cancer. Using stable cell lines with overexpression or knockdown of TOPK, we have shown that TOPK can promote cell migration, invasion, and clonogenic activity in lung cancer cells, suggesting its crucial role in lung tumorigenesis. To evaluate the prognostic value of TOPK expression in resected stage I lung adenocarcinoma, a retrospective analysis of 203 patients diagnosed with pathological stage I lung adenocarcinoma was carried out to examine the expression of TOPK by immunohistochemistry (IHC). The prognostic significance of TOPK overexpression was examined. Overexpression of TOPK (IHC score >3) was detected in 67.0% of patients, and these patients were more frequently characterized with disease recurrence and angiolymphatic invasion. Using multivariate analysis, patient age (>65 years old; P = 0.002) and TOPK overexpression (IHC score >3; P < 0.001) significantly predicted a shortened overall survival. Moreover, TOPK overexpression (IHC score >3; P = 0.005) also significantly predicted a reduced time to recurrence in the patients. Our results indicate that overexpression of TOPK could predetermine the metastatic capability of tumors and could serve as a significant prognostic predictor of shortened overall survival and time to recurrence.
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Adenocarcinoma/enzimologia , Células Matadoras Ativadas por Linfocina/metabolismo , Neoplasias Pulmonares/enzimologia , Proteínas Serina-Treonina Quinases/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno , Prognóstico , Recidiva , Linfócitos T/metabolismoRESUMO
This study aimed to explore the factors affecting the behavioral intentions of older adults toward advance care planning (ACP). A questionnaire survey was conducted at 2 medical wards and a senior activity center in northern Taiwan. Four hundred one participants were older adults aged over 65 years, comprising hospitalized patients, their caregivers, and members of a senior activity center. The regression model revealed that participant type (patient, caregiver, or community resident); financial support; discussion of ACP with family; and knowledge, attitudes, and subjective norms accounted for 46.3% of the variance in behavioral intentions. The behavioral intention of caregivers was higher than that of patients. The behavioral intention of participants who were financially dependent on the family was lower than that of pensioners. Regarding discussing ACP with family, older adults in the contemplation and preparation stages score higher on behavioral intention than those in the precontemplation stage. This study supports the theory of reasoned action. Older adults' ACP knowledge and attitudes need to be enhanced through education. Caregivers' behavioral intentions tend to perform ACP. Sharing their caring experiences may be a strategy for promoting ACP. Older adults' financial status affects their behavioral intentions. Therefore, financial planning should be performed early and should incorporate ACP.
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BACKGROUND: Studies have indicated that the advance care planning knowledge and attitudes of elderly individuals strongly affect their implementation of advance care planning. A measurement with a theoretical base for evaluating elderly individuals' knowledge, attitudes, and behavioral intentions regarding advance care planning is lacking. OBJECTIVES: To develop a questionnaire and understand elderly individuals' knowledge, attitudes, and behavioral intentions regarding implementing advance care planning. METHODS: A cross-sectional questionnaire survey was conducted. The content validity index, and statistical methods, including discrimination, factor, and reliability analysis, were adopted for psychometric testing. Descriptive statistics mainly presented data analysis. RESULTS: 401 elderly individuals were recruited from a medical center and one senior activity center. The content validity index was approximately 0.71-0.92 for the developed questionnaires, the Kuder-Richardson formula 20 was 0.84 for advance care planning knowledge, and the Cronbach's alpha was 0.86, 0.94, 0.76, and 0.92 for attitudes, behavioral intentions, influencing factors, and subjective norms, respectively. The average score for advance care planning knowledge for elderly individuals was 4.42, with a correct answer rate of 49.1%. They lacked knowledge of advance care planning-related legislation. The mean score for attitudes and behavioral intentions was 14.32 and 3.48, respectively. Elderly individuals agreed that advance care planning has benefits but were worried about the emotional distress caused by advance care planning discussions. Elderly individuals with positive behavioral intentions tend to implement advance care planning. Spouses, children, doctors, and nurses are significant reference people for elderly individuals. CONCLUSIONS: The developed questionnaire exhibits good validity and reliability for understanding elderly individuals' knowledge, attitudes, and behavioral intentions concerning advance care planning. Advance care planning materials or decision aids suitable for elderly individuals must be developed to increase their understanding of advance care planning. Additionally, the role of nurses is indispensable in promoting advance care planning among elderly individuals.
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Planejamento Antecipado de Cuidados , Conhecimentos, Atitudes e Prática em Saúde , Idoso , Criança , Estudos Transversais , Humanos , Intenção , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
AIM: This study aimed to develop a video-based advance care planning intervention, and examine the effectiveness of the intervention on knowledge, behavioral intentions and advance directive signing among older patients admitted to a geriatric unit in Taiwan. METHODS: This randomized controlled trial was carried out in two geriatric wards of a medical center in northern Taiwan, between June 2014 and June 2015. The participants were randomly assigned to the intervention (n = 39) or control (n = 43) group. Participants in the intervention group watched a 5-min video regarding advance care planning. The control group received usual care. Structured questionnaires on advance care planning knowledge and behavioral intentions were administered to both groups before and after the intervention. Advance directive signing was carried out until 2 weeks after hospital discharge through a chart review. RESULTS: The intervention group showed a significantly higher advance care planning knowledge score and behavioral intention score than the control group post-intervention. The rate of advance directive signing was 33.3% in the intervention group and 9.3% in the control group (P = 0.01). CONCLUSIONS: This study showed the effectiveness of video-based interventions in increasing advance care planning knowledge, behavioral intention and advance directive signing among hospitalized older patients. Geriatric wards could use our model to promote advance care planning among older patients. Geriatr Gerontol Int 2021; 21: 478-484.
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Planejamento Antecipado de Cuidados , Diretivas Antecipadas , Idoso , Hospitalização , Humanos , Inquéritos e Questionários , TaiwanRESUMO
Brian metastasis, which is diagnosed in 30% of triple-negative breast cancer (TNBC) patients with metastasis, causes poor survival outcomes. Growing evidence has characterized miRNAs involving in breast cancer brain metastasis; however, currently, there is a lack of prognostic plasma-based indicator for brain metastasis. In this study, high level of miR-211 can act as brain metastatic prognostic marker in vivo. High miR-211 drives early and specific brain colonization through enhancing trans-blood-brain barrier (BBB) migration, BBB adherence, and stemness properties of tumor cells and causes poor survival in vivo. SOX11 and NGN2 are the downstream targets of miR-211 and negatively regulate miR-211-mediated TNBC brain metastasis in vitro and in vivo. Most importantly, high miR-211 is correlated with poor survival and brain metastasis in TNBC patients. Our findings suggest that miR-211 may be used as an indicator for TNBC brain metastasis.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Neoplasias Encefálicas/genética , MicroRNAs/genética , Proteínas do Tecido Nervoso/genética , Fatores de Transcrição SOXC/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Invasividade Neoplásica/genética , Metástase Neoplásica , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Background: Surrogates often do not accurately predict older people's preferences about end-of-life (EOL) care. Few studies have examined the impact of advance care planning (ACP) on EOL decision-making consistency between older people and their surrogates, and these studies have yielded conflicting results. Objectives: To evaluate the effectiveness of ACP in improving EOL decision-making consistency between older people and their surrogates. Design: The intervention in this pre-post quasi-experimental design included an informative video, a brochure about ACP, and a guided discussion about EOL wishes. Setting: Two geriatric wards in a medical center in northern Taiwan. Subjects: One hundred eight participants, as 54 pairs of older people and their surrogates, were randomly assigned to either the experimental or control group. The experimental group received an intervention, while the control group received usual care. Measurements: Life-Support Preferences Questionnaire. Results: The intervention did not improve decision-making consistency between older people and their surrogates. This was the first time that most pairs discussed specific EOL decisions, so additional preparation may improve comfort with this topic. This study also found that some older people had difficulty concentrating on the educational brochure or understanding the related terms. Conclusions: Preparation for ACP discussion is needed for older people and their surrogates. Longer-term effects of ACP should be monitored because ACP interventions may have enhanced empathy between older people and their surrogates. Additionally, a culturally sensitive illustrated questionnaire that explains life-support preferences and ACP topics may improve communication between older people and their surrogates.
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Planejamento Antecipado de Cuidados , Assistência Terminal , Idoso , Morte , Tomada de Decisões , Humanos , Inquéritos e Questionários , TaiwanRESUMO
Mammalian STE20-like kinase 1 (MST1/STK4/KRS2) encodes a serine/threonine kinase that is the mammalian homolog of Drosophila Hippo. STK4 plays an important role in controlling cell growth, apoptosis, and organ size. STK4 has been studied in many cancers with previous studies indicating an involvement in colon cancer lymph node metastasis and highlighting its potential as a diagnostic marker for colon cancer. However, the role of STK4 defect in promoting colon cancer progression is still understudied. Here, we found that STK4 was significantly downregulated in colon cancer and was associated with distal metastasis and poor survival. Furthermore, STK4 knockdown enhanced sphere formation and metastasis in vitro and promoted tumor development in vivo. We found that STK4 colocalized with ß-catenin and directly phosphorylated ß-catenin resulting in its degradation via the ubiquitin-mediated pathway. This may suggest that STK4 knockdown causes ß-catenin phosphorylation failure and subsequently ß-catenin accumulation, consequently leading to anchorage-independent growth and metastasis in colon cancer. Our results support that STK4 may act as a potential candidate for the assessment of ß-catenin-mediated colon cancer prognosis.
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Movimento Celular/genética , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Serina-Treonina Quinases/genética , Proteólise , beta Catenina/metabolismo , Idoso , Animais , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Camundongos Endogâmicos NOD , Camundongos SCID , Modelos Biológicos , Invasividade Neoplásica , Metástase Neoplásica , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fosforilação , Ligação Proteica , Proteínas Serina-Treonina Quinases/metabolismo , Análise de Sobrevida , Transcrição GênicaRESUMO
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer in Asia and demonstrates poor survival rates following a therapeutic regimen. METHODS: Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and treatment failure in cancers. Therefore, identification and characterization of CSCs may help to improve clinical outcomes for ESCC patients. Tumor sphere formation assay are performed to isolate cancer stem-like ESCC cells. QRT-PCR, tumor initiation, metastasis, CCRT treatment are used to evaluate ESCC cells' stemness properties in vitro and in vivo. RESULTS: The authors' data demonstrates that cancer stem-like ESCC cells harbored stemness characteristics including self-renewal, differentiation, and transdifferentiation, and possess tumor initiation, metastasis, and treatment inefficiency properties. For the identification of useful biomarkers of cancer stem-like ESCC cells, the authors further identified that CLDN4 was upregulated in cancer stem-like ESCC cells when compared with bulk cancer cells. High-CLDN4 cells harbored stemness and cisplatin/concurrent chemoradiation therapy (CCRT) resistance properties and a high level of CLDN4 was correlated with poor prognosis and poor CCRT response in ESCC patients. Importantly, thiamine tetrahydrofurfuryl disulfide (TTFD) decreased CLDN4 and attenuated stemness in ESCC cells, and TTFD combined with CCRT improved CCRT response in vivo. CONCLUSIONS: CLDN4 was suggested as prognostic and a CCRT response indicator for ESCC patients. TTFD combined with CCRT has potential to improve ESCC patient's clinical outcomes in the future.
RESUMO
Triple-negative breast cancer (TNBC) patients usually lead to poor prognosis and survival because of metastasis. The major sites for TNBC metastasis include the lungs, brain, liver, and bone. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts longer than 200 nucleotides and have been reported as important regulators in BC metastasis. However, the underlying mechanisms for lncRNAs regulating TNBC metastasis are not fully understood. Here we found that linc-ZNF469-3 was highly expressed in lung-metastatic LM2-4175 TNBC cells and overexpression of linc-ZNF469-3 enhanced invasion ability and stemness properties in vitro and lung metastasis in vivo. Furthermore, we found linc-ZNF469-3 physically interacted with miR-574-5p and overexpression of miR-574-5p attenuated ZEB1 expression. Importantly, endogenous high expressions of linc-ZNF469-3 and ZEB1 were correlated with tumor recurrence in TNBC patients with lung metastasis. Taken together, our findings suggested that linc-ZNF469-3 promotes lung metastasis of TNBC through miR-574-5p-ZEB1 signaling axis and may be used as potential prognostic marker for TNBC patients.