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1.
Prev Med ; 183: 107976, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38688347

RESUMO

OBJECTIVES: This longitudinal observational cohort study aimed to clarify the relationship between perceived value (PV) to adopt new behaviors and incident disability in community-dwelling older adults. METHOD: Participants were 5073 community-dwelling older adults aged ≥65 years in Japan (Mage = 74.0 ± 5.6 years; female = 55.1%). The mean follow-up time was 34.5 months. Baseline data were collected during health checkups in a prospective cohort study. Measurements included engagement in physical activity (PA), cognitive activity (CA), and social activity (SA), PV, health and physical conditions, and demographic characteristics. PV was assessed by asking whether participants thought it was valuable to adopt new behaviors related to PA, CA, and SA. Participants were classified as having higher/lower PV, PA, CA, and SA. Cox proportional hazard models were used to analyze the association between PV and incident disability. PV was examined both as an independent variable and in combination as follows: higher PV and higher PA/CA/SA (high/high); lower PV and higher PA/CA/SA (low/high); higher PV and lower PA/CA/SA (high/low); and lower PV and lower PA/CA/SA (low/low). RESULTS: Higher PV was significantly associated with a lower hazard ratio (HR) for incident disability. The low/high, high/low, and low/low significantly increased the HR compared to high/high in the analyses of PV & PA and CA. The analysis of PV & SA showed that only low/low increased the HR compared to high/high. CONCLUSION: Having both higher PV and higher activity engagement may contribute to preventing disability development. Both support for activities and value education in older adults may be needed.


Assuntos
Pessoas com Deficiência , Exercício Físico , Vida Independente , Humanos , Feminino , Masculino , Idoso , Japão , Estudos Longitudinais , Pessoas com Deficiência/estatística & dados numéricos , Pessoas com Deficiência/psicologia , Estudos Prospectivos , Idoso de 80 Anos ou mais , Comportamentos Relacionados com a Saúde , Incidência , População do Leste Asiático
2.
Geriatr Nurs ; 58: 232-237, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38838405

RESUMO

Few studies have reported an association between diversity in productive activities and life satisfaction; hence, this cross-sectional study conducted in Japan aimed to clarify this association. We assessed the life satisfaction of 4,498 Japanese community-dwelling older adults engaged in productive activities (e.g., paid work, volunteering, taking care of children, and supporting others) using the Life Satisfaction Scale. We took the sum of the number of engaging productive activities as the diversity in productive activities score. A dose-response relationship was observed for each additional productive activity on life satisfaction. Participants who engaged in one, two, three, or four productive activities were more likely to have higher life satisfaction than those who did not engage; the odds ratios (95 % confidence intervals) were 1.19 (1.02-1.39), 1.19 (1.00-1.42), 1.71 (1.37-2.13), and 2.27 (1.58-3.27), respectively. Diversity in productive activities may enhance higher life satisfaction likelihood among Japanese community-dwelling older adults.

3.
Int J Cancer ; 153(12): 1997-2010, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37548077

RESUMO

Sarcomatoid carcinoma (SC), which can occur in any organ, is a rare disease. To elucidate common characteristics of SC beyond organs, we evaluated clinicopathological and immunological features of SC defined by the single histological criterion beyond organs compared to randomly matched conventional carcinoma (non-SC) adjusted for the disease stage. Immunological features were assessed by multiplex immunohistochemistry, comparing immune cell density in tumor tissues and tumor programmed death-ligand 1 (PD-L1) expression. A total of 101 patients with SC or non-SC (31 lung, 19 esophagus, 22 pancreas, 15 liver, 4 bile duct, 6 kidney, 2 uterus and 2 ovary) were identified among 7197 patients who underwent surgery at our institute (1997-2020). SC was significantly associated with worse survival (HR: 1.571; 95% CI: 1.084-2.277; P = .017). The frequency of postoperative progression within 6 months was significantly higher for SC patients (54% vs 28%; P = .002). The immune profiling revealed the densities of CD8+ T cells (130 vs 72 cells/mm2 ; P = .004) and tumor-associated macrophages (566 vs 413 cells/mm2 ; P < .0001) and the tumor PD-L1 expression score (40% vs 5%; P < .0001) were significantly higher in SCs than in non-SCs. Among 73 SC patients with postoperative progression, multivariate Cox regression analysis showed that immunotherapy tended to be associated with favorable survival (HR: 0.256; 95% CI: 0.062-1.057; P = .060). Collectively, SCs shared clinicopathological and immunological features across organs. Our study can initiate to standardize the pathological definition of SC and provide a rationale for the investigation and development for this rare disease in a cross-organ manner.


Assuntos
Carcinoma , Neoplasias Pulmonares , Feminino , Humanos , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Prognóstico , Doenças Raras/metabolismo , Carcinoma/metabolismo , Neoplasias Pulmonares/patologia
4.
Gerontology ; 69(5): 641-649, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36587607

RESUMO

INTRODUCTION: Delaying the onset of disability is important for maintaining independence and quality of life in community-dwelling older adults. Given that social isolation is a significant risk factor for disability, effective means associated with social isolation are needed to alleviate disability. Although information and communication technology (ICT) may be a reasonable measure considering the recent social contexts due to the coronavirus disease 2019 pandemic, further insights are required. This study aimed to investigate whether ICT use can alleviate the onset of disability in community-dwelling older adults with and without social isolation. METHODS: This longitudinal cohort study on 4,346 community-dwelling independent Japanese older adults (mean age, 73.5 ± 5.3 years) was conducted between 2017 and 2018. Participants were classified into four groups based on social isolation (the condition where two or more of the following measures were met: domestic isolation, less social contact, and social disengagement) and ICT users (those who had recently used a computer or a smartphone) and followed up to assess disability incidence for 24 months after baseline assessments. Cox proportional-hazards regression models were used to identify the effect of social isolation and ICT use on the risk of disability onset by adjusting for age, sex, education history, number of medications, eye disease, level of annual income, Mini-Mental State Examination, Geriatric Depression Scale 15, and gait speed. RESULTS: The group comprised nonsocial isolation and ICT users (44.7%), social isolation and ICT users (5.4%), nonsocial isolation and ICT nonusers (41.7%), and social isolation and ICT nonusers (8.2%). At the follow-up, 2.2%, 2.4%, 5.5%, and 12.4% of the participants in the above order developed disability (p < 0.01). Cox regression models revealed a significantly higher risk of disability onset in the social isolation and ICT nonusers group than in the social isolation and ICT users group (HR = 2.939; 95% confidence interval (CI) 1.029-8.397; p = 0.044). In the subgroup analysis stratified by social isolation, ICT use significantly reduced the risk of disability onset in the socially isolated group (HR = 0.320; 95% CI 0.109-0.943; p = 0.039), although the same association was not observed in the nonsocially isolated group (HR = 0.845; 95% CI 0.565-1.264; p = 0.411). CONCLUSION: ICT use can alleviate the onset of disability in socially isolated older adults in a community setting. Considering ICT-applied methods for alleviating disability is beneficial for older adults in social isolation.


Assuntos
COVID-19 , Qualidade de Vida , Humanos , Idoso , Estudos Longitudinais , COVID-19/epidemiologia , Isolamento Social , Estudos de Coortes , Vida Independente , Comunicação , Tecnologia
5.
BMC Geriatr ; 23(1): 483, 2023 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-37563564

RESUMO

BACKGROUND: This study examined the effect of neighborhood amenities on disability risk among community-dwelling older adults in Japan, based on lifestyle activities. METHOD: This was an observational prospective cohort study. Participants comprised 13,258 older adults from the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. We calculated participants' Walk Score using their home addresses and divided them into three groups: "car-dependent," "somewhat walkable," and "very walkable." We then calculated the average value of lifestyle activities. We divided the neighborhood amenity groups into two groups, "fewer lifestyle activities" and "more lifestyle activities," for a total of six groups. After identifying interactions between neighborhood amenities and lifestyle activities, Cox proportional hazard models to calculate hazard ratios for incident disability risk, based on neighborhood amenities and lifestyle activities. RESULTS: An interaction occurred between neighborhood amenities and lifestyle activities (p < 0.05). Survival probabilities for incident disability based on lifestyle activities were estimated for each neighborhood amenity group: car-dependent, 1.62 (95% CI 1.07 to 2.46); somewhat walkable, 1.08 (95% CI 0.84 to 1.40); and very walkable, 1.05 (95% CI 0.87 to 1.27). Those with fewer lifestyle activities in the car-dependent group exhibited the highest risk of incident disability in the unadjusted and adjusted models. CONCLUSION: Given that the aging population is increasing steadily, considering older adults' neighborhood amenities and lifestyle activities in their day-to-day lives can help clinicians to deliver more older adult-centered care. Incorporating the lifestyle activities and neighborhood amenities of older adults into care planning will lead to the design and development of integrated clinical and community screening programs.


Assuntos
Características de Residência , Caminhada , Humanos , Idoso , Incidência , Estudos Prospectivos , Estilo de Vida
6.
Int Arch Occup Environ Health ; 96(9): 1225-1234, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37486376

RESUMO

OBJECTIVE: This prospective cohort study investigates the relationship between the onset of disability and employment status. METHODS: We investigated 3,741 community-dwelling adults aged 70 or older, who participated in a population-based cohort study in Japan. Their onset of disability was monitored monthly using the long-term care insurance certification registration system, for five years from baseline. Based on an employment status questionnaire, we categorized participants into three groups: (1) employee, (2) self-employed, and (3) not working. Covariates included demographic information, medical history, number of medications, educational level, living alone, social group engagement, smoking status, walking speed, instrumental activities of daily living, global cognitive function, and depressive symptoms. Missing values were managed using multiple imputation. Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for incident disability risk by employment status. RESULTS: The disability incidence rates were 15.3/1,000 (95% CIs: 10.7-22.0) person-years among employees, and 33.0/1000 (95% CIs: 24.4-44.6) and 39.6/1000 (95% CIs: 36.5-43.0) person-years among self-employed and non-working participants, respectively. The adjusted HRs for the onset of disability among non-working and self-employed participants were 1.69 (95% CIs: 1.16-2.46, p = 0.007) and 1.63 (95% CIs: 1.01-2.62, p = 0.044) compared with employees, respectively. Similar results were found among men. Among women, disability onset was not associated with employment status. CONCLUSIONS: Older adults' risk of disability onset differed according to their employment status. Older employees had a lower risk of disability onset than those not working or self-employed.


Assuntos
Pessoas com Deficiência , Vida Independente , Masculino , Humanos , Feminino , Idoso , Atividades Cotidianas , Estudos de Coortes , Estudos Prospectivos , População do Leste Asiático , Emprego , Japão/epidemiologia
7.
BMC Public Health ; 23(1): 998, 2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-37254091

RESUMO

BACKGROUND: The current study examines the negative impact of the coronavirus disease 2019 (COVID-19) emergency declarations on physical activity among the community-dwelling older adults, the participants of a physical activity measurement program, in Japan. METHODS: This retrospective observational study included 1,773 community-dwelling older adults (aged 74.6 ± 6.3 years, 53.9% women) who had participated in the physical activity measurement project from February 2020 to July 2021. We measured physical activity using a tri-axial accelerometer during 547 consecutive days. Three emergency declarations, requesting people to avoid going outside, occurred during the observational period. We multiply-imputed missing values for daily physical activity, such as steps, light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) for several patterns of datasets according to the maximum missing rates on a person level. We mainly report the results based on less than 50% of the maximum missing rate (n = 1,056). Other results are reported in the supplemental file. Changes in physical activity before and after the start of each emergency declaration were examined by the regression discontinuity design (RDD) within 14-, 28-, and 56-day bandwidths. RESULTS: For all the participants in the multiply-imputed data with the 14-day bandwidth, steps (coefficients [[Formula: see text]][Formula: see text] 964.3 steps), LPA ([Formula: see text] 5.5 min), and MVPA ([Formula: see text] 4.9 min) increased after the first emergency declaration. However, the effects were attenuated as the RDD bandwidths were widened. No consistent negative impact was observed after the second and third declarations. After the second declaration, steps ([Formula: see text]-609.7 steps), LPA ([Formula: see text]-4.6 min), and MVPA ([Formula: see text]-2.8 min) decreased with the 14-day bandwidth. On the other hand, steps ([Formula: see text] 143.8 steps) and MVPA ([Formula: see text] 1.3 min) increased with the 56-day bandwidth. For the third declaration, LPA consistently decreased with all the bandwidths ([Formula: see text]-2.1, -3.0, -0.8 min for the 14, 28, 56-day bandwidth), whereas steps ([Formula: see text]-529 steps) and MVPA ([Formula: see text]-2.6 min) decreased only with the 28-day bandwidth. CONCLUSIONS: For the community-dwelling older adults who regularly self-monitor their physical activity, the current study concludes that there is no evidence of consistently negative impacts of the emergency declarations by the COVID-19 pandemic.


Assuntos
COVID-19 , Vida Independente , Humanos , Feminino , Idoso , Masculino , Pandemias , Exercício Físico , Estudos Retrospectivos
8.
Cancer Sci ; 113(2): 784-795, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34808009

RESUMO

The utility of Schlafen 11 (SLFN11) expression as a predictive biomarker for platinum-based chemotherapy has been established for cancers from different histologies. However, the therapeutic relevance of SLFN11 in bladder cancer (BC) is unknown. Here, we examined the clinicopathologic significance of SLFN11 expression across 120 BC cases by immunohistochemistry. We divided the cases into two cohorts, one including 50 patients who received adjuvant or neoadjuvant platinum-based chemotherapy, and the other including 70 BC patients treated by surgical resection without chemotherapy. In the cohort of 50 BC cases treated with platinum-based chemotherapy, the SLFN11-positive group (n = 25) showed significantly better overall survival than the SLFN11-negative group (n = 25, P = .012). Schlafen 11 expression correlated significantly with the expression of luminal subtype marker GATA3. Multivariate analyses identified SLFN11 expression as an independent prognostic predictor (odds ratio, 0.32; 95% confidence interval, 0.11-0.91; P = .033). Conversely, in the cohort of 70 BC cases not receiving platinum-based chemotherapy, the SLFN11-positive group (n = 29) showed significantly worse overall survival than the SLFN11-negative group (n = 41, P = .034). In vitro analyses using multiple BC cell lines confirmed that SLFN11 KO rendered cells resistant to cisplatin. The epigenetic modifying drugs 5-azacytidine and entinostat restored SLFN11 expression and resensitized cells to cisplatin and carboplatin in SLFN11-negative BC cell lines. We conclude that SLFN11 is a predictive biomarker for BC patients who undergo platinum-based chemotherapy and that the combination of epigenetic modifiers could rescue refractory BC patients to platinum derivatives by reactivating SLFN11 expression.


Assuntos
Antineoplásicos/uso terapêutico , Proteínas Nucleares/metabolismo , Platina/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Antineoplásicos/farmacologia , Azacitidina/farmacologia , Benzamidas/farmacologia , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Sinergismo Farmacológico , Feminino , Fator de Transcrição GATA3/metabolismo , Humanos , Masculino , Proteínas Nucleares/genética , Platina/farmacologia , Prognóstico , Piridinas/farmacologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/cirurgia
9.
Dement Geriatr Cogn Disord ; 51(4): 322-330, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35896063

RESUMO

INTRODUCTION: The prevalence of hearing and visual impairment (HI and VI) and dual sensory impairment (DSI), which is a combination of both, is increasing as the population ages. These sensory impairments are expected to increase the cognitive load of information processing from hearing and vision and impair appropriate cognitive processing. Although an association between DSI and cognitive decline has been reported, a more detailed study of the effects on each cognitive domain is required. This study aimed to investigate the prevalence of self-reported sensory impairment in community-dwelling older adults and to examine the impact of DSI on the severity of mild cognitive impairment (MCI) and on each cognitive domain (memory, attention, executive function, and processing speed). METHODS: The participants were recruited from a sub-cohort of the National Center for Geriatric Gerontology-Study on Geriatric Syndromes (NCGG-SGS) conducted by the National Center for Geriatrics and Gerontology. We included 4,471 community-dwelling older adults (age: 75.9 ± 4.3 years; females: 52.3%) who fulfilled the inclusion criteria. The HI and VI were identified using a self-report questionnaire. Cognitive and other parameters were also assessed by trained staff. Logistic regression analysis was used to evaluate the relationship between the presence of HI and VI and the severity of MCI, and functional decline in each cognitive domain. RESULTS: DSI was identified in 11.4% of community-dwelling older adults. Regarding sensory impairment and MCI severity, the odds ratio (OR) for single-domain MCI was significantly higher in VI (OR: 1.31; 95% CI: 1.06-1.61), and the OR for multiple-domain MCI was significantly higher in DSI (OR: 1.58; 95% CI: 1.10-2.29). In relation to the four cognitive domains, ORs for impaired executive function were higher for VI and DSI (VI, OR: 1.37; 95% CI: 1.09-1.72. DSI, OR: 1.39; 95% CI: 1.06-1.81). DSI also exhibited a higher odds ratio for reduced processing speed (OR: 2.03; 95% CI: 1.42-2.91). DISCUSSION/CONCLUSION: DSI is predicted to increase as the population ages and is associated with various health problems. Further, DSI has been reported to decrease quality of life, which needed to establish appropriate treatment and prevention measures.


Assuntos
Disfunção Cognitiva , Perda Auditiva , Feminino , Humanos , Idoso , Idoso de 80 Anos ou mais , Transtornos da Visão/epidemiologia , Transtornos da Visão/complicações , Transtornos da Visão/psicologia , Qualidade de Vida , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/complicações , Perda Auditiva/complicações , Vida Independente
10.
J Opt Soc Am A Opt Image Sci Vis ; 39(9): 1682-1693, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36215637

RESUMO

A reconstruction algorithm for the defect profile beneath a dielectric rough surface using scattered far fields is proposed. This is a fundamental technique for optical measurements, such as diffraction tomography, for defect inspection of microfabricated devices. In general, the profile reconstruction process is considerably time consuming. We propose a domain-boundary integral hybrid method to reduce the number of operations while maintaining the rigor of scattering; the polarization properties, scattering, and multiscattering in the sample are considered. We present reconstruction simulations to validate the proposed algorithm. The reconstruction limit as well as its dependency on sample illumination and rough surface shape are also discussed.

11.
BMC Geriatr ; 22(1): 870, 2022 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-36384448

RESUMO

BACKGROUND: Physical frailty is associated with social activity. However, the relationship between physical frailty and levels of engagement with other people during social activities remains unclear. Thus, we aimed to clarify the relationship between physical frailty and social activity using a taxonomy of activity levels among community-dwelling older adults in Japan. METHODS: This cross-sectional observational study analyzed data from 12,788 older adults (7001 women, mean age: 73.8 years, standard deviation = 5.9; range: 60-96 years) from the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. Physical frailty was assessed using the following components: slow walking speed, muscle weakness, exhaustion, low activity, and weight loss. We asked participants about seven social activities that included social participation and engagement and examined their relationship to physical frailty. RESULTS: Physical frailty was independently associated with all social activities. Exercise circle activity, which includes a level of social participation, was strongly associated with physical pre-frailty and physical frailty. Results of sub-analyses indicated that the level of social engagement was independently associated with physical frailty in the older group (over 75 years) but not in the younger group (60-74 years). CONCLUSIONS: Our results indicate that the strength of the association between social activity and physical frailty differs by the level of social participation. Given the increasingly high prevalence of physical frailty in Japan and its strong association with numerous adverse health outcomes, the relationship between physical frailty and levels of social participation may assist in developing measures to prevent the incidence and progression of physical frailty.


Assuntos
Fragilidade , Feminino , Humanos , Idoso , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/complicações , Vida Independente , Idoso Fragilizado , Estudos Transversais , Japão/epidemiologia , Avaliação Geriátrica/métodos
12.
Sensors (Basel) ; 22(10)2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35632145

RESUMO

Current step-count estimation techniques use either an accelerometer or gyroscope sensors to calculate the number of steps. However, because of smartphones unfixed placement and direction, their accuracy is insufficient. It is necessary to consider the impact of the carrying position on the accuracy of the pedometer algorithm, because of people carry their smartphones in various positions. Therefore, this study proposes a carrying-position independent ensemble step-counting algorithm suitable for unconstrained smartphones in different carrying positions. The proposed ensemble algorithm comprises a classification algorithm that identifies the carrying position of the smartphone, and a regression algorithm that considers the identified carrying position and calculates the number of steps. Furthermore, a data acquisition system that collects (i) label data in the form of the number of steps estimated from the Force Sensitive Resistor (FSR) sensors, and (ii) input data in the form of the three-axis acceleration data obtained from the smartphones is also proposed. The obtained data were used to allow the machine learning algorithms to fit the signal features of the different carrying positions. The reliability of the proposed ensemble algorithms, comprising a random forest classifier and a regression model, was comparatively evaluated with a commercial pedometer application. The results indicated that the proposed ensemble algorithm provides higher accuracy, ranging from 98.1% to 98.8%, at self-paced walking speed than the commercial pedometer application, and the machine learning-based ensemble algorithms can effectively and accurately predict step counts under different smart phone carrying positions.


Assuntos
Aprendizado de Máquina , Smartphone , Actigrafia , Algoritmos , Humanos , Reprodutibilidade dos Testes
13.
Cancer Sci ; 112(3): 1196-1208, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33423358

RESUMO

5-Fluorouracil (5-FU) is one of the most frequently used pharmacological agents in the treatment of colorectal cancer (CRC). Resistance to chemotherapy is a major cause of treatment failure of CRC, and it is a well known fact that cancer stem cells play a significant role in the acquisition of drug resistance. In this study, we focused on the KHDRBS3 gene that encodes KH RNA Binding Domain Containing, Signal Transduction Associated 3. We first clarified the relationship between KHDRBS3 and 5-FU resistance. We then observed higher expression levels of KHDRBS3 in KRAS-mutant organoids and cell lines in comparison with KRAS wild-type organoids and cell lines. Immunohistochemical analysis using CRC cases revealed that the prognosis of KHDRBS3-positive patients was significantly worse compared with that of KHDRBS3-negative patients. Univariate and multivariate Cox proportional hazards analyses showed that KHDRBS3 was an independent prognostic factor in patients with CRC. We determined that KHDRBS3 might play a crucial role in the acquisition of stem cell properties, such as drug resistance and spheroid/organoid formation, by regulating CD44 variant expression and the Wnt signaling pathway. In an immunodeficient mouse model, KHDRBS3-positive cells showed efficient tumor formation and formed metastatic lesions in the lungs. These results indicated that KHDRBS3 plays a crucial role in drug resistance and anchorage-independent growth by maintaining stem cell-like features in CRC cells. KHDRBS3 could be a promising candidate marker for predicting chemotherapeutic effect and prognosis in CRC patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Colorretais/terapia , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Ligação a RNA/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Colectomia , Colo/patologia , Colo/cirurgia , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Receptores de Hialuronatos/genética , Masculino , Camundongos , Pessoa de Meia-Idade , Mutação , Células-Tronco Neoplásicas/patologia , Organoides/efeitos dos fármacos , Organoides/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas de Ligação a RNA/genética , Análise de Sobrevida , Via de Sinalização Wnt/genética , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Br J Cancer ; 125(1): 65-77, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33785877

RESUMO

BACKGROUND: Although unresectable or recurrent gastric cancers (GC) are frequently treated with platinum-based chemotherapy, response to treatment remains unpredictable. Because Schlafen 11 (SLFN11) is recently identified as a critical determinant of platinum sensitivity, we investigated the potential clinical utility of SLFN11 in the treatment of GC. METHODS: We analysed the correlation between SLFN11 expression and overall survival in 169 GC patients by our established immunohistochemical approach. The impact of SLFN11 expression on the response to platinum and transition of SLFN11 expression upon long-term treatment with platinum were examined using GC cell lines and organoids. RESULTS: GC patients with high-SLFN11 expression exhibited significantly better survival than those with low-SLFN11 expression, and the significance increased when we selected patients treated with platinum-based chemotherapy. Knockout of SLFN11 and reactivation of SLFN11 in GC cells conferred resistance and sensitivity to platinum, respectively. In GC cells and organoids, long-term treatment with oxaliplatin suppressed SLFN11 expression while imparting drug resistance. The acquired resistance to oxaliplatin was reversed by reactivation of SLFN11 with epigenetic modifying drugs. CONCLUSIONS: This is the first report revealing definitive clinical implications of SLFN11 in the treatment of GC patients and providing novel strategies for the drug selection based on SLFN11 expression.


Assuntos
Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Platina/farmacologia , Neoplasias Gástricas/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Platina/uso terapêutico , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Análise de Sobrevida , Resultado do Tratamento
15.
J Transl Med ; 19(1): 448, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702306

RESUMO

BACKGROUND: Established clinical assessments for detecting dementia risk often require time, cost, and face-to-face meetings. We aimed to develop a Simplified Telephone Assessment for Dementia risk (STAD) (a new screening tool utilizing telephonic interviews to predict dementia risk) and examine the predictive validity of the STAD for the incidence of dementia. METHODS: We developed STAD based on a combination of literature review, statistical analysis, and expert opinion. We selected 12 binary questions on subjective cognitive complaints, depressive symptoms, and lifestyle activities. In the validation study, we used STAD for 4298 community-dwelling older adults and observed the incidence of dementia during the 24-month follow-up period. The total score of STAD ranging from 0 to 12 was calculated, and the cut-off point for dementia incidence was determined using the Youden index. The survival rate of dementia incidence according to the cut-off points was determined. Furthermore, we used a decision-tree model (classification and regression tree, CART) to enhance the predictive ability of STAD for dementia risk screening. RESULTS: The cut-off point of STAD was set at 4/5. Participants scoring ≥ 5 points showed a significantly higher risk of dementia than those scoring ≤ 4 points, even after adjusting for covariates (hazard ratio [95% confidence interval], 2.67 [1.40-5.08]). A decision tree model using the CART algorithm was constructed using 12 nodes with three STAD items. It showed better performance for dementia prediction in terms of accuracy and specificity as compared to the logistic regression model, although its sensitivity was worse than the logistic regression model. CONCLUSIONS: We developed a 12-item questionnaire, STAD, as a screening tool to predict dementia risk utilizing telephonic interviews and confirmed its predictive validity. Our findings might provide useful information for early screening of dementia risk and enable bridging between community and clinical settings. Additionally, STAD could be employed without face-to-face meetings in a short time; therefore, it may be a suitable screening tool for community-dwelling older adults who have negative attitudes toward clinical examination or are non-adherent to follow-up assessments in clinical trials.


Assuntos
Demência , Vida Independente , Idoso , Demência/diagnóstico , Demência/epidemiologia , Humanos , Japão/epidemiologia , Programas de Rastreamento , Inquéritos e Questionários
16.
Gastric Cancer ; 24(6): 1264-1277, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34272617

RESUMO

BACKGROUND: The attainment of drug resistance in gastric cancer (GC) is a problematic issue. Although many studies have shown that cancer stem cells (CSCs) play an important role in the acquisition of drug resistance, there is no clinically available biomarker for predicting oxaliplatin (L-OHP) resistance in relation to CSCs. Organoid technology, a novel 3D cell culture system, allows harboring of patient-derived cancer cells containing abundant CSCs using niche factors in a dish. METHODS: In this study, we established L-OHP-resistant gastric cancer organoids (GCOs) and evaluated their gene expression profile using microarray analysis. We validated the upregulated genes in the L-OHP-resistant GCOs compared to their parental GCOs to find a gene responsible for L-OHP resistance by qRT-PCR, immunohistochemistry, in vitro, and in vivo experiments. RESULTS: We found myoferlin (MYOF) to be a candidate gene through microarray analysis. The results from cell viability assays and qRT-PCR showed that high expression of MYOF correlated significantly with the IC50 of L-OHP in GCOs. Immunohistochemistry of MYOF in GC tissue samples revealed that high expression of MYOF was significantly associated with poor prognosis, T grade, N grade, and lymphatic invasion, and showed MYOF to be an independent prognostic indicator, especially in the GC patients treated with platinum-based chemotherapy. The knockdown of MYOF repressed L-OHP resistance, cell growth, stem cell features, migration, invasion, and in vivo tumor growth. CONCLUSIONS: Our results suggest that MYOF is highly involved in L-OHP resistance and tumor progression in GC. MYOF could be a promising biomarker and therapeutic target for L-OHP-resistant GC cases.


Assuntos
Antineoplásicos/uso terapêutico , Proteínas de Ligação ao Cálcio/metabolismo , Resistencia a Medicamentos Antineoplásicos , Proteínas de Membrana/metabolismo , Proteínas Musculares/metabolismo , Organoides/metabolismo , Oxaliplatina/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Idoso , Técnicas de Cultura de Células em Três Dimensões , Feminino , Humanos , Japão , Masculino , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Análise de Sobrevida
17.
Echocardiography ; 37(6): 928-929, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32437591

RESUMO

A 70-year-old asymptomatic male who had undergone a right nephrectomy for renal pelvic cancer was referred to us with a thrombus in the ascending aorta detected by contrast-enhanced computed tomography after chemotherapy with gemcitabine/cisplatin. Transesophageal echocardiography revealed a 4-cm mobile mural thrombus in the ascending aorta. An emergency thoracotomy for planned aortic root replacement was performed, but the intraoperative epi-aortic ultrasound indicated that the thrombus had disappeared, and it showed prominent spontaneous-echo contrast (SEC) in the ascending aorta. We speculate that vascular endothelium damage due to the cisplatin-based chemotherapy induced the thrombus and SEC in the ascending aorta.


Assuntos
Cardiopatias , Tromboembolia , Trombose , Idoso , Aorta/diagnóstico por imagem , Cisplatino/efeitos adversos , Ecocardiografia Transesofagiana , Humanos , Masculino , Trombose/diagnóstico por imagem
18.
Phys Rev Lett ; 123(9): 090601, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31524449

RESUMO

We investigate the informational aspect of (1+1)-dimensional directed percolation, a canonical model of a nonequilibrium continuous transition to a phase dominated by a single special state called the "absorbing" state. Using a tensor network scheme, we numerically calculate the time evolution of state probability distribution of directed percolation. We find a universal relaxation of Rényi entropy at the absorbing phase transition point as well as a new singularity in the active phase, slightly but distinctly away from the absorbing transition point. At the new singular point, the second-order Rényi entropy has a clear cusp. There we also detect a singular behavior of "entanglement entropy," defined by regarding the probability distribution as a wave function. The entanglement entropy vanishes below the singular point and stays finite above. We confirm that the absorbing state, though its occurrence is exponentially rare in the active phase, is responsible for these phenomena. This interpretation provides us with a unified understanding of time evolution of the Rényi entropy at the critical point as well as in the active phase.

19.
Opt Express ; 26(17): 22197-22207, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30130916

RESUMO

An optical vortex with orbital angular momentum (OAM) can be used to induce microscale chiral structures in various materials. Such chiral structures enable the generation of a nearfield vortex, i.e. nearfield OAM light on a sub-wavelength scale, thereby leading to further nanoscale mass-transport. We report on the formation of a nanoscale chiral surface relief in azo-polymers due to nearfield OAM light. The resulting nanoscale chiral relief exhibits a diameter of ca. 400 nm, which corresponds to less than 1/5-1/6th of the original chiral structure (ca. 2.1 µm). Such a nanoscale chiral surface relief is established by the simple irradiation of uniform visible plane-wave light with an intensity of <500 mW/cm2.

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