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1.
Opt Lett ; 48(17): 4590-4592, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37656562

RESUMO

For the practical implementation of microdisk resonators as active nanophotonic devices, it is essential that they can be electrically driven. However, it is difficult to inject current in such small-scale devices without severely degrading their optical properties. We demonstrate the successful fabrication of an electrically injected microdisk based on Eu-doped GaN, in which an SiO2 spacer is used to prevent the interaction of the metal contact with the optical resonances. The microdisk shows Eu-related emission upon electrical injection and from the observed resonance peak, a cavity quality (Q)-factor of 3400 is concluded.

2.
Occup Med (Lond) ; 73(3): 161-166, 2023 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-36893360

RESUMO

BACKGROUND: No easy-to-use fall risk assessment tools have been devised to assess occupational fall risk in older workers. AIMS: To develop an Occupational Fall Risk Assessment Tool (OFRAT) and report its predictive validity and reliability in older workers. METHODS: The baseline fall risk assessment was completed by 1113 participants aged ≥60 years who worked ≥4 days/month in Saitama, Japan. Participants were followed up for falls during occupational activities for 1 year, and 30 participants were assessed twice for test-retest reliability. The following assessment measures were summed to form the OFRAT risk score: older age, male sex, history of falls, physical work participation, diabetes, use of medications increasing fall risk, reduced vision, poor hearing, executive dysfunction and slow stepping. The scores were then classified into four grades (0-2 points: very low, 3 points: low, 4 points: moderate and ≥5 points: high). RESULTS: During follow-up, 112 participants fell 214 times during work. The negative binomial regression model showed that participants with higher grades had a higher incidence rate ratio [95% confidence interval] for falls than those with very low grades (low: 1.64 [1.08-2.47], moderate: 4.23 [2.82-6.34] and high: 6.12 [3.83-9.76]). The intraclass correlation coefficient for risk score was 0.86 [0.72-0.93], and the weighted kappa coefficient for grade assessment was 0.74 [0.52-0.95]. CONCLUSIONS: The OFRAT is a valid and reliable tool for estimating the occupational fall risk in older workers. It may assist occupational physicians implement strategies to prevent falls in this group.


Assuntos
Exame Físico , Humanos , Masculino , Idoso , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco
3.
Br J Surg ; 108(8): 976-982, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34155509

RESUMO

BACKGROUND: Use of neoadjuvant therapy for elderly patients with pancreatic cancer has been debatable. With FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, oxaliplatin) or gemcitabine plus nab-paclitaxel (GnP) showing tremendous effects in improving the overall survival of patients with borderline resectable and locally advanced pancreatic cancer, there is no definitive consensus regarding the use of this regimen in the elderly. METHODS: This study evaluated the eligibility of elderly patients with borderline resectable or locally advanced pancreatic cancer for neoadjuvant therapy. Patients registered in the database of pancreatic cancer at the University of Colorado Cancer Center, who underwent neoadjuvant treatment between January 2011 and March 2019, were separated into three age groups (less than 70, 70-74, 75 or more years) and respective treatment outcomes were compared. RESULTS: The study included 246 patients with pancreatic cancer who underwent neoadjuvant treatment, of whom 154 and 71 received chemotherapy with FOLFIRINOX and GnP respectively. Among these 225 patients, 155 were younger than 70 years, 36 were aged 70-74 years, and 34 were aged 75 years or older. Patients under 70 years old received FOLFIRINOX most frequently (124 of 155 versus 18 of 36 aged 70-74 years, and 12 of 34 aged 75 years or more; P < 0.001). Resectability was similar among the three groups (60.0, 58.3, and 55.9 per cent respectively; P = 0.919). Trends towards shorter survival were observed in the elderly (median overall survival time 23.6, 18.0, and 17.6 months for patients aged less than 70, 70-74, and 75 or more years respectively; P = 0.090). After adjusting for co-variables, age was not a significant predictive factor. CONCLUSION: The safety and efficacy of multiagent chemotherapy in patients aged 75 years or over were similar to those in younger patients. Modern multiagent regimens could be a safe and viable treatment option for clinically fit patients aged at least 75 years.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Pancreáticas/terapia , Cooperação do Paciente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Pancreáticas/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento , Estados Unidos/epidemiologia
4.
Opt Lett ; 45(14): 3973-3976, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32667331

RESUMO

GaN-based micro-LEDs typically suffer from a size-dependent efficiency due to the relatively long carrier lifetime and sidewall-related recombination effects. We demonstrate that for red-emitting Eu-doped GaN, sidewall-related recombination is hardly an issue for emission efficiency. We determine the photoluminescence quantum efficiency (PL QE) of Eu-related emission as a function of the size of square structures ranging from 3 to 192 µm. With the support of finite-difference time-domain simulations, we show that the light extraction efficiency and material losses are responsible for the decrease in PL QE for large sizes. For sizes smaller than 24 µm, there is an influence of the sidewall-related non-radiative recombination of carriers on the PL QE; however, it is only minor as a result of the limited carrier diffusion lengths in the Eu-doped material. These properties combined with the high efficiency of luminescence indicate the potential of this material for micro-LED applications.

5.
Phys Rev Lett ; 124(2): 025002, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-32004031

RESUMO

The transition between isotope-mixing and nonmixing states in hydrogen-deuterium mixture plasmas is observed in the isotope (hydrogen and deuterium) mixture plasma in the Large Helical Device. In the nonmixing state, the isotope density ratio profile is nonuniform when the beam fueling isotope species differs from the recycling isotope species and the profile varies significantly depending on the ratio of the recycling isotope species, although the electron density profile shape is unchanged. The fast transition from nonmixing state to isotope-mixing state (nearly uniform profile of isotope ion density ratio) is observed associated with the change of electron density profile from peaked to hollow profile by the pellet injection near the plasma periphery. The transition from nonmixing to isotope-mixing state strongly correlates with the increase of turbulence measurements and the transition of turbulence state from TEM to ion temperature gradient is predicted by gyrokinetic simulation.

8.
J Oral Rehabil ; 45(8): 598-604, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29761827

RESUMO

Clinicians' evaluations of older adults sometimes reveal inconsistencies between objective and subjective dental status. This study investigated which factors contribute both to good objective masticatory function (OMF) and the poor subjective masticatory function (SMF) that often becomes a clinical issue. Study participants included 635 elderly community-dwelling Japanese adults who underwent a comprehensive geriatric health examination in 2012. SMF was assessed with a question from the Kihon Checklist on eating difficulties (poor or good). OMF was assessed by a colour-changing gum (poor or good). Also investigated were age, sex, depressive symptoms, instrumental activities of daily living (I-ADLs), number of people who joined the participant at dinner, grip strength, usual walking speed, number of remaining teeth, number of functional teeth and their occlusal force. The group with good OMF and good SMF, defined as group 1, and the group with good OMF but poor SMF, group 2, were compared. Logistic regression analyses confirmed that the number of remaining and functional teeth participants had was statistically unrelated to differences between OMF and SMF. Instead, differences were related to stronger depressive symptoms (OR = 1.67, CI = 1.14-2.44), less ability to conduct I-ADL activities (OR = 0.73, CI = 0.59-0.91), slower usual walking speeds (OR = 0.18, CI = 0.06-0.58) and less occlusal force (OR = 0.99, CI = 0.99-1.00). Depressive symptoms, I-ADLs, and physical function are shown to be significantly related to divergence between objective and subjective masticatory function in elderly Japanese. This suggests that dissociations between objective and subjective dental evaluations of elderly adults indicate need for assessment of their mental and physical function.


Assuntos
Depressão/epidemiologia , Ingestão de Alimentos/fisiologia , Avaliação Geriátrica , Mastigação/fisiologia , Saúde Bucal/estatística & dados numéricos , Atividades Cotidianas , Idoso , Força de Mordida , Estudos Transversais , Feminino , Força da Mão/fisiologia , Humanos , Vida Independente , Japão , Masculino
9.
Spinal Cord ; 55(10): 940-943, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28555661

RESUMO

STUDY DESIGN: A retrospective, consecutive case series. OBJECTIVES: The relationship between dysphagia and acute cervical spinal cord injury (CSCI) has been recently reported; however, the cause and mechanism of dysphagia are still not well understood. No definitive factors have yet been established according to multivariate analysis. The objective is to elucidate the incidence and risk factors of dysphagia in patients with acute CSCI. SETTING: Spinal Injuries Center, Fukuoka, Japan. METHODS: A total of 298 patients with acute CSCI, who were evaluated for neurological impairment within 3 days after injury, were reviewed. CSCI patients with tube dependence due to obvious aspiration after injury were defined as having dysphagia. The factors postulated to increase the risk for dysphagia, including the patient's age, sex, American Spinal Injury Association (ASIA) impairment scale at 3 days after injury, level of injury, tracheostomy and operative treatment, were analyzed using a multiple logistic regression model. RESULTS: Of 298 patients, 21 were suffering from severe dysphagia after acute CSCI (7.0%). Of these 21 patients, 12 (57%) had CSCI at the C3-C4 level. Multivariable logistic regression analysis revealed that old age (>72 years), severe ASIA impairment scale (A or B) and presence of tracheostomy were significant risk factors of dysphagia. Level of injury ⩾C3-C4 was not a significant risk factor after adjustment for several potential confounders. CONCLUSION: The incidence of severe dysphagia associated with aspiration was 7%. Old age, severe paralysis and presence of tracheostomy may be the risk factors for dysphagia. The risk for dysphagia should be evaluated to prevent aspiration pneumonia.


Assuntos
Medula Cervical/lesões , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/epidemiologia , Doença Aguda , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Vértebras Cervicais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Traqueostomia , Adulto Jovem
10.
Br J Cancer ; 115(4): 411-9, 2016 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-27415010

RESUMO

BACKGROUND: We aimed to analyse clinical and gene expression profiles to predict pathologic complete response and disease-free survival using two consecutive, prospective, preoperative chemotherapy trial cohorts. METHODS: Clinicopathological and gene expression data were evaluated in a cohort from two consecutive phase II preoperative studies that included patients with stage IIA-IIIC breast cancer of all subtypes. Analysed specimens were obtained before preoperative chemotherapy, and cDNA microarray analyses were performed using the Affymetrix Gene Chip U133 plus 2.0. RESULTS: Between December 2005 and December 2010, 122 patients were analysed. The pathologic complete response rate was significantly higher in HER2+ and HR-/HER2- cancers. Age, pathologic complete response, HR-/HER2- status, and lymph node positivity (⩾4) were significant poor prognostic factors for disease-free survival. For the cDNA microarray analyses, sufficient tumour samples were available from 78 of the 107 patients (73%). An 8-gene signature predictive of pathologic complete response and a 17-gene signature predictive of prognosis were identified. Patients were categorised into low-risk (n=45) and high-risk groups (n=33) (HR 70.0, P=0.004). CONCLUSIONS: This study yielded preliminary data on the expression of specific genes predicting pathologic complete response and disease-free survival in a cohort of chemonaïve breast cancer patients. Further validation may distinguish those who would benefit most from perioperative chemotherapy as well as those needing further intervention.


Assuntos
Neoplasias da Mama/genética , Carcinoma/genética , RNA Mensageiro/metabolismo , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma/tratamento farmacológico , Carcinoma/metabolismo , Carcinoma/patologia , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Docetaxel , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Prognóstico , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Taxoides/administração & dosagem , Análise Serial de Tecidos , Transcriptoma , Trastuzumab/administração & dosagem , Resultado do Tratamento , Adulto Jovem
11.
Ann Oncol ; 27(12): 2242-2250, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27765756

RESUMO

BACKGROUND: The human IgG4 monoclonal antibody nivolumab targets programmed cell death-1 (PD-1) and promotes antitumor response by blocking the interaction of PD-1 with its ligands. This single-center phase Ib study investigated the tolerability, safety, and pharmacokinetics of nivolumab combined with standard chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients who had stage IIIB without indication for definitive radiotherapy, stage IV, or recurrent NSCLC were eligible. Regimens were nivolumab 10 mg/kg + gemcitabine/cisplatin (arm A), pemetrexed/cisplatin (arm B), paclitaxel/carboplatin/bevacizumab (arm C), or docetaxel (arm D). Regimens A, B, and D were repeated every 3 weeks for up to four cycles and regimen C was repeated for up to six cycles; nivolumab alone (arm A), with pemetrexed (arm B), bevacizumab (arm C), or docetaxel (arm D) was continued every 3 weeks as maintenance therapy until disease progression or unacceptable toxicity. Dose-limiting toxicity (DLT) was evaluated during the first treatment cycle. RESULTS: As of March 2014, six patients were enrolled in each arm. The combination of nivolumab 10 mg/kg and chemotherapy was well tolerated. DLT was observed in only one patient in arm A (alanine aminotransferase increased). Select adverse events (those with a potential immunologic cause) of any grade were observed in six, four, six, and five patients in arms A, B, C, and D, respectively. Three, three, six, and one patient achieved partial response while median progression-free survival was 6.28, 9.63 months, not reached, and 3.15 months in arms A, B, C, and D, respectively. CONCLUSIONS: Combination of nivolumab 10 mg/kg and chemotherapy showed an acceptable toxicity profile and encouraging antitumor activity in patients with advanced NSCLC. CLINICAL TRIALS NUMBER: Japanese Pharmaceutical Information Center Clinical Trials Information (JapicCTI)-132071.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Docetaxel , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Estadiamento de Neoplasias , Nivolumabe , Paclitaxel/administração & dosagem , Pemetrexede/administração & dosagem , Taxoides/administração & dosagem , Gencitabina
12.
Dis Esophagus ; 29(3): 278-84, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25604848

RESUMO

Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Although the mechanisms of this association have not been fully elucidated, nighttime reflux plays a central role. However, the detailed characteristics of nighttime reflux occurring during sleep are unknown. The aim of the present study was to examine the characteristics and prevalence of nighttime reflux in the natural sleep environment of GERD patients. Seventeen patients experiencing daily moderate-to-severe heartburn and/or regurgitation were studied using multichannel intraluminal impedance pH monitoring and electroencephalography off-proton pump inhibitor treatment. Nighttime reflux was divided based on reflux type (liquid or gas), acidity (acidic, weakly acidic, or alkaline) and extent (distal only or proximal migration) according to the standard criteria. Nighttime phases were divided as follows: recumbent-awake before falling asleep, nonrapid eye movement, rapid eye movement, awakening from sleep, and post-awakening in the morning. Among 184 nighttime refluxes, 43 (23%) occurred during recumbent-awake before falling asleep, 28 (15%) during nonrapid eye movement, 14 (8%) during rapid eye movement, 86 (46%) during awakening from sleep, and 13 (7%) during post-awakening in the morning. Liquid reflux was more common in awakening during sleep (92%), nonrapid eye movement (100%), and rapid eye movement (100%) compared with awakening before falling asleep (68%). The prevalence of proximal migration was significantly lower in nonrapid eye movement and rapid eye movement than in the other phases. There were no differences in acidity and bolus clearance time among the phases. Thirteen (65%) of 20 events with GERD symptoms had nighttime reflux, suggesting that only 7.1% (13 of 184) of nighttime refluxes were symptomatic. Nighttime reflux was observed in 48 (11%) of 425 awakening episodes during sleep. Different reflux patterns at each phase during nighttime might explain the pathogenesis of GERD and its related sleep disturbances.


Assuntos
Eletroencefalografia/métodos , Monitoramento do pH Esofágico/métodos , Refluxo Gastroesofágico/fisiopatologia , Transtornos do Sono-Vigília/diagnóstico , Sono/fisiologia , Adulto , Idoso , Ritmo Circadiano , Impedância Elétrica , Feminino , Refluxo Gastroesofágico/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Sono-Vigília/etiologia
13.
J Radiol Prot ; 36(1): 49-66, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26613195

RESUMO

Twelve high schools in Japan (of which six are in Fukushima Prefecture), four in France, eight in Poland and two in Belarus cooperated in the measurement and comparison of individual external doses in 2014. In total 216 high-school students and teachers participated in the study. Each participant wore an electronic personal dosimeter 'D-shuttle' for two weeks, and kept a journal of his/her whereabouts and activities. The distributions of annual external doses estimated for each region overlap with each other, demonstrating that the personal external individual doses in locations where residence is currently allowed in Fukushima Prefecture and in Belarus are well within the range of estimated annual doses due to the terrestrial background radiation level of other regions/countries.


Assuntos
Acidente Nuclear de Fukushima , Doses de Radiação , Monitoramento de Radiação , Estudantes , Feminino , França , Humanos , Masculino , Polônia , República de Belarus
14.
Br J Cancer ; 112(3): 547-55, 2015 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-25562433

RESUMO

BACKGROUND: Myxoid liposarcoma (MLS) is the second most common subtype of liposarcoma, and metastasis occurs in up to one-third of cases. However, the mechanisms of invasion and metastasis remain unclear. Tumour-associated macrophages (TAMs) have important roles in tumour invasion, metastasis, and/or poor prognosis. The aim of this study was to investigate the relationship between TAMs and MLS. METHODS: Using 78 primary MLS samples, the association between clinical prognosis and macrophage infiltration was evaluated by immunochemistry. The effects of macrophages on cell growth, cell motility, and invasion of MLS cell lines were investigated in vitro. In addition, clinicopathological factors were analysed to assess their prognostic implications in MLS. RESULTS: Higher levels of CD68-positive macrophages were associated with poorer overall survival in MLS samples. Macrophage-conditioned medium enhanced MLS cell motility and invasion by activating epidermal growth factor receptor (EGFR), with the key ligand suggested to be heparin-binding EGF-like growth factor (HB-EGF). The phosphoinositide 3-kinase/Akt pathway was mostly involved in HB-EGF-induced cell motility and invasion of MLS. The expression of phosphorylated EGFR in MLS clinical samples was associated with macrophage infiltration. In addition, more significant macrophage infiltration was associated with poor prognosis even in multivariate analysis. CONCLUSIONS: Macrophage infiltration in MLS predicts poor prognosis, and the relationship between TAMs and MLS may be a new candidate for therapeutic targets of MLS.


Assuntos
Movimento Celular , Lipossarcoma Mixoide/patologia , Macrófagos/patologia , Animais , Células Cultivadas , Receptores ErbB/metabolismo , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/metabolismo , Humanos , Camundongos , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia , Células U937
15.
Surg Today ; 45(5): 618-24, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25113071

RESUMO

PURPOSE: Recent advances in laparoscopic surgical technology have made it possible to perform advanced high-level surgery, such as lymph node dissection for malignancy. Grasping the anatomy during such procedures is important for a safe operation. We have developed a new image information system that provides three-dimensional (3D) reconstructed CT images synchronized with the motion of the laparoscope. This study assesses this new navigation system. METHODS: Enhanced CT using a custom-made software program can provide 3D angiography images reconstructed as a laparoscopic view. A motion sensor mounted on the laparoscope can detect the direction angle of the laparoscope. The real-time rendered 3D CT images are synchronized with the laparoscopic video images according to the motion of the scope. These 3D CT images are projected on another monitor close to the laparoscopic video monitor. Lymph node dissection can be performed with the help of the real-time navigation system that provides a detailed 3D view of the vasculature. RESULTS: Ten laparoscopic gastrectomies were performed using this navigation system. Real-time intraoperative navigation of the vasculature was available, allowing for an excellent surgical outcome. No complications occurred in this series. CONCLUSION: Our intraoperative navigation system allows for safe laparoscopic gastric lymph node dissection.


Assuntos
Gastrectomia/métodos , Imageamento Tridimensional/métodos , Laparoscopia/métodos , Excisão de Linfonodo/métodos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Cirurgia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Software , Resultado do Tratamento
16.
Ann Oncol ; 25(10): 1973-1979, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25009009

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) patients are a poor prognostic subgroup, and currently, there is no biomarker for targeted therapy. PATIENTS AND METHODS: Tissue samples were obtained from 75 TNBC patients with lymph-node metastases who had received adjuvant chemotherapy. We examined 11 biomarkers, including PIK3CA and AKT1mutation, with regard to event-free survival (EFS) and overall survival (OS) of patients. RESULTS: In the tumor tissues, phospho-AKT (pAKT) expression was significantly related to HER4 expression. Expression of each of these biomarkers was significantly related to longer EFS (P = 0.024 and 0.03, respectively). pERK expression was also a good prognostic factor regarding EFS and OS in TNBC (P = 0.002 and 0.006, respectively). We also identified a correlation between epidermal growth factor receptor positivity and insulin-like growth factor receptor type 1 positivity (P = 0.001). pERK and T-stage (1-3 versus >3) were independent good prognostic factors by multivariate analysis. CONCLUSIONS: We determined that tumors expressing pAKT or pERK are a good prognostic subtype in node-positive TNBC. Different targeted therapies may be necessary for TNBC that involves activation of PI3K/AKT or MAPK pathways.


Assuntos
Fosfatidilinositol 3-Quinases/biossíntese , Prognóstico , Proteínas Proto-Oncogênicas c-akt/biossíntese , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/terapia , Adulto , Idoso , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Classe I de Fosfatidilinositol 3-Quinases , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Estadiamento de Neoplasias , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Receptor ErbB-2/genética , Receptor ErbB-4/biossíntese , Neoplasias de Mama Triplo Negativas/patologia
17.
Curr Oncol ; 21(2): 84-90, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24764697

RESUMO

BACKGROUND: Prediction of prognosis is important for patients so that they can make the most of the rest of their lives. Oncologists could predict survival, but the accuracy of such predictions is unclear. METHODS: In this observational prospective cohort study, 14 oncologists treating 9 major adult solid malignancies were asked to complete questionnaires predicting survival based on performance status, oral intake, and other clinical factors when patients experienced progressive disease after standard chemotherapies. Clinically predicted survival (cps) was calculated by the oncologists from the date of progressive disease to the predicted date of death. Actual survival (as) was compared with cps using Kaplan-Meier survival curves, and factors affecting inaccurate prediction were determined by logistic regression analysis. The prediction of survival time was considered accurate when the cps/as ratio was between 0.67 and 1.33. RESULTS: The study cohort consisted of 75 patients. Median cps was 120 days (interquartile range: 60-180 days), and median as was 121 days (interquartile range: 40-234 days). The participating oncologists accurately predicted as within a 33% range 36% of the time; the survival time was overestimated 36% of time and underestimated 28% of the time. The factors affecting the accuracy of the survival estimate were the experience of the oncologist, patient age, and information given about the palliative care unit. CONCLUSIONS: Prediction of cps was accurate for just slightly more than one third of all patients in this study. Additional investigation of putative prognostic factors with a larger sample size is warranted.

18.
ESMO Open ; 9(4): 102981, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38613908

RESUMO

BACKGROUND: Comprehensive genome profiling (CGP) serves as a guide for suitable genomically matched therapies for patients with cancer. However, little is known about the impact of the timing and types of cancer on the therapeutic benefit of CGP. MATERIALS AND METHODS: A single hospital-based pan-cancer prospective study (TOP-GEAR; UMIN000011141) was conducted to examine the benefit of CGP with respect to the timing and types of cancer. Patients with advanced solid tumors (>30 types) who either progressed with or without standard treatments were genotyped using a single CGP test. The subjects were followed up for a median duration of 590 days to examine therapeutic response, using progression-free survival (PFS), PFS ratio, and factors associated with therapeutic response. RESULTS: Among the 507 patients, 62 (12.2%) received matched therapies with an overall response rate (ORR) of 32.3%. The PFS ratios (≥1.3) were observed in 46.3% (19/41) of the evaluated patients. The proportion of subjects receiving such therapies in the rare cancer cohort was lower than that in the non-rare cancer cohort (9.6% and 17.4%, respectively; P = 0.010). However, ORR of the rare cancer patients was higher than that in the non-rare cancer cohort (43.8% and 20.0%, respectively; P = 0.046). Moreover, ORR of matched therapies in the first or second line after receiving the CGP test was higher than that in the third or later lines (62.5% and 21.7%, respectively; P = 0.003). Rare cancer and early-line treatment were significantly and independently associated with ORR of matched therapies in multivariable analysis (P = 0.017 and 0.004, respectively). CONCLUSION: Patients with rare cancer preferentially benefited from tumor mutation profiling by increasing the chances of therapeutic response to matched therapies. Early-line treatments after profiling increase the therapeutic benefit, irrespective of tumor types.


Assuntos
Neoplasias , Medicina de Precisão , Humanos , Neoplasias/genética , Neoplasias/tratamento farmacológico , Feminino , Medicina de Precisão/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Adulto , Idoso de 80 Anos ou mais , Intervalo Livre de Progressão , Adulto Jovem , Doenças Raras/genética , Doenças Raras/tratamento farmacológico , Genômica/métodos
19.
Nat Genet ; 21(4): 396-9, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10192390

RESUMO

Plasma iron circulates bound to transferrin (Trf), which solubilizes the ferric ion and attenuates its reactivity. Diferric Trf interacts with cell-surface Trf receptor (Trfr) to undergo receptor-mediated endocytosis into specialized endosomes. Endosomal acidification leads to iron release, and iron is transported out of the endosome through the activity of divalent metal transporter 1 (DMT1, formerly Nramp2), a transmembrane iron transporter that functions only at low pH. Trf and Trfr then return to the cell surface for reuse, completing a highly efficient cycle. Although the Trf cycle is assumed to be the general mechanism for cellular iron uptake, this has not been validated experimentally. Mice with hypotransferrinaemia (hpx) have little or no plasma Trf. They have severe anaemia, indicating that the Trf cycle is essential for iron uptake by erythroid cells. Other hpx tissues, however, are generally normal, and there is a paradoxical increase in intestinal iron absorption and iron storage. To test the hypothesis that the Trf cycle has unique importance for erythropoiesis, we disrupted the Trfr gene in mice. This results in elimination of the Trf cycle, but leaves other Trf functions intact. Mice lacking Trfr have a more severe phenotype than hpx mice, affecting both erythropoiesis and neurologic development. Furthermore, haploinsufficiency for Trfr results in impaired erythroid development and abnormal iron homeostasis.


Assuntos
Eritrócitos/fisiologia , Sistema Nervoso/embriologia , Receptores da Transferrina/genética , Anemia/genética , Anemia/patologia , Animais , Embrião de Mamíferos/química , Embrião de Mamíferos/patologia , Eritropoese/genética , Homeostase , Homozigoto , Absorção Intestinal , Ferro/sangue , Ferro/metabolismo , Camundongos , Camundongos Endogâmicos , Camundongos Mutantes , Reticulócitos/metabolismo , Transferrina/deficiência , Transferrina/genética
20.
J Nutr Health Aging ; 27(11): 946-952, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37997714

RESUMO

OBJECTIVES: Accumulating evidence from cross-sectional studies suggests that the serum creatinine-to-cystatin C ratio (CCR) may be a useful biomarker for sarcopenia. This study aimed to assess the cross-sectional and longitudinal associations of CCR with sarcopenia and its parameters in community-dwelling older adults. DESIGN: Cross-sectional and longitudinal study. SETTING AND PARTICIPANTS: This 6-year prospective cohort study included the repeated measurement data from 1,253 Japanese residents (662 males and 591 females) aged ≥65 years who underwent medical checkups in Kusatsu and Hatoyama, Japan. A total of 4,421 observations were collected. MEASUREMENTS: The CCR was grouped into quartiles by sex (Q1-Q4) using Q4 as the reference category. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 algorithm. Skeletal muscle mass index (SMI) measured using segmental multifrequency bioelectrical impedance analysis, handgrip strength (HGS), usual gait speed (UGS), and maximal gait speed (MGS) were measured repeatedly as sarcopenia parameters. The association of the CCR with changes in sarcopenia, SMI, HGS, UGS, and MGS during the 6-year period were analyzed using a generalized linear mixed-effects model. RESULTS: The prevalence of sarcopenia at baseline was 13.1% (11.9% in males and 14.5% in females). In a cross-sectional analysis, the CCR quartile was inversely associated with sarcopenia and was positively associated with SMI, HGS, and MGS (P for trend < 0.001). In a longitudinal analysis during the 6 years, a significant increase in sarcopenia in Q2 (B = 1.1% point/year; P = 0.026 for group-by-time interaction) and significant declines in SMI (B = -0.01 kg/m2/year; P = 0.044 for group-by-time interaction) and MGS (B = -0.008 m/sec/year; P = 0.041 for group-by-time interaction) in Q1 were observed compared with Q4. However, the dose-response relationship was significant only for MGS (P = 0.033 for trend). No significant group-by-time interaction was observed for HGS. CCR was not significantly associated with UGS either cross-sectionally or longitudinally. CONCLUSIONS: CCR is a useful biomarker regarding the status of sarcopenia. It may be used for sarcopenia screening even in older adults whose physical function is difficult to assess. However, further longitudinal studies are needed to determine whether CCR can be a predictor of future sarcopenia.


Assuntos
Sarcopenia , Masculino , Feminino , Humanos , Idoso , Sarcopenia/epidemiologia , Sarcopenia/diagnóstico , Estudos Longitudinais , Creatinina , Estudos Transversais , Força da Mão , Estudos Prospectivos , Cistatina C , Biomarcadores
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