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1.
Odontology ; 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38703257

RESUMO

The present study aimed to elucidate the correlation between the uptake of 11C-methionine (MET) by a primary tumor and the survival of patients with oral squamous cell carcinoma (OSCC). This study enrolled 31 patients who underwent radical surgery for OSCC. The patients underwent pretreatment MET-positron emission tomography (PET) scanning. We analyzed correlations between the maximum standardized uptake value (SUVmax) of MET-PET in a primary tumor and the clinicopathological features. Further, we compared overall survival (OS), disease-specific survival (DSS), and loco-regional recurrence (LRR) rates between the two groups according to SUVmax of MET-PET. SUVmax of MET-PET in a primary tumor was higher in patients with advanced T-classification and advanced clinical stage, with significant differences (P = 0.001 and P = 0.016, respectively). The patients with SUVmax of MET-PET ≥ 4.4 showed significantly lower DSS rates and higher LRR rates than those with SUVmax of < 4.4 (P = 0.015 and P = 0.016, respectively). SUVmax of MET-PET and OS rates showed no significant correlation (P = 0.073). The present study revealed that SUVmax of MET-PET may predict clinical outcomes and prognosis in patients with OSCC who underwent radical surgery.

2.
Gastrointest Endosc ; 97(4): 722-731.e7, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36343675

RESUMO

BACKGROUND AND AIMS: The need for mastering standard imaging techniques for convex EUS in the biliopancreatic regions has been increasing; however, large variations in the aptitude for achieving EUS competency hinder expert development. Therefore, we investigated the factors influencing the achievement of expert competency in EUS using a new assessment tool for multiple imaging items. METHODS: Between January 2018 and February 2022, 3277 consecutive EUS procedures conducted by 5 beginners (EUS procedures <250), 7 intermediate trainees (250-749), and 2 experts (≥750) were prospectively evaluated. Immediately after each EUS procedure, the success or failure of imaging for each item was recorded using a newly developed EUS assessment tool that requires 17 items to be photographed. After correcting for missing values using multiple imputation, learning curves of EUS scores were created, and a competency was set based on expert scores. Finally, a comparative analysis between high and low performers was performed to extract factors influencing EUS scores. RESULTS: Although 3 of 7 intermediates (43%; mean, 317 cases) achieved competency, none of the beginners achieved competency. During a comparative analysis, although no significant difference in the number of EUS procedures performed was observed between the high and low performers, the former had significantly higher scores in the written test (theoretical knowledge). CONCLUSIONS: Our results showed that theoretical knowledge, rather than the number of EUS cases, may be a possible influencing factor for distinguishing high and low performers after treating 250 cases. (Clinical trial registration number: UMIN 000043271.).


Assuntos
Competência Clínica , Curva de Aprendizado , Humanos , Estudos Prospectivos , Endossonografia/métodos
3.
Surg Endosc ; 35(12): 6696-6707, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33258029

RESUMO

BACKGROUND: Post-ERCP pancreatitis (PEP) with trans-papillary approach remains a major issue, and the multi-factorial etiology can lead to the development of unpredictable PEP. Therefore, the early identification of PEP is highly desirable to assist with the health cost containment, the reduction in unnecessary admissions, earlier appropriate primary care, and intensive care for preventing progression of severe pancreatitis. This study aimed to establish a simplified predictive scoring system for PEP. METHODS: Between January 1, 2012, and December 31, 2019, 3362 consecutive trans-papillary ERCP procedures were retrospectively analyzed. Significant risk factors were extracted by univariate, multivariate, and propensity score analyses, and the probability of PEP in the combinations of each factor were quantified using propensity score analysis. The results were internally validated using bootstrapping resampling. RESULTS: In the scoring system with four stratifications using combinations of only five extracted risk factors, the very high-risk group showed 28.79% (95% confidence interval [CI], 18.30%-41.25%; P < 0.001) in the predicted incidence rate of PEP, and 9.09% (95% CI, 3.41%-18.74%; P < 0.001) in that of severe PEP; although the adjusted prevalence revealed 3.74% in PEP and 0.90% in severe PEP, respectively. The prediction model had an area under the curve of 0.86 (95% CI, 0.82-0.89) and the optimism-corrected model as an internal validation had an area under the curve of 0.81 (95% CI, 0.77-0.86). CONCLUSIONS: We established and validated a simplified predictive scoring system for PEP using five risk factors immediately after ERCP to assist with the early identification of PEP.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Pancreatite , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Humanos , Pancreatite/etiologia , Pancreatite/prevenção & controle , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco
4.
J Card Fail ; 26(8): 685-693, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31533068

RESUMO

BACKGROUND: Skeletal muscle is quantitatively and qualitatively impaired in patients with heart failure (HF), which is closely linked to lowered exercise capacity. Ultrasonography (US) for skeletal muscle has emerged as a useful, noninvasive tool to evaluate muscle quality and quantity. Here we investigated whether muscle quality based on US-derived echo intensity (EI) is associated with exercise capacity in patients with HF. METHODS AND RESULTS: Fifty-eight patients with HF (61 ± 12 years) and 28 control subjects (58 ± 14 years) were studied. The quadriceps femoris echo intensity (QEI) was significantly higher and the quadriceps femoris muscle thickness (QMT) was significantly lower in the patients with HF than the controls (88.3 ± 13.4 vs 81.1 ± 7.5, P= .010; 5.21 ± 1.10 vs 6.54 ±1.34 cm, P< .001, respectively). By univariate analysis, QEI was significantly correlated with age, peak oxygen uptake (VO2), and New York Heart Association class in the HF group. A multivariable analysis revealed that the QEI was independently associated with peak VO2 after adjustment for age, gender, body mass index, and QMT: ß-coefficient = -11.80, 95%CI (-20.73, -2.86), P= .011. CONCLUSION: Enhanced EI in skeletal muscle was independently associated with lowered exercise capacity in HF. The measurement of EI is low-cost, easily accessible, and suitable for assessment of HF-related alterations in skeletal muscle quality.


Assuntos
Insuficiência Cardíaca , Índice de Massa Corporal , Tolerância ao Exercício , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Músculo Esquelético/diagnóstico por imagem , Consumo de Oxigênio , Ultrassonografia
5.
Cardiovasc Diabetol ; 19(1): 142, 2020 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-32950064

RESUMO

BACKGROUND: Although type 2 diabetes mellitus (T2DM) is one of the most frequent comorbidities in patients with chronic heart failure (CHF), the effects of T2DM on the exercise capacity of CHF patients are fully unknown. Here, we tested the hypothesis that the coexistence of T2DM lowers CHF patients' peak aerobic capacity. METHODS: We retrospectively analyzed the cases of 275 Japanese CHF patients with non-reduced ejection fraction (left ventricular ejection fraction [LVEF] ≥ 40%) or reduced EF (LVEF < 40%) who underwent cardiopulmonary exercise testing. We divided them into diabetic and nondiabetic groups in each CHF cohort. RESULTS: The mean peak oxygen uptake (VO2) value was 16.87 mL/kg/min in the non-reduced LVEF cohort and 15.52 mL/kg/min in the reduced LVEF cohort. The peak VO2 was lower in the diabetics versus the nondiabetics in the non-reduced LVEF cohort with the mean difference (95% confidence interval [95% CI]) of - 0.93 (- 1.82 to - 0.04) mL/kg/min and in the reduced LVEF cohort with the mean difference of - 1.05 (- 1.96 to - 0.15) mL/kg/min, after adjustment for age-squared, gender, anemia, renal function, LVEF, and log B-type natriuretic peptide (BNP). The adjusted VO2 at anaerobic threshold (AT), a submaximal aerobic capacity, was also decreased in the diabetic patients with both non-reduced and reduced LVEFs. Intriguingly, the diabetic patients had a lower adjusted peak O2 pulse than the nondiabetic patients in the reduced LVEF cohort, but not in the non-reduced LVEF cohort. A multivariate analysis showed that the presence of T2DM was an independent predictor of lowered peak VO2 in CHF patients with non-reduced LVEF and those with reduced LVEF. CONCLUSIONS: T2DM was associated with lowered peak VO2 in CHF patients with non-reduced or reduced LVEF. The presence of T2DM has a negative impact on CHF patients' exercise capacity, and the degree of impact is partly dependent on their LV systolic function.


Assuntos
Limiar Anaeróbio/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Consumo de Oxigênio/fisiologia , Adulto , Idoso , Cardiomiopatia Dilatada , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Tolerância ao Exercício , Feminino , Insuficiência Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica , Volume Sistólico
6.
BMC Cancer ; 19(1): 52, 2019 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-30634950

RESUMO

BACKGROUND: Cancers of unknown primary origin (CUPs) are reported to be the 3-4th most common causes of cancer death. Recent years have seen advances in mutational analysis and genomics profiling. These advances could improve accuracy of diagnosis of CUPs and might improve the prognosis of patients with CUPs. CASE PRESENTATION: A 76-year old male with an adenocarcinoma of unknown primary origin in the lung presented with another tumor of the palate mucosa. The tumor cells in the pleural effusion were all negative for immunohistochemical markers (TTF-1 and Napsin A) and lung-specific oncogenic driver alterations (EGFR mutation and ALK translocation). The tumor of the palate mucosa was likewise identified as an adenocarcinoma, and the cells showed cytological similarities with the tumor cells in the pleural effusion; TTF-1, Napsin A, EGFR mutation and ALK translocation were all negative. This result suggested that origins of the tumors of the palate mucosa and in the lung were the same, even though the origin had not yet been determined. Next, we addressed whether the tumor of the palate mucosa was a primary tumor or not. Secretory carcinoma (SC), which is a common type of minor salivary gland tumor (MSGT), was suspected; however, mammaglobin was negative and ETV6-NTRK3 (EN) fusion was not observed. Other MSGTs were excluded based on histological and immunohistochemical findings. Furthermore, an additional examination demonstrated an oncogenic KRAS mutation at codon 12 (p.G12D) in both palate tumor and in pleural effusion. KRAS mutation is known to exist in one-third of lung adenocarcinomas (LUADs), but quite rare in MSGTs. The possibility of metastasis from other organs was considered unlikely from the results of endoscopic and imaging studies. This result indicated that the primary site of the CUP was indeed the lung, and that the tumor of the palate mucosa was a metastasis of the LUAD. CONCLUSIONS: A tumor of the palate mucosa that showed diagnostic difficulties was determined to be a metastatic LUAD by genomic alterations and histopathological findings.


Assuntos
Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Mucosa Bucal/patologia , Palato/patologia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Idoso , Quinase do Linfoma Anaplásico/genética , Biomarcadores Tumorais , Análise Mutacional de DNA , Receptores ErbB/genética , Testes Genéticos , Humanos , Imuno-Histoquímica , Queratina-7/metabolismo , Masculino , Mucosa Bucal/metabolismo , Mutação , Palato/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Tomografia Computadorizada por Raios X
8.
Plant Physiol ; 175(4): 1760-1773, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29018096

RESUMO

Histone acetylation is an essential process in the epigenetic regulation of diverse biological processes, including environmental stress responses in plants. Previously, our research group identified a histone deacetylase (HDAC) inhibitor (HDI) that confers salt tolerance in Arabidopsis (Arabidopsis thaliana). In this study, we demonstrate that class I HDAC (HDA19) and class II HDACs (HDA5/14/15/18) control responses to salt stress through different pathways. The screening of 12 different selective HDIs indicated that seven newly reported HDIs enhance salt tolerance. Genetic analysis, based on a pharmacological study, identified which HDACs function in salinity stress tolerance. In the wild-type Columbia-0 background, hda19 plants exhibit tolerance to high-salinity stress, while hda5/14/15/18 plants exhibit hypersensitivity to salt stress. Transcriptome analysis revealed that the effect of HDA19 deficiency on the response to salinity stress is distinct from that of HDA5/14/15/18 deficiencies. In hda19 plants, the expression levels of stress tolerance-related genes, late embryogenesis abundant proteins that prevent protein aggregation and positive regulators such as ABI5 and NAC019 in abscisic acid signaling, were induced strongly relative to the wild type. Neither of these elements was up-regulated in the hda5/14/15/18 plants. The mutagenesis of HDA19 by genome editing in the hda5/14/15/18 plants enhanced salt tolerance, suggesting that suppression of HDA19 masks the phenotype caused by the suppression of class II HDACs in the salinity stress response. Collectively, our results demonstrate that HDIs that inhibit class I HDACs allow the rescue of plants from salinity stress regardless of their selectivity, and they provide insight into the hierarchal regulation of environmental stress responses through HDAC isoforms.


Assuntos
Arabidopsis/efeitos dos fármacos , Arabidopsis/fisiologia , Histona Desacetilases/metabolismo , Proteínas de Plantas/metabolismo , Salinidade , Sistemas CRISPR-Cas , Regulação Enzimológica da Expressão Gênica/fisiologia , Regulação da Expressão Gênica de Plantas/fisiologia , Histona Desacetilases/genética , Mutação , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas de Plantas/genética , Cloreto de Sódio/toxicidade , Estresse Fisiológico
9.
Wound Repair Regen ; 26(3): 284-292, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-30265416

RESUMO

The authors aimed to assess the factors that impair cell proliferation in the granulation tissue of pressure ulcers using immunohistochemistry for the cell proliferation marker Ki-67. This was a single center, cross-sectional study. The study included 86 patients with stage III or IV pressure ulcers. Two granulation tissue biopsy specimens were obtained from 86 patients. The specimens were used for histological examination, Ki-67 immunohistochemistry, and bacterial count assessment. The % of Ki-67-stained cells was considered as the Ki-67 index. Pearson's product-moment correlation coefficient (r) was used to assess the relationship between the Ki-67 index and other quantitative variables, including age, body mass index, bacterial count (Log10 CFU/g), serum albumin level, hemoglobin level, white blood cell count, and C-reactive protein level. The Mann-Whitney U test was used to compare the mean Ki-67 index according to gender, diabetes, smoking status, and wound culture. Univariate and multivariate linear regression analyses were used to assess the association between the Ki-67 index and other parameters. The Mann-Whitney U test revealed that the bacteria-positive group had a lower Ki-67 index (p = 0.045). Bacterial count demonstrated a significant negative correlation with the Ki-67 index (r = -0.325, p = 0.002). Multivariate linear regression analysis showed that bacterial count was a significant predictor of the Ki-67 index. The adjusted ß-coefficient was -1.34 (95% confidence interval, -2.01 to -0.66, p < 0.001). Among the isolated bacteria, Corynebacterium spp. and Staphylococcus aureus were significantly associated with a low Ki-67 index, but Pseudomonas aeruginosa was not. These results suggest a negative relationship between bacterial count and cell proliferation in pressure ulcer granulation tissue, as indicated by the Ki-67 index. Granulation tissue formation in pressure ulcers may be accelerated if high bacterial load is treated appropriately.


Assuntos
Carga Bacteriana/fisiologia , Proliferação de Células/fisiologia , Infecções por Corynebacterium/complicações , Tecido de Granulação/microbiologia , Tecido de Granulação/patologia , Úlcera por Pressão/microbiologia , Úlcera por Pressão/patologia , Idoso , Infecções por Corynebacterium/fisiopatologia , Estudos Transversais , Feminino , Humanos , Antígeno Ki-67/fisiologia , Masculino , Pessoa de Meia-Idade , Úlcera por Pressão/complicações , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/patologia , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/patologia , Cicatrização/fisiologia
10.
Circ J ; 82(11): 2753-2760, 2018 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-30175799

RESUMO

BACKGROUND: Oxygen uptake (V̇O2) at peak workload and anaerobic threshold (AT) workload are often used for grading heart failure (HF) severity and predicting all-cause mortality. The clinical relevance of respiratory exchange ratio (RER) during exercise, however, is unknown. Methods and Results: We retrospectively studied 295 HF patients (57±15 years, NYHA class I-III) who underwent cardiopulmonary exercise testing. RER was measured at rest; at AT workload; and at peak workload. Peak V̇O2 had an inverse correlation with RER at AT workload (r=-0.256), but not at rest (r=-0.084) or at peak workload (r=0.090). Using median RER at AT workload, we divided the patients into high RER (≥0.97) and low RER (<0.97) groups. Patients with high RER at AT workload were characterized by older age, lower body mass index, anemia, and advanced NYHA class. After propensity score matching, peak V̇O2 tended to be lower in the high-RER than in the low-RER group (14.9±4.5 vs. 16.1±5.0 mL/kg/min, P=0.06). On Kaplan-Meier analysis, HF patients with a high RER at AT workload had significantly worse clinical outcomes, including all-cause mortality and rate of readmission due to HF worsening over 3 years (29% vs. 15%, P=0.01). CONCLUSIONS: High RER during submaximal exercise, particularly at AT workload, is associated with poor clinical outcome in HF patients.


Assuntos
Terapia por Exercício , Insuficiência Cardíaca , Adulto , Idoso , Intervalo Livre de Doença , Teste de Esforço , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Frequência Cardíaca , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Estudos Retrospectivos , Taxa de Sobrevida
11.
Biochem Biophys Res Commun ; 483(1): 277-282, 2017 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-28025150

RESUMO

Bacterial chemotaxis allows cells to swim toward a more favorable environment. Capillary assays are a major method for exploring bacterial responses to attractive and repellent chemicals, but the accumulation process obtained using a capillary containing chemicals has not been investigated fully. In this study, we quantitatively analyzed the response of Salmonella cells to serine as an attractant diffusing from a capillary placed in a cell suspension. Video microscopy showed that cells gradually accumulated near the tip of the capillary and thereafter directed flows were generated. Flow analysis using microspheres as tracers showed that the flow comprised millimeter-scale convection, which originated at the point source where serine was supplied by the capillary. The generation of convection was attributable to cell accumulation and gravitational force, thereby suggesting that it is a variant of bioconvection. We recorded the time courses of the changes in cell numbers and the convection flow speed at different positions near the capillary, which showed that the number of cells increased initially until an almost saturated level, and the convection flow speed then accelerated as the cell accumulation area increased in size. This result indicates that cell accumulation at the stimulation source and enlargement of the accumulation area were essential for generating the convection.


Assuntos
Quimiotaxia/fisiologia , Salmonella enterica/fisiologia , Bioensaio , Gravitação , Microscopia de Vídeo , Microesferas , Movimento , Oxigênio/química , Serina/química , Temperatura
12.
Chin J Cancer Res ; 29(5): 379-384, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29142456

RESUMO

Secretory carcinoma (SC), previously described as mammary analogue secretory carcinoma (MASC), is a recently described salivary gland tumor which morphologically resembles mammary secretory carcinoma. The first description of SC/MASC, reported by Skálová et al. in 2010, was as a rare salivary carcinoma imitating secretory carcinoma of the breast. SC/MASC is a unique salivary gland tumor with morphological overlap with acinic cell carcinoma (AciCC), mucoepidermoid carcinoma (MEC), and adenocarcinoma not otherwise specified (ADC-NOS). SC/MASC shares similar clinicopathological features with AciCC. As a critical difference between SC/MASC and AciCC, SC/MASC characteristically has the chromosomal translocation t(12;15)(p13;q25) which leads to a fusion gene between the ETV6 gene on chromosome 12 and the NTRK3 gene on chromosome 15. This genetic background is an important differential diagnostic finding for excluding other salivary gland tumors and may be a critical factor determining the prognosis for patients with SC/MASC. Research in recent years has provided a large body of new data on SC/MASC and suggests the possibility that the ETV6-NTRK3 translocation could be a therapeutic target. Here, we review the morphological and clinicopathological features of SC/MASC and discuss new directions for therapy.

13.
Cytokine ; 83: 1-7, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26999703

RESUMO

The nitrogen-containing bisphosphonate (BP) zoledronic acid (ZA) is a potent antiresorptive drug used in conjunction with standard cancer therapy to treat osteolysis or hypercalcemia due to malignancy. However, it is unclear how ZA influences the circulating levels of bone remodeling factors. The aim of this study was to evaluate the effects of ZA on the serum levels of soluble receptor activator of NF-kB ligand (sRANKL) and osteoprotegerin (OPG). The following four groups of C57BL/6 mice were used (five mice per group): (1) the placebo+phosphate-buffered saline (PBS) group, in which placebo-treated mice were injected once weekly with PBS for 4weeks; (2) the placebo+ZA group, in which placebo-treated mice were injected once weekly with ZA for 4weeks; (3) the prednisolone (PSL)+PBS group, in which PSL-treated mice were injected once weekly with PBS for 4weeks; and (4) the PSL+ZA group, in which PSL-treated mice were injected once weekly with ZA for 4weeks. At the 3-week time point, all mice were subjected to oral inflammatory stimulation with bacterial lipopolysaccharide (LPS). The sera of these mice were obtained every week and the levels of sRANKL and OPG were measured using enzyme-linked immunosorbent assay. At the time of sacrifice, femurs were prepared for micro-computed tomography (micro-CT), histological, and histomorphometric analyses. Our data indicated that ZA administration remarkably reduced bone turnover and significantly increased the basal level of sRANKL. Interestingly, the PSL+ZA group showed a dramatically elevated sRANKL level after LPS stimulation. In contrast, the PSL+ZA group in nonobese diabetic mice with severe combined immunodeficiency disease (NOD-SCID mice), which are characterized by the absence of functional T- and B-lymphocytes, showed no increase in the sRANKL level. Our data suggest that, particularly with combination treatment of ZA and glucocorticoids, surviving lymphocytes might be the source of inflammation-induced sRANKL. Thus, circulating sRANKL levels might be modulated by ZA.


Assuntos
Linfócitos B/metabolismo , Difosfonatos/farmacologia , Glucocorticoides/farmacologia , Imidazóis/farmacologia , Lipopolissacarídeos/toxicidade , Ligante RANK/sangue , Linfócitos T/metabolismo , Animais , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Osteoprotegerina/sangue , Ácido Zoledrônico
14.
BMC Cancer ; 16: 350, 2016 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-27255271

RESUMO

BACKGROUND: Early detection of oral squamous cell carcinomas (OSCCs) is urgently needed to improve the prognosis and quality of life (QOL) of patients. Oral leukoplakias (OLs), known as the most common premalignant lesions in the oral cavity, often precede OSCCs. Especially, OLs with dysplasia are known to have a high risk of malignant transformation. Here, we searched for the promoter methylation characteristic of high-risk OLs. METHODS: To identify methylation-silenced genes, a combined analysis of methylated DNA immunoprecipitation (MeDIP) - CpG island (CGI) microarray analysis and expression microarray analysis after treatment with a demethylating agent was performed in two OSCC cell lines (Ca9-22 and HSC-2). The methylation statuses of each gene were examined by methylation-specific PCR. RESULTS: A total of 52 genes were identified as candidates for methylation-silenced genes in Ca9-22 or HSC-2. The promoter regions of 13 genes among the 15 genes randomly selected for further analysis were confirmed to be methylated in one or more of five cell lines. In OSCC tissues (n = 26), 8 of the 13 genes, TSPYL5, EGFLAM, CLDN11, NKX2-3, RBP4, CMTM3, TRPC4, and MAP6, were methylated. In OL tissues (n = 24), seven of the eight genes, except for EGFLAM, were found to be methylated in their promoter regions. There were significantly greater numbers of methylated genes in OLs with dysplasia than in those without dysplasia (p < 0.0001). CONCLUSIONS: OLs at high risk for malignant transformation were associated with aberrant promoter methylation of multiple genes.


Assuntos
Transformação Celular Neoplásica/genética , Metilação de DNA/genética , Leucoplasia Oral/genética , Regiões Promotoras Genéticas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Detecção Precoce de Câncer/métodos , Feminino , Perfilação da Expressão Gênica , Humanos , Imunoprecipitação , Leucoplasia Oral/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Transcriptoma
17.
Biomedicines ; 12(5)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38790935

RESUMO

BACKGROUND: Photodynamic therapy (PDT) is a cancer-targeted treatment that uses a photosensitizer (PS) and irradiation of a specific wavelength to exert cytotoxic effects. To enhance the antitumor effect against head and neck squamous cell carcinoma (HNSCC), we developed a new phototherapy, intelligent targeted antibody phototherapy (iTAP). This treatment uses a combination of immunotoxin (IT) and a PS for PDT and light irradiation. In our prior study, we demonstrated that an immunotoxin (IT) consisting of an anti-ROBO1 antibody conjugated to saporin, when used in combination with the photosensitizer (PS) disulfonated aluminum phthalocyanine (AlPcS2a) and irradiated with light at the appropriate wavelength, resulted in increased cytotoxicity against head and neck squamous cell carcinoma (HNSCC) cells. ROBO1 is a receptor known to be involved in the progression of cancer. In this study, we newly investigate the iTAP targeting epidermal growth factor receptor (EGFR) which is widely used as a therapeutic target for HNSCC. METHODS: We checked the expression of EGFR in HNSCC cell lines, SAS, HO-1-u-1, Sa3, and HSQ-89. We analyzed the cytotoxicity of saporin-conjugated anti-EGFR antibody (cetuximab) (IT-Cmab), mono-L-aspartyl chlorin e6 (NPe6, talaporfin sodium), and light (664 nm) irradiation (i.e., iTAP) in SAS, HO-1-u-1, Sa3, and HSQ-89 cells. RESULTS: EGFR was expressed highly in Sa3, moderately in HO-1-u-1, SAS, and nearly not in HSQ-89. Cmab alone or IT-Cmab alone did not show cytotoxic effects in Sa3, HO-1-u-1, and HSQ-89 cells, which have moderate or low expression levels of EGFR protein. However, the iTAP method enhanced the cytotoxicity of IT-Cmab by the photodynamic effect in Sa3 and HO-1-u-1 cells, which have moderate levels of EGFR expression. CONCLUSION: Our study is the first to report on the iTAP method using IT-Cmab and NPe6 for HNSCC. The cytotoxic effects are enhanced in cell lines with moderate levels of EGFR protein expression, but not in nonexpressing cell lines, which is expected to expand the range of therapeutic windows and potentially reduce complications.

18.
Cureus ; 16(6): e63479, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39077267

RESUMO

Introduction Oxidative stress, an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, plays an important role in various dental diseases. Local anesthetics are frequently used in dentistry. The potential antioxidant activity of dental local anesthetics can contribute to dental practice. Therefore, this study aimed to investigate the ROS-scavenging activities of three commonly used dental local anesthetics, lidocaine, prilocaine, and articaine, focusing on their effects on hydroxyl radicals (HO•) and superoxide anions (O2 •-). Materials and methods The electron spin resonance (ESR) spin-trapping technique was employed to specifically measure the ROS-scavenging activities of these local anesthetics at varying concentrations. Results Lidocaine, prilocaine, and articaine exhibited concentration-dependent HO•-scavenging activities, with IC50 values of 0.029%, 0.019%, and 0.014%, respectively. Lidocaine and prilocaine showed concentration-dependent O2 •--scavenging activity, with IC50 values of 0.033% and 0.057%, respectively. However, articaine did not scavenge O2 •-. Conclusions The proactive use of dental local anesthetics may mitigate oxidative injury and inflammatory damage through direct ROS scavenging. However, further research is needed to elucidate the specific mechanisms underlying the antioxidant effects of these dental local anesthetics and their potential impact on the dental diseases associated with oxidative stress.

19.
Cureus ; 16(1): e52320, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38357064

RESUMO

INTRODUCTION: Oropharyngeal throat packs (OPTPs) are frequently used to administer general anesthesia during oral surgery and dental procedures. However, the use of OPTPs has remained controversial, with concerns about their effectiveness, the potential for falling short of expectations, and the inherent risk of serious oversight in removing them. This study aimed to assess the awareness of dental anesthesiologists in the United States of America (USA) and Japan regarding the use of OPTPs. METHODS: An online questionnaire was distributed to 41 dental anesthesia education facilities in May 2023 and responses were obtained from 32 facilities. RESULTS: The responses to the questionnaire indicated that dental anesthesiologists in both the USA and Japan believe that using OPTPs during general anesthesia with airway securement is of significant importance, albeit with varying primary purposes for their application. In contrast, notable disparities were observed between the USA and Japan regarding the perceived importance and routine use of OPTPs during open-airway general anesthesia. In both countries, there is a common understanding that the residual risks of OPTPs are severe and that multiple preventive procedures are required. CONCLUSIONS:  The present study showed that dental anesthesiologists in the USA and Japan believed that the use of OPTPs was generally necessary for dental anesthesia. However, there was a difference in awareness between Japan and the USA regarding the importance of OPTPs for open-airway general anesthesia. Therefore, there should be a consensus among dental anesthesiologists in Japan and the USA on using OPTPs during open-airway general anesthesia in the near future.

20.
Eur Heart J Digit Health ; 5(2): 152-162, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38505484

RESUMO

Aims: Although frailty assessment is recommended for guiding treatment strategies and outcome prediction in elderly patients with heart failure (HF), most frailty scales are subjective, and the scores vary among raters. We sought to develop a machine learning-based automatic rating method/system/model of the clinical frailty scale (CFS) for patients with HF. Methods and results: We prospectively examined 417 elderly (≥75 years) with symptomatic chronic HF patients from 7 centres between January 2019 and October 2023. The patients were divided into derivation (n = 194) and validation (n = 223) cohorts. We obtained body-tracking motion data using a deep learning-based pose estimation library, on a smartphone camera. Predicted CFS was calculated from 128 key features, including gait parameters, using the light gradient boosting machine (LightGBM) model. To evaluate the performance of this model, we calculated Cohen's weighted kappa (CWK) and intraclass correlation coefficient (ICC) between the predicted and actual CFSs. In the derivation and validation datasets, the LightGBM models showed excellent agreements between the actual and predicted CFSs [CWK 0.866, 95% confidence interval (CI) 0.807-0.911; ICC 0.866, 95% CI 0.827-0.898; CWK 0.812, 95% CI 0.752-0.868; ICC 0.813, 95% CI 0.761-0.854, respectively]. During a median follow-up period of 391 (inter-quartile range 273-617) days, the higher predicted CFS was independently associated with a higher risk of all-cause death (hazard ratio 1.60, 95% CI 1.02-2.50) after adjusting for significant prognostic covariates. Conclusion: Machine learning-based algorithms of automatically CFS rating are feasible, and the predicted CFS is associated with the risk of all-cause death in elderly patients with HF.

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