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1.
Oral Dis ; 29(3): 1282-1290, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34967949

RESUMO

OBJECTIVE: Whether oral lichen planus (OLP) was potentially malignant remains controversial. Here, we examined associations of ZNF582 methylation (ZNF582m ) with OLP lesions, dysplastic features and squamous cell carcinoma (OSCC). MATERIALS AND METHODS: This is a case-control study. ZNF582m was evaluated in both lesion and adjacent normal sites of 42 dysplasia, 90 OSCC and 43 OLP patients, whereas ZNF582m was evaluated only in one mucosal site of 45 normal controls. High-risk habits affecting ZNF582m such as betel nut chewing and cigarette smoking were also compared in those groups. RESULTS: OLP lesions showed significantly lower ZNF582m than those of dysplasia and OSCC. At adjacent normal mucosa, ZNF582m increased from patients of OLP, dysplasia, to OSCC. In addition, ZNF582m at adjacent normal sites in OLP patients was comparable to normal mucosa in control group. Dysplasia/OSCC patients with high-risk habits exhibited significantly higher ZNF582m than those without high-risk habits. However, ZNF582m in OLP patients was not affected by those high-risk habits. CONCLUSIONS: OLP is unlikely to be potentially malignant based on ZNF582m levels. ZNF582m may also be a potential biomarker for distinguishing OLP from true dysplastic features and OSCC, and for monitoring the malignant transformation of OLP, potentially malignant disorders with dysplastic features and OSCC.


Assuntos
Carcinoma de Células Escamosas , Líquen Plano Bucal , Neoplasias Bucais , Humanos , Metilação , Estudos de Casos e Controles , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Líquen Plano Bucal/genética , Líquen Plano Bucal/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Fatores de Transcrição Kruppel-Like/genética
2.
BMC Med Educ ; 20(1): 155, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32414406

RESUMO

BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) core competencies (CC) in general medicine-based primary care are essential for junior medical trainees. In this country, a regular faculty development (FD) program aimed at training faculty in instructing (teaching and assessing) these CC had operated. However, leadership was not emphasized. In a new intervention module, the roles and associated responsibilities of clinical instructors to conduct, design, and lead CC-based education were emphasis. AIMS: This follow-up explanatory case study compares the effectiveness of intervention module with that of the previous regular module. METHODS: The regular group (n = 28) comprised clinical instructors who participated in the FD module during the 2013-2014 year while the intervention group (n = 28) was composed of 2015-2016 participants. Prior to the formal (hands-on) training, participants in the intervention group were asked to study the online materials of the regular module. These participants then received a 30-h hands-on training in conducting, designing, and leading skills. Finally, they prepared a 10-h reflective end-of-module presentation of their real-world practices. RESULTS: Following the training, a higher degree improvement in participants self-reported familiarity with CC education, self-confidence in their ability to deliver CC education and sustained involve CC education were noted among the intervention FD group, compared with the regular FD group. In the intervention group, senior academicians (associate and full professor) are more substantially involved in designing and leading CC-based courses than junior academicians (lecturers and assistant professors). Among non-teaching award winners of in the intervention FD group, the follow-up degree of sustained involvement in delivering, designing and leading CC-based courses was significantly higher than that of the regular group. CONCLUSIONS: Our study demonstrated that leadership training in the intervention FD modules substantially motivated clinical instructors to become leaders in CC education.


Assuntos
Competência Clínica , Educação Médica , Docentes de Medicina/educação , Liderança , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Taiwan
3.
BMC Med Educ ; 20(1): 167, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32450878

RESUMO

BACKGROUND: This study aims to assess the feasibility, reliability and validity of the panel-based Equal Z-score (EZ) method applied to objective structural clinical examination (OSCE) of Chinese medical students and undertaking a comparison with the statistical techniques-based Borderline Regression Method (BRM). METHODS: Data received from two cohorts of 6th and 7th year medical students in Taiwan who set the mock OSCE as a formative assessment. Traditionally this medical school uses BRM to set the pass/fail cut-score. For the current study, 31 OSCE panellists volunteered to participate in the EZ method in parallel to the BRM. RESULTS: In the conduct of this study, each panel completed this task for an OSCE exam comprising 12 stations within less than 60 min. Moreover, none of the 31 panellists, whose are busy clinicians, had indicated that the task was too difficult or too time-consuming. Although EZ method yielded higher cut-scores than the BRM it was found reliable. Intraclass correlation (ICC) measuring absolute agreement, across the three groups of panellists was .893 and .937 for the first and second rounds respectively, demonstrating high level of agreement across groups with the EZ method and the alignment between the BRM and the EZ method was visually observed. The paired t-test results identified smaller differences between the cut-scores within methods than across methods. CONCLUSIONS: Overall this study suggests that the EZ method is a feasible, reliable and valid standard setting method. The EZ method requires relatively little resources (takes about an hour to assess a 12 station OSCE); the calculation of the cut-score is simple and requires basic statistical skills; it is highly reliable even when only 10 panellists participate in the process; and its validity is supported by comparison to BRM. This study suggests that the EZ method is a feasible, reliable and valid standard setting method.


Assuntos
Competência Clínica , Educação de Graduação em Medicina/normas , Avaliação Educacional/normas , Exame Físico/normas , Estudos de Viabilidade , Humanos , Reprodutibilidade dos Testes , Taiwan
4.
Int J Mol Sci ; 21(24)2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33322437

RESUMO

Oral squamous cell carcinoma (OSCC) is among the leading causes of cancer-associated deaths worldwide. Family members in miR-371/372/373 miRNA cluster, which is localized at human chromosome 19q13.4, are co-expressed in both human stem cells and malignancies. The individual miRNA in this cluster are also involved in modulating the pathogenesis of malignancies as either oncogenes or suppressors. The 19q13 region is frequently gained in head and neck cancers. High expression of miR-372 and miR-373 are survival predictors for OSCC. However, the role of the miR-371/372/373 cluster in oral carcinogenesis remains to be fully investigated. We use the clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9 system to establish OSCC cell subclones that had the miR-371/372/373 cluster deleted. In addition, further subclones were established that had the promoter of this cluster deleted. Concordant silencing in SAS cells of miR-371/372/373 decreased oncogenic potential, increased cisplatin sensitivity, activated p53, and upregulated the expression of Bad and DKK1. We also employed the CRISPR/dCas9 synergistic activation mediator system, which allowed robust transcriptional activation of the whole miR-371/372/373 cistron. Upregulation of endogenous miR-371/372/372 expression increased both oncogenicity and drug resistance. These were accompanied by a slight activation of AKT, ß-catenin, and Src. This study identifies the oncogenic role of the miR-371/372/373 cluster in OSCC. Using CRISPR based strategy can be a powerful paradigm that will provide mechanistic insights into miRNA cluster functionality, which will also likely help the development of targeting options for malignancies.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , MicroRNAs/metabolismo , Neoplasias Bucais/metabolismo , Animais , Antineoplásicos/uso terapêutico , Apoptose/genética , Apoptose/fisiologia , Western Blotting , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Cisplatino/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Família Multigênica/genética , Família Multigênica/fisiologia , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Carcinogenesis ; 39(11): 1320-1330, 2018 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-30102337

RESUMO

In recent years, the incidence and mortality rates of head and neck squamous cell carcinoma (HNSCC) have increased worldwide. Therefore, understanding genomic alterations in HNSCC carcinogenesis is crucial for appropriate diagnosis and therapy. Protocadherin FAT1, which encodes 4588 amino acid residues, regulates complex mechanisms to promote oncogenesis or suppression of malignancies. Multiplex PCR-based next-generation sequencing (NGS) revealed FAT1 somatic mutations. The clinicopathologic implications of FAT1 in HNSCC were investigated using expression assays, and the functional role of FAT1 in HNSCC pathogenesis was determined using ectopic expression and knockdown experiments. Approximately 29% patients with HNSCC harbored damaging FAT1 mutations. InVEx algorithm identified FAT1 as a significant functional mutation burden. Each type of mutation (missense, nonsense and frameshift) accounted for nearly one-third of deleterious mutations. FAT1 mutations correlated with lower FAT1 expression in tumors. The knockdown of the endogenous expression of FAT1 and exogenous expression of crucial FAT1 domains unequivocally indicated that FAT1 suppressed the migration and invasion capability of HNSCC cells. Functional analysis suggested that nonsense mutations in FAT1 result in the loss of the suppression of tumor progression. FAT1 mutations and downregulation defined nodal involvement, lymphovascular permeation and tumor recurrence. In addition, FAT1 mutations and downregulation are independent predictors of poor disease-free survival in patients with HNSCC. This study is the first to perform multiplex PCR-based NGS to indicate marked non-synonymous FAT1 mutations in HNSCC, which are prognostic indicators. The gene analysis strategy proposed for detecting FAT1 mutations may be a valid method for mutation screening.


Assuntos
Caderinas/genética , Transformação Celular Neoplásica/genética , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Códon sem Sentido/genética , Progressão da Doença , Intervalo Livre de Doença , Feminino , Mutação da Fase de Leitura/genética , Predisposição Genética para Doença/genética , Neoplasias de Cabeça e Pescoço/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase Multiplex , Mutação de Sentido Incorreto/genética , Invasividade Neoplásica/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Sequenciamento do Exoma
7.
Int J Mol Sci ; 19(11)2018 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-30352977

RESUMO

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a disease that affects patients worldwide. DNA of dead cells is released into the blood stream and may be isolated from plasma or serum samples. This DNA is termed cell-free DNA (cfDNA). cfDNA is increased in several types of malignancies. We investigated if there was a correlation between cfDNA levels and the progression of OSCC. METHODS: Using quantitative spectrometry, we measured plasma cfDNA in 121 patients with OSCC and 50 matched controls. Mann Whitney and Wilcoxon tests were used to compare differences among various clinical variants. Receiver operating characteristic (ROC) analysis was used to obtain levels suitable for the separation of the clinical subsets. Kaplan-Meier analysis was used to assess correlation with survival. RESULTS: Plasma cfDNA was significantly elevated in patients with OSCC relative to controls. Plasma cfDNA levels correlated with larger tumor size, cervical lymph node metastasis and late stage. Higher plasma cfDNA levels were associated with a poor prognosis of OSCC, which is a new finding. CONCLUSION: Plasma cfDNA could serve as a novel and easily accessible biomarker in OSCC, providing diagnostic and prognostic value.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Ácidos Nucleicos Livres/sangue , Neoplasias Bucais/sangue , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
Carcinogenesis ; 35(5): 1162-71, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24480806

RESUMO

Oral squamous cell carcinoma (OSCC) is a prevalent malignancy worldwide. MicroRNAs are short non-coding RNAs that regulate gene expression and are crucial for tumorigenesis. Previously, we have identified that miR-31 is frequently upregulated in OSCC and that this miR-31 increase, together with downstream effector modulation, enhances oral carcinogenesis. We have identified higher levels of miR-31 expression in oral potential malignant disorder (OPMD) tissues compared with normal oral mucosa. Exogenous miR-31 and human telomerase reverse transcriptase (hTERT) expression were introduced into cultured normal oral keratinocytes (NOKs), which led to the immortalization; these lines were designated M31OK1 and M31OK3. These immortalized lines maintained the capability to undergo squamous differentiation. In addition, migration by both cell lines was attenuated by hTERT and miR-31 knockdown. M31OK1 carries a p53 gene mutation at codon 273. A serum-tolerant subline, M31OK1-D, exhibits potent anchorage-independent growth that is attenuated by knockdown of both hTERT and miR-31. miR-31-targeted factors inhibiting HIF (FIH), which upregulated vascular endothelial growth factor (VEGF), was found crucial for oral tumorigenesis. The proliferation, migration and epithelial-mesenchymal transition of M31OK1-D are associated with downregulation of FIH and upregulation of VEGF, which require miR-31 expression. High miR-31 expression is correlated with higher VEGF expression and lower E-cadherin expression in OPMD tissue. It can be concluded that miR-31 collaborates with hTERT to immortalize NOKs and that this may contribute to early stage oral carcinogenesis. The targeting of downstream factors by miR-31 may further advance the neoplastic progression of immortalized NOKs, allowing them to become malignant.


Assuntos
Transformação Celular Neoplásica/genética , Regulação da Expressão Gênica , Queratinócitos/metabolismo , Queratinócitos/patologia , MicroRNAs/genética , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Lesões Pré-Cancerosas , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Transformada , Linhagem Celular Tumoral , Transformação Celular Neoplásica/metabolismo , Transição Epitelial-Mesenquimal , Humanos , MicroRNAs/metabolismo , Fenótipo , Telomerase/genética , Telomerase/metabolismo , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
Int J Cancer ; 134(4): 811-21, 2014 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-23824713

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is a prevalent disease worldwide, and the survival of HNSCC has not improved significantly over the last few decades. MicroRNAs (miRNAs) have an important regulatory role during carcinogenesis. Our study investigated the pathogenic implications of miR-134 in head and neck carcinogenesis. The clinicopathologic implications of miR-134 in HNSCC were investigated using expression assays and the functional role of miR-134 in HNSCC pathogenesis was determined using ectopic expression, knockdown and reporter assay experiments. Xenographic tumorigenesis and orthotopic nodal metastasis were assayed in mouse models. In situ hybridization and immunohistochemistry were used to detect the expression of miR-134 and the WWOX gene in human HNSCC. The results indicated that miR-134 was upregulated in HNSCC tissues relative to control mucosa. High expression of miR-134 was associated with nodal metastasis and mortality of patients. Decreased plasma miR-134 levels after tumor ablation indicated a better prognosis for patients. Multivariate analysis showed that high miR-134 expression in HNSCC was an independent predictor of poor survival. Ectopic miR-134 expression significantly enhanced in vitro oncogenic phenotypes and the orthotopic growth and metastasis of HNSCC cells. miR-134 targeted WW domain-containing oxidoreductase (WWOX) gene and cell invasion enhanced by miR-134 expression was abrogated by ectopic WWOX expression in HNSCC cells. miR-134 expression was reversely associated with the WWOX expression in HNSCC tissues. Evidences from our study substantiated that miR-134 expression contributes to head and neck carcinogenesis by targeting the WWOX.


Assuntos
Carcinoma de Células Escamosas/secundário , Transformação Celular Neoplásica/patologia , Neoplasias de Cabeça e Pescoço/patologia , MicroRNAs/genética , Oxirredutases/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Apoptose , Western Blotting , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Adesão Celular , Movimento Celular , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Células Cultivadas , Feminino , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Técnicas Imunoenzimáticas , Hibridização In Situ , Queratinócitos/citologia , Queratinócitos/metabolismo , Microdissecção e Captura a Laser , Luciferases/metabolismo , Metástase Linfática , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , Oxirredutases/genética , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Proteínas Supressoras de Tumor/genética , Oxidorredutase com Domínios WW
10.
Cancer ; 119(24): 4259-67, 2013 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-24301303

RESUMO

BACKGROUND: Patterns of global histone modifications have been suggested to be predictors of clinical outcome in many cancers. However, the role of global histone modification patterns in oral squamous cell carcinoma (OSCC) is unclear. METHODS: A retrospective clinicopathologic analysis was undertaken of 186 patients with oral squamous cell carcinoma who received complete ablative surgical treatment. Tissue arrays were made from those paraffin-embedded OSCC samples and examined by immunohistochemistry for histone 3 lysine 4 acetylation (H3K4ac), histone 3 lysine 18 acetylation (H3K18ac), histone 3 lysine 4 trimethylation (H3K4me3), histone 3 lysine 9 trimethylation (H3K9me3), and histone 3 lysine 27 trimethylation (H3K27me3). RESULTS: A low level of H3K4ac and a high level of H3K27me3 were associated with advanced T status, N status, tumor stage, and perineural invasion. They were also correlated with cancer-specific survival (CSS) and disease-free survival (DFS). The 5-year CSS and DFS in H3K4ac(low) vs. H3K4ac(high) were 74.8% versus 92.5% (P = .010), and 51.4% versus 76.2% (P = .001), respectively. The 5-year CSS and DFS in H3K27me3(low) versus H3K27me3(high) were 94.7% versus 62.3% (P < .001) and 76.4% versus 32.3% (P < .001), respectively. We also found improved prediction for DFS after combining the H3K4ac(low) and H3K27me3(high) profiles and comparing the scores with the other modification patterns (P < .0001). CONCLUSIONS: This research demonstrates the potential prognostic utility of global histone modification analysis for OSCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Histonas/metabolismo , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/cirurgia , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/cirurgia , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço
11.
J Chin Med Assoc ; 86(2): 135-137, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36524941

RESUMO

The Omicron variant BA.2 is the dominant form of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in many countries, including those that have already implemented the strictest quarantine mandates that effectively contained the spread of the previous variants. Although many individuals were partially or fully vaccinated, confirmed Omicron infections have far surpassed all other variants combined in just a couple of months since the Omicron variant emerged. The ChAdOx1-S (AstraZeneca), BNT162b2 (Pfizer-BioNTech), and mRNA-1273 (Moderna) vaccines offer protection against the severe illness of SARS-CoV-2 infection; however, these currently available vaccines are less effective in terms of preventing Omicron infections. As a result, a booster dose of BNT162b2 or mRNA-1273 is recommended for individuals >12 years old who had received their second dose of the approved vaccines for >5 months. Herein, we review the studies that assessed the clinical benefits of the booster dose of vaccines against Omicron infections. We also analyzed public data to address whether early booster vaccination effectively prevented the surge of the Omicron infections. Finally, we discuss the consideration of a fourth dose of vaccine as a way to prevent possible upcoming infections.


Assuntos
Vacina de mRNA-1273 contra 2019-nCoV , COVID-19 , Humanos , Criança , Vacina BNT162 , COVID-19/prevenção & controle , SARS-CoV-2
12.
Cancer Sci ; 103(9): 1672-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22632121

RESUMO

Microvascular free flap transfer for post-oncologic reconstructive surgery in oral cancer is considered to be a challenge due to the complexity of the anatomy and function of the region. We sought to identify possible factors associated with microsurgical complications and to assess the impact of these complications in relation to patient survival. Following the inclusion and exclusion protocol, 142 patients with stage III and IV oral squamous cell carcinoma (OSCC) who underwent immediate free flap reconstruction after tumor ablation were included in the study. Clinical and surgical procedural-related factors were retrieved from a database and analyzed retrospectively; survival data were evaluated using the Kaplan-Meier method. Major complications that required re-anastomosis of the flap vessels occurred in 23 patients (16.2%); total necrosis of the flaps, regardless of salvage treatment, occurred in seven cases, with 95.1% of full flap survival. The American Society of Anesthesiologists classification, types of neck dissection, and number of flaps were regarded as strong predictors for surgical complications. Patients with these complications appeared to have a shortened survival (5-year cancer-specific survival of approximately 60%, both in stage III and IV OSCC). However, the impact of surgical complications on survival was significant only in stage III OSCC (P = 0.037). Strategies to minimize surgical complications should be used to ensure better prognoses for these patients.


Assuntos
Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/cirurgia , Neoplasias Bucais/complicações , Neoplasias Bucais/cirurgia , Complicações Pós-Operatórias/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidade , Feminino , Humanos , Masculino , Microcirurgia , Pessoa de Meia-Idade , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/mortalidade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco
13.
J Surg Oncol ; 106(2): 149-54, 2012 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-22354873

RESUMO

OBJECTIVES: In this study, we examined the role of p16(INK4A) , a surrogate biomarker of HPV-related head and neck cancers with better prognosis, in an endemic area of betel quid (BQ)-related oral squamous cell carcinoma (OSCC). METHODS: p16(INK4A) immunohistochemistry was examined in 165 OSCCs, statistical analyses were performed to elucidate the correlation between p16(INK4A) expression and BQ habits/pathologic features, and the prognostic impact of p16(INK4A) and different parameters were analyzed. RESULTS: The incidence of p16(INK4A) expression was similar between BQ chewers and non-chewers. p16(INK4A) expression was significantly associated with nodal metastasis (P = 0.005). There was a trend suggesting that the loss of p16(INK4A) expression was more frequent in higher T stages, however, this was found only in patients without lymph node metastasis (P = 0.059). A poorer prognosis and a higher risk of tumor recurrence were found in OSCCs without p16(INK4A) expression. (The HR for cancer-specific mortality and cancer recurrence was 3.55 and 1.89, respectively.) CONCLUSION: Although it has been suggested that BQ chewers had a greater tendency toward tumor recurrence and poor outcome, our data demonstrated that p16(INK4A) expression is unrelated to BQ habit and that p16(INK4A) downregulation is a strong predictor for OSCC progression, recurrence and survival in Taiwan.


Assuntos
Areca/efeitos adversos , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/patologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Neoplasias Bucais/química , Neoplasias Bucais/etiologia , Neoplasias Bucais/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/mortalidade , Estudos de Coortes , Progressão da Doença , Regulação para Baixo , Feminino , Hábitos , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Invasividade Neoplásica , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Recidiva , Estudos Retrospectivos , Sobrevida , Taiwan/epidemiologia
14.
J Pathol ; 223(4): 482-95, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21294122

RESUMO

MicroRNA-200c (miR200c) is emerging as an important regulator of tumourigenicity and cancer metastasis with a strong capacity for inducing epithelial-mesenchymal transitions. However, the role of miR200c in head and neck squamous cell carcinoma (HNSCC) and HNSCC-associated cancer stem cells (HNSCC-CSCs) is unknown. In this study, the expression of miR200c in the regional metastatic lymph node of HNSCC tissues was significantly decreased, but BMI1 expression was increased as compared to parental tumours. Importantly, site-directed mutagenesis with a luciferase reporter assay showed that miR200c targeted the 3' UTR of BMI1 in HNSCC cells. Isolated HNSCC-derived ALDH1(+) /CD44(+) cells displayed CSC-like tumour initiating and radio-resistant properties. The expression levels of miR200c were significantly down-regulated while BMI1 was increased in HNSCC-ALDH1(+) /CD44(+) compared to the other subsets of HNSCC cells. Furthermore, increased miR200c expression or knockdown of BMI1 could significantly inhibit the malignant CSC-like properties of ALDH1(+) /CD44(+) cells. miR200c over-expression further down-regulated the expressions of ZEB1, Snail and N-cadherin, but up-regulated E-cadherin expression in ALDH1(+) /CD44(+) cells. Finally, a xenotransplantion study confirmed that over-expression of miR200c or BMI1 knockdown effectively inhibited the lung metastatic ability and prolonged the survival rate of ALDH1(+) /CD44(+) -transplanted mice. In summary, miR200c negatively modulates the expression of BMI1 but also significantly inhibits the metastatic capability of epithelial-mesenchymal transitions in malignant HNSCC by reducing the expression of BMI1/ZEB1. Restoration of miR200c in HNSCC and CSCs may be a promising therapeutic approach.


Assuntos
MicroRNAs/genética , Células-Tronco Neoplásicas/patologia , RNA Neoplásico/genética , Adulto , Idoso , Aldeído Desidrogenase/análise , Família Aldeído Desidrogenase 1 , Animais , Carcinoma/genética , Carcinoma/patologia , Carcinoma/secundário , Carcinoma/terapia , Carcinoma de Células Escamosas , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Transformação Celular Neoplásica/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Terapia Genética/métodos , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/secundário , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Receptores de Hialuronatos/análise , Isoenzimas/análise , Metástase Linfática , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Mutagênese Sítio-Dirigida , Proteínas de Neoplasias/metabolismo , Neoplasias de Células Escamosas/genética , Neoplasias de Células Escamosas/patologia , Neoplasias de Células Escamosas/secundário , Neoplasias de Células Escamosas/terapia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/efeitos da radiação , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Complexo Repressor Polycomb 1 , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Retinal Desidrogenase , Carcinoma de Células Escamosas de Cabeça e Pescoço , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Int J Mol Sci ; 13(3): 3277-3290, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22489152

RESUMO

Although surgery or the combination of chemotherapy and radiation are reported to improve the quality of life and reduce symptoms in patients with oral cancer, the prognosis of oral cancer remains generally poor. DNA alkylating agents, such as N-mustard, play an important role in cancer drug development. BO-1051 is a new 9-anilinoacridine N-mustard-derivative anti-cancer drug that can effectively target a variety of cancer cell lines and inhibit tumorigenesis in vivo. However, the underlying mechanism of BO-1051-mediated tumor suppression remains undetermined. In the present study, BO-1051 suppressed cell viability with a low IC(50) in oral cancer cells, but not in normal gingival fibroblasts. Cell cycle analysis revealed that the tumor suppression by BO-1051 was accompanied by cell cycle arrest and downregulation of stemness genes. The enhanced conversion of LC3-I to LC3-II and the formation of acidic vesicular organelles indicated that BO-1501 induced autophagy. The expression of checkpoint kinases was upregulated as demonstrated with Western blot analysis, showing that BO-1051 could induce DNA damage and participate in DNA repair mechanisms. Furthermore, BO-1051 treatment alone exhibited a moderate tumor suppressive effect against xenograft tumor growth in immunocompromised mice. Importantly, the combination of BO-1051 and radiation led to a potent inhibition on xenograft tumorigenesis. Collectively, our findings demonstrated that BO-1051 exhibited a cytotoxic effect via cell cycle arrest and the induction of autophagy. Thus, the combination of BO-1051 and radiotherapy may be a feasible therapeutic strategy against oral cancer in the future.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Neoplasias Bucais/tratamento farmacológico , Compostos de Mostarda Nitrogenada/farmacologia , Animais , Antineoplásicos Alquilantes/administração & dosagem , Autofagia/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quinase 1 do Ponto de Checagem , Quinase do Ponto de Checagem 2/metabolismo , Dano ao DNA , Relação Dose-Resposta a Droga , Feminino , Gengiva/citologia , Gengiva/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , Proteínas Associadas aos Microtúbulos/metabolismo , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Compostos de Mostarda Nitrogenada/administração & dosagem , Fosforilação , Proteínas Quinases/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
16.
J Chin Med Assoc ; 85(4): 431-437, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35125403

RESUMO

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a type of malignancy characterized by high relapse and recurrence rates in the late stage despite optimal surgical intervention and postoperative chemoradiotherapy. Because the management of relapse following definitive treatment is challenging, accurate risk stratification is of clinical significance to improve treatment outcomes. Circular RNAs (circRNAs) are noncoding RNAs featured with cell-type specificity and high stability, owing to their circular structure, making these molecules excellent biomarkers for a variety of diseases. METHODS: The levels of hsa_circ_0000190 and 0001649 in plasma samples from 30 healthy controls and 66 OSCC patients were determined by droplet digital polymerase chain reaction. The same primer sets were used with PCR to examine the expression of these two circRNAs in cancerous and adjacent normal tissues. A receiver operating characteristics curve was generated to evaluate the diagnostic value. The Kaplan-Meier method with a log-rank test was used for survival analysis. RESULTS: We identified two circRNAs as potential biomarkers for OSCC, showing that the plasma level of hsa_circ_0000190 was significantly decreased in the late stage and marginally correlated with the development of second primary OSCC. We also found that the decreased plasma hsa_circ_0001649 was correlated with the recurrence and poor prognosis of patients. Additionally, we found that high plasma hsa_circ_0000190, but not hsa_circ_0001649, possibly predicted a better response of patients to induction chemotherapy. CONCLUSION: Our study demonstrated the potential of biomarkers in plasma to inform not just the tumor but the entire oral cavity, thereby offering a prediction for early recurrence and second primary OSCC. The plasma circRNAs remain valuable for OSCC, albeit the easy accessibility to the oral cavity.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Biomarcadores , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Humanos , Neoplasias Bucais/terapia , Recidiva Local de Neoplasia , RNA/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço
17.
Medicine (Baltimore) ; 101(2): e28570, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35029229

RESUMO

BACKGROUND: Virtual reality (VR)-based simulation in hospital settings facilitates the acquisition of skills without compromising patient safety. Despite regular text-based training, a baseline survey of randomly selected healthcare providers revealed deficiencies in their knowledge, confidence, comfort, and care skills regarding tracheostomy. This prospective pre-post study compared the effectiveness of regular text- and VR-based intervention modules in training healthcare providers' self-efficacy in tracheostomy care skills. METHODS: Between January 2018 and January 2020, 60 healthcare providers, including physicians, nurses, and respiratory therapists, were enrolled. For the intervention, a newly developed head-mounted display (HMD) and web VR materials were implemented in training and clinical services. Subsequently, in-hospital healthcare providers were trained using either text or head-mounted display virtual reality (HMD-VR) materials in the regular and intervention modules, respectively. For tracheostomy care skills, preceptors directly audited the performance of trainees and provided feedback. RESULTS: At baseline, the degree of trainees' agreement with the self-efficacy-related statements, including the aspects of familiarity, confidence, and anxiety about tracheostomy-related knowledge and care skills, were not different between the control and intervention groups. At follow-up stage, compared with the regular group, a higher percentage of intervention group' trainees reported that they are "strongly agree" or "somewhat agree" that the HMD-VR simulation increases their self-efficacy, including the aspects of familiarity and confidence, and reduced their anxiety about tracheostomy-related knowledge and care skills. After implementation, a higher degree of trainees' average satisfaction with VR-based training and VR materials was observed in the intervention group than in the regular group. Most reported that VR materials enabled accurate messaging and decreased anxiety. The increasing trend of the average written test and hands-on tracheostomy care skills scores among the intervention group trainees was significant compared to those in the regular group. The benefits of HMD-VR simulations and web-VR material-based clinical services for in-hospital healthcare providers and patient families persisted until 3 to 4 weeks later. CONCLUSION: The current study suggests that VR materials significantly enhance trainees' self-efficacy (increased familiarity, increased confidence, and reduced anxiety) and their satisfaction with the training, while motivating them to use acquired knowledge and skills in clinical practice.


Assuntos
Pessoal de Saúde/educação , Autoeficácia , Traqueostomia/educação , Realidade Virtual , Hospitais , Humanos , Estudos Prospectivos
18.
Artigo em Inglês | MEDLINE | ID: mdl-36252990

RESUMO

PURPOSE: Undertaking a standard-setting exercise is a common method for setting pass/fail cut scores for high-stakes examinations. The recently introduced equal Z standard-setting method (EZ method) has been found to be a valid and effective alternative for the commonly used Angoff and Hofstee methods and their variants. The current study aims to estimate the minimum number of panelists required for obtaining acceptable and reliable cut scores using the EZ method. METHODS: The primary data were extracted from 31 panelists who used the EZ method for setting cut scores for a 12-station of medical school's final objective structured clinical examination (OSCE) in Taiwan. For this study, a new data set composed of 1,000 random samples of different panel sizes, ranging from 5 to 25 panelists, was established and analyzed. Analysis of variance was performed to measure the differences in the cut scores set by the sampled groups, across all sizes within each station. RESULTS: On average, a panel of 10 experts or more yielded cut scores with confidence more than or equal to 90% and 15 experts yielded cut scores with confidence more than or equal to 95%. No significant differences in cut scores associated with panel size were identified for panels of 5 or more experts. CONCLUSION: The EZ method was found to be valid and feasible. Less than an hour was required for 12 panelists to assess 12 OSCE stations. Calculating the cut scores required only basic statistical skills.


Assuntos
Competência Clínica , Avaliação Educacional , Avaliação Educacional/métodos , Humanos , Reprodutibilidade dos Testes , Projetos de Pesquisa , Faculdades de Medicina , Taiwan
19.
BMJ Open ; 12(1): e055953, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34987046

RESUMO

OBJECTIVE/DESIGN/SETTING: This study aims to develop preprocedural communication-specific framework that emphasises the use of audiovisual materials and compares its acceptability by trainees with a regular module. TRAINEES: Between October 2018 and July 2021, 96 medical clerks were enrolled and randomly divided into regular and intervention groups. Another 48 trainees whose did not join the framework-based training but complete self-assessments were enrolled as the control group. INTERVENTIONS: In the intervention training module, the key steps of preprocedural communication-specific skills were structuralised into a framework using the acronym of OSCAR. PRIMARY AND SECONDARY OUTCOME MEASURES: This study compared the acceptability of trainees for two modules by measuring the degree of increase in the end-of-rotation and follow up (4 weeks later) competency from baseline by trainees' self-assessments and physician assessments after serial trainings. RESULTS: In comparison with regular group trainees, greater degree of improvements (framework-1 statement: 111%±13% vs 27%±5%, p<0.001; framework-2 statement: 77%±9% vs 48%±2%, p<0.05; skill-1 statement: 105%±9% vs 48%±3%, p<0.001); skill-2 statement: 71%±11% vs 50%±9%, p<0.05) were noted in the framework-related and skill-related statement 1-2 (the familiarity and confidence to use the framework and skills) than those of intervention group. At the end-of-rotation stage, the trainees ability to use the 'A-step: using audiovisual materials' of the OSCAR was significantly improved (229%±13%, p<0.001), compared with other steps. In the intervention group, the degree of improvement of the end-of-rotation data of trainees' self-assessment from baseline was significantly correlated with the degree of the improvement in physicians' assessment data in the aspects of skills, framework and steps in framework (R=0.872, p<0.01; R=0.813, p<0.001; R=0.914, p<0.001). CONCLUSIONS: The OSCAR framework-based intervention module is well accepted by medical clerks and motivates them to integrate the acquired skills in clinical practice, which leads to trainees' primary care patients being satisfied with their preprocedural communication.


Assuntos
Competência Clínica , Meios de Comunicação , Comunicação , Humanos , Aprendizagem , Autoavaliação (Psicologia)
20.
Diagnostics (Basel) ; 12(7)2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35885450

RESUMO

BACKGROUND: Visual oral examination (VOE) is a conventional oral cancer screening method. This study aimed to evaluate the value of methylation marker to assist VOE in identifying oral epithelial dysplasia and oral squamous cell carcinoma (OED/OSCC) from non-cancerous lesions in a real-world situation. METHODS: 201 patients with high-risk personal habits who self-perceived oral anomaly were VOE examined, ZNF582 methylation (ZNF582m) tested, and histologically diagnosed. RESULTS: Among them, 132 patients (65.7%) were histologically diagnosed OED/OSCC. Using VOE, 56.1% OED/OSCC patients had possible oral cancer, whereas 37.7% non-OED/OSCC patients had leukoplakia. ZNF582m-positive was detected in 90.2% OED/OSCC patients and 44.9% non-OED/OSCC patients. Various logistic regression models were postulated to evaluate the diagnostic performance of conventional VOE and new strategies using ZNF582m. ROC analysis and its corresponding C-index demonstrated that either triage or co-testing models of VOE and ZNF582m could improve diagnostic performance and discriminative abilities compared with the VOE only approach. CONCLUSIONS: In conclusion, methylation marker test shows equivalent performance to an experienced judgment by oral maxillofacial surgeons and plays a significantly supplementary role in increasing the efficacy in identifying oral malignant lesions. ZNF582m may be an especially important tool for family physicians or general dentists to properly diagnose suspicious oral lesions.

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