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1.
EMBO Rep ; 25(5): 2441-2478, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38649663

RESUMO

Ago2 differentially regulates oncogenic and tumor-suppressive miRNAs in cancer cells. This discrepancy suggests a secondary event regulating Ago2/miRNA action in a context-dependent manner. We show here that a positive charge of Ago2 K212, that is preserved by SIR2-mediated Ago2 deacetylation in cancer cells, is responsible for the direct interaction between Ago2 and Caveolin-1 (CAV1). Through this interaction, CAV1 sequesters Ago2 on the plasma membranes and regulates miRNA-mediated translational repression in a compartment-dependent manner. Ago2/CAV1 interaction plays a role in miRNA-mediated mRNA suppression and in miRNA release via extracellular vesicles (EVs) from tumors into the circulation, which can be used as a biomarker of tumor progression. Increased Ago2/CAV1 interaction with tumor progression promotes aggressive cancer behaviors, including metastasis. Ago2/CAV1 interaction acts as a secondary event in miRNA-mediated suppression and increases the complexity of miRNA actions in cancer.


Assuntos
Proteínas Argonautas , Caveolina 1 , MicroRNAs , Metástase Neoplásica , Proteínas Argonautas/metabolismo , Proteínas Argonautas/genética , MicroRNAs/metabolismo , MicroRNAs/genética , Caveolina 1/metabolismo , Caveolina 1/genética , Humanos , Linhagem Celular Tumoral , Animais , Regulação Neoplásica da Expressão Gênica , Vesículas Extracelulares/metabolismo , Camundongos , Ligação Proteica , Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/patologia , Sirtuína 2/metabolismo , Sirtuína 2/genética
2.
Microsurgery ; 43(3): 286-296, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36259780

RESUMO

BACKGROUND: No consensus exists regarding the most effective reconstruction after total laryngectomy with partial pharyngectomy (TLwPP). This study aims to compare different reconstructive techniques (pectoralis major myo-cutaneous flap, PMMCF; anterolateral thigh flap, ALTF; radial forearm free flap, RFFF) after TLwPP in terms of pharyngocutaneous fistula (PCF), stenosis and feeding tube dependence (FTD) incidence. METHODS: The Scopus, PubMed/MEDLINE, Cochrane Library, and Google Scholar databases were searched. A single-arm meta-analysis was performed for PCF incidence, stenosis incidence, and FTD incidence on the entire cohort. An arm-based network analysis was conducted to compare three different surgical interventions (PMMCF, ALTF, RFFF). RESULTS: A total of 13 studies and 232 patients were included in the network meta-analysis. The lowest PCF absolute risk was measured for the RFFF (11.7%, 95% CI: 2.8%-33.4%), compared to the ALTF (13.4%, 95% CI: 4.5%-32.1%) and the PMMC (49.0%, 95% CI: 19.2%-79.3%). The RFFF showed a stenosis absolute risk of 0.0% (95% CI: 0.0%-1.1%), while a higher stenosis incidence was measured for the ALTF (5.7%, 95% CI: 0.8%-25.2%) and the PMMCF (11.6%, 95% CI: 0.8%-55.1%). The RFFF showed the lowest absolute risk of FTD incidence (6.8%, 95% CI: 0.5%-28.1%) compared to the other reconstructive techniques (PMMCF: 12.4%, 95% CI: 2.4%-42.1%; ALTF: 17.5%, 95% CI: 6.4%-38.9%). CONCLUSIONS: The RFFF seems the best choice for reconstruction of partial pharyngeal defects after TLwPP due to the lower incidence of PCF, stenosis and FTD compared to the ALTF and the PMMCF.


Assuntos
Fístula Cutânea , Retalhos de Tecido Biológico , Demência Frontotemporal , Doenças Faríngeas , Humanos , Faringectomia/efeitos adversos , Laringectomia/efeitos adversos , Coxa da Perna/cirurgia , Metanálise em Rede , Constrição Patológica/cirurgia , Músculos Peitorais , Demência Frontotemporal/complicações , Demência Frontotemporal/cirurgia , Estudos Retrospectivos , Fístula Cutânea/cirurgia , Doenças Faríngeas/etiologia
3.
Medicina (Kaunas) ; 58(12)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36557011

RESUMO

Background and objectives: Among patients with pathologically proven T2N0 oral squamous cell carcinoma (OSCC), a notable amount of patients still die from tumor recurrence although they have radical surgery for early stage cancers. In literature, the prognostic indicators of this specific disease entity were rarely reported. This study aims at analyzing the prognostic factors of T2N0 OSCC patients and discussing possible managements to improve the survival. MATERIALS AND METHODS: From January 2012 to December 2017, the data of 166 pathologically proven T2N0 oral cancer patients proved by radical surgery were retrospectively collected. The clinical and pathologic factors including age, gender, tumor differentiation grade, perineural invasion (PNI), angiolymphatic invasion (ALI), margin status, and adjuvant therapy were analyzed by univariate and multivariate analysis to determine their association with disease-specific survival (DSS), and disease-free survival (DFS), which were calculated by Kaplan-Meier method. RESULTS: After median follow up time of 43.5 months, overall 3-year rates of DSS and DFS were 86.1% and 80.1% respectively for our 166 patients. Univariate analysis showed that the 3-year DSS of 90.8% for PNI negative patients was significantly better than DSS of 57.0% for PNI positive patients (p = 0.0006). The 3-year DFS of 84.2% for PNI negative patients was also significantly better than DFS of 54.6% for PNI positive patients (p = 0.001). Further multivariate analysis revealed PNI was the only independent prognostic factor associated with both DSS (Hazard Ratio (HR) = 5.02; 95% Confidence Interval (CI) = 1.99-12.6; p = 0.001), and DFS (HR = 3.92; 95% CI = 1.65-9.32; p = 0.002). Nearly 10% (16) of the 166 patients had adverse pathologic feature of PNI only. In the 11 patients without adjuvant therapy, 5 patients died from OSCC. No patients had recurrence or mortality after they received adjuvant therapy with chemotherapy ± radiotherapy. CONCLUSION: PNI was an independent prognostic factor for T2N0 oral cancer patients. Adjuvant chemotherapy and radiotherapy may benefit the survival of this specific disease entity, but further investigations are needed to elucidate the optimal regimen.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Humanos , Prognóstico , Carcinoma de Células Escamosas/patologia , Estudos Retrospectivos , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias
5.
Clin Gastroenterol Hepatol ; 18(7): 1466-1474.e4, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31546059

RESUMO

BACKGROUND & AIMS: Patients with isolated laryngopharyngeal reflux symptoms (LPRS) defined as those without concomitant typical reflux symptoms (CTRS) are clinically challenging to manage due to unclear pathophysiology. We investigated esophageal physiology in patients with isolated LPRS and their response to proton-pump inhibitors (PPI) therapy. METHODS: This is a multi-center observational study conducted in referral hospitals in Taiwan. Patients with predominant LPRS, but without common non-reflux causes, underwent esophageal manometry, 24-hr ambulatory esophagopharyngeal pH testing, and Bernstein test, followed by a 12-week esomeprazole 40 mg twice-daily treatment. Participants with pathological reflux were divided into the isolated LPRS group (ie, LPRS without CTRS, n = 40) and the CTRS group (ie, LPRS with CTRS, n = 66). Participants without pathological reflux or esophagitis (n = 132) served as the nonreflux controls. RESULTS: The PPI-responsiveness was similar between the isolated LPRS group and CTRS group (63% vs 57%, P = .8), but lower in the nonreflux controls (32%, P = .005). Despite similar distal esophageal acid exposure time (P = .7) when compared to those with CTRS, the isolated LPRS group had a lower prevalence of both positive Bernstein test (P = .001) and ineffective esophageal motility disorder (P = .03), and fewer pharyngeal acid reflux episodes (P < .0001). CONCLUSIONS: Our findings indicate similar distal esophageal acid exposure and PPI-responsiveness between LPRS patients with and without CTRS. The lack of CTRS in the isolated LPRS group is likely due to esophageal acid hyposensitivity and fewer pharyngeal acid reflux episodes, thus implicating distinct pathophysiology of isolated LPRS from those with CTRS.


Assuntos
Transtornos da Motilidade Esofágica , Refluxo Laringofaríngeo , Monitoramento do pH Esofágico , Azia , Humanos , Manometria , Inibidores da Bomba de Prótons
6.
Jpn J Clin Oncol ; 50(6): 653-660, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32236415

RESUMO

OBJECTIVE: For recurrent laryngeal cancers, trans-oral robotic surgery has been used to perform total laryngectomy, but limited cases had been reported without long-term outcome follow-up. This study aims at presenting the largest longitudinal retrospective cohort in a single tertiary referral medical center. METHODS: From November 2013 to August 2017, seven patients with recurrent laryngeal cancers without evidence of neck metastasis were selected to receive trans-oral robotic surgery-assisted TL without neck dissection. The para-operative details including the surgical success rates, surgical methods, resection extent, drainage tube placement, pharyngeal wound closure, console surgical time, pathologic findings and long-term complications were reviewed and described. The study end points include survival rates and preservation of swallowing function without tube feeding. RESULTS: Trans-oral robotic surgery-assisted total laryngectomy was successfully performed on all seven patients with mean surgical console time of 111 ± 66 min. Strap muscles and hyoid bone were resected like open surgery in six and five patients, respectively. For all the seven patients, there was no severe pharyngo-cutaneous fistula formation requiring repair in a second surgery, but tracheostoma stenosis was not uncommon (57%). Three patients received adjuvant chemotherapy/radiotherapy. After follow-up of 36.1 ± 15.8 months, two patients had neck recurrence, and one patient died 19 months after surgery, but the other five patients were alive without disease recurrence. The overall survival rate was 85.7% (6/7), and all patients had good swallowing function without tube feeding. CONCLUSIONS: Trans-oral robotic surgery-assisted total laryngectomy is a feasible approach for selected patients with recurrent laryngeal cancers. The oncologic and functional outcomes were satisfactory. Further larger cohort study is worthwhile to further elucidate the value of trans-oral robotic surgery-assisted total laryngectomy.


Assuntos
Neoplasias Laríngeas/cirurgia , Laringectomia , Recidiva Local de Neoplasia , Procedimentos Cirúrgicos Robóticos , Idoso , Humanos , Neoplasias Laríngeas/patologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Duração da Cirurgia , Estudos Retrospectivos , Resultado do Tratamento
7.
J Formos Med Assoc ; 119(1 Pt 3): 392-398, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31280909

RESUMO

BACKGROUND: There are still oral cancer patients without surgery. To improve the survival, it is necessary to know the causes of the oral cancer patients without surgery. METHODS: 23,217 patients with a newly-diagnosed oral cancer in Taiwan Cancer Registry (TCR) database between 2011 and 2015 were enrolled. Data from TCR database named "Reason for No Surgery of Primary Site" were extracted for analysis of the causes of those without surgery. Overall survival plots were presented using the Kaplan-Meier method with log-rank test. RESULTS: 3263 (14%) patients did not received surgery. Among them, there were 720 patients (group 3) without surgery although surgery was advised, 154 patients (group 2) because of poor condition or death before surgery, and 2389 patients (group 1) because of other causes. Twenty-four percent of the patients with surgery were treated one month and more after diagnosis. The 5-year overall survival rates were 68.7%, 25.2%, 9.1% and 17.3% for surgery group, group 3, 2 and 1, respectively (p < 0.001). The mean age of the patients with and without surgery were 54.8 and 59.3, respectively (p < 0.01). Female patients were commoner in group 3 (p < 0.01). The patients without surgery was commoner in the middle (15.7%) and southern (14.8%) than in Northern Taiwan (12.1%). All groups without surgery had more advanced stage and lower BMI (p < 0.01). CONCLUSION: One-sevenths of patients were not treated surgically because of refusal, poor condition, older age, low BMI, and advanced stage. It is necessary to encourage the patients to undergo surgery with shortening the diagnosis-to-treatment interval.


Assuntos
Neoplasias Bucais/mortalidade , Neoplasias Bucais/cirurgia , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Análise de Sobrevida , Taiwan/epidemiologia , Fatores de Tempo
9.
Support Care Cancer ; 25(5): 1529-1536, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28039504

RESUMO

PURPOSE: Head and neck cancers (HNCs) usually present a poor prognosis and cause high morbidity rates. Recent surveys have demonstrated that HNC incidence rates are still on the increase in many countries. Our study objective was to assess the end-of-life care for patients with HNCs in Taiwan. METHODS: Data was retrieved from Taiwan's National Health Insurance Research Database, where we identified patients who had been diagnosed with HNCs from January 1997 to December 2010. Each patient's annual trend of opioid use and hospice care needs, along with the distribution of place of death in the study cohort, were all analyzed. RESULTS: A total of 98,211 HNC patients diagnosed between 1997 and 2010 were eligible for this study. The majority of HNC patients died in hospital. Patients who were male, lived in capital area, had a higher income, had received palliative hospice care, and had been prescribed opioids tended to choose to die at home or in hospice wards. Both opioid prescription and hospice care have increased during the past 10 years; however, the rate of palliative hospice care remained below 50%. CONCLUSIONS: Our results demonstrate that greater efforts are needed to implement palliative care for HNC patients in Taiwan.


Assuntos
Neoplasias de Cabeça e Pescoço/terapia , Cuidados Paliativos na Terminalidade da Vida/métodos , Assistência Terminal/psicologia , Planejamento em Saúde Comunitária , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade
10.
Eur Arch Otorhinolaryngol ; 274(1): 431-439, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27430224

RESUMO

The aim of this study was to investigate the association between microsatellite alteration in the surgical margins and local recurrence of oral cavity squamous cell carcinoma patients. Surgical specimens confirmed by pathological examination and corresponding surgical margins were collected from 120 oral cavity squamous cell carcinoma patients. Ten microsatellite markers were examined in the tumor specimens and paired surgical margins, which proved to be negative on pathological assessment. The specimens and surgical margins were amplified by polymerase chain reaction followed by computerized analysis. Forty-two specimens (35.0 %) with microsatellite instability (MSI) in at least one marker were found, and more than half of the specimens (n = 73, 60.8 %) had loss of heterozygosity (LOH) in at least one marker. Although MSI and LOH were not associated with the prognosis of oral cavity squamous cell carcinoma patients, presence of MSI in the tumor-free surgical margins increased the risk of local recurrence (hazard ratio: 9.549; 95 % confidence interval: 4.143-22.01). Genetic analysis of tumor-free surgical margins is a useful tool for identifying oral cavity squamous cell carcinoma patients who are vulnerable to local recurrence.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Perda de Heterozigosidade , Margens de Excisão , Instabilidade de Microssatélites , Neoplasias Bucais/cirurgia , Recidiva Local de Neoplasia/genética , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Modelos de Riscos Proporcionais , Estudos Prospectivos
11.
Eur Arch Otorhinolaryngol ; 273(1): 245-50, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26156227

RESUMO

We investigated the impact of fibrin glue on postoperative drainage amount and duration in head and neck cancer patients who underwent neck dissection. This study was a prospective randomized controlled trial. Patients who were scheduled to undergo neck dissection due to head and neck cancer were eligible for this study. After receiving a detailed explanation, all patients signed an informed consent form before enrollment. Patients were then randomly assigned to the study group (fibrin glue) or control group. In the study group, 2 ml of fibrin glue (Tissucol(®); Duploject, Baxter AG) was applied on the surface of the surgical wound before closure. Basic demographic data along with tumor-related features, operation-related variables, postoperative drainage amount/duration, postoperative pain, and analgesic usage were collected and analyzed. A total of 15 patients were included in the final analyses, with eight patients in the study group and seven patients in the control group. No significant differences were found between the two groups in age, gender, primary site, clinical N stage, neck dissection levels, perioperative bleeding, postoperative drainage amount/duration, hospitalization duration, and postoperative pain status. The application of 2 ml fibrin glue by the method described herein did not reduce the postoperative drainage amount/duration nor the postoperative pain status in patients who underwent neck dissection.


Assuntos
Adesivo Tecidual de Fibrina/administração & dosagem , Neoplasias de Cabeça e Pescoço , Esvaziamento Cervical , Dor Pós-Operatória/prevenção & controle , Hemorragia Pós-Operatória/prevenção & controle , Cicatrização/efeitos dos fármacos , Idoso , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical/efeitos adversos , Esvaziamento Cervical/métodos , Dor Pós-Operatória/diagnóstico , Hemorragia Pós-Operatória/diagnóstico , Estudos Prospectivos , Adesivos Teciduais/administração & dosagem , Resultado do Tratamento
12.
Value Health ; 18(4): 396-403, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26091593

RESUMO

BACKGROUND: Different end-point measures may contribute to inconsistent therapeutic responses in relief of laryngopharyngeal reflux (LPR) symptoms. OBJECTIVES: We aimed to determine an a priori responder definition for a patient-reported outcome instrument, the Reflux Symptom Index (RSI), using an anchor-based method, to interpret individual treatment benefit in patients with LPR, on the basis of the US Food and Drug Administration guidance. METHODS: Patients with chronic laryngeal symptoms suggestive of LPR underwent twice-daily 40 mg esomeprazole treatment for 12 weeks. We used a 50% or more reduction in the primary laryngeal symptom at week 12, an empirical criterion, as an anchor to dichotomize the participants into two groups, and to establish a responder definition of the RSI score change. The optimal cutoff point of the RSI score change was determined on the basis of the maximal Youden index of the receiver operating characteristic analysis. RESULTS: The mean reduction in the RSI score was significantly greater in subjects with a 50% or more reduction in the primary laryngeal symptom than in those without (-11.0 ± 7.8 vs. -3.1 ± 8.3, P < 0.0001). A reduction of six points or more in the RSI score at week 12 was considered to be the responder definition with a sensitivity of 0.79 and a specificity of 0.70. CONCLUSIONS: We propose an a priori responder definition derived from an empirical criterion according to the Food and Drug Administration guidance: a reduction of six points or more in the RSI score at week 12. This preliminary estimate provides a clinically meaningful change at an individual level, although additional studies and validations across various languages are required.


Assuntos
Refluxo Laringofaríngeo/tratamento farmacológico , Avaliação de Resultados da Assistência ao Paciente , Guias de Prática Clínica como Assunto/normas , Inibidores da Bomba de Prótons/uso terapêutico , Autorrelato/normas , United States Food and Drug Administration/normas , Adulto , Esomeprazol/uso terapêutico , Feminino , Seguimentos , Humanos , Refluxo Laringofaríngeo/diagnóstico , Refluxo Laringofaríngeo/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Estados Unidos/epidemiologia
13.
Eur Arch Otorhinolaryngol ; 272(11): 3475-82, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25359197

RESUMO

The aim of this study was to investigate the factors associated with infection at the recipient site of pectoralis major myocutaneous flap (PMMF) of head and neck cancer patients. We retrospectively reviewed head and neck cancer patients who underwent PMMF reconstruction and identified those with recipient site infection. Variables of patients with and without infection were compared and associated factors were investigated by logistic regression model. A total of 478 patients were included in the final analysis and 183 patients (38.3%) developed recipient site infection. Lower margin of skin island, concurrent tracheotomy, diabetes mellitus, mandibular plate reconstruction, prior radiation, and peri-operative blood transfusion were independent factors associated with recipient site infection of PMMF. Skin island of PMMF beyond the eighth intercostal space markedly increased the risk of recipient site infection after major head and neck cancer surgery. Recognition of relevant factors associated with infection may help surgeons to identify those at risk.


Assuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Retalho Miocutâneo , Músculos Peitorais/transplante , Infecção da Ferida Cirúrgica/etiologia , Adulto , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
14.
Cereb Cortex ; 23(6): 1410-23, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22617848

RESUMO

Glia-guided migration (glia-guided locomotion) during radial migration is a characteristic yet unique mode of migration. In this process, the directionality of migration is predetermined by glial processes and not by growth cones. Prior to the initiation of glia-guided migration, migrating neurons transform from multipolar to bipolar, but the molecular mechanisms underlying this multipolar-bipolar transition and the commencement of glia-guided migration are not fully understood. Here, we demonstrate that the multipolar-bipolar transition is not solely a cell autonomous event; instead, the interaction of growth cones with glial processes plays an essential role. Time-lapse imaging with lattice assays reveals the importance of vigorously active growth cones in searching for appropriate glial scaffolds, completing the transition, and initiating glia-guided migration. These growth cone activities are regulated by Abl kinase and Cdk5 via WAVE2-Abi2 through the phosphorylation of tyrosine 150 and serine 137 of WAVE2. Neurons that do not display such growth cone activities are mispositioned in a more superficial location in the neocortex, suggesting the significance of growth cones for the final location of the neurons. This process occurs in spite of the "inside-out" principle in which later-born neurons are situated more superficially.


Assuntos
Movimento Celular/genética , Cones de Crescimento/fisiologia , Proteínas de Homeodomínio/metabolismo , Neuroglia/fisiologia , Neurônios/citologia , Família de Proteínas da Síndrome de Wiskott-Aldrich/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Fatores Etários , Animais , Caderinas/metabolismo , Proliferação de Células , Células Cultivadas , Córtex Cerebral/citologia , Chlorocebus aethiops , Sulfato de Dextrana/metabolismo , Embrião de Mamíferos , Feminino , Regulação da Expressão Gênica no Desenvolvimento/genética , Técnicas de Transferência de Genes , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Proteínas de Homeodomínio/genética , Imunoprecipitação , Técnicas In Vitro , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mutação/genética , Neurônios/fisiologia , Gravidez , Interferência de RNA/fisiologia , Transfecção , Família de Proteínas da Síndrome de Wiskott-Aldrich/genética
15.
Head Neck ; 46(5): 1063-1073, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38385970

RESUMO

BACKGROUND: For R/M HNSCC, the differences in prognosis and treatment options between distant metastasis (DM) and locoregional recurrence, especially in the DM group, remain unclear. METHODS: From the Taiwan Head Neck Society registry database, patients who were diagnosed with R/M HNSCC and received cetuximab-based frontline therapy were collected for analysis. RESULTS: Among the enrolled patients, 59.3% (491/827) belonged to the DM group. The DM group had less primary site of oral cavity, less betel nut chewing, higher lactate dehydrogenase (LDH) levels, and higher LDH/albumin ratio compared with the non-DM group. For the patients with primary site of oral cavity and current smokers, DM coexisted with poorer outcomes. In the DM group, EXTREME-like regimen was more suitable for older patients, those with elevated LDH, and those with higher LDH/albumin ratio than TPExtreme-like regimen. CONCLUSION: DM coexisted with poorer prognosis in certain groups. LDH-associated biomarkers may aid treatment options for DM patients.


Assuntos
Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Cetuximab/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Taiwan , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/patologia , Albuminas
16.
J Neurosci ; 32(32): 11050-66, 2012 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-22875938

RESUMO

Neuronal migration is a critical feature to ensure proper location and wiring of neurons during cortical development. Postmitotic neurons migrate from the ventricular zone into the cortical plate to establish neuronal lamina in an "inside-out" gradient of maturation. Here, we report that the mitotic kinase Aurora-A is critical for the regulation of microtubule organization during neuronal migration via an Aurora-A-NDEL1 pathway in the mouse. Suppression of Aurora-A activity by inhibitors or siRNA resulted in severe impairment of neuronal migration of granular neurons. In addition, in utero injection of the Aurora-A kinase-dead mutant provoked defective migration of cortical neurons. Furthermore, we demonstrated that suppression of Aurora-A impaired microtubule modulation in migrating neurons. Interestingly, suppression of CDK5 by an inhibitor or siRNA reduced Aurora-A activity and NDEL1 phosphorylation by Aurora-A, which led to defective neuronal migration. We found that CDK5RAP2 is a key molecule that mediates functional interaction and is essential for centrosomal targeting of Aurora-A. Our observations demonstrated novel and surprising cross talk between Aurora-A and CDK5 during neuronal migration.


Assuntos
Movimento Celular/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Microtúbulos/metabolismo , Neurônios/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Amiodarona , Análise de Variância , Animais , Animais Recém-Nascidos , Aurora Quinase A , Aurora Quinases , Bromodesoxiuridina/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Cerebelo/citologia , Quinase 5 Dependente de Ciclina/genética , Quinase 5 Dependente de Ciclina/metabolismo , Inibidores Enzimáticos/farmacologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/genética , Proteínas de Fluorescência Verde/genética , Masculino , Camundongos , Camundongos Transgênicos , Microscopia Confocal , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Mutação/genética , Neurônios/efeitos dos fármacos , Fosforilação/genética , Piperazinas/farmacologia , Gravidez , Proteínas Serina-Treonina Quinases/genética , Purinas/farmacologia , RNA Interferente Pequeno/farmacologia , Roscovitina , Fatores Sexuais , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
17.
Diagnostics (Basel) ; 13(9)2023 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-37175034

RESUMO

Laryngopharyngeal reflux (LPR) is a variant of gastroesophageal reflux disease (GERD) in which gastric refluxate irritates the lining of the aerodigestive tract and causes troublesome airway symptoms or complications. LPR is a prevalent disease that creates a significant socioeconomic burden due to its negative impact on quality of life, tremendous medical expense, and possible cancer risk. Although treatment modalities are similar between LPR and GERD, the diagnosis of LPR is more challenging than GERD due to its non-specific symptoms/signs. Due to the lack of pathognomonic features of endoscopy, mounting evidence focused on physiological diagnostic testing. Two decades ago, a dual pH probe was considered the gold standard for detecting pharyngeal acidic reflux episodes. Despite an association with LPR, the dual pH was unable to predict the treatment response in clinical practice, presumably due to frequently encountered artifacts. Currently, hypopharygneal multichannel intraluminal impedance-pH catheters incorporating two trans-upper esophageal sphincter impedance sensors enable to differentiate pharyngeal refluxes from swallows. The validation of pharyngeal acid reflux episodes that are relevant to anti-reflux treatment is, therefore, crucial. Given no diagnostic gold standard of LPR, this review article aimed to discuss the evolution of objective diagnostic testing and its predictive role of treatment response.

18.
J Voice ; 37(6): 970.e19-970.e27, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34226090

RESUMO

The self-reporting voice-related quality of life (V-RQOL) instrument has been viewed as a modular index of quality of life for speakers using tracheoesophageal, esophageal (ES), or electrolaryngeal speech. However, V-RQOL has never been studied with pneumatic artificial laryngeal (PA) individuals. This study attempted to quantify the self-assessed voice-related performance of PA and ES speakers in Taiwan via the V-RQOL questionnaire, and further to compare the results for PA and ES speakers. METHODS: V-RQOL was assessed in 79 PA and 25 ES speakers undergoing total laryngectomy without using tracheoesophageal puncture. Data were collected from members of Taiwan's Association of Laryngectomees. RESULTS: There was no significant difference between PA and ES participants in social-emotional, physical functioning and total scores, suggesting both may consider their quality of life comparable with each other. In ES participants, there was a significant effect of time after total laryngectomy in physical functioning and total scores. CONCLUSIONS: PA speakers did not exhibit more dissatisfaction or disability than ES speakers on 10 statements in the V-RQOL, but after total laryngectomy the ES have been shown to improve over time. Information on the experience of PA and ES speakers could be used by clinicians to inform patients of potential outcomes, and help them select suitable rehabilitation techniques.


Assuntos
Laringe Artificial , Voz , Humanos , Qualidade de Vida/psicologia , Qualidade da Voz , Voz Esofágica , Laringectomia/efeitos adversos , Laringectomia/reabilitação
19.
Biol Direct ; 18(1): 44, 2023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37550720

RESUMO

BACKGROUND: Patients with triple-negative breast cancer (TNBC) tend to develop visceral metastasis within five years, making them the most challenging BC patients to treat. The MAP7 protein family is a group of microtubule-binding proteins with a well-known role in microtubule-related cell migration, but its role in metastasis-related properties of TNBC remains unclear. METHODS: qRT-PCR and western blot were used to validate mRNA and protein expression of the MAP7 family in the isogenic pairs of TNBC cell lines with low and high metastasis potential. Functional characterization of MAP7D3 was carried out using cell-based and mouse models. The clinical association between MAP7D3 and TNBC was established using datasets in the public domain. RESULTS: MAP7D3 expression was consistently upregulated in the metastatic subline IV2 and 468-LN at both mRNA and protein levels. Knockdown of MAP7D3 inhibited the 3D colony-forming ability, cell migration, and invasion ability of IV2 and 468-LN, indicating its significant contribution to the metastasis phenotypes. Mechanistically, inhibition of MAP7D3 could significantly increase the sensitivity of metastatic TNBC cells to docetaxel and gemcitabine treatment by reducing the expression of proteins related to breast cancer-initiating cells (BCICs) and drug resistance, as well as suppressing the activity of Rac1. The animal study showed that the depletion of MAP7D3 drastically reduced TNBC tumor growth and impaired the metastatic capability of TNBC cells. Elevated expression of MAP7D3 was found in the metastatic lymph nodes and was significantly associated with advanced stage and higher grade TNBC. Moreover, MAP7D3 expression was significantly correlated with the TNBC population, and its high expression was significantly associated with lymph node metastasis and poor survival outcomes of patients with TNBC. CONCLUSION: Our study indicates that targeting MAP7D3 could be a promising therapeutic strategy for addressing the progression of TNBC, and MAP7D3 may serve as a novel predictive biomarker for the survival outcomes of triple-negative breast cancer.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Neoplasias de Mama Triplo Negativas/genética , Prognóstico , Movimento Celular/genética , Proteínas de Transporte/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica
20.
Cancer Med ; 12(6): 6802-6810, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36426417

RESUMO

BACKGROUND: Hepatitis B virus (HBV) affects the occurrence and survival outcome of various malignant disorders. The study aimed to evaluate the survival outcome of head and neck squamous cell cancer (HNSCC) patients with or without HBV infection. METHODS: This study included patients with HNSCC who visited Taichung Veterans General Hospital from 2007 to 2015. HBV infection was defined by hepatitis B surface antigen (HBsAg) seropositivity. By propensity score matching, we compared survival outcomes, including progression-free survival (PFS) and overall survival (OS), among patients with or without HBV infection. RESULTS: The prevalence of HBV infection in our cohort was 12.3%. Among the 1,015 patients included in the matched analysis, a higher risk of baseline liver cirrhosis (11.3% vs. 3.4%, p < 0.001) and initial hepatic dysfunction (10.8% vs. 5.4%, p = 0.005) rates were observed than those without HBV infection at baseline. The 5-year OS was 43.1% and 53.2% (p < 0.001) and the 5-year PFS was 37.4% and 42.3% (p = 0.007) in patients with and without HBV infection, respectively. The incidence of subsequent hepatic dysfunction showed no difference between patients with and without HBV infection (29.6% vs. 26.8%, p = 0.439). CONCLUSIONS: Patients with HNSCC and HBV infection were younger and had a higher risk of cirrhosis compared to those without HBV infection. Moreover, HBV infection significantly influenced the OS and PFS outcomes but not subsequent hepatic dysfunction in patients with HNSCC.


Assuntos
Neoplasias de Cabeça e Pescoço , Hepatite B , Neoplasias de Células Escamosas , Humanos , Vírus da Hepatite B , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Estudos Retrospectivos , Hepatite B/complicações , Hepatite B/epidemiologia , Antígenos de Superfície da Hepatite B , Cirrose Hepática/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia
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