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1.
J Med Virol ; 92(12): 3807-3814, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32492214

RESUMO

OBJECTIVE: This study aimed to evaluate the incidence of and factors associated with persistence and clearance of oral human papillomavirus (HPV) infections. METHOD: A prospective cohort study invited 458 subjects (231 HPV-positive and 227 HPV-negative at baseline) to attend follow-ups at 12 months. Those 231 HPV-positive subjects and 10 new infections were invited to reassessment at 24 months. We used next-gen sequencing for detection and genotyping of HPV. RESULTS: α-HPV infections showed higher persistence rates than ß/γ-HPV (22.7% vs 9.2% at 12 months [P < .05], 10.6% vs 6.8% at 24 months [P = .30]). Clearance rates of α-HPV were lower than ß/γ-HPV at 12 months (31.8% vs 45.1%; P = .05) and higher at 24 months (7.6% vs 4.8%; P = .36). Persistence of ß/γ-HPV was positively associated with males (crude odds ratio [COR] = 3.8, 95% confidence interval [CI] = 1.3-11.2), elderly (51-65 vs 16-50 years; COR = 5.1, 95% CI = 1.2-22.3), and smoking (COR = 4.3, 95% CI = 1.9-9.6). Drinking (COR = 0.5, 95% CI = 0.3-0.9), handwashing less than 90% of times before meals (COR = 0.6, 95% CI = 0.3-0.9), and using public bath more than once per month (COR = 0.5, 95% CI = 0.2-0.9) were risk factors hindering ß/γ-HPV clearance. CONCLUSIONS: This study identified factors associated with persistence and clearance of oral HPV infections among Chinese. Studies on other ethnogeographic groups may further inform prevention strategies of oral HPV infection and immunization programmes.

2.
Eur Radiol ; 29(10): 5627-5634, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30903340

RESUMO

OBJECTIVES: MRI can detect early-stage nasopharyngeal carcinoma (NPC), but the detection is more challenging in early-stage NPCs because they must be distinguished from benign hyperplasia in the nasopharynx. This study aimed to determine whether intravoxel incoherent motion diffusion-weighted imaging (IVIM DWI) MRI could distinguish between these two entities. METHODS: Thirty-four subjects with early-stage NPC and 30 subjects with benign hyperplasia prospectively underwent IVIM DWI. The mean pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC) values were calculated for all subjects and compared between the 2 groups using Student's t test. Receiver operating characteristics with the area under the curve (AUC) was used to identify the optimal threshold for all significant parameters, and the corresponding diagnostic performance was calculated. A p value of < 0.05 was considered statistically significant. RESULTS: Compared with benign hyperplasia, early-stage NPC exhibited a significantly lower D mean (0.64 ± 0.06 vs 0.87 ± 0.11 × 10-3 mm2/s), ADC0-1000 mean (0.77 ± 0.08 vs 1.00 ± 0.13 × 10-3 mm2/s), ADC300-1000 (0.63 ± 0.05 vs 0.86 ± 0.10 × 10-3 mm2/s) and a higher D* mean (32.66 ± 4.79 vs 21.96 ± 5.21 × 10-3 mm2/s) (all p < 0.001). No significant difference in the f mean was observed between the two groups (p = 0.216). The D and ADC300-1000 mean had the highest AUC of 0.985 and 0.988, respectively, and the D mean of < 0.75 × 10-3 mm2/s yielded the highest sensitivity, specificity and accuracy (100%, 93.3% and 96.9%, respectively) in distinguishing early-stage NPC from benign hyperplasia. CONCLUSION: DWI has potential to distinguish early-stage NPC from benign hyperplasia and D and ADC300-1000 mean were the most promising parameters. KEY POINTS: • Diffusion-weighted imaging has potential to distinguish early-stage nasopharyngeal carcinoma from benign hyperplasia in the nasopharynx. • The pure diffusion coefficient, pseudo-diffusion coefficient from intravoxel incoherent motion model and apparent diffusion coefficient from conventional diffusion-weighted imaging were significant parameters for distinguishing these two entities in the nasopharynx. • The pure diffusion coefficient, followed by apparent diffusion coefficient, may be the most promising parameters to be used in screening studies to help detect early-stage nasopharyngeal carcinoma.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Detecção Precoce de Câncer/métodos , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Estadiamento de Neoplasias/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Hiperplasia/diagnóstico , Masculino , Pessoa de Meia-Idade , Doenças Nasofaríngeas/diagnóstico , Curva ROC , Reprodutibilidade dos Testes
3.
Mol Ther ; 26(9): 2295-2303, 2018 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-30005868

RESUMO

Thyroid cancer is rapidly increasing in incidence worldwide. Although most thyroid cancer can be cured with surgery, radioactive iodine, and/or chemotherapy, thyroid cancers still recur and may become chemoresistant. Autophagy is a complex self-degradative process that plays a dual role in cancer development and progression. In this study, we found that miR-125b was downregulated in tissue samples of thyroid cancer as well as in thyroid cancer cell lines, and the expression of Foxp3 was upregulated. Further, we demonstrated that miR-125b could directly act on Foxp3 by binding to its 3' UTR and inhibit the expression of Foxp3. A negative relationship between miR-125b and Foxp3 was thus revealed. Overexpression of miR-125b markedly sensitized thyroid cancer cells to cisplatin treatment by inducing autophagy through an Atg7 pathway in vitro and in vivo. Taken together, our findings demonstrate a novel mechanism by which miR-125b has the potential to negatively regulate Foxp3 to promote autophagy and enhance the efficacy of cisplatin in thyroid cancer. miR-125 may be of therapeutic significance in thyroid cancer.


Assuntos
Autofagia/efeitos dos fármacos , Fatores de Transcrição Forkhead/metabolismo , MicroRNAs/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Regiões 3' não Traduzidas/efeitos dos fármacos , Regiões 3' não Traduzidas/genética , Autofagia/genética , Linhagem Celular Tumoral , Cisplatino/farmacologia , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Técnicas In Vitro , MicroRNAs/genética , Neoplasias da Glândula Tireoide/genética
4.
J Infect Dis ; 218(3): 388-397, 2018 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-29982800

RESUMO

Background: Knowledge of the prevalence of and risk factors for oral human papillomavirus (HPV) infection, especially cutaneous types, is limited. Methods: A population-based study using next-generation sequencing consecutively recruited asymptomatic individuals aged 18-64 years from a proportional sampling of the general population of Hong Kong, according to age groups, gender, and regions of residence. We examined associations of alpha-, beta-, and gamma-HPVs from oral rinse samples with participants' sociodemographics by logistic regression models. Results: The prevalence of oral HPV infection among 1426 ethnic Chinese was 15.5% (95% confidence interval [CI], 13.7%-17.5%), 2.5% (95% CI, 1.8%-3.5%), 11.9% (95% CI, 10.3%-13.6%), and 2.9% (95% CI, 2.1%-3.9%) for any type, alpha-, beta-, and gamma-HPV, respectively. Prevalence of any high-risk HPV was 0.8% (95% CI, 0.4%-1.4%), and that of HPV-16 was 0.4% (95% CI, 0.2%-0.8%). HPV-8 and HPV-98 were the most common beta types detected, while HPV-4 and HPV-SD2R were the most common gamma types. Prevalence of alpha- and beta/gamma-HPV infection showed a similar pattern of increase with age, and was higher in men than women. Smoking, drinking, oral sex, and more sexual partners were associated with alpha-HPV. Teeth brushing before sleep was protective for beta/gamma-HPVs. Discussion: The epidemiologic factors associated with oral infection with alpha-HPVs are different from those of beta/gamma-HPVs, suggesting different modes of acquisition and persistence.


Assuntos
Alphapapillomavirus/isolamento & purificação , Betapapillomavirus/isolamento & purificação , Gammapapillomavirus/isolamento & purificação , Doenças da Boca/epidemiologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Adolescente , Adulto , Idoso , Alphapapillomavirus/classificação , Alphapapillomavirus/genética , Povo Asiático , Doenças Assintomáticas , Betapapillomavirus/classificação , Betapapillomavirus/genética , Demografia , Feminino , Gammapapillomavirus/classificação , Gammapapillomavirus/genética , Sequenciamento de Nucleotídeos em Larga Escala , Hong Kong/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Boca/virologia , Papillomaviridae/classificação , Infecções por Papillomavirus/virologia , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Inquéritos e Questionários , Adulto Jovem
5.
J Cell Biochem ; 117(11): 2473-81, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-26970173

RESUMO

Oxidative stress-induced DNA damage is a known causing factor for many types of tumors, but information on the role of oxidants and antioxidants in thyroid tumors is limited. The aim of this study was to determine antioxidant levels in thyroid tumors. In this study, tumor and its matched non-tumor thyroid tissue samples were obtained from 53 patients with thyroid tumors. The levels of manganese superoxide dismutase (MnSOD), thioredoxin reductase 2 (TXNRD2), glutathione (GSH), glutathione peroxidase (Gpx), catalase (CAT), and 27 kd heat-shock protein (hsp27) were determined in both thyroid tissue samples and cultured thyroid cells by immunohistochemical staining and western blot. Hydrogen peroxide (H2 O2 ) was used to generate oxidant stress in the cell culture experiments. We found that the levels of MnSOD, TXNRD2, GSH, Gpx, and Hsp27 were increased in both malignant and benign tumors, while the level of CAT was decreased. To verify the results of the tissue study, we treated cultured thyroid cells with H2 O2 and found the same pattern of antioxidant changes. Hsp27 was also increased after H2 O2 treatment. The expression of hsp27 was upregulated by 8.24-, 6.96-, and 3.09-fold in thyroid cancer, follicular adenoma, multinodular goiter, respectively. Collectively, our study demonstrated that the levels of hsp27 together with MnSOD, TXNRD2, GSH, and Gpx were significantly upregulated by H2 O2 in thyroid tumors. The increase of these antioxidants is observed in both malignant and benign tumors, particularly in the former. The upregulation of antioxidants is likely a protective mechanism of tumor cells to maintain their survival and growth. J. Cell. Biochem. 117: 2473-2481, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Adenocarcinoma Folicular/metabolismo , Antioxidantes/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Papilar/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Adenocarcinoma Folicular/patologia , Carcinoma Papilar/patologia , Células Cultivadas , Regulação Neoplásica da Expressão Gênica , Proteínas de Choque Térmico , Humanos , Técnicas Imunoenzimáticas , Chaperonas Moleculares , Estresse Oxidativo , Neoplasias da Glândula Tireoide/patologia
6.
J Med Virol ; 88(5): 877-87, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26467027

RESUMO

HPV plays a role in the development of a portion of head and neck squamous cell carcinoma (HNSCC), but only limited information on its role in southern Chinese population is available. A multicenter case-control study was conducted. HPV type, viral integration, E6/7 mRNA expression status, and TP53 mutation were determined. A total of 228 HNSCC were recruited including 137 (60.1%) oral SCC, 34 (14.9%) oropharyngeal SCC, 31 (13.6%) laryngeal SCC, 21 (9.2%) hypopharyngeal SCC, and 5 (2.2%) lip and paranasal sinus SCC. High-risk HPV infection was found in 7.5% (17/228) of HNSCC, but only a small proportion of samples had evidence of viral integration (5.3%, 12/228) or E6/7 mRNA expression (4.4%, 10/228). HPV infection with oncogenic phenotype (integration and E6/7 mRNA expression) was significantly more common in oropharyngeal SCC than controls (9/34, 26.5% vs. 0/42, 0.0%, P < 0.001). Smoking showed a significant association with HNSCC, oropharyngeal SCC, and laryngeal SCC. TP53 mutation was associated with HNSCC (P < 0.001). Older age, TP53 mutation, and HPV16 infection with oncogenic phenotypes were independently associated factors for HNSCC with odds ratios of 1.03 (1.02-1.05), 3.38 (1.71-6.66), and 9.19 (1.13-74.68), respectively. High-risk HPV infection of head and neck mucosa is not uncommon in the Hong Kong population. This study found that 26-30% of oropharyngeal carcinoma was associated with HPV infection, mostly HPV16, and that smoking which predisposes to TP53 mutations was another important risk factor.


Assuntos
Carcinoma de Células Escamosas/virologia , Neoplasias de Cabeça e Pescoço/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Perfilação da Expressão Gênica , Neoplasias de Cabeça e Pescoço/epidemiologia , Hong Kong/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Oncogênicas Virais/biossíntese , Proteínas Oncogênicas Virais/genética , Papillomaviridae/classificação , Infecções por Papillomavirus/epidemiologia , Fatores de Risco , Fumar , Proteína Supressora de Tumor p53/genética , Integração Viral , Adulto Jovem
7.
Eur Arch Otorhinolaryngol ; 273(10): 3363-9, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26897607

RESUMO

Endoscopy is often used to screen for nasopharyngeal carcinoma. A normal nasopharynx on white light endoscopy may yet harbor subclinical or occult malignancy. This study assessed whether the vascular pattern seen on narrow band imaging endoscopy could indicate this and thus be useful for detecting suspected nasopharyngeal carcinoma. The nasopharynx of 156 patients who failed serological screening for or presented with symptoms of nasopharyngeal carcinoma was graded under white light and narrow band imaging endoscopy and a biopsy taken. The accuracy of assessing the nasopharynx as being probably or definitely malignant on white light endoscopy was high (area under the curve = 0.924), as it was of being normal on narrow band imaging endoscopy (=0.799). The sensitivity and specificity of white light and narrow band imaging endoscopy for nasopharyngeal carcinoma was 93 and 22 %, and 92 and 98 %, respectively. Significantly associated with nasopharyngeal carcinoma was a high index of suspicion or definitely malignant grade on white light endoscopy (p < 0.0005, odds 58.978) and vascular tufts on narrow band imaging endoscopy (p = 0.020, odds 41.210). Narrow band imaging endoscopy of vasculature alone for suspected nasopharyngeal carcinoma is not more useful than white light endoscopy of nasopharyngeal morphology, nor does it add to or surpass the diagnostic accuracy of white light endoscopy in this regard.


Assuntos
Endoscopia/métodos , Imagem de Banda Estreita , Neoplasias Nasofaríngeas/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Nasofaringe/diagnóstico por imagem , Nasofaringe/patologia , Sensibilidade e Especificidade , Adulto Jovem
8.
Cancer ; 120(1): 142-53, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24114184

RESUMO

BACKGROUND: Estrogen receptor (ER) and peroxisome proliferator-activated receptor gamma (PPARγ) are associated with thyroid tumorigenesis and treatment. However, the interaction between them has not been studied. METHODS: The impact of ER over-expression or down-expression by DNA/small interfering RNA (siRNA) transfection, ERα agonists, and the ERß agonist diarylpropiolnitrile (DPN) on PPARγ expression/activity was examined in papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC) cells. The effects of PPARγ modulation by rosiglitazone (RTZ), a PPARγ ligand, and of PPARγ siRNA on ER expression were determined. Cellular functions reflected by cell proliferation and migration were assayed. Apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick-end labeling, and apoptotic-related proteins were evaluated by Western blot analysis. RESULTS: PPARγ protein and activity were reduced by the over-expression of either ERα or ERß, whereas repression of ERα or ERß increased PPARγ expression. The administration of RTZ counteracted the effects of ER and also reduced their expression, particularly in PTC cells. Moreover, knockdown of PPARγ increased ER expression and activity. Functionally, ERα activation offset the inhibitory effect of PPARγ on cellular functions, but ERß activation aggregated it and induced apoptosis, particularly in PTC cells. Finally, the interaction between ERß and PPARγ enhanced the expression of proapoptotic molecules, such as caspase-3 and apoptosis-inducing factor. CONCLUSIONS: This study provides evidence supporting a cross-talk between ER and PPARγ. The reciprocal interaction between PPARγ and ERß significantly inhibits the proliferation and migration of thyroid cancer cells, providing a new therapeutic strategy against thyroid cancer.


Assuntos
Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , PPAR gama/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Receptor alfa de Estrogênio/biossíntese , Receptor alfa de Estrogênio/deficiência , Receptor beta de Estrogênio/biossíntese , Receptor beta de Estrogênio/deficiência , Técnicas de Silenciamento de Genes , Humanos , PPAR gama/biossíntese , Receptor Cross-Talk , Rosiglitazona , Transdução de Sinais , Tiazolidinedionas/farmacologia , Neoplasias da Glândula Tireoide/patologia , Transfecção
9.
J Endocrinol ; 261(1)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38329368

RESUMO

The solute carrier (SLC) family is a large group of membrane transport proteins. Their dysfunction plays an important role in the pathogenesis of thyroid cancer. The most well-known SLC is the sodium-iodide symporter (NIS), also known as sodium/iodide co-transporter or solute carrier family 5 member 5 (SLC5A5) in thyroid cancer. The dysregulation of NIS in thyroid cancer is well documented. The role of NIS in the uptake of iodide is critical in the treatment of thyroid cancer, radioactive iodide (RAI) therapy in particular. In addition to NIS, other SLC members may affect the autophagy, proliferation, and apoptosis of thyroid cancer cells, indicating that an alteration in SLC members may affect different cellular events in the evolution of thyroid cancer. The expression of the SLC members may impact the uptake of chemicals by the thyroid, suggesting that targeting SLC members may be a promising therapeutic strategy in thyroid cancer.


Assuntos
Simportadores , Neoplasias da Glândula Tireoide , Humanos , Iodetos/metabolismo , Neoplasias da Glândula Tireoide/genética , Simportadores/genética , Simportadores/metabolismo
10.
Facial Plast Surg Aesthet Med ; 26(1): 15-22, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37256708

RESUMO

Background: An implant (porous polyethylene) is an alternative to rib cartilage for microtia reconstruction but carries a risk of extrusion. Objective: To evaluate the outcome of a hybrid framework of implant with rib cartilage for microtia reconstruction. Methods: Patients who underwent Nagata's technique for microtia reconstruction were reviewed for complications and aesthetic score. In stage 1, a rib cartilage framework or a hybrid framework of implant with rib cartilage was used. In stage 2, the framework was elevated and supported by an implant for projection. Postoperative outcomes were reported for both groups. Results: Forty-four ears of 40 patients underwent surgery. Eleven ears received a rib auricular framework and 33 ears a hybrid auricular framework. The mean postoperative follow-up for the rib and hybrid groups was 76.3 and 43.1 months, respectively. No supporting postauricular implant extruded, whereas stainless-steel wires extruded in seven ears (15.9%). Five (15.2%) hybrid frameworks were removed due to infection or extrusion. Mean operating time was 2 h shorter in the hybrid group. Aesthetic outcomes were similar for both groups. Conclusion: A hybrid framework of rib and implant that requires less harvested cartilage is feasible for microtia reconstruction, but caution should be used due to its higher explantation rate.


Assuntos
Microtia Congênita , Procedimentos de Cirurgia Plástica , Humanos , Microtia Congênita/cirurgia , Polietileno , Porosidade , Cartilagem/transplante , Costelas/cirurgia
11.
J Natl Cancer Inst ; 116(5): 665-672, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38171488

RESUMO

BACKGROUND: Although contrast-enhanced magnetic resonance imaging (MRI) detects early-stage nasopharyngeal carcinoma (NPC) not detected by endoscopic-guided biopsy (EGB), a short contrast-free screening MRI would be desirable for NPC screening programs. This study evaluated a screening MRI in a plasma Epstein-Barr virus (EBV)-DNA NPC screening program. METHODS: EBV-DNA-screen-positive patients underwent endoscopy, and endoscopy-positive patients underwent EGB. EGB was negative if the biopsy was negative or was not performed. Patients also underwent a screening MRI. Diagnostic performance was based on histologic confirmation of NPC in the initial study or during a follow-up period of at least 2 years. RESULTS: The study prospectively recruited 354 patients for MRI and endoscopy; 40/354 (11.3%) endoscopy-positive patients underwent EGB. Eighteen had NPC (5.1%), and 336 without NPC (94.9%) were followed up for a median of 44.8 months. MRI detected additional NPCs in 3/18 (16.7%) endoscopy-negative and 2/18 (11.1%) EGB-negative patients (stage I/II, n = 4; stage III, n = 1). None of the 24 EGB-negative patients who were MRI-negative had NPC. MRI missed NPC in 2/18 (11.1%), one of which was also endoscopy-negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI, endoscopy, and EGB were 88.9%, 91.1%, 34.8%, 99.4%, and 91.0%; 77.8%, 92.3%, 35.0%, 98.7%, and 91.5%; and 66.7%, 92.3%, 31.6%, 98.1%, and 91.0%, respectively. CONCLUSION: A quick contrast-free screening MRI complements endoscopy in NPC screening programs. In EBV-screen-positive patients, MRI enables early detection of NPC that is endoscopically occult or negative on EGB and increases confidence that NPC has not been missed.


Assuntos
Detecção Precoce de Câncer , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Imageamento por Ressonância Magnética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Neoplasias Nasofaríngeas/virologia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/patologia , Masculino , Pessoa de Meia-Idade , Feminino , Imageamento por Ressonância Magnética/métodos , Detecção Precoce de Câncer/métodos , Adulto , Herpesvirus Humano 4/isolamento & purificação , Carcinoma Nasofaríngeo/virologia , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/patologia , Estudos Prospectivos , Idoso , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , DNA Viral/sangue , Carcinoma/diagnóstico por imagem , Carcinoma/virologia , Carcinoma/diagnóstico , Carcinoma/patologia , Sensibilidade e Especificidade , Endoscopia/métodos , Estadiamento de Neoplasias , Programas de Rastreamento/métodos , Meios de Contraste/administração & dosagem
12.
Head Neck ; 46(7): 1637-1659, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38235957

RESUMO

BACKGROUND: The prevalence of gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) in post-irradiated patients with nasopharyngeal carcinoma (NPC) is unknown. MATERIALS AND METHODS: In a cross-sectional study, 31 NPC and 12 control patients completed questionnaires for GERD/LPR before esophageal manometry and 24-h pH monitoring. The DeMeester score and reflux finding score (RFS) were used to define GERD and LPR, respectively. Risk factors were identified. RESULTS: 51.6% of NPC and 8.3% of control patients, and 77.4% of NPC and 33% of control patients, were GERD-positive and LPR-positive, respectively. The GERD/LPR questionnaire failed to identify either condition in patients with NPC. No parameter differences in esophageal manometry or pneumonia incidence were noted between GERD/LPR-positive and GERD/LPR-negative patients. Post radiotherapy duration, high BMI, lack of chemotherapy, and dysphagia were positive risk factors for GERD/LPR. CONCLUSIONS: A high prevalence of GERD/LPR in patients with post-irradiated NPC exists, but reflux symptoms are inadequate for diagnosis.


Assuntos
Transtornos de Deglutição , Refluxo Gastroesofágico , Refluxo Laringofaríngeo , Manometria , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Feminino , Refluxo Laringofaríngeo/epidemiologia , Refluxo Laringofaríngeo/etiologia , Pessoa de Meia-Idade , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/complicações , Estudos Transversais , Prevalência , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/epidemiologia , Adulto , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/complicações , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/complicações , Idoso , Inquéritos e Questionários , Carcinoma/radioterapia , Fatores de Risco , Monitoramento do pH Esofágico , Estudos de Casos e Controles
13.
Radiology ; 266(2): 531-8, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23151830

RESUMO

PURPOSE: To determine the diagnostic performance of diffusion-weighted (DW) imaging for the prediction of treatment failure in primary head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: The study was approved by the local institutional ethics committee and conducted with informed written consent in patients with primary HNSCC treated with radiation therapy and chemotherapy. DW imaging of the primary tumor was performed before treatment in 37 patients and was repeated within 2 weeks of treatment in 30 patients. Histograms of apparent diffusion coefficients (ADCs) were analyzed, and mean ADC, kurtosis, skewness, and their respective percentage change were correlated for local failure and local control at 2 years by using the Student t test. Univariate and multivariate analyses of the ADC parameters, T stage, and tumor volume were performed by using logistic regression for prediction of local failure. RESULTS: Local failure occurred in 16 of 37 (43%) patients and local control occurred in 21 of 37 (57%) patients. Pretreatment ADC parameters showed no correlation with local failure. There was significant intratreatment increase in mean ADC and a decrease in skewness and kurtosis (P < .001, P < .001, P = .024, respectively) for the whole group of patients when compared with those before treatment. During treatment, primary tumors showed a significantly lower increase in percentage change of mean ADC, higher skewness, and higher kurtosis for local failure than for local control (P = .016, .015, and .040, respectively). These ADC parameters also were significant for predicting local failure with use of univariate but not multivariate analysis. CONCLUSION: Early intratreatment DW imaging has the potential to allow prediction of treatment response at the primary site in patients with HNSCC.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/terapia , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Idoso , Terapia Combinada , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Curva ROC , Sensibilidade e Especificidade , Falha de Tratamento , Resultado do Tratamento
14.
Am J Pathol ; 180(3): 1215-1222, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22226739

RESUMO

The substantial T lymphocyte infiltrate found in cases of nasopharyngeal carcinoma (NPC) has been implicated in the promotion of both tumor growth and immune escape. Conversely, because malignant NPC cells harbor the Epstein-Barr virus, this tumor is a candidate for virus-specific T cell-based therapies. Preventing the accumulation of tumor-promoting T cells or enhancing the recruitment of tumor-specific cytotoxic T cells offers therapeutic potential. However, the mechanisms involved in T cell recruitment to this tumor are poorly understood. Comparing memory T cell subsets that have naturally infiltrated NPC tissue with their counterparts from matched blood revealed enrichment of CD8(+), CD4(+), and regulatory T cells expressing the chemokine receptor CXCR6 in tumor tissue. CD8(+) and (nonregulatory) CD4(+) T cells also were more frequently CCR5(+) in tumor than in blood. Ex vivo studies demonstrated that both receptors were functional. CXCL16 and CCL4, unique chemokine ligands for CXCR6 and CCR5, respectively, were expressed by the malignant cells in tumor tissue from the majority of NPC cases, as was another CCR5 ligand, CCL5. The strongest expression of CXCL16 was found on tumor-infiltrating cells. CCL4 was detected on the tumor vasculature in a majority of cases. These findings suggest that CXCR6 and CCR5 play important roles in T cell recruitment and/or retention in NPC and have implications for the pathogenesis and treatment of this tumor.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Neoplasias Nasofaríngeas/imunologia , Receptores CCR5/metabolismo , Receptores de Quimiocinas/metabolismo , Receptores Virais/metabolismo , Subpopulações de Linfócitos T/imunologia , Carcinoma , Linhagem Celular Tumoral , Humanos , Memória Imunológica/fisiologia , Linfócitos do Interstício Tumoral/imunologia , Carcinoma Nasofaríngeo , Receptores CCR5/fisiologia , Receptores CXCR6 , Receptores de Quimiocinas/fisiologia , Receptores Virais/fisiologia
15.
Diagn Interv Imaging ; 104(2): 67-75, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36096875

RESUMO

PURPOSE: The purpose of this study was to retrospectively evaluate the diagnostic performances of diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) for discriminating between benign and malignant salivary gland tumors (SGTs). MATERIALS AND METHODS: Sixty-seven patients with 71 SGTs who underwent MRI examination at 3 Tesla were included. There were 34 men and 37 women with a mean age of 57 ± 17 (SD) years (age range: 20-90 years). SGTs included 21 malignant tumors (MTs) and 50 benign SGTs (33 pleomorphic adenomas [PAs] and 17 Warthin's tumors [WTs]). For each SGT, DWI and IVIM parameters, mean, skewness, and kurtosis of apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*) and perfusion volume fraction (f) were calculated and further compared between SGTs using univariable analysis. Areas under the curves (AUC) of receiver operating characteristic of significant parameters were compared using the Delong test. RESULTS: Significant differences in ADCmean, Dmean and D*mean were found between SGTs (P < 0.001). The highest AUC values were obtained for ADCmean (0.949) for identifying PAs and D*mean (0.985) for identifying WTs and skewness and kurtosis did not outperform mean. To discriminate benign from malignant SGTs with thresholds set to maximize Youden index, IVIM and DWI produced accuracies of 85.9% (61/71; 95% CI: 75.6-93.0) and 77.5% (55/71; 95% CI: 66.0-86.5) but misdiagnosed MTs as benign in 28.6% (6/21) and 61.9% (13/21) of SGTs, respectively. After maximizing specificity to 100% for benign SGTs, the accuracies of IVIM and DWI decreased to 76.1% (54/71; 95% CI: 64.5-85.4) and 64.8% (46/71; 95% CI: 52.5-75.8) but no MTs were misdiagnosed as benign. IVIM and DWI correctly diagnosed 66.0% (33/50) and 50.0% (25/50) of benign SGTs and 46.5% (33/71) and 35.2% (25/71) of all SGTs, respectively. CONCLUSION: IVIM is more accurate than DWI for discriminating between benign and malignant SGTs because of its advantage in detecting WTs. Thresholds set by maximizing specificity for benign SGTs may be advantageous in a clinical setting.


Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias das Glândulas Salivares , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Curva ROC , Neoplasias das Glândulas Salivares/diagnóstico por imagem
16.
Am J Cancer Res ; 13(4): 1457-1470, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37168357

RESUMO

We aimed to explore the role of lenvatinib-mediated autophagy in papillary thyroid cancer (PTC). K1 and BCPAP, were tested for cell viability, proliferation, and apoptosis after treatment with lenvatinib or chloroquine (CQ) or both. The levels of angiogenesis vascular endothelial growth factor A (VEGFA) were measured by ELISA. Transwell and wound-healing assays were performed using endothelial HUVECs cells. The dynamics of microvessels were detected by tubular formation assay. Western blotting was used to determine the expression of LC3-I/II and Atg-7 and alterations in the PI3K/Akt/mTOR and MEK/ERK pathways. In vivo tumor growth assay and immunohistochemical staining (IHC) was also performed. The results showed that lenvatinib inhibited the viability of K1 and BCPAP cells and caused apoptosis. We further showed that lenvatinib also upregulated autophagy levels in thyroid cancer cells in a dose-dependent manner through the PI3K/Akt/mTOR and MEK/ERK pathways. Co-administration of lenvatinib with CQ resulted in a greater decrease of VEGFA in the tumor supernatant than with either lenvatinib or CQ alone. Autophagy inhibition enhanced the cytotoxicity and anti-angiogenic ability of lenvatinib, which was supported by the HUVECs migration, wound healing, and tube formation assays. Inhibiting autophagy chemically or genetically enhanced lenvatinib's cytotoxic effects and anti-angiogenic efficacy in thyroid cancer cells in vitro and in vivo. In conclusion, lenvatinib inhibited cell viability and induced apoptosis and autophagy in human PTC cells. Significantly, the combination of lenvatinib and autophagy inhibition may represent a novel and effective treatment option for PTC, which may be able to overcome drug resistance.

17.
Laryngoscope Investig Otolaryngol ; 8(6): 1532-1546, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38130249

RESUMO

Background: Exercise-based swallowing training (EBST) and transcutaneous neuromuscular electrical stimulation (TNMES) are common modalities used to treat late dysphagia after radiotherapy for nasopharyngeal carcinoma (NPC). We aimed to investigate and compare the efficacies of EBST and TNMES as proactive treatments administered early after radiotherapy. Methods: Patients with early post-radiotherapy NPC (n = 120) underwent either TNMES or EBST. Flexible endoscopic evaluation of swallowing (FEES), quality of life (QOL), and swallowing function questionnaires were completed before the intervention as well as immediately, 6, and 12 months after the intervention. Outcome measures included the scores for the swallowing function score (SFS), penetration and aspiration scale (PAS), dynamic imaging grade of swallowing toxicity (DIGEST), functional oral intake scale (FOIS), swallowing performance status scale (SPSS), pharyngeal motor impairment (PMI), pharyngeal function impairment (PFI), and functional assessment after cancer therapy-nasopharyngeal (FACT-NP) questionnaire. Results: Three months after radiotherapy, 31 and 34 patients underwent TNMES and EBST, respectively, and completed swallowing assessments at all four assessment timepoints. All patients showed post-radiotherapy impairments in the SFS, PAS, DIGEST, PMI, and PFI. Compared with the EBST group, the TNMES group showed significant improvements in the PFI and PMI scores, with small-to-medium effect sizes. Additionally, compared with the EBST group, the TNMES group demonstrated a trend toward slightly better improvements in the PAS, DIGEST, FOIS, and SPSS scores immediately and 6 months after the intervention. The SFS scores improved from baseline in both groups; however, the TNMES group showed an earlier improvement. Finally, the TNMES group showed better QOL according to the FACT-NP than the EBST group. Conclusion: Proactive TMNES and EBST are safe and feasible modalities for improving swallowing in patients with NPC when administered early after radiotherapy. Although TNMES showed better results than EBST, these results should be interpreted with caution given the study limitations. Level of evidence: 1B.

18.
J Natl Cancer Inst ; 115(4): 355-364, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-36723440

RESUMO

A meeting of experts was held in November 2021 to review and discuss available data on performance of Epstein-Barr virus (EBV)-based approaches to screen for early stage nasopharyngeal carcinoma (NPC) and methods for the investigation and management of screen-positive individuals. Serum EBV antibody and plasma EBV DNA testing methods were considered. Both approaches were found to have favorable performance characteristics and to be cost-effective in high-risk populations. In addition to endoscopy, use of magnetic resonance imaging (MRI) to investigate screen-positive individuals was found to increase the sensitivity of NPC detection with minimal impact on cost-effectiveness of the screening program.


Assuntos
Carcinoma , Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Detecção Precoce de Câncer/métodos , DNA Viral/genética
19.
Radiology ; 263(2): 437-43, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22403169

RESUMO

PURPOSE: To document the magnetic resonance (MR) imaging appearances of benign nasopharyngeal mucosa and adenoids and to correlate quantitative thickness measurements with histologic findings from nasopharyngeal biopsy specimens. MATERIALS AND METHODS: MR imaging studies and nasopharyngeal biopsy specimens were analyzed retrospectively in 100 adults (51 men, 49 women) with benign histologic findings; local institutional review board approval and informed consent had been obtained as part of a previous imaging study. At T1-weighted gadolinium-enhanced MR imaging, the nasopharyngeal roof and adenoid was classified as follows: 1, pencil thin, less than 3 mm; 2, smooth thickening, 3 mm or larger; 3, small tags or stripes; or 4, focal adenoid mass with a vertical striped appearance. The posterior and lateral walls were classified as follows: pattern 1, pencil thin, less than 3 mm; pattern 2, mild thickening, 3 mm or larger with moderate enhancement; or pattern 3, thickening with hypoenhancement along the posterior wall. The frequency of these patterns, as well as cysts, symmetry, and pharyngeal recess patency, were documented. Wall thickness was measured and correlated with age, sex, and histologic findings from biopsy specimens by using Spearman rank correlation and Mann-Whitney U tests. RESULTS: In 100 patients, roof patterns 1-4 were identified in 16 (16%), seven (7%), 33 (33%), and 44 (44%); posterior and lateral wall patterns 1-3 were identified in 20 (20%), 55 (55%), and 25 (25%) patients. Symmetry was identified in 95 (95%) patients, cysts in 41 (41%) patients, and pharyngeal recess patency was identified in 24 (12%) of 200 sides. Roof including adenoid thickness was higher in men (P = .05) and correlated inversely with age (P <.01). In 62 (62%) of 100 patients, biopsy specimens contained lymphoid follicles. Roof including adenoid (P = .01) and posterior wall (P = .03) thickness at MR imaging was higher if follicles were identified in biopsy specimens. CONCLUSION: Nasopharyngeal hyperplasia has typical MR imaging appearances, including stripes in adenoid bulges and symmetry, which may be useful to differentiate this condition from nasopharyngeal malignancy.


Assuntos
Tonsila Faríngea/patologia , Imageamento por Ressonância Magnética/métodos , Nasofaringe/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Meios de Contraste , Feminino , Humanos , Masculino , Meglumina , Pessoa de Meia-Idade , Compostos Organometálicos , Estudos Retrospectivos , Estatísticas não Paramétricas
20.
Cancers (Basel) ; 14(23)2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36497285

RESUMO

The lack of a consistent MRI radiomic signature, partly due to the multitude of initial feature analyses, limits the widespread clinical application of radiomics for the discrimination of salivary gland tumors (SGTs). This study aimed to identify the optimal radiomics feature category and MRI sequence for characterizing SGTs, which could serve as a step towards obtaining a consensus on a radiomics signature. Preliminary radiomics models were built to discriminate malignant SGTs (n = 34) from benign SGTs (n = 57) on T1-weighted (T1WI), fat-suppressed (FS)-T2WI and contrast-enhanced (CE)-T1WI images using six feature categories. The discrimination performances of these preliminary models were evaluated using 5-fold-cross-validation with 100 repetitions and the area under the receiver operating characteristic curve (AUC). The differences between models' performances were identified using one-way ANOVA. Results show that the best feature categories were logarithm for T1WI and CE-T1WI and exponential for FS-T2WI, with AUCs of 0.828, 0.754 and 0.819, respectively. These AUCs were higher than the AUCs obtained using all feature categories combined, which were 0.750, 0.707 and 0.774, respectively (p < 0.001). The highest AUC (0.846) was obtained using a combination of T1WI + logarithm and FS-T2WI + exponential features, which reduced the initial features by 94.0% (from 1015 × 3 to 91 × 2). CE-T1WI did not improve performance. Using one feature category rather than all feature categories combined reduced the number of initial features without compromising radiomic performance.

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