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BACKGROUND: Liquid-based cytology (LBC), now used globally for the head and neck region, has been used at our hospital since 2011. This study was designed to analyze the efficacy of LBC with immunocytochemical staining on preoperative diagnosis of salivary gland tumors. METHODS: This retrospective analysis of fine-needle aspiration (FNA) performance for salivary gland tumors was conducted at Fukui University Hospital. Salivary gland tumor operations conducted during April 2006 - December 2010 (84 cases) were classified as the Conventional Smear (CS) group, which were diagnosed morphologically by Papanicolaou and Giemsa staining. Those done during January 2012 - April 2017 (112 cases) were classified as the LBC group, which were diagnosed using LBC samples with immunocytochemical staining. The FNA results and pathological diagnosis of both groups were analyzed to calculate the FNA performance. RESULTS: Compared to the CS group, cases of inadequate and indeterminate FNA sample were not reduced significantly by LBC with immunocytochemical staining. As for FNA performance, the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CS group were, respectively, 88.7%, 53.3%, 100%, 100%, and 87.0%. Those of LBC group were all 100%, representing significant improvement over the CS group. CONCLUSIONS: Analysis results indicated the usefulness of LBC with immunocytochemical staining for preoperative diagnosis of salivary gland tumors.
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Neoplasias das Glândulas Salivares , Humanos , Biópsia por Agulha Fina/métodos , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/patologia , Citodiagnóstico , Coloração e Rotulagem , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Cervical esophageal cancer (CEC) carries a poor prognosis; however, due to its low incidence, optimal treatment for CEC remains to be established. The purpose of this study was to clarify the current status of treatment of CEC in Japan and obtain evidence for establishing the appropriate treatment method. PATIENTS AND METHODS: We asked specialist training facilities accredited by the Japanese Broncho-Esophageal Society to register data on CEC cases that received curative treatment from January 2009 to December 2014, and conducted a retrospective review of the clinical data of 302 cases registered from 27 facilities. RESULTS: In regard to the initial therapy, of the 302 patients, 33 had undergone endoscopic resection, 41 had undergone surgery, 67 had received induction chemotherapy (IC), and 143 had received chemoradiotherapy (CRT). There were no significant differences in the 5-year overall survival rates among the patient groups that had received surgery, IC or CRT as the initial treatment; advanced stage and recurrent nerve invasion were identified as independent poor prognostic factors. Among the patients who had received IC or CRT as laryngeal-preserving surgery was not indicated at the time of the initial diagnosis, the functional laryngeal preservation rate at the end of the observation period was 34.8%. CONCLUSION: Even in patients with advanced CEC, there is the possibility of preserving the larynx by adopting IC or CRT. However, if the laryngeal function cannot be preserved, there is a risk of complications from aspiration pneumonia, so that the choice of treatment should be made carefully.
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Neoplasias Esofágicas , Laringe , Quimiorradioterapia , Neoplasias Esofágicas/tratamento farmacológico , Humanos , Quimioterapia de Indução/métodos , Japão/epidemiologia , Laringe/cirurgiaRESUMO
PURPOSE: This study aimed to evaluate the utility of inflammation-based prognostic scores (IBPS) and systemic immune-inflammation index (SII) in the treatment of oral cancer patients. METHODS: For the 183 patients enrolled in this study, IBPS and SII were calculated from peripheral blood samples obtained before and after treatment and at the time of relapse. We examined overall survival (OS) and disease-free survival (DFS) using previously reported cut-off values for IBPS. Cut-off values of neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were analyzed as NLR 1.79, PLR 114.97, LMR 5, and PNI 52.44. The cut-off value for SII was set at 569. OS and DFS were analyzed by Kaplan-Meier methods using the cutoff of each IBPS and SII. Univariate analysis and multivariate analysis using Cox proportional hazards were performed for OS and DFS. RESULTS: Kaplan-Meier methods showed the high-PNI group showed good prognosis including OS and DFS, while the high-SII group displayed poor DFS. Univariate analysis showed that pre-treatment high PNI and low SII were significantly associated with better prognosis. Multivariate analysis identified pre-treatment PNI as independently associated with OS. For DFS, univariate analysis using Cox proportional hazards modeling showed that pre-treatment high NLR and high SII were significantly associated with worse prognosis, while high PNI was significantly associated with better prognosis. Multivariate analysis identified pre-treatment PNI and SII as independently associated with DFS. Parameters of PNI and SII components were compared between pre-treatment, post-treatment and at relapse in the high- and low-PNI groups. PNI was predominantly decreased in both high- and low-PNI groups at post-treatment and at relapse compared to pre-treatment. This trend was also observed for albumin. CONCLUSIONS: Higher pre-treatment PNI was associated with better OS, while lower pre-treatment PNI and higher treatment SII were associated with poorer DFS in oral cancer patients. Our data indicated that PNI and SII might offer useful biomarkers for gauging prognosis and the efficacy of conventional therapies.
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Neoplasias Bucais , Avaliação Nutricional , Humanos , Inflamação , Neoplasias Bucais/terapia , Recidiva Local de Neoplasia , Neutrófilos , Prognóstico , Estudos RetrospectivosRESUMO
INTRODUCTION: The chromosomal region 17q21 harbors the human orosomucoid-like 3 (ORMDL3) gene and has been linked to asthma and other inflammatory diseases. ORMDL3 is involved in the unfolded protein response (UPR), lipid metabolism, and inflammatory reactions. We investigated the effects of ORMDL3 overexpression in RBL-2H3 cells to determine the contribution of ORMDL3 to inflammatory disease development. METHODS: We generated ORMDL3 stably overexpressing RBL-2H3 cells to assess degranulation, transcriptional upregulation of interleukin-4 (IL-4), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and mitogen-activated protein kinase (MAPK) phosphorylation via FcεRI. In addition, we examined the effects of ORMDL3 overexpression on thapsigargin (TG)-mediated proinflammatory cytokine transcription and UPR by monitoring MAPK, protein kinase-like endoplasmic reticulum kinase (PERK), and inositol-requiring enzyme 1 (IRE1) phosphorylation. RESULTS: Overexpression of ORMDL3 enhanced IL-4, TNF-α, and MCP-1 expression after FcεRI cross-linking, whereas the sphingosine-1-phosphate (S1P) agonist FTY720 suppressed this enhancement. There was no significant difference in degranulation and MAPK phosphorylation via FcεRI-mediated activation between vector-transfected and ORMDL3-overexpressing cells. ORMDL3 overexpression accelerated TG-mediated PERK phosphorylation, while MAPK phosphorylation and proinflammatory cytokine expression showed no significant changes in ORMDL3-overexpressing cells. CONCLUSIONS: Our findings suggest that ORMDL3 plays an important role in regulating proinflammatory cytokine expression via the S1P pathway and selectively affects the UPR pathway in mast cells.
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Citocinas , Receptores de IgE , Degranulação Celular , Citocinas/metabolismo , Retículo Endoplasmático/metabolismo , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Orosomucoide , Fosforilação , Receptores de IgE/genética , Tapsigargina/farmacologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Japanese herbal medicine Shin'iseihaito was reported to ameliorate the airway type 2 inflammatory response in clinical and experimental studies. Airway type 2 inflammatory diseases, including bronchial asthma and eosinophilic chronic rhinosinusitis (ECRS), often coexist and interact with each other. However, it is still unclear how Shin'iseihaito exerts its pharmacological effects on cells involved in airway mucosa. AIM OF THE STUDY: This study aims to examine the direct effect of baicalin, a representative bioactive compound of Shin'iseihaito, on type 2 immune responses in human airway epithelial cells and mast cells. MATERIAL AND METHODS: We measured the plasma pharmacokinetics of flavonoids derived from Shin'iseihaito and investigated the effects of baicalin on type 2 immune responses in human airway epithelial cells and human mast cells. RESULTS: Baicalin, wogonin, and wogonoside were detected in the plasma. The maximum plasma concentration of baicalin was highest at 1610 ng/ml (3.6 µM). In the normal human bronchial epithelial cells treated with baicalin, with or without stimulation by IFN-γ, the IL-33 expression was significantly downregulated. However, baicalin treatment did not affect the levels of thymic stromal lymphopoietin and IL-25. We noted that IL-33-dependent expression of tryptase mRNA in mast cells was significantly inhibited by baicalin. Also, the expression of IL-5 in mast cells enhanced by stimulation with TSLP plus IL-1ß was significantly downregulated by baicalin treatment. Moreover, the enhancement of IL-13 expression in mast cells by IL-33 simulation was also significantly inhibited by baicalin. CONCLUSIONS: Our results prove that by breaking off the vicious circle of mast cells and airway epithelial cells, baicalin may be an effective alternative therapeutic option for the treatment of type 2 inflammatory diseases, such as ECRS and comorbid asthma.
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Brônquios/efeitos dos fármacos , Comunicação Celular/efeitos dos fármacos , Flavonoides/farmacologia , Imunossupressores/farmacologia , Mastócitos/efeitos dos fármacos , Animais , Brônquios/citologia , Brônquios/imunologia , Brônquios/metabolismo , Células Cultivadas , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Flavonoides/sangue , Flavonoides/farmacocinética , Regulação da Expressão Gênica , Humanos , Imunossupressores/sangue , Imunossupressores/farmacocinética , Interleucina-33/genética , Interleucina-33/metabolismo , Interleucina-5/genética , Interleucina-5/metabolismo , Masculino , Mastócitos/imunologia , Mastócitos/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Triptases/genética , Triptases/metabolismoRESUMO
BACKGROUND: The pathological features of chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) tissues include an eosinophilic infiltration pattern (eosinophilic CRS (ECRS)) or a less eosinophilic pattern (non-ECRS). Recently, it has been suggested that 15-lipoxygenase 1 (15-LOX-1) may have significant roles in allergic disease; however, the significance of 15-LOX-1 in CRS is not well understood. The objective of this study was to demonstrate the expression of 15-LOX-1 in CRS. METHODS: The mRNA expression levels of 15-LOX-1 and periostin in nasal tissues were measured by quantitative real-time polymerase chain reaction. We also performed an immunofluorescence study of nasal tissues. Cells of the Eol-1 eosinophilic leukemic cell line were stimulated with interleukin-33 to test the induction of 15-LOX-1. RESULTS: The expression level of 15-LOX-1 mRNA in nasal polyps (NPs) was significantly higher in ECRS patients than in non-ECRS patients. The immunofluorescence study revealed that both airway epithelial cells and eosinophils in NPs expressed 15-LOX-1. A significant correlation was seen between the number of eosinophils and the mRNA expression levels of 15-LOX-1 and periostin in nasal polyps. Moreover, interleukin-33 enhanced 15-LOX-1 expression in Eol-1 cells. CONCLUSIONS: 15-LOX-1 was shown to be a significant molecule that facilitates eosinophilic inflammation in ECRS.
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Araquidonato 15-Lipoxigenase/biossíntese , Moléculas de Adesão Celular/biossíntese , Eosinófilos/metabolismo , Rinorreia/metabolismo , Sinusite/metabolismo , Adulto , Idoso , Araquidonato 15-Lipoxigenase/genética , Moléculas de Adesão Celular/genética , Doença Crônica , Eosinófilos/patologia , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Rinorreia/genética , Rinorreia/patologia , Sinusite/genética , Sinusite/patologiaRESUMO
OBJECTIVE: Integrated PET/MRI with [18F]FDG is advantageous in that it enables simultaneous PET and MR imaging with higher soft-tissue contrast, multiplanar image acquisition, and functional imaging capability without using fat suppression and gadolinium-based contrast agents (GBCAs). The aims of this study were to demonstrate the feasibility of [18F]FDG PET/MRI for assessing the extent of the primary tumor (T) in oral tongue cancer (OTC) based on the 8th edition of American Joint Committee on Cancer (AJCC) cancer staging system, and to compare the diagnostic accuracy between [18F]FDG PET/MRI and contrast-enhanced MRI (ceMRI). METHODS: 18 patients with biopsy-proven operable OTC underwent preoperative regional [18F]FDG PET/MRI and ceMRI within 2 weeks. For [18F]FDG PET/MRI, rainbow-colored PET images were overlaid on the corresponding MR images. Tumor size and the depth of invasion (DOI) were visually measured on [18F]FDG PET/MRI and ceMRI. The size, DOI, and clinical T stage were evaluated using the final surgical pathology as the reference. RESULTS: Of the 18 OTCs, one was not detected by ceMRI due to metal artifacts from an artificial denture, and another due to superficial type (pathological DOI = 0 mm). Tumor sizes measured by ceMRI and [18F]FDG PET/MRI had significant positive correlations with the pathological size (r = 0.80 and r = 0.90, respectively), and DOIs measured by ceMRI and [18F]FDG PET/MRI had significant positive correlations with the pathological DOI (r = 0.74 and r = 0.64, respectively). The means ± SD of size (mm) were 20.4 ± 9.1, 22.9 ± 10.9, and 26.2 ± 10.0, and those of DOI (mm) were 7.1 ± 2.5, 6.9 ± 2.2, and 5.8 ± 3.2 for ceMRI, [18F]FDG PET/MRI, and pathology, respectively. A significant difference was observed in tumor size between ceMRI and pathology (p < 0.05), whereas no significant differences were observed between any other sizes, DOIs, or T stages. The accuracy for T status was 72% (13/18 including 2 undetectable cases) for ceMRI and 89% (16/18) for [18F]FDG PET/MRI. CONCLUSIONS: Although shallow DOIs are often overestimated, regional [18F]FDG PET/MRI without fat suppression and gadolinium enhancement is comparable to and may be substituted for ceMRI in preoperative T staging for OTC patients, reducing metal artifacts and avoiding the adverse effects of GBCAs.
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Fluordesoxiglucose F18 , Imageamento por Ressonância Magnética , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Neoplasias da Língua/diagnóstico por imagem , Neoplasias da Língua/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Sensibilidade e EspecificidadeRESUMO
PURPOSE: The aims of this study were to demonstrate the feasibility of zero echo time (ZTE) MRI for jawbone identification, and to evaluate the quantitative performance of F-FDG PET/MRI with ZTE-based attenuation correction (ZTE-AC) compared with PET/CT and PET/MRI with Dixon MR-based AC (Dixon-AC) in patients with oral cavity cancer (OCC). MATERIALS AND METHODS: Thirteen OCC patients underwent whole-body F-FDG PET/CT and subsequent regional PET/MRI with Dixon-AC and ZTE-AC in 1 day. SUVs of the primary OCC and metastatic cervical lymph nodes (CLNs) were measured on PET/CT (SUVCT), PET/MRI with Dixon-AC (SUVDixon), and ZTE-AC (SUVZTE). The SUVs were then compared. RESULTS: The ZTE MRI scans minimized the effects of metal artifacts from dentures, and ZTE-AC maps correctly delineated the jawbones. SUVDixon and SUVZTE had significant positive correlations with SUVCT (Pearson r = 0.97 and r = 0.99 for OCC, and r = 0.98 and r = 0.98 for CLNs, respectively). The mean ± SD of SUVCT, SUVDixon, and SUVZTE were 14.4 ± 8.0, 14.5 ± 8.6, and 15.6 ± 8.8 for OCC, and 6.3 ± 3.0, 8.0 ± 4.0, and 7.6 ± 3.9 for CLNs, respectively. For OCCs, SUVZTE was significantly higher than SUVCT (P < 0.05), whereas there was no significant difference between SUVCT and SUVDixon or between SUVDixon and SUVZTE. For CLNs, SUVDixon and SUVZTE were significantly higher than SUVCT (P < 0.01 and P < 0.05, respectively), and SUVDixon was significantly higher than SUVZTE (P < 0.01). CONCLUSIONS: ZTE MRI can correctly identify jawbones while minimizing the effects of metal artifacts. The ZTE-AC method in F-FDG PET/MRI reduces the underestimation of tracer uptake due to Dixon-AC jawbone errors and improves the quantitative performance of PET for OCC patients.
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Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética , Neoplasias Bucais/diagnóstico por imagem , Imagem Multimodal , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
The present study aimed to clarify the incidence and clinical outcomes of nasopharyngeal carcinoma (NPC) in the Chubu region of Japan from 2006 to 2015, compared with previous reports. A retrospective analysis was conducted based on medical records from 40 hospitals located in the Chubu region in the central Japanese main island, with a population of around 22.66 million individuals. This study was designed in line with to two previous clinical studies into NPC conducted in the same area of Japan. We recruited NPC patients diagnosed in hospitals across this area over a 10-year period (2006-2015) using a questionnaire about sex, age, primary site, clinical symptoms, pathology, Union for International Cancer Control (UICC) staging, serological exam, treatment, and survival. A total of 620 NPC patients were identified. The age-standardized incidence of NPC from 2006 to 2015 was 0.27 per 100,000 individuals per year. There were no significant differences between this study and the previous two studies conducted in the same area of Japan. The five-year overall survival rate for all patients was 75.9%, while those for patients with stages I, II, III, and IVA were 97%, 91%, 79%, and 68%, respectively. The age-standardized annual incidence of NPC in the present study was 0.27 per 100,000 individuals per year, which was relatively low and stable. The five-year overall survival rate for all NPC patients was significantly improved in this decade compared with previous studies. The smoking rates in male and female NPC patients were 64.5% and 18.8%, respectively, thereby suggesting the involvement of smoking in the incidence of NPC.
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BACKGROUND: Most patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD) suffer from recurrence of nasal polyps. However, little is known about the specific cellular and molecular mechanisms contributing to the pathogenesis of nasal polyp development in patients with NERD in particular, especially at baseline when cyclooxygenase 1 inhibitors are not present. The objectives of this study were to identify proteins involved in the pathogenesis of nasal polyps in patients with NERD. METHODS: We collected nasal polyp tissue from patients with NERD and from patients with aspirin-tolerant chronic rhinosinusitis with nasal polyps (CRSwNP). Protein profiles were analyzed by 2-dimensional electrophoresis and identified several proteins, including L-plastin, as highly expressed. We examined L-plastin and tissue factor (TF) expression by immunohistochemical and immunofluorescence analyses. To examine the role of L-plastin in eosinophils, we knocked down L-plastin expression in Eol-1 cells by using siRNA transfection. RESULTS: L-plastin protein levels in nasal polyp tissue were increased in patients with NERD relative to those in patients with aspirin tolerant CRSwNP. Immunofluorescence analysis revealed that L-plastin was dominantly expressed in eosinophils and L-plastin and TF were co-expressed in eosinophils in NERD nasal polyp tissue. Knockdown of L-plastin in Eol-1 cells disrupted the cell surface distribution of TF by stimulation with granulocyte macrophage colony-stimulating factor. CONCLUSION: Increased expression of L-plastin by eosinophils may contribute to abnormal fibrin deposition through TF translocation to the eosinophil cell surface in NERD nasal polyp tissue, which in turn may contribute to the pathogenesis of NERD.
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Anti-Inflamatórios não Esteroides/efeitos adversos , Regulação da Expressão Gênica , Glicoproteínas de Membrana/genética , Proteínas dos Microfilamentos/genética , Pólipos Nasais/complicações , Pólipos Nasais/genética , Hipersensibilidade Respiratória/complicações , Hipersensibilidade Respiratória/etiologia , Endotélio/metabolismo , Eosinófilos/imunologia , Eosinófilos/metabolismo , Feminino , Fibrina/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Glicoproteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Pólipos Nasais/imunologia , RNA Interferente Pequeno/genética , Tromboplastina/metabolismoRESUMO
BACKGROUND: In Eosinophilic chronic rhinosinusitis (ECRS), it is difficult to estimate the refractoriness and recurrence risk for each patient. Fraction of exhaled nitric oxide (FeNO) is known as a biomarker of eosinophilic inflammation in lower airway. It has been reported that nasal NO has some crucial functions in the upper and lower airways. However, in upper airway, paranasal sinuses, the usefulness of NO measurement remains controversial. The purpose of this study is to identify the usefulness of nasal NO measurement in ECRS and the involvement of nasal NO in the pathogenesis of ECRS. METHODS: We compared the nasal NO levels of ECRS, non-ECRS, and normal control groups. Correlation between nasal NO levels and clinical findings were observed. Then, we compared nasal NO levels before and after endoscopic sinus surgery (ESS). We also examine whether nasal NO levels might discriminate ECRS by the receiver operating characteristic (ROC) curve analysis. RESULTS: Nasal NO levels were significantly decreased in ECRS compared to the other two groups. Moreover, nasal NO levels in ECRS significantly and negatively correlated with eosinophil levels and CT score. However, they did not correlate with the nasal polyp score. Nasal NO levels were not upregulated soon after opening the sinus ostium by ESS. The ROC curves for nasal NO levels were used to discriminate all CRS patients and ECRS patients from normal controls. CONCLUSIONS: Nasal NO may be useful as a marker of ECRS severity and low nasal NO levels in ECRS may contribute to its pathogenesis.
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Eosinofilia/metabolismo , Mucosa Nasal/metabolismo , Óxido Nítrico/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Adolescente , Adulto , Idoso , Doença Crônica , Endoscopia , Eosinofilia/cirurgia , Humanos , Pessoa de Meia-Idade , Pólipos Nasais/metabolismo , Pólipos Nasais/cirurgia , Rinite/cirurgia , Índice de Gravidade de Doença , Sinusite/cirurgia , Adulto JovemRESUMO
INTRODUCTION: Cisplatin is used as a standard chemotherapeutic agent for head and neck cancer treatment. However, some head and neck cancers have cisplatin resistance, leading to difficulty in treatment and poor prognosis. Overcoming cisplatin resistance remains an important strategy to improve prognoses for head and neck cancer patients. OBJECTIVE: Elucidation of the mechanisms underlying cisplatin resistance can suggest novel targets to enhance the anticancer effects of cisplatin for treating head and neck cancers. MATERIAL AND METHODS: We used a cisplatin-resistant human maxillary cancer cell line, IMC-3CR to analyse the cisplatin resistance mechanisms. Cisplatin-induced genes were analysed in IMC-3CR cells using PCR array. Among the genes with expression increased by cisplatin, we specifically examined SESN1. SESN family reportedly regenerates peroxiredoxin and suppresses oxidative DNA injury by reactive oxygen species (ROS), which can be induced by chemotherapeutic agents such as cisplatin, radiation, and hyperthermia. The function of SESN1 in cisplatin resistance and ROS generation were analysed using specific RNAi. RESULTS: Results show that SESN1 was induced by cisplatin treatment in IMC-3CR cells. Suppression of SESN1 by RNAi induced apoptosis and reduced cell viability through enhancement of ROS after cisplatin treatment. Moreover, suppression of SESN1 enhanced the cell-killing effects of hyperthermia with increased ROS, but did not affect the cell-killing effects of radiation. CONCLUSIONS: This study demonstrated the participation of SESN1 in cisplatin and hyperthermia resistance of human head and neck cancers. SESN1 is a novel molecular target to overcome cisplatin resistance and hyperthermia resistance and improve head and neck cancer treatment.
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Cisplatino/farmacologia , Proteínas de Choque Térmico/antagonistas & inibidores , Hipertermia Induzida/métodos , Neoplasias Maxilares/terapia , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico/biossíntese , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Neoplasias Maxilares/genética , Neoplasias Maxilares/metabolismo , Neoplasias Maxilares/patologia , Interferência de RNA , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , TransfecçãoRESUMO
We previously reported that chronic rhinosinusitis with nasal polyps (CRSwNP) was subdivided into four chronic rhinosinusitis (CRS) subtypes using the JESREC scoring system. We sought to identify the gene expression profile and biomarkers related with CRSwNP by RNA-sequence. RNA-sequencing was performed to identify differentially expressed genes between nasal polyps (NPs) and inferior turbinate mucosa from 6 patients with CRSwNP, and subsequently, quantitative real-time PCR was performed to verify the results. ELISA was performed to identify possible biomarkers for postoperative recurrence. In the RNA-sequencing results, periostin (POSTN) expression was the highest in NP. We focused on POSTN and investigated the protein level of POSTN by immunohistochemistry and ELISA. POSTN was diffusely expressed in moderate and severe eosinophilic CRS using immunohistochemistry, and its staining pattern was associated with the severity of the phenotype of the CRSwNP (P < 0.05). There was a significant difference between the POSTN high/low groups for postoperative recurrence when the cutoff point was set at 115.5 ng/ml (P = 0.0072). Our data suggests that the protein expression level of POSTN was associated with the severity of CRSwNP, and serum POSTN can be a novel biomarker for postoperative recurrence of CRSwNP.
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Moléculas de Adesão Celular/sangue , Pólipos Nasais/patologia , Rinite/sangue , Rinite/complicações , Sinusite/sangue , Sinusite/complicações , Biomarcadores/sangue , Moléculas de Adesão Celular/genética , Doença Crônica , Regulação para Baixo/genética , Eosinófilos/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/metabolismo , Pólipos Nasais/cirurgia , Curva ROC , Recidiva , Rinite/cirurgia , Sinusite/genética , Sinusite/cirurgia , Transcriptoma/genética , Regulação para Cima/genéticaRESUMO
PURPOSE: We investigated whether PET radiomic features are affected by differences in the scanner, scan protocol, and lesion location using 18F-FDG PET/CT and PET/MR scans. RESULTS: SUV, TMR, skewness, kurtosis, entropy, and homogeneity strongly correlated between PET/CT and PET/MR images. SUVs were significantly higher on PET/MR0-2 min and PET/MR0-10 min than on PET/CT in gynecological cancer (p = 0.008 and 0.008, respectively), whereas no significant difference was observed between PET/CT, PET/MR0-2 min, and PET/MR0-10 min images in oral cavity/oropharyngeal cancer. TMRs on PET/CT, PET/MR0-2 min, and PET/MR0-10 min increased in this order in gynecological cancer and oral cavity/oropharyngeal cancer. In contrast to conventional and histogram indices, 4 textural features (entropy, homogeneity, SRE, and LRE) were not significantly different between PET/CT, PET/MR0-2 min, and PET/MR0-10 min images. CONCLUSIONS: 18F-FDG PET radiomic features strongly correlated between PET/CT and PET/MR images. Dixon-based attenuation correction on PET/MR images underestimated tumor tracer uptake more significantly in oral cavity/oropharyngeal cancer than in gynecological cancer. 18F-FDG PET textural features were affected less by differences in the scanner and scan protocol than conventional and histogram features, possibly due to the resampling process using a medium bin width. METHODS: Eight patients with gynecological cancer and 7 with oral cavity/oropharyngeal cancer underwent a whole-body 18F-FDG PET/CT scan and regional PET/MR scan in one day. PET/MR scans were performed for 10 minutes in the list mode, and PET/CT and 0-2 min and 0-10 min PET/MR images were reconstructed. The standardized uptake value (SUV), tumor-to-muscle SUV ratio (TMR), skewness, kurtosis, entropy, homogeneity, short-run emphasis (SRE), and long-run emphasis (LRE) were compared between PET/CT, PET/MR0-2 min, and PET/MR0-10 min images.
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The American Joint Committee on Cancer (AJCC) released the 8th edition of the AJCC cancer staging manual in 2017 that includes significant modifications from the 7th edition in the sections on oral cavity cancer (OCC) and oropharyngeal cancer (OPC). These highlights comprise the incorporation of the depth of invasion and exclusion of extrinsic tongue muscle involvement in the T staging of OCC, the separation of OPC staging based on the high-risk human papilloma virus status, and the inclusion of extranodal extension in N staging. The recent introduction of integrated positron emission tomography and magnetic resonance imaging (PET/MRI) with 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) has demonstrated the advantages of simultaneous PET and MR imaging with higher soft-tissue contrast, multiplanar image acquisition, and functional imaging capability. This pictorial essay discusses the role of 18F-FDG PET/MRI in the diagnosis of OCC and OPC based on the new cancer staging system.
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Boca/diagnóstico por imagem , Estadiamento de Neoplasias/métodos , Neoplasias Orofaríngeas/diagnóstico por imagem , Neoplasias Orofaríngeas/patologia , Tomografia por Emissão de Pósitrons , Sociedades Médicas , Tomografia Computadorizada por Raios X , HumanosRESUMO
Patients with immunodeficiency or immunosuppression are at risk of developing a lymphoproliferative disorder (LPD). Methotrexate (MTX) is an iatrogenic cause of LPD, which in up to 50% cases occurs in extranodal sites. The occurrence of MTX-related LPD with osteonecrosis of the jaw (ONJ) has rarely been reported. Moreover, there are no clear diagnostic criteria and treatment strategies for management of these lesions. In the present cases, discontinuing MTX and debridement of the necrotic bone were effective. This report describes 3 cases of MTX-related LPD in patients with longstanding rheumatoid arthritis (RA) who presented with ONJ. The first patient was a 74-year-old man with RA who had received treatment with MTX for 7 years before presenting with ONJ and submental lymphadenopathy. The second patient was a 79-year-old woman who had been treated for 21 years with MTX and who presented with ONJ. The third patient was a 67-year-old man who had been treated with MTX for more than 15 years. In all 3 cases, biopsy, histology, and immunohistochemistry using a panel of lymphoid markers (Epstein-Barr virus [EBV], CD79a, CD20, PAX-5, CD3, and CD30) resulted in the diagnosis of EBV-driven T-cell, B-cell, and Hodgkin-like LPD. All 3 patients recovered after cessation of MTX and surgical debridement. Biopsy examination, diagnostic immunohistochemistry using lymphoid immune markers, and imaging studies using computed tomography, magnetic resonance imaging, and positron-emission tomographic computed tomography were useful for the correct diagnosis of this condition.
Assuntos
Transtornos Linfoproliferativos/induzido quimicamente , Doenças Mandibulares/induzido quimicamente , Doenças Maxilares/induzido quimicamente , Metotrexato/efeitos adversos , Osteonecrose/induzido quimicamente , Idoso , Artrite Reumatoide/tratamento farmacológico , Biópsia , Desbridamento , Feminino , Humanos , Imuno-Histoquímica , Transtornos Linfoproliferativos/diagnóstico por imagem , Transtornos Linfoproliferativos/cirurgia , Masculino , Doenças Mandibulares/diagnóstico por imagem , Doenças Mandibulares/cirurgia , Doenças Maxilares/diagnóstico por imagem , Doenças Maxilares/cirurgia , Osteonecrose/diagnóstico por imagem , Osteonecrose/cirurgia , Fatores de RiscoRESUMO
BACKGROUND/AIM: World population has been ageing, and oral-maxillofacial trauma of geriatric population is expected to increase. The aim of this study was to analyse the characteristic features of oral-maxillofacial trauma in the geriatric population. MATERIALS AND METHODS: Data from 127 patients aged 65 years old or older, who were treated for oral-maxillofacial trauma at the Department of Oral and Maxillofacial Surgery, Hirosaki University, from 2000 to 2014, were retrospectively analysed. The data from 292 patients aged 20-64 years were used as a comparison. RESULTS: Oral-maxillofacial trauma in the geriatric population had been increasing over 15-year period. The male to female ratio was 1.05:1 in the older group and 2.3:1 in the younger group. In the older group, 117 patients (92.1%) had one or more underlying systemic diseases, and 16 (12.6%) had suffered injuries in association with acute medical disorders. The most common injuries in the older group were bone fractures (46.5%). The ratio of fractures in the older group was lower than in the younger group (69.2%). Trauma in the older group most frequently occurred because of falls from a standing height or lower (52.0%), and the mandible was the most common site of fracture (74.6%). A conservative form of treatment for maxillofacial fractures was most commonly (86.4%) chosen for the older group, whilst surgical treatment was most commonly in the younger group (55.0%). CONCLUSION: Oral-maxillofacial trauma in the geriatric population shows characteristic features in terms of aetiology, patterns and treatment modalities.
Assuntos
Traumatismos Maxilofaciais/epidemiologia , Traumatismos Maxilofaciais/etiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão/epidemiologia , MasculinoRESUMO
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is often comorbid with asthma and resistant to therapeutic interventions. We recently reported that excessive fibrin deposition caused by impairment of fibrinolysis might play pivotal role in forming nasal polyp. Nattokinase (NK), a serine protease produced by Bacillus subtilis, has been reported to be a strong fibrinolytic enzyme. NK could be a promising drug candidate for use in the treatment of both CRSwNP and asthma. The objective of this study was to investigate the effects of NK on nasal polyp tissues from patients with CRSwNP. The nasal discharge from patients with CRSwNP and sputum from subjects with asthma were also used to investigate whether NK influences the viscosity of mucus. METHODS: To examine the effects on NK on nasal polyp tissues, pieces of nasal polyps were incubated either with saline or NK (10-1000 FU/ml) at 37 °C for 24 h. We assessed the presence of fibrin in nasal polyp tissue incubated with NK by means of immunohistochemistry. To examine the effects of NK on nasal discharge and sputum from patients with CRSwNP and asthma, respectively, were incubated with NK solution at 37 °C for 1 h. RESULTS: NK effectively shrinks the nasal polyp tissue through fibrin degradation. We also found that the viscosity of the nasal discharge and sputum from patients with CRSwNP and asthma, respectively, was significantly reduced by incubation with NK solution. CONCLUSIONS: NK may be an effective alternative therapeutic option in patients with CRSwNP and comorbid asthma by causing fibrin degradation.
Assuntos
Muco/metabolismo , Pólipos Nasais/metabolismo , Pólipos Nasais/patologia , Subtilisinas/metabolismo , Adulto , Idoso , Animais , Asma/imunologia , Asma/metabolismo , Asma/patologia , Doença Crônica , Modelos Animais de Doenças , Eosinófilos/imunologia , Eosinófilos/metabolismo , Eosinófilos/patologia , Feminino , Fibrina/metabolismo , Humanos , Imunoglobulina E/imunologia , Contagem de Leucócitos , Masculino , Camundongos , Pessoa de Meia-Idade , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Pólipos Nasais/imunologia , Proteólise , Rinite/metabolismo , Rinite/patologia , Sinusite/metabolismo , Sinusite/patologia , ViscosidadeRESUMO
OBJECTIVE: Against recent reports concerning cytokine or chemokine in mouse or rat inner ear cells, it is almost unknown whether human inner ear cells would produce cytokine or chemokine. We have for the first time established the human inner-ear-derived fibroblasts from endolymphatic sac. METHODS: The expression levels of Toll-like receptors (TLRs) in human endolymphatic sac fibroblasts, and the effect on cytokine or chemokine production of the TLR ligands have been examined. To demonstrate the intracellular pathways involved in the regulation of cytokine-production, we used specific inhibitors of c-Jun N-terminal kinase (JNK), extracellular signal-related kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK)-signaling and N-acetyl-l-cysteine (NAC). RESULTS: TLR 2, 3, 4 and 9 were highly expressed in human endolymphatic sac fibroblasts. The TLR 3 ligand, polyinosinic-polycytidylic acid (poly(I:C)) significantly enhanced the secretion of thymic stromal lymphopoietin (TSLP), B lymphocyte stimulator (BLyS), IFNγ-inducible protein 10 (IP-10), and macrophage inflammatory protein 1 alpha (MIP-1α) from the cells. The inhibitor of JNK strongly reduced the poly(I:C)-induced TSLP-production. The antioxidant drug, NAC also reduced the TSLP-production in fibroblasts stimulated with poly(I:C). CONCLUSION: Our findings suggest human inner-ear-endolymphatic sac derived fibroblasts can produce the cytokine and chemokine in response to TLR ligands and play a certain role during the initiation of an immune response.
Assuntos
Citocinas/metabolismo , Saco Endolinfático/metabolismo , Fibroblastos/metabolismo , Receptores Toll-Like/metabolismo , Acetilcisteína/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Fator Ativador de Células B/efeitos dos fármacos , Fator Ativador de Células B/metabolismo , Quimiocina CXCL10/efeitos dos fármacos , Quimiocina CXCL10/metabolismo , Quimiocinas/metabolismo , Citocinas/efeitos dos fármacos , Saco Endolinfático/citologia , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Sequestradores de Radicais Livres/farmacologia , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Poli I-C/farmacologia , Receptor 2 Toll-Like/metabolismo , Receptor 3 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Receptor Toll-Like 9/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Linfopoietina do Estroma do TimoRESUMO
PURPOSE: Tumor redox is an important factor for cancer progression, resistance to treatments, and a poor prognosis. The aim of the present study was to define tumor redox (over-reduction) using 62Cu-diacetyl-bis(N4-methylthiosemicarbazone) (62Cu-ATSM) PET and compare its prognostic potential in head and neck cancer (HNC) with that of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG). METHODS: Thirty HNC patients (stage II-IV) underwent pretreatment 62Cu-ATSM and 18F-FDG PET scans. Maximum standardized uptake values (SUVATSM and SUVFDG) and tumor-to-muscle activity concentration ratios (TMRATSM and TMRFDG) were measured. Reductive-tumor-volume (RTV) was then determined at four thresholds (40%, 50%, 60%, and 70% SUVATSM), and total-lesion-reduction (TLR) was calculated as the product of the mean SUV and RTV for 62Cu-ATSM. In 18F-FDG, metabolic-tumor-volume (MTV) and total-lesion-glycolysis (TLG) were obtained at a threshold of 40%. A ROC analysis was performed to determine % thresholds for RTV and TLR showing the best predictive performance, and these were then used to determine the optimal cut-off values to stratify patients for each parameter. Progression-free-survival (PFS) and cause-specific-survival (CSS) were evaluated by the Kaplan-Meier method. RESULTS: The means ± standard deviations of PFS and CSS periods were 16.4±13.4 and 19.2±12.4 months, respectively. A ROC analysis determined that the 70% SUVATSM threshold for RTV and TLR was the best for predicting disease progression and cancer death. Optimal cut-offs for each index were SUVATSM = 3.6, SUVFDG = 7.9, TMRATSM = 3.2, TMRFDG = 5.6, RTV = 2.9, MTV = 8.1, TLR = 14.0, and TLG = 36.5. When the cut-offs for TMRATSM and TLR were set as described above in 62Cu-ATSM PET, patients with higher TMRATSM (p = 0.03) and greater TLR (p = 0.02) showed significantly worse PFS, while patients with greater TLR had significantly worse CSS (p = 0.02). Only MTV in 18F-FDG PET predicted differences in PSF and CSS (p = 0.03 and p = 0.03, respectively). CONCLUSION: Tumor redox parameters measured by 62Cu-ATSM PET may be determinants of HNC patient outcomes and help define optimal patient-specific treatments.