RESUMEN
Apoptosis plays a dual role in cancer development and malignancy. The role of apoptosis-related caspases in cancer remains controversial, particularly in oral tongue squamous cell carcinoma (OTSCC). In this study, we examined the protein levels of cleaved caspase-3, caspase-3, caspase-8, and caspase-9 on tissue microarrays consisting of samples from 246 OTSCC patients by immunohistochemistry. Wilcoxon signed-rank test indicated that the protein levels of cleaved caspase-3, caspase-3, caspase-8, and caspase-9 in tumor tissues were significantly higher compared to those in adjacent normal tissues (all p<0.001). The expression level of caspase-8 in tumors was elevated in patients with lymph node invasion. Moreover, positive expression of cleaved caspase-3 was associated with shorter disease-free survival (DFS) in OTSCC patients with moderate differentiation and lymph node invasion. Combination of either positive cleaved caspase-3 or higher caspase-3 expression or both was associated with poor DFS. Interestingly, stratification analysis showed that co-expression levels of positive cleaved caspase-3 or/and higher caspase-3 were associated with better disease-specific survival in patients with advanced stages of the disease, such as large tumor size and lymph node invasion, whereas it was associated with poor DFS in OTSCC patients with moderate cell differentiation and small tumor size. Taken together, cleaved caspase-3 and caspase-3/8/9 could be biomarkers for tumorigenesis in OTSCC patients. The co-expression level of cleaved caspase-3 and caspase-3 might be a prognostic biomarker for OTSCC patients, particular in those patients with certain tumor stages and cell differentiation status.
Asunto(s)
Carcinogénesis/metabolismo , Carcinoma de Células Escamosas/enzimología , Carcinoma de Células Escamosas/patología , Caspasa 3/metabolismo , Neoplasias de la Lengua/enzimología , Neoplasias de la Lengua/patología , Adulto , Carcinogénesis/patología , Caspasa 8/metabolismo , Caspasa 9/metabolismo , Diferenciación Celular , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
OBJECTIVES: To review cases of peritonsillar abscess and investigate the initial clinical factors that may influence the duration of hospitalization. To determine the predictive factors of prolonged hospital stay in adult patients with peritonsillar abscess. METHODS: Subjects were adults hospitalized with peritonsillar abscess. We retrospectively reviewed 377 medical records from 1990 to 2013 in a tertiary medical center in southern Taiwan. The association between clinical characteristics and the length of hospital stay was analyzed with independent t-test, univariate linear regression and multiple linear regression analysis. RESULTS: The mean duration of hospitalization was 6.2±6.0 days. With univariate linear regression, a prolonged hospital stay was associated with several variables, including female gender, older ages, nonsmoking status, diabetes mellitus, hypertension, band forms in white blood cell (WBC) counts, and lower hemoglobin levels. With multiple linear regression analysis, four independent predictors of hospital stay were noted: years of age (P<0.001), history of diabetes mellitus (P<0.001), ratio of band form WBC (P<0.001), and hemoglobin levels (P<0.001). CONCLUSION: In adult patients with peritonsillar abscess, older ages, history of diabetes mellitus, band forms in WBC counts and lower hemoglobin levels were independent predictors of longer hospitalization.
RESUMEN
MicroRNAs (miRs) are a class of small endogenous non-coding RNAs of ~21-24 nucleotides in length. Previous studies have indicated that miR-196b has either an oncogenic or tumor-suppressive function in various types of cancer. However, the biological role of miR-196b in oral squamous cell carcinoma (OSCC) remains unclear. In the present study, the expression levels of miR-196b were examined in oral cancer tissues and corresponding adjacent normal tissues from 69 OSCC patients using stem-loop reverse transcription-quantitative polymerase chain reaction. The results indicated that miR-196b was significantly overexpressed in OSCC tissues compared with the corresponding adjacent normal tissue samples (64 of 69, 92.7%, P<0.001). Analysis of the methylation status of the miR-196b gene indicated more frequent hypomethylation of the CpG islands located upstream of the miR-196b gene in the OSCC tissues than in the adjacent normal tissues (32 of 69, 46.3%), and the methylation status of miR-196b correlated inversely with its expression levels. Furthermore, the unmethylated status of the miR-196b promoter correlated with poor disease-specific survival in OSCC patients (P=0.035). Functional analysis revealed that ectopic miR-196b expression promoted oral cancer cell migration and invasion abilities, and that silencing of miR-196b could abrogate in vitro migration and invasion of oral cancer cells. Collectively, the present findings indicate that the epigenetic regulation of miR-196b expression plays a crucial role in modulating cell migration and invasion during OSCC progression, and thus may serve as a potential prognosis marker or therapeutic target for OSCC.
RESUMEN
BACKGROUND: OCT4, SOX2, and NANOG are major transcription factors related to stem cell self-renewal and differentiation. The aim of this study was to examine the association of OCT4, SOX2, and NANOG expression levels with the development and prognosis of patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Expression levels of OCT4, SOX2, and NANOG were evaluated by immunohistochemistry with tissue microarray slides of 436 OSCC, 362 corresponding tumor-adjacent normal (CTAN) tissues, and 71 normal uvula epithelium tissues. The clinicopathologic and follow-up data of the OSCC patients were recorded. RESULTS: OCT4 expression was significantly higher in normal and CTAN tissues than in tumor tissue (both P < 0.001). SOX2 expression in CTAN tissue was significantly higher than that in normal (P = 0.021) and tumor tissues (P < 0.001). However, NANOG expression was significantly higher in CTAN (P = 0.014) and tumor tissues (P = 0.009) than in normal tissue. Higher OCT4 and SOX2 expressions were associated with earlier AJCC stage (P = 0.002 and P < 0.001), small tumor size (P = 0.017 and P = 0.001), and the absence of lymph node metastasis (P = 0.015 and P = 0.025). Higher levels of SOX2 expression were associated with better disease-specific survival (P = 0.002) even after adjustment for clinicopathologic factors. DISCUSSION: OCT4 and SOX2 are biomarkers of tumorigenesis and early stage OSCC. SOX2 is an independent prognostic factor for OSCC.
Asunto(s)
Biomarcadores de Tumor , Carcinoma de Células Escamosas/metabolismo , Progresión de la Enfermedad , Neoplasias de la Boca/metabolismo , Proteína Homeótica Nanog/biosíntesis , Factor 3 de Transcripción de Unión a Octámeros/biosíntesis , Factores de Transcripción SOXB1/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Carcinogénesis/genética , Carcinogénesis/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Proteína Homeótica Nanog/genética , Proteína Homeótica Nanog/metabolismo , Células Madre Neoplásicas/patología , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Pronóstico , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo , Factores de Transcripción/metabolismo , Adulto JovenRESUMEN
BACKGROUNDS: Oral cancer is the 4th leading cause of cancer death for males and the top cancer in young adult males in Taiwan. Tongue squamous cell carcinoma (TSCC) is a common oral cancer and generally associated with poor prognosis. Global DNA hypomethylation at the 5 position of cytosine (5mC) is a well-known epigenetic feature of cancer. Therefore, the purpose of this study was to investigate the relationship of the global 5mC content with the tumorigenesis and prognosis of patients with TSCC. METHODS: The levels of global 5mC were evaluated by immunohistochemistry using tissue microarray slides of 248 surgically resected TSCC and 202 corresponding tumor adjacent normal (TAN) tissues. RESULTS: We found that the level of 5mC in TSCC (P < 0.001) was significantly decreased as compared to TAN. Among TSCC tissues, decreased levels of 5mC were associated with female gender (P = 0.036). In addition, the global hypomethylation was associated with the poor disease-specific survival in TSCC patients (adjusted hazard ratio: 1.55, P = 0.043), especially for patients in older age group (> 50 years, P = 0.013), with moderate or poor cell differentiation (P = 0.044), early stage of disease (I-II, P = 0.046), small tumor size (T1-T2, P = 0.005), without lymph node involvement (P = 0.041), and ever received postoperative radiotherapy (P = 0.009). CONCLUSIONS: Global hypomethylation was an independent biomarker for the development and poor prognosis of TSCC.
Asunto(s)
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Metilación de ADN , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Neoplasias de la Lengua/genética , Neoplasias de la Lengua/patología , 5-Metilcitosina/metabolismo , Adulto , Biomarcadores de Tumor/genética , Carcinogénesis/patología , Carcinoma de Células Escamosas/metabolismo , Diferenciación Celular/fisiología , Epigenómica , Femenino , Neoplasias de Cabeza y Cuello/metabolismo , Humanos , Inmunohistoquímica , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello , Tasa de Supervivencia , Neoplasias de la Lengua/metabolismoRESUMEN
OBJECTIVE: Interleukin (IL)-4 is a key cytokine in humoral and adaptive immunity. This study aimed to evaluate the association of IL-4 genetic variants (-590C>T and VNTR in intron 3) with the risk and prognosis of oral and pharyngeal squamous cell carcinoma (OPSCC). DESIGN: A total of 1215 subjects, which included 623 healthy controls and 592 OPSCC cases (463 oral squamous cell carcinoma (OSCC) and 129 pharyngeal squamous cell carcinoma (PSCC) cases), were recruited. The genotypes were determined by TaqMan real-time assay and PCR-based assay. RESULTS: The IL-4 genotypes at locus -590C>T and intron 3 VNTR were not correlated with increased risk of OSCC, PSCC, and OPSCC, with the exception of early-stage OPSCC (at -590C>T: T/T vs. C/C+C/T, adjusted odds ratio (AOR)=1.42, 95% CI: 1.02-1.98; at intron 3 VNTR: RP1/RP1 vs. RP2/RP2+RP2/RP1, AOR=1.46, 95% CI: 1.05-2.04). Compared with other IL-4 diplotypes, the T,RP1/T,RP1 diplotype was associated with an increased risk of OPSCC (AOR=1.37, 95% CI: 1.03-1.81), particularly early-stage OSCC (AOR=1.43, 95% CI: 1.02-2.00), PSCC (AOR=2.35, 95% CI: 1.06-5.19), and OPSCC (AOR=1.52, 95% CI: 1.10-2.11). Interactions between the IL-4 diplotype and the alcohol drinking status were found to contribute to the risk of early-stage OPSCC (p=0.024). In addition, the T,RP1/T,RP1 diplotype was correlated with better disease-specific survival (T,RP1/T,RP1 vs. other diplotypes, adjusted hazard ratio=0.70, 95% CI: 0.50-0.97). CONCLUSION: The T, RP1/T, RP1 diplotype of IL-4 was associated with an increased risk but favourable prognosis of OPSCC.
Asunto(s)
Carcinoma de Células Escamosas/genética , Genotipo , Interleucina-4/genética , Neoplasias de la Boca/genética , Recurrencia Local de Neoplasia/genética , Neoplasias Faríngeas/genética , Polimorfismo Genético , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Areca/efectos adversos , Estudios de Casos y Controles , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Reacción en Cadena de la Polimerasa , Pronóstico , Modelos de Riesgos Proporcionales , Riesgo , Fumar/efectos adversosRESUMEN
OBJECTIVE: The present study investigated the relationship between the expression of manganese superoxide dismutase (MnSOD), catalase, glutathione peroxidase (GPx), and myeloperoxidase (MPO) in buccal mucosal squamous cell carcinoma (SCC), and the risk of second primary tumors (SPTs). STUDY DESIGN: Immunohistochemistry was performed to examine the expression of MnSOD, GPx, catalase, and MPO in tissue microarray slides of 173 male patients with buccal mucosal SCC who had undergone potentially curative resections. RESULTS: Forty-five (26.01%) patients developed SPTs. The prevalent subsites of SPTs were buccal mucosa (48.89%), tongue (13.33%), and lip (11.11%). High expression level of MPO was correlated with an increased risk of SPTs, even after adjustment for development of clinicopathologic parameters (high vs. low expression, adjusted hazard ratio = 3.89; 95% confidence interval, 1.33-11.41; P = .013). CONCLUSIONS: SPTs are common in male buccal mucosal SCC patients. Higher MPO expression in buccal mucosal SCC is a risk factor for SPTs.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/enzimología , Mucosa Bucal/patología , Neoplasias de la Boca/enzimología , Neoplasias Primarias Secundarias/metabolismo , Peroxidasa/metabolismo , Adulto , Anciano , Carcinoma de Células Escamosas/patología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Neoplasias Primarias Secundarias/epidemiología , Modelos de Riesgos Proporcionales , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To compare trends, risk factors, prevalence rates, and hospital resource utilization between tympanoplasty and revision tympanoplasty. STUDY DESIGN: Retrospective review. SETTING: All hospitals. PATIENTS: This study analyzed 58,038 tympanoplasty procedures and 953 revision tympanoplasty procedures performed in Taiwan from 1996 to 2007. MAIN OUTCOME MEASURES: Administrative claims data from the Bureau of National Health Insurance of Taiwan. Odds ratio and 95% confidence intervals were calculated to assess the relative change rate. Regression models were used to predict length of stay (LOS) and hospital treatment costs. RESULTS: The number of tympanoplasties performed per 100,000 patients was 22.97 in 1996. It gradually increased to 26.7 in 2001 and then gradually decreased to 16.61 in 2007. The number of revision tympanoplasties per 100,000 patients during the same period, however, was 0.29 to 0.48. During the study period, the LOS associated with both tympanoplasty and revision tympanoplasty decreased, whereas hospital treatment costs associated with the 2 procedures increased. Considerably decreased LOS and increased hospital treatment costs were associated with age, sex, number of comorbidities, hospital level, hospital volume, surgeon volume, and LOS. CONCLUSION: High-volume hospitals and surgeons obtained the largest improvements in tympanoplasty outcomes, particularly in LOS and hospital treatment costs. Health care providers and patients should recognize that hospital resource utilization may depend on hospital attributes as well as patient attributes.
Asunto(s)
Recursos en Salud/estadística & datos numéricos , Hospitales/estadística & datos numéricos , Timpanoplastia/estadística & datos numéricos , Factores de Edad , Anciano , Comorbilidad , Femenino , Cirugía General , Costos de Hospital , Humanos , Revisión de Utilización de Seguros , Tiempo de Internación , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Análisis de Regresión , Reoperación , Factores de Riesgo , Factores Sexuales , Taiwán/epidemiología , Perforación de la Membrana Timpánica/complicaciones , Perforación de la Membrana Timpánica/epidemiología , Timpanoplastia/economía , Recursos HumanosRESUMEN
BACKGROUND: We investigated the relationship of the immunohistochemical expression status of manganese superoxide dismutase (MnSOD), catalase, glutathione peroxidase (GPx), and myeloperoxidase (MPO) in buccal mucosal squamous cell carcinoma (SCC) with clinicopathologic parameters and prognosis. METHODS: The expression status of MnSOD, GPx, catalase, and MPO was evaluated by immunohistochemistry in a series of 216 surgically resected buccal mucosal SCC specimens, using tissue microarray slides. RESULTS: MnSOD, GPx, catalase, and MPO were commonly expressed in buccal mucosal SCC. The high expression level of MnSOD was associated with better disease-specific survival (p = .009), especially for patients in moderate or poor cell differentiation (p = .045), pathologic stage I (p = .002) and postoperative radiotherapy (p = .048). The high expression level of GPx was also correlated with better disease-specific survival (p = .042), especially for patients in pathologic stage IV (p = .010) and postoperative radiotherapy (p = .018). CONCLUSIONS: MnSOD and GPx are significant prognostic factors for favorable survival in patients with buccal mucosal SCC.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/enzimología , Glutatión Peroxidasa/metabolismo , Mucosa Bucal/patología , Neoplasias de la Boca/enzimología , Superóxido Dismutasa/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Biomarcadores de Tumor/análisis , Biopsia con Aguja , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Supervivencia sin Enfermedad , Femenino , Glutatión Peroxidasa/análisis , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Estadificación de Neoplasias , Peroxidasa/análisis , Peroxidasa/metabolismo , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Muestreo , Sensibilidad y Especificidad , Estadísticas no Paramétricas , Superóxido Dismutasa/análisis , Análisis de Supervivencia , Adhesión del Tejido , Adulto JovenRESUMEN
BACKGROUND: NAT2, the most important phase II metabolic enzyme for betel quid (BQ), might modify the risk of BQ-related oral and pharyngeal squamous cell carcinoma (OPSCC) in Taiwan. STUDY DESIGN: PCR-RFLP and TaqMan assay were conducted for genotyping of NAT2 in 172 OPSCC cases and 170 healthy controls who habitually chewed BQ. RESULTS: The genotypic and allelic type of T341C and C481T in NAT2 are associated with the risk of OPSCC. There were linear trends between increased risk of OPSCC and slowness of NAT2 acetylation haplotypes (P = .017), especially for young subjects (P < .001), light BQ chewers (P = .005), light smokers (P = .023), and alcohol drinkers (P = .001). The interactions on risk of OPSCC were found for NAT2 acetylation haplotypes with status of age, BQ chewing, and alcohol drinking. CONCLUSIONS: The NAT2 acetylation haplotypes might be genetic markers for risk of BQ-related OPSCC.
Asunto(s)
Areca/efectos adversos , Arilamina N-Acetiltransferasa/genética , Carcinoma de Células Escamosas/genética , Haplotipos/genética , Neoplasias de la Boca/genética , Neoplasias Faríngeas/genética , Acetilación , Adenina , Adulto , Factores de Edad , Consumo de Bebidas Alcohólicas , Estudios de Casos y Controles , Citosina , Frecuencia de los Genes/genética , Marcadores Genéticos/genética , Genotipo , Guanina , Humanos , Desequilibrio de Ligamiento/genética , Masculino , Persona de Mediana Edad , Polimorfismo de Longitud del Fragmento de Restricción/genética , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo , Fumar , TiminaRESUMEN
OBJECTIVE: Betel quid (BQ) components induce the secretion of tumour necrosis factor-alpha (TNF-α) in oral keratinocytes, which promotes oral mucosal inflammation and oral cancer. This study was carried out to evaluate the association of TNFA genetic variants (-308G>A and -238G>A) with the risk and prognosis of BQ-related oral and pharyngeal squamous cell carcinoma (OPSCC). DESIGN: A total of 403 subjects (205 cancer cases and 198 healthy controls) who habitually chewed BQ were recruited. The genotypes were determined by TaqMan real-time assays. RESULTS: G allele and G/G genotype at TNFA -308 were associated with a 1.95-fold (95%CI: 1.16-3.28, p(corrected)=0.024) and 2.28-fold (95%CI: 1.30-4.00, p(corrected)=0.008) increased risk of cancer as compared to those with A allele or A/A+A/G genotypes, respectively. In addition, G allele (p=0.080) and G/G genotype (p=0.076) at TNFA -238 were associated with a borderline but statistically significant increased risk of OPSCC. The combined G/G+G/G genotype at both loci had a 2.37-fold increased risk of OPSCC as compared to those with other combined genotypes (95%CI: 1.41-4.00, p=0.001). Interactions between combined genotypes and smoking status were also found to contribute to risk of BQ-related OPSCC. There was no association of TNFA genotypes with clinicopathologic findings or the survival of OPSCC patients. CONCLUSIONS: BQ-chewers who carry the G allele or G/G genotype in TNFA -308 may have an increased risk of OPSCC. The intensity of cigarette smoking modulates the effect of the combined TNFA genotypes on risk of BQ-related OPSCC.
Asunto(s)
Areca/efectos adversos , Carcinoma de Células Escamosas/etiología , Neoplasias de la Boca/etiología , Neoplasias Faríngeas/etiología , Polimorfismo de Nucleótido Simple/genética , Factor de Necrosis Tumoral alfa/genética , Adenina , Adulto , Anciano , Consumo de Bebidas Alcohólicas/efectos adversos , Alelos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/secundario , Estudios de Casos y Controles , Mapeo Cromosómico , Etnicidad , Predisposición Genética a la Enfermedad/genética , Variación Genética/genética , Genotipo , Guanina , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Faríngeas/genética , Neoplasias Faríngeas/patología , Pronóstico , Factores de Riesgo , Fumar/efectos adversos , Tasa de Supervivencia , TaiwánRESUMEN
Mucosa-associated lymphoid tissue (MALT) lymphoma is usually associated with a chronic inflammatory disease or autoimmune disorders from which lymphoid tissue of MALT type arises as a prerequisite for lymphoma proliferation. Primary hematopoietic neoplasms of the larynx are rare. MALT lymphomas of the larynx are believed to arise from preexisting or acquired lymphoid tissue of the upper airway which is documented in the supraglottic region. Therefore, these are mainly located in the supraglottic and glottic areas, with only a few reported in the subglottic region. We report on a 50-year-old woman with a hoarseness, stridor, and developing exertional dyspnea. On indirect laryngoscope, multiple nodular lesions with smooth surface over the subglottis with subglottic steonsis was found. The biopsy confirmed the diagnosis of a MALT lymphoma. We hope to promote awareness and consideration of MALT lymphoma in the differential diagnosis in subglottic steonsis.
Asunto(s)
Glotis , Neoplasias Laríngeas/complicaciones , Laringoestenosis/etiología , Linfoma de Células B de la Zona Marginal/complicaciones , Femenino , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND: Our previous study showed a close relationship between computed tomography (CT)-derived bidimensional measurement of primary tumor and retropharyngeal nodes (BDMprn) and gross tumor volume of primary tumor and retropharyngeal nodes (GTVprn) in nasopharyngeal carcinoma (NPC) and better prognosis for NPC patients with smaller BDMprn. In this study, we report the results on of a study to validate the use of BDM in a separate cohort of NPC patients. METHODS: We retrospectively reviewed 103 newly diagnosed NPC cases who were treated with radiotherapy/concurrent chemoradiotherapy (CCRT) or CCRT with adjuvant chemotherapy from 2002 to 2009. We used magnetic resonance imaging (MRI) to measure BDMprn. We calculated overall survival, recurrence-free and distant metastasis-free survival curves and set a BDMprn cut off point to categorize patients into a high- or low-risk group. We then used Cox proportional hazard model to evaluate the prognostic influence of BDMprn after correcting age, gender and chemotherapy status. RESULTS: After adjusting for age, gender, and chemotherapy status, BDMprn remained an independent prognostic factor for distant metastasis [Hazard ratio (HR) = 1.046; P = 0.042] and overall survival (HR = 1.012; P = 0.012). Patients with BDMprn < 15 cm2 had a greater 3-year overall survival rate than those with BDMprn > or = 15 cm2 (92.3% vs. 73.7%; P = 0.009). They also had a greater 3-year distant metastasis-free survival (94% vs.75%; P = 0.034). CONCLUSION: The predictive ability of BDMprn was validated in a separate NPC cohort. A BDMprn of 15 cm2 can be used to separate NPC patients into high- and low-risk groups and predict survival rates and metastasis potential. It can, therefore, be used as a reference to design clinical trials, predict prognosis, and make treatment decisions.
Asunto(s)
Imagen por Resonancia Magnética , Neoplasias Nasofaríngeas/patología , Tomografía Computarizada por Rayos X , Antineoplásicos/uso terapéutico , Terapia Combinada , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/terapia , Estadificación de Neoplasias , Pronóstico , Radioterapia , Estudios RetrospectivosRESUMEN
BACKGROUND: The literature regarding interleukin (IL)-10 polymorphisms and coronary artery lesions (CALs) in Kawasaki disease (KD) is limited. We investigated whether 3 IL-10 genetic polymorphisms (-1082 A/G, -819 T/C, and -592 A/C) are associated with development of CALs in KD. METHODS AND RESULTS: The genotyping of IL-10 polymorphisms was conducted for 279 KD children (172 without and 107 with CALs in acute stage). Thirty-three patients had CALs in chronic stage and 74 only with transient CALs. The homozygous variant genotype CC of IL-10-819 and IL-10-592 was associated with 80% (P=0.006) and 79% (P=0.008) reduction in risk of CALs in acute stage, respectively. The C allele of IL-10-819 and IL-10-592 was associated with 34% (P=0.034) and 33% (P=0.044) reduction in risk of CALs in acute stage, respectively. Compared with ATA haplotype (adjusted odds ratio (AOR) 0.63, P=0.029) or non-ACC haplotype (AOR 0.64, P=0.033), ACC haplotype was associated with a significantly reduced risk for CALs in acute stage, but not for CALs in chronic stage. Compared with non-ATA haplotype (AOR 1.53, P=0.034), ATA haplotype was associated with a significantly increased risk of CALs, except for CALs in the chronic stage. CONCLUSIONS: The effects of IL-10 gene polymorphism on CALs in acute KD are important. The persistence of CALs in chronic stage depends much more on other factors such as the times of intravenous immunoglobulin treatment.
Asunto(s)
Alelos , Enfermedad Coronaria/genética , Interleucina-10/genética , Síndrome Mucocutáneo Linfonodular/genética , Polimorfismo Genético , Enfermedad Aguda , Niño , Preescolar , Enfermedad Crónica , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/patología , Vasos Coronarios/patología , Femenino , Haplotipos , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Factores Inmunológicos/administración & dosificación , Lactante , Masculino , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Síndrome Mucocutáneo Linfonodular/patología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
AIMS: Oral squamous cell carcinoma (OSCC) is a common worldwide malignancy and there has been little improvement in survival rates in recent decades. Ovatodiolide, a diterpenoid from a Chinese herb, has been reported to exhibit cytotoxicity against several human cancer cell lines. In the present study, the mechanism of action of ovatodiolide was further investigated in the p53 mutant OSCC cell line Ca9-22. MAIN METHODS: The effect of ovatodiolide on cell viability was examined by MTT assay. Cell cycle analysis, DNA fragmentation, and reactive oxygen species (ROS) were investigated by flow cytometry. Caspases and other regulatory molecules were studied by Western blotting. KEY FINDINGS: Treatment of Ca9-22 cells with ovatodiolide led to cell cycle arrest at G2/M phase. Ovatodiolide treatment also induced apoptosis, as indicated by caspase activation, DNA fragmentation, and poly (ADP-ribose) polymerase (PARP) cleavage. By using specific inhibitors of caspase-9 and -8, we demonstrated that ovatodiolide-induced apoptosis is dependent on both intrinsic and extrinsic pathways. The action of ovatodiolide was correlated with a rapid and sustained increase in ROS production and down-regulation of FLICE inhibitory protein (FLIP), which is an endogenous caspase-8 inhibitor and is sensitive to intracellular redox status. Pretreatment of Ca9-22 cells with N-acetylcysteine, a thiol antioxidant, abolished all of ovatodiolide-induced effects, including ROS generation, down-regulation of FLIP, caspase activation, apoptosis as well as cell cycle arrest. SIGNIFICANCE: Our results suggest that ovatodiolide causes cell cycle arrest and apoptosis in Ca9-22 cells through disturbance of intracellular redox balance. Furthermore, ovatodiolide may serve as a lead compound for developing new anticancer drugs.
Asunto(s)
Antineoplásicos Fitogénicos , Apoptosis/efectos de los fármacos , Carcinoma de Células Escamosas/tratamiento farmacológico , Ciclo Celular/efectos de los fármacos , Diterpenos/toxicidad , Neoplasias de la Boca/tratamiento farmacológico , Western Blotting , Carcinoma de Células Escamosas/patología , Caspasas/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Genes p53/genética , Humanos , Neoplasias de la Boca/patología , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/metabolismo , Sales de Tetrazolio , TiazolesRESUMEN
BACKGROUND: Primary tumor volume (PTV) is known to be a significant prognostic factor in malignant tumor. There have been several studies of nasopharyngeal carcinoma (NPC) relating tumor volume to treatment outcome. Our study was designed to evaluate the effect of PTV on treatment outcomes in NPC treated with radiotherapy (RT)/concurrent chemoradiotherapy (CCRT) or CCRT with adjuvant chemotherapy. METHODS: We retrospectively reviewed 100 cases with newly diagnosed NPC who were treated with RT/CCRT or CCRT with adjuvant chemotherapy from 2002 to 2006. Magnetic resonance imaging-derived PTV was calculated using the summation-of-area technique. Kaplan-Meier plots and the log-rank test were used to estimate tumor recurrence (locoregional, distant, or both) and overall survival. Cox proportional hazards regression analysis was used to assess the prognostic impact of PTV. RESULTS: The median PTV was 12.94 mL. PTV remained an independent prognostic factor for distant metastasis (hazard ratio [HR], 1.04; p=0.03), for any relapse (HR, 1.04; p=0.02), and for overall survival (HR, 1.09; p<0.001) in multivariate analysis. In the large tumor volume group (PTV>15 mL), patients' metastasis-free survival rates, with and without adjuvant chemotherapy, were 100% and 68.3%, respectively (p=0.002). Their 3-year recurrence-free survival rates, with and without adjuvant chemotherapy, were 94.1% and 69.6%, respectively (p=0.006). In the small tumor volume group (PTV
Asunto(s)
Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Recurrencia Local de Neoplasia/patología , Humanos , Neoplasias Nasofaríngeas/terapia , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
The dried seeds of XANTHIUM STRUMARIUM (Asteraceae) are used after thorough stir-frying as an ingredient in traditional Chinese medicines for relieving allergy. Two new compounds, xanthialdehyde ( 2) and (-)-xanthienopyran ( 7), as well as 26 known compounds were isolated in the present study. The structures of the isolates were elucidated by spectroscopic methods. Among them, compound 7 exhibited significant selective inhibition of superoxide anion generation by human neutrophils induced by formyl- L-methionyl- L-leucyl- L-phenylalanine, with an IC50 value of 1.72 microg/mL.
Asunto(s)
Aldehídos/aislamiento & purificación , Neutrófilos/efectos de los fármacos , Piranos/farmacología , Superóxidos/metabolismo , Xantinas/aislamiento & purificación , Xantinas/farmacología , Xanthium/química , Aldehídos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Medicamentos Herbarios Chinos/química , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Neutrófilos/metabolismo , Piranos/química , Piranos/aislamiento & purificación , Semillas/química , Xantinas/químicaRESUMEN
BACKGROUND: The purpose of this research was to evaluate the prognostic significance of clinicopathologic variables on the survival rate for squamous cell carcinoma of the buccal mucosa (BMSCC). We analyzed the outcomes of surgical therapy for this aggressive cancer and compared these results with those in the literature. METHODS: We reviewed the medical charts of 172 patients treated in our institution between 1990 and 2005. There were 22 patients excluded from our studies: 20 patients with advanced tumors who received no treatment or palliative treatment, and 2 patients who had received preoperative radiotherapy (RT). The remaining 150 patients were treated with surgeries and among them, 56 patients had undergone postoperative RT. The influence of clinicopathologic factors on the survival rate was analyzed with the Kaplan-Meier method and log-rank test. Multivariate analysis was assessed with Cox's regression model. RESULTS: There were 148 males and 2 females, with a mean age of 53.5 years. The prevalence rate of habitual betel quid chewing documented in charts among 113 patients was 75%. The 5-year overall survival rate and disease-specific survival rate for all patients were 64% and 69%, respectively. For patients with stages I, II, III, and IV disease, the 5-year disease-specific survival rates were 90%, 77%, 52%, and 47%, respectively (p<0.001). According to the multivariate analysis, the pathologic staging and histologic grading of the tumor were independently the important prognostic factors affecting survival rate. There were 80 patients who developed locoregional recurrence in lymph nodes in the follow-up diagnoses. Distant metastases occurred in 14 patients, with 11 of them also having locoregional recurrence. The distant metastases were found in the lungs (8/14), T-spine (3/14), liver (2/14) and brain (1/14). CONCLUSION: Pathologic stage and histologic grade are the most important prognostic factors.
Asunto(s)
Carcinoma de Células Escamosas/mortalidad , Mucosa Bucal/patología , Neoplasias de la Boca/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Recurrencia Local de Neoplasia , Pronóstico , Análisis de Regresión , Tasa de SupervivenciaRESUMEN
BACKGROUND: Spindle cell carcinoma (SpCC) is considered to be a rare variant of squamous cell carcinoma (SCC). The behavior of such tumors is unclear. The aim of this study was to elucidate the treatment and outcome of oral and oropharyngeal SpCC. METHODS: All the medical records of patients with the diagnosis of SpCC in the oral cavity and oropharynx in our hospital from 1994 to 2005 were reviewed. The clinical features, treatments and survival of the patients were evaluated. RESULTS: Within the 11-year study period, 18 patients were diagnosed with oral and oropharyngeal SpCC. There were 3 cases of AJCC (American Joint Committee on Cancer) stage I, 3 of stage II, 2 of stage III, 9 of stage IV, and 1 case without definite staging. Twelve patients died of their diseases. The median overall survival time was 8.89 months. The 1-year overall survival rate was 36.7% and the 3-year overall survival rate was 27.5%. In the early stage group, the 1-year and 3-year survival rates were both 100%. In the late stage group, the 1-year survival rate was 9%, and the 3-year survival rate was 0%. The factors influencing overall survival were tumor grade, lymph nodes, metastasis, stage, vascular invasion and distant recurrence. A high local recurrence rate (73.3%) and distant metastasis rate (33.3%) were observed. CONCLUSION: The behavior of SpCC seems to be more aggressive than that of SCC at a similar stage. Setting wider safety margins (> 2 cm) during surgical intervention is suggested. In the case of locoregional recurrence, salvage operation showed some benefit. Seeking an effective chemotherapy protocol is important for the control of distant recurrence.