RESUMEN
Background: A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Methods: Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. Results: 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. Clinical Trials Registration: NCT00543543; NCT00943722.
Asunto(s)
Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/virología , Vacunas contra Papillomavirus/efectos adversos , Vacunas contra Papillomavirus/inmunología , Adolescente , Adulto , Anticuerpos Antivirales/sangre , Asia/epidemiología , Niño , Método Doble Ciego , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Genitales Femeninos/virología , Humanos , Masculino , Papillomaviridae/genética , Infecciones por Papillomavirus/epidemiología , Vacunas contra Papillomavirus/administración & dosificación , Resultado del Tratamiento , Adulto JovenRESUMEN
Belching may result from transient lower esophageal sphincter relaxation; therefore, it has been proposed that belching may be a manifestation of gastroesophageal reflux disease (GERD). This study was conducted to investigate the frequency of belching during esophagogastroduodenoscopy (EGD) and its association with GERD. A retrospective review was performed on prospectively collected clinical and endoscopic data from 404 subjects who underwent EGD without sedation from December 2012 to May 2013 in a training hospital in Korea. All detectable belching events during endoscopy were counted. Frequency and severity of belching events were compared between the group with and without GERD using an ordinal logistic regression model. There were 145 GERD patients (26 erosive reflux disease and 119 nonerosive reflux disease [NERD]). In the multivariable analysis, GERD was significantly associated with a higher frequency of belching events (odds ratio = 6.59, P < 0.001). Central obesity, female, and younger age were also risk factors for frequent belching during EGD. Subgroup analyses were performed in subjects without erosive reflux disease (n = 378) and NERD (n = 293). NERD was also a predictive factor for frequent belching during EGD (odds ratio = 6.61, P < 0.001), and the frequency of belching was significantly correlated with GERD severity according to the Los Angeles classification (P < 0.05). Frequent belching during EGD was associated with GERD, including NERD. Future research should focus on its adjuvant role in the diagnosis of GERD/NERD and the necessity for applying differentiated endoscopy strategies for GERD patients, leading to less discomfort during EGD in patients at risk for intolerability.
Asunto(s)
Endoscopía del Sistema Digestivo , Eructación , Esfínter Esofágico Inferior , Reflujo Gastroesofágico/fisiopatología , Adulto , Factores de Edad , Endoscopía del Sistema Digestivo/efectos adversos , Endoscopía del Sistema Digestivo/métodos , Eructación/diagnóstico , Eructación/etiología , Eructación/fisiopatología , Esfínter Esofágico Inferior/diagnóstico por imagen , Esfínter Esofágico Inferior/fisiopatología , Femenino , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Factores de Riesgo , Factores Sexuales , Estadística como AsuntoRESUMEN
BACKGROUND: MicroRNAs (miRNAs) have a key role in carcinogenesis through negative regulation of their target genes. Therefore, genetic variations in miRNAs or their target sites may affect miRNA-mRNA interactions, thereby result in altered expression of target genes. This study was conducted to investigate the associations between single-nucleotide polymorphisms (SNP) located in the miRNA target sites (poly-miRTSs) and survival of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: Using public SNP database and miRNA target sites prediction program, 354 poly-miRTSs were selected for genotyping. Among these, 154 SNPs applicable to Sequenom's MassARRAY platform were investigated in 357 patients. A replication study was carried out on an independent patient population (n = 479). Renilla luciferase assay and reverse transcription-polymerase chain reaction were conducted to examine functional relevance of potentially functional poly-miRTSs. RESULTS: Of the 154 SNPs analyzed in a discovery set, 14 SNPs were significantly associated with survival outcomes. Among these, KRT81 rs3660G>C was found to be associated with survival outcomes in the validation cohort. In the combined analysis, patients with the rs3660 GC + CC genotype had a significantly better overall survival compared with those with GG genotype [adjusted hazard ratio (aHR) for OS, 0.65; 95% confidence interval (CI) 0.50-0.85; P = 0.001]. An increased expression of the reporter gene for the C allele of rs3660 compared with the G allele was observed by luciferase assay. Consistently, the C allele was associated with higher relative expression level of KRT81 in tumor tissues. CONCLUSION: The rs3660G>C affects KRT81 expression and thus influences survival in early-stage NSCLC. The analysis of the rs3660G>C polymorphism may be useful to identify patients at high risk of a poor disease outcome.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Queratinas Específicas del Pelo/genética , Queratinas Tipo II/genética , Neoplasias Pulmonares/genética , MicroARNs/genética , Polimorfismo de Nucleótido Simple , Regiones no Traducidas 3' , Anciano , Sitios de Unión , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Biología Computacional , Bases de Datos Genéticas , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Células HEK293 , Humanos , Estimación de Kaplan-Meier , Queratinas Específicas del Pelo/metabolismo , Queratinas Tipo II/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Estadificación de Neoplasias , Fenotipo , Modelos de Riesgos Proporcionales , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Riesgo , Factores de Tiempo , TransfecciónRESUMEN
BACKGROUND: In this study, we aimed to identify demographic and clinical variables that correlate with perceived information provision among cancer patients and determine the association of information provision with decisional conflict (DC). PATIENTS AND METHODS: We enrolled a total of 625 patients with cancer from two Korean hospitals in 2012. We used the European Organization for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire (QLQ-INFO26) to assess patients' perception of the information received from their doctors and the Decisional Conflict Scale (DCS) to assess DC. To identify predictive sociodemographic and clinical variables for adequate information provision, backward selective logistic regression analyses were conducted. In addition, adjusted multivariate logistic regression analyses were carried out to identify clinically meaningful differences of perceived level of information subscales associated with high DC. RESULTS: More than half of patients with cancer showed insufficient satisfaction with medical information about disease (56%), treatment (73%), other services (83%), and global score (80%). In multiple logistic regression analyses, lower income and education, female, unmarried status, type of cancer with good prognosis, and early stage of treatment process were associated with patients' perception of inadequate information provision. In addition, Information about the medical tests with high DCS values clarity [adjusted odds ratio (aOR), 0.54; 95% confidence interval (CI) 0.30-0.97] and support (aOR, 0.53; 95% CI 0.33-0.85) showed negative significance. For inadequate information perception about treatments and other services, all 5 DCS scales (uncertainty, informed, values clarity, support, and effective decision) were negatively related. Global score of inadequate information provision also showed negative association with high DCS effective decision (aOR, 0.43; 95% CI 0.26-0.71) and DCS uncertainty (aOR, 0.46; 95% CI 0.27-0.77). CONCLUSION: This study found that inadequate levels of perceived information correlated with several demographic and clinical characteristics. In addition, sufficient perceived information levels may be related to low levels of DC.
Asunto(s)
Comunicación , Conflicto Psicológico , Toma de Decisiones , Relaciones Médico-Paciente , Escolaridad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/terapia , Educación del Paciente como Asunto , Calidad de Vida , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
The skeleton normally responds to mechanical environment to maintain the resulting elastic deformation (strain) of bone, while increased bone strength by an osteoporosis drug results in decreased bone strain. Thus, it can be hypothesized that the effect of osteoporosis therapy is limited by natural homeostatic system in the skeleton. This logic is consistent with the fact that there exists a powerful effect that returns bone mass to its pre-treatment level after the withdrawal of treatment with osteoporosis agents. The present hypothesis provides a new significant insight into the mechanisms by which osteoporosis drugs improve bone fragility. Here we briefly discuss the effects of teriparatide, romosozumab, and odanacatib on bones in animals and humans.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Compuestos de Bifenilo/farmacología , Conservadores de la Densidad Ósea/farmacología , Remodelación Ósea/efectos de los fármacos , Osteoporosis/tratamiento farmacológico , Teriparatido/farmacología , Animales , Resorción Ósea/tratamiento farmacológico , Humanos , Estrés MecánicoRESUMEN
The aim of this study was to evaluate the reliability of using tumour grade and cell type on preoperative endometrial biopsy for the selection of patients for conservative hormone treatment. We retrospectively reviewed results of 643 patients with endometrial carcinoma for tumour grade and 817 for tumour cell type who underwent endometrial biopsy followed by surgery. Of the 357 patients with a grade 1 tumour on preoperative endometrial biopsy, 58 (16.2%) were upgraded based on a final pathology report from hysterectomy specimens. For grade 1, the preoperative endometrial biopsy showed a sensitivity of 80.4%, a specificity of 78.6%, a positive predictive value (PPV) of 83.8% and a negative predictive value (NPV) of 74.5%. Of the 672 patients with the endometrioid cell type on preoperative biopsy, 46 (5.6%) showed a different cell type on final pathology. For the endometrioid cell type, preoperative endometrial biopsy had a sensitivity of 91.3%, a specificity of 64.9%, a PPV of 93.2% and an NPV of 58.6%. This weak predictive value should be considered when selecting patients for conservative hormone treatment.
Asunto(s)
Carcinoma Endometrioide/patología , Neoplasias Endometriales/patología , Endometrio/patología , Biopsia/estadística & datos numéricos , Femenino , Humanos , Cuidados Preoperatorios , Estudios RetrospectivosRESUMEN
BACKGROUND: The objective of this study is to construct a preoperative nomogram predicting lymph node metastasis (LNM) in early-cervical cancer patients. METHODS: Between 2009 and 2012, 493 early-cervical cancer patients received hysterectomy and pelvic/para-aortic lymphadenectomy. Patients who were diagnosed during 2009-2010 were assigned to a model-development cohort (n=304) and the others were assigned to a validation cohort (n=189). A multivariate logistic model was created from preoperative clinicopathologic data, from which a nomogram was developed and validated. A predicted probability of LNM<5% was defined as low risk. RESULTS: Age, tumour size assessed by magnetic resonance imaging, and LNM assessed by positron emission tomography/computed tomography were independent predictors of nodal metastasis. The nomogram incorporating these three predictors demonstrated good discrimination and calibration (concordance index=0.878; 95% confidence interval (CI), 0.833-0.917). In the validation cohort, the discrimination accuracy was 0.825 (95% CI, 0.736-0.895). In the model-development cohort, 34% of them were classified as low risk and negative predictive value (NPV) was 99.0%. In the validation cohort, 38% were identified as low risk and NPV was 95.8%. Integrating the model-development and validation cohorts, negative likelihood ratio was 0.094 (95% CI, 0.036-0.248). CONCLUSION: A robust nomogram predicting LNM in early cervical cancer was developed. This model may improve clinical trial design and help physicians to decide whether lymphadenectomy should be performed.
Asunto(s)
Ganglios Linfáticos/patología , Nomogramas , Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Modelos Logísticos , Ganglios Linfáticos/cirugía , Metástasis Linfática , Imagen por Resonancia Magnética , Persona de Mediana Edad , Imagen Multimodal , Análisis Multivariante , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Valor Predictivo de las Pruebas , Neoplasias del Cuello Uterino/cirugía , Adulto JovenRESUMEN
BACKGROUND: In this study, we sought to identify a criterion for the intermediate-risk grouping of patients with cervical cancer who exhibit any intermediate-risk factor after radical hysterectomy. METHODS: In total, 2158 patients with pathologically proven stage IB-IIA cervical cancer with any intermediate-risk factor after radical hysterectomy were randomly assigned to two groups, a development group and a validation group, at a ratio of 3 : 1 (1620 patients:538 patients). To predict recurrence, multivariate models were developed using the development group. The ability of the models to discriminate between groups was validated using the log-rank test and receiver operating characteristic (ROC) analysis. RESULTS: Four factors (histology, tumour size, deep stromal invasion (DSI), and lymphovascular space involvement (LVSI)) were significantly associated with disease recurrence and included in the models. Among the nine possible combinations of the four variables, models consisting of any two of the four intermediate-risk factors (tumour size ≥3 cm, DSI of the outer third of the cervix, LVSI, and adenocarcinoma or adenosquamous carcinoma histology) demonstrated the best performance for predicting recurrence. CONCLUSION: This study identified a 'four-factor model' in which the presence of any two factors may be useful for predicting recurrence in patients with cervical cancer treated with radical hysterectomy.
Asunto(s)
Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Histerectomía/efectos adversos , Histerectomía/métodos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , República de Corea , Riesgo , Adulto JovenRESUMEN
OBJECTIVE: To investigate the prognostic value of metabolic tumour volume (MTV) and total lesion glycolysis (TLG), measured by preoperative positron emission tomography and computerised tomography (PET/CT), in women with endometrial cancer. DESIGN: Retrospective cohort study. SETTING: A tertiary referral centre. POPULATION: Women with endometrial cancer who underwent preoperative (18)F-FDG PET/CT in the period 2004-2009. METHODS: Clinicopathological data for 84 women with endometrial cancer were reviewed from medical records. Cox proportional hazards modelling identified recurrence predictors. The receiver operating characteristic (ROC) curve was used to determine the cut-off value for predicting recurrence. MAIN OUTCOME MEASURE: Disease-free survival (DFS). RESULTS: The number of patients with International Federation of Gynecology and Obstetrics (FIGO) stages were: I (58); II (11); III (13); and IV (2). The median DFS was 48 (1-85) months. By univariate analysis, DFS was significantly associated with FIGO stage, histology, peritoneal cytology, myometrial invasion, nodal metastasis, serum CA-125, MTV, and TLG. Using multivariate analysis, the MTV (P = 0.010; hazard ratio, HR = 1.010; 95% confidence interval, 95% CI = 1.002-1.018) and TLG (P = 0.024; HR = 1.001; 95% CI = 1.000-1.002) were associated with DFS. The area under the ROC curve was 0.679 (95% CI = 0.505-0.836) after discriminating for recurrence using an MTV cut-off value of 17.15 ml. Regarding TLG, the cut-off value was 56.43 g and the area under the ROC plot was 0.661 (95% CI = 0.501-0.827). Kaplan-Meier survival graphs demonstrated a significant difference in DFS between groups categorised using the cut-off values for MTV and TLG (P < 0.022 for MTV and P < 0.047 for TLG, by log-rank test). CONCLUSIONS: Preoperative MTV and TLG could be independent prognostic factors predicting the recurrence of endometrial cancer.
Asunto(s)
Neoplasias Endometriales/diagnóstico por imagen , Recurrencia Local de Neoplasia/diagnóstico , Adulto , Anciano , Supervivencia sin Enfermedad , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Femenino , Fluorodesoxiglucosa F18 , Glucólisis , Humanos , Persona de Mediana Edad , Tomografía de Emisión de Positrones/métodos , Cuidados Preoperatorios/métodos , Pronóstico , Radiofármacos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Adulto JovenRESUMEN
Lung resection surgery has been associated with numerous postoperative complications. Seventy-eight patients scheduled for elective video-assisted thoracoscopic lung resection were randomly assigned to receive standard postoperative care with incentive spirometry or standard care plus positive vibratory expiratory pressure treatment using the Acapella(®) device. There was no significant difference between incentive spirometry and the Acapella device in the primary outcome, forced expiratory volume in 1 s, on the third postoperative day, mean (SD) 53% (16%) vs 59% (18%) respectively, p = 0.113. Patients treated with both devices simultaneously found incentive spirometry to be less comfortable compared with the Acapella device, using a numeric rating scale from 1 to 5 with lower scores indicating higher comfort, median (IQR [range]) 3 (2-3 [2-4]) vs 1 (1-2 [1-3]) respectively, p < 0.001. In addition, 37/39 patients (95%) stated a clear preference for the Acapella device. Postoperative treatment with the Acapella device did not improve pulmonary function after thoracoscopic lung resection surgery compared with incentive spirometry, but it may be more comfortable to use.
Asunto(s)
Modalidades de Fisioterapia/instrumentación , Neumonectomía , Espirometría/métodos , Toracoscopía , Anciano , Femenino , Humanos , Pulmón/fisiopatología , Masculino , Persona de Mediana EdadRESUMEN
Nanocytalline TiN films were deposited on non-alkali glass and Al substrates by reactive DC magnetron sputtering (DCMS) with an electromagnetic field system (EMF). The microstructure and corrosion resistance of the TiN-coated Al substrates were estimated by X-ray diffraction (XRD), scanning electron microscopy (SEM) and electrochemical methods. All the TiN films shows that they have a (111) preferred orientation at room temperature. TiN films deposited on Al substrate using only DCMS 400 W showed a sheet resistance of 3.22 x 10-1 omega/symbol see texts (resistivity, 3.22 x 10-5 omegacm). On the other hand, a relatively low sheet resistance of 1.91 x 10-1 omega/symbol see text (1.91 x 10-5 omegacm) was obtained for the dense nanocrystalline TiN film deposited on Al substrate using DCMS 375 W+ EMF 25 W, indicating that the introduction of an EMF system enhanced the electrical properties of the TiN film. TiN films deposited on Al substrate at 400 degreesC had a (200) preferred orientation with the lowest sheet resistance of 1.28x10-1 omega/symbol see texts (1.28 x 10-5 omegacm) which was attributed to reduced nano size defects and an improvement of the crystallinity. Potentiostatic and Potentiodynamic tests with a TiN-coated Al showed good corrosion resistance (l/corr, = 2.03 microA/cm2, Ecorr = -348 mV) compared to the uncoated Al substrate (/corr = 4.45 microA/cm2, Ecorr = -650 mV). Furthermore, EMF system showed that corrosion resistance of the TiN film also was enhanced compared to DCMS only. For the TiN film deposited on Al substrate at 400 degreesC, corrosion current and potential was 0.63 micro/cm2 and -1.5 mV, respectively. This improved corrosion resistance of the TiN film could be attributed to the densification of the film caused by enhancement of nitrification with increasing high reactive nitrogen radicals.
Asunto(s)
Cristalización/métodos , Membranas Artificiales , Nanoestructuras/química , Nanoestructuras/ultraestructura , Gases em Plasma/química , Titanio/química , Corrosión , Calor , Sustancias Macromoleculares/química , Imanes , Ensayo de Materiales , Conformación Molecular , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
BACKGROUND: To compare the long-term survival outcomes between laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH). METHOD: We matched patients with stage IA2 to IIA cervical cancer with known risk factors for recurrence who underwent ORH and LRH. RESULTS: Compared with ORH (n = 263), LRH (n = 263) did not have higher risks of recurrence [hazard ratio (HR) = 1.28; 95% confidence interval (CI) 0.62-2.64] or death (HR = 1.46; 95% CI 0.62-3.43). Even in patients with tumors >2 cm in diameter, the risks of recurrence (HR = 0.82; 95% CI 0.31-2.16) or death (HR = 1.01; 95% CI 0.35-2.95) were not higher for LRH than for ORH. The LRH and ORH group had 5-year recurrence-free survival rates of 92.8% and 94.4%, respectively (P = 0.499). LRH resulted in significantly lower estimated blood loss (379.6 versus 541.1 ml, P < 0.001) and shorter postoperative hospital stay (12.5 versus 20.3 days, P < 0.001). Intraoperative complication rates were similar in the two groups (6.8% versus 5.7%, P = 0.711), but postoperative complication rate was lower in the LRH than in the ORH group (9.2% versus 21%, P < 0.001). CONCLUSION: LRH is an oncologically safe alternative to ORH and was associated with fewer postoperative complication and earlier recovery.
Asunto(s)
Adenocarcinoma/cirugía , Carcinoma de Células Escamosas/cirugía , Histerectomía/métodos , Laparoscopía , Neoplasias del Cuello Uterino/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patologíaRESUMEN
BACKGROUND: Biological complexity leads to significant variation in the survival of patients with stage I non-small-cell lung cancer (NSCLC). DNA damage response (DDR) pathways play a critical role in maintaining genomic stability and in the progression of NSCLC. Therefore, the development of a prognostic biomarker focusing on DDR pathways is an intriguing issue. PATIENTS AND METHODS: Expression of several proteins (ATM, ATMpS1981, γH2AX, 53BP1, 53BP1pS25, Chk2, Chk2pT68, MDC1, MDC1pS964, BRCA1pS1423, and ERCC1) and overall survival were investigated in 889 pathological stage I NSCLC patients. RESULTS: Low expression of BRCA1pS1423 or ERCC1 was significantly associated with worse survival in the whole cohort of patients. Analysis performed based on histology revealed that low expression of γH2AX, Chk2pT68, or ERCC1 was a poor prognostic factor in squamous cell carcinoma patients [adjusted hazard ratio (aHR), Cox P: 1.544, 0.012 for γH2AX; 1.624, 0.010 for Chk2pT68; 1.569, 0.011 for ERCC1]. The analysis of the interaction between two proteins showed that this effect was more pronounced in squamous cell carcinoma patients. However, these effects were not detected in adenocarcinoma patients. CONCLUSIONS: The proteins involved in DDR pathways exhibited differential expression between squamous cell carcinoma and adenocarcinoma and were important determinants of survival in stage I squamous cell carcinoma patients.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Daño del ADN , Neoplasias Pulmonares/genética , Proteínas de Neoplasias/genética , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Quimioterapia Adyuvante , Femenino , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Estadificación de Neoplasias , Tasa de SupervivenciaRESUMEN
BACKGROUND AND OBJECTIVE: Human periodontal ligament stem cells (hPDLSCs) have been reported to play the pivotal role in periodontal regeneration. However, the dynamic cellular healing process initiated by hPDLSCs still remains to be elucidated. In the present study, the sequence of regeneration by hPDLSCs was assessed using histological and immunohistochemical observation in an ectopic transplantation model, which is a well-standardized assessment tool that excludes the innate healing factors from the animals. MATERIAL AND METHODS: Human periodontal ligament stem cells that were isolated and characterized from teeth (n=12) extracted for the purpose of orthodontic treatment were transplanted with carriers into ectopic subcutaneous pouches in immunocompromised mice (n=20). Animals were killed after several different healing periods: 3 d (n=4), 1 (n=4), 2 (n=4), 4 (n=4) and 8 wk (n=4). Histological analysis for regenerated tissues formed by hPDLSCs was conducted using hematoxylin and eosin, Masson's trichrome and picrosirius red staining. In addition, immunohistochemical staining was performed to observe the sequential expression of osteogenic/cementogenic and periodontal ligament tissue-specific markers associated with periodontal regeneration. RESULTS: The whole healing process by transplanted hPDLSCs could be broadly divided into four distinctive phases. In the first phase, proliferated hPDLSCs migrated evenly all over the carrier, and collagenous tissues appeared in the form of amorphous collagen matrices. In the second phase, collagen fibers were well arranged among the carriers, and cementoid-like tissues were observed. In the third phase, the formation of mature collagen fibers, resembling Sharpey's fibers, was associated with active mineralization of cementum-like tissues, and in the fourth phase, the maturation of cementum-like tissues was observed on carrier surfaces. Various osteogenic/cementogenic markers related to the regeneration processes were expressed in a well-orchestrated time order. Interestingly, well-organized cementum-like and periodontal ligament fiber-like tissues and cells with early and late osteogenic/cementogenic markers were frequently observed in the secluded area of carrier surfaces. We termed this area the cell-rich zone. CONCLUSION: The results from this study clearly demonstrated the sequential histological changes during periodontal tissue regeneration by hPDLSCs. Understanding of this process would potentially enable us to develop better cell-based treatment techniques.
Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Ligamento Periodontal/citología , Ligamento Periodontal/fisiología , Regeneración/fisiología , Ingeniería de Tejidos/métodos , Fosfatasa Alcalina/biosíntesis , Análisis de Varianza , Animales , Regeneración Ósea/fisiología , Fosfatos de Calcio , Adhesión Celular , Cementogénesis/fisiología , Fenómenos Cronobiológicos , Colágeno Tipo I/biosíntesis , Colágeno Tipo III/biosíntesis , Subunidad alfa 1 del Factor de Unión al Sitio Principal/biosíntesis , Durapatita , Humanos , Técnicas para Inmunoenzimas , Masculino , Ratones , Ratones SCID , Modelos Biológicos , Osteocalcina/biosíntesis , Osteopontina/biosíntesis , Estadísticas no Paramétricas , Tejido Subcutáneo/cirugía , Andamios del TejidoRESUMEN
Anterior vaginal wall prolapse is the most common type of pelvic organ prolapse. Vaginal wall samples were obtained from women with (n =12) and without (n =12) anterior vaginal wall prolapse. No reports have been published on the content of fibulin-3 in the vaginal walls of patients with prolapse; thus, we compared the expression of fibulin-3 in the vaginal walls of women with and without anterior vaginal wall prolapse. RT-PCR was performed to measure mRNA expression and the expression of protein was assessed by immunohistochemistry. Statistical analysis was performed to determine differences between the two groups of women. Age, parity and menopausal status did not differ between women with and without prolapse. The expressions of fibulin-3 mRNA and protein were not different between the prolapse and no prolapse groups. It is unlikely that abnormal expression of fibulin-3 has a major role in the pathogenesis of anterior vaginal wall prolapse.
Asunto(s)
Proteínas de la Matriz Extracelular/metabolismo , Prolapso Uterino/metabolismo , Vagina/metabolismo , Adulto , Proteínas de la Matriz Extracelular/genética , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Persona de Mediana Edad , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: this study investigated the outcomes after radical hysterectomy according to tumor size divided by 2-cm interval in patients with International Federation of Obstetrics and Gynecology stage IA2-IIA cervical cancer. PATIENTS AND METHODS: a total of 1415 patients were eligible for participation in the study and were retrospectively analyzed. Patients were divided into four groups according to tumor size (i.e. ≤ 2, 2-4, 4-6 and >6 cm). The relationships between tumor size and other clinicopathologic risk factors, the probability of adjuvant therapy, survival parameters, recurrence-free survival (RFS) and overall survival (OS) were analyzed. RESULTS: the incidence of intermediate- and high-risk factors gradually increased with increasing tumor size. Adjuvant therapy was required in 13.6%, 34.0%, 56.7% and 92.9% of patients with tumor sizes of ≤ 2, 2-4, 4-6 and >6 cm, respectively (P < 0.001). The risks of recurrence and death gradually increased with increasing tumor size, after adjusting for other significant prognostic factors in multivariate analysis (P < 0.001 and < 0.001, respectively). Even in patients with no intermediate- or high-risk factors, tumor size was a significant predictor of RFS and OS (P < 0.001 and < 0.001, respectively). Immediate surgical parameters did not significantly differ according to tumor size. CONCLUSIONS: tumor size divided by a 2-cm interval was an independent prognostic factor and correlated well with other risk factors and with the need for adjuvant therapy.