RESUMEN
BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric and gastroesophageal adenocarcinoma (GEA) is globally treated with chemotherapy plus trastuzumab. Novel therapeutic strategies strive to not only optimize efficacy, but also limit toxicities. In MAHOGANY cohort A, margetuximab, an Fc-engineered, anti-HER2 monoclonal antibody (mAb) was combined with retifanlimab, an anti-programmed cell death protein 1 mAb, in the first-line HER2-positive/programmed death-ligand 1 (PD-L1)-positive GEA. PATIENTS AND METHODS: MAHOGANY cohort A part 1 is a single-arm trial to evaluate margetuximab plus retifanlimab in patients with HER2 immunohistochemistry 3+, PD-L1-positive (combined positive score ≥1%), and non-microsatellite instability-high tumors. Primary objectives for cohort A were safety/tolerability and the confirmed objective response rate (ORR). RESULTS: As of 3 August 2021, 43 patients were enrolled and received margetuximab/retifanlimab. Nine grade 3 treatment-related adverse events (TRAEs) were reported in eight (18.6%) patients and eight serious TRAEs in seven (16.3%) patients. There were no grade 4/5 TRAEs. Three patients discontinued margetuximab/retifanlimab because of immune-related adverse events. The ORR by independent assessment was 53% [21/40 (95% confidence interval (CI) 36.1-68.5)], with a median duration of response of 10.3 months (95% CI 4.6-not evaluable); disease control rate was 73% [29/40 (95% CI 56.1-85.4)]. The study sponsor discontinued the study in advance of the planned enrollment when it became apparent that the study design would no longer meet the requirements for drug approval because of recent advances in the treatment of GEA. CONCLUSIONS: The chemotherapy-free regimen of combined margetuximab/retifanlimab as first-line treatment in double biomarker-selected patients demonstrated a favorable toxicity profile compared with historical outcomes using chemotherapy plus trastuzumab. The ORR observed in this study compares favorably versus ORR observed with other chemotherapy-free approaches.
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Adenocarcinoma , Neoplasias Gástricas , Humanos , Antígeno B7-H1/metabolismo , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Trastuzumab/farmacología , Trastuzumab/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Inhibidores de Puntos de Control InmunológicoRESUMEN
BACKGROUND: The RAINBOW trial showed that second-line ramucirumab with paclitaxel prolongs overall survival (OS) and progression-free survival (PFS) compared with placebo plus paclitaxel for treatment of advanced gastric/gastroesophageal junction cancer. Plasma samples were collected from patients during the trial and tested to identify predictive and prognostic biomarkers. PATIENTS AND METHODS: Circulating factors in plasma samples from mutually exclusive subsets of RAINBOW patients were assayed using: Intertek assays (24 markers, 380 samples, 57% of patients) and Lilly-developed assay (LDA) platform (5 markers, 257 samples, 39% of patients). Time-trend plots were generated for each marker from the Intertek assays. Baseline patient data were dichotomized into low- and high-marker subgroups. Markers were analyzed for predictive effects using interaction models and for prognostic effects using main-effects models. RESULTS: The Intertek and LDA populations were representative of the full trial population. Plasma levels of VEGF-D and PlGF increased from baseline levels during treatment, then declined after treatment discontinued. Angiopoietin-2 exhibited a decrease during treatment, then increased after treatment discontinuation. No clear time trend was evident with the other markers. Analyses of baseline biomarker expression and its relationship with efficacy variables found no biomarker was predictive for efficacy outcomes, including VEGF-D. However, CRP, HGF, ICAM-3, IL-8, SAA, and VCAM-1 were identified as potential prognostic markers with low baseline levels corresponding to longer OS and PFS. CONCLUSIONS: Pharmacodynamic and prognostic relationships were found from the exploratory biomarker analyses in RAINBOW; however, no predictive markers for ramucirumab in gastric cancer were identified in this trial.
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Adenocarcinoma/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/sangre , Neoplasias Esofágicas/sangre , Unión Esofagogástrica/patología , Neoplasias Gástricas/sangre , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Anticuerpos Monoclonales Humanizados/administración & dosificación , Método Doble Ciego , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Unión Esofagogástrica/efectos de los fármacos , Estudios de Seguimiento , Humanos , Paclitaxel/administración & dosificación , Pronóstico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Factor D de Crecimiento Endotelial Vascular/sangre , RamucirumabRESUMEN
BACKGROUND: Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is an early biomarker of renal injury. We examined the feasibility of using uNGAL as an early predictor of renal impairment in patients under calcineurin inhibitors in liver transplant recipients. METHODS: From urine samples obtained from liver transplant recipients, the glomerular filtration rate (GFR) at the time of urine sampling was compared with that at 5 to 7 months later. Patients were divided into 3 groups according to initial GFR and then divided into 2 groups according to the uNGAL level of 25 ng/mL. Progression of renal injury (PRI) was defined as a decrease in the GFR of more than 5 mL/min/1.73 m2 in the mild or moderate groups, or if a normal group patient shifted to the mild or moderate group. RESULTS: Fifty-one patients were enrolled. The mean uNGAL level was higher in the moderate group than in the normal and mild groups (18.38 ± 14.31 vs 7.74 ± 8.13; P < .01). A proportion of uNGAL-high was also higher in the moderate group than in the mild group (40% vs 5%; P = .03). uNGAL-high was a risk factor for 6-month PRI (odds ratio, 60.375; 95% confidence interval, 1.283-4088.25; P = .037) and 1-year PRI (odds ratio, 21.311; % confidence interval, 0.947-479.578; P = .054). CONCLUSIONS: A uNGAL of >25 ng/mg can be a marker for moderate renal impairment (GFR of 30-59 mL/min/1.73 m2) and a predictor of PRI at 6 months in patients using calcineurin inhibitors. Renal protection strategies should be considered in liver transplant recipients with a uNGAL of >25 ng/mg in spot urine sampling.
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Lesión Renal Aguda/inducido químicamente , Inhibidores de la Calcineurina/efectos adversos , Inmunosupresores/efectos adversos , Lipocalina 2/orina , Trasplante de Hígado , Lesión Renal Aguda/orina , Adulto , Biomarcadores/orina , Femenino , Tasa de Filtración Glomerular , Humanos , Trasplante de Hígado/métodos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Background: Paclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, and pharmacokinetics to i.v. paclitaxel as a second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure. Methods and materials: Patients were randomized 1 : 1 to DHP107 (200 mg/m2 orally twice daily days 1, 8, 15 every 4 weeks) or i.v. paclitaxel (175 mg/m2 day 1 every 3 weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6 weeks. Primary end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, first with a non-inferiority margin of 1.48, then with a margin of 1.25. Results: Baseline characteristics were balanced in the 236 randomized patients (n = 118 per arm). Median PFS (per-protocol) was 3.0 (95% CI 1.7-4.0) months for DHP107 and 2.6 (95% CI 1.8-2.8) months for paclitaxel (hazard ratio [HR] = 0.85; 95% CI 0.64-1.13). A sensitivity analysis on PFS using independent central review showed similar results (HR = 0.93; 95% CI 0.70-1.24). Median OS (full analysis set) was 9.7 (95% CI 7.1 - 11.5) months for DHP107 versus 8.9 (95% CI 7.1-12.2) months for paclitaxel (HR = 1.04; 95% CI 0.76-1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%). Conclusions: DHP107 as a second-line treatment of AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC. ClinicalTrials.gov: NCT01839773.
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Antineoplásicos Fitogénicos/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Paclitaxel/administración & dosificación , Neoplasias Gástricas/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Criterios de Evaluación de Respuesta en Tumores Sólidos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Análisis de SupervivenciaRESUMEN
BACKGROUND: The phase III RAINBOW trial demonstrated that the addition of ramucirumab to paclitaxel improved overall survival, progression-free survival, and tumor response rate in fluoropyrimidine-platinum previously treated patients with advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. Here, we present results from quality-of-life (QoL) and performance status (PS) analyses. PATIENTS AND METHODS: Patients with Eastern Cooperative Oncology Group PS of 0/1 were randomized to receive ramucirumab (8 mg/kg i.v.) or placebo on days 1 and 15 of a 4-week cycle, with both arms receiving paclitaxel (80 mg/m(2)) on days 1, 8, and 15. Patient-reported outcomes were assessed with the QoL/health status questionnaires EORTC QLQ-C30 and EQ-5D at baseline and 6-week intervals. PS was assessed at baseline and day 1 of every cycle. Time to deterioration (TtD) in each QLQ-C30 scale was defined as randomization to first worsening of ≥10 points (on 100-point scale) and TtD in PS was defined as first worsening to ≥2. Hazard ratios (HRs) for treatment effect were estimated using stratified Cox proportional hazards models. RESULTS: Of the 665 patients randomized, 650 (98%) provided baseline QLQ-C30 and EQ-5D data, and 560 (84%) also provided data from ≥1 postbaseline time point. Baseline scores for both instruments were similar between arms. Of the 15 QLQ-C30 scales, 14 had HR < 1, indicating similar or longer TtD in QoL for ramucirumab + paclitaxel. Treatment with ramucirumab + paclitaxel was also associated with a delay in TtD in PS to ≥2 (HR = 0.798, P = 0.0941). Alternate definitions of PS deterioration yielded similar results: PS ≥ 3 (HR = 0.656, P = 0.0508), deterioration by ≥1 PS level (HR = 0.802, P = 0.0444), and deterioration by ≥2 PS levels (HR = 0.608, P = 0.0063). EQ-5D scores were comparable between treatment arms, stable during treatment, and worsened at discontinuation. CONCLUSION: In patients with previously treated advanced gastric/GEJ adenocarcinoma, addition of ramucirumab to paclitaxel prolonged overall survival while maintaining patient QoL with delayed symptom worsening and functional status deterioration. CLINICALTRIALSGOV: NCT01170663.
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Adenocarcinoma/tratamiento farmacológico , Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Esofágicas/tratamiento farmacológico , Paclitaxel/administración & dosificación , Adenocarcinoma/patología , Adulto , Anciano , Anticuerpos Monoclonales Humanizados , Supervivencia sin Enfermedad , Neoplasias Esofágicas/patología , Unión Esofagogástrica/efectos de los fármacos , Unión Esofagogástrica/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Resultado del Tratamiento , RamucirumabRESUMEN
Capecitabine, a prodrug of 5-FU, has been reported to generate maximal tumour activity at tumour sites and/or to improve drug tolerability as compared with 5-FU infusion, and it has also been demonstrated to act synergistically with irinotecan against some solid cancers. A previous study concluded that dose-intensified biweekly capecitabine seems to be more effective at increasing both response rate and progression-free survival time than conventional dose and schedule of capecitabine in colon cancer. We conducted this study to ascertain the efficacy and toxicity of dose-intensified biweekly capecitabine and irinotecan combination chemotherapy in chemotherapy-naïve advanced or metastatic gastric cancer patients. Patients were treated with irinotecan 130 mg m(-2) intravenously for 90 min on days 1 and 15. Capecitabine at 3500 mg m(-2) day(-1), divided into two sessions per day, was administered for seven consecutive days from days 1 and 15, and followed by a 7-day drug-free period, respectively. Fifty-five eligible patients were enrolled in this study from November 2003 to April 2006. There were 22 women and 33 men: median patient age was 54 years (range: 27-81). A total of 200 treatment cycles were administered at a median number of four per patient (range: 1-9). Intent-to-treatment analysis showed that one patient achieved complete response (1.8%), 23 partial response (41.8%), 15 stable disease (27.3%), 10 progressive disease (18.2%) and 6 were non-evaluable (10.9%). The overall response rate was 43.6% (95% confidence interval: 30.2-56.9). The common grade 3-4 toxicities were neutropenia in 12 (21.8%), nausea/vomiting in 3 (5.4%) and diarrhea in 4 (7.2%) patients. Median time to progression was 5 months (range: 0.5-11 months), median survival duration was 11 months (range: 0.5-45 months) and median response duration was 6 months (range: 0.5-9 months). Biweekly dose-intensified capecitabine and irinotecan combination chemotherapy was active for the treatment of advanced or metastatic gastric cancers with a tolerable safety profile.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/análogos & derivados , Desoxicitidina/análogos & derivados , Fluorouracilo/análogos & derivados , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/patología , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias Gástricas/patología , Resultado del TratamientoRESUMEN
We conducted this study to ascertain the efficacy and toxicity of docetaxel and cisplatin combined with oral UFT and leucovorin as a first-line treatment for patients with advanced gastric cancer. In all, 52 patients received courses of docetaxel 60 mg m(-2) intravenously (i.v.) for 1 h and then cisplatin 75 mg m(-2) i.v. for 2 h on day 1. Oral UFT at 400-600 mg day(-1), as determined by body surface area, and leucovorin at 75 mg day(-1) were administered for 21 consecutive days from day 1, and this was followed by a 7-day drug-free interval. A total of 225 courses were administered, and the median number of courses per patient was four. Four complete responses (7.7%) and 22 partial responses (42.3%) were achieved, giving an overall response rate of 50% (95% Confidence Interval: 36.4-63.6%). The major toxicity was neutropenia, which reached grade 3/4 in 36 patients (69.3%). Grade 3/4 nausea and vomiting was observed in 12 patients (23.1%). Median time to progression was 22 weeks (4 to 156+ weeks), median survival duration was 48 weeks (4 to 156+ weeks), and median response duration was 24 weeks (6-152 weeks). We conclude that docetaxel, cisplatin, oral UFT, and leucovorin combination chemotherapy is effective and tolerable for the treatment of advanced gastric cancer.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Docetaxel , Combinación de Medicamentos , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Gástricas/patología , Análisis de Supervivencia , Taxoides/administración & dosificación , Tegafur/administración & dosificación , Resultado del Tratamiento , Uracilo/administración & dosificaciónRESUMEN
We generated new fusion genes carrying positive- and negative-selection markers, and a reporter gene in a single reading frame. The new genes were constructed by sequentially linking the coding sequences of drug-resistance genes (hygro, or puro), a green fluorescence protein (GFP) gene (gfp), and the thymidine kinase gene (tk). The new synthetic genes (hygro/gfp/tk and puro/ gfp/tk) were inserted into retroviral vectors to test their usefulness as selective markers and reporters. The genes were functional in a positive selection in the presence of hygromycin (hygro/gfp/tk) or puromycin (puro/gfp/ tk). In addition, cells expressing the new fusion genes were clearly identifiable by their green fluorescence emitted from GFP. At the same time, these cells were sensitive to a gancyclovir treatment, allowing efficient removal of the transduced cells. The presently described synthetic genes will be valuable tools in both gene therapy and basic gene transfer studies, where positive selection of the transduced cells, monitoring gene expression, and negative selection of the transduced cells are simultaneously required.
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Fusión Artificial Génica , Resistencia a Medicamentos/genética , Genes/genética , Vectores Genéticos , Proteínas Luminiscentes/genética , Timidina Quinasa/genética , Antibacterianos/farmacología , Antivirales/farmacología , Línea Celular , ADN Recombinante/genética , ADN Recombinante/metabolismo , Citometría de Flujo , Ganciclovir/farmacología , Técnicas de Transferencia de Gen , Genes Reporteros , Proteínas Fluorescentes Verdes , Humanos , Higromicina B/farmacología , Immunoblotting , Puromicina/farmacología , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Retroviridae/genética , Retroviridae/metabolismo , Simplexvirus/enzimología , Simplexvirus/genéticaRESUMEN
PURPOSE: This investigation was designed to determine whether heat pressing and/or simulated heat treatments affect the flexure strength and microstructure of the lithium disilicate glass-ceramic of the IPS Empress 2 system. MATERIALS AND METHODS: Four groups of the lithium disilicate glass-ceramic were prepared as follows: group 1 = as-received material; group 2 = heat-pressed material; group 3 = heat-pressed and stimulated initial heat-treated material; and group 4 = heat-pressed and simulated heat-treated material with full firings for a final restoration. Three-point bending tests and scanning electron microscopy (SEM) analysis were conducted. RESULTS: The flexure strength of group 2 was significantly higher than that of group 1. However, there were no significant differences in strength among groups 2, 3, and 4, or between groups 1 and 4. The SEM micrographs of the lithium disilicate glass-ceramic showed a closely packed, multidirectionally interlocking microstructure of numerous lithium disilicate crystals protruding from the glass matrix. The crystals in the glass matrix of the heat-pressed materials (groups 2, 3, and 4) were a little more homogeneous and about 2 times bigger than those of the as-received material (group 1). These changes of the microstructure were greatest between groups 1 and 2. However, there were no marked differences among groups 2, 3, and 4. CONCLUSION: Although there were significant increases in the strength and some changes of the microstructure after the heat-pressing operation, the combination of heat pressing and simulated subsequent heat treatments did not produce an increase of strength of IPS Empress 2 glass-ceramic.
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Porcelana Dental/química , Compuestos de Litio/química , Cristalización , Calor , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Docilidad , Tecnología Odontológica/métodosRESUMEN
PRK1, a receptor-like kinase that is expressed in pollen, pollen tubes, and ovaries, has been shown to play important roles in pollen development and embryo sac development in Petunia inflata. We have used the kinase domain of PRK1 as a bait in the yeast two-hybrid system to identify PRK1-interacting proteins. The screening resulted in isolation of a cDNA encoding a protein highly homologous to the human and yeast beta-subunit of translation initiation factor 2B (eIF2B-beta), which was designated NeIF2Bbeta. eIF2B is a guanine nucleotide exchange protein that functions in the regulation of translation in eukaryotic cells. Deletion mutants of NeIF2Bbeta were analyzed for their interaction with PRK1, and the results suggested that the N-terminal half of NeIF2Bbeta, especially the region between residue 103 and 235, is important for the interaction. This protein association was confirmed by in vitro binding assay of the recombinant NeIF2Bbeta and PRK1 proteins. Despite high sequence homology between NeIF2Bbeta and its yeast counterpart, the NeIF2Bbeta cDNA could not rescue the phenotype of the yeast mutant strain lacking the GCD7 gene encoding eIF2B-beta, when transferred into the mutant strain.
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Factor 2B Eucariótico de Iniciación/química , Nicotiana/química , Plantas Tóxicas , Proteínas Tirosina Quinasas Receptoras/metabolismo , Secuencia de Aminoácidos , Sitios de Unión , Factor 2B Eucariótico de Iniciación/metabolismo , Biblioteca de Genes , Humanos , Datos de Secuencia Molecular , Factores de Iniciación de Péptidos/química , Factores de Iniciación de Péptidos/metabolismo , Fosfotransferasas/química , Fosfotransferasas/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Unión Proteica , Proteínas Serina-Treonina Quinasas , Estructura Terciaria de Proteína , Subunidades de Proteína , Proteínas Tirosina Quinasas Receptoras/química , Alineación de Secuencia , Nicotiana/genética , Técnicas del Sistema de Dos Híbridos , Levaduras/genéticaRESUMEN
PURPOSE: This article reviews recent research on the esthetics of the smile, covering the attractiveness of the smile, the effect of aging on the smile, oral condition and the smile, personality and smile, and smile exercises. MATERIAL AND METHODS: The subjects were Koreans with normal occlusion. Photographs of a full smile were taken and the esthetic quality of the subjects' smiles was estimated. Smile scores were correlated with oral condition, personality, the practice of smile exercises, and elements of the smile, such as the position of the lip in a smile. The personality of the subjects was assessed by means of a Sixteen Personality Factor Questionnaire. Gibson's smile exercises were used to investigate the effect of smile exercise. RESULTS: In an attractive smile, the full shape of the maxillary anterior teeth was shown between the upper and lower lip, the upper lip curved upward or was straight, the maxillary anterior incisal curve was parallel to the lower lip, and teeth were displayed to the first molar. The amount of maxillary incisal exposure gradually decreased with age, accompanied by a gradual increase in mandibular incisal exposure. Personality traits such as warmth, calmness, extroversion, and low anxiety were closely related to an attractive smile. Smile exercises were an effective means of improving the esthetic level of the smile if patients exercised continuously. CONCLUSION: An attractive smile is important for esthetic treatment. The lip position, oral condition, personality traits, and smile exercise affect the esthetics of the smile.
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Estética Dental , Cara/anatomía & histología , Sonrisa , Envejecimiento , Pueblo Asiatico , Humanos , Arcada Parcialmente Edéntula/patología , Labio/anatomía & histología , Maloclusión/patología , PersonalidadRESUMEN
The idea of combining the network of HMMs and the dynamic programming-based search is highly relevant to online handwriting recognition. The word model of HMM network can be systematically constructed by concatenating letter and ligature HMM's while sharing common ones. Character recognition in such a network can be defined as the task of best aligning a given input sequence to the best path in the network. One distinguishing feature of the approach is that letter segmentation is obtained simultaneously with recognition but no extra computation is required.
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The effect of intravesical Bacillus Calmette-Guérin (BCG) on N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) induced urinary bladder carcinogenesis was pathologically evaluated. As a suppressive study of BCG on initiation, F344 female rats given 0.05% BBN orally for 6 weeks had intravesical instillation of either BCG or saline 3 times during BBN administration (Group A). As an inhibitory study of BCG on promotion, F344 female rats given the same strength BBN for 10 weeks had intravesical instillation of either BCG or saline 4 times starting at 7th week of BBN administration (Group B). The bladders were extirpated at 18th or 36th week after BBN administration in Group A and at 10th or 18th week in Group B. The lesions in the bladder were classified into 4 pathological findings; simple hyperplasia, papillary or nodular hyperplasia, papilloma and transitional cell carcinoma. The incidence of the lesions and the number of the lesions per 10 cm basement membrane were observed. BCG did not inhibit the growth of transitional cell carcinoma in Group A nor in Group B, rather partly promoted carcinogenesis. These results indicate that BCG have no inhibitory effect on carcinogenesis. We concluded that prophylactic effect of intravesical BCG is not due to inhibition of carcinogenesis but elimination of residual tumors by strong antitumor effect of BCG.
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Vacuna BCG/farmacología , Carcinoma de Células Transicionales/patología , Papiloma/patología , Neoplasias de la Vejiga Urinaria/patología , Administración Intravesical , Animales , Vacuna BCG/administración & dosificación , Butilhidroxibutilnitrosamina , Carcinoma de Células Transicionales/inducido químicamente , Femenino , Papiloma/inducido químicamente , Ratas , Ratas Endogámicas F344 , Neoplasias de la Vejiga Urinaria/inducido químicamenteRESUMEN
Fifty-two patients with ulcerative colitis and colorectal cancer undergoing colectomy at the Mount Sinai Hospital between 1973 and 1988 were studied retrospectively to determine the correlation of age, sex, duration of colitis, tumor location, number of cancers, tumor differentiation, colloid content, presence of signet ring cells, Dukes' classification, and DNA ploidy with survival. The mean age was 45 years, with a mean duration of colitis of 21 years. Five patients (10%) had Dukes' A lesions, 17 (33%) had Dukes' B lesions, 17 (33%) had Dukes' C lesions, and 13 (25%) had distant metastases. Thirty patients (58%) had well- or moderately differentiated tumors, whereas tumors were poorly differentiated in 22 (42%). Twenty-eight patients (54%) had colloid tumors, and, in 14 (27%), signet ring cells were present. Thirty-one patients (60%) had nondiploid tumors. Actuarial analysis revealed that the 5-year survival rate was significantly worse for patients with nondiploid tumors (76% versus 32%). When stratified by stage, only patients with Dukes' C lesions showed a significant difference in survival for diploid versus nondiploid tumors. Multivariate analysis showed that the Dukes' classification was the best prognostic indicator, followed by tumor differentiation and DNA ploidy. Tumor location, colloid content, number of cancers, duration of disease, age, and sex did not correlate with the prognosis.
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Adenocarcinoma/mortalidad , Colitis Ulcerosa/mortalidad , Neoplasias Colorrectales/mortalidad , Análisis Actuarial , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Factores de Edad , Colitis Ulcerosa/epidemiología , Colitis Ulcerosa/patología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , ADN de Neoplasias/análisis , Citometría de Flujo , Humanos , Metástasis de la Neoplasia , Estadificación de Neoplasias , Ciudad de Nueva York/epidemiología , Ploidias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores SexualesRESUMEN
Existing approaches to routing hazardous material shipments by rail recognize that track condition is an important influence, but have not included it in the risk assessment and routing models. This note explores the influence of track condition based on predictions of internal defects in the rail. The method developed predicts the expected frequency of accidents and subsequent consequences in terms of the expected number of fatalities accounting for one aspect of track condition-internal defects. It is intended to indicate the magnitude and impact of track condition. The formulation integrates models of consequences and the risk of a hazardous spill found in the literature with the frequency of accidents as a function of the number of defects. The number of defects may be based on observations or predicted as a function of the cumulative traffic. The models are used to calculate the expected number of fatalities per year for a particular route. Application of the methodology to a hypothetical route shows that the risk associated with the transportation of hazardous material shipments varies significantly with the expected number of defects in the track. Therefore, risk not only varies from route to route but over time for any section of track as the condition deteriorates.
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Prevención de Accidentes , Sustancias Peligrosas , Vías Férreas , Factores de Riesgo , Estados UnidosRESUMEN
Several studies have shown that the presence of DNA ploidy abnormalities, measured by flow cytometry, may correlate with a poor prognosis in a variety of cancers. The predictive value of these DNA abnormalities in young patients with colorectal cancer has not been well studied. Fifty patients aged 40 years and younger with colorectal adenocarcinoma were studied to determine the correlation of tumor DNA abnormalities with survival. DNA content was determined by flow cytometric analysis and each tumor was categorized as diploid or nondiploid. Of the parameters studied, Dukes' classification and tumor DNA ploidy were found to be significant prognostic indicators. Determination of DNA content seems to provide additional useful prognostic information in young patients with colorectal cancer.