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1.
Eur Rev Med Pharmacol Sci ; 23(4): 1451-1458, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30840266

RESUMEN

OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. However, effective therapeutics for ccRCC are lacking. Novel biomarkers could provide critical information when determining prognoses for patients with ccRCC. In this study, we sought to determine if the expression of receptor tyrosine kinase (TEK) could be a potential novel prognostic biomarker for ccRCC. TEK, originally identified as an endothelial cell-specific receptor, plays an important role in the modulation of vasculogenesis and remodeling. Altered TEK expression has been observed in tumor tissues (e.g., oral squamous cell carcinomas, leukemia) and breast, gastric and thyroid cancers. However, the role of TEK in ccRCC remains unknown. PATIENTS AND METHODS: Differential TEK expression between non-metastatic (stage M0) and metastatic (stage M1) ccRCC patient cohorts was determined from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). Furthermore, TEK expression was assessed as a prognostic factor using the time-dependent area under the curve (AUC) of Uno's C-index, the AUC value of the receiver operating characteristics (ROC) at 5 years, Kaplan-Meier survival curves and multivariate analyses. RESULTS: A Kaplan-Meier curve analysis revealed that the downregulation of TEK expression was associated with a poor prognosis for patients with ccRCC with good discrimination (p<0.0001 and p=0.0044 for the TGCA and ICGC cohorts, respectively). Analyses of C-indices and receiver operating characteristic AUC values further support this discriminative ability. Moreover, multivariate analyses showed the prognostic significance of TEK expression levels (p<0.001). CONCLUSIONS: Although additional clinical investigations will be needed, our results suggest that TEK is a potential biomarker for ccRCC.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Receptor TIE-2/metabolismo , Anciano , Área Bajo la Curva , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/mortalidad , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/metabolismo , Neoplasias Renales/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Curva ROC , Receptor TIE-2/genética
2.
Br J Cancer ; 102(4): 710-8, 2010 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-20087351

RESUMEN

BACKGROUND: Stathmin1 is a microtubule-regulating protein that has an important role in the assembly and disassembly of the mitotic spindle. The roles of stathmin1 in carcinogenesis of various cancers, including prostate and breast cancer, have been explored. However, its expression and roles in gastric cancer have not yet been described. METHODS: Stathmin1 expression in paraffin-embedded tissue sections from 226 patients was analysed by immunohistochemistry. Roles of stathmin1 were studied using a specific small interfering RNA (siRNA). RESULTS: The expression of stathmin1 was positively correlated with lymph node metastasis, TNM stages and vascular invasion, and negatively with recurrence-free survival, in the diffuse type of gastric cancer. The median recurrence-free survival in patients with a negative and positive expression of stathmin1 was 17.0 and 7.0 months, respectively (P=0.009). When the expression of stathmin1 was knocked down using siRNA, the proliferation, migration and invasion of poorly differentiated gastric cancer cells in vitro were significantly inhibited. Moreover, stathmin1 siRNA transfection significantly slowed the growth of xenografts in nude mice. CONCLUSION: These results suggest that stathmin1 can be a good prognostic factor for recurrence-free survival rate and is a therapeutic target in diffuse-type gastric cancer.


Asunto(s)
Carcinoma/genética , Movimiento Celular/genética , Proliferación Celular , Estatmina/genética , Neoplasias Gástricas/genética , Anciano , Animales , Carcinoma/metabolismo , Carcinoma/mortalidad , Carcinoma/patología , Estudios de Casos y Controles , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , ARN Interferente Pequeño/farmacología , Estatmina/antagonistas & inhibidores , Estatmina/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Regulación hacia Arriba/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
3.
Optometry ; 79(1): 18-22, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18156092

RESUMEN

BACKGROUND: Oculomotor dysfunctions are among the most common abnormalities found in the brain-injured population. The purpose of the current study was to determine retrospectively the effectiveness of conventional optometric vision therapy for oculomotor disorders of vergence and version in a sample of ambulatory, visually symptomatic, predominantly adult outpatients who had either mild traumatic brain injury (TBI) or cerebrovascular accident (CVA). METHODS: A computer-based query for acquired brain injury patients examined between the years of 2000 and 2003 was conducted in our clinic. This yielded 160 individuals with mild TBI and 60 with CVA. Of these patients, only those for whom vision therapy was prescribed and who completed an optometric vision therapy program for remediation of their oculomotor dysfunctions were selected. This included 33 with TBI and 7 with CVA. The criterion for treatment success was denoted by marked/total improvement in at least 1 primary symptom and at least 1 primary sign. RESULTS: Ninety percent of those with TBI and 100% of those with CVA were deemed to have treatment success. These improvements remained stable at retesting 2 to 3 months later. CONCLUSION: Nearly all patients in the current clinic sample exhibited either complete or marked reduction in their oculomotor-based symptoms and improvement in related clinical signs, with maintenance of the symptom reduction and sign improvements at the 2- to 3-month follow-up. These findings show the efficacy of optometric vision therapy for a range of oculomotor abnormalities in the primarily adult, mild brain-injured population. Furthermore, it shows considerable residual neural plasticity despite the presence of documented brain injury.


Asunto(s)
Lesiones Encefálicas/complicaciones , Trastornos de la Motilidad Ocular/terapia , Ortóptica/métodos , Accidente Cerebrovascular/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Lesiones Encefálicas/diagnóstico , Niño , Movimientos Oculares , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos de la Motilidad Ocular/diagnóstico , Trastornos de la Motilidad Ocular/etiología , Calidad de Vida , Lectura , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico
4.
Optometry ; 78(4): 155-61, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17400136

RESUMEN

BACKGROUND: The purpose of this retrospective study was to determine the frequency of occurrence of oculomotor dysfunctions in a sample of ambulatory outpatients who have acquired brain injury (ABI), either traumatic brain injury (TBI) or cerebrovascular accident (CVA), with associated vision symptoms. METHODS: Medical records of 220 individuals with either TBI (n = 160) or CVA (n = 60) were reviewed retrospectively. This was determined by a computer-based query spanning the years 2000 through 2003, for the frequency of occurrence of oculomotor dysfunctions including accommodation, version, vergence, strabismus, and cranial nerve (CN) palsy. RESULTS: The majority of individuals with either TBI (90%) or CVA (86.7%) manifested an oculomotor dysfunction. Accommodative and vergence deficits were most common in the TBI subgroup, whereas strabismus and CN palsy were most common in the CVA subgroup. The frequency of occurrence of versional deficits was similar in each diagnostic subgroup. CONCLUSION: These new findings should alert the clinician to the higher frequency of occurrence of oculomotor dysfunctions in these populations and the associated therapeutic, rehabilitative, and quality-of-life implications.


Asunto(s)
Lesiones Encefálicas/complicaciones , Trastornos de la Motilidad Ocular/epidemiología , Acomodación Ocular/fisiología , Adolescente , Adulto , Niño , Preescolar , Movimientos Oculares/fisiología , Humanos , Incidencia , Lactante , Recién Nacido , Persona de Mediana Edad , Trastornos de la Motilidad Ocular/etiología , Trastornos de la Motilidad Ocular/fisiopatología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Estados Unidos/epidemiología
5.
Brain Inj ; 20(10): 1079-86, 2006 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17060141

RESUMEN

PRIMARY OBJECTIVE: To determine retrospectively the relative risk of ocular disease in a selected, visually-symptomatic sample of clinic patients having traumatic brain injury (TBI; n=160) vs. cerebrovascular accident (CVA; n=60), with all initially presenting at the clinic with symptoms and/or signs of vision dysfunction. METHODS AND PROCEDURES: To review retrospectively 220 medical records of individuals with TBI (n=160) vs. CVA (n=60), as determined by a computer-based query spanning the years 2000-2003, to ascertain the frequency of occurrence of ocular disease in the two major sub-groups of acquired brain injury. MAIN OUTCOMES AND RESULTS: Conditions with high relative risk unique to TBI included corneal abrasion, blepharitis, chalazion/hordeolum, dry eye, traumatic cataract, vitreal prolapse and optic atrophy. This is distinct from those ophthalmic conditions unique to CVA, which included sub-conjunctival haemorrhage and ptosis. CONCLUSION: These new findings should alert clinicians to the potential increased frequency of occurrence of specific ocular diseases in a selected, visually-symptomatic population with TBI and their associated rehabilitative and quality-of-life implications.


Asunto(s)
Lesiones Encefálicas/complicaciones , Oftalmopatías/etiología , Accidente Cerebrovascular/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo
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