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1.
Scand J Rheumatol ; 50(3): 231-238, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33243053

RESUMEN

Objective: To investigate the relationship between the monocyte-to-high-density lipoprotein cholesterol ratio (MHR) and clinical manifestations in patients with systemic sclerosis (SSc).Method: This was a cross-sectional analysis of a cohort study comprising 111 female SSc patients recruited from a tertiary care rheumatology centre. We also assessed 222 age-matched female healthy controls. Serum MHR was measured in all study participants. Digital ulcer (DU) was defined as an active or healed ulceration, and the magnitude of skin fibrosis was determined according to the modified Rodnan skin score (mRSS).Results: The mean age and median disease duration in patients with SSc were 56.3 years and 98 months, respectively. The MHR in SSc patients was significantly higher than that in controls. DU was found in 35 patients (31.5%) with SSc (active in 12 and healed in 23), and the median mRSS was 8. SSc patients with DU had a significantly higher median MHR than those without (11.43 vs 7.62, p < 0.001), and MHR significantly positively correlated with mRSS (ρ = 0.289, p = 0.002). Multivariable logistic regression revealed that an elevated MHR was independently associated with increased risk of DU (odds ratio = 1.21; 95% confidence interval = 1.07-1.35; p = 0.002). In the multivariable linear regression analysis, higher MHR showed a significant association with increased log-transformed mRSS (unstandardized ß = 0.052, p = 0.003).Conclusion: Our findings suggest that the MHR could be serve as a potential biomarker of the risk of DU and advanced skin fibrosis in patients with SSc.


Asunto(s)
HDL-Colesterol/sangre , Fibrosis/sangre , Monocitos/metabolismo , Esclerodermia Sistémica/sangre , Úlcera Cutánea/sangre , Piel/patología , Biomarcadores/sangre , Estudios Transversales , Femenino , Fibrosis/patología , Humanos , Persona de Mediana Edad , Esclerodermia Sistémica/patología , Úlcera Cutánea/patología
2.
Int J Oral Maxillofac Surg ; 45(9): 1147-53, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27256011

RESUMEN

After a sinus lifting procedure, the compartment around the implants under the sinus mucosal lining in the sinus floor is filled with a blood clot from surrounding bleeding. The aim of this study was to evaluate the feasibility of bone formation following graftless sinus lifting with the simultaneous placement of dental implants. Thirty graftless sinus lifting procedures were performed and 72 dental implants placed in 18 consecutive patients, using the lateral window approach. Clinical and radiological follow-up was conducted throughout the 6-month healing period. Biopsies of 30 cases were collected at 6 months post-treatment: 15 biopsies were taken from the newly formed bone near the basal floor and 15 from the newly formed bone near the elevated membrane. New bone consolidation in the maxillary sinus was apparent radiologically and histologically at 6 months after sinus augmentation, providing an average 6.14±1.34mm of bone-gain. Based on histological analysis and histomorphometric data, the consolidated bone in the augmented sinus comprised 56.7±11.9% to 59.9±13.4% vital bone tissue. Out of the 72 implants placed, only four failed, indicating a 94% overall implant survival rate. Based on this case series, blood clot can be considered autologous osteogenic graft material, to which osteoprogenitors can migrate, differentiate, and regenerate bone.


Asunto(s)
Implantación Dental Endoósea , Seno Maxilar/diagnóstico por imagen , Osteogénesis , Elevación del Piso del Seno Maxilar/métodos , Adulto , Implantes Dentales , Fracaso de la Restauración Dental/estadística & datos numéricos , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Seno Maxilar/fisiología , Persona de Mediana Edad , Resultado del Tratamiento
3.
Colorectal Dis ; 18(7): O243-51, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27166857

RESUMEN

AIM: The study was designed to assess the correlation between lymph node (LN) size and LN metastasis in patients with rectal neuroendocrine tumours (NETs). METHOD: Forty patients who underwent curative resection with lymphadenectomy for a rectal NET between January 2007 and December 2012 were included. The short and long diameters of entire nodes were microscopically measured using a slide gauge. RESULTS: In all, 1052 LNs were collected from the 40 patients, with 49 (4.7%) showing evidence of metastasis. Metastasis-positive LNs had significantly greater long and short diameters (P < 0.001) than metastasis-negative LNs. Of the 49 metastatic LNs, 29 (59.2%) were ≤ 5 mm in largest diameter. In five patients, the largest metastatic LN was only 2-3 mm in diameter. In clinically node-negative (cN0) patients, 18 (51.4%) patients had metastatic LNs (pN1). CONCLUSION: The size of LNs containing metastasis varied widely, with some being very small. LN size alone is therefore not a sufficient predictor of tumour metastasis in rectal NETs. Radical surgery with lymphadenectomy should be considered for patients with rectal NETs with high risk factors for LN metastasis, even those without LN enlargement.


Asunto(s)
Ganglios Linfáticos/patología , Metástasis Linfática , Tumores Neuroendocrinos/patología , Neoplasias del Recto/patología , Adulto , Anciano , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/cirugía , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Factores de Riesgo
4.
Colorectal Dis ; 18(9): 852-60, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26589573

RESUMEN

AIM: Little is known about the long-term outcome of T1 colorectal cancer (CRC) following curative resection. The present study addressed the long-term outcome of locally or radically resected T1 CRCs. METHOD: A total of 430 patients with T1 CRC who underwent local or radical resection were considered. Unfavourable histological factors were defined as positive resection margin, deep submucosal invasion, vascular invasion, Grade 3 and budding. The patients were classified as low-risk (unfavourable histological factor negative, n = 65) or high-risk (unfavourable histological factor positive, n = 365). RESULTS: Over a median follow-up of 78.4 months, disease recurred in 16 (3.7%) patients in the high-risk group, and no recurrence in the low-risk group. Resection type and vascular invasion were significantly associated with recurrence. In the vascular invasion (+) high-risk group, both 5-year disease-free survival rate and 5-year overall survival rate were significantly associated with resection type (radical 94.6%, local 43.8%, P < 0.001, and radical 99.1%, local 66.7%, P < 0.001). In the vascular invasion (-) high-risk group, 5-year disease-free survival rate was also significantly associated with resection type (radical 98.9%, local 84.7%, P = 0.001). However, 5-year overall survival rate was not associated with resection type (radical 98.9%, local 95.2%, P = 0.816). CONCLUSION: Local resection may be effective and oncologically safe in low-risk T1 CRC. Although additional surgery should be recommended for the locally resected high-risk T1 CRC cases, intensive surveillance without additional surgery and timely salvage operation may offer another treatment option, if vascular invasion is negative.


Asunto(s)
Adenocarcinoma/cirugía , Neoplasias Colorrectales/cirugía , Recurrencia Local de Neoplasia/epidemiología , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Colectomía , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos
5.
Scand J Med Sci Sports ; 25(6): 828-39, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25693627

RESUMEN

The purpose of this investigation was to evaluate differences in quadriceps corticospinal excitability, spinal-reflexive excitability, strength, and voluntary activation before, 2 weeks post and 6 months post-anterior cruciate ligament reconstruction (ACLr). This longitudinal, case-control investigation examined 20 patients scheduled for ACLr (11 females, 9 males; age: 20.9 ± 4.4 years; height:172.4 ± 7.5 cm; weight:76.2 ± 11.8 kg) and 20 healthy controls (11 females, 9 males; age:21.7 ± 3.7 years; height: 173.7 ± 9.9 cm; weight: 76.1 ± 19.7 kg). Maximal voluntary isometric contractions (MVIC), central activation ratio (CAR), normalized Hoffmann spinal reflexes, active motor threshold (AMT), and normalized motor-evoked potential (MEP) amplitudes at 120% of AMT were measured in the quadriceps muscle at the specific time points. ACLr patients demonstrated bilateral reductions in spinal-reflexive excitability compared with controls before surgery (P = 0.02) and 2 weeks post-surgery (P ≤ 0.001). ACLr patients demonstrated higher AMT at 6 months post-surgery (P ≤ 0.001) in both limbs. No MEP differences were detected. Quadriceps MVIC and CAR were lower in both limbs of the ACLr group before surgery and 6 months post-surgery (P ≤ 0.05) compared with controls. Diminished excitability of spinal-reflexive and corticospinal pathways are present at different times following ACLr and occur in combination with clinical deficits in quadriceps strength and activation. Early rehabilitation strategies targeting spinal-reflexive excitability may help improve postoperative outcomes, while later-stage rehabilitation may benefit from therapeutic techniques aimed at improving corticospinal excitability.


Asunto(s)
Reconstrucción del Ligamento Cruzado Anterior , Fuerza Muscular , Músculo Cuádriceps/inervación , Músculo Cuádriceps/fisiopatología , Adolescente , Adulto , Estudios de Casos y Controles , Electromiografía , Potenciales Evocados Motores , Femenino , Humanos , Contracción Isométrica , Estudios Longitudinales , Masculino , Tractos Piramidales/fisiopatología , Reflejo Anormal , Estimulación Magnética Transcraneal , Adulto Joven
6.
Rheumatol Int ; 35(1): 107-14, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24948375

RESUMEN

To determine the prevalence of and associated factors to work instability (WI) in rheumatoid arthritis (RA) Argentinean patients. Observational cross-sectional study that assessing employment status in currently working RA patients. They answered the validated version of RA work instability scale (RA-WIS). High-risk WI was considered when RA-WIS was ≥17. Factors associated with high-risk WI were examined by univariable and multivariable analysis. Four-hundred and fifty RA patients were enrolled; of these, 205 patients were currently employed, but only 172 have completed questionnaires required [RA-WIS and health assessment questionnaire (HAQ-A)]. Their mean age was 49.3 ± 10.8 years; 81.3 % were female; and their mean disease duration was 8.1 ± 7.2 years. Fifty-two percent of patients were doing manual work. The mean RA-WIS score was 11.4 ± 6.8, and 41 % of patients had a high-risk WI. High-risk WI was associated with radiographic erosions (p < 0.001) and HAQ-A >0.87 (p < 0.001) in the univariable analysis, whereas in the multivariable logistic regression analysis the variables associated with a high-risk WI were as follows: HAQ-A >0.87 [odds ratio (OR) 12.31; 95 % CI 5.38-28.18] and the presence of radiographic erosions (OR 4.848; 95 % CI 2.22-10.5). In this model, having a higher monthly income (OR 0.301; 95 % CI 0.096-0.943) and a better functional class (OR 0.151; 95 % CI 0.036-0.632) were protective. Forty-one percent of RA working patients had high-risk WI. The predictors of high RA-WIS were HAQ-A ≥0.87 and radiographic erosions, whereas having a better functional class and have higher incomes were protective.


Asunto(s)
Artritis Reumatoide , Evaluación de la Discapacidad , Empleo , Adulto , Argentina , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios
7.
Genet Mol Res ; 13(2): 3697-703, 2014 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-24854655

RESUMEN

Radixin (RDX) is part of the ezrin-radixin-moesin (ERM) protein family. It functions as a membrane-cytoskeletal linker in actin-rich cell surface structures and is thought to be essential for cortical cytoskeleton organization, cell motility, adhesion, and proliferation. An increase in phosphorylated ERM in fibroblast-like synoviocytes contributes to rheumatoid arthritis (RA) synovial hyperplasia. We examined the genetic association between the RDX gene and RA in a Korean population. To identify the relationship between RDX gene polymorphisms and RA, we genotyped 2 single nucleotide polymorphisms (SNPs; rs11213326 and rs12575162) of RDX using a direct sequencing method in 296 RA patients and 493 control subjects. In this study, the 2 SNPs showed no association with RA disease susceptibility. However, further analysis based on clinical information of the RA patient group showed that the SNPs were associated with the erythrocyte sedimentation rate (ESR) in RA patients. These data suggest an association between RDX polymorphisms and the clinical features of RA patients, particularly the ESR.


Asunto(s)
Artritis Reumatoide/genética , Sedimentación Sanguínea , Proteínas del Citoesqueleto/genética , Estudios de Asociación Genética , Proteínas de la Membrana/genética , Adulto , Artritis Reumatoide/patología , Pueblo Asiatico , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Población , República de Corea
8.
Cell Death Dis ; 4: e859, 2013 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-24136223

RESUMEN

The p90 ribosomal S6 kinase (RSK) family is a group of highly conserved Ser/Thr kinases that promote cell proliferation, growth, motility and survival. As they are almost exclusively activated downstream of extracellular signal-regulated kinases 1 and 2 (ERK1/2), therapeutic intervention by RSK inhibition is less likely to produce such severe side effects as those observed following inhibition of the upstream master regulators Raf, MEK and ERK1/2. Here, we report that BI-D1870, a potent small molecule inhibitor of RSKs, induces apoptosis, although preferentially, in a p21-deficient background. On the other hand, BI-D1870 also induces a strong transcription- and p53-independent accumulation of p21 protein and protects cells from gamma irradiation (γIR)-induced apoptosis, driving them into senescence even in the absence of γIR. Although we identified p21 in in vitro kinase assays as a novel RSK substrate that specifically becomes phosphorylated by RSK1-3 at Ser116 and Ser146, RNA-interference, overexpression and co-immunoprecipitation studies as well as the use of SL0101, another specific RSK inhibitor, revealed that BI-D1870 mediates p21 accumulation via a yet unknown pathway that, besides its off-site targets polo-like kinase-1 and AuroraB, also does also not involve RSKs. Thus, this novel off-target effect of BI-D1870 should be taken into serious consideration in future studies investigating the role of RSKs in cellular signaling and tumorigenesis.


Asunto(s)
Apoptosis/efectos de la radiación , Senescencia Celular/efectos de los fármacos , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Rayos gamma , Pteridinas/farmacología , Proteínas Quinasas S6 Ribosómicas 90-kDa/antagonistas & inhibidores , Proteína p53 Supresora de Tumor/metabolismo , Apoptosis/efectos de los fármacos , Aurora Quinasas/metabolismo , Benzopiranos/farmacología , Proteínas de Ciclo Celular/metabolismo , Senescencia Celular/efectos de la radiación , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/farmacología , Técnicas de Silenciamiento del Gen , Células HCT116 , Humanos , Isoenzimas/metabolismo , Monosacáridos/farmacología , Fosforilación/efectos de los fármacos , Fosforilación/efectos de la radiación , Fosfoserina/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Quinasas S6 Ribosómicas 90-kDa/metabolismo , Estrés Fisiológico/efectos de los fármacos , Estrés Fisiológico/efectos de la radiación , Especificidad por Sustrato/efectos de los fármacos , Especificidad por Sustrato/efectos de la radiación , Transcripción Genética/efectos de los fármacos , Transcripción Genética/efectos de la radiación , Quinasa Tipo Polo 1
9.
Colorectal Dis ; 15(3): e124-9, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23294594

RESUMEN

AIM: Background adenoma (BGA) is defined as benign adenomatous tissue contiguous to resected carcinomas, and the absence of BGA in a tumour is considered a histological criterion of de novo cancers. The present study aimed to identify the clinicopathological characteristics of T1 colorectal cancer (CRC) without BGA. METHOD: A retrospective review was carried out of prospectively collected data from two centres: the National Cancer Center, Korea; and Chonnam National University Hwasun Hospital, Korea. A total of 590 patients with T1 CRC, treated by endoscopic or surgical resection between January 2001 and August 2011, were enrolled. Details regarding gender, age, tumour location, endoscopic gross type, tumour size, depth of submucosal (SM) invasion, angiolymphatic invasion, tumour grade, budding and lymph node (LN) metastasis were evaluated with regard to the presence or absence of BGA. RESULTS: BGA was absent in 197 (33.4%) patients. Tumour size <20 mm, flat or depressed type, deep SM depth and tumour budding were associated with the absence of BGA in univariate and multivariate analyses (P < 0.05). In surgically resected patients, LN metastases were significantly associated with the absence of BGA (P = 0.022). CONCLUSION: T1 CRC without BGA presented several characteristics of small size (<20 mm), flat or depressed type, deep SM depth (SM 2/3), LN metastasis and tumour budding. These results indicate that de novo cancers may have a more invasive potential.


Asunto(s)
Adenoma/diagnóstico , Neoplasias Colorrectales/patología , Estadificación de Neoplasias/métodos , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Colonoscopía , Neoplasias Colorrectales/secundario , Femenino , Estudios de Seguimiento , Humanos , Mucosa Intestinal/patología , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo
10.
J Hum Hypertens ; 27(1): 7-12, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22237632

RESUMEN

The relation between left ventricular (LV) hypertrophy and LV function is well known. However, less is known about the vascular changes influenced by LV geometry. We sought to investigate the relationship of LV geometry to carotid arterial and LV function. A total of 476 hypertensive patients were prospectively recruited. All subjects underwent echocardiography and carotid ultrasound. LV geometry is categorized into four groups according to relative wall thickness (RWT) and LV mass index (LVMI). Concentric LV geometry was associated with increased carotid intima-media thickness (IMT), ß-stiffness, and lower strain. All of the carotid parameters showed a stepwise change according to RWT of LV, whereas LV function was worse in hypertrophic geometry, as reflected by significantly lower systolic mitral annular velocity, higher left atrial volume index and E/E' ratio (P<0.001). By multivariate analysis after adjustment for clinical and laboratory parameters, IMT was independently associated with RWT, whereas myocardial function was independently associated with LVMI. Carotid arterial function and IMT showed worse values in concentric geometry, whereas LV systolic and diastolic function were worse in hypertrophic geometry, suggesting a discrepancy between carotid arterial and LV function in hypertensive patients.


Asunto(s)
Arterias Carótidas/patología , Hipertensión/patología , Hipertrofia Ventricular Izquierda/patología , Miocardio/patología , Adulto , Anciano , LDL-Colesterol/sangre , Estudios Transversales , Femenino , Humanos , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Análisis Multivariante , Función Ventricular Izquierda
11.
Gene Ther ; 20(7): 717-22, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23151518

RESUMEN

The purpose of this phase I clinical trial was to evaluate the safety, tolerability and potential efficacy of VM202, naked DNA expressing two isoforms of hepatocyte growth factor, as an adjunct therapy to coronary artery bypass grafting (CABG) in patients with ischemic heart disease (IHD). Nine patients were assigned to receive increasing doses (0.5 to 2.0 mg) of VM202 injected into the right coronary artery (RCA) territory following completion of CABG for the left coronary artery territory. Patients were evaluated for safety and tolerability, and changes in myocardial functions were monitored via echocardiography, cardiac magnetic resonance imaging and myocardial single photon emission computed tomography throughout 6-month follow-up period. No serious complication related to VM202 was observed throughout the 6-month follow-up period. Global myocardial functions (wall motion score index, P=0.0084; stress perfusion, P=0.0002) improved during the follow-up period. In the RCA region, there was an increase in the stress perfusion (baseline vs 3-month, P=0.024; baseline vs 6-month, P=0.024) and also in the wall thickness of the diastolic and systolic phases. Intramyocardial injection of VM202 can be safely used in IHD patients with the tolerable dose of 2.0 mg. In addition, VM202 might appear to have improved regional myocardial perfusion and wall thickness in the injected region.


Asunto(s)
Puente de Arteria Coronaria , Técnicas de Transferencia de Gen , Corazón/diagnóstico por imagen , Factor de Crecimiento de Hepatocito/genética , Isquemia Miocárdica/terapia , Vacunas de ADN/administración & dosificación , Anciano , Femenino , Corazón/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/genética , Isquemia Miocárdica/cirugía , Miocardio , Neovascularización Fisiológica/genética , Radiografía , Tomografía Computarizada de Emisión de Fotón Único , Vacunas de ADN/genética
12.
Mol Biol (Mosk) ; 47(4): 618-24, 2013.
Artículo en Ruso | MEDLINE | ID: mdl-24466751

RESUMEN

The upregulation of dopaminergic neuronal differentiation is necessary for stem cell therapy in Parkinson's disease (PD). In this study, neuronal differentiation efficiency increased by more than 2 times in P19 embryonic stem cells (ESCs) induced by N-acetylcysteine (NAC) and retinoic acid (RA) as compared to RA alone, with suppressed glial differentiation. The majority of NAC-treated stem cells grafted into brains of PD mice differentiated into dopaminergic neurons and persisted well for 6 weeks. Parkinsonism was also greatly improved after grafting NAC-treated cells in comparison to cells treated with only RA. Our results strongly suggest that NAC treatment may be an effective strategy for generating stem cells fated to become dopaminergic neurons for PD clinical therapy.


Asunto(s)
Acetilcisteína/farmacología , Diferenciación Celular/efectos de los fármacos , Células Madre Embrionarias/efectos de los fármacos , Neuronas/efectos de los fármacos , Trastornos Parkinsonianos/patología , Trastornos Parkinsonianos/terapia , Animales , Encéfalo/patología , Células Cultivadas , Modelos Animales de Enfermedad , Dopamina/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Trasplante de Células Madre , Tretinoina/farmacología
13.
Mol Biol (Mosk) ; 46(5): 741-6, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23156673

RESUMEN

We examined whether N-acetylcysteine (NAC) enhanced embryonic body (EB) formation and neuronal differentiation in terms of EB formation, neuronal marker (microtubule-associated protein 2; MAP-2) expression, and neuron maturation using P19 embryonic stem cells. The size and numbers of EBs were greatly increased, together with the up-regulated N-cadherin expression. Also, MAP-2 expression and neurite outgrowth were much increased with activation of serine/threonine protein kinase (Akt) and blocked by addition of an Akt inhibitor (LY294002). Our results suggested that NAC increased EB formation by up-regulating the N-cadherin expression. Furthermore, NAC-enhanced neuronal differentiation was mediated by activation of Akt.


Asunto(s)
Acetilcisteína/farmacología , Cadherinas/metabolismo , Cuerpos Embrioides/metabolismo , Células Madre Embrionarias/efectos de los fármacos , Neuronas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Cadherinas/genética , Recuento de Células , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Línea Celular , Cromonas/farmacología , Cuerpos Embrioides/citología , Células Madre Embrionarias/citología , Células Madre Embrionarias/metabolismo , Ratones , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Morfolinas/farmacología , Neuronas/citología , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/genética , Transducción de Señal/efectos de los fármacos , Activación Transcripcional/efectos de los fármacos
14.
Endoscopy ; 44(6): 590-5, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22638780

RESUMEN

BACKGROUND AND STUDY AIMS: It is critical that the risk of lymph node metastasis (LNM) is evaluated for determining the suitability of endoscopic resection for T1 colorectal cancer (CRC). Reported risk factors for LNM in completely resected T1 CRC are deep submucosal invasion, grade 3, angiolymphatic invasion, and budding. The aim of the present study was to identify the histopathologic factors associated with LNM in T1 CRC. PATIENTS AND METHODS: The study involved 435 patients with T1 CRC treated by endoscopic or surgical resection between January 2001 and April 2010 at the National Cancer Center, Korea. The 435 patients were classified into two groups - those undergoing surgical resection (n = 324) and those undergoing endoscopic resection (n = 111). In the surgically resected group, details regarding depth of submucosal invasion, angiolymphatic invasion, tumor grade, budding, and background adenoma (BGA) were evaluated with respect to presence or absence of LNM. In the endoscopically resected group, the results of follow-ups and additional salvage surgeries were studied. RESULTS: In the surgically resected group, LNM was detected in 42 patients (13.0 %). Grade 3, angiolymphatic invasion, budding, and the absence of BGA were identified as factors associated with LNM in univariate and multivariate analyses (P < 0.05). Among the 50 patients in the endoscopically resected group with high risk, three were diagnosed as being LNM-positive during the follow-up period. There was no LNM in the endoscopically resected group with low risk. CONCLUSIONS: Grade 3, angiolymphatic invasion, budding, and the absence of BGA are the risk factors that predict LNM in patients with T1 CRC. In cases where endoscopically resected T1 CRC has no risk factor, cautious follow-up could be recommended. However, if the tumor has any risk factor, additional surgical resection should be considered.


Asunto(s)
Adenocarcinoma/patología , Adenoma/patología , Neoplasias Colorrectales/patología , Endoscopía Gastrointestinal , Adenocarcinoma/cirugía , Adenoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Vasos Sanguíneos/patología , Distribución de Chi-Cuadrado , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Modelos Logísticos , Metástasis Linfática , Vasos Linfáticos/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Estudios Retrospectivos , Factores de Riesgo
15.
Cell Death Differ ; 18(10): 1664-74, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21475302

RESUMEN

Although caspase-2 represents the most conserved caspase across species and was the second caspase identified, its precise function remains enigmatic. In several cell types we show that knockdown of caspase-2 specifically impaired DNA damage-induced p21 expression, whereas overexpression of a caspase-2 mutant increased p21 levels. Caspase-2 did not influence p21 mRNA transcription; moreover, various inhibitors targeting proteasomal or non-proteasomal proteases, including caspases, could not restore p21 protein levels following knockdown of caspase-2. As, however, silencing of caspase-2 impaired exogenous expression of p21 constructs containing 3'-UTR sequences, our results strongly indicate that caspase-2 regulates p21 expression at the translational level. Intriguingly, unlike depletion of caspase-2, which prevented p21 expression and thereby reverted the γ-IR-induced senescent phenotype of wild-type HCT116 colon carcinoma cells into apoptosis, knockdown of none of the caspase-2-interacting components RAIDD, RIP or DNA-PKcs was able to mimic these processes. Together, our data suggest that this novel role of caspase-2 as a translational regulator of p21 expression occurs not only independently of its enzymatic activity but also does not require known caspase-2-activating platforms.


Asunto(s)
Caspasa 2/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Daño del ADN/fisiología , Regiones no Traducidas 3'/genética , Apoptosis/genética , Apoptosis/fisiología , Western Blotting , Caspasa 2/genética , Ciclo Celular/genética , Ciclo Celular/fisiología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Daño del ADN/genética , Células HCT116 , Humanos
16.
Endoscopy ; 43(6): 526-32, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21425040

RESUMEN

BACKGROUND AND STUDY AIMS: Several reports have demonstrated the safety of pure natural-orifice transluminal endoscopic surgery (P-NOTES) using transanal endoscopic microsurgery (TEM) and embryonic NOTES (E-NOTES; laparoscopic surgery through the umbilicus). This study was performed to compare the safety and applicability of NOTES rectosigmoidectomy between E-NOTES and P-NOTES in a swine model. PATIENTS AND METHODS: E-NOTES was conducted through a single port using laparoscopic instruments (n = 11). P-NOTES was performed using TEM with transgastric endoscopic assistance (n = 11). Gastrotomies were created using a needle knife and the balloon dilatation technique, and closed using T-anchors. Blood samples were collected to evaluate changes in systemic cytokine levels during the preoperative and postoperative periods; operative outcomes were also evaluated and compared between the groups. The necropsy findings were recorded after sacrifice at 1 week after the procedure. RESULTS: The mean operative time for P-NOTES was significantly longer than that for E-NOTES (239 vs. 103 minutes, P < 0.001). The mean distance from the anal verge to colorectal anastomosis in the P-NOTES group was significantly less than that in the E-NOTES group (2.9 vs. 17.6 cm, P < 0.001). On necropsy, the complication rate of P-NOTES was higher than that of E-NOTES, but without statistical significance (54.5 % vs. 18.2 %, P = 0.091). The differences in changes in TNF-α, C-reactive protein, interleukin-6, and interleukin-1ß between P-NOTES and E-NOTES were not significant. CONCLUSIONS: E-NOTES rectosigmoidectomy in the swine model is safe, but remains challenging for use in pelvic dissection. P-NOTES rectosigmoidectomy using TEM may be a promising tool for pelvic dissection, but the transgastric approach involves a high degree of risk.


Asunto(s)
Colectomía/métodos , Hematoma/etiología , Cirugía Endoscópica por Orificios Naturales/métodos , Enfermedades Peritoneales/etiología , Absceso Abdominal/etiología , Canal Anal , Animales , Ascitis/etiología , Proteína C-Reactiva/metabolismo , Colectomía/efectos adversos , Interleucina-1beta/sangre , Interleucina-6/sangre , Laparoscopía , Masculino , Modelos Animales , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Infección de la Herida Quirúrgica/etiología , Porcinos , Factores de Tiempo , Adherencias Tisulares/etiología , Factor de Necrosis Tumoral alfa/sangre , Ombligo
18.
Endoscopy ; 43(2): 100-7, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21165823

RESUMEN

BACKGROUND AND STUDY AIMS: Laterally spreading tumors (LST) are classified into two subtypes, with the nongranular type harboring a higher risk of (pre)malignant changes than the granular type. Further subdifferentiation into two subgroups each has been suggested, but the clinical significance of such a subdifferentiation has not previously been studied in detail in larger numbers. PATIENTS AND METHODS: Out of 6499 patients diagnosed with colorectal adenomas between January 2006 and November 2008, 153 patients (2.35 %) had 158 LSTs, 96 with a granular and 62 with a nongranular pattern. The former group was subdivided into homogeneous and nodular mixed, the latter group into flat elevated and pseudodepressed. Clinical and histopathological parameters were compared among the four subtypes. RESULTS: Parameters were variably distributed between the four groups, with nodular mixed tumors being larger than the other three types ( P < 0.0001). As in other studies, malignant transformation and premalignant lesion (HGIN/CIS) were more frequent in nodular mixed than in homogeneous tumors (45.0 % vs. 5.6 %, P < 0.001), and also more common in pseudodepressed than in flat elevated tumors (41.7 % vs. 13.2 %, P = 0.011). Submucosal invasive cancer was present in 8.3 % of nodular mixed tumors, 7.9 % of flat elevated, and 12.5 % of pseudodepressed, while it was absent in homogeneous tumors. Serrated adenoma was identified in 10.8 % of all LSTs, and sessile serrated adenoma tended to be more common in flat elevated tumors. CONCLUSIONS: Further subdifferentiation of the LST lesions to identify lesions at risk of malignant transformation makes most sense in the granular type. Among nongranular LSTs, both subtypes carry a significant risk.


Asunto(s)
Adenoma/patología , Neoplasias Colorrectales/patología , Mucosa Intestinal/patología , Adenoma/clasificación , Anciano , Análisis de Varianza , Neoplasias Colorrectales/clasificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estudios Retrospectivos , Carga Tumoral
19.
Int J Impot Res ; 22(5): 291-7, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20861845

RESUMEN

Impotence is one of the common complications after the radical prostatectomy. One of the main reasons of this complication is due to the dysfunction of the veins in corpus cavernosum. Recent studies have shown that the erectile function is improved after the long-term therapy of phosphodiesterase type 5 inhibitor among patients with post-prostatectomy erectile dysfunction. In this study, we evaluated the effects of mirodenafil on the penile erection and corpus cavernosum tissues in the rat model of cavernosal nerve injury. Rats were divided into four groups: (1) control group, (2) bilateral cavernosal nerve injury group, (3) mirodenafil 10 mg therapy group after the nerve injury and (4) mirodenafil 20 mg therapy group after the nerve injury. After we identified the nerve from the pelvic nerve complex on the lateral side of the prostate, the rats in the control group were sutured without causing any nerve injury and in other groups we damaged the nerve by compressing it with a vessel clamp. Then, 10 and 20 mg kg(-1) of mirodenafil were orally administered to two experimental groups. After 8 weeks, the intracavernosal pressure (ICP) was recorded. The immunohistochemical staining and western blot were performed, and the effect of mirodenafil on the expression of cyclic guanosine monophosphate (cGMP) was evaluated through enzyme-linked immunosorbent assay. The ICP of nerve-injured group was decreased compared with the control group; however, the ICP of the mirodenafil-administered groups was improved compared with the nerve-injured group. The Masson's trichrome staining confirmed that the smooth muscle (SM) component was increased in the mirodenafil-administered groups. The nitric oxide synthase expression and cGMP of mirodenafil-administered groups was increased compared with the nerve-injured group. Long-term therapy of mirodenafil may improve the erectile function after the radical prostatectomy by preserving the SM content and inhibiting the fibrosis of the corpus cavernosum.


Asunto(s)
Disfunción Eréctil/tratamiento farmacológico , Erección Peniana/efectos de los fármacos , Traumatismos de los Nervios Periféricos , Inhibidores de Fosfodiesterasa 5/farmacología , Complicaciones Posoperatorias/tratamiento farmacológico , Pirimidinonas/farmacología , Sulfonamidas/farmacología , Animales , GMP Cíclico/metabolismo , Modelos Animales de Enfermedad , Masculino , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo I , Óxido Nítrico Sintasa de Tipo III/metabolismo , Complicaciones Posoperatorias/metabolismo , Complicaciones Posoperatorias/fisiopatología , Prostatectomía/efectos adversos , Ratas , Ratas Sprague-Dawley
20.
Heart ; 96(13): 1050-5, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20483902

RESUMEN

BACKGROUND: Left atrial (LA) volume is an independent prognosticator in various cardiac diseases. The authors assessed the changes of LA volume after successful percutaneous mitral valvuloplasty (PMV) and the impact of LA enlargement on long-term clinical outcome after PMV. METHODS AND RESULTS: From a prospective PMV registry started in 1988, 303 patients (242 women, age: 39.3+/-10.8 years) who had undergone successful PMV were followed for 4-20 years (median 11 years). Echocardiographic examination including LA volume measurement was performed before PMV and repeated after PMV. LA volume decreased from 92+/-50 to 69+/-42 ml (p < 0.001) immediately after PMV and remained stationary until 1 year after PMV. Since then, LA volume subsequently increased exceeding the pre-PMV level by 8 years after PMV. Multivariate analysis showed that LA volume increase at 10 years after PMV was independently related to the post-PMV mitral valve area, the echo score, the presence of atrial fibrillation and post-PMV LA volume. On multiple regression analysis, pre-PMV LA volume and percentage change of LA volume immediately after PMV emerged as independent predictors of event-free survival along with age, pre-PMV tricuspid regurgitation and post-PMV mitral valve area. Ten-year survival rate was 93% in patients with smaller LA before PMV (< or =72 ml/m(2)), whereas it was only 60% in those with larger LA (>72 ml/m(2)). CONCLUSIONS: Progressive increase of LA volume was observed even after successful PMV. Larger pre-PMV LA volume was associated with poor prognosis.


Asunto(s)
Angioplastia , Función del Atrio Izquierdo/fisiología , Estenosis de la Válvula Mitral/terapia , Volumen Sistólico/fisiología , Adulto , Métodos Epidemiológicos , Femenino , Atrios Cardíacos/patología , Humanos , Masculino , Persona de Mediana Edad , Estenosis de la Válvula Mitral/diagnóstico por imagen , Estenosis de la Válvula Mitral/mortalidad , Resultado del Tratamiento , Ultrasonografía
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