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OBJECTIVE: To investigate the function of HMGB2 in renal tumor ACHN cells in vitro and in vivo and to study the underlying molecular mechanisms. PATIENTS AND METHODS: Kaplan-Meier analysis was used to study the relationship between expression of HMGB2 and prognosis of renal tumor. MTT assay was employed to examine cell proliferation and flow cytometry analysis was used to study the role of HMGB2 in cell apoptosis in ACHN cells. Transwell assays were used to explore the migration and invasion of ACHN cells. The effect of HMGB2 on tumor growth was investigated in vivo. Western blot was performed to evaluate the expression levels of p-JNK, p-ERK and p-p38MAPK. RESULTS: HMGB2 was upregulated in renal tumor and correlated with worse overall survival in renal tumor patients. Down-regulation of HMGB2 suppressed ACHN cells proliferation, invasion and migration in vitro. Moreover, down-regulation of HMGB2 inhibited tumor growth in vivo and HMGB2 exerts the oncogene function partly via the inhibition of p-p38MAPK activation. CONCLUSIONS: Our results provide novel insights into neuropathic pain and help to explore therapeutic targets in the treatment.
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Carcinoma de Células Renales/metabolismo , Proliferación Celular/fisiología , Técnicas de Silenciamiento del Gen/métodos , Proteína HMGB2/deficiencia , Neoplasias Renales/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Femenino , Proteína HMGB2/antagonistas & inhibidores , Proteína HMGB2/genética , Humanos , Neoplasias Renales/genética , Neoplasias Renales/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Proteínas Quinasas p38 Activadas por Mitógenos/genéticaRESUMEN
Transoral endoscopic thyroid surgery (TOET) is a new, minimally-invasive approach that does not result in a scar in the anterior neck. To prevent infection of the surgical site from oral cavity flora into the thyroidectomy area, postoperative antibiotics are generally given orally for 3-7 days. However, there is no clinical evidence to support this approach. This study was an open-label, randomised, controlled trial to evaluate the clinical usefulness of postoperative antibiotics given orally to patients having TOET. Patients were randomly assigned to receive amoxicillin-clavulanate 625mg orally three times a day for a week after operation (treated group) or no antibiotics (untreated group). Fifty patients - 25 treated and 25 untreated - were enrolled. Maximum body temperature, pulse rate, white blood cell count, and C-reactive protein concentrations did not differ between the two groups. Evaluation of the surgical site showed no significant differences between them. Seven patients in the treated group developed nausea, vomiting, and diarrhoea compared with none in the untreated group. The results suggest that postoperative oral antibiotics are not essential after TOET. Large-scale prospective series are required to confirm this finding.
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Cirugía Endoscópica por Orificios Naturales , Tiroidectomía , Antibacterianos , Endoscopía , Humanos , Estudios Prospectivos , Glándula TiroidesRESUMEN
OBJECTIVE: Long noncoding RNA (lncRNA) GIHCG has been reported as an oncogene in hepatocellular carcinoma. However, the expression, roles, and clinical values of GIHCG in renal cell carcinoma (RCC) remain unclear. The aim of this study was to investigate the expression, roles, diagnostic and prognostic values of GIHCG in RCC. PATIENTS AND METHODS: The expression of GIHCG in 46 pairs of RCC tissues and adjacent normal renal tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). GIHCG serum level in 46 RCC patients, 46 age- and sex-matched healthy controls, 20 pre- and post-surgery RCC patients was measured by qRT-PCR. The diagnostic values of serum GIHCG were evaluated by receiver operating characteristic (ROC) curves analysis. The effect of GIHCG on RCC cell proliferation was evaluated using Cell Count Kit-8 assay, and the effect of GIHCG on RCC cell migration was evaluated using transwell migration assay. RESULTS: GIHCG is upregulated in RCC tissues compared with adjacent normal renal tissues. Increased expression of GIHCG is positively correlated with advanced TNM stages, Fuhrman grades, and poor prognosis. Serum GIHCG level is also significantly upregulated in RCC patients and correlated with advanced TNM stages. Serum GIHCG could accurately discriminate RCC patients from healthy controls, and also early stage RCC patients from healthy controls. Furthermore, serum GIHCG level is positively correlated with GIHCG expression in RCC tissues. Serum GIHCG level is significantly reduced after radical resection of RCC. Functional assays showed that knockdown of GIHCG significantly represses proliferation and migration of RCC cells. CONCLUSIONS: Long noncoding RNA GIHCG would sever as a novel diagnostic and prognostic biomarker and therapeutic target for RCC.
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Biomarcadores de Tumor/genética , Carcinoma de Células Renales/diagnóstico , Neoplasias Renales/diagnóstico , ARN Largo no Codificante/metabolismo , Área Bajo la Curva , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/genética , Estudios de Casos y Controles , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Neoplasias Renales/genética , Masculino , Persona de Mediana Edad , Pronóstico , Interferencia de ARN , ARN Largo no Codificante/antagonistas & inhibidores , ARN Largo no Codificante/sangre , ARN Largo no Codificante/genética , ARN Interferente Pequeño/metabolismo , Curva ROC , Regulación hacia ArribaRESUMEN
BACKGROUND: In spite of more than 20 yr of research, the mechanism whereby local anaesthetics act on the brain to mediate anaesthesia still remains unclear. Furthermore, the effect of local anaesthetics on neuronal excitability and synaptic transmission in the hippocampus has not been reported. Thus, the purpose of the present study was to find out the differences between the local anaesthetics, bupivacaine and ropivacaine, in their actions on synaptic transmission of brain in the context of hippocampal field potential. METHODS: Brains were removed from 3- to 4-week-old rats and transverse slices (300 microm thick) were prepared using a microslicer. A slice was then placed on the centre on a multielectrode dish probe. To record evoked field potentials at 64 sites, a pair of single planar microelectrodes delivering bipolar constant current pulses (45-90 microA, 0.1 ms) was applied. Electrophysiological recordings were measured using the 64-channel multielectrode dish. RESULTS: The amplitude of field potential in the rat CA1 region was inhibited by both bupivacaine and ropivacaine. The inhibitory effects of bupivacaine and ropivacaine on field potential amplitudes in CA1 were similar. For bupivacaine 10 microg ml(-1), inhibited field potentials were incompletely recovered; in contrast, for 10 ropivacaine microg ml(-1), inhibited field potentials were completely recovered after washing out with incubation solution. CONCLUSIONS: Inhibitory effects of bupivacaine and ropivacaine on hippocampal field potential amplitude and recovery rate after washout after bupivacaine or ropivacaine treatment represent the underlying mechanisms of the systemic toxicity of local anaesthetics.
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Amidas/farmacología , Anestésicos Locales/farmacología , Bupivacaína/farmacología , Hipocampo/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Potenciales Evocados/efectos de los fármacos , Femenino , Hipocampo/fisiología , Masculino , Ratas , Ratas Sprague-Dawley , Ropivacaína , Transmisión Sináptica/fisiología , Técnicas de Cultivo de TejidosRESUMEN
The hemocompatibility of plasma-treated, silicon-incorporated, diamond-like carbon (Si-DLC) films was investigated. Si-DLC films with a Si concentration of 2at.% were prepared on Si (100) or Nitinol substrates using a capacitively coupled radiofrequency plasma-assisted chemical vapor deposition method using a mixed gas of benzene (C(6)H(6)) and diluted silane (SiH(4):H(2)=10:90). The Si-DLC films were then treated with O(2), CF(4) or N(2) glow discharge for surface modification. The plasma treatment revealed an intimate relationship between the polar component of the surface energy and its hemocompatibility. All in vitro characterizations, i.e. protein absorption behavior, activated partial thromboplastin time measurement and platelet adhesion behavior, showed improved hemocompatibility of the N(2-)- or O(2)-plasma-treated surfaces where the polar component of the surface energy was significantly increased. Si-O or Si-N surface bonds played an important role in improving hemocompatibility, as observed in a model experiment. These results support the importance of a negatively charged polar component of the surface in inhibiting fibrinogen adsorption and platelet adhesion.
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Carbono/química , Diamante/química , Silicio/química , Adsorción , Albúminas/química , Aleaciones/química , Humanos , Modelos Estadísticos , Nitrógeno/química , Oxígeno/química , Tiempo de Tromboplastina Parcial , Adhesividad Plaquetaria , Propiedades de Superficie , Factores de Tiempo , AguaRESUMEN
To clarify the usefulness of multiplex reverse transcription polymerase chain reaction (mRT-PCR) in diagnosing acute leukemia, mRT-PCR detecting 28 different translocations was performed on bone marrow aspirates of 156 patients with acute leukemia, and the results were compared with conventional chromosomal karyotypes. About 113 of 156 patients had acute myeloid leukemia (AML), and 36 had acute lymphoid leukemia (ALL) with patients' ages ranging from 1 to 84 (median: 34.5). Concordance rate between karyotyping and mRT-PCR was 50% (51% in AML and 44% in ALL). Karyotype revealed chromosomal abnormalities in 70 patients (45%) while mRT-PCR showed some aberrations in 59 patients (38%). mRT-PCR detected t(1;19), t(4;11), t(9;11), t(10;11), t(11;19), t(12;21), and TAL1d, which were not detected by G-banding. In addition, 10 patients with t(15;17), one patient with t(8;21), and four patients with t(9;22) detected by mRT-PCR revealed normal karyotypes. However, mRT-PCR did not detect numerical abnormalities, deletions, and translocations other than the 28 translocations included in the assay as expected. In conclusion, although it cannot be a substitute of the conventional chromosome analysis, mRT-PCR could be a complementary diagnostic strategy of acute leukemia.
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Leucemia Mieloide Aguda/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Humanos , Lactante , Cariotipificación , Persona de Mediana Edad , Adulto JovenRESUMEN
Both 5-fluorouracil and doxorubicin are commonly used agents in chemotherapy of gastric cancer in adjuvant setting as well as metastatic disease. In a variety of malignancies, high expression of multidrug resistance-associated protein1 and P-glycoprotein has been associated with resistance to doxorubicin, whereas 5-fluorouracil resistance has correlated with the level of thymidylate synthase expression. We evaluated the expression of multidrug resistance-associated protein1, P-glycoprotein, and thymidylate synthase using immunohistochemistry in 103 locally advanced gastric cancer patients (stage IB-IV) who underwent 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection and investigated the association between their expression and clinicopathologic characteristics including prognosis of the patients. While high expression (> or =5% of tumour cells positive) of multidrug resistance-associated protein1 and P-glycoprotein was observed in 70 patients (68%) and 42 patients (41%), respectively, 65 patients (63%) had primary tumours with high expression (> or =25% of tumour cells positive) of thymidylate synthase. There was a significant association between multidrug resistance-associated protein1 and P-glycoprotein expression (P<0.0001) as well as P-glycoprotein and thymidylate synthase expression (P<0.0001). High multidrug resistance-associated protein1 and P-glycoprotein expressions were associated with well and moderately differentiated histology (P<0.0001 and P=0.03, respectively) and intestinal type (P<0.0001 and P=0.009, respectively). High multidrug resistance-associated protein1 expression correlated with lymph node metastasis (P=0.037), advanced stage (P=0.015), and older age (P=0.021). Five-year disease-free survival and overall survival of total patients were 55.2% and 56.2%, respectively, with a median follow-up of 68 months. There were no significant differences in disease-free survival and overall survival according to the expression of multidrug resistance-associated protein1 (P=0.902 and P=0.975, respectively), P-glycoprotein (P=0.987 and P=0.955, respectively), and thymidylate synthase (P=0.604 and P=0.802, respectively). Concurrent high expression of these proteins (high multidrug resistance-associated protein1/P-glycoprotein, high multidrug resistance-associated protein1/thymidylate synthase, high P-glycoprotein/thymidylate synthase) did not correlate with disease-free survival or overall survival. Even high expression of all three proteins was not associated with poor disease-free survival (P=0.919) and overall survival (P=0.852). In conclusion, high expression of multidrug resistance-associated protein1, P-glycoprotein, and thymidylate synthase did not predict poor prognosis of gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy. A larger study including patients treated with surgical resection alone would be necessary.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/análisis , Adenocarcinoma/química , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Gastrectomía , Proteínas de Neoplasias/análisis , Neoplasias Gástricas/química , Timidilato Sintasa/análisis , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Adenocarcinoma/terapia , Anciano , Quimioterapia Adyuvante , Terapia Combinada , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Inmunoterapia , Lentinano/administración & dosificación , Tablas de Vida , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Picibanil/administración & dosificación , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/terapia , Análisis de SupervivenciaRESUMEN
BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide expressed in a wide variety of tumors, and it stimulates angiogenesis and increases vascular permeability. Increased expression of VEGF may be associated with advanced stage and poor prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: Using enzyme-linked immunosorbent assay, the levels of VEGF were determined in serum from 41 patients with untreated NSCLC (Stage: IIB, 3; IIIA, 6; IIIB, 17; IV, 15; HISTOLOGY: squamous cell carcinoma, 18; adenocarcinoma. 14; undetermined, 9). RESULTS: The median VEGF level was 312 pg/ml, ranging from 70 to 1440 pg/ml. Patients were divided into high VEGF (>312 pg/ml) and low VEGF (< or =312 pg/ml) groups using the median value as a cut-off. There were no significant associations between the serum VEGF levels and various clinicopathologic characteristics including age, gender, histologic type, stage and treatment. A significant positive correlation was found between serum VEGF levels and platelet counts (r=0.495; P=0.001). In addition, serum VEGF levels also correlated with leukocyte counts (r=0.478; P=0.002). In seven patients with measurement of follow-up serum VEGF levels at the end of treatment (chemotherapy and/or radiotherapy), the median serum VEGF level significantly decreased after the treatment (416 pg/ml; range, 96-812 pg/ml vs. 185 pg/ml; range, 49-487 pg/ml; P=0.028). However, the median platelet count (317,000/microl; range, 190,000-395,000/microl vs. 246,000/microl; range, 72,000-271,000/microl; P=0.028) and leukocyte count (10,000/microl; range, 8700-17,200/microl vs. 5100/microl; range, 3900-9500/microl; P=0.018) also decreased after the treatment. There was no statistically significant difference in the median survival of the patients between high VEGF group and low VEGF group (8 months vs. 9 months, P=0.647). CONCLUSIONS: Although serum VEGF level was significantly associated with platelet and leukocyte counts in NSCLC patients, it did not correlate with tumor burden and prognosis of the patients.
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Adenocarcinoma/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Células Escamosas/sangre , Factores de Crecimiento Endotelial/sangre , Recuento de Leucocitos , Neoplasias Pulmonares/sangre , Linfocinas/sangre , Recuento de Plaquetas , Adenocarcinoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Células Escamosas/terapia , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
We evaluated the expression of thymidylate synthase (TS) in locally advanced gastric cancer patients treated with adjuvant chemotherapy after curative resection and investigated the association between TS expression and clinicopathologic characteristics including prognosis of the patients. TS expression was evaluated by immunohistochemical staining using TS106 monoclonal antibody in 103 locally advanced gastric cancer patients (stage IB-IV) who underwent 5-fluorouracil (5-FU) and doxorubicin-based adjuvant chemotherapy after curative resection. 65 patients (63%) had primary tumours with high TS expression (> or = 25% of tumour cells positive), and 38 patients (37%) demonstrated low TS expression (< 25% of tumour cells positive or no staining). High TS expression was associated with male gender (P = 0.002), poorly differentiated histology (P = 0.015), and mixed type in Lauren's classification (P = 0.027). There were no statistically significant differences in 4-year disease-free survival (60.0% vs. 57.2%, P = 0.548) and overall survival (59.6% vs. 59.3%, P = 0.792) between high-TS group and low-TS group. In conclusion, although high TS expression was associated with poorly differentiated histology and mixed type in Lauren's classification, it did not predict poor disease-free and overall survival in gastric cancer patients treated with 5-FU and doxorubicin-based adjuvant chemotherapy after curative resection. Further prospective studies including the evaluation of other biological markers associated with the resistance to 5-FU and doxorubicin are necessary.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Timidilato Sintasa/efectos de los fármacos , Adulto , Anciano , Quimioterapia Adyuvante , Terapia Combinada , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Estómago/efectos de los fármacos , Estómago/enzimología , Estómago/patología , Neoplasias Gástricas/enzimología , Neoplasias Gástricas/cirugía , Análisis de Supervivencia , Timidilato Sintasa/biosíntesis , Resultado del TratamientoRESUMEN
Gastric adenocarcinoma is one of the most common malignancies in the world, and yet little is known about its molecular process of development and progression. Recent studies have suggested that ingestion of nonsteroid anti-inflammatory drugs reduces the risk of colon cancer, presumably by inhibiting the cyclooxygenase (COX) enzyme. COX-2, one isoform of the COX enzyme, is the rate-limiting enzyme in prostaglandin synthesis, and the function of this enzyme is thought to relate to inflammatory processes and carcinogenesis. To understand the role of COX enzyme in gastric cancer, we measured COX-2 expression in 104 human gastric carcinoma tissues by immunohistochemical analysis. We obtained tissue specimens from 104 surgically resected gastric adenocarcinoma patients. We performed immunohistochemical stain for human COX-2 with polyclonal antibody in gastric carcinoma. After curative resection and extensive lymph node dissection, all patients received adjuvant chemotherapy containing 5-fluorouracil. Expression of COX-2 showed cytoplasmic staining, not only in cancer cells but also in precancerous lesions such as metaplastic and adenomatous cells. We confirmed up-regulation of COX-2 in gastric cancer tissues compared with normal paired mucosa using Western blot analysis. There was no correlation between clinicopathological characteristics of gastric cancer patients and intensity of COX-2 protein expression. This study indicates that COX-2 protein over-expression may contribute to an early event of gastric cancer development, and it further suggests that selective inhibition of COX-2 may provide a chemopreventive effect against gastric carcinogenesis.
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Adenocarcinoma/enzimología , Adenocarcinoma/patología , Isoenzimas/metabolismo , Prostaglandina-Endoperóxido Sintasas/metabolismo , Neoplasias Gástricas/enzimología , Neoplasias Gástricas/patología , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Adulto , Anciano , Ciclooxigenasa 2 , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Isoenzimas/análisis , Masculino , Proteínas de la Membrana , Persona de Mediana Edad , Estadificación de Neoplasias , Prostaglandina-Endoperóxido Sintasas/análisis , Estudios Retrospectivos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Tasa de Supervivencia , Factores de TiempoRESUMEN
Bit allocation or the quantizer assignment problem is a basic and essential issue in lossy picture coding. The optimal solution for the bit allocation problem can be found by the Lagrangian method. However, it requires much computational time and memory. To reduce complexity overhead, we propose a fast scheme using a picture activity measure. Comparison among the existing activity measurement methods is presented to select the most reliable activity measure and the mapping relation between the activity value, and a quantization parameter is proposed.