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1.
J Robot Surg ; 18(1): 1, 2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38175325

RESUMEN

AIM: Robotic-assisted pancreatectomy has been widely used. Organ-preserving pancreatectomy (OPP) and parenchymal-sparing pancreatectomy (PSP) has been gradually adopted for pancreatic benign or low-grade malignant tumors. This study aimed to evaluate the safety and efficacy of robotic-assisted OPP/PSP in our institute. METHODS: Patients undergoing robotic-assisted OPS/PSP at First Affiliated Hospital of Sun Yat-sen University between July 2015 and October 2021 were included in this study. The short-term and long-term outcomes of patients were retrospectively analyzed. RESULTS: Seventy-two patients were enrolled, including spleen-preserving distal pancreatectomy, central pancreatectomy, duodenum-preserving pancreatic head resection, and enucleation. Patients included were more likely to be young female (female: 46/72, median age: 47 years old). The median intraoperative blood loss and operation time was 50 ml and 255 min, respectively. Clinically relevant postoperative pancreatic fistula was 20.8% (grade B: 15/72, 20.8%; no grade C). The overall complication rate was 22.2% with the median postoperative length-of-stay of 8 days. At a median follow-up time of 28.5 months, the 5-year overall survival and recurrence-free survival rate were 100.0% and 100.0%, respectively. CONCLUSION: The short-term and long-term outcomes of patients receiving robotic-assisted OPP/PSP were acceptable. Robotic-assisted OPP/PSP was a feasible and safe technique for pancreatic benign or low-grade malignant lesions.


Asunto(s)
Neoplasias , Procedimientos Quirúrgicos Robotizados , Humanos , Femenino , Persona de Mediana Edad , Pancreatectomía , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/métodos , Páncreas/cirugía , Complicaciones Posoperatorias/epidemiología
2.
BMC Surg ; 23(1): 382, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38114974

RESUMEN

AIM: Splenic vessel-preserving spleen-preserving distal pancreatectomy (SVP-SPDP) has a lower risk of splenic infarction than the splenicvessel-sacrificing SPDP, but it is more technically demanding. Learning curve of robotic-assisted SVP-SPDP (RSVP-SPDP) remains unreported. This study sought to analyze the perioperative outcomes and learning curve of RSVP-SPDP by one single surgeon. METHODS: Seventy-four patients who were intended to receive RSVP-SPDP at the First Affiliated Hospital of Sun Yat-sen University between May 2015 and January 2023 were included. The learning curve were retrospectively analyzed by using cumulative sum (CUSUM) analyses. RESULTS: Sixty-two patients underwent RSVP-SPDP (spleen preservation rate: 83.8%). According to CUSUM curve, the operation time (median, 318 vs. 220 min; P < 0.001) and intraoperative blood loss (median, 50 vs. 50 mL; P = 0.012) was improved significantly after 16 cases. Blood transfusion rate (12.5% vs. 3.4%; P = 0.202), postoperative major morbidity rate (6.3% vs. 3.4%; P = 0.524), and postoperative length-of-stay (median, 10 vs. 8 days; P = 0.120) improved after 16 cases but did not reach statistical difference. None of the patients had splenic infarction or abscess postoperatively. CONCLUSION: RSVP-SPDP was a safe and feasible approach for selected patients after learning curve. The improvement of operation time and intraoperative blood loss was achieved after 16 cases.


Asunto(s)
Laparoscopía , Neoplasias Pancreáticas , Procedimientos Quirúrgicos Robotizados , Infarto del Bazo , Cirujanos , Humanos , Pancreatectomía , Estudios Retrospectivos , Pérdida de Sangre Quirúrgica , Infarto del Bazo/etiología , Infarto del Bazo/cirugía , Curva de Aprendizaje , Resultado del Tratamiento , Arteria Esplénica/cirugía , Neoplasias Pancreáticas/cirugía
3.
Gastroenterol Rep (Oxf) ; 11: goad042, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37502197

RESUMEN

Background: Robotic-assisted pancreatoduodenectomy (RPD) has been routinely performed in a few of centers worldwide. This study aimed to evaluate the perioperative outcomes and the learning curves of resection and reconstruction procedures in RPD by one single surgeon. Methods: Consecutive patients undergoing RPD by a single surgeon at the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between July 2016 and October 2022 were included. The perioperative outcomes and learning curves were retrospectively analysed by using cumulative sum (CUSUM) analyses. Results: One-hundred and sixty patients were included. According to the CUSUM curve, the times of resection and reconstruction procedures were shortened significantly after 30 cases (median, 284 vs 195 min; P < 0.001) and 45 cases (median, 138 vs 120 min; P < 0.001), respectively. The estimated intraoperative blood loss (median, 100 vs 50 mL; P < 0.001) and the incidence of clinically relevant post-operative pancreatic fistula (29.2% vs 12.5%; P = 0.035) decreased significantly after 20 and 120 cases, respectively. There were no significant differences in the total number of lymph nodes examined, post-operative major complications, or post-operative length-of-stay between the two groups. Conclusions: Optimization of the resection procedure and the acquisition of visual feedback facilitated the performance of RPD. RPD was a safe and feasible procedure in the selected patients.

4.
Gastroenterol Rep (Oxf) ; 11: goad018, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37051578

RESUMEN

Background: The application of robotic-assisted radical resection in perihilar cholangiocarcinoma (pCCA) remains poorly defined. This study aimed to evaluate the safety and efficacy of robotic-assisted radical resection for pCCA in our institute. Methods: Between July 2017 and July 2022, pCCA patients undergoing robotic-assisted and open radical resection at First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) were included. The short-term outcomes were compared by using propensity-scored matching (PSM) analysis. Results: Eighty-six pCCA patients were enrolled. After PSM at a ratio of 1:2, 10 and 20 patients were assigned to the robotic-assisted and open groups, respectively. There were no significant disparities in the clinicopathological features between the two groups. The robotic-assisted group had significantly longer operation time (median: 548 vs 353 min, P = 0.004) and larger total number of lymph nodes examined (median: 11 vs 5, P = 0.010) than the open group. The robotic-assisted group tended to have a lower intraoperative blood loss (median: 125 vs 350 mL, P = 0.067), blood transfusion rates (30.0% vs 70.0%, P = 0.056), and post-operative overall morbidities (30.0% vs 70.0%, P = 0.056) than the open group, even though the differences were not statistically significant. There were no significant differences in the negative resection margin, post-operative major morbidities, or post-operative length-of-stay between the robotic-assisted and open groups (all P > 0.05). Conclusions: Robotic-assisted radical resection of pCCA may get a larger total number of lymph nodes examined than open surgery. Provided robotic-assisted surgery may be a feasible and safe technique for selected pCCA patients.

5.
Gastroenterol Rep (Oxf) ; 11: goad010, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36911142

RESUMEN

Background and objective: The value of debulking surgery for unresectable well-differentiated metastatic pancreatic neuroendocrine tumor (m-PNET) remains poorly defined. This study aimed to evaluate the outcomes of m-PNET following debulking surgery in our institute. Methods: Patients with well-differentiated m-PNET in our hospital between February 2014 and March 2022 were collected. Clinicopathological and long-term outcomes of patients treated with radical resection, debulking surgery, and conservative therapy were compared retrospectively. Results: Fifty-three patients with well-differentiated m-PNET were reviewed, including 47 patients with unresectable m-PNET (debulking surgery, 25; conservative therapy, 22) and 6 patients with resectable m-PNET (radical resection). Patients undergoing debulking surgery had a post-operative Clavien-Dindo ≥ III complication rate of 16.0% without mortality. The 5-year overall survival (OS) rate of patients treated with debulking surgery was significantly higher than that of those treated with conservative therapy alone (87.5% vs 37.8%, log-rank P = 0.022). Besides, the 5-year OS rate of patients treated with debulking surgery was comparable to that of patients with resectable m-PNET undergoing radical resection (87.5% vs 100%, log-rank P = 0.724). Conclusions: Patients with unresectable well-differentiated m-PNET who underwent resection had better long-term outcomes than those who received conservative therapy alone. The 5-year OS of patients undergoing debulking surgery and radical resection were comparable. Debulking surgery could be considered for patients with unresectable well-differentiated m-PNET if no contraindication exists.

6.
Asian J Surg ; 45(1): 265-268, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34120821

RESUMEN

OBJECTIVE: To compare the safety and short-term outcomes between robotic-assisted and laparoscopic left hemi-hepatectomies in a single academic medical center. METHODS: A cohort of 52 patients, who underwent robotic-assisted or laparoscopic left hemi-hepatectomies between April 2015 and January 2020 in Department of Pancreatobiliary Surgery, the First Affiliated Hospital of Sun Yat-Sen University was recruited into the study. Their clinicopathological features and short-term outcomes were analyzed retrospectively. RESULTS: There were 25 robotic-assisted and 27 laparoscopic cases, with a median age of 55 years (34-77 years). There was one conversion to open in laparoscopic group. There were no significant differences in clinicopathological features between two groups, except robotic group had higher body mass index (23.9 vs. 22.0 kg/m2, p = 0.047). Robotic-assisted and laparoscopic groups had similar operative time (300 vs. 310 min, p = 0.515), length of hospital stay (8 vs. 8 days, p = 0.981) and complication rates (4.0% vs. 14.8%, p = 0.395), but the former had less blood loss (100 vs. 200 ml, p < 0.001) and lower incidence of blood transfusion (0% vs. 22.2%, p = 0.023) in comparison with laparoscopic group. R0 resection was achieved for all patients with malignancies. There was no perioperative mortality in both groups. The cost of robotic group was higher than laparoscopic group (105,870 vs. 64,191 RMB yuan, p = 0.02). CONCLUSION: The robotic-assisted and laparoscopic approaches had similar safety and short-term outcomes in left hemi-hepatectomy, and the former can reduce operative blood loss and blood transfusion. However, the costs were higher in robotic group.


Asunto(s)
Laparoscopía , Procedimientos Quirúrgicos Robotizados , Hepatectomía , Humanos , Tiempo de Internación , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento
7.
Cancer Biol Ther ; 21(8): 726-732, 2020 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-32644887

RESUMEN

INTRODUCTION: The hyperthermic intraperitoneal chemotherapy (HIPEC) has been widely applied in clinical practice for peritoneal carcinomatosis (PC). The temperature is one of the important elements affecting the efficacy of HIPEC, and it can become fluctuant by several factors. This study is aimed to explore the role of a stable perfusion temperature in promoting bowel recovery of PC patients due to gastrointestinal malignancies. METHODS: Between January 2012 and July 2013, 59 PC patients undergoing cytoreductive surgery and three-cycle HIPEC were included. Patients having stable perfusion temperature for all cycles were assigned into the study group, with the rest having unstable temperature into the control group. Time of flatus and defecation passage and initiation time of enteral nutrition were compared between both groups to detect the significance in bowel function recovery, with visual analogue scale (VAS) pain intensity and overall survival (OS) compared meanwhile. RESULTS: In sum, 33 (55.9%) patients obtained stable temperature during HIPEC, and the rest of 26 (44.1%) developed fluctuant perfusion temperature. Average time of flatus (2.3 ± 1.2 vs 3.9 ± 2.2 days, P =.002), defecation passage (5.2 ± 2.1 vs 7.1 ± 2.9 days, P =.004) and enteral nutrition initiation (4.3 ± 1.5 vs 6.7 ± 2.3 days, P <.001) were much shorter in the study group than the control group. Additionally, the VAS score (4.5 ± 2.3 vs 6.3 ± 1.3, P <.001) and 5-year OS rate (17.8% vs 11.1%, P=.135) were both improved, with significance observed in postoperative pain control. CONCLUSIONS: During HIPEC, a precise temperature control could promise an early recovery of bowel function and reduce postoperative pain, without survival significance found based on the current cohort.


Asunto(s)
Tracto Gastrointestinal/fisiopatología , Quimioterapia Intraperitoneal Hipertérmica/métodos , Temperatura , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
8.
Gastroenterol Rep (Oxf) ; 8(2): 134-142, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32280473

RESUMEN

BACKGROUND: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is a rare subtype of primary liver cancers. Its prognostic factors remain unclear. The study aimed to evaluate its long-term outcome and prognostic factors by retrospectively reviewing the series of cHCC-CC after curative resection from our institute. METHODS: A total of 55 pathologically confirmed cHCC-CC patients undergoing curative resections between January 2003 and January 2018 at the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) were included. The clinicopathological and follow-up data were retrieved. Overall survival (OS) and recurrence-free survivals (RFS) were analysed by Kaplan-Meier curve. The independent prognostic factors were determined by using univariate and multivariate Cox analyses. RESULTS: There were 41 males and 14 females, with a median age of 51.0 (interquartile range, 44.0-60.0) years. The 1-, 3-, and 5-year OS and RFS rates in cHCC-CC were 80.0%, 25.5%, and 16.4%, respectively, and 52.7%, 21.8%, and 10.9%, respectively. The median OS and RFS were 24.9 and 14.5 months, respectively. Univariate and multivariate analyses revealed that elevated alpha-fetal protein (AFP) and/or CA19-9, vascular invasion, local extra-hepatic invasion, and lymph-node metastasis (LNM) were independent unfavorable prognostic factors for OS and RFS (all P < 0.005). Furthermore, elevated AFP and/or CA19-9 were independent unfavorable prognostic factors in various subgroups of cHCC-CC, including patients aged <60 years, positive hepatitis B surface antigen, cirrhosis, single tumor, tumor size ≥5 cm, no vascular invasion, no LNM, and no local extra-hepatic invasion (all P < 0.05). CONCLUSIONS: Elevated AFP and/or CA19-9, vascular invasion, local extra-hepatic invasion, and LNM were independent unfavorable prognostic factors for long-term survival of cHCC-CC undergoing curative resections. Patients with normal levels of AFP and CA19-9 had better prognosis.

9.
Cancer Lett ; 475: 119-128, 2020 04 10.
Artículo en Inglés | MEDLINE | ID: mdl-32014458

RESUMEN

Extracellular communication in the tumor microenvironment is critical. Results of qRT-PCR show that circ-0051443 is significantly lower in the plasma exosomes and tissues from patients with hepatocellular carcinoma (HCC) than healthy controls. Compared with the producer cells, circ-0051443 is mainly packaged into exosomes. A receiver operating characteristic curve (ROC) shows that the patients with HCC can be distinguished from the controls by exosomal circ-0051443. The role of exosomal circ-0051443 in HCC was determined by animal and cell analyses. Circ-0051443 is transmitted from normal cells to HCC cells via exosomes and suppresses the malignant biological behaviors by promoting cell apoptosis and arresting the cell cycle. Exosomal circ-0051443 decreases the weight and volume of the xenograft tumors in nude mice via BAK1 upregulation in these tumors. BAK1 expression is mediated by exosomal circ-0051443 through competitive bound to miR-331-3p. Therefore, exosomal circ-0051443 can serve as a predictor and potential therapeutic target for HCC.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/patología , Exosomas/genética , Neoplasias Hepáticas/patología , MicroARNs/genética , ARN Circular/genética , Proteína Destructora del Antagonista Homólogo bcl-2/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Ratones , Ratones Desnudos , Pronóstico , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína Destructora del Antagonista Homólogo bcl-2/genética
10.
Hum Cell ; 33(1): 148-158, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31776854

RESUMEN

Hepatocellular carcinoma (HCC) remains one of the most common and aggressive human cancers worldwide. Accumulating evidences indicate that non-coding RNAs are critical regulators implicated in various physiological processes including HCC development. Long non-coding RNA (lncRNA) MYCN opposite-strand (MYCNOS) was reported to be up-regulated in several human cancers, yet its role in HCC progression is still elusive. In the present study, MYCNOS was up-regulated in both HCC tissues and cell lines, and elevated MYCNOS expression was correlated to shorter survival time of HCC patients. We knocked down MYCNOS expression using short hairpin RNAs specifically targeting MYCNOS. MYCNOS knockdown significantly inhibited proliferation in HCC cells in vitro accompanied by exacerbated cell apoptosis; it also suppressed tumor growth in mouse model in vivo. Besides, the migration and invasion of HCC cells were remarkably inhibited after MYCNOS knockdown. In addition, MYCNOS acted as a negative regulator of miR-340 in HCC cells, and all effects of MYCNOS knockdown were abrogated by further miR-340 inhibition. We also discovered that oncogene phosphatidylinositol-3, 4, 5-trisphosphate-dependent Rac exchange factor 2 (PREX2) was a downstream target of miR-340, and PREX2 expression was positively correlated to that of MYCNOS in HCC tissues. In conclusion, our findings demonstrated that MYCNOS knockdown inhibited HCC progression through regulating miR-340.


Asunto(s)
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , ARN Largo no Codificante/genética , Proliferación Celular/genética , Humanos , Invasividad Neoplásica/genética
11.
Pancreas ; 48(6): 795-798, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31210659

RESUMEN

OBJECTIVE: The World Health Organization (WHO) grading system for the stratification of G1 and G2 pancreatic neuroendocrine tumors (pNETs) using an optimal Ki-67 index cutoff is still controversial. The present study aimed at finding one optimal Ki-67 cutoff value that distinguishes G1 and G2 tumors by analyzing the prognosis of patients with pNET in our center. METHODS: Data from 84 patients with pNET undergoing surgical resection in The First Affiliated Hospital of Sun Yat-sen University between March 2003 and October 2015 were retrospectively analyzed. RESULTS: The 5-year overall survival rate was 74.2%. Univariate analysis revealed that functional secretion, WHO grade, and TNM stage were significantly associated with long-term survival (all P < 0.05). Multivariate analysis demonstrated that WHO grade (P = 0.023) and TNM stage (P = 0.040) were independent prognostic factors. The receiver operating characteristic curve showed that the Ki-67 index of 5% had the best predictive ability (76.7%) for 5-year survival with a hazard ratio of 44.7. The hazard ratio was only 8.14 when the Ki-67 index cutoff was 2%. CONCLUSIONS: TNM stage and WHO grade were independent prognostic factors of pNETs. A Ki-67 index of 5% is better than 2% in stratifying G1 and G2 pNET tumors.


Asunto(s)
Antígeno Ki-67/análisis , Clasificación del Tumor/métodos , Tumores Neuroendocrinos/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Tumores Neuroendocrinos/metabolismo , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Pronóstico , Curva ROC , Estudios Retrospectivos , Organización Mundial de la Salud , Adulto Joven
12.
Dig Surg ; 36(5): 426-432, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30481744

RESUMEN

AIMS: This study aimed to develop a valuable nomogram by integrating molecular markers and tumor-node-metastasis (TNM) staging system for predicting the long-term outcome of patients with hepatocellular carcinoma (HCC). METHODS: The gene expression profiles of HCC patients undergoing liver resection were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. One hundred and ninety-nine patients from TCGA and 94 patients from GEO were selected to be part of the training cohort and validation cohort respectively. Univariate and multivariate cox analyses were performed to identify genes with independent prognostic values for overall survival (OS) of HCC patients in training cohort. Risk score was calculated based on the coefficients and Z-score of 3 genes for each patient. The nomogram was developed based on the risk score and TNM staging system. Discrimination and predictive accuracy of the nomogram were measured by using the concordance index (C-index) and calibration curve. The efficacy of the nomogram was tested in the external validation cohort. RESULTS: Univariate and multivariate cox analyses revealed that EXT2 (p = 0.035, hazard ratio 13.412), ETV5 (p = 0.010, hazard ratio 4.325), and CHODL (p < 0.001, hazard ratio 6.286) were independent prognostic factors and chosen for further nomogram establishment. The C-index of the nomogram for predicting the OS in the training cohort was superior to that of the TNM staging system (0.77 vs. 0.64, p < 0.01). The calibration curve of predicted 1-, 3-, and 5-year OS showed satisfactory accuracy. The external validation cohort showed good performance of comprehensive nomogram as well. CONCLUSION: The novel nomogram by integrating the molecular markers and TNM staging system has better performance in predicting long-term prognosis in HCC patients than the TNM staging system alone.


Asunto(s)
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Nomogramas , Biomarcadores de Tumor/genética , Proteínas de Unión al ADN/genética , Bases de Datos Genéticas , Femenino , Humanos , Lectinas Tipo C/genética , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , N-Acetilglucosaminiltransferasas/genética , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Tasa de Supervivencia , Factores de Transcripción/genética , Transcriptoma
13.
J Cell Biochem ; 119(7): 6045-6056, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29574975

RESUMEN

In the present study, we aimed to search for dysregulated lnRNAs in Hepatocellular carcinoma (HCC) tissues, and analyze the relationship of its expression level with the clinicopathological feature and patient prognosis. The biological function of FLVCR1-AS1, the identified lncRNA, in the process of HCC development, and progression was investigated in vitro and in vivo. The underlying molecular mechanism was further explored. We determined FLVCR1-AS1 expression in HCC tissues and peri-tumor tissues by bioinformatic analysis, qRT-PCR, Northern blot and in situ hybridization. The relationship between FLVCR1-AS1 expression level and prognosis was determined by analyzing clinical samples. The effects of FLVCR1-AS1 knockdown on HCC cell proliferation, apoptosis, migration, and invasion were investigated by CCK8, FACS, and tanswell assay, respectively. Tumor xenograft model was used to determine the influence of down-regulated FLVCR1-AS1 on tumor growth and metastasis. lncRNA FLVCR1-AS1 was extremely up-regulated in HCC tissues and cell lines. FLVCR1-AS1 expression level was positively correlated with tumor severity. FLVCR1-AS1 knockdown remarkably inhibited HCC cell proliferation, migration, and invasion in vitro and in vivo while induced cell apoptosis. In mechanism, FLVCR1-AS1 acted as a competitive endogenous RNAs to sponge miR-513c which targeted the mRNA of MET for degradation. By directly sponging miR-513c, FLVCR1-AS1 increased MET expression in HCC, and then promoted HCC progression. It was demonstrated that FLVCR1-AS1 played a positive role in HCC development and progression according to the study in its mechanism, function and clinical manifestation, so that it could be expected to become a new target in HCC prevention and treatment.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/patología , Movimiento Celular , Proliferación Celular , Neoplasias Hepáticas/patología , MicroARNs/genética , ARN Largo no Codificante/genética , Animales , Apoptosis , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/cirugía , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/cirugía , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Eur J Endocrinol ; 168(5): 675-81, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23416953

RESUMEN

OBJECTIVE: Alterations in microRNA (miRNA) expression have been described in thyroid tumors, suggesting a role for miRNAs in thyroid carcinogenesis. BRAF(V600E) is the most frequently identified genetic alteration in papillary thyroid carcinoma (PTC). We investigated the link between BRAF(V600E) status and the expression of miRNAs in PTC and analyzed the associations of these factors with clinicopathological characteristics. DESIGN AND METHODS: Prospective study of patients who underwent thyroid surgery between October 8, 2008 and November 1, 2010. BRAF(V600E) status was determined by mutant allele-specific amplification PCR and direct sequencing of exon 15 of the BRAF gene in 69 PTC tissues and 69 respective paracancerous normal thyroid tissues. Initially, miRNA expression was analyzed in 12 PTC tissues and three associated paracancerous tissues using a miRNA microarray. miRNAs differentially expressed between BRAF(V600E)-positive and -negative PTC tissues were then validated by real-time quantitative PCR on 69 PTC tissues and 69 paracancerous tissues. We also explored the associations between BRAF(V600E) status or differential miRNA expression and clinicopathological characteristics. RESULTS: The mutation rate of BRAF(V600E) in PTC was 47.8%. Twelve miRNAs were upregulated and six were downregulated in PTC tissues, among which miR-15a, 15a*, 34a*, 34b*, 551b, 873, 876-3p, and 1274a were first identified. miR-21* and 203 were significantly dysregulated (P<0.05) in PTC tissues with BRAF(V600E). Additionally, there were significant associations (P<0.05) between BRAF(V600E) and a higher tumor-node-metastasis staging (III/IV), and between miR-21* over-expression and lymph node metastasis. CONCLUSIONS: We identified two miRNAs that are differentially expressed in PTC tissues with BRAF(V600E) and revealed their associations with clinicopathological features. These findings may lead to the development of a potential diagnostic biomarker or prognostic indicator of PTC.


Asunto(s)
Carcinoma Papilar/genética , MicroARNs/genética , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias de la Tiroides/genética , Adolescente , Adulto , Anciano , Alelos , Biomarcadores de Tumor/genética , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patología , Femenino , Humanos , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología
15.
Biochem Biophys Res Commun ; 431(3): 535-41, 2013 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-23321310

RESUMEN

IL-8 is a multi-functional pro-inflammatory chemokine, which is highly expressed in cancers, such as ER-negative breast cancer. The present study demonstrates the pervasive role of IL-8 in the malignant progression of ER-negative breast cancer. IL-8 siRNA inhibited proliferation and delayed the G1 to S cell cycle progression in MDA-MB-231 and BT549 cells. IL-8 silencing resulted in the upregulation of the CDK inhibitor p27, the downregulation of cyclin D1, and the reduction of phosphorylated-Akt and NF-κB activities. IL-8 depletion also increased the chemosensitivity to docetaxel. These results indicate a role for IL-8 in promoting tumor cell survival and resistance to docetaxel and highlight the potential therapeutic significance of IL-8 depletion in ER-negative breast cancer patients.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Resistencia a Antineoplásicos/genética , Interleucina-8/fisiología , Taxoides/uso terapéutico , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular , Docetaxel , Femenino , Humanos , Integrina beta3/genética , Interleucina-8/genética , Persona de Mediana Edad , Interferencia de ARN , ARN Interferente Pequeño/genética
16.
J Transl Med ; 10: 208, 2012 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-23039040

RESUMEN

BACKGROUND: Splenectomy is the most effective treatment for patients with primary immune thrombocytopenia (ITP) who fail to respond to steroid therapy. Thus far, there is no effective means to predict the long-term haematological response of the procedure. The purpose of this study was to identify serum biomarkers as predictors of long-term response based on a proteomics approach. METHODS: The serum samples of ITP patients were collected before splenectomy and seven days after surgery. After depletion of the abundant serum proteins, pooled preoperative serum samples from four responders to splenectomy, four nonresponders and four healthy controls were subjected to two-dimensional gel electrophoresis (2-DE). Nine protein spots with at least a five-fold alteration in expression between responders and nonresponders were all identified as haptoglobin (Hp) by matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometer (MS) analysis. The validation of serum Hp expression was performed using enzyme-linked immunosorbent assays (ELISA) in thirty-seven responders, thirteen nonresponders and twenty-one healthy controls. RESULTS: The preoperative serum levels of Hp in the nonresponders (925.9 ± 293.5 µg/ml) were significantly lower than those in the responders (1417.4 ± 315.0 µg/ml, p <0.001) and the healthy controls (1409.1 ± 354.2 µg/ml, p <0.001), while there was no significant difference between the latter two groups. The postoperative serum levels of Hp in responders and nonresponders were (1414.1 ± 225.0 µg/ml) and (952.9 ± 202.4 µg/ml), respectively. There were no significant differences between the serum Hp levels before and after surgery in both responders and nonresponders (p>0.05). The preoperative serum levels of Hp did not significantly correlate with preoperative platelet count of the same blood samples (r = 0.244, p = 0.087), while it positively correlated with postoperative peak platelet count (r = 0.622, p < 0.001). The optimal cutoff value of preoperative serum Hp levels (1173.80 µg/ml) derived from the receiver operating characteristic (ROC) curve led to 78.4% sensitivity and 84.6% specificity. CONCLUSIONS: These results suggest that serum Hp levels may serve as a favourable predictor for the long-term response to splenectomy in ITP and may help to understand the pathophysiological differences between responders and nonresponders.


Asunto(s)
Biomarcadores/sangre , Haptoglobinas/metabolismo , Proteómica , Esplenectomía , Trombocitopenia/sangre , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Humanos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Trombocitopenia/inmunología
17.
Langmuir ; 28(29): 10725-32, 2012 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-22746205

RESUMEN

The fabrication of core-shell structural nanosilica@liposome nanocapsules as a drug delivery vehicle is reported. SiO(2) nanoparticles are encapsulated within liposomes by a W/O/W emulsion approach to form supramolecular assemblies with a core of colloidal particles enveloped by a lipid bilayer shell. A nanosilica core provides charge compensation and architectural support for the lipid bilayer, which significantly improves their physical stability. A preliminary application of these core-shell nanocapsules for hemoglobin (Hb) delivery is described. Through the H-bonding interaction between the hydroxyl groups on nanosilicas and the amino nitrogens of Hb, Hb-SiO(2) nanocomplexes in which the saturated adsorption amount of Hb on SiO(2) is 0.47 g g(-1) are coated with lipids to generate core-shell Hb-SiO(2)@liposome nanocapsules with mean diameters of 60-500 nm and Hb encapsulation efficiency of 48.4-87.9%. Hb-SiO(2)@liposome supramolecular nanovehicles create a mode of delivery that stabilizes the encapsulated Hb and achieves long-lasting release, thereby improving the efficacy of the drug. Compared with liposome-encapsulated Hb and Hb-loaded SiO(2) particles, such core-shell nanovehicles show substantially enhanced release performance of Hb in vitro. This finding opens up a new window of liposome-based formulations as drug delivery nanovehicles for widespread pharmaceutical applications.


Asunto(s)
Sistemas de Liberación de Medicamentos , Hemoglobinas/química , Liposomas/química , Nanoestructuras/química , Dióxido de Silicio/química , Adsorción , Sustancias Macromoleculares/química , Modelos Moleculares , Conformación Molecular , Tamaño de la Partícula , Propiedades de Superficie
18.
Int J Pharm ; 427(2): 354-7, 2012 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-22348875

RESUMEN

A novel liposome-encapsulated hemoglobin/silica nanoparticle (LEHSN) was fabricated by a water-in-oil-in-water (W/O/W) double emulsion approach. Bovine hemoglobin (Hb) was first adsorbed onto the surfaces of silica nanoparticles (SNs), and then the complex of Hb/SNs was encapsulated by liposome to form LEHSN which has a core-shell supramolecular structure. On the one hand, liposomes built a cell membrane-like environment for the controlled release of Hb. On the other hand, SNs which act as rigid core provide a supported framework for lecithin membrane, and enhance the stability of liposomes. In comparison with liposome-encapsulated Hb (LEH), LEHSN shows substantially enhanced stability and improved release property of Hb in vitro. This study highlights the potential of the novel LEHSN as an oxygen carrier for pharmaceutical applications.


Asunto(s)
Sustitutos Sanguíneos/administración & dosificación , Hemoglobinas/administración & dosificación , Oxígeno/administración & dosificación , Adsorción , Animales , Sustitutos Sanguíneos/farmacocinética , Bovinos , Coloides , Preparaciones de Acción Retardada , Composición de Medicamentos , Estabilidad de Medicamentos , Emulsiones , Hemoglobinas/farmacocinética , Lecitinas/química , Liposomas , Membranas Artificiales , Microscopía Electrónica de Transmisión , Nanopartículas , Tamaño de la Partícula , Dióxido de Silicio , Espectroscopía Infrarroja por Transformada de Fourier
19.
Chin Med J (Engl) ; 124(15): 2347-53, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21933567

RESUMEN

BACKGROUND: Little attention has been paid to the expression of heat shock protein 27 (HSP27) in patients with reflux esophagitis (RE), and few studies of the importance of HSP27 in esophagitis have been carried out in animal models. This study aimed to explore the expression of HSP27 in the esophageal tissue of rats with RE. METHODS: Eighty female Wistar rats were randomly divided into experimental groups A and B and control groups C and D (n = 20 in each group). To establish RE, rats in the two experimental groups received pylorus and forestomach ligations, while rats in the control group received gastrostomy and gastric perforation repair. The rats in groups A and C were sacrificed 7 days after surgery, and the rats in groups B and D were sacrificed 14 days after surgery. In groups A and B, 10 and 8 rats were diagnosed with RE by pathological examination, respectively (they were included in groups A' and B', respectively). The histopathological diagnosis of all the lower esophageal tissues in groups C and D was normal and 20 normal specimens were randomly selected for groups C' and D' with 10 specimens in each group. Macroscopic and microscopic esophagitis scores were assessed for the specimens in groups A' and B'. Lower esophageal tissues were collected from groups A', B', C', and D', and paraffin-embedded slices were made using part of the tissues. The expression of HSP27 in the tissues was detected using the two-step streptavidin-peroxidase immunohistochemical method. Some collected tissues were frozen, and expressions of HSP27 mRNA were detected using fluorescence quantitative polymerase chain reaction (FQ-PCR). RESULTS: Median macroscopic and microscopic esophagitis scores in groups A' (n = 10) and B' (n = 8) were 1.0 and 1.5, and 2.0 and 2.5, respectively. There were no significant differences in the macroscopic or microscopic esophagitis scores between the two groups (Z = -0.330, P = 0.741; Z = -0.142, P = 0.887, respectively). Immunohistochemical staining showed that HSP27 was expressed in all layers of the esophageal epithelia in RE and control rats. FQ-PCR showed that HSP27 mRNA levels in the lower esophageal tissue in RE group (groups A' and B') were higher than those in control group (groups C' and D') (Z = -0.249, P = 0.001). HSP27 mRNA expression in the lower esophageal tissue was significantly different in groups B' and D' (Z = -3.027, P = 0.002). And the levels of HSP27 mRNA expression in severe RE group (microscopic esophagitis score: 3) were higher than in mild RE group (microscopic esophagitis score: 1-2) and control group (Z = -3.396, P = 0.001; Z = -3.855, P < 0.001). CONCLUSIONS: HSP27 mRNA expression in the lower esophageal tissue of rats with RE is significantly higher than in the normal controls. Although reflux is a persistent stimulating factor, increased expression of HSP27 in the lower esophageal tissue of rats with RE requires aggravated esophageal injury.


Asunto(s)
Esofagitis Péptica/metabolismo , Esófago/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Animales , Esófago/patología , Femenino , Proteínas de Choque Térmico HSP27/genética , Inmunohistoquímica , Reacción en Cadena de la Polimerasa , Ratas , Ratas Wistar
20.
Appl Opt ; 50(20): 3538-46, 2011 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-21743564

RESUMEN

Four non-zero-dispersion-shifted fibers with almost the same large effective area (A(eff)) and optimized dispersion properties are realized by novel index profile designing and modified vapor axial deposition and modified chemical vapor deposition processes. An A(eff) of greater than 71 µm(2) is obtained for the designed fibers. Three of the developed fibers with positive dispersion are improved by reducing the 1550 nm dispersion slope from 0.072 ps/nm(2)/km to 0.063 ps/nm(2)/km or 0.05 ps/nm(2)/km, increasing the 1550 nm dispersion from 4.972 ps/nm/km to 5.679 ps/nm/km or 7.776 ps/nm/km, and shifting the zero-dispersion wavelength from 1500 nm to 1450 nm. One of these fibers is in good agreement with G655D and G.656 fibers simultaneously, and another one with G655E and G.656 fibers; both fibers are beneficial to high-bit long-haul dense wavelength division multiplexing systems over S-, C-, and L-bands. The fourth developed fiber with negative dispersion is also improved by reducing the 1550 nm dispersion slope from 0.12 ps/nm(2)/km to 0.085 ps/nm(2)/km, increasing the 1550 nm dispersion from -4 ps/nm/km to -6.016 ps/nm/km, providing facilities for a submarine transmission system. Experimental measurements indicate that the developed fibers all have excellent optical transmission and good macrobending and splice performances.

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