RESUMEN
Photoreduction of highly toxic U(VI) to less toxic U(IV) is crucial for mitigating radioactive contamination. Herein, a CoWO4/TpDD p-n heterojunction is synthesized, with TpDD serving as the n-type semiconductor substrate and CoWO4 as the p-type semiconductor grown in situ on its surface. The Fermi energy difference between TpDD and CoWO4 provides the electrochemical potential for charge-hole separation. Moreover, the Coulombic forces from the distinct carrier types between the two materials synergistically facilitate the transfer of electrons and holes. Hence, an internal electric field directed from TpDD to CoWO4 is established. Under photoexcitation conditions, charges and holes migrate efficiently along the curved band and internal electric field, further enhancing charge-hole separation. As a result, the removal capacity of CoWO4/TpDD increases from 515.2 mg/g in the dark to 1754.6 mg/g under light conditions. Thus, constructing a p-n heterojunction proves to be an effective strategy for remediating uranium-contaminated environments.
RESUMEN
Plasmonic photocatalysis is an effective strategy to solve radioactive uranium hazards in wastewater. A plasmonic photocatalyst Bi/Bi2O3-x@COFs was synthesized by in-situ growth of covalent organic frameworks (COFs) on Bi/Bi2O3-x surface for the U(VI) adsorption and plasmonic photoreduction in rare earth tailings wastewater. The presence of oxygen vacancy in Bi/Bi2O3-x and Schottky potential well formed by Bi and Bi2O3-x interface increased the number of free electrons, which induced localized surface plasmon resonance (LSPR) and enhanced the light absorption performance of composites. In addition, oxygen vacancy improved the Fermi level of Bi/Bi2O3-x, leading to another potential well between Bi2O3-x and COFs interface. The electron transport direction was reversed, thus increasing the electron density of COFs layer. COFs was an N-type semiconductor with specific binding U(VI) groups and suitable band structure, which could be used as an active reaction site. Bi/Bi2O3-x@COFs had 1411.5 mg g-1 removal capacity and high separation coefficient for U(VI) due to the synergistic action of photogenerated electrons and hot electrons. Moreover, the removal rate of uranium from rare earth tailings wastewater by regenerated Bi/Bi2O3-x@COFs was over 93.9%. The scheme of introducing LSPR and Schottky potential well provides another way to improve the photocatalytic effect.
RESUMEN
Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Humanos , Inmunosupresores/efectos adversos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/métodos , Estudios Multicéntricos como Asunto , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estudios Prospectivos , Calidad de Vida , Sirolimus/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Tumor recurrence after orthotopic liver transplantation (OLT) remains a serious threat for long-term survival of the recipients with hepatocellular carcinoma (HCC), since very few factors or measures have shown impact on overcoming HCC recurrence after OLT. Postoperative infection suppresses tumor recurrence and improves patient survival in lung cancer and malignant glioma probably via stimulating the immune system. Post-transplant infection (PTI), a common complication, is deemed to be harmful for the liver transplant recipients from a short-term perspective. Nevertheless, whether PTI inhibits HCC recurrence after OLT and prolongs the long-term survival of HCC patients needs to be clarified. AIM: To investigate the potential influence of PTI on the survival and tumor recurrence of patients with HCC after OLT. METHODS: A total of 238 patients with HCC who underwent OLT between August 2002 and July 2016 at our center were retrospectively included and accordingly subdivided into a PTI group (53 patients) and a non-PTI group (185 patients). Univariate analyses, including the differences of overall survival (OS), recurrence-free survival (RFS), and post-recurrence survival (PRS), between the PTI and non-PTI subgroups as well as survival curve analysis were performed by the Kaplan-Meier method, and the differences were compared using the log rank test. The variables with a P-value < 0.1 in univariate analyses were included in the multivariate survival analysis by using a Cox proportional-hazards model. RESULTS: The 1-, 3-, and 5-year OS and RFS rates of the whole cohort were 86.6%, 69.0%, and 63.6%, and 75.7%, 60.0%, and 57.3%, respectively. The 1-, 3-, and 5-year OS rates for the PTI patient group (96.0%, 89.3%, and 74.0%) were significantly higher than those for the non-PTI group (84.0%, 63.4%, and 60.2%) (P = 0.033). The absence of PTI was an independent risk factor for dismal OS (relative risk [RR] = 2.584, 95%CI: 1.226-5.449) and unfavorable RFS (RR = 2.683, 95%CI: 1.335-5.390). Subgroup analyses revealed that PTI remarkably improved OS (P = 0.003) and RFS (P = 0.003) rates of HCC patients with vascular invasion (IV), but did not impact on OS (P = 0.404) and RFS (P = 0.304) of patients without VI. Among the patients who suffered post-transplant tumor recurrence, patients with PTI showed significantly better OS (P = 0.026) and PRS (P = 0.042) rates than those without PTI. CONCLUSION: PTI improves OS and RFS of the transplant HCC patients at a high risk for post-transplant death and tumor recurrence, which is attributed to suppressive effect of PTI on HCC recurrence.
Asunto(s)
Carcinoma Hepatocelular/mortalidad , Tolerancia Inmunológica , Infecciones/epidemiología , Neoplasias Hepáticas/mortalidad , Trasplante de Hígado , Recurrencia Local de Neoplasia/epidemiología , Complicaciones Posoperatorias/epidemiología , Adulto , Carcinoma Hepatocelular/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Incidencia , Infecciones/inmunología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/inmunología , Complicaciones Posoperatorias/inmunología , Estudios Retrospectivos , Análisis de Supervivencia , Tasa de Supervivencia , Factores de TiempoRESUMEN
Recent studies have demonstrated that ubiquitin-specific protease 10 (USP10) plays a catalytic role in tumour suppression mainly by deubiquitinating its target proteins to enhance their stabilities. However, we found that USP10 could interact with and regulate the expression of oncogenic factor Musashi-2 (MSI2). We investigated whether USP10 positively regulates the expression of MSI2 by deubiquitination and confirmed the type of polyubiquitin chain that is linked to MSI2. We also explored the role of USP10 in regulating the proliferation of colon cancer through different experiments. This study provides a completely new perspective in understanding the role of USP10 in deubiquitination. In the future, USP10 may serve as a target for colon cancer treatment.
Asunto(s)
Neoplasias del Colon/metabolismo , Proteínas de Unión al ARN/química , Proteínas de Unión al ARN/metabolismo , Ubiquitina Tiolesterasa/metabolismo , Células CACO-2 , Línea Celular Tumoral , Proliferación Celular , Neoplasias del Colon/genética , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Células HEK293 , Células HT29 , Humanos , Lisina , Estabilidad Proteica , Proteínas de Unión al ARN/genética , Ubiquitina Tiolesterasa/genética , Ubiquitinación , Regulación hacia ArribaRESUMEN
Conditionally replicating adenoviral vectors constructed with tumor-specific promoters (TSPs) offers a viable tool for the treatment of cholangiocarcinoma. The aim of the present study was to investigate cholangiocarcinoma-specific TSPs that remain active in adenoviral constructs in gene therapy. The mRNA expressions of cyclooxygenase-2, cytokeratin-19 (CK19), mucin-1, midkine and telomerase reverse transcriptase were determined in human cholangiocarcinoma cell lines, primary human hepatocytes and cholangiocytes using reverse transcription-quantitative polymerase chain reaction. The candidate promoters constructed in adenoviral vectors were analyzed for their activities in cholangiocarcinoma cell lines, primary human hepatocytes and cholangiocytes using dual-luciferase reporter assays. The mRNA expression of CK19 was markedly higher in the QBC939 cell line, indicating specificity to cholangiocarcinoma. Moreover, the promoter activity of CK19 in the adenoviral vector in infected cholangiocarcinoma cells was found to be significantly stronger compared with that in infected primary human hepatocytes and cholangiocytes. CK19 may be implicated in the pathogenesis of cholangiocarcinoma, as demonstrated by the stronger activity of its promoter, as well as the higher expression of mRNA in tumor cells. Therefore, the use of the promoter sequence of the CK19 gene may represent a potential tool in cholangiocarcinoma-specific adenoviral gene therapy.
RESUMEN
PURPOSE: Recent studies have determined that cartilage oligomeric matrix protein (COMP) plays a vital role in carcinogenesis. We sought to clarify the role of COMP in colon cancer. METHODS: We investigated gene expression data from The Cancer Genome Atlas (TCGA) dataset. Tissue microarrays (TMA) containing paired samples from 253 patients with colon cancer were subjected to immunostaining. COMP levels in serum of colon cancer patients and healthy donors were measured with ELISA. We established COMP-knockout cells using the CRISPR/Cas9 system and COMP-overexpressing cells using lentiviral vectors to detect the effects of COMP on colon cancer cells using Cell Counting Kit-8 (CCK8), colony formation, apoptosis detection kit, and tumorigenesis assays in nude mice. RESULTS: The analysis of TCGA dataset and the results of the TMA suggested that COMP expression levels were significantly higher in cancer tissues than in adjacent normal tissues. Moreover, high COMP expression was correlated with the poor outcome of colon cancer patients. COMP levels in the sera of preoperative patients with colon cancer were much higher than those in healthy donors and were significantly reduced after colectomy. Colon cancer cells without COMP were defective with respect to the ability to proliferate, colony formation, the ability to resist 5-Fluorouracil-induced apoptosis and the growth of xenograft tumors in mice. Contrasting results were observed in COMP overexpressed cells. COMP promoted colon cancer cell proliferation partially through the activation of PI3K/ Akt/ mTOR/ p70S6K pathway. CONCLUSIONS: COMP may be a novel prognostic indicator and biomarker and also a potential therapeutic target for colon cancer.
Asunto(s)
Proteína de la Matriz Oligomérica del Cartílago/biosíntesis , Neoplasias del Colon/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Anciano , Animales , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Células CACO-2 , Proteína de la Matriz Oligomérica del Cartílago/sangre , Proteína de la Matriz Oligomérica del Cartílago/genética , Línea Celular Tumoral , Proliferación Celular/fisiología , Neoplasias del Colon/sangre , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Bases de Datos Genéticas , Supervivencia sin Enfermedad , Femenino , Células HCT116 , Células HEK293 , Células HT29 , Xenoinjertos , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Estadificación de Neoplasias , Transducción de Señal , Tasa de Supervivencia , Análisis de Matrices Tisulares , Transcriptoma , Regulación hacia ArribaRESUMEN
PURPOSE: The purpose of this study was to retrospectively evaluate the association between Interleukin-18 (IL-18) gene polymorphisms of the donor and recipient in liver transplant patients with bacterial infections. METHODS: Five single nucleotide polymorphisms (SNPs) (rs7106524, rs5744247, rs1946518, rs549908 and rs187238) of the IL-18 gene from the donors were genotyped and their association with post-operative bacterial infections was evaluated in liver transplant patients (N=113). A second independent group of liver transplant patients from a different organ transplant centre was also recruited for validation purposes (N=44). RESULTS: IL-18 mRNA mean expression levels and protein levels were significantly lower in liver transplant patients with bacterial infections. For the donor SNP rs1946518, more recipients carried the A allele in the bacterial-infected group than the uninfected group (61.4% vs 39.7%; P ≤0.002). The mean IL-18 mRNA expression and protein levels were significantly lower in the transplanted livers of recipients carrying the rs1946518 AA genotype compared with those from recipients with CC genotype (3.64, 3.33 vs. 2.75, P≤0.048). The A allele of rs1946518 also resulted in lower luciferase activity than the C allele in a reporter assay. The area under ROC curve indicated that the rs1946518 SNP genotype in the donor liver predicted an increased risk of bacterial infection after liver transplantation (AUROC>0.82). CONCLUSIONS: These findings indicate that the IL-18 rs1946518 SNP in the donor liver is a risk factor for developing bacterial infection after liver transplantation.
Asunto(s)
Alelos , Infecciones Bacterianas/genética , Interleucina-18/genética , Trasplante de Hígado/efectos adversos , Polimorfismo de Nucleótido Simple , Complicaciones Posoperatorias/genética , Donantes de Tejidos , Adulto , Infecciones Bacterianas/etiología , Femenino , Regulación de la Expresión Génica , Humanos , MasculinoRESUMEN
Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of l-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor-κB (NF-κB) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-κB activation and less release of TNF-α and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that inhibition of XIAP represents a potential therapeutic strategy for the treatment of acute pancreatitis.
Asunto(s)
Muerte Celular/fisiología , Proteínas Inhibidoras de la Apoptosis/metabolismo , FN-kappa B/metabolismo , Pancreatitis/metabolismo , Pancreatitis/patología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Arginina/metabolismo , Caspasas/metabolismo , Muerte Celular/efectos de los fármacos , Línea Celular , Ceruletida/farmacología , Inflamación/metabolismo , Interleucina-6/metabolismo , Ratones , Ratones Endogámicos C57BL , Necrosis/metabolismo , Necrosis/patología , Páncreas/diagnóstico por imagen , Páncreas/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Proteína Inhibidora de la Apoptosis Ligada a X/metabolismoRESUMEN
This study investigated the significance of La-related protein 1 (LARP1) in the development and progression of colorectal cancer (CRC). Quantitative real-time polymerase chain reaction and Western blot analyses were carried out to determine the mRNA and protein expression of LARP1 in CRC tumor tissues and paired adjacent normal mucosa. The expression of LARP1 was upregulated in CRC. Immunohistochemical analysis using tissue microarray was performed. A positive correlation between LARP1 and proliferating cell nuclear antigen (PCNA) in the area of proliferation was observed using the Spearman's correlation coefficient test (r = 0.332, P < 0.01). The elevated expression of LARP1 significantly correlated with T stage (P = 0.02), N stage (P = 0.006), M stage (P < 0.001), American Joint Committee on Cancer (AJCC) stage (P = 0.04), differentiation rank (P < 0.001), and PCNA level (P < 0.001). In addition, the inhibitory effect of LARP1 knockdown on CRC cell proliferation was demonstrated using Cell Counting Kit-8 (CCK8) and colony-forming cell (CFC) assays. Multivariate analysis showed that LARP1 was an independent prognostic factor for overall survival (OS; hazard rate (HR) = 0.244; 95 % confidence interval (CI), 0.078-0.769; P = 0.016) and disease-free survival (DFS; HR = 0.281; 95 % CI, 0.086-0.917; P = 0.035) in CRC patients. LARP1 plays an important role in the proliferation of colorectal cancer and represents a new prognostic indicator.
Asunto(s)
Autoantígenos/biosíntesis , Autoantígenos/genética , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Antígeno Nuclear de Célula en Proliferación/biosíntesis , ARN Mensajero/biosíntesis , Ribonucleoproteínas/biosíntesis , Ribonucleoproteínas/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/biosíntesis , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Interferencia de ARN , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Matrices Tisulares , Antígeno SS-BRESUMEN
Serpina family A member 4 (SERPINA4), also known as kallistatin, exerts important effects in inhibiting tumor growth and angiogenesis in many malignancies. However, the precise role of SERPINA4 in CRC has not been fully elucidated. The present study aimed to investigate the expression of SERPINA4 and its clinical significance in CRC. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses showed that the mRNA and protein expression of SERPINA4 in colorectal cancer (CRC) specimens was significantly decreased than that in adjacent normal mucosa. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of SERPINA4 by using a tissue microarray (TMA) containing 327 archived paraffin-embedded CRC specimens. Statistical analyses revealed that decreased SERPINA4 expression was significantly associated with invasion depth, nodal involvement, distant metastasis, American Joint Committee on Cancer (AJCC) stage, and tumor differentiation. SERPINA4 was also an independent prognostic indicator of disease-free survival and overall survival in patients with CRC. Furthermore, the impact of altered SERPINA4 expression on CRC cells was analyzed with a series of in vitro and in vivo assays. The results demonstrated that SERPINA4 significantly inhibits malignant tumor progression and serves as a novel prognostic indicator and a potential therapeutic target for CRC.
RESUMEN
OBJECTIVE: To examine the therapeutic effects of tocilizumab, an antibody against interleukin-6 receptor, on experimental severe acute pancreatitis and associated acute lung injury. The optimal dose of tocilizumab and the activation of interleukin-6 inflammatory signaling were also investigated. DESIGN: Randomized experiment. SETTING: Research laboratory at a university hospital. SUBJECT: Experimental severe acute pancreatitis in rats. INTERVENTIONS: Severe acute pancreatitis was induced by retrograde injection of sodium taurocholate (50 mg/kg) into the biliopancreatic duct. In dose-study, rats were administered with different doses of tocilizumab (1, 2, 4, 8, and 16 mg/kg) through the tail vein after severe acute pancreatitis induction. In safety-study, rats without severe acute pancreatitis induction were treated with high doses of tocilizumab (8, 16, 32, and 64 mg/kg). Serum and tissue samples of rats in time-study were collected for biomolecular and histologic evaluations at different time points (2, 6, 12, 18, and 24 hr). MEASUREMENTS AND MAIN RESULTS: 1) Under the administration of tocilizumab, histopathological scores of pancreas and lung were decreased, and severity parameters related to severe acute pancreatitis and associated lung injury, including serum amylase, C-reactive protein, lung surfactant protein level, and myeloperoxidase activity, were all significant alleviated in rat models. 2) Dose-study demonstrated that 2 mg/kg tocilizumab was the optimal treatment dose. 3) Basing on multi-organ pathologic evaluation, physiological and biochemical data, no adverse effect and toxicity of tocilizumab were observed in safety-study. 4) Pancreatic nuclear factor-κB and signal transducer and activator of transcription 3 were deactivated, and the serum chemokine (C-X-C motif) ligand 1 was down-regulated after tocilizumab administration. CONCLUSIONS: Our study demonstrated tocilizumab, as a marketed drug commonly used for immune-mediated diseases, was safe and effective for the treatment of experimental severe acute pancreatitis and associated acute lung injury. Our findings provide experimental evidences for potential clinical application of tocilizumab in severe acute pancreatitis and associated complications.
Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/farmacología , Interleucina-6/metabolismo , Pancreatitis/tratamiento farmacológico , Enfermedad Aguda , Amilasas/metabolismo , Animales , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Proteína C-Reactiva/metabolismo , Quimiocina CXCL1/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , FN-kappa B/biosíntesis , Peroxidasa/metabolismo , Proteínas Asociadas a Surfactante Pulmonar/metabolismo , Distribución Aleatoria , Ratas , Índice de Severidad de la Enfermedad , Transducción de Señal/efectos de los fármacos , Factores de Transcripción/efectos de los fármacosRESUMEN
BACKGROUND: The number and survival rate of simultaneous liver-kidney transplant (SLKT) recipients have increased dramatically since 2002. However, the long-term effectiveness of SLKT in patients with hepatitis B is unknown. MATERIAL/METHODS: Forty-six patients who visited the Organ Transplant Center of the Shanghai First People's Hospital between January 2001 and May 2005 had hepatitis B virus infection and renal failure (any degree), and underwent organ transplantation: 21 patients underwent SLKT and 25 patients underwent liver transplant (LT) alone. RESULTS: The 1-, 3-, and 5-year survival rates of SLKT recipients were 90.5%, 81.0%, and 81.0%, respectively. Incidence of acute hepatic allograft rejection between SLKT recipients and LT recipients (33% vs. 16%) did not reach significance (P=0.170). Despite higher infection rate, more prevalent hepatitis B relapse, and longer stay in the intensive care unit, SLKT recipients experienced significantly higher 1-year survival rate (90.5%) compared with LT recipients (60%, P=0.019). Multivariate regression analysis revealed that postoperative renal failure (odds ratio (OR)=48, P=0.003) and Risk/Injury/Failure/Loss/End-stage (RIFLE) stage (OR=8, P=0.012) were independent risk factors for postoperative death after LT. CONCLUSIONS: SLKT in patients with hepatitis B had higher early-stage infection rate, but had a higher long-term survival rate compared with the LT group. Although the incidence of postoperative hepatitis B relapse in SLKT recipients was higher, timely and reasonable treatment can ensure long-term survival of patients. Worsening RIFLE stage of recipients can predict high mortality when only given LT. SLKT might be a better choice for RIFLE stage 2 or 3 patients than LT alone.
Asunto(s)
Hepatitis B/terapia , Trasplante de Riñón , Trasplante de Hígado , Adulto , Causas de Muerte , Femenino , Humanos , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/mortalidad , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Cuidados Posoperatorios , Complicaciones Posoperatorias/etiología , Cuidados Preoperatorios , Pronóstico , Recurrencia , Factores de Riesgo , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
Octamer transcription factor 1 (OCT1) was found to influence the genesis and progression of numerous cancers except for colorectal cancer (CRC). This study tried to explore the role of OCT1 in CRC and clarify the association between its expression and patients' clinical outcome. Transcriptional and post-transcriptional expression of OCT1 was detected in CRC cancerous tissues and paired normal mucosae by real-time PCR as well as immunohistochemistry. Moreover, the effect of OCT1 knockdown on CRC cell proliferation was investigated both in vitro and in vivo using Cell Counting Kit-8 assay, colony-forming assay, and mouse tumorigenicity assay. Expression of OCT1 was found to be elevated in CRC. Suppression of OCT1 significantly inhibited CRC cell proliferation both in vitro and in vivo. Furthermore, upregulated level of OCT1 was significantly associated with N stage, M stage, and American Joint Committee on Cancer (AJCC) stage (P = 0.027, 0.014, and 0.002, respectively) as well as differential degree (P = 0.022). By using multivariate Cox hazard model, OCT1 was also shown to be a factor independently predicting overall survival (OS; P = 0.013, hazard ratio = 2.747, 95 % confidence interval 1.125 to 3.715) and disease-free survival (DFS; P = 0.004, hazard ratio = 2.756, 95 % confidence interval 1.191 to 4.589) for CRC patients. Our data indicate that OCT1 carries weight in colorectal carcinogenesis and functions as a novel prognostic indicator and a promising target of anti-cancer therapy for CRC.
Asunto(s)
Transformación Celular Neoplásica/genética , Colon/metabolismo , Neoplasias Colorrectales/genética , Factor 1 de Transcripción de Unión a Octámeros/genética , Anciano , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Colon/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Ratones Desnudos , Persona de Mediana Edad , Análisis Multivariante , Factor 1 de Transcripción de Unión a Octámeros/metabolismo , Valor Predictivo de las Pruebas , Pronóstico , Interferencia de ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Trasplante Heterólogo , Regulación hacia ArribaRESUMEN
Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure with considerable mortality. Recently, resolvin D1 (RvD1) as an endogenous anti-inflammatory lipid mediator has been confirmed to protect against many inflammatory diseases. This study was designed to investigate the effects of RvD1 in acute pancreatitis and associated lung injury. Acute pancreatitis varying from mild to severe was induced by cerulein or cerulein combined with LPS, respectively. Mice were pretreated with RvD1 at a dose of 300 ng/mouse 30 min before the first injection of cerulein. Severity of AP was assessed by biochemical markers and histology. Serum cytokines and myeloperoxidase (MPO) levels in pancreas and lung were determined for assessing the extent of inflammatory response. NF-κB activation was determined by Western blotting. The injection of cerulein or cerulein combined with LPS resulted in local injury in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the cerulein and LPS group. Pretreated RvD1 significantly reduced the degree of amylase, lipase, TNF-α, and IL-6 serum levels; the MPO activities in the pancreas and the lungs; the pancreatic NF-κB activation; and the severity of pancreatic injury and associated lung injury, especially in the severe acute pancreatitis model. These results suggest that RvD1 is capable of improving injury of pancreas and lung and exerting anti-inflammatory effects through the inhibition of NF-κB activation in experimental acute pancreatitis, with more notable protective effect in severe acute pancreatitis. These findings indicate that RvD1 may constitute a novel therapeutic strategy in the management of severe acute pancreatitis.
Asunto(s)
Ácidos Docosahexaenoicos , Inflamación , Lesión Pulmonar , Pancreatitis Aguda Necrotizante , Animales , Antiinflamatorios/metabolismo , Antiinflamatorios/farmacología , Ceruletida/farmacología , Modelos Animales de Enfermedad , Ácidos Docosahexaenoicos/metabolismo , Ácidos Docosahexaenoicos/farmacología , Fármacos Gastrointestinales/farmacología , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Interleucina-6/metabolismo , Pulmón/metabolismo , Pulmón/patología , Lesión Pulmonar/etiología , Lesión Pulmonar/metabolismo , Lesión Pulmonar/patología , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Páncreas/metabolismo , Páncreas/patología , Pancreatitis Aguda Necrotizante/complicaciones , Pancreatitis Aguda Necrotizante/metabolismo , Pancreatitis Aguda Necrotizante/patología , Peroxidasa/metabolismo , Sustancias Protectoras/metabolismo , Sustancias Protectoras/farmacología , Transducción de Señal/efectos de los fármacosRESUMEN
Gastric cancer (GC) is a malignant cancer with poor prognosis. This study aims to investigate the roles of homeobox A10 (HOXA10) in GC and the correlations between HOXA10/CD44 expression and GC prognosis. Based on qRT-PCR and Western Blot analyses in 50 pairs of fresh GC samples and adjacent normal samples, it is identified that HOXA10 was significantly up-regulated in GC tissues at mRNA and protein levels. Cell proliferation, migration, and invasion were enhanced in GC cells with overexpressed HOXA10, while inhibited in cells with silenced HOXA10. Through IPA software, HOXA10 was predicted to interact with CD44 via MSN, which was preliminarily confirmed by using Western Blot. Through immunohistochemistry and tissue microarray (N=264), it is found that HOXA10 expression was significantly correlated with tumor size (P=0.011) and CD44 expression (P<0.001), while CD44 expression was significantly correlated with tumor size (P<0.001), depth of tumor invasion (P<0.001), lymph node metastasis (P<0.001), distant metastasis (P=0.001), UICC stage (P<0.001), histological differentiation (P<0.001), and HOXA10 expression (P<0.001). Additionally, the over-all survival and disease-free survival of HOXA10(+)/CD44(+) patients were dramatically decreased in comparison with that of HOXA10(+)/CD44(-), HOXA10(-)/CD44(+), or HOXA10(-)/CD44(-) patients (P<0.001), suggesting that the combinatory expression of HOXA10 and CD44 was correlated with poor GC prognosis. In conclusion, HOXA10 and CD44 might play roles in GC tumorigenesis, metastasis, and invasion. HOXA10(+)/CD44(+) expression might serve as a prognostic biomarker for GC, which needs more studies to validate.
Asunto(s)
Adenocarcinoma/metabolismo , Biomarcadores de Tumor/metabolismo , Proteínas de Homeodominio/metabolismo , Receptores de Hialuranos/sangre , Neoplasias Gástricas/metabolismo , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidad , Anciano , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Supervivencia sin Enfermedad , Femenino , Expresión Génica , Proteínas Homeobox A10 , Proteínas de Homeodominio/genética , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Transducción de Señal , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidadRESUMEN
Our recent study observed that the expression of Musashi-2 (MSI2), a member of the Musashi family, was up-regulated in hepatitis B virus (HBV) related hepatocellular carcinoma parenchymal cells. Using quantitative PCR, tissue microarray (TMA) and immunohistochemical staining, we evaluated MSI2 mRNA and protein levels in tumor tissues from patients with different stages of hepatocellular carcinoma with paired adjacent noncancerous sample sets. The following techniques were used to further investigate MSI2 function and its potential molecular mechanism: RNAi, wound healing assay, Transwell assay, quantitative PCR and western blot analysis. Immunohistochemical detection of MSI2 on a TMA containing 106 paired specimens showed that increased cytoplasmic and nuclear MSI2 staining was significantly associated with tumor size, tumor differentiation, recurrence, TNM stage, vessel invasion and Ki-67 proliferative index. Patients with MSI2-positive tumors had a significantly higher disease recurrence rate and poorer survival than patients with MSI2-negative tumors after radical surgery. Based on univariate analysis, MSI2 expression showed an unfavorable influence on both disease-free survival and overall survival. Multivariate analysis revealed that higher MSI2 expression, together with tumor size, tumor differentiation, tumor thrombus, and Ki-67 expression were independent predictors of overall survival. With MSI2 knockdown, hepatoma cell migration and invasion were inhibited and the expression of ß-catenin, T cell factor (TCF) and lymphoid enhancer factor (LEF) were dysregulated. Thus, we propose that MSI2 may predict unfavorable outcomes in hepatitis B virus related hepatocellular carcinoma and promote cancer progression via the Wnt/ß-catenin signaling pathway.
RESUMEN
We found that the difference in miR10b expression between the tumor tissue and adjacent nontumor tissue was significant. Outer periphery and portal vein serum miR10b concentrations were significantly higher than those of the control. However, the outer periphery vein miR10b concentrations were not significant when compared with the portal vein serum concentration in colorectal cancer. The expression levels of miR10b were associated with highergrade colorectal cancer. MiR10b levels were markedly elevated in lymph node metastasis-positive tumor tissue compared with those in lymph node metastasis-free tumor tissue, and were correlated with a downregulation in Hoxd10 expression. Rhoc protein expression in tumor tissue was significantly amplified when compared to that of the control tissue group. An inverse correlation between Hoxd10 and Rhoc in immunohistochemistry and western blot analysis was observed (P<0.05). MiR-10b expression was also inversely correlated with Hoxd10 protein expression (P<0.05). Thus, miR10b is potentially involved in the invasion of colorectal cancer.
Asunto(s)
Neoplasias Colorrectales/patología , Proteínas de Homeodominio/biosíntesis , MicroARNs/genética , Invasividad Neoplásica/genética , Factores de Transcripción/biosíntesis , Proteínas de Unión al GTP rho/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática/genética , Metástasis Linfática/patología , Masculino , MicroARNs/biosíntesis , MicroARNs/sangre , Persona de Mediana Edad , Vena Porta/metabolismo , Proteína rhoC de Unión a GTPRESUMEN
BACKGROUND: Central lymph node metastasis(CLNM) is common in papillary thyroid microcarcinoma (PTMC). The aim of this study was to define the pathohistologic risk grading based on surgical outcomes. MATERIALS AND METHODS: Statistical analysis was performed to figure out the optimal cut-off values of size in preoperative ultrasound images for defining the risk of CLNM in papillary thyroid microcarcinoma. Receiver operating characteristic curves (ROC) studies were carried out to determine the cutoff value(s) for the predictor(s). All the patients were divided into two groups according to the above size and the clinic-pathological and immunohistochemical parameters were compared to determine the significance of findings. RESULTS: The optimal cut-off value of tumor size to predict the risk of CLNM in papillary thyroid microcarcinoma was 0.575 cm (area under the curve 0.721) according to the ROC curves. Significant differences were observed on the multifocality, extrathyroidal extension and central lymph node metastasis between two groups which were divided according to the tumor size by the cutoff values. Patients in two groups showed different positive rate and intensity of Ki67. CONCLUSIONS: The size of PTMC in ultrasound images are helpful to predict the aggressiveness of the tumors, it could be an easy predictor for PTMC prognosis and assist us to choose treatment.
Asunto(s)
Carcinoma Papilar/patología , Ganglios Linfáticos/patología , Neoplasias de la Tiroides/patología , Carga Tumoral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Curva ROC , Factores de Riesgo , Adulto JovenRESUMEN
The present study aimed to assess the efficacy of surgery and adjuvant therapy in older patients (age≥70 years) with colorectal cancer (CRC). Older CRC patients are under-represented in available clinical trials, and therefore their outcomes after receiving surgery and adjuvant therapy are unclear. From two prospective Swedish databases, we assessed a cohort of 1021 patients who underwent curative surgery for stage I, II, or III primary CRC, with or without adjuvant chemotherapy/radiotherapy. Of the patients with colon cancer (n=467), 182 (39%) were aged <70 years, 162 (35%) aged 70 to 80 years, and 123 (26%) were aged ≥80 years. Of rectal cancer patients (n=554), 264 (48%) were aged <70 years, 234 (42%) aged 70 to 80 years, and 56 (10%) aged ≥80 years. Older patients with either colon or rectal cancer had higher comorbidity than did younger patients. Older patients with colon cancer had equivalent postoperative morbidity and 30-day mortality to younger patients. Rectal cancer patients aged ≥80 years had a higher 30-day mortality than younger patients (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.6-4.55; P=0.03). For either colon or rectal cancer, adjuvant chemotherapy compromised the 5-year overall survival (OS) of older patients with stage II disease and had no effect on those with stage III disease. Receiving adjuvant chemotherapy was a poor factor of OS for older patients with either colon (HR 1.88, 95% CI: 1.20-4.35, P=0.03) or rectal cancer (HR 1.72, 95% CI: 1.05-2.26, P=0.004). Preoperative short-course radiotherapy improved both OS and local control for older patients with stage III rectal cancer and had no effect on those with stage II disease. Radiotherapy was a favorable factor for the OS of the older patients with rectal cancer (HR 0.42, 95% CI: 0.21-3.57, P=0.01). In conclusion, Older CRC patients had equal safety of surgery as younger patients, except rectal cancer patients aged ≥80 years that had a higher mortality. Adjuvant 5FU-based chemotherapy did not benefit older CRC patient, while neoadjuvant radiotherapy improved the prognosis of older patients with stage III rectal cancer.