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1.
Cancer Med ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31701652

RESUMO

PURPOSE: The aim of our study was to propose a strategy based on indocyanine green (ICG) (SBI) to provide better clinical guidelines for transarterial chemoembolization (TACE) treatments for Barcelona clinic liver cancer (BCLC) stage C hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: From October 2005 to December 2012, 112 BCLC stage C HCC patients initially treated with TACE were investigated, randomly divided into a training cohort (n = 79) and validation cohort (n = 33). In training group, the patients were grouped based on their 15 minutes ICG retention rate (ICG R15), different chemo drugs and dose of lipidol in TACE. Overall survival (OS) and progression-free survival (PFS) were analyzed in subgroups. Strategy based on ICG was built and verified in validation group. RESULTS: For those patients with ICG R15 values >10%, the lipiodol ≤10 mL group showed better survival than the lipiodol >10 mL group. For those patients with ICG R15 values ≤10%, the group that received triple-drug chemotherapy treatments with lipiodol diameter ratio values between 1 and 3 showed better survival than the other group. Patients who conformed with the SBI had better survival times than those who did not conform with the SBI, in both the training cohort (median OS 10.3 vs 5.1 months; P < .001; median PFS, 3.3 vs 2.1 months; P = .006) and the validation cohort (median OS 8.9 vs 7.1 months; P = .087; median PFS, 6.6 vs 2.3 months; P < .001). CONCLUSIONS: The SBI is suitable and may provide survival benefits for TACE treatments in BCLC stage C HCC patients.

2.
Surg Laparosc Endosc Percutan Tech ; 29(5): 313-320, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31436649

RESUMO

BACKGROUND: The effectiveness of multiband mucosectomy (MBM) for early esophageal cancer and precancerous lesions is still in uncertainty. We aimed to evaluate the efficacy and safety of this procedure and to compare it with cap-assisted endoscopic resection (EMR-cap). METHODS: A systematic search of both English and Chinese databases was performed from inception to April 30, 2019. Complete resection rate, local recurrence rate, and procedure time were considered the primary outcome measures. Prevalence of complications was considered the secondary outcome measure. All data analyses were performed using Review Manager Software. RESULTS: Two randomized controlled trials (RCTs) and 3 non-RCTs were included in the final meta-analysis. When compared with the EMR-cap technique, MBM had a similar complete resection rate [odds ratio (OR)=2.09, 95% confidence interval (CI): 0.78-5.60, P=0.14], a similar local recurrence rate (OR=0.50, 95% CI: 0.09-2.67, P=0.42), a shorter resection time (mean difference: -9.08, 95% CI: -13.86 to -4.30, P=0.0002), a shorter procedure time (mean difference: -13.36, 95% CI: -17.85 to -8.86, P<0.00001), a lower bleeding rate (OR=0.45, 95% CI: 0.24-0.83, P=0.01), a similar perforation rate (OR=0.55, 95% CI: 0.15-2.06, P=0.37), and a similar stricture rate (OR=0.77, 95% CI: 0.10-5.84, P=0.80). The results of non-RCTs were consistent with those of RCTs. CONCLUSIONS: MBM is similar to EMR-cap in terms of efficacy and safety for endoscopic resection of early cancer and precancerous lesions of the esophagus. However, MBM is less time-consuming.

3.
Curr Med Sci ; 39(3): 426-430, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31209814

RESUMO

Restoration of fracture alignment by osteotomy is crucial for the management of humeral nonunion. In the present study, we introduced a new way of osteotomy (Z-shaped) in treating humeral shaft nonunion secondary to failed plate osteosynthesis. Clinical data of 24 patients with humeral shaft nonunion following implant failure (from 2010 to 2014) were retrospectively evaluated. These patients underwent Z-shaped osteotomy in revision surgery after the initial surgery, plate osteosynthesis, was failed. Outcomes were evaluated using visual analogue scale (VAS) and Constant and Murley score. Repeated analysis of variance (ANOVA) was used for statistical analysis. Patients were followed up for a minimum of 24 months (26.83±4.33 months). The operative time was 102.33±10.16 min, and hospital stay averaged 9.75±2.13 days. All patients achieved clinical union at the latest follow-up. Complications included radial palsy (n=1) and superficial wound infection (n=1). The postoperative VAS scores decreased significantly compared to preoperative score (F=257.99, P<0.01). Constant and Murley score increased and reached 81.33±0.95 at 24 months' follow-up (F=247.35, P<0.01). Among all the cases, 15 cases were graded as "excellent", and 9 as "good". In conclusion, Z-shaped osteotomy was easy to perform, and it provided additional medial support with more bone contact areas. Revision surgery using locking plate and Z-shaped osteotomy achieved high union rate and improved functional outcome. It was a reasonable and safe option for treating humeral nonunion following implant failure.

4.
J Stroke Cerebrovasc Dis ; 28(7): 1860-1865, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31064695

RESUMO

BACKGROUND AND PURPOSE: Previous studies have shown that common variants within CYP3A4 and CYP3A5 are associated with statin pharmacokinetics and the risk of cardiovascular disease. However, the association of variants in CYP3A4 and CYP3A5 with the prognosis of ischemic stroke remains undetermined. Therefore, we investigated this herein. METHODS: Four hundred thirty-three consecutive patients with acute ischemic stroke were recruited. The outcome at the 1-year follow-up was assessed using the modified Rankin Scale (mRS). Two variants, CYP3A4*1G and CYP3A5*3, were genotyped by the improved Multiple Ligase Detection Reaction platform. RESULTS: Binary logistic regression analysis showed that the CYP3A4*1G/*1G homozygote was associated with poor outcome at 1 year (mRS score ≥2) after adjustment for conventional factors in the additive model (odds ratio [OR] = 2.92; 95% confidence interval, 1.07-7.98; P = .037) and recessive model (OR = 3.37; 95% confidence interval, 1.26-9.04; P = .016). Subgroup analysis indicated that the CYP3A4*1G/*1G homozygote was associated with poor prognosis at 1 year among patients with stable high-intensity atorvastatin therapy (40-80 mg/d) after adjustment for conventional factors in the additive model (OR = 8.16; 95% confidence interval, 1.50-44.44; P = .015) and recessive model (OR = 9.06; 95% confidence interval, 1.72-47.64; P = .009). No significant association was identified between CYP3A5*3 and the 1-year outcome of patients with ischemic stroke. CONCLUSIONS: Our study findings suggest that the CYP3A4*1G/CYP3A4*1G genotype may be associated with poor prognosis at 1 year after acute ischemic stroke in the Han Chinese population.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Isquemia Encefálica/genética , Citocromo P-450 CYP3A/genética , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Idoso , Atorvastatina/administração & dosagem , Atorvastatina/farmacocinética , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/enzimologia , Isquemia Encefálica/etnologia , China/epidemiologia , Citocromo P-450 CYP3A/metabolismo , Avaliação da Deficiência , Feminino , Frequência do Gene , Homozigoto , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Prevenção Secundária/métodos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/enzimologia , Acidente Vascular Cerebral/etnologia , Fatores de Tempo , Resultado do Tratamento
5.
Cell Death Dis ; 10(5): 369, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31068575

RESUMO

In our previous report, we identified miR-34c-3p as an independent factor contributing to the carcinogenesis of hepatocellular carcinoma (HCC) by targeting NCK Associated Protein 1 (NCKAP1). NCKAP1 has been known to promote the malignancy of cancer cells by disrupting the structural stability of WAS protein family member 1 (WASF1) and is correlated with poor prognosis of patients in several cancer types. Our results, however, show that NCKAP1 is correlated with a favorable outcome in HCC patients. The underlying mechanism of this contradictory phenomenon is unknown. The current study was designed to explore the mechanism of NCKAP1 in HCC. As a result, clinicopathological correlations and results from in vivo and in vitro models indicated that NCKAP1 was a tumor suppressor gene. Cell cycle analysis suggested that NCKAP1 inhibit cells from entering G2/M phase. Western blot analysis showed that WASF1 was barely expressed in HCC cell lines compared to that of breast cancer cell lines, which serve as positive controls. Furthermore, Rb1 and p53 expression was upregulated in cell lines overexpressing NCKAP1. Expression of several cell cycle regulating proteins also varied in the HCC cell lines. In conclusion, although previous studies have identified NCKAP1 as a cell invasion promoter by binding to WASF1, we found that NCKAP1 is a tumor suppress gene that modulates the cell cycle of HCC cell lines by targeting Rb1/p53 regulation.

6.
Dig Liver Dis ; 51(10): 1430-1437, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31054962

RESUMO

BACKGROUND AND AIMS: The liver function reserve in Child-Pugh (C-P) grade A hepatocellular carcinoma (HCC) patients varies widely, and the value of platelet-albumin-bilirubin (PALBI) grade in predicting posthepatectomy liver failure (PHLF) grade B/C and overall survival (OS) remains unknown. METHODS: From Dec 2004 to Dec 2013, 2038 C-P grade A HCC patients after resection were enrolled. Univariate and multivariate analyses were performed to clarify the risk factors for PHLF grade B/C and OS. RESULTS: The PALBI grade had higher area under the curve values than albumin-bilirubin (ALBI) and C-P grade in predicting PHLF grade B/C (0.693, 0.683, 0.529 in the entire cohort; 0.677, 0.646, 0.516 in patients who underwent major resection). PALBI grade differentiated C-P grade A patients into three groups with distinct prognoses (P < 0.001), whereas ALBI grade differentiated C-P grade A patients into two groups (P < 0.001). Furthermore, PALBI grade identified three groups with clearly different prognoses in ALBI grade 1 patients (P = 0.032). Multivariate analyses showed that PALBI grade was one of the independent and significant prognostic factors of PHLF grade B/C and OS. CONCLUSIONS: PALBI grade offers a simple, objective and discriminatory method for risk stratification of PHLF grade B/C and OS in C-P grade A HCC patients following resection.

7.
Cancer Commun (Lond) ; 38(1): 61, 2018 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-30305149

RESUMO

BACKGROUND: The optimal strategy for adjuvant therapy after curative resection for hepatocellular carcinoma (HCC) patients with solitary tumor and microvascular invasion (MVI) is controversial. This trial evaluated the efficacy and safety of adjuvant transcatheter arterial chemoembolization (TACE) after hepatectomy versus hepatectomy alone in HCC patients with a solitary tumor ≥ 5 cm and MVI. METHODS: In this randomized, open-labeled, phase III trial, HCC patients with a solitary tumor ≥ 5 cm and MVI were randomly assigned (1:1) to receive either 1-2 cycles of adjuvant TACE after hepatectomy (Hepatectomy-TACE) or hepatectomy alone (Hepatectomy Alone). The primary endpoint was disease-free survival (DFS); the secondary endpoints included overall survival (OS) and adverse events. RESULTS: Between June 1, 2009, and December 31, 2012, 250 patients were enrolled and randomly assigned to the Hepatectomy-TACE group (n = 125) or the Hepatectomy Alone group (n = 125). Clinicopathological characteristics were balanced between the two groups. The median follow-up time from randomization was 37.5 months [interquartile range 18.3-48.2 months]. The median DFS was significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group [17.45 months (95% confidence interval [CI] 11.99-29.14) vs. 9.27 months (95% CI 6.05-13.70), hazard ratio [HR] = 0.70 (95% CI 0.52-0.95), P = 0.020], respectively. The median OS was also significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group [44.29 months (95% CI 25.99-62.58) vs. 22.37 months (95% CI 10.84-33.91), HR = 0.68 (95% CI 0.48-0.97), P = 0.029]. Treatment-related adverse events were more frequently observed in the Hepatectomy-TACE group, although these were generally mild and manageable. The most common grade 3 or 4 adverse events in both groups were neutropenia and liver dysfunction. CONCLUSION: Hepatectomy followed by adjuvant TACE is an appropriate option after radical resection in HCC patients with solitary tumor ≥ 5 cm and MVI, with acceptable toxicity.

8.
Front Physiol ; 9: 899, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30057554

RESUMO

Background: Fibroblast proliferation is a critical feature during heart failure development. Previous studies reported regulatory T-lymphocytes (Tregs)' protective role against myocardial fibrosis. However, notably, Tregs also secrete fibrogenic cytokine TGF-ß when activated. This study aimed to clarify the intriguing link between Tregs and fibrosis, the role of Tregs Kv1.3 potassium channel (regulating T-lymphocytes activation) in the fibrosis process, and how selective aldosterone receptor antagonist Eplerenone affects Tregs and fibrosis through its action on Kv1.3 channel. Methods and Results: After co-incubation with Tregs, cardiac fibroblast proliferation (CCK-8 assay) and levels of collagen I, III, and Matrix metalloproteinase2 (ELISA) significantly elevated. Cell viability assays, Kv1.3 channel mRNA (RT-qPCR), and protein expression (In-Cell Western Blotting) revealed Tregs were activated/proliferated when co-cultured with fibroblasts. Treg intracellular TGF-ß level increased by 5.8-fold, far more than that of intracellular IL-10, extracellular TGF-ß and IL-10 (ELISA). And 30 µM eplerenone suppressed Tregs proliferation by 82.77% and furthermore, suppressed intracellular TGF-ß level to a significantly greater extent than that of intracellular IL-10, extracellular TGF-ß and IL-10. Moreover, the Kv1.3 current (whole-cell patch clamp) of Tregs in congestive heart failure patients and rats (induced by coronary artery ligation and exhaustive exercise) elevated by >4-fold than that of healthy volunteers and control rats, whereas 30 µM eplerenone suppressed the current by >60% in control Tregs. In addition, docking calculations (AutoDock software 4.0 suite) showed eplerenone has higher H-bond energy with Kv1.3 channel than other selective blockers. Conclusion: Immuno-regulation in the late stage of CHF activates Tregs proliferation via the upregulation of Kv1.3 channels, which promotes cardiac fibrosis by primarily secreting TGF-ß. Taken together, eplerenone's high affinity to Kv1.3 channel enables it to antagonize the Kv1.3 channels directly to suppress Tregs proliferation, which in turn may play an immuno-regulatory role during CHF.

9.
Sci Rep ; 8(1): 6379, 2018 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-29686306

RESUMO

Necroptosis is an essential pathophysiological process in cerebral ischemia-related diseases. Therefore, targeting necroptosis may prevent cell death and provide a much-needed therapy. Ansiomycin is an inhibitor of protein synthesis which can also activate c-Jun N-terminal kinases. The present study demonstrated that anisomycin attenuated necroptosis by upregulating CHIP (carboxyl terminus of Hsc70-interacting protein) leading to the reduced levels of receptor-interacting protein kinase 1 (RIPK1) and receptor-interacting protein kinase 3 (RIPK3) proteins in two in vitro models of cerebral ischemia. Further exploration in this research revealed that losing neither the co-chaperone nor the ubiquitin E3 ligase function of CHIP could abolish its ability to reduce necroptosis. Collectively, this study identifies a novel means of preventing necroptosis in two in vitro models of cerebral ischemia injury through activating the expression of CHIP, and it may provide a potential target for the further study of the disease.

10.
Clin Exp Pharmacol Physiol ; 45(8): 779-787, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29570827

RESUMO

Mitochondrial dysfunction contributes to the pathogenesis of cardiac hypertrophy. The disequilibrium of mitochondrial dynamic, which refers to mitochondrial fusion and fission, leads to mitochondrial morphology alteration and dysfunction. Enhanced understanding of the molecular mechanisms in depth may shed light on the therapy of the disease. In this study, we show that mitochondrial fission factor (MFF) is up-regulated upon hypertrophic agonist noradrenaline (NA) treatment. Knockdown of MFF attenuated NA induced mitochondrial fission and cardiac hypertrophy. Mitochondrial fission factor is a direct target of miR-376b-3p, which attenuated expression enhanced MFF expression through binding to its 3'UTR. Expression of miR-376b-3p weakened the fragmentation of mitochondria as well as decreased hypertrophic response through regulating MFF in NA treated neonatal rat ventricular cells (NRVCs). This study suggested that miR-376b-3p is a novel modulator affecting mitochondrial morphology through targeting MFF.

11.
Nat Plants ; 4(2): 82-89, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29379155

RESUMO

Gnetophytes are an enigmatic gymnosperm lineage comprising three genera, Gnetum, Welwitschia and Ephedra, which are morphologically distinct from all other seed plants. Their distinctiveness has triggered much debate as to their origin, evolution and phylogenetic placement among seed plants. To increase our understanding of the evolution of gnetophytes, and their relation to other seed plants, we report here a high-quality draft genome sequence for Gnetum montanum, the first for any gnetophyte. By using a novel genome assembly strategy to deal with high levels of heterozygosity, we assembled >4 Gb of sequence encoding 27,491 protein-coding genes. Comparative analysis of the G. montanum genome with other gymnosperm genomes unveiled some remarkable and distinctive genomic features, such as a diverse assemblage of retrotransposons with evidence for elevated frequencies of elimination rather than accumulation, considerable differences in intron architecture, including both length distribution and proportions of (retro) transposon elements, and distinctive patterns of proliferation of functional protein domains. Furthermore, a few gene families showed Gnetum-specific copy number expansions (for example, cellulose synthase) or contractions (for example, Late Embryogenesis Abundant protein), which could be connected with Gnetum's distinctive morphological innovations associated with their adaptation to warm, mesic environments. Overall, the G. montanum genome enables a better resolution of ancestral genomic features within seed plants, and the identification of genomic characters that distinguish Gnetum from other gymnosperms.

12.
Clin Interv Aging ; 12: 2047-2054, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29238180

RESUMO

Purpose: The incidence of proximal humeral fractures is high in the elderly, and the superior management of these fractures remains a controversy. The study aims to compare clinical outcomes of intramedullary nails, locking plates and conservative treatment for the management of displaced proximal humeral fractures in the elderly. Patients and methods: In this prospective study, a total of 198 patients with 2- or 3-part proximal humeral fractures who received fixation of locking plates or intramedullary nails or conservative treatment were included. The primary outcome was the 24-month Constant-Murley score. The secondary outcomes included the American Shoulder and Elbow Surgeons (ASES) scores, the visual analog scale (VAS) pain scores, shoulder range of motion and complication rate. Results: There were no statistically significant differences in the Constant-Murley scores and ASES scores among the plate group, the nail group and the conservative group for 2-part fractures. For 3-part fractures, Constant-Murley scores and ASES scores were lower in the conservative group compared with those in the plate group and the nail group. Besides, the conservative group showed a significantly lower external rotation during follow-ups. The complication rate was comparable among the plate group, the nail group and the conservative group for both 2-part and 3-part fractures. Conclusion: Similar satisfactory functional outcomes can be achieved with the locking plates, intramedullary nails or conservative treatment for 2-part proximal humeral fractures in the elderly. The advantages in functional outcomes favor locking plates and intramedullary nails in the management of 3-part proximal humeral fractures.


Assuntos
Fixação Intramedular de Fraturas/métodos , Fixadores Internos , Fraturas do Ombro/cirurgia , Idoso , Idoso de 80 Anos ou mais , Pinos Ortopédicos , Placas Ósseas , Tratamento Conservador , Feminino , Humanos , Incidência , Masculino , Satisfação do Paciente , Estudos Prospectivos , Amplitude de Movimento Articular , Resultado do Tratamento
13.
Oncotarget ; 8(52): 89867-89875, 2017 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-29163794

RESUMO

Recently, a novel locus at chromosome 6p25 (rs12204590, near FOXF2) associated with an increased risk of stroke in European populations was identified. However, whether polymorphisms in FOXF2 are also associated with the incidence of ischemic stroke in other populations remains unknown. In this case-control study, 803 Chinese Han patients with ischemic stroke and 803 matched control individuals were enrolled. Four tag SNPs and rs12204590 located in or near FOXF2 were selected, and the associations between genotypes/alleles and ischemic stroke were analyzed. In our study, we did not detect an association between the previously reported locus rs12204590 and ischemic stroke. By the genotype analysis, a novel SNP rs1711972, near FOXF2, was observed to be associated with an increased risk of ischemic stroke(CA genotype, adjusted OR = 1.35; 95% CI, 1.07 to 1.70), but not significantly after Bonferroni corrections for multiple tests. However, in the subgroup analysis, we discovered that rs1711972 was associated with an increased risk of large-artery atherosclerotic stroke in the additive model (P = 0.020; CA genotype, adjusted OR = 1.50; 95%CI, 1.09 to 2.07) and dominant model (P = 0.010; OR = 1.47; 95%CI, 1.09 to 1.99). Collectively, these results indicate that a novel SNP near FOXF2 may influence the risk of large-artery atherosclerotic stroke in Chinese Han population.

14.
Chin J Cancer ; 36(1): 83, 2017 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-29061175

RESUMO

BACKGROUND: Transarterial chemoembolization (TACE) is recommended as the standard care for unresectable hepatocellular carcinoma (HCC) at Barcelona Clinic Liver Cancer (BCLC) stage A-B. However, the efficacy of TACE on large (≥ 10 cm) stage A-B HCC is far from satisfactory, and it is proposed that hepatic artery infusion chemotherapy (HAIC) might be a better first-line treatment of this disease. Hence, we compared the safety and efficacy of HAIC with the modified FOLFOX (mFOLFOX) regimen and those of TACE in patients with massive unresectable HCC. METHODS: A prospective, non-randomized, phase II study was conducted on patients with massive unresectable HCC. The protocol involved HAIC with the mFOLFOX regimen (oxaliplatin, 85 mg/m2 intra-arterial infusion; leucovorin, 400 mg/m2 intra-arterial infusion; and fluorouracil, 400 mg/m2 bolus infusion and 2400 mg/m2 continuous infusion) every 3 weeks and TACE with 50 mg of epirubicin, 50 mg of lobaplatin, 6 mg of mitomycin, and lipiodol and polyvinyl alcohol particles. The tumor responses, time-to-progression (TTP), and safety were assessed. RESULTS: A total of 79 patients were recruited for this study: 38 in the HAIC group and 41 in the TACE group. The HAIC group exhibited higher partial response and disease control rates than did the TACE group (52.6% vs. 9.8%, P < 0.001; 83.8% vs. 52.5%, P = 0.004). The median TTPs for the HAIC and TACE groups were 5.87 and 3.6 months (hazard radio [HR] = 2.35, 95% confidence interval [CI] = 1.16-4.76, P = 0.015). More patients in the HAIC group than in the TACE group underwent resection (10 vs. 3, P = 0.033). The proportions of grade 3-4 adverse events (AE) and serious adverse events (SAE) were lower in the HAIC group than in the TACE group (grade 3-4 AEs: 13 vs. 27, P = 0.007; SAEs: 6 vs. 15, P = 0.044). More patients in the TACE group than in the HAIC group had the study treatment terminated early due to intolerable treatment-related adverse events or the withdrawal of consent (10 vs. 2, P = 0.026). CONCLUSIONS: HAIC with mFOLFOX yielded significantly better treatment responses and less serious toxicity than did TACE. HAIC might represent a feasible and promising first-line treatment for patients with massive unresectable HCC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Resultado do Tratamento
15.
Cell Death Dis ; 8(9): e3043, 2017 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-28880268

RESUMO

We have previously reported that Cezanne could be a prognostic biomarker for survival in hepatocellular carcinoma (HCC) patients. However, the role of Cezanne genes in HCC cells and its response to postoperative adjuvant transcatheter arterial chemoembolization (TACE) in HCC patients remains unknown. In this study, Cezanne expression was detected in human HCC using real-time PCR, western blot and immunohistochemistry. The function of Cezanne in HCC cells was determined by Transwell invasion assays and nude mice metastasis assay. The response of Cezanne in patients who received adjuvant TACE after hepatectomy was evaluated. Functional study demonstrated that interference of Cezanne expression promoted the migration and invasion of HCC cells in vitro and boosted metastasized HCC formation in mice. Upregulation of Cezanne diminished the adhesion and migration of hepatoma cells. Further study indicated that Cezanne might inhibit invasion of HCC cells by inducing epithelial-mesenchymal transition (EMT). In addition, patients with low Cezanne expression had significant improvement in prognosis after receiving adjuvant TACE. In contrast, patients with high Cezanne expression had a poorer response to adjuvant TACE. Moreover, Cezanne status was associated with response to adjuvant TACE in patients subgroup stratified by vascular invasion, tumor size and tumor number. In conclusion, Cezanne may be a novel antioncogene that has a pivotal role in the invasion of HCC and contribute to the selection of patients who may benefit from adjuvant TACE to prevent recurrence.


Assuntos
Carcinoma Hepatocelular/genética , Quimioembolização Terapêutica , Endopeptidases/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , Recidiva Local de Neoplasia/genética , Idoso , Animais , Antígenos CD , Caderinas/genética , Caderinas/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/secundário , Carcinoma Hepatocelular/cirurgia , Linhagem Celular Tumoral , Movimento Celular , Progressão da Doença , Endopeptidases/metabolismo , Transição Epitelial-Mesenquimal , Feminino , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/cirurgia , Transplante de Neoplasias , Prognóstico , Transdução de Sinais , Carga Tumoral , Vimentina/genética , Vimentina/metabolismo
16.
World J Gastroenterol ; 23(23): 4278-4284, 2017 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-28694668

RESUMO

AIM: To investigate the evaluation of neogalactosylalbumin (NGA) for liver function assessment based on positron emission tomography technology. METHODS: Female Kunming mice were assigned randomly to two groups: fibrosis group and normal control group. A murine hepatic fibrosis model was generated by intraperitoneal injection of 10% carbon tetrachloride (CCl4) at 0.4 mL every 48 h for 42 d. 18F-labeled NGA ([18F]FNGA) was synthesized and administered at a dosage of 3.7 MBq/mouse to both fibrosis mice and normal control mice. Distribution of [18F]FNGA amongst organs was examined, and dynamic scanning was performed. Parameters were set up to compare the uptake of tracers by fibrotic liver and healthy liver. Serologic tests for liver function were also performed. RESULTS: The liver function of the fibrosis model mice was significantly impaired by the use of CCl4. In the fibrosis model mice, hepatic fibrosis was verified by naked eye assessment and pathological analysis. [18F]FNGA was found to predominantly accumulate in liver and kidneys in both control group (n = 21) and fibrosis group (n = 23). The liver uptake ability (LUA), peak time (Tp), and uptake rate (LUR) of [18F]FNGA between healthy liver (n = 8) and fibrosis liver (n = 10) were significantly different (P < 0.05, < 0.01, and < 0.05, respectively). LUA was significantly correlated with total serum protein level (TP) (P < 0.05). Tp was significantly correlated with both TP and glucose (Glu) concentration (P < 0.05 both), and LUR was significantly correlated with both total bile acid and Glu concentration (P < 0.01 and < 0.05, respectively). CONCLUSION: [18F]FNGA mainly accumulated in liver and remained for sufficient time. Functionally-impaired liver showed a significant different uptake pattern of [18F]FNGA compared to the controls.


Assuntos
Albuminas/química , Cirrose Hepática/diagnóstico por imagem , Fígado/diagnóstico por imagem , Animais , Tetracloreto de Carbono , Modelos Animais de Doenças , Feminino , Processamento de Imagem Assistida por Computador , Rim/diagnóstico por imagem , Rim/patologia , Ligantes , Hepatopatias/metabolismo , Testes de Função Hepática , Camundongos , Tomografia por Emissão de Pósitrons
17.
Nan Fang Yi Ke Da Xue Xue Bao ; 37(6): 802-806, 2017 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-28669956

RESUMO

OBJECTIVE: To investigate the changes in the expression level of sRNA SpR19 and its potential target protein GroEL in clinical isolates of Streptococcus mutans with different cariogenicity exposed to different pH conditions and explore the possibility of using these molecules as biomarkers for assessing the cariogenicity of the bacteria. METHODS: The total RNAs were extracted from the clinical isolates of Streptococcus mutans with high (strain 17) and low cariogenicity (strain 5) for high-throughput sequencing for profiling of the differentially expressed sRNAs. The candidate sRNA, SpR19, was selected for further study on the basis of bioinformatics analysis considering the role of its potential target in the cariogenic process. The differential expression levels of SpR19 in the strains exposed to both pH5.5 and pH7 culture conditions were verified by quantitative real-time PCR. The expression of the potential target of SpR19, GroEL, was also investigated at both the protein and mRNA level using Western blotting and quantitative real-time PCR. RESULTS: Bioinformatic analysis suggested multiple potential target sites of SpR19 both in GroEL mRNA and in the upstream and downstream inter-genic regions. Under different pH conditions, the highly cariogenic strain 17 expressed consistently low levels of SpR19 as compared with the strain 5 with a low cariogenicity; GroEL showed a reverse expression pattern in the 2 strains. An inverse correlation was found between the expressions of SpR19 and GroEL. CONCLUSION: The highly cariogenic strain 17 expressed low levels of SpR19 and high levels of GroEL in both acidic and neutral culture conditions. SpR19 may negatively regulate the cariogenicity of Streptococcus mutants by targeting at GroEL.


Assuntos
Chaperonina 60/metabolismo , MicroRNAs/genética , RNA Bacteriano/genética , Streptococcus mutans/genética , Streptococcus mutans/patogenicidade , Chaperonina 60/genética , Cárie Dentária/microbiologia
19.
World J Gastroenterol ; 23(17): 3122-3132, 2017 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-28533669

RESUMO

AIM: To investigate whether the preoperative neutrophil-to-lymphocyte ratio (NLR) could predict the prognosis of hepatocellular carcinoma (HCC) patients with portal/hepatic vein tumor thrombosis (PVTT/HVTT) after hepatectomy. METHODS: The study population included 81 HCC patients who underwent hepatectomy and were diagnosed with PVTT/HVTT based on pathological examination. The demographics, laboratory analyses, and histopathology data were analyzed. RESULTS: Overall survival (OS) and disease-free survival (DFS) were determined in the patients with a high (> 2.9) and low (≤ 2.9) NLR. The median OS and DFS duration in the high NLR group were significantly shorter than those in the low NLR group (OS: 6.2 mo vs 15.7 mo, respectively, P = 0.007; DFS: 2.2 mo vs 3.7 mo, respectively, P = 0.039). An NLR > 2.9 was identified as an independent predictor of a poor prognosis of OS (P = 0.034, HR = 1.866; 95%CI: 1.048-3.322) in uni- and multivariate analyses. Moreover, there was a significantly positive correlation between the NLR and the Child-Pugh score (r = 0.276, P = 0.015) and the maximum diameter of the tumor (r = 0.435, P < 0.001). Additionally, the NLR could enhance the prognostic predictive power of the CLIP score for DFS in these patients. CONCLUSION: The preoperative NLR is a prognostic predictor after hepatectomy for HCC patients with PVTT/HVTT. NLR > 2.9 indicates poorer OS and DFS.


Assuntos
Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/sangue , Linfócitos , Neutrófilos , Trombose Venosa/sangue , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Hepatectomia , Veias Hepáticas/patologia , Humanos , Estimativa de Kaplan-Meier , Fígado/irrigação sanguínea , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Veia Porta/patologia , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Trombose Venosa/etiologia , Trombose Venosa/patologia
20.
J Cancer ; 8(6): 1030-1037, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28529616

RESUMO

Objective: Great heterogeneity exists in clinical behavior and survival outcome in patients with stage IE/IIE extranodal natural killer/T-cell lymphoma, nasal type (ENKTL). In this study, we proposed lymphocyte/monocyte ratio (LMR) as a new prognostic factor for these early stage ENKTL. Methods: We retrospectively examined the LMR as a prognostic variable in a cohort of 379 patients with newly diagnosed stage IE/IIE ENKTL. The relationship between the LMR and clinicopathologic variables were analyzed in Kaplan-Meier log-rank survival analysis, and the Cox proportional hazards model was used to determine the survival significance of the LMR for both progression-free survival (PFS) and overall survival (OS). Results: Patients were categorized into two different groups based on the LMR using cut-off value of 2.0. The 5-year PFS rates in the low and high LMR group were 43.9% and 62.7%, respectively, and the 5-year OS rates in the two groups were 59.1% and 77.7%, respectively. In multivariate analysis, low LMR at diagnosis was associated with worse PFS (hazard ratio 1.611, 95% confidence interval: 1.027-2.525, P =0.038) independent of age (P=0.033) and treatment stratagem (P<0.001), and indicated worse OS (hazard ratio 2.003, 95% confidence interval: 1.124-3.569, P =0.018) independent of age (P=0.007), LDH level (P=0.042), local tumor invasiveness (P=0.008), and treatment stratagem (P<0.001). Conclusion: The LMR is an independent prognostic factor for both DFS and OS in patients with stage IE/IIE ENKTL, and provides additional prognostic value beyond standard clinicopathological parameters.

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