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1.
Chem Commun (Camb) ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34636370

RESUMO

MAO-A promotes the proliferation of human glioma cells. Herein, we report a series of MAO-A specific two-photon small molecular fluorescent probes (A1-5) based on an intramolecular charge transfer enhancing strategy. The activity of endogenous MAO-A can be selectively imaged using A3 as a representative probe in different biological samples including human glioma cells/tissues via two-photon fluorescence microscopy. The study provides new tools for the visual detection of glioma.

2.
J Hazard Mater ; : 127409, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34629196

RESUMO

In-situ microemulsion flushing is an effective remediation technology for the removal of dense non-aqueous phase liquids (DNAPLs) from aquifers. Nitrobenzene (NB) is a typical DNAPL pollutant that is responsible for the serious contamination of many groundwater systems, while its removal using the flushing method has rarely been studied. In this study, bench scale, 1-D column and 2-D tank experiments were conducted to establish an efficient salt-free sodium dodecyl sulfate (SDS)/1-butanol based in-situ microemulsion flushing system for NB contaminated aquifers. Results showed that the NB/SDS/1-butanol/water microemulsion increased dissolved NB concentrations by more than 15-fold compared to the SDS-only solution. The formulation also presented good solubilization capacity at low temperature (5 â„ƒ) and with clay media. NB was effectively removed from the aquifer by solubilization and mobilization via the formation of the microemulsion with the injected SDS/1-butanol solution. The flushing system also reduced the tailing phenomenon in later remediation stages, and exhibited weak reagent adsorption onto aquifer media. Furthermore, the vertical DNAPL migration to deeper aquifer was effectively controlled. Therefore, the constructed in-situ microemulsion flushing system is a highly efficient treatment method for NB contaminated aquifers, with this study providing valuable reference information on the optimal reagent parameters and the remediation mechanism.

3.
J Hematol Oncol ; 14(1): 165, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34641921

RESUMO

BACKGROUND AND AIMS: Although adjuvant transcatheter arterial chemoembolization (TACE) for resected hepatocellular carcinoma (HCC) may improve survival for some patients, identifying which patients can benefit remains challenging. The present study aimed to construct a survival prediction calculator for individualized estimating the net survival benefit of adjuvant TACE for patients with resected HCC. METHODS: From a multicenter database, consecutive patients undergoing curative resection for HCC were enrolled and divided into the developing and validation cohorts. Using the independent survival predictors in the developing cohort, two nomogram models were constructed for patients with and without adjuvant TACE, respectively, which predictive performance was validated internally and externally by measuring concordance index (C-index) and calibration. The difference between two estimates of the prediction models was the expected survival benefit of adjuvant TACE. RESULTS: A total of 2514 patients met the inclusion criteria for the study. The nomogram prediction models for patients with and without adjuvant TACE were, respectively, built by incorporating the same eight independent survival predictors, including portal hypertension, Child-Pugh score, alpha-fetoprotein level, tumor size and number, macrovascular and microvascular invasion, and resection margin. These two prediction models demonstrated good calibration and discrimination, with all the C-indexes of greater than 0.75 in the developing and validation cohorts. A browser-based calculator was generated for individualized estimating the net survival benefit of adjuvant TACE. CONCLUSIONS: Based on large-scale real-world data, an easy-to-use online calculator can be adopted as a decision aid to predict which patients with resected HCC can benefit from adjuvant TACE.

4.
ACS Chem Neurosci ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34668369

RESUMO

Elevated HClO gets involved in the pathogenesis of Parkinson's disease (PD). Herein, a novel fluorescent probe NUU-1 was designed and synthesized. Distinct from the general strategies, NUU-1 features two distinct HClO reactive sites, a HClO-specific reaction site and a HClO-nonspecific reactive site, which in turn endows NUU-1 with the "0 + 1 > 1" amplification effect, that thus dramatically promotes the selectivity. NUU-1 displayed a fast response rate (within 15 s), remarkable fluorescence enhancement (about 538-fold), and excellent sensitivity (LOD = 25.8 nM) in response to HClO while the remaining fluorescence silence toward other common ROS (H2O2, •OH, ONOO-, O2•-, and 1O2) even at high concentrations (up to 0.5 mM). NUU-1 allows for the imaging of both exogenous and endogenous HClO in living dopaminergic cells (SH-SY5Y). Moreover, by employing NUU-1 as the probe, the image of HClO in C. elegans and zebrafish was successfully achieved. Significantly, in the first trial, NUU-1 was successfully utilized for the brain basal HClO imaging in PD mice models and distinguished PD brain tissues from normal control, thereby holding great potential for in-depth biological applications.

5.
Stem Cell Rev Rep ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34546510

RESUMO

Adult neurogenesis is the ongoing generation of functional new neurons from neural progenitor cells (NPCs) in the mammalian brain. However, this process declines with aging, which is implicated in the recession of brain function and neurodegeneration. Understanding the mechanism of adult neurogenesis and stimulating neurogenesis will benefit the mitigation of neurodegenerative diseases. Autophagy, a highly conserved process of cellular degradation, is essential for maintaining cellular homeostasis and normal function. Whether and how autophagy affects adult neurogenesis remains poorly understood. In present study, we revealed a close connection between impaired autophagy and adult neurogenetic decline. Expression of autophagy-related genes and autophagic activity were significantly declined in the middle-adult subventricular/subgranular zone (SVZ/SGZ) homogenates and cultured NPCs, and inhibiting autophagy by siRNA interference resulted in impaired proliferation and differentiation of NPCs. Conversely, stimulating autophagy by rapamycin not only revitalized the viability of middle-adult NPCs, but also facilitated the neurogenesis in middle-adult SVZ/SGZ. More importantly, autophagic activation by rapamycin also ameliorated the olfactory sensitivity and cognitional capacities in middle-adult mice. Taken together, our results reveal that compromised autophagy is involved in the decline of adult neurogenesis, which could be reversed by autophagy activation. It also shed light on the regulation of adult neurogenesis and paves the way for developing a therapeutic strategy for aging and neurodegenerative diseases.

6.
Biomed Res Int ; 2021: 8849415, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34337056

RESUMO

Hepatocellular carcinoma (HCC) is a common malignant tumor of the digestive system, and its early asymptomatic characteristic increases the difficulty of diagnosis and treatment. This study is aimed at obtaining some novel biomarkers with diagnostic and prognostic meaning and may find out potential therapeutic targets for HCC. We screen differentially expressed genes (DEGs) from the HCC gene expression profile GSE14520 using GEO2R. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted by using the clusterProfiler software while a protein-protein interaction (PPI) network was performed based on the STRING database. Then, prognosis analysis of hub genes was conducted using The Cancer Genome Atlas (TCGA) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to further verify the expression of hub genes and explore the correlation between gene expression and clinicopathological parameters. A total of 1053 DEGs were captured, containing 497 upregulated genes and 556 downregulated genes. GO and KEGG analysis indicated that the downregulated DEGs were mainly enriched in the fatty acid catabolic process while upregulated DEGs were primarily enriched in the cell cycle. Simultaneously, ten hub genes (CYP3A4, UGT1A6, AOX1, UGT1A4, UGT2B15, CDK1, CCNB1, MAD2L1, CCNB2, and CDC20) were identified by the PPI network. Five prognosis-related hub genes (CYP3A4, CDK1, CCNB1, MAD2L1, and CDC20) were uncovered by the survival analysis based on TCGA database. The ten hub genes were further validated by qRT-PCR using samples obtained from our hospital. The prognosis-related hub genes such as CYP3A4, CDK1, CCNB1, MAD2L1, and CDC20 could be considered potential diagnosis biomarkers and prognosis targets for HCC. We also use Oncomine for further verification, and we found CCNB1, CCNB2, CDK1, and CYP3A4 which were highly expressed in HCC. Meanwhile, CCNB1, CCNB2, and CDK1 are highly expressed in almost all cancer types, which may play an important role in cancer. Still, further functional study should be conducted to explore the underlying mechanism and biological effect in the near future.


Assuntos
Carcinoma Hepatocelular/genética , Biologia Computacional , Redes Reguladoras de Genes , Neoplasias Hepáticas/genética , Transdução de Sinais/genética , Adulto , Idoso , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Análise de Sobrevida , Transcriptoma , Regulação para Cima/genética
7.
Front Oncol ; 11: 700228, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395268

RESUMO

Background: Hepatocellular carcinoma (HCC) is one of the most serious consequences of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. This study sought to investigate long-term outcomes after liver resection for HCC among patients with HBV/HCV co-infection (HBV/HCV-HCC) compared with patients with HBV infection (HBV-HCC). Methods: Patients who underwent curative-intent liver resection for HCC were identified from a multicenter Chinese database. Using propensity score matching (PSM), patients with HBV/HCV-HCC were matched one-to-one to patients with HBV-HCC. Overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups before and after PSM. Results: Among 2,467 patients identified, 93 (3.8%) and 2,374 (96.2%) patients had HBV/HCV-HCC and HBV-HCC, respectively. Compared with patients with HBV-HCC, patients with HBV/HCV-HCC were older, have poorer liver-related characteristics but better tumor-related characteristics. PSM created 88 pairs of patients with comparable liver- and tumor-related characteristics (all P > 0.2). In the PSM cohort, the 3- and 5-year RFS rates in patients with HBV/HCV-HCC were 48.3% and 38.9%, which were significantly poorer than patients with HBV-HCC (61.8% and 49.2%, P = 0.037). Meanwhile, the 3- and 5-year OS rates in patients with HBV/HCV-HCC were also poorer than patients with HBV-HCC (65.4% and 51.1% vs. 73.7% and 63.0%), with a difference close to be significant between them (P = 0.081). Conclusion: Comparing to patients with HBV-HCC, liver resection resulted in relatively poorer long-term surgical outcomes in patients with HBV/HCV-HCC.

8.
Bioresour Technol ; 338: 125523, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34265594

RESUMO

Light spectrum can influence microalgal growth and metabolites accumulation significantly. However, the related mechanism has not been fully elucidated. Here, an oleaginous microalga Eustigmatos cf. polyphem, which also featured with high content of palmitoleic acid (POA) and ß-carotene, was cultured with LEDs-based red light (RL) and blue light (BL). The results showed that the biomass, total lipid content and POA content were much higher under RL than these under BL, regardless of nitrogen concentration. However, the ß-carotene content under RL was significantly lower than that under BL. Transcriptomic analysis revealed that photosynthesis, central carbon metabolism, fatty acid and glycerolipid biosynthesis were elevated, supporting the fast cell growth and high lipid content with POA under RL. In contrast, upregulation of key enzymes in carotenoids biosynthesis and suppression of ß-carotene conversion promoted ß-carotene accumulation under BL. These findings provide a feasible strategy for promoting lipids, POA and ß-carotene in E. cf. polyphem.


Assuntos
Microalgas , Estramenópilas , Biomassa , Luz , Estramenópilas/genética , Transcriptoma/genética , beta Caroteno
9.
Int J Clin Oncol ; 26(9): 1575-1586, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34160742

RESUMO

Surgical resection is the only potentially curative treatment for patients with resectable perihilar cholangiocarcinoma (PHC). There is still no consensus on the value of lymphadenectomy despite evidence indicating lymph node (LN) status is an important prognostic indicator for postoperative long-term survival. We sought to perform a meta-analysis to summarize the current evidence on the value of lymphadenectomy among patients undergoing surgery for PHC. The PubMed (OvidSP), Embase and Cochrane Library were systematically searched for studies published before July 2020 that reported on lymphadenectomy at the time of surgery for PHC after curative surgery. 7748 patients from 28 studies were included in the meta-analysis. No survival benefit was identified with increased number of LN resected (all P > 0.05). Meanwhile, overall LN status was an important prognostic factor. Patients with lymph node metastasis had a pooled estimate hazard ratio of death that was over two-fold higher than patients without lymph node metastasis (HR 2.07, 95% CI 1.65-2.59, P < 0.001). The examination of 5 LNs on histology was associated with better staging of lymph node status and stratification of patients into positive or negative LN groups. While the extent of LN dissection was not associated with a survival benefit, examination of more than 5 LNs better staged patients into positive or negative LN groups with a lower risk of nodal understaging.

10.
J Mater Chem B ; 9(28): 5583-5598, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34161402

RESUMO

Gold nanomaterials have potential applications in biosensors and biomedicine due to their controllable synthesis steps, high biocompatibility, low toxicity and easy surface modification. However, there are still various limitations including low water solubility and stability, which greatly affect their applications. In addition, some synthetic methods are very complicated and costly. Therefore, huge efforts have been made to improve their properties. This review mainly introduces the strategies for surface modification of gold nanomaterials, such as amines, biological small molecules and organic small molecules as well as the biological applications of these functionalized AuNPs. We aim to provide effective ideas for better functionalization of gold nanomaterials in the future.

11.
Eur J Surg Oncol ; 47(10): 2551-2560, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33934940

RESUMO

BACKGROUND & AIMS: Postoperative morbidity following hepatectomy for hepatocellular carcinoma (HCC) is common and its impact on long-term oncological outcome remains unclear. This study aimed to investigate if postoperative morbidity impacts long-term survival and recurrence following hepatectomy for HCC. METHODS: The data from a multicenter Chinese database of curative-intent hepatectomy for HCC were analyzed, and independent risks of postoperative 30-day morbidity were identified. After excluding patients with postoperative early deaths (≤90 days), early (≤2 years) and late (>2 years) recurrence rates, overall survival (OS), and time-to-recurrence (TTR) were compared between patients with and without postoperative morbidity. RESULTS: Among 2,161 patients eligible for the study, 758 (35.1%) had postoperative 30-day morbidity. Multivariable logistic regression analysis showed that diabetes mellitus, obesity, Child-Pugh grade B, cirrhosis, and intraoperative blood transfusion were independent risks of postoperative morbidity. The rates of early and late recurrence among patients with postoperative morbidity were higher than those without (50.7% vs. 38.8%, P < 0.001; and 41.7% vs. 34.1%, P = 0.017). Postoperative morbidity was associated with decreased OS (median: 48.1 vs. 91.6 months, P < 0.001) and TTR (median: 19.8 vs. 46.1 months; P < 0.001). After adjustment of confounding factors, multivariable Cox-regression analyses revealed that postoperative morbidity was associated with a 27.8% and 18.7% greater likelihood of mortality (hazard ratio 1.278; 95% confidence interval: 1.126-1.451; P < 0.001) and recurrence (1.187; 1.058-1.331; P = 0.004). CONCLUSION: This large multicenter study provides strong evidence that postoperative morbidity adversely impacts long-term oncologic prognosis after hepatectomy for HCC. The prevention and management of postoperative morbidity may be oncologically important.

12.
Environ Sci Technol ; 55(10): 6828-6837, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-33929820

RESUMO

Zero valent iron (ZVI) applications to remediation of shallow groundwaters can be affected by dissolved oxygen (DO) and organic ligands. To explore the intersection between these complicating factors, this study thoroughly characterized the reactions of nitrobenzene (NB) with ZVI in the presence DO and the model ligand ethylene diamine tetraacetic acid (EDTA). The results showed that NB is degraded by both ZVI reduction and ZVI-induced advanced oxidation under oxygen-limited conditions. The contribution of ·OH to the degradation of NB increased with time so that nearly 39% of NB was oxidized by ·OH at 15 min (pH = 3), but reduction was still the main pathway of NB transformation throughout. NB reduction products, such as aniline (AN), were also oxidized by ·OH. The lower the pH, the greater the contribution of advanced oxidation, but DO was the limiting factor for ·OH generation. Only 4.7% NB was fully degraded by ring opening and/or mineralization because the production of •OH was limited by low DO. After the transformation of NB and AN, other benzene ring and nitrogen-containing intermediates were identified (e.g., p-nitrophenol, p-aminophenol, hydroquinone, and p-benzoquinone). The removal of total organic carbon and total organic nitrogen was minimal. The results suggested that the relative doses of ZVI, DO, and iron-complexing ligands can be balanced for the optimal (rapid and deep) removal of organic contaminants.


Assuntos
Ferro , Poluentes Químicos da Água , Ácido Edético , Etilenos , Nitrobenzenos/análise , Oxirredução , Poluentes Químicos da Água/análise
13.
Appl Biochem Biotechnol ; 193(8): 2430-2442, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33710521

RESUMO

Tribonema biomass is considered promising biorefinery feedstock for the co-production of biodiesel and valuable bioproducts; however, the extraction of these useful compounds produces large amounts of algal residues, which produce increased environmental concerns. Herein, cellulose was extracted from the waste residue of T. utriculosum via alkalization and bleaching, followed by the production of high-value-added cellulose nanocrystals (CNCs) via acid hydrolysis. The hydrolysis was performed with 60% (wt%) H2SO4 at a yield of 13.31%, resulting in the generation of rod-shaped nanoparticles averaging 39.5 nm in diameter and 239.2 nm in length. The structural characterization analysis revealed that the prepared CNCs had high crystallinity (73.0%) due to the removal of non-cellulose components and amorphous regions by chemical treatment, as well as possessing good aqueous suspension stability (zeta potential = - 40.1 mV). Although the CNCs showed lower thermal stability than extracted cellulose, they spanned a broader temperature range due to two-stage degradation behaviour, with higher residue weight (16.7%). This work represents the first report on the preparation of a high-value-added industrial product, CNCs, from the filamentous microalga T. utriculosum, aiming to maximize benefits from waste algal residue reutilization.


Assuntos
Celulose/química , Chrysophyta/química , Microalgas/química , Nanopartículas/química , Hidrólise
14.
Am J Surg ; 222(4): 751-758, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33741185

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is common among adolescents and young adults (AYAs) in areas with endemic hepatitis B virus infection. We sought to characterize clinical features and long-term outcomes among AYAs versus older adults (OAs) who underwent HCC resection. METHODS: From a Chinese multicenter database, patients were categorized as AYA (aged 13-39 years) versus OA (aged ≥40 years). Patient clinical features, perioperative outcomes, overall survival (OS) and time-to-recurrence (TTR) were compared. Multivariable Cox-regression analyses were performed to identify the impact of age on OS and TTR. RESULTS: Among 1952 patients, 354(22.2%) were AYAs. AYAs were less likely to have cirrhosis yet were likely to have advanced tumor pathological characteristics than OAs. Postoperative morbidity and mortality were comparable. Compared with OAs, AYAs had a comparable OS but a decreased TTR. Multivariable analyses identified that young age (<40 years) was independently associated with poorer TTR. CONCLUSIONS: Compared with OAs, AYAs had a higher incidence of recurrence following liver resection among patients with HCC, suggesting that enhanced surveillance for postoperative recurrence may be required among AYAs.


Assuntos
Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Hepatite B/epidemiologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Adolescente , Adulto , Carcinoma Hepatocelular/mortalidade , China/epidemiologia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Recidiva Local de Neoplasia , Fatores de Risco , Taxa de Sobrevida
15.
J Hepatocell Carcinoma ; 8: 103-118, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33748017

RESUMO

Background: High alpha-fetoprotein (AFP) expressions (>400 ng/mL) are associated with poor oncological characteristics for hepatocellular carcinoma (HCC). However, prognosis after liver resection for high-AFP HCC is poorly studied. To investigate long-term recurrence and survival after hepatectomy for high-AFP HCC, and to identify the predictive value of postoperative incomplete biomarker response (IBR) on overall survival (OS) and recurrence-free survival (RFS). Methods: Patients undergoing curative resection for high-AFP HCC were analyzed. According to the decline magnitude of serum AFP as measured at first follow-up (4~6 weeks after surgery), all patients were divided into the complete biomarker response (CBR) and IBR groups. Characteristics, recurrence, and survival rates were compared. Univariate and Multivariate Cox-regression analyses were performed to identify independent predictors associated with poorer OS and RFS after liver resection for high-AFP HCC. Results: Among 549 patients, the overall and early recurrence rates in patients with IBR were significantly higher than patients with CBR (97.8%vs.56.4%, and 92.5%vs.33.3%, both P<0.001). On multivariate analysis, postoperative IBR was the strongest risk factor with the highest hazard ratio in predicting poor OS (HR 2.97; 95% CI 2.49~3.45; P<0.001) and RFS (HR 4.29; 95% CI 3.31~5.55; P<0.001). Conclusion: Postoperative biomarker response of serum AFP can be used in predicting recurrence and survival for high-AFP HCC patients. Once postoperative IBR was identified at first follow-up, subsequent enhanced recurrence surveillance and available treatments against recurrence should actively be considered.

16.
J Phycol ; 57(4): 1151-1166, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33529378

RESUMO

Commercial cultivation of eukaryotic microalgae has so far employed a unicellular form of species only (e.g., Chlorella pyrenoidosa, Dunaliella salina, and Haematococcus pluvialis). In this study, we assessed the feasibility of using the filamentous eukaryotic microalga Klebsormidium sp. LGX80 as a new cultivar for biomass and lipid production. The effects of different forms and concentrations of nitrogen on growth and lipid production of Klebsormidium sp. LGX80 were studied by using a glass column (ø4.5 × 60 cm) photobioreactor under laboratory conditions. Growth and lipid production of the new strain were further evaluated in an outdoor pilot-scale tubular photobioreactor. The results showed that when supplied with urea as a source of nitrogen Klebsormidium sp. LGX80 yielded a final biomass concentration of 8.49 ± 0.10 g · L-1 in which a cellular lipid content was 59.2 ± 0.4% DW. Under such conditions, the biomass and lipid productivities were 471.7 ± 5.9 and 248.1 ± 0.0 mg · L-1  · d-1 , respectively. Fatty acid analysis revealed that the main fatty acids of Klebsormidium sp. LGX80 were palmitic acid (C16:0), linoleic acid (C18:2ω6), and linolenic acid (C18:3ω3), of which linoleic acid (C18:2ω6) accounted for up to 67.5 ± 0.1% of total fatty acids. When grown outdoors in a 13,000-L tubular photobioreactor with an initial nitrogen concentration of 3 mM urea, Klebsormidium sp. LGX80 reached the highest biomass concentration of 2.63 ± 0.09 g · L-1 with the cells containing 38.0 ± 0.5% lipids (% DW), resulting in the volumetric biomass and lipid productivities of 147.2 ± 3.6 and 37.9 ± 0.9 mg · L-1  d-1 , respectively. The results of light:dark cycle experiment showed that a durative and prolonged light irradiation hindered the biosynthesis of chlorophyll a and chlorophyll b in the cells, but promoted the carotenoid accumulation. These results suggested that Klebsormidium sp. LGX80 can be a potential oleaginous filamentous microalga for commercial production of microalgal oils.

17.
Ther Adv Gastrointest Endosc ; 14: 2631774521993065, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33629062

RESUMO

Data on prognostic factors associated with outcome following resection of perihilar cholangiocarcinoma vary. We sought to define and characterize current available evidence on prognostic factors associated with perihilar cholangiocarcinoma after resection. The PubMed, Embase, and Cochrane library were systematically searched for relevant studies published before December 2019. Prognostic factors were identified from multivariate regression analyses in studies. Only high-quality studies were included (Newcastle-Ottawa Scale > 6 stars). A total of 45 studies involving 7338 patients were analyzed. The meta-analysis demonstrated that serum bilirubin levels (hazard ratio: 1.76, 95% confidence interval: 1.27-2.44), serum CA19-9 levels (hazard ratio: 1.32, 95% confidence interval: 1.05-1.65), tumor size (hazard ratio: 1.27, 95% confidence interval: 1.04-1.55), major vascular involvement (hazard ratio: 1.61, 95% confidence interval: 1.09-2.38), distance metastasis (hazard ratio: 17.60, 95% confidence interval: 2.01-154.09), perioperative blood transfusion (hazard ratio: 1.36, 95% confidence interval: 1.15-1.62), T-stage (hazard ratio: 1.96, 95% confidence interval: 1.47-2.61), lymph node metastasis (hazard ratio: 2.06, 1.83-2.31), resection margin status (hazard ratio: 2.34, 95% confidence interval: 1.89-2.89), not-well histology differentiation (hazard ratio: 2.03, 95% confidence interval: 1.69-2.44), perineural invasion (hazard ratio: 2.37, 95% confidence interval: 1.59-3.55), and lymphovascular invasion (hazard ratio: 1.41, 95% confidence interval: 1.15-1.73) were prognostic factors for poorer overall survival. Adjuvant chemotherapy (hazard ratio: 0.37, 95% confidence interval: 0.25-0.55) had a positive effect on prolonged overall survival. In addition, positive resection margin status (hazard ratio: 1.96, 95% confidence interval: 1.47-2.61) and lymph node metastasis (hazard ratio: 2.06, 95% confidence interval: 1.83-2.31) were associated with poorer disease-free survival. The prognostic factors identified in the present meta-analysis can be used to characterize patients in clinical practice and enrich prognostic tools, which could be included in future trial designs and generate hypotheses to be tested in future research to promote personalized treatment.

18.
Hepatol Int ; 15(2): 459-471, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33534082

RESUMO

BACKGROUND: Evidence-based decision-making is critical to optimize the benefits and mitigate futility associated with surgery for patients with malignancies. Untreated hepatocellular carcinoma (HCC) has a median survival of only 6 months. The objective was to develop and validate an individualized patient-specific tool to predict preoperatively the benefit of surgery to provide a survival benefit of at least 6 months following resection. METHODS: Using an international multicenter database, patients who underwent curative-intent liver resection for HCC from 2008 to 2017 were identified. Using random assignment, two-thirds of patients were assigned to a training cohort with the remaining one-third assigned to the validation cohort. Independent predictors of postoperative death within 6 months after surgery for HCC were identified and used to construct a nomogram model with a corresponding online calculator. The predictive accuracy of the calculator was assessed using C-index and calibration curves. RESULTS: Independent factors associated with death within 6 months of surgery included age, Child-Pugh grading, portal hypertension, alpha-fetoprotein level, tumor rupture, tumor size, tumor number and gross vascular invasion. A nomogram that incorporated these factors demonstrated excellent calibration and good performance in both the training and validation cohorts (C-indexes: 0.802 and 0.798). The nomogram also performed better than four other commonly-used HCC staging systems (C-indexes: 0.800 vs. 0.542-0.748). CONCLUSIONS: An easy-to-use online prediction calculator was able to identify patients at highest risk of death within 6 months of surgery for HCC. The proposed online calculator may help guide surgical decision-making to avoid futile surgery for patients with HCC.

19.
Pathol Res Pract ; 219: 153345, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33517164

RESUMO

The bromodomain protein zinc finger MYND-type containing 8 (ZMYND8) plays a critical role in human breast cancer. However, the expression and biological function of ZMYND8 in hepatocellular carcinoma (HCC) are poorly understood. In this study, ZMYND8 expression was found to be elevated in HCC based on the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases. Next, we confirmed that ZMYND8 was frequently overexpressed in HCC tissues compared with adjacent non-tumor tissues. The up-regulated level of ZMYND8 was also observed in HCC cell lines. Elevated ZMYND8 expression was correlated with unfavorable clinicopathological features and poor prognosis of HCC patients. Functionally, ectopic expression of ZMYND8 potentiated the proliferation, migration, and invasion of Hep3B cells. Conversely, ZMYND8 knockdown led to the reduced proliferation and invasiveness of HCCLM3 cells. ZMYND8 silencing restrained the growth of HCCLM3 cells in vivo. Mechanistically, ZMYND8 enhanced glucose consumption, lactate production, and ATP level in HCC cells. Pharmacological inhibition of glycolysis using 2-DG blocked the promoting effects of ZMYND8 on HCC cell proliferation and mobility. Furthermore, hexokinase 2 (HK2), a key enzyme of glycolysis, was identified as the downstream target of ZMYND8 in HCC cells. ZMYND8 promoted HK2 transcription by recruiting bromodomain containing 4 (BRD4) to its promoter. Knockdown of HK2 abrogated the oncogenic functions of ZMYND8 in HCC. Altogether, these data indicated that ZMYND8 promoted the growth and metastasis of HCC by promoting HK2-mediated glycolysis and might serve as a promising biomarker and therapeutic target for HCC.

20.
Onco Targets Ther ; 14: 111-122, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33442270

RESUMO

Background: Gastric cancer (GC) is one of the most common malignant tumors and the second most frequent cause of cancer death worldwide. Crocin is a kind of bioactive constituent found in the stigmas of saffron, which has shown various pharmacological activities. Methods: In this study, we investigated the inhibitory effect of crocin on gastric cancer AGS cells proliferation and explored the underlying mechanism. A series of methods were used including cell counting kit assay, gene microarray analysis, qRT-PCR, Celigo image cytometry, cell clone formation assay, Western blot, and cell xenograft growth in vivo. Results: The results indicated that crocin inhibited AGS cells proliferation and promoted cell apoptosis. Further studies suggested that crocin decreased a series of genes expression, among which TPM4 gene downregulation inhibited the tumor cells proliferation and tumor growth in mice, and overexpression of TPM4 gene abolishes the inhibitory effect of crocin. Further study using microarray analysis suggested that knocking down of TPM4 altered genes related to the proliferation and apoptosis of cells. Discussion: Crocin could inhibit the gastric cancer cells AGS cells proliferation by regulating TPM4 gene expression, and TPM4 may be a promising therapeutic target for GC treatment.

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