Publications by authors named "Wenwu Liu"

72 Publications

Circular RNA circ_0090231 promotes atherosclerosis in vitro by enhancing NLR family pyrin domain containing 3-mediated pyroptosis of endothelial cells.

Bioengineered 2021 Oct 12. Epub 2021 Oct 12.

Department of Cardiology, Affiliated Suzhou Science and Technology City Hospital of Nanjing Medical University, Suzhou, China.

Atherosclerosis (AS) is an inflammatory disease caused by multiple factors. Multiple circRNAs are involved in the development of AS. The present study focusses on delineating the role of circ_0090231 in AS. Human aortic endothelial cells (HAECs) were treated with oxidized low-density lipoprotein (ox-LDL) to construct an AS model. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the levels of circ_0090231, IL-1β, and IL-18 transcripts. CircRNA/ target gene interactions were predicted using StarBase and TargetScan and confirmed using an RNA pull-down assay and dual luciferase reporter assay. Further, 3-(4,5)-dimethylthiahiazo(-2)-3,5-diphenytetrazoliumromide (MTT) and lactate dehydrogenase (LDH) release assays were performed to evaluate cell viability and damage in the AS model, respectively. Cell pyroptosis and protein expression were determined using flow cytometry and western blotting respectively. The treatment of HAECs with ox-LDL not only led to significant increase in the levels of circ_0090231 but also resulted in improved cell viability as well as reduced cell injury and pyroptosis as compared to that in non-treated cells. The circ_0090231 was also identified to function as a sponge for miR-635, knockdown of which reverses the effects of circ_0090231 inhibition. Furthermore, our results revealed that levels of NLRP3, a miR-635 target, are not only augmented in the AS model but its overexpression also weakens the miR-635 regulatory effects in the AS development. Taken together, the circ_0090231/miR-635/NLRP3 axis affects the development of AS by regulating cell pyroptosis, thus providing new insights into the mechanism of AS development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21655979.2021.1989260DOI Listing
October 2021

Design, synthesis and biological evaluation of harmine derivatives as potent GSK-3β/DYRK1A dual inhibitors for the treatment of Alzheimer's disease.

Eur J Med Chem 2021 Oct 29;222:113554. Epub 2021 May 29.

School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang 110840, People's Republic of China. Electronic address:

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease, characterized by irreversible cognitive impairment, memory loss and behavioral disturbances, ultimately leading to death. Glycogen synthase kinase 3β (GSK-3β) and dual-specificity tyrosine phosphorylation regulated kinase1A (DYRK1A) have gained a lot of attention for its role in tau pathology. To search for potential dual GSK-3β/DYRK1A inhibitors, we focused on harmine, a natural β-carboline alkaloid, which has been extensively studied for its various biological effects on the prevention of AD. In this study, a new series of harmine derivatives were designed, synthesized and evaluated as dual GSK-3β/DYRK1A inhibitors for their multiple biological activities. The in vitro results indicated that most of them displayed promising activity against GSK-3β and DYRK1A. Among them, compound ZDWX-25 showed potent inhibitory effects on GSK-3β and DYRK1A with IC values of 71 and 103 nM, respectively. Molecular modelling and kinetic studies verified that ZDWX-25 could interact with the ATP binding pocket of GSK-3β and DYRK1A. Western blot analysis revealed that ZDWX-25 inhibited hyperphosphorylation of tau protein in okadaic acid (OKA)-induced SH-SY5Y cells. In addition, ZDWX-25 showed good blood-brain barrier penetrability in vitro. More importantly, ZDWX-25 could ameliorate the impaired learning and memory in APP/PS1/Tau transgenic mice. These results indicated that the harmine-based compounds could be served as promising dual-targeted candidates for AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2021.113554DOI Listing
October 2021

Cimicifuga dahurica extract inhibits the proliferation, migration and invasion of breast cancer cells MDA-MB-231 and MCF-7 in vitro and in vivo.

J Ethnopharmacol 2021 Sep 23;277:114057. Epub 2021 Mar 23.

School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110006, PR China; Liaoning Provincial Key Laboratory of TCM Resources Conservation and Development, Shenyang Pharmaceutical University, Shenyang, 110006, PR China. Electronic address:

Ethnopharmacological Relevance: Cimicifuga dahurica (Turcz.) Maxim (C. dahurica) has a long history of treating breast cancer. From the Qing Dynasty to the Tang Dynasty and even earlier, C. dahurica has been documented in the treatment of breast carbuncle (Breast cancer is classified as breast carbuncle in Chinese medicine). In traditional prescriptions such as "Sheng Ge Decoction", "Sheng Ma Powder" and "Breast Carbuncle Pill", as the main medicine, C. dahurica plays an important role. At present, the systematic studies on the in vitro and in vivo effects of Cimicifuga against breast cancer are rare, especially the C. dahurica.

Aim Of The Study: In this article, we evaluated the in vitro activity and in vivo effects of CREE (extract of the root of C. dahurica) against breast cancer, and discussed the possible mechanism of CREE in promoting breast cancer cell apoptosis.

Materials And Methods: The main component in the CREE was analyzed by HPLC. The effects of CREE on the proliferation, migration and invasion of human breast cancer cells were evaluated through SRB, colony assay, LDH release, wound healing and transwell assay. The pro-apoptotic effect of CREE was investigated in Hochest33342 and Annexin V-FITC/PI assay. To verify the results of CREE in vivo effects, we applied nude mice subcutaneous xenograft experiments. The possible mechanism of CREE treating breast cancer was investigated through mitochondrial membrane potential and western blot experiments.

Results: CREE contains cycloartane triterpene saponins. CREE can significantly inhibit the proliferation, migration and invasion of human breast cancer MCF-7 and MDA-MB-231 cells in vitro and it can effectively inhibit the growth of MDA-MB-231 cell subcutaneous tumors in vivo. Besides, we also found that CREE up-regulated the expression levels of Bax, caspase-9/3 and cytochrome C, and down-regulated the expression of Bcl-2. Therefore, regulation of the mitochondrial pathway may be one of the mechanisms by which CREE promotes breast cancer cell apoptosis.

Conclusions: CREE exhibits sufficient anti-breast cancer activity in vivo and in vitro, this study provides persuasive evidence for the further research and development of C. dahurica.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2021.114057DOI Listing
September 2021

Elafin promotes tumour metastasis and attenuates the anti-metastatic effects of erlotinib via binding to EGFR in hepatocellular carcinoma.

J Exp Clin Cancer Res 2021 Mar 26;40(1):113. Epub 2021 Mar 26.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China.

Background: Elafin is a serine protease inhibitor critical for host defence. We previously reported that Elafin was associated with the recurrence of early-stage hepatocellular carcinoma (HCC) after surgery. However, the exact role of Elafin in HCC remains obscure.

Methods: HCC tissue microarrays were used to investigate the correlation between Elafin expression and the prognosis of HCC patients. In vitro migration, invasion and wound healing assays and in vivo lung metastasis models were used to determine the role of Elafin in HCC metastasis. Mass spectrometry, co-immunoprecipitation, western blotting, and immunofluorescence staining assays were performed to uncover the mechanism of Elafin in HCC. Dual-luciferase reporter and chromatin immunoprecipitation assays were employed to observe the transcriptional regulation of Elafin.

Results: Elafin expression was frequently increased in HCC tissues compared to normal tissues, and high Elafin expression in HCC tissues was correlated with aggressive tumour phenotypes and a poor prognosis in HCC patients. Elafin dramatically enhanced the metastasis of HCC cells both in vitro and in vivo by interacting with EGFR and activating EGFR/AKT signalling. Moreover, Elafin attenuated the suppressive effects of erlotinib on HCC metastasis. Besides, Elafin was transcriptionally regulated by Sp1 in HCC cells. Clinically, Elafin expression was positively correlated with Sp1, Vimentin, and EGFR signalling in both our HCC tissue microarrays and TCGA database analysis.

Conclusions: Upregulation of Elafin by Sp1 enhanced HCC metastasis via EGFR/AKT pathway, and overexpression of Elafin attenuated the anti-metastatic effects of erlotinib, suggesting a valuable prognostic biomarker and therapeutic target for HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13046-021-01904-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995733PMC
March 2021

Arctium lappa L. roots ameliorates cerebral ischemia through inhibiting neuronal apoptosis and suppressing AMPK/mTOR-mediated autophagy.

Phytomedicine 2021 May 21;85:153526. Epub 2021 Feb 21.

Department of Pharmacy, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenyang, Liaoning 110016, China; School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China. Electronic address:

Background: Arctium lappa L. roots are very popular cultivated vegetables, which possesses various pharmacological activities. Our previous studies have demonstrated that Arctium lappa L. roots exerted protective effects against HO, glutamate and N-methyl-D-aspartic acid (NMDA)-induced neuronal injury in vitro. However, whether Arctium lappa L. roots could prevent against cerebral ischemia and the underlying mechanism remain unclear.

Purpose: The objective of the present study was to investigate the neuroprotective effects of ethyl acetate extract of Arctium lappa L. roots (EAL) and the active ingredient 4,5-O-dicaffeoyl-1-O-[4-malic acid methyl ester]-quinic acid (DCMQA) in EAL against cerebral ischemia and explore the underlying mechanism.

Study Design: The neuroprotective effects of EAL and DCMQA were investigated in rats with permanent middle cerebral artery occlusion (MCAO) and in oxygen glucose deprivation/reoxygenation (OGD/R)-stimulated SH-SY5Y cells, respectively.

Methods: The infarct volume, brain edema and neurological deficits were measured following MCAO. TUNEL and Nissl staining were performed to detect neuronal loss and apoptosis of neurons in rat brains. Cell survival was measured by MTT and LDH assay. In addition, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) levels were determined by DCFH-DA and JC-1 fluorescent probe, respectively. Hoechst 33342 staining and Annexin V-FITC/PI double staining were performed to evaluate neuronal apoptosis. The expression levels of proteins were evaluated by western blot.

Results: EAL reduced brain infarct volume, ameliorated brain edema and improved neurological deficits in MCAO rats. In addition, EAL inhibited oxidative stress and inflammatory responses following MCAO. Besides, active compound DCMQA alleviated cytotoxicity as well as inhibited over-production of intracellular ROS and loss of MMP induced by OGD/R in SH-SY5Y cells. Moreover, EAL and DCMQA inhibited apoptosis by decreasing the expressions of pro-apoptotic proteins including bax, cytochrome c and cleaved caspase-3 while promoting the bcl-2 expression in MCAO rats and OGD/R-stimulated neurons, respectively. In addition, DCMQA suppressed the production of autophagosomes and down-regulated expression of Beclin 1 and LC3. Furthermore, inhibiting AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway contributed to DCMQA-mediated suppression of autophagy induced by OGD/R.

Conclusion: Our findings demonstrate that Arctium lappa L. roots protect against cerebral ischemia through inhibiting apoptosis and AMPK/mTOR-mediated autophagy in vitro and in vivo, providing a theoretical basis for the development of CQAs in Arctium lappa L. roots as neuroprotective drugs for the prevention and treatment of ischemic stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2021.153526DOI Listing
May 2021

Long-term outcome for colorectal liver metastases: combining hepatectomy with intraoperative ultrasound guided open microwave ablation versus hepatectomy alone.

Int J Hyperthermia 2021 ;38(1):372-381

Department of Ultrasound, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, PR China.

Objective: To compare the long-term outcome of combining hepatectomy with intraoperative ultrasound (IOUS)-guided open microwave ablation (MWA) versus hepatectomy alone in patients with colorectal cancer liver metastases (CRLM).

Method: A retrospective analysis of patients with CRLM who underwent hepatectomy alone (HT group; 380 patients) or hepatectomy combined with IOUS-guided open MWA (HT + MWA group; 57 patients) from April 2002 to September 2018 was conducted at our center. A propensity score-matched (PSM) analysis was used to reduce data bias between the two groups.

Results: The overall survival (OS) and disease-free survival (DFS) were not significantly different between the two groups after matching. Although intrahepatic recurrence was more frequent in the HT + MWA group in both the whole and matched cohort, the two groups exhibited similar rates of extrahepatic recurrence as well as concomitant intra- and extrahepatic recurrence. A higher number of CRLM (>3), larger maximum-size and absence of response to induction chemotherapy were independent risk factors for OS.

Conclusion: The oncological outcomes of hepatectomy combined with intraoperative open ablation was not significantly different to hepatectomy alone and should be considered as a safe and fair option for patients with difficultly resectable CRLM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02656736.2021.1892835DOI Listing
July 2021

Protective effects of pulmonary surfactant on decompression sickness in rats.

J Appl Physiol (1985) 2021 02 3;130(2):400-407. Epub 2020 Dec 3.

Department of Diving and Hyperbaric Medicine, Naval Special Medical Center, Naval Medical University, Shanghai, China.

Decompression sickness (DCS) is a systemic pathophysiological process featured by bubble load. Lung dysfunction plays a harmful effect on off-gassing, which contributes to bubble load and subsequent DCS occurrence. This study aimed to investigate the effects of pulmonary surfactant on DCS as it possesses multiple advantages on the lung. Rats were divided into three groups: the normal ( = 10), the surfactant ( = 36), and the saline ( = 36) group. Animals in surfactant or saline group were administered aerosol surfactant or saline 12 h before a stimulated diving, respectively. Signs of DCS were recorded and bubble load was detected. The contents of phospholipid and surfactant protein A (SPA), protein, IL-1 and IL-6 in bronchoalveolar lavage fluid (BALF), and lung wet/dry (W/D) ratio were determined. Serum levels of IL-6, ICAM-1, E-selectin, GSH, and GSSG were detected. In surfactant-treated rats, the morbidity and mortality of DCS markedly decreased ( < 0.01 and < 0.05, respectively). Survival time prolonged and the latency to DCS dramatically delayed ( < 0.01). More importantly, bubble load markedly decreased ( < 0.01). The increases of protein, IL-1 and IL-6 in BALF, and lung W/D ratio were alleviated. Restoration of total phospholipid and SPA in BALF and ICAM-1 and E-selectin in serum was observed. The inflammation and oxidation were attenuated ( < 0.01). In conclusion, prediving administrating exogenous surfactant by aerosolization is an efficient, simple, and safe method for DCS prevention in rats. This is the first study exploring the effects of aerosol surfactant on DCS prevention and it was proven to be an efficient and simple method. The role of surfactant in facilitating off-gassing was thought to be the critical mechanism in bubble degrading and subsequent DCS prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/japplphysiol.00807.2020DOI Listing
February 2021

Surgical Resection versus Re-Ablation for Intrahepatic Recurrent Hepatocellular Carcinoma after Initial Ablation Therapy.

Dig Surg 2021 5;38(1):46-57. Epub 2020 Nov 5.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China,

Background And Aims: Whether surgical resection or repeated ablation should be recommended for intrahepatic recurrent hepatocellular carcinoma (HCC) conforming to the Milan criteria after initial ablation remains unclear. In this study, we compared the outcomes of patients who underwent surgical resection with those who underwent re-ablation for recurrent HCC after initial curative-intent ablation.

Methods: The data of 28 and 98 patients who underwent surgical resection and re-ablation, respectively, for recurrent HCC after initial ablation between January 2003 and 2017 were analyzed using propensity score matching.

Results: Before matching, the 1-, 3-, and 5-year overall survival (OS) rates were 95.7, 83.0, and 74.4% for the ablation group, compared to 92.9, 89.1, and 70.9% for the resection group (p = 0.490). The corresponding disease-free survival (DFS) rates were 67.5, 40.1, and 25.6% for the ablation group and were 85.4, 59.9, and 53.3% for the resection group (p = 0.018). After matching, the 1-, 3-, and 5-year OS rates for the ablation and resection group were 95.2, 85.5 and 81.8% versus 96.0, 96.0, and 76.4%, respectively (p = 0.550). The 1-, 3-, and 5-year DFS rates were 58.0, 39.5, and 29.9% for the ablation group and were 95.8, 67.2, and 59.8% for the resection group (p = 0.004). Cox proportional hazards model identified surgical resection as the only significant prognostic factor for DFS but not for OS.

Conclusion: For intrahepatic recurrent HCC patients after initial ablation, surgical resection could provide better DFS than re-ablation, while no difference in OS was observed between the 2 treatment groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000511157DOI Listing
October 2021

The overlap between Alzheimer's disease and epilepsy uncovered by transcriptome sequencing.

Clin Transl Med 2020 Sep;10(5):e169

Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, P. R. China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ctm2.169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507445PMC
September 2020

Apatinib versus sorafenib in patients with advanced hepatocellular carcinoma: a preliminary study.

Ann Transl Med 2020 Aug;8(16):1000

State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.

Background: Apatinib, a selective inhibitor of vascular endothelial growth factor receptor 2 (VEGFR 2), has exhibited modest antitumor efficacy in hepatocellular carcinoma (HCC). We aimed to evaluate the effectiveness and tolerability of apatinib versus sorafenib in patients with advanced HCC.

Methods: All patients with advanced HCC who underwent sorafenib or apatinib between January 2016 to December 2017 were retrospectively reviewed. Seventy-two patients received apatinib (26 patients, 500 mg, daily) or sorafenib (46 patients, 400 mg, twice daily) until disease progression or intolerable toxicities. Primary outcome was progression-free survival (PFS). Secondary outcomes included overall survival (OS), objective response rate (ORR) per modified response evaluation criteria in solid tumors (RECIST), disease control rate (DCR), and safety.

Results: The median follow-up was 13.2 (5.7-20.7) months. The 1-year OS for apatinib of 62.0% was comparable to that of sorafenib [64.2%, hazard ratio (HR), 1.15; 95% confidence interval (CI), 0.369-3.58]. The median PFS was 4.1 months in the apatinib group (95% CI, 3.2 to 7.4 months) and 3.6 months in the sorafenib group (95% CI, 2.7 to 5.9 months; HR, 1.03; 95% CI, 0.586 to 1.800; P=0.925). The apatinib group exhibited higher ORR (19.2% 2.2%, P=0.012) but similar DCR (57.7% 50%, P=0.530) compared with the sorafenib group. The most common any-grade adverse events in the apatinib and sorafenib groups were hand and foot syndrome (53.8% 50%), hypertension (50% 19.6%), diarrhea (34.6% 28.3%), and elevated transaminase (57.7% 63%).

Conclusions: Compared with sorafenib, apatinib yielded comparable PFS and OS, and even better ORR, in patients with advanced HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-5298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475472PMC
August 2020

The predictive role of the neutrophil-lymphocyte ratio in the prognosis of adult patients with stroke.

Chin Neurosurg J 2020 1;6:22. Epub 2020 Jul 1.

Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, 150001 Heilongjiang Province People's Republic of China.

Our study aimed to determine the effect of the neutrophil-lymphocyte ratio on the prognosis of adult patients with acute stroke. We searched the Web of Science, PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure databases and selected all of the potentially eligible studies. From the included studies, we extracted characteristics such as the stroke type and acquisition time until routine blood collection and the odds ratios across studies. The 95% confidence intervals and odds ratios were pooled to calculate the effect size for the neutrophil-lymphocyte ratio in acute stroke patients. We defined poor function outcomes according to the modified Rankin Scale ≥ 3 or Glasgow Outcome Scale< 3.Thirteen studies with 4443 patients were included in our analysis, including 7 ischemic and 6 hemorrhagic stroke studies. The pooled odds ratios for poor functional outcome at 3 months with a higher neutrophil-lymphocyte ratio in acute ischemic and hemorrhagic patients were 1.689 (95% CI = 1.184-2.409, < 0.001) and 1.125 (95% CI = 1.022-1.239, < 0.001), respectively, and the overall pooled odds ratio for poor functional outcome following stroke was 1.257 (95% CI = 1.146-1.379, < 0.001). At the same time, the overall combined odds ratio for death at 3 months was 1.632 (95% CI = 1.155-2.306, < 0.001).The neutrophil-lymphocyte ratio, an easily calculated marker, plays a predictive role in the short-term outcomes of adult patients (mean age ≥ 50 years) following acute ischemic and hemorrhagic stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s41016-020-00201-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398197PMC
July 2020

Kukoamine A Protects against NMDA-Induced Neurotoxicity Accompanied with Down-Regulation of GluN2B-Containing NMDA Receptors and Phosphorylation of PI3K/Akt/GSK-3β Signaling Pathway in Cultured Primary Cortical Neurons.

Neurochem Res 2020 Nov 5;45(11):2703-2711. Epub 2020 Sep 5.

School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, People's Republic of China.

Kukoamine (KuA) is a spermine alkaloid present in traditional Chinese medicine Cortex Lycii radices, which possesses various pharmacological properties. Our previous studies have demonstrated that KuA exerts neuroprotective effects against HO-induced oxidative stress, radiation-induced neuroinflammation, oxidative stress and neuronal apoptosis, as well as neurotoxin-induced Parkinson's disease through apoptosis inhibition and autophagy enhancement. The present study aimed to investigate the neuroprotective effects of KuA against NMDA-induced neuronal injury in cultured primary cortical neurons and explore the underlying mechanism. Incubation with 200 μM NMDA for 30 min induced excitotoxicity in primary cultured cortical neurons. The results demonstrated that pretreatment with KuA attenuated NMDA induced cell injury, LDH leakage and neuronal apoptosis. KuA also regulated apoptosis-related proteins. Thus, incubation with the alkaloid decreased the ratio of Bax/Bcl-2, and inhibited the release of cytochrome C, the expression of p53 and the cleavage of caspase-3. Moreover, KuA prevented the upregulation of GluN2B-containing NMDA receptors (NMDAR). Additionally, pretreatment with KuA reversed NMDA-induced dephosphorylation of Akt and GSK-3β and the protective effect of KuA on NMDA-induced cytotoxicity was abolished by wortmannin, a PI3K inhibitor. Taken together, these results indicated that KuA exerted neuroprotective effects against NMDA-induced neurotoxicity in cultural primary cortical neurons and caused the down-regulation of GluN2B-containing NMDARs as well as the phosphorylation of proteins belonging to the PI3K/Akt/GSK-3β signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11064-020-03114-yDOI Listing
November 2020

Current Advances in Naturally Occurring Caffeoylquinic Acids: Structure, Bioactivity, and Synthesis.

J Agric Food Chem 2020 Sep 17;68(39):10489-10516. Epub 2020 Sep 17.

School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, People's Republic of China.

Caffeoylquinic acids (CQAs) are a broad class of secondary metabolites that have been found in edible and medicinal plants from various families. It has been 100 years since the discovery of chlorogenic acid in 1920. In recent years, a number of naturally derived CQAs have been isolated and structurally elucidated. Accumulated evidence demonstrate that CQAs have a wide range of biological activities, such as antioxidation, antibacterial, antiparasitic, neuroprotective, anti-inflammatory, anticancer, antiviral, and antidiabetic effects. Up to date, some meaningful progresses on the biosynthesis and total synthesis of CQAs have also been made. Therefore, it is necessary to comprehensively summarize the structure, biological activity, biosynthesis, and chemical synthesis of CQAs. This review provides extensive coverage of naturally occurring CQAs discovered from 1990 until 2020. Modern isolation techniques, chemical data (including structure, biosynthesis, and total synthesis), and bioactivity are summarized. This would be helpful for further research of CQAs as potential pharmaceutical agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.0c03804DOI Listing
September 2020

A natural BACE1 and GSK3β dual inhibitor Notopterol effectively ameliorates the cognitive deficits in APP/PS1 Alzheimer's mice by attenuating amyloid-β and tau pathology.

Clin Transl Med 2020 Jul 11;10(3):e50. Epub 2020 Jul 11.

Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ctm2.50DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418795PMC
July 2020

A comprehensive description of GluN2B-selective N-methyl-D-aspartate (NMDA) receptor antagonists.

Eur J Med Chem 2020 Aug 16;200:112447. Epub 2020 May 16.

School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China; Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, 110840, People's Republic of China. Electronic address:

l-glutamate is an excitatory neurotransmitter in the central nervous system (CNS), which can activate ionotropic receptors (iGluRs) and metabotropic (mGluRs) receptors. N-methyl-D-aspartate (NMDA) receptor is a ligand-gated ion channel belonging to the iGluRs family. Among NMDA receptor subtypes, GluN2B subtype plays a crucial role in CNS diseases. In this review, we summarize, classify and discuss the reports on GluN2B antagonists, published from the 1990s to 2020, to provide the therapeutic potential of GluN2B antagonists on various disorders. The GluN2B antagonists are broadly classified into two categories, which are prototypical antagonists and atypical antagonists. And the latter are further divided into amidine derivatives, 4-aminoquinolines, indole derivatives, benzimidazole derivatives, oxamide derivatives, carbamate derivatives, EVT-101 analogues, 1H-pyrrolo[3,2-b]pyridine derivatives, benzazepin derivatives, other heterocyles and radiotracers. This review will provide a comprehensive description including structure, structure-activity relationship (SAR), and pharmacology of novel GluN2B-subtype selective NMDA antagonists to the medicinal chemists, which would be helpful in rational designing effective drugs aimed toward related CNS disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2020.112447DOI Listing
August 2020

DCMQA, a caffeoylquinic acid derivative alleviates NMDA-induced neurotoxicity via modulating GluN2A and GluN2B-containing NMDA receptors in vitro.

Toxicol In Vitro 2020 Sep 19;67:104888. Epub 2020 May 19.

School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, People's Republic of China; Department of Pharmacy, General Hospital of Northern Military Area, 83 Wenhua Road, Shenyang, Liaoning 110016, People's Republic of China. Electronic address:

Compound DCMQA (4, 5-O-dicaffeoyl-1-O-[4-malic acid methyl ester]-quinic acid) is a natural caffeoylquinic acid derivative isolated from Arctium lappa L. roots. Caffeoylquinic acid derivatives have been reported to possess neuroprotective effects through inhibiting oxidative stress and apoptosis in vitro. However, whether DCMQA exerts protective effects on N-methyl-D-aspartate (NMDA)-induced neurotoxicity and the underlying mechanism has not been elucidated. In this study, the results indicated that pretreatment of DCMQA prevented the loss of cell viability and attenuated the LDH leakage in SH-SY5Y cells exposed to NMDA. Hoechst 33342 staining and Annexin V-PI double staining illustrated that DCMQA suppressed NMDA-induced morphological damage and neuronal apoptosis. Moreover, DCMQA inhibited NMDA-mediated Ca influx, excessive intracellular ROS generation and loss of mitochondrial membrane potential (MMP). Western blot analysis showed that DCMQA attenuated the Bax/Bcl-2 ratio, release of cytochrome c as well as expression of caspase-9 and caspase-3. Besides, DCMQA down-regulated GluN2B-containing NMDA receptors (NMDARs) and up-regulated GluN2A-containing NMDARs, promoted the disruption of nNOS and PSD95 as well as activation of CaMK II-α. Furthermore, computational docking study indicated that DCMQA possessed a good affinity for NMDARs. These results indicated that DCMQA protects SH-SY5Y cells against NMDA-induced neuronal damage. In addition, the underlying mechanisms of DCMQA-mediated neuroprotection are associated with modulating NMDARs and disruption of nNOS-PSD95 as well as the activation of CaMK II-α.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tiv.2020.104888DOI Listing
September 2020

Dysregulated Sp1/miR-130b-3p/HOXA5 axis contributes to tumor angiogenesis and progression of hepatocellular carcinoma.

Theranostics 2020 6;10(12):5209-5224. Epub 2020 Apr 6.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P. R. China.

Angiogenesis, one of the hallmarks of cancer, is essential for both tumor growth and metastasis. However, its molecular mechanisms in hepatocellular carcinoma (HCC) are largely unknown. Here, we report the role of HOXA5 in tumor angiogenesis of HCC. : The expression of miR-130b-3p and HOXA5 was determined by qRT-PCR and immunohistochemistry, respectively. Capillary tube formation assay, chicken chorioallantoic membrane assay, and subcutaneous xenograft experiments were performed to investigate the role of miR-130-3p and HOXA5. Luciferase reporter assay and chromatin immunoprecipitation assay were performed to evaluate the interaction between Sp1, miR-130b-3p and HOXA5. : miR-130b-3p was found up-regulated in HCC and correlated with a poor prognosis. miR-130b-3p promoted HCC angiogenesis both and . Mechanistically, HOXA5 was validated as a direct target of miR-130b-3p. Furthermore, we demonstrated that HOXA5 was down-regulated in HCC and its down-regulation was associated with larger tumor size, shorter overall survival, and higher recurrence probability. Moreover, HOXA5 was significantly associated with angiogenesis biomarkers such as CD31 and CD34. Functional studies revealed that the knockdown of HOXA5 also significantly promoted HCC angiogenesis both and . Knocking-down HOXA5 significantly provoked HCC cells to induce the capillary tube formation, migration and proliferation of endothelial cells. In xenograft animal models, we found that a decrease of HOXA5 effectively enhanced tumor growth and increased microvessel densities. We further demonstrated that miR-130b-3p could be directly transcriptionally regulated by Sp1. : This study showed that a dysregulation in the Sp1/miR-130b-3p/HOXA5 axis contributed to HCC progression and angiogenesis, and that HOXA5 can be considered as a promising therapeutic target for treating HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.43640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196310PMC
July 2021

Hydrogen gas protects against delayed encephalopathy after acute carbon monoxide poisoning in a rat model.

Neurol Res 2020 Jan 3;42(1):22-30. Epub 2019 Nov 3.

Department of Critical Care Unit, Zhongshan Hospital, Fudan University, Shanghai, PR China.

: The protective effects of 2%-4% hydrogen gas in delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) have been previously reported. This study aimed to assess the neuroprotective effects of high concentration hydrogen (HCH) on DEACMP.: A total of 36 male Sprague-Dawley rats were divided into 3 groups. In the DEACMP group, rats were exposed to CO to induce CO poisoning; in the HCH group, the animals were exposed to 67% H and 33% O at 3,000 mL/min for 90 min immediately after CO poisoning. Neurological function was evaluated at 1 and 9 days after poisoning. Then, the contents of malondialdehyde, 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine, as well as superoxide dismutase activity in the serum, cortex and hippocampus were detected by ELISA. Additionally, the mRNA and protein expression levels of Nrf2 and downstream genes were detected by RT-PCR and Western blotting, respectively.: Our results showed that CO poisoning significantly impaired neurological function which was improved over time, and HCH markedly attenuated neurological impairment following CO poisoning. In addition, CO poisoning resulted in increased levels of malondialdehyde, 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine and markedly reduced superoxide dismutase activity at 1 and 9 days, which were significantly inhibited by HCH at 9 days. Finally, CO poisoning increased the mRNA and protein levels of Nrf2 and downstream genes, and HCH further induced the anti-oxidative capability.: These findings indicate the neuroprotective effects of HCH on DEACMP, which are related to the activation of Nrf2 signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/01616412.2019.1685064DOI Listing
January 2020

Identification of hub genes and small-molecule compounds related to intracerebral hemorrhage with bioinformatics analysis.

PeerJ 2019 25;7:e7782. Epub 2019 Oct 25.

The First Affiliated Hospital of Harbin Medical University, Department of Neurosurgery, Harbin, Heilongjiang Province, People's Republic of China.

Background: Because of the complex mechanisms of injury, conventional surgical treatment and early blood pressure control does not significantly reduce mortality or improve patient prognosis in cases of intracerebral hemorrhage (ICH). We aimed to identify the hub genes associated with intracerebral hemorrhage, to act as therapeutic targets, and to identify potential small-molecule compounds for treating ICH.

Methods: The GSE24265 dataset, consisting of data from four perihematomal brain tissues and seven contralateral brain tissues, was downloaded from the Gene Expression Omnibus (GEO) database and screened for differentially expressed genes (DEGs) in ICH, with a fold change (FC) value of (|log2FC|) > 2 and a -value of <0.05 set as cut-offs. The functional annotation of DEGs was performed using Gene Ontology (GO) resources, and the cell signaling pathway analysis of DEGs was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG), with a -value of <0.05 set as the cut-off. We constructed a protein-protein interaction (PPI) network to clarify the interrelationships between the different DEGs and to select the hub genes with significant interactions. Next, the DEGs were analyzed using the CMap tool to identify small-molecule compounds with potential therapeutic effects. Finally, we verified the expression levels of the hub genes by RT-qPCR on the rat ICH model.

Result: A total of 59 up-regulated genes and eight down-regulated genes associated with ICH were identified. The biological functions of DEGs associated with ICH are mainly involved in the inflammatory response, chemokine activity, and immune response. The KEGG analysis identified several pathways significantly associated with ICH, including but not limited to HIF-1, TNF, toll-like receptor, cytokine-cytokine receptor interaction, and chemokine molecules. A PPI network consisting of 57 nodes and 373 edges was constructed using STRING, and 10 hub genes were identified with Cytoscape software. These hub genes are closely related to secondary brain injury induced by ICH. RT-qPCR results showed that the expression of ten hub genes was significantly increased in the rat model of ICH. In addition, a CMap analysis of three small-molecule compounds revealed their therapeutic potential.

Conclusion: In this study we obtained ten hub genes, such as IL6, TLR2, CXCL1, TIMP1, PLAUR, SERPINE1, SELE, CCL4, CCL20, and CD163, which play an important role in the pathology of ICH. At the same time, the ten hub genes obtained through PPI network analysis were verified in the rat model of ICH. In addition, we obtained three small molecule compounds that will have therapeutic effects on ICH, including Hecogenin, Lidocaine, and NU-1025.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.7782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6816389PMC
October 2019

Comparison of the prognostic value of inflammation-based scores in early recurrent hepatocellular carcinoma after hepatectomy.

Liver Int 2020 01 28;40(1):229-239. Epub 2019 Nov 28.

State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Background & Aims: Inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), Prognostic Index (PI), Prognostic Nutritional Index (PNI), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR) and systemic immune-inflammation index (SII), are correlated with the survival of hepatocellular carcinoma (HCC) patients, while remain unclear for recurrent HCC. This study aimed to compare the prognostic value of inflammation-based prognostic scores for post-recurrence survival (PRS) in patients with early recurrent HCC (ErHCC, within 2 years after hepatectomy).

Methods: A total of 580 patients with ErHCC were enrolled retrospectively. The association between the independent baseline and the time-dependent variables and PRS was evaluated by cox regression. The prediction accuracy of the inflammation-based prognostic scores was assessed by time-dependent receiver operating characteristic (ROC) and Harrell's concordance index (C-index) analyses.

Results: The GPS, mGPS, PI, PNI, NLR, PLR, LMR and SII were all related to the PRS of ErHCC patients, while only the SII (P < .001) remained an independent predictor for PRS in multivariate analysis (hazard ratio: 1.92, 95% confidence interval: 1.33-2.79). Both the C-index of the SII (0.65) and the areas under the ROC curves showed that the SII score was superior to the other inflammation-based prognostic scores for predicting the PRS of ErHCC patients.

Conclusions: The SII is a useful prognostic indicator for PRS in patients with ErHCC after hepatectomy and is superior to the other inflammation-based prognostic scores in terms of prognostic ability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.14281DOI Listing
January 2020

Microwave ablation resection for hepatocellular carcinoma within the Milan criteria: a propensity-score analysis.

Ther Adv Med Oncol 2019 11;11:1758835919874652. Epub 2019 Sep 11.

State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Centre, 651 Dongfeng East Road, Guangzhou, Guangdong 510060, PR China.

Background: Whether the efficient heat-generating mechanism of microwave ablation (MWA) is comparable with resection (RES) in treating hepatocellular carcinoma (HCC) remains unclear.

Methods: This retrospective cohort study comprised 126 and 1183 patients with HCC meeting the Milan criteria who received MWA or RES between 2002 and 2017. We compared 5-year overall survival (OS) and recurrence-free survival (RFS) using both propensity-score matching (PSM) and inverse-probability-of-treatment-weighting (IPW) analysis and investigated the prognostic factors with multivariate Cox analysis.

Results: After PSM (1:2), although MWA ( = 116) offered decreased 5-year RFS (30.6% 57.5%,  < 0.001) compared with RES ( = 212), both treatments provided similar 5-year OS (82.2% 80.5%,  = 0.360) because most patients with intrahepatic recurrence remained eligible for repeat treatments; similar results were found in the IPW analysis. Additionally, the comparable efficacy of MWA and RES was consistent across all subgroups: those with solitary HCC ⩽ 3.0 cm or >3.0 cm, or multifocal HCCs within the Milan criteria, patients with liver function of albumin-bilirubin grade 1 or 2, and older (⩾60 years) or younger (<60 years) patients. Multivariate Cox analysis confirmed that no difference was seen between MWA and RES in OS (hazard ratio = 0.85;  = 0.581) in the overall population; similar results were obtained in the propensity-score-matched and IPW cohorts.

Conclusions: Compared with RES, MWA offered worse RFS for HCC within the Milan criteria; however, both treatments provided equivalent long-term OS because most patients with intrahepatic recurrence remained eligible for repeat treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1758835919874652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6740202PMC
September 2019

Resection vs Ablation for Multifocal Hepatocellular Carcinomas meeting the Barcelona-Clinic Liver Cancer A Classification: A Propensity Score Matching Study.

J Cancer 2019 2;10(13):2857-2867. Epub 2019 Jun 2.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China.

With development of surgical technology, we aimed to investigate whether resection could challenge the standard treatment, ablation, in treating multifocal hepatocellular carcinomas meeting the Barcelona-Clinic Liver Cancer A stage. From January 2005 to January 2017, the oncological outcomes of patients undergoing resection (n = 72) or ablation (n = 63) were retrospectively analysed using propensity score matching. At baseline, patients in the ablation group had more tri-focal lesions (30.2% vs. 6.9%, P = 0.001) and smaller tumours (2.00 cm vs. 2.50 cm, P = 0.002) than resection group. After matching, the baseline was well-balanced between treatments (n = 46 pairs); resection provided comparable 5-year overall survival (77.0% vs. 83.6, P = 0.790) and superior 5-year recurrence-free survival (40.4% vs. 16.9%, P = 0.022) to ablation. The multivariate Cox model confirmed that ablation was not associated with worse overall survival (HR = 0.89; 95% CI, 0.33 - 2.42, P = 0.819), but identified ablation as an unfavourable predictor of recurrence-free survival (HR = 2.13; 95% CI, 1.27 - 3.57, P <0.001). For subgroup patients with multifocal tumours located in different segments, both treatments offered similar 5-year overall survival (74.3% vs. 95.5%, P = 0.190) and 5-year recurrence-free survival (42.9 vs. 25.9%, P = 0.170). Additionally, ablation resulted in less major complications than resection (3.2% vs 13.9%, P = 0.035). Compared with ablation, resection achieved comparable overall survival and even superior recurrence-free survival for patients with multifocal hepatocellular carcinomas meeting the BCLC A stage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.31246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590028PMC
June 2019

Lipiodol deposition in portal vein tumour thrombus predicts treatment outcome in HCC patients after transarterial chemoembolisation.

Eur Radiol 2019 Nov 16;29(11):5752-5762. Epub 2019 Apr 16.

State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.

Objective: To study lipiodol deposition in portal vein tumour thrombus (PVTT) in predicting the treatment outcome of hepatocellular carcinoma (HCC) patients after transarterial chemoembolisation (TACE).

Methods: We retrospectively reviewed data from 379 HCC patients with PVTT who underwent TACE as the initial treatment at Sun Yat-Sen University Cancer Center from January 2008 to December 2015. Patients were grouped by positive and negative lipiodol deposition based on the extent of lipiodol deposition in PVTT. The overall survival (OS) and progression-free survival (PFS) were compared between negative and positive lipiodol deposition groups; furthermore, the value of the combinatorial evaluation of tumour responses and lipiodol deposition in PVTT in predicting prognosis was analysed in subgroup patients with stable disease (SD) after TACE.

Results: Of the 379 patients, 264 (69.7%) had negative and 115 (30.3%) had positive lipiodol deposition in PVTT after TACE. Multivariate analysis identified positive lipiodol deposition in PVTT as an independent prognostic factor for favourable OS (p = 0.001). The median OS and PFS of negative and positive lipiodol deposition groups were 4.70 vs. 8.97 months (p = 0.001) and 3.1 months vs. 5.8 months (p < 0.001). In subgroup patients, the median OS and PFS of negative and positive lipiodol deposition groups were 4.7 months vs. 10.5 months (p < 0.001) and 3.5 months vs. 7.0 months (p < 0.001), respectively.

Conclusions: The patients with positive lipiodol deposition in PVTT had a longer OS than those with negative lipiodol deposition. Furthermore, the positive lipiodol deposition in PVTT can further differentiate HCC patients with favourable prognosis from SD patients.

Key Points: • Lipiodol deposition in PVTT is a prognostic indicator for HCC patients after TACE treatment. • Positive lipiodol deposition in PVTT is associated with a better prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-019-06157-0DOI Listing
November 2019

Impact of follow-up interval on patients with hepatocellular carcinoma after curative ablation.

BMC Cancer 2018 Nov 29;18(1):1186. Epub 2018 Nov 29.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Background: The optimal follow-up strategy after curative thermal ablation of hepatocellular carcinoma (HCC) remains unclear.

Methods: We retrospectively analyzed a prospective series of 616 patients who underwent curative thermal ablation for HCC within the Milan criteria. Multivariate Cox model was used to identify independent predictive factors for recurrence; accordingly, patients were stratified into 2 groups with different relapse risks: a low-risk group (solitary tumor ≤3 cm) and a high-risk group (multiple tumors ≤3 cm or solitary tumor between 3 and 5 cm). Then, patients were classified into short- (< 4 months) or long-interval (4-6 months) surveillance groups according to follow-up intensity within the first 2 years after ablation. The overall survival (OS) of patients were compared between short- and long-interval groups in low- or high-risk groups, as well as the stage of recurrent tumors and the proportion of patients who received curative-intent retreatments.

Results: In the low-risk group, 54 (83.0%) and 18 (72.0%) of patients exhibited early relapse at the Barcelona Clinic Liver Cancer (BCLC) 0/A stage in the short- and long-interval groups, respectively (P = 0.172); accordingly, 44 (77.2%) and 18 (81.8%) of patients received curative-intent retreatment (P = 0.086) after recurrence. Hence, 5-year OS was similar between short- and long-interval groups (80.4% vs. 77.5%, P = 0.400) in low-risk patients. However, in the high-risk group, patients with a short interval exhibited early relapse more frequently at the BCLC 0/A stage (83% vs. 72%, P = 0.028), with a trend showing that the corresponding proportion of patients who received curative-intent retreatment greater than that in the long-interval group (64.2% vs. 37.5%, P = 0.087). Moreover, the short-interval group showed better 5-year OS than the long-interval group in high-risk patients (69.9% vs. 42.7%, P = 0.020).

Conclusions: Compared to a short surveillance interval, a long surveillance interval does not reduce OS in low-risk patients; however, a long surveillance interval compromises OS in high-risk patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-018-5069-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267022PMC
November 2018

Letter: is microwave ablation superior to radiofrequency ablation for early stage hepatocellular carcinoma? Authors' reply.

Aliment Pharmacol Ther 2018 12;48(11-12):1326-1327

State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Centre, Guangzhou, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.15048DOI Listing
December 2018

Letter: microwave vs radiofrequency ablation for hepatocellular carcinoma within the Milan criteria-Authors' reply.

Aliment Pharmacol Ther 2018 11;48(9):1027-1028

State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Centre, Guangzhou, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.14984DOI Listing
November 2018

Resection versus Resection with Preoperative Transcatheter Arterial Chemoembolization for Resectable Hepatocellular Carcinoma Recurrence.

J Cancer 2018 16;9(16):2778-2785. Epub 2018 Jul 16.

State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.

The value of preoperative transcatheter arterial chemoembolization (TACE) for patients with recurrent hepatocellular carcinoma (rHCC) after liver resection is uncertain. We aimed to determine its effect on postoperative complication and survival. There were 33 patients who received preoperative TACE and repeated liver resection (TACE-LR) and 119 patients who received repeated liver resection (LR) alone for rHCC. Seventy-eight patients (TACE-LR, 28; LR, 50) were identified by propensity score matching (PSM) analysis for comparison of postoperative complication, disease-free survival (DFS) and overall survival (OS). Univariable and multivariable analyses were used to identify predictors for survival. Before matching, the TACE-LR group had more intraoperative blood loss than the LR group (P < 0.05). After matching, the TACE-LR group had more intraoperative blood loss and a longer operation time (Both P < 0.05). In all and matched patients, both groups had similar postoperative complications rate (TACE-LR, 21.2%; LR, 7.6%; P = 0.052 and TACE-LR, 21.4%; LR, 12.0%; P = 0.435), DFS (P = 0.81 and P = 0.41) and OS (P = 0.87 and P = 0.79). Preoperative TACE was not a predictor for DFS and OS in multivariable analyses. Preoperative TACE for resectable rHCC prolongs operating time and increases intraoperative blood loss without improving survival; thus, it should not be recommended as a routine procedure before repeated resection for patients with rHCCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.25033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096377PMC
July 2018

Microwave vs radiofrequency ablation for hepatocellular carcinoma within the Milan criteria: a propensity score analysis.

Aliment Pharmacol Ther 2018 09 31;48(6):671-681. Epub 2018 Jul 31.

State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Centre, Guangzhou, China.

Background: Whether microwave ablation (MWA) challenges the standard role of radiofrequency ablation (RFA) in treating early-stage hepatocellular carcinoma (HCC) remains unclear.

Aim: To compare the efficacy of MWA vs RFA for treating primary HCC within the Milan criteria.

Methods: From January 2002 to January 2017, the oncological outcomes after MWA (126 patients) and RFA (436 patients) were analysed by propensity score matching.

Results: Before propensity score matching, for overall patients, MWA resulted in similar 5-year overall survival to RFA (80.1% vs 75.8%, P = 0.190) but better 5-year recurrence-free survival (28.1% vs 19.6%, P = 0.036). For solitary HCC ≤ 3 cm, MWA resulted in comparable 5-year overall survival (81.8% vs 77.1%, P = 0.170) to RFA but better 5-year recurrence-free survival (34.6% vs 24.0%, P = 0.042). After propensity score matching, MWA resulted in better 5-year overall survival (79.3% vs 68.4%, P = 0.021) and 5-year recurrence-free survival (27.9% vs 6.4%, P < 0.001) than RFA for HCC. For solitary HCC ≤3 cm, MWA resulted in comparable 5-year overall survival (81.2% vs 66.3%, P = 0.062) and 5-year recurrence-free survival (37.7% vs 17.4%, P = 0.088) to RFA. In Cox analysis, RFA modality, tumours located in risk areas and low serum albumin levels were unfavourable prognostic factors for overall survival. RFA modality, multiple tumours, tumour size and low serum albumin levels were unfavourable prognostic factors for recurrence-free survival (all P < 0.05).

Conclusions: RFA is inferior to MWA for treating HCC within the Milan criteria, but has comparable efficacy to MWA for solitary HCC ≤ 3 cm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apt.14929DOI Listing
September 2018

Long- versus short-interval follow-up after resection of hepatocellular carcinoma: a retrospective cohort study.

Cancer Commun (Lond) 2018 05 21;38(1):26. Epub 2018 May 21.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.

Background: Average postoperative follow-up intervals vary in patients undergoing hepatocellular carcinoma (HCC) resection because of limited evidence regarding the optimal interval. We aimed to compare the associations of long-versus short-interval follow-up with survival and recurrence in risk-stratified HCC patients.

Methods: We performed a retrospective cohort study between 2007 and 2014. In total, 1227 patients treated by curative resection of Barcelona Clinic Liver Cancer stage A or B HCC were stratified as having a low (n = 865) or high (n = 362) risk of early recurrence (within the first 2 years after resection) based on prognostic factors identified by the least absolute shrinkage and selection operation algorithm. Patients were further classified into long-interval (every 4-6 months) and short-interval (every 2-4 months) follow-up subgroups based on follow-up within 2 years after resection (low risk, long vs. short: n = 390 vs. n = 475; high-risk, long vs. short: n = 149 vs. n = 213).

Results: The short-interval follow-up did not prolong overall survival in either the low-risk (hazard ratio [HR] = 1.152; 95% confidence interval [CI] 0.720-1.843) or high-risk (HR = 1.213; 95% CI 0.702-2.094) patients. Early recurrence occurred in 401 patients. For high-risk patients, the short-interval follow-up subgroup exhibited smaller intrahepatic recurrence than did the long-interval group (2.6 vs. 3.5 cm, respectively, P = 0.045). However, no significant difference in the rate of Barcelona Clinic Liver Cancer stage 0/A recurrence was found between the long- and short-interval follow-up groups in either low- or high-risk patients (63.1% vs. 68.2%, respectively, P = 0.580; 31.3% vs. 41.5%, respectively, P = 0.280). The rate of curative intent treatment for recurrence (34.5% vs. 39.7%, respectively, P = 0.430; 14.6% vs. 20.3%, respectively, P = 0.388) was also similar between the follow-up groups for low- and high-risk patients.

Conclusions: Shortening the postoperative follow-up interval from every 4-6 months to every 2-4 months within the first 2 years after resection did not increase the rate of curative intent treatment or prolong the overall survival of patients with Barcelona Clinic Liver Cancer stage A or B HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40880-018-0296-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993133PMC
May 2018
-->