Publications by authors named "Wei Ou"

64 Publications

Hospital-based case control study and animal study on the relationship between nonylphenol exposure and depression.

PeerJ 2021 18;9:e11384. Epub 2021 May 18.

School of Public Health, Zunyi Medical University, Zunyi, Guizhou, PR China.

Objectives: The aim of this work is to explore the association between chronic exposure to nonylphenol (NP), a representative environmental endocrine disruptor (EED), and the risk of depression and its potential mechanism.

Methods: A hospital-based case control study was conducted from August to December 2018. Forty-one patients with confirmed depression and 47 healthy volunteers were recruited. In vitro, 20 rats were randomly divided into the control group (corn oil) and NP exposure group (=10 per group), which were gavaged at a dose of 4 mg/kg w/day for 180 days.

Results: The depressed patient group had higher Zung Self-Rating Depression Scale (SDS) (<0.001) and Self-Rating Anxiety Scale (SAS) (<0.001) scores than the healthy group. The serum NP level (=0.009) in the depressed group was higher than that in the healthy group, and the BDNF level (=0.001) was lower. The serum levels of monoamine neurotransmitters dopamine (DA) (=0.070), epinephrine (E) (=0.001), and noradrenaline (NE) (=0.000) were lower than those in the healthy group. In the sucrose preference test, the sucrose preference time for the exposure group of rats was lower than that of the control group (<0.001). In the forced swim test, a longer resting time was measured for the exposure group of rats as compared to the control group (<0.05). The level of NP (<0.001) in the brain tissue of the NP exposure group was higher than that in the control group, and the serum level of brain-derived neurotrophic factor (BDNF) (=0.004) was lower. Histopathological examination of the brain biopsies illustrated that the neuronal cells and nuclei in the hippocampus of the exposed group exhibited slight shrinkage.

Conclusion: Chronic exposure to NP at environmental doses will result in the accumulation of NP in the brain and blood, and induction of depression, which might be associated with the alterations in the expression levels of BDNF and monoamine neurotransmitters.
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http://dx.doi.org/10.7717/peerj.11384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139269PMC
May 2021

Hypoxic acclimation improves cardiac redox homeostasis and protects heart against ischemia-reperfusion injury through upregulation of O-GlcNAcylation.

Redox Biol 2021 Jul 30;43:101994. Epub 2021 Apr 30.

Laboratory of Mitochondria and Metabolism, Department of Anesthesiology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, 610041, China; Laboratory of Anesthesia and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, 610041, China. Electronic address:

Ischemia-reperfusion (I/R) injury is detrimental to cardiovascular system. Alteration in glucose metabolism has been recognized as an important adaptive response under hypoxic conditions. However, the biological benefits underlying this metabolic phenotype remain to be elucidated. This study was designed to investigate the impact of hypoxic acclimation (HA) on cardiac I/R injury and the antioxidative mechanism(s). Male adult mice were acclimated in a hypoxic chamber (10% oxygen [O]) for 8 h/day for 14 days, and then subjected to cardiac I/R injury by ligation of left anterior descending coronary artery for 30 min and reperfusion for 24 h or 7 days. Our results showed that HA attenuated oxidative stress and reduced infarct size in the I/R hearts. This cardioprotective effect is coupled with an elevation of protein O-linked N-acetylglucosamine (O-GlcNAc) modification partially due to inflammatory stimulation. Hyperglycosylation activated glucose-6-phosphate dehydrogenase (G6PDH), the rate-limiting enzyme in the pentose phosphate pathway, resulting in an upregulation of NADPH/NADP and GSH/GSSG couples and enhancement of redox homeostasis in the heart. Pharmacological suppression of O-GlcNAcylation totally abolished the influence of HA on the G6PDH activity, redox balance and post-I/R damage in the hearts and cultured cardiomyocytes, whereby augmentation of O-GlcNAcylation further enhanced the benefits, suggesting a central role of O-GlcNAcylation in HA-initiated antioxidative and cardioprotective effects. These findings, therefore, identified HA as a promising anti-I/R strategy for the heart and proposed O-GlcNAc modification of G6PDH as a therapeutic target in ischemic heart disease.
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http://dx.doi.org/10.1016/j.redox.2021.101994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121980PMC
July 2021

Effects of propofol on cardiac function and miR-494 expression in rats with hepatic ischemia/reperfusion injury.

J Int Med Res 2021 Mar;49(3):300060521990988

Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.

Objective: This study aimed to investigate the effects of propofol on cardiac function and miR-494 expression in rats with hepatic ischemia/reperfusion (I/R) injury.

Methods: Forty healthy adult male Sprague-Dawley rats were allocated to the sham operation group and three hepatic I/R injury groups. The I/R injury groups included I/R injury only (I/R group), treatment with propofol (propofol group), and treatment with propofol + overexpressed miR-494 (propofol+miR-494 group). Apoptosis of myocardial cells and changes in cardiac function indices, including left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and left ventricular posterior wall thickness, as well as changes in miR-494, were monitored.

Results: The apoptotic rate of myocardial cells in the I/R group was higher, cardiac function was deteriorated, and miR-494 levels were elevated compared with the sham group. The apoptotic rate was lower, cardiac function was improved, and miR-494 levels were suppressed in the propofol group compared with the I/R group. The apoptotic rate was higher, cardiac function was deteriorated, and miR-494 levels were elevated in the propofol+miR-494 group compared with the propofol group.

Conclusion: Propofol plays a vital role in preventing myocardial cell apoptosis and improvement of cardiac function by suppressing miR-494 in a hepatic I/R injury rat model.
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http://dx.doi.org/10.1177/0300060521990988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944537PMC
March 2021

Circulating Tumor DNA Analyses as a Potential Marker of Recurrence and Effectiveness of Adjuvant Chemotherapy for Resected Non-Small-Cell Lung Cancer.

Front Oncol 2020 15;10:595650. Epub 2021 Feb 15.

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

Background: Although adjuvant chemotherapy is established for patients with non-small-cell lung cancer (NSCLC), the long-term survival remains to be improved. Postsurgical circulating tumor DNA (ctDNA) analysis of resectable NSCLC may identify patients at high risk of recurrence after adjuvant chemotherapy and facilitate personalized therapy.

Methods: This analysis included 38 patients who underwent curative-intent resection and received adjuvant chemotherapy for NSCLC. ctDNA analyses of tumor tissue, and pre- and post-operative plasma samples were performed with next-generation sequencing targeting 425 cancer-relevant genes. We define a ctDNA positive event as at least one shared mutation identified simultaneously in the plasma and tumor specimens. The primary endpoint was recurrence-free survival (RFS).

Results: At least one somatic mutation was identified in the tumor tissue of all 38 patients. Tumor tissue-specific mutated ctDNA was detected in the preoperative plasma samples of 19 (50%) patients. ctDNA in preoperative plasma was in good accordance with that in tissue. ctDNA was detectable in the first post-operative pre-chemotherapy samples of 8 of 35 (22.9%) patients and was associated with inferior RFS (HR, 3.69; P = 0.033). ctDNA was detected in the first post-chemotherapy samples of 8 of 36 (22.2%) patients and was also associated with inferior RFS (HR, 8.76; P < 0.001).

Conclusions: Postoperative and post-chemotherapy ctDNA is a promising prognostic marker for resected NSCLC. ctDNA analyses may define a subgroup that remains at high risk of relapse despite standard adjuvant chemotherapy, and may help to inform intensified therapeutic strategies.
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http://dx.doi.org/10.3389/fonc.2020.595650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919598PMC
February 2021

Deficiency of Mitochondrial Functions and Peroxidation of Frontoparietal Cortex Enhance Isoflurane Sensitivity in Aging Mice.

Front Aging Neurosci 2020 3;12:583542. Epub 2020 Dec 3.

Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China.

: Hypersensitivity to general anesthetics may predict poor postoperative outcomes, especially among the older subjects. Therefore, it is essential to elucidate the mechanism underlying hypersensitivity to volatile anesthetics in the aging population. Given the fact that isoflurane sensitivity increases with aging, we hypothesized that deficiencies of mitochondrial function and elevated oxidative levels in the frontoparietal cortex may contribute to the enhanced sensitivity to isoflurane in aging mice. : Isoflurane sensitivity in aging mice was determined by the concentration of isoflurane that is required for loss of righting reflex (LORR). Mitochondrial bioenergetics of the frontoparietal cortex was measured using a Seahorse XFp analyzer. Protein oxidation and lipid oxidation in the frontoparietal cortex were assessed using the Oxyblot protein oxidation detection kit and thiobarbituric acid reactive substance (TBARS) assay, respectively. Contributions of mitochondrial complex II inhibition by malonate and peroxidation by ozone to isoflurane sensitivity were tested . Besides, effects of antioxidative therapy on mitochondrial function and isoflurane sensitivity in mice were also measured. : The mean concentration of isoflurane that is required for LORR in aging mice (14-16 months old) was 0.83% ± 0.13% (mean ± SD, = 80). Then, the mice were divided into three groups as sensitive group (S group, mean - SD), medium group (M group), and resistant group (R group, mean + SD) based on individual concentrations of isoflurane required for LORR. Activities of mitochondrial complex II and complex IV in mice of the S group were significantly lower than those of the R group, while frontoparietal cortical malondialdehyde (MDA) levels were higher in the mice of S group. Both inhibition of mitochondrial complexes and peroxidation significantly decreased the concentration of isoflurane that is required for LORR . After treatment with idebenone, the levels of lipid oxidation were alleviated and mitochondrial function was restored in aging mice. The concentration of isoflurane that required for LORR was also elevated after idebenone treatment. : Decreased mitochondrial functions and higher oxidative stress levels in the frontoparietal cortex may contribute to the hypersensitivity to isoflurane in aging mice.
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http://dx.doi.org/10.3389/fnagi.2020.583542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744615PMC
December 2020

Room-Temperature Palladium-Catalyzed Deuterogenolysis of Carbon Oxygen Bonds towards Deuterated Pharmaceuticals.

Angew Chem Int Ed Engl 2021 03 9;60(12):6357-6361. Epub 2021 Feb 9.

International Collaborative Laboratory of 2D Materials for Optoelectronic Science & Technology, Engineering Technology Research Center for 2D Materials Information Functional Devices and Systems of Guangdong Province, Institute of Microscale Optoelectronics, Shenzhen University, Shenzhen, 518060, China.

Site-specific incorporation of deuterium into drug molecules to study and improve their biological properties is crucial for drug discovery and development. Herein, we describe a palladium-catalyzed room-temperature deuterogenolysis of carbon-oxygen bonds in alcohols and ketones with D balloon for practical synthesis of deuterated pharmaceuticals and chemicals with benzyl-site (sp C-H) D-incorporation. The highlights of this deoxygenative deuteration strategy are mild conditions, broad scope, practicability and high chemoselectivity. To enable the direct use of D O, electrocatalytic D O-splitting is adapted to in situ supply D on demand. With this system, the precise incorporation of deuterium in the metabolic position (benzyl-site) of ibuprofen is demonstrated in a sustainable and practical way with D O.
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http://dx.doi.org/10.1002/anie.202014196DOI Listing
March 2021

Targeting Mitochondria-Inflammation Circuit by β-Hydroxybutyrate Mitigates HFpEF.

Circ Res 2021 Jan 12;128(2):232-245. Epub 2020 Nov 12.

Laboratory of Mitochondrial and Metabolism, Department of Anesthesiology, National Clinical Research Center for Geriatrics (Y.D., M.X., Q.L., W.O., Y. Zhang, H.Y., Y. Zheng, Y.L., C.J., G.C., D.D., W.Z., S.W., M.G., T.L.), West China Hospital of Sichuan University, Chengdu.

Rationale: Over 50% of patients with heart failure have preserved ejection fraction (HFpEF), rather than reduced ejection fraction. Complexity of its pathophysiology and the lack of animal models hamper the development of effective therapy for HFpEF.

Objective: This study was designed to investigate the metabolic mechanisms of HFpEF and test therapeutic interventions using a novel animal model.

Methods And Results: By combining the age, long-term high-fat diet, and desoxycorticosterone pivalate challenge in a mouse model, we were able to recapture the myriad features of HFpEF. In these mice, mitochondrial hyperacetylation exacerbated while increasing ketone body availability rescued the phenotypes. The HFpEF mice exhibited overproduction of IL (interleukin)-1β/IL-18 and tissue fibrosis due to increased assembly of NLPR3 inflammasome on hyperacetylated mitochondria. Increasing β-hydroxybutyrate level attenuated NLPR3 inflammasome formation and antagonized proinflammatory cytokine-triggered mitochondrial dysfunction and fibrosis. Moreover, β-hydroxybutyrate downregulated the acetyl-CoA pool and mitochondrial acetylation, partially via activation of CS (citrate synthase) and inhibition of fatty acid uptake.

Conclusions: Therefore, we identify the interplay of mitochondrial hyperacetylation and inflammation as a key driver in HFpEF pathogenesis, which can be ameliorated by promoting β-hydroxybutyrate abundance.
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http://dx.doi.org/10.1161/CIRCRESAHA.120.317933DOI Listing
January 2021

Spatiotemporal variation and distribution characteristics of crop residue burning in China from 2001 to 2018.

Environ Pollut 2021 Jan 27;268(Pt A):115849. Epub 2020 Oct 27.

Jilin Academy of Agricultural Sciences, Changchun, 130033, China. Electronic address:

In this study, we integrated a remote-sensing fire product (MOD14A1) and land-use product (MCD12Q1) to extract the number of crop-residue burning (CRB) spots and the fire radiative power (FRP) in China from 2001 to 2018. Moreover, we conducted three trend analyses and two geographic distribution analyses to quantify the interannual variations and summarize the spatial characteristics of CRB on grid (0.25° × 0.25°) and regional scales. The results indicated that CRB presents distinctive seasonal patterns with each sub-region. All trend analyses suggested that the annual number of CRB spots in China increased significantly from 2001 to 2018; the linear trend reached 2615 spots/year, the Theil-Sen slope was slightly lower at 2557 spots/year, and the Mann-Kendal τ was 0.75. By dividing the study period into two sub-periods, we found that the five sub-regions presented different trends in the first and second sub-periods; e.g., the Theil-Sen slope of eastern China in the first sub-period (2001-2009) was 1021 spots/year but was -1599 spots/year in the second period (2010-2018). This suggests that summer CRB has been effectively mitigated in eastern China since 2010. Further, the average FRP of CRB spots presented a decreasing trend from 27.5 MW/spot in 2001 to only 15.8 MW/spot in 2018; this may be attributable to more scattered CRB rather than aggregated CRB. Collectively, the fire spots, FRP, and average FRP indicated that spring, summer, and autumn CRB had dropped dramatically over previous levels by 2018 due to strict mitigation measures by local governments.
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http://dx.doi.org/10.1016/j.envpol.2020.115849DOI Listing
January 2021

LncRNA SNHG16 as a potential biomarker and therapeutic target in human cancers.

Biomark Res 2020 10;8:41. Epub 2020 Sep 10.

Thoracic Surgery Department 2, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013 PR China.

Long non-coding RNAs (lncRNAs) represent an important class of RNAs comprising more than 200 nucleotides, which are produced by RNA polymerase II. Although lacking an open reading framework and protein-encoding activity, lncRNAs can mediate endogenous gene expression by serving as chromatin remodeler, transcriptional or post-transcriptional modulator, and splicing regulator during gene modification. In recent years, increasing evidence shows the significance of lncRNAs in many malignancies, with vital roles in tumorigenesis and cancer progression. Moreover, lncRNAs were also considered potential diagnostic and prognostic markers in cancer. The lncRNA small nuclear RNA host gene 16 (SNHG16), found on chromosome 17q25.1, represents a novel tumor-associated lncRNA. SNHG16 was recently found to exhibit dysregulated expression in a variety of malignancies. There are growing evidence of SNHG16's involvement in characteristics of cancer, including proliferation, apoptosis, together with its involvement in chemoresistance. In addition, SNHG16 has been described as a promising diagnostic and prognostic biomarker in cancer patients. The current review briefly summarizes recently reported findings about SNHG16 and discuss its expression, roles, mechanisms, and diagnostic and prognostic values in human cancers.
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http://dx.doi.org/10.1186/s40364-020-00221-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487997PMC
September 2020

Parthenolide Inhibits Angiogenesis in Esophageal Squamous Cell Carcinoma Through Suppression of VEGF.

Onco Targets Ther 2020 29;13:7447-7458. Epub 2020 Jul 29.

Department of the 2nd Thoracic Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China.

Background: Parthenolide (PT), the effective active ingredient of the medicinal plant, feverfew (), has been used as an anti-inflammatory drug due to its involvement in the inhibition of the NF-кB pathway. Moreover, recent studies have demonstrated the anti-tumor effect of PT in several cancers. However, the effect of PT on esophageal carcinoma remains unclear to date. In this study, we examined the inhibitory effects of PT and its underlying mechanism of action in human esophageal squamous cell carcinoma (ESCC) cells - Eca109 and KYSE-510.

Methods: The proliferation ability of Eca109 and KYSE-510 treated with PT was detected using the Cell Counting Kit-8 and colony forming assay. The Transwell assay and the wound healing assay were used to analyze the cell invasion and migration ability, respectively. The tube formation assay was used to investigate the effect of PT on tube formation of endothelial cells. The expression level of NF-кB, AP-1 and VEGF was analyzed by Western blot.

Results: We demonstrated that PT attenuates the proliferation and migration ability of ESCC cells in vitro and also inhibits tumor growth in the mouse xenograft model. In addition, PT exhibited anti-angiogenesis activity by weakening the proliferation, invasion and tube formation of endothelial cells in vitro and reduced microvessel density in the xenograft tumors. Further studies revealed that PT reduced the expression level of NF-кB, AP-1 and VEGF in ESCC cells.

Conclusion: Collectively, the results of our study demonstrated that PT exerts anti-tumor and anti-angiogenesis effects possibly by inhibiting the NF-кB/AP-1/VEGF signaling pathway on esophageal carcinoma and might serve as a promising therapeutic agent for ESCC.
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http://dx.doi.org/10.2147/OTT.S256291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398702PMC
July 2020

Undetectable circulating tumor DNA levels correlate with low risk of recurrence/metastasis in postoperative pathologic stage I lung adenocarcinoma patients.

Lung Cancer 2020 08 20;146:327-334. Epub 2020 Jun 20.

Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address:

Objectives: The application of circulating tumor DNA (ctDNA) monitoring after resection in pathologic(p) stage I lung adenocarcinoma (LUAD) patients remains controversial and it is of great clinical interest to decipher the difference of genetic features between ground-glass opacity (GGO) and solid nodules (non-GGO) subgroups. We aim to assess the utility of ctDNA in tracking early recurrence or metastasis following surgery and reveal the genetic differences between GGO and non-GGO.

Materials And Methods: Tumor tissues and matched postoperative plasma samples were collected from a total of 82 (p)stage I LUAD patients. Comprehensive genomic profiling was performed using capture-based hybrid next generation sequencing by targeting 422 cancer relevant genes.

Results: EGFR and TP53 represent commonly mutated genes in this cohort of (p)stage I lung adenocarcinoma, followed by alterations in ALK, PIK3CA, STK11 and MYC. For a median follow-up period of 22.83 months after surgery, 65 out of 67 ctDNA-negative patients remained progression-free, while 3 out of 15 ctDNA-positive patients progressed [P = 0.040; positive predictive value = 0.20, 95 % confidence interval (CI), 0.04-0.48; negative predictive value = 0.97, 95 % CI, 0.9-1]. With time-dependent Cox regression analysis, we observed that ctDNA positivity significantly correlated with increased probability of early tumor recurrence or metastasis (P = 0.02, HR=8.5). Further comparison between GGO and non-GGO subgroups indicated the frequency of TP53 mutations in non-GGO was markedly higher than that in GGO (47 % vs 21 %, P < 0.05). Pathway analysis showed the epigenetic regulation pathway was more frequently affected in GGO subgroup, while impaired apoptosis/cell cycle pathway was more enriched in non-GGO LUADs.

Conclusions: Our longitudinal ctDNA monitoring data showed that undetectable ctDNA may predict low risk of tumor recurrence or metastasis in postoperative (p)stage I LUAD patients, while it requires further investigation on how robust the positive ctDNA results could predict tumor relapse in these patients.

Clinical Registration Number: NCT03172156.
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http://dx.doi.org/10.1016/j.lungcan.2020.06.009DOI Listing
August 2020

Chronic Alcohol Intake Exacerbates Cardiac Dysfunction After Myocardial Infarction.

Alcohol Alcohol 2020 Aug;55(5):524-530

Laboratory of Mitochondrial Biology and Anesthesia, West China-Washington Mitochondria and Metabolism Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, No 37 Wainan Guoxue Road, Chengdu 610041, PR China.

Aims: Alcohol intake is a risk factor for cardiovascular diseases. This study was designed to investigate whether chronic alcohol intake affects myocardial infarction (MI)-induced cardiac remodeling and heart failure.

Methods: Eight-week-old male C57BL/6 mice were randomly divided into four groups: Sham group (Sham), MI plus drinking water group (MI + Vehicle), and MI plus daily alcohol intake for 6 weeks with or without gavage of additional alcohol every 3 days (MI + Alcohol and MI + Alcohol + G). The MI were induced by permanent left anterior descending (LAD) coronary artery ligation surgery before vehicle or alcohol treatment. The blood alcohol concentration (BAC), cardiac function, release of cardiac enzymes, pathological changes and mitochondrial function were measured.

Results: As expected, supplementation of alcohol in drinking water significantly increased random BAC in mice. Long-term exposure to alcohol further reduced body weight, ejection fraction and fractional shortening in comparison with the MI + Vehicle group. Histopathological data showed that alcohol increased fibrosis in infarct zone, which was well correlated with the functional decline. Also, as compared to the MI + Vehicle group, the adenosine diphosphate-supported respiratory function of freshly isolated cardiac mitochondria was inhibited in the MI + Alcohol + G group. Besides, upon MI-induced cardiac damage, we did not observe further changes in heart weight, cardiomyocyte enlargement in remote zone, exercise capacity, lung edema and the release of cardiac enzyme after chronic alcohol intake.

Conclusions: Our study demonstrated that chronic daily alcohol exposure exacerbated MI-induced cardiac dysfunction, which is related to promoted myocardial fibrosis and inhibited mitochondrial function.
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http://dx.doi.org/10.1093/alcalc/agaa055DOI Listing
August 2020

Involvement of noncoding RNAs in epigenetic modifications of esophageal cancer.

Biomed Pharmacother 2019 Sep 11;117:109192. Epub 2019 Jul 11.

Department of the 2nd Thoracic Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, PR China. Electronic address:

Esophageal cancer (EC) is a serious digestive malignancy and is a leading cause of cancer-related mortality. Apart from genetic mutations, many epigenetic alterations including DNA methylation and histone modifications associated with chromatin remodeling have been identified in the regulation of gene expression in EC. Recently, noncoding RNAs, and mainly lncRNAs and miRNAs, have been revealed to be involved in the epigenetic regulation of EC. In this review, we focus on describing new insights on epigenetic processes associated with noncoding RNAs, which have been characterized to be responsible for the development and progression of EC.
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http://dx.doi.org/10.1016/j.biopha.2019.109192DOI Listing
September 2019

Factors Influencing Aspirin Hyporesponsiveness in Elderly Chinese Patients.

Med Sci Monit 2019 Jul 13;25:5191-5200. Epub 2019 Jul 13.

Department of Geriatrics, Peking University First Hospital, Peking University, Beijing, China (mainland).

BACKGROUND Aspirin hyporesponsiveness increases the risk of ischemic events. Therefore, it is important to investigate the factors influencing aspirin hyporesponsiveness. MATERIAL AND METHODS Patients aged 60 years or older who did not take aspirin before enrollment were included, with aspirin 100 mg/day administered after enrollment. The arachidonic acid-induced platelet aggregation rate (Ara) was measured by light transmission assay to evaluate aspirin responsiveness. Patients with Ara in the upper quartile after taking aspirin were assigned to the aspirin hyporesponsive group (Ara-Q4). RESULTS A total of 292 elderly patients were included. The median value of Ara after taking aspirin was 5.87% (interquartile range 3.86-10.04%). Compared with the aspirin non-hyporesponsive group (Ara-Q1-3, Ara ≤10.04%, n=220), the level of uric acid (UA) (341.30 µmol/L vs. 299.10 µmol/L, p=0.027) and the ratios of ß-blockers (9.72% vs. 2.27%, p=0.015) and diuretics (6.94% vs. 1.36%, p=0.036) were higher in the aspirin hyporesponsive group (Ara-Q4, Ara >10.04%, n=72). After multivariate adjustment, the results demonstrated baseline Ara (odds ratio [OR]: 1.030, 95% confidence interval [CI]: 1.004-1.056, p=0.021), UA level (OR: 1.003, 95% CI: 1.000-1.006, p=0.038), and ß-blockers use (OR: 5.487, 95% CI: 1.515-19.870, p=0.010) were independently and positively associated with aspirin hyporesponsiveness. CONCLUSIONS This study found that baseline Ara, UA level, and ß-blockers use were independently and positively associated with aspirin hyporesponsiveness in elderly Chinese patients, which needs to be validated in large-scale studies.
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http://dx.doi.org/10.12659/MSM.917654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647928PMC
July 2019

Dynamic monitoring of depressive behavior induced by nonylphenol and its effect on synaptic plasticity in rats.

Sci Total Environ 2019 Nov 17;689:1012-1022. Epub 2019 Jun 17.

School of Public Health, Zunyi Medical University, Zunyi, Guizhou 563000, PR China. Electronic address:

The etiology of depression is not known, it is thought that endocrine-disrupting chemicals (EDCs) contribute to the disease. Results of our previous research have shown that nonylphenol (NP), a well-known EDC, has neurotoxic effects, however, whether NP can induce depressive behavior by affecting synaptic plasticity has not yet been clearly elucidated. The depressive behavior induced by subchronic exposure to NP and its effect on the neuronal synaptic plasticity in rats are dynamically observed. Thirty Sprague-Dawley rats were randomly divided into 3 groups: control group (C, corn oil), NP group (NP, 4 mg/kg), and depression model group (D, corticosterone 20 mg/kg). There were 8 rats in each group. The depressive behavior of rats was tested by sucrose preference test, open-field test, and forced swimming test once a month for 3 months. The serum levels of brain-derived neurotrophic factor (BDNF) and corticosterone were detected by ELISA assay, and cellular morphological changes were observed by hematoxylin-eosin (HE) staining. The number of nerve cells, the length of dendrites, and the density of dendritic spines were observed by Golgi staining, and the synaptic cleft width, the postsynaptic density (PSD) thickness, and the synaptic interface curvature were observed by transmission electron microscope. Compared with the control group, the consumption of sucrose solution decreased in the NP group at the 2nd and 3rd month compared to the 1st month (F = 9.887, P = 0.002). The number of central square entries, the central square duration, and the total distance of movement were all decreased, and the decreasing degrees at the 3rd month were greater than those at the 1st month (F = 21.191, P < 0.001; F = 9.836, P = 0.002). The time of immobility for the NP group at the 1st month was higher than that in the control group (F = 6.912, P = 0.002). The expression of BDNF in the NP-treated group was higher than the control, while the expression of corticosterone in the NP-treated group was lower than the control. In the NP group, the cytoplasm of nerve cells contracted and appeared disordered. The neuron arrangement was disordered, and the number of cells, the length of the apex, the length of the basal dendrites, and the dendritic spine density were all lower in the NP group than those in the control group. The PSD thickness, the synaptic cleft width, and synaptic interface curvatures were all decreased in the NP group when compared to the control group. Subchronic exposure to 4 mg/kg NP led to depressive behavior in rats, and the depressive behavior and alterations in synaptic plasticity were more obvious with longer exposure time.
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http://dx.doi.org/10.1016/j.scitotenv.2019.06.250DOI Listing
November 2019

Apatinib monotherapy for advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy.

Thorac Cancer 2018 10 20;9(10):1285-1290. Epub 2018 Aug 20.

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

Background: Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), has proven to be effective and safe for treating patients with advanced gastric cancer after second-line chemotherapy failure. As VEGFR-2 targeted therapy has made encouraging progress for the treatment of a broad range of malignancies, we explored the efficacy and safety of apatinib for the treatment of advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy.

Methods: We retrospectively analyzed the data of 34 patients (11 with squamous carcinoma and 23 with adenocarcinoma) who were treated with apatinib alone in a daily oral dose of 250 mg in the second-line or third-line setting from January 2016 to July 2017. The primary endpoint was progression-free survival (PFS).

Results: EGFR mutation or amplification was detected in 15 patients. The median PFS of the whole group was four months (95% confidence interval 0.3-7.7). A partial response was observed in 2 patients (5.88%) and stable disease in 19 (55.88%). The disease control rate was 61.76%. Common side effects of apatinib were hypertension (n = 12), hand-foot syndrome (n = 8), and proteinuria (n = 5), which accounted for 35.30%, 23.53%, and 14.71%, respectively, and no grade 3/4 adverse reactions occurred. Apatinib toxicity was controllable and tolerable.

Conclusions: Apatinib appears to be effective and safe for advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy.
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http://dx.doi.org/10.1111/1759-7714.12836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166085PMC
October 2018

Iridium-Catalyzed Reductive Alkylations of Secondary Amides.

Angew Chem Int Ed Engl 2018 Aug 31;57(35):11354-11358. Epub 2018 Jul 31.

Department of Chemistry, Fujian Provincial Key Laboratory of Chemical Biology, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005, P. R. China.

Reported herein is the first direct, metal-catalyzed reductive functionalization of secondary amides to give functionalized amines and heterocycles. The method is shown to have exceptionally broad scope with respect to suitable nucleophiles, which cover both hard and soft C nucleophiles as well as a P nucleophile. The reaction exhibits good chemoselectivity and tolerates several sensitive functional groups.
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http://dx.doi.org/10.1002/anie.201806747DOI Listing
August 2018

Contrast-Enhanced Ultrasound Improves the Pathological Outcomes of US-Guided Core Needle Biopsy That Targets the Viable Area of Anterior Mediastinal Masses.

Biomed Res Int 2018 18;2018:9825709. Epub 2018 Jan 18.

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

Based on the option that ultrasound-guided core needle biopsy (US-CNB) of the enhanced portion of anterior mediastinal masses (AMMs) identified by contrast-enhanced ultrasound (CEUS) would harvest viable tissue and benefit the histological diagnoses, a retrospective study was performed to elucidate the correlation between the prebiopsy CEUS and diagnostic yield of AMMs and found that CEUS potentially improved the diagnostic yield of AMMs compared with conventional US with a significant increase in the cellularity of samples. Furthermore, the marginal blood flow signals and absence of necrosis can predict the diagnostic yield of AMM. It was concluded that US-CNB of the viable part of AMMs, as verified by CEUS, was able to harvest sufficient tissue with more cellularity that could be used for ancillary studies and improve the diagnostic yield. And CEUS was recommended to those patients with AMMs undergoing repeated US-CNB, with the absence of marginal blood signals or presence of necrosis.
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http://dx.doi.org/10.1155/2018/9825709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822857PMC
September 2018

Model checking optimal finite-horizon control for probabilistic gene regulatory networks.

BMC Syst Biol 2017 12 14;11(Suppl 6):104. Epub 2017 Dec 14.

Department of Mathematics and Statistics, University of Calgary, Calgary, Canada.

Background: Probabilistic Boolean networks (PBNs) have been proposed for analyzing external control in gene regulatory networks with incorporation of uncertainty. A context-sensitive PBN with perturbation (CS-PBNp), extending a PBN with context-sensitivity to reflect the inherent biological stability and random perturbations to express the impact of external stimuli, is considered to be more suitable for modeling small biological systems intervened by conditions from the outside. In this paper, we apply probabilistic model checking, a formal verification technique, to optimal control for a CS-PBNp that minimizes the expected cost over a finite control horizon.

Results: We first describe a procedure of modeling a CS-PBNp using the language provided by a widely used probabilistic model checker PRISM. We then analyze the reward-based temporal properties and the computation in probabilistic model checking; based on the analysis, we provide a method to formulate the optimal control problem as minimum reachability reward properties. Furthermore, we incorporate control and state cost information into the PRISM code of a CS-PBNp such that automated model checking a minimum reachability reward property on the code gives the solution to the optimal control problem. We conduct experiments on two examples, an apoptosis network and a WNT5A network. Preliminary experiment results show the feasibility and effectiveness of our approach.

Conclusions: The approach based on probabilistic model checking for optimal control avoids explicit computation of large-size state transition relations associated with PBNs. It enables a natural depiction of the dynamics of gene regulatory networks, and provides a canonical form to formulate optimal control problems using temporal properties that can be automated solved by leveraging the analysis power of underlying model checking engines. This work will be helpful for further utilization of the advances in formal verification techniques in system biology.
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http://dx.doi.org/10.1186/s12918-017-0481-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751526PMC
December 2017

Pricing, Carbon Emission Reduction, Low-Carbon Promotion and Returning Decision in a Closed-Loop Supply Chain under Vertical and Horizontal Cooperation.

Int J Environ Res Public Health 2017 11 1;14(11). Epub 2017 Nov 1.

School of Knowledge Science, Japan Advanced Institute of Science and Technology, Asahidai 1-1, Nomi City, Ishikawa 923-1292, Japan.

In this paper, we examine the influences of vertical and horizontal cooperation models on the optimal decisions and performance of a low-carbon closed-loop supply chain (CLSC) with a manufacturer and two retailers, and study optimal operation in the competitive pricing, competitive the low-carbon promotion, the carbon emission reduction, the used-products collection and the profits. We consider the completely decentralized model, M-R vertical cooperation model, R-R horizontal cooperation model, M-R-R vertical and horizontal cooperation model and completely centralized model, and also identify the optimal decision results and profits. It can be observed from a systematic comparison and numerical analysis that the completely centralized model is best in all optimal decision results among all models. In semi-cooperation, the M-R vertical cooperation model is positive, the R-R horizontal cooperation model is passive, and the positivity of the M-R-R vertical and horizontal cooperation model decreases with competitive intensity increasing in the used-products returning, carbon emissions reduction level, low-carbon promotion effort and the profits of the manufacturer and the entire supply chain.
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http://dx.doi.org/10.3390/ijerph14111332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707971PMC
November 2017

Clinico-radiological features and next generation sequencing of pulmonary epithelioid hemangioendothelioma: A case report and review of literature.

Thorac Cancer 2017 11 4;8(6):687-692. Epub 2017 Aug 4.

Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.

Epithelioid hemangioendothelioma is a very rare, vascular, low-grade malignant tumor found in the lungs, liver, bone, and other soft tissues. Most patients with pulmonary epithelioid hemangioendothelioma (PEH) are asymptomatic but usually present with multiple bilateral nodular lesions in the lungs. Currently, surgical lung biopsy, histology, and immunohistochemical methods are essential for diagnosis. However, there is no standard therapy for the treatment for PEH. Our paper describes the clinico-radiologic features and genomics of PEH based on next-generation sequencing (NGS) in a 43-year-old male we encountered. The patient came to the hospital with right chest pain. After investigation, a lesion in the middle lobe of the right lung was found, together with smaller multiple lesions in both lungs. After resection of the lesion, histopathological analysis showed positive findings for PEH. The patient's blood and tumor tissue were sent for NGS analysis for further investigation. Results from the analysis revealed mutations of multiple genes. The information obtained from the genomic analysis of PEH using NGS may be significant for the planning and monitoring of treatment for this disease.
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http://dx.doi.org/10.1111/1759-7714.12474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668507PMC
November 2017

Impacts of EGFR mutation and EGFR-TKIs on incidence of brain metastases in advanced non-squamous NSCLC.

Clin Neurol Neurosurg 2017 Sep 29;160:96-100. Epub 2017 Jun 29.

Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. Electronic address:

Objective: Brain metastases remain lethal in lung cancer patients. The impacts of epidermal growth factor receptor (EGFR) mutations and EGFR tyrosine kinase inhibitors (TKIs) on the incidence of brain metastases in patients with advanced non-squamous non-small cell lung cancer (NSCLC) are still uncertain.

Patients And Methods: A total of 1672 patients with advanced non-squamous NSCLC with a definitive report on EGFR mutation status between January 2005 and June 2013 were retrospectively analyzed. The impacts of EGFR mutation status and EGFR TKIs use on the incidence of brain metastases and survival were investigated.

Results: Of the 1672 patients, 465 (27.8%) had an EGFR mutation, and 1207 (72.2%) did not. Four hundred and eighteen (25.0%) patients had baseline brain metastases. The cumulative incidence of brain metastases for patients in EGFR+ group was significantly higher than patients in EGFR- group (HR, 1.27; 95% CI 1.06-1.52; P=0.008). The cumulative incidence of brain metastases was also higher for patients who received an EGFR-TKI as their first-line treatment than those who received other first-line treatment (HR, 1.36; 95% CI 1.14-1.64; P=0.001). Patients harboring EGFR mutations had prolonged overall survival (OS) than patients with wild-type EGFR (HR, 0.47; 95% CI 0.41-0.54; P<0.001; median, 25.2 vs. 12.9 months).

Conclusions: Both the EGFR mutation-positive status and the use of a TKI are associated with higher incidence of brain metastases for patients with advanced non-squamous NSCLC.
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http://dx.doi.org/10.1016/j.clineuro.2017.06.022DOI Listing
September 2017

Propofol inhibits hepatocellular carcinoma growth and invasion through the HMGA2-mediated Wnt/β-catenin pathway.

Exp Ther Med 2017 May 22;13(5):2501-2506. Epub 2017 Mar 22.

Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guizhou, Guiyang 550001, P.R. China.

Propofol is a commonly used intravenous anesthetic in tumor surgery. Recently, studies have confirmed that propofol has an antitumor effect on hepatocellular carcinoma (HCC); however, the molecular mechanism underlying this effect has not been elucidated until now. The present study aimed to investigate the mechanism of propofol on HepG2 cell proliferation, apoptosis and invasion, focusing on High Mobility Group AT-Hook 2 (HMGA2)-mediated Wnt/β-catenin pathway. The HepG2 cells were treated with various concentrations of propofol for 24 h, the relative protein levels of HMGA2, Wnt3a, β-catenin, Snail Family Zinc Finger 1 and c-myc were determined by western blot analysis. HMGA2-pcDNA3.1 plasmid was transfected into the HepG2 cells to overexpress HMGA2. Cell proliferation, apoptosis and invasion were examined by MTT assays, flow cytometry and Transwell-matrigel invasion assays, respectively. The results showed that propofol suppressed HMGA2 expression and Wnt/β-catenin signaling in a dose-dependent manner. Propofol was able to inhibit cell proliferation and invasion, and induce cell apoptosis of HepG2 cells; however, these effects were attenuated by HMGA2 overexpression. The suppressed Wnt/β-catenin signaling in HepG2 cells by treatment with propofol was also reversed by HMGA2 overexpression. In conclusion, this study provided a novel mechanism underlying the anti-tumor function of propofol on HCC. To the best of our knowledge, the present study is the first to demonstrate that propofol could downregulate the expression of HMGA2, which inhibited the Wnt/β-catenin pathway, thus leading to the inhibition of cell proliferation and invasion, as well as the apoptosis of HepG2 cells.
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http://dx.doi.org/10.3892/etm.2017.4253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443290PMC
May 2017

Elevated pretreatment neutrophil/white blood cell ratio and monocyte/lymphocyte ratio predict poor survival in patients with curatively resected non-small cell lung cancer: Results from a large cohort.

Thorac Cancer 2017 07 22;8(4):350-358. Epub 2017 May 22.

Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.

Background: The prognostic values of preoperative neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), and platelet/lymphocyte ratio (PLR) in non-small cell lung cancer (NSCLC) have been previously described. This study assessed the prognostic values of other pretreatment complete blood cell parameters in Chinese patients with curatively resected NSCLC.

Methods: A total of 1466 consecutive NSCLC patients who received curative surgery from January 1, 2005 to December 31, 2009 with complete data from pretreatment blood tests were enrolled in this retrospective study. Correlations between each blood test parameter and overall survival were examined by Kaplan-Meier method or Cox proportional hazards regression, followed by a stratification analysis of significant variables.

Results: Optimal cut-off values of 0.55 for neutrophil/white blood cell ratio (NWR), 0.28 for lymphocyte/white blood cell ratio (LWR), 0.09 for monocyte/white blood cell ratio (MWR), 2.06 for NLR, 0.35 for MLR, 204.00 for PLR, and 38.25 for platelet/white blood cell ratio (PWR) were identified using X-tile software. Univariate analysis suggested that NWR ≥ 0.55, LWR < 0.28, MWR ≥ 0.09, NLR ≥ 2.06, MLR ≥ 0.35, and PLR ≥ 204.00 predicted a poor prognosis in NSCLC patients. However, only NWR and MLR were identified as independent significant prognostic factors in multivariable analysis, especially in tumor node metastasis stage I and I/II/III NSCLCs.

Conclusion: Pretreatment NWR, MWR, LWR, NLR, MLR, and PLR values are associated with poor overall survival for patients with curatively resected NSCLC. NWR and MLR are independent prognostic factors in curatively resected NSCLC.
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http://dx.doi.org/10.1111/1759-7714.12454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5494473PMC
July 2017

Effect of dexmedetomidine on hippocampal neuron development and BDNF-TrkB signal expression in neonatal rats.

Neuropsychiatr Dis Treat 2016 9;12:3153-3159. Epub 2016 Dec 9.

Department of Anesthesia, Guizhou Medical University Affiliated Hospital, Guiyang, People's Republic of China.

The study aimed to explore the effect of dexmedetomidine (DEX) on hippocampal neuron development process and on molecular expression of brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling pathway in neonatal rats. The hippocampal neuron cells were isolated from newborn neonatal rats and cultured in vitro. One control group and three treated groups with 1, 10, and 100 μmol/L DEX were used for the study. Cell activity and apoptosis were detected by the MTT and terminal deoxynucleotidyl transferase-mediated biotinylated uridine triphosphate (UTP) nick end labeling assays. The synaptophysin (SYN) and postsynaptic density 95 (PSD95) were detected by quantitative polymerase chain reaction. There was no difference in the viability of neuron cells among the different dose groups of DEX and the control group during days 2-10 (>0.05). Compared to the control group, there was no significant difference (>0.05) in the expressions of SYN and PSD95 in the groups treated with 1 and 10 μmol/L DEX, whereas significant difference in the expression was observed in the group treated with 100 μmol/L DEX (<0.01). Compared with the control group, the expression of BDNF was significantly upregulated (<0.05) in the group treated with 100 μmol/L DEX. There were no significant differences in TrkB expression among the four groups. The expression of p-N-methyl-D-aspartate receptor increased with an increase in the concentration of DEX; however, only the high dose revealed a significant upregulation compared with the control group. The neuroprotective effect of DEX may be achieved by upregulating the expression of BDNF and phosphorylation level of N-methyl-D-aspartate receptor.
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http://dx.doi.org/10.2147/NDT.S120078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5158139PMC
December 2016

Chemoselective reductive alkynylation of tertiary amides by Ir and Cu(i) bis-metal sequential catalysis.

Chem Commun (Camb) 2016 Sep;52(80):11967-11970

Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian Province, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, P. R. China.

We report herein a convenient and versatile method for the direct reductive alkynylation of tertiary amides to give propargylic amines through sequential Ir-catalysed hydrosilylation-Cu(i)-catalysed alkynylation. The reactions proceed chemoselectively at the amide group in the presence of several sensitive functional groups including the very reactive aldehyde group on either the amide or the alkyne coupling partner. The method is general for tert-amides with or without α-hydrogen.
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http://dx.doi.org/10.1039/c6cc05318aDOI Listing
September 2016

Phase 2 trial of neoadjuvant bevacizumab plus pemetrexed and carboplatin in patients with unresectable stage III lung adenocarcinoma (GASTO 1001).

Cancer 2016 Mar 23;122(5):740-7. Epub 2015 Dec 23.

Breast Tumor Center, Sun Yat-sen Memorial Hospital; Sun Yat-sen University, Guangzhou, China.

Background: The objective of this phase 2 trial was to assess the efficacy and safety of induction bevacizumab plus chemotherapy followed by surgery in patients with unresectable stage III lung adenocarcinoma.

Methods: The authors investigated induction bevacizumab (7.5 mg/kg) plus pemetrexed (500 mg/m(2) and carboplatin (area under the receiver operating characteristic curve = 5) followed by surgery for patients with unresectable stage III lung adenocarcinoma ages 18 to 65 years. The patients received neoadjuvant therapy every 3 weeks for 4 cycles. Surgery was scheduled 3 to 4 weeks after the last neoadjuvant therapy; then, the medical team assessed each patient's resectability status. The primary endpoint was the resectability rate.

Results: From April 2012 to April 2014, 42 patients were enrolled and received bevacizumab plus pemetrexed and carboplatin. Grade 3 or 4 induction-related AEs included fatigue in 5 patients, neutropenia in 4 patients, hypertension in 1 patient, anemia in 1 patient, and thrombocytopenia in 1 patient. One patient achieved a complete response, 22 achieved a partial response, 17 had stable disease, and 2 had progressive disease. After neoadjuvant therapy, 31 patients (73.8%) underwent surgery, including 11 who underwent pneumonectomy. Complete (R0) resection was achieved in 22 patients (52.4%). Reoperation was required in 1 patient because of a bleeding intercostal artery. No perioperative thromboembolic events or wound-healing problems were observed. The median event-free survival was 15.4 months, and the 1-year event-free survival rate was 56.1%.

Conclusions: Treatment with neoadjuvant bevacizumab in combination with pemetrexed and carboplatin followed by surgery appears to be feasible and safe in patients with unresectable stage III lung adenocarcinoma. Cancer 2016;122:740-747. © 2015 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.29800DOI Listing
March 2016

Prognostic role of the ABO blood types in Chinese patients with curatively resected non-small cell lung cancer: a retrospective analysis of 1601 cases at a single cancer center.

Chin J Cancer 2015 Sep 28;34(10):475-82. Epub 2015 Sep 28.

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

Background: A positive association between the ABO blood types and survival has been suggested in several malignancies. The aim of this study was to assess the role of the ABO blood types in predicting the prognosis of Chinese patients with curatively resected non-small cell lung cancer (NSCLC).

Methods: We retrospectively analyzed 1601 consecutive Chinese patients who underwent curative surgery for NSCLC between January 1, 2005 and December 31, 2009. The relationship between the ABO blood types and survival was investigated. In addition, univariate and multivariate analyses were performed.

Results: Group 1 (patients with the blood type O or B) had significantly prolonged overall survival (OS) compared with group 2 (patients with the blood type A or AB), with a median OS of 74.9 months versus 61.5 months [hazard ratio (HR) 0.83; 95% confidence interval (CI) 0.72-0.96; P = 0.015]. Additionally, group 1 had significantly longer disease-free survival (DFS; HR 0.86; 95% CI 0.76-0.98; P = 0.022) and locoregional relapse-free survival (LRFS; HR 0.79; 95% CI 0.64-0.98; P = 0.024) than group 2. The association was not significantly modified by other risk factors for NSCLC, including smoking status, pathologic tumor-node-metastasis stage, pT category, pN category, and chemotherapy.

Conclusions: There is an association between the ABO blood types and the survival of Chinese patients with resected NSCLC. Patients with the blood type O or B had significantly prolonged OS, DFS, and LRFS compared with those with the blood type A or AB.
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http://dx.doi.org/10.1186/s40880-015-0054-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593379PMC
September 2015

Elevated serum bilirubin levels are associated with improved survival in patients with curatively resected non-small-cell lung cancer.

Cancer Epidemiol 2015 Oct 7;39(5):763-8. Epub 2015 Jul 7.

Department of Thoracic Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, China. Electronic address:

Background: Bilirubin levels have been associated with risk of several malignancies. The association between pretreatment serum bilirubin levels and survival of curatively resected non-small-cell lung cancer (NSCLC) is unclear.

Methods: This analysis was performed retrospectively in a cohort of 1617 consecutive patients with bilirubin levels within the range considered normal, who received curative resection for NSCLC. The receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off points. The significance of pretreatment serum total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) levels in the prognosis of patients with curatively resected NSCLC was investigated.

Results: The cutoff points of serum TBIL, DBIL and IBIL were 9.50μmol/L, 3.45μmol/L and 6.95μmol/L, respectively. High TBIL was observed in 65.2% of entire patient population, high DBIL 50%, and high IBIL 56.8%. The high-TBIL group had significantly lengthened overall survival (OS; hazard ratio [HR], 0.73; 95% confidence interval [CI] 0.63-0.84; P<0.001), disease-free survival (DFS; HR, 0.72; 95% CI 0.64-0.82; P<0.001) and distant metastasis-free survival (DMFS; HR, 0.74; 95% CI 0.60-0.91; P=0.004). Similarly, high-DBIL and high-IBIL levels were associated with longer OS, DFS, and DMFS with significant differences. In multivariable analysis, IBIL level was identified as an independent significant prognostic factor.

Conclusions: Moderately elevated pretreatment bilirubin levels are associated with longer OS, DFS, and DMFS for patients with curatively resected NSCLC. IBIL is an independent prognostic factor in curative resected NSCLC.
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http://dx.doi.org/10.1016/j.canep.2015.06.007DOI Listing
October 2015

[Safety of Neoadjuvant Bevacizumab plus Pemetrexed and Carboplatin 
in Patients with IIIa Lung Adenocarcinoma].

Zhongguo Fei Ai Za Zhi 2015 Jun;18(6):365-8

Sun Yat-sen University Cancer Center, State Key laboratory of South China, Guangzhou 510060, China.

Background And Objective: Bevacizumab has showed its efficacy in advanced non-squamous lung cancer. The aim of this study is to assess the safety of bevacizumab plus pemetrexed and carboplatin neoadjuvant chemotherapy in patients with lung adenocarcinoma.

Methods: 25 patients with IIIa lung adenocarcinoma undergoing lobectemy or pneumonectomy with mediastinal lymphadenectomy after induction bevacizumab (Bev) plus pemetrexed/carboplatin (PC) were selected. Toxicity of chemotherapy and postoperative complications were analyzed.

Results: Grade 3 or 4 neoadjuvant-related adverse events included fatigue (3 patients), neutropenia (3 patients), hypertension (1 patient). The adverse events thought to be related to bevacizumab included epistaxis in 2 patients (grade 1: 1; grade 2: 1) and hypertension in 3 patients (grade 1: 2; grade 3: 1). Postoperative complications included pneumonia in 2 patients, bronchial stump insufficiency in 1 case, atelectasis in 2 cases, and arrhythmia in 1 case. Hemorrhage events, thromboembolic events and wound-healing problems were not observed in the perioperative period.

Conclusions: The treatment modality of neoadjuvant Bev-PC appears to be safe and tolerant in patients with stage IIIa lung adenocarcinoma.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2015.06.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999904PMC
June 2015