Publications by authors named "Yong Fang"

355 Publications

Apatinib plus gefitinib as first-line treatment in advanced EGFR-mutant non-small cell lung cancer: the phase III ACTIVE study (CTONG1706).

J Thorac Oncol 2021 May 22. Epub 2021 May 22.

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

Introduction: Blocking vascular endothelial growth factor (VEGF) pathway can enhance the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC). ACTIVE is the first phase III study conducted in China, evaluating apatinib, a VEGFR2 TKI, plus gefitinib as first-line therapy in EGFR-mutant NSCLC.

Methods: Treatment-naïve patients with stage IIIB/IV non-squamous NSCLC, an ECOG PS of 0/1 and EGFR ex19del or ex21L858R mutation were randomized 1:1 to receive oral gefitinib (250 mg/day), plus apatinib (500 mg/day; A+G group) or placebo (P+G group). Stratification factors: mutation type, sex and PS. The primary endpoint was PFS by blinded independent radiology review committee (IRRC). Secondary endpoints: investigator-assessed PFS, OS, quality of life (QoL), safety, etc. Next-generation sequencing was used to explore efficacy predictors and acquired resistance.

Results: 313 patients were assigned to the A+G (n=157) or P+G group (n=156). Median IRRC-PFS in the A+G group was 13.7 months vs 10.2 months in the P+G group (HR 0.71; P=.0189). Investigator- and IRRC-assessed PFS were similar. OS was immature. The most common treatment-emergent adverse events ≥grade 3 were hypertension (46.5%) and proteinuria (17.8%) in the A+G group and increased ALT (10.4%) and AST (3.2%) in the P+G group. QoL in the two groups had no statistical differences. Post-hoc analysis showed PFS benefits tended to favor the A+G group in patients with TP53 ex8 mutation.

Conclusions: Apatinib+gefitinib as first-line therapy demonstrated superior PFS in advanced EGFR-mutant NSCLC vs placebo+gefitinib. Combination therapy brought more adverse events but did not interfere QoL.
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http://dx.doi.org/10.1016/j.jtho.2021.05.006DOI Listing
May 2021

[Intramedullary nailing through suprapatellar approach with semiextended position for the treatment of tibial fractures].

Zhongguo Gu Shang 2021 May;34(5):452-7

The Second Department of Orthopaedics, the First People's Hospitalof Xiaoshan, Hangzhou 311201, Zhejiang, China.

Objective: To explore clinical effects of intramedullary nailing through suprapatellar approach with semiextended position in treating tibial fractures.

Methods: From January 2018 to June 2019, 23 patients with tibia fractures were treated with suprapatellar approach intramedullary nailing on knee semiextended position, including 18 males and 5 females, aged from 26 to 67 years old with an average age of (38.5±9.6) years old. Eight patients were tibial proximal fractures, 7 patients were tibial shaft fractures, 6 patients were tibial distal fractures and 2 patients were tibial segmental fractures. Operation time, intraoperative blood loss, complications and fracture healing time were recorded. Range of motivation of knee joint between 3 days and 3 months after operation were compared, Hospital for Special Surgery (HSS) score and visual analogue scale (VAS) were used to evaluate clinical effects.

Results: All patients were followed up from 8 to 19 months with an average of (12.3±7.6) months. Operation time was (55.3±5.1) min, intraoperative blood loss was (84.0±8.7) ml. No obvious complications occurred. All patients were achieved bony union at stageⅠ, fracture healing time ranged from 3 to 8 months with an average of (4.6±1.5) months. Flexion extension range of knee motion at 3 days after operation was (110.4±15.3)°, and increased to (123.7±16.5)° at 3 months after operation (=6.57, <0.001). Postoperative VAS at 3 days was (0.22±0.74) scores, and decreased to (0.04±0.20) scores at 3 months after operation (=1.09, >0.05). Postoperative HSS score at 6 months was 86.2± 11.5, and 19 got excellent result and 4 good.

Conclusion: Intramedullary nailing through suprapatellar approach with semiextended position in treating tibia fractureshas advantages of simple operation, less trauma for soft tissue, less pain, rapid recovery of function and less complication. It is especially suitable for patients with tibial multi-segment fracture and multiple fractures of ipsilateral lower limb for safety and simple.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2021.05.011DOI Listing
May 2021

Isolation, structural characterization and neuroprotective activity of exopolysaccharide from Paecilomyces cicada TJJ1213.

Int J Biol Macromol 2021 May 8;183:1034-1046. Epub 2021 May 8.

College of Food Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, PR China. Electronic address:

Two exopolysaccharide fractions (EPS1 and EPS2) were obtained from Paecilomyces cicadae TJJ 1213, and their structures were elucidated. The EPS1 and EPS2 were mainly composed of mannose and galactose with molar ratios of 3.2: 1.0 and 2.7: 1.0, respectively. They possessed average molecular weights of 1.69 × 10 and 8.06 × 10 Da, respectively. Structural characterization indicated that the backbone of EPS1 was consisted of →4)-α-D-Manp (1→, →3,4)-α-D-Manp (1 → and →2,6)-α-D-Manp (1→, →6)-α-D-Galp (1→, →6)-β-D-Galp (1→, and side chain was consisted of α-D-Manp residue. The backbone of EPS2 was composed of →6)-β-D-Galp-(1→, →4)-α-D-Manp-(1→, →2,6)-α-D-Manp-(1 → and →6)-α-D-Galp-(1→, and the branching point was also consisted of α-D-Manp residue. In addition, EPS1 and EPS2 had potential in protective effects of PC12 cells against hydrogen peroxide induced oxidative stress by inhibiting the production of ROS, reducing LDH leakage and alleviating mitochondrial damage. These results indicated that EPS1 and EPS2 might serve as therapeutic agents for neuronal disorders.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.047DOI Listing
May 2021

The prognostic significance of electrocardiography findings in patients with coronavirus disease 2019: A retrospective study.

Clin Cardiol 2021 May 11. Epub 2021 May 11.

Department of Cardiology, Intervention Cardiology Center, Wuhan No.1 Hospital, No.215 Zhongshan Avenue, QiaoKou District, Wuhan, China.

Background: Coronavirus disease 2019 (COVID-19) has reached a pandemic level. Cardiac injury is not uncommon among COVID-19 patients. We sought to describe the electrocardiographic characteristics and to identify the prognostic significance of electrocardiography (ECG) findings of patients with COVID-19.

Hypothesis: ECG abnormality was associated with higher risk of death.

Methods: Consecutive patients with laboratory-confirmed COVID-19 and definite in-hospital outcome were retrospectively included. Demographic characteristics and clinical data were extracted from medical record. Initial ECGs at admission or during hospitalization were reviewed. A point-based scoring system of abnormal ECG findings was formed, in which 1 point each was assigned for the presence of axis deviation, arrhythmias, atrioventricular block, conduction tissue disease, QTc interval prolongation, pathological Q wave, ST-segment change, and T-wave change. The association between abnormal ECG scores and in-hospital mortality was assessed in multivariable Cox regression models.

Results: A total of 306 patients (mean 62.84 ± 14.69 years old, 48.0% male) were included. T-wave change (31.7%), QTc interval prolongation (30.1%), and arrhythmias (16.3%) were three most common found ECG abnormalities. 30 (9.80%) patients died during hospitalization. Abnormal ECG scores were significantly higher among non-survivors (median 2 points vs 1 point, p < 0.001). The risk of in-hospital death increased by a factor of 1.478 (HR 1.478, 95% CI 1.131-1.933, p = 0.004) after adjusted by age, comorbidities, cardiac injury and treatments.

Conclusions: ECG abnormality was common in patients admitted for COVID-19 and was associated with adverse in-hospital outcome. In-hospital mortality risk increased with increasing abnormal ECG scores.
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http://dx.doi.org/10.1002/clc.23628DOI Listing
May 2021

[Expert Consensus for Thermal Ablation of Pulmonary Subsolid Nodules (2021 Edition)].

Zhongguo Fei Ai Za Zhi 2021 May 26;24(5):305-322. Epub 2021 Apr 26.

Department of Oncology, Tengzhou Central People's Hospital, Tengzhou 277500, China.

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2021.101.14DOI Listing
May 2021

Persistent 2-3 σ-bonded heteronuclear radical cations centered on S/Se and P/As atoms.

Chem Commun (Camb) 2021 May;57(41):5067-5070

State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.

The two-center three-electron (2c-3e) bonded species are important in chemical and biological science. Reported isolable 2c-3e σ-bonded species are usually constructed in homoatomic radicals. The one-electron oxidation of main-group heteronuclear species Nap(SPh)(P(Mes)2) (1), Nap(SePh)(P(Mes)2) (2), Nap(SPh)(As(Mes)2) (3) and Nap(SePh)(As(Mes)2) (4) produced persistent radical cations 1˙+-4˙+ in solution. Large couplings of heteroatoms in EPR spectra of 1˙+-4˙+, shorter bond distances and bigger Wiberg bond orders of Ch-Pn in 1˙+-4˙+ than those in 1-4 in DFT calculations indicate large amounts of spin densities over heteroatoms and the formation of 2c-3e σ-bonds between chalcogen and pnicogen atoms. This work provides evidence of 2c-3e σ-bonds constructed between main-group heteronuclears and rare examples of radical cations involving three-electron σ-bonds between S/Se and P/As atoms.
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http://dx.doi.org/10.1039/d1cc01117kDOI Listing
May 2021

Selenium in cereals: Insight into species of the element from total amount.

Compr Rev Food Sci Food Saf 2021 May 9;20(3):2914-2940. Epub 2021 Apr 9.

College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing, 210023, China.

Selenium (Se) is a trace mineral micronutrient essential for human health. The diet is the main source of Se intake. Se-deficiency is associated with many diseases, and up to 1 billion people suffer from Se-deficiency worldwide. Cereals are considered a good choice for Se intake due to their daily consumption as staple foods. Much attention has been paid to the contents of Se in cereals and other foods. Se-enriched cereals are produced by biofortification. Notably, the gap between the nutritional and toxic levels of Se is fairly narrow. The chemical structures of Se compounds, rather than their total contents, contribute to the bioavailability, bioactivity, and toxicity of Se. Organic Se species show better bioavailability, higher nutritional value, and less toxicity than inorganic species. In this paper, we reviewed the total content of Se in cereals, Se speciation methods, and the biological effects of Se species on human health. Selenomethionine (SeMet) is generally the most prevalent and important Se species in cereal grains. In conclusion, Se species should be considered in addition to the total Se content when evaluating the nutritional and toxic values of foods such as cereals.
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http://dx.doi.org/10.1111/1541-4337.12748DOI Listing
May 2021

Clinical value of endobronchial ultrasound-guided aspiration and local isoniazid injection in the treatment of mediastinal tuberculous lymphadenitis.

Ann Palliat Med 2021 Apr 23;10(4):4289-4298. Epub 2021 Mar 23.

Department of Endoscopy, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.

Background: This study aimed to investigate the value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) guided purulence aspiration and local isoniazid injection after lymph node puncture in the treatment of refractory mediastinal tuberculous lymphadenitis (MTLA) as compared to systemic anti-tuberculosis treatment.

Methods: This was a retrospective study. A total of 92 patients with MTLA and suppurative lymphadenitis who were treated in the Shanghai Pulmonary Hospital between January 2015 and December 2018 were included into present study and divided into systemic chemotherapy (CT) group and interventional therapy (IT) group. In the CT group, patients received systemic chemotherapy alone; in the IT group, patients received EBUS-TBNA guided lymph node aspiration and local isoniazid injection besides systemic chemotherapy. The recovery of lymphadenitis and adverse effects were observed.

Results: Seventy patients were included for final analysis, 35 patients in each group. In the IT group, aspiration and local injection were done 137 times; 4R (53.1%) and 7 groups of lymph nodes (30.6%) were the most common site of aspiration; the median number of local treatment was 3 times, and the median duration of local injection was 29 days. The recovery rate of lymphadenitis was 88.6% (31/35) in the IT group and 57.1% (20/35) in the CT group, showing marked difference (χ2=8.741, P<0.05). The most common symptoms of patients with MTLA were cough, fever, dyspnea and anorexia, and the time to recovery of these symptoms in the IT group was 0.83±0.32, 0.89±0.29, 1.00±0.18 and 1.07±0.15 months, respectively, which were markedly shorter than in the CT group 2.60±0.74, 2.46±0.73, 2.70±0.40 and 2.67±0.43 months (t=7.608, P<0.05; t=6.442, P<0.05; t=6.755, P<0.05; t=5.237, P<0.05). All the patients received EBUS-TBNA under local anesthesia, and evident adverse effects were not observed. They were followed up for 2 years, and recurrence was not noted.

Conclusions: As compared to systemic chemotherapy, EBUS-TBNA guided lymph node aspiration and local isoniazid injection combined with systemic chemotherapy may significantly improve the therapeutic efficacy, which provides a new, safe and reliable management for the refractory MTLA.
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http://dx.doi.org/10.21037/apm-20-1809DOI Listing
April 2021

Novel Nutrition-Based Nomograms to Assess the Outcomes of Lung Cancer Patients Treated With Anlotinib or Apatinib.

Front Oncol 2021 8;11:628693. Epub 2021 Mar 8.

Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Background: Previous studies have indicated that the changes in body composition during treatment are prognostic in lung cancer. The question which follows is it may be too late to identify vulnerable patients after treatment and to improve outcomes for these patients. In our study, we sought to explore the alterations of body composition and weight before the outset of the antiangiogenic treatment and its role in predicting clinical response and outcomes.

Methods: In this retrospective study, 122 patients with advanced lung cancer treated with anlotinib or apatinib were analyzed. The changes in weight and body composition including skeletal muscle index (SMI), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) for 3 months before the outset of antiangiogenic treatment and other clinical characteristics were evaluated with LASSO Cox regression and multivariate Cox regression analysis, which were applied to construct nomograms. The performance of the nomograms was validated internally by using bootstrap method with 1,000 resamples models and was assessed by the concordance index (C-index), calibration plots, decision curve analysis (DCA).

Results: The median progression-free survival (PFS) and overall survival (OS) were 128 (95% CI 103.2-152.8) days and 292 (95% CI 270.9-313.1) days. Eastern Cooperative Oncology Group performance status (ECOG PS), brain metastases, the Glasgow Prognostic Score (GPS), clinical response, therapeutic regimen, and ΔL1SMI per 90 days were significantly associated with PFS, while ECOG PS, GPS, clinical response, therapeutic regimen, ΔL1SMI per 90 days were identified for OS. The C-index for the nomograms of PFS and OS were 0.763 and 0.748, respectively. The calibration curves indicated excellent agreement between the predicted and actual survival outcomes of 3- and 4-month PFS and 7- and 8-month OS. DCA showed the considerable value of the model.

Conclusion: Nomograms were developed from clinical features and nutritional indicators to predict the probability of achieving 3-month and 4-month PFS and 7-month and 8-month OS with antiangiogenic therapy for advanced lung cancer. Dynamic changes in body composition before the initiation of treatment contributed to early detection of poor outcome.
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http://dx.doi.org/10.3389/fonc.2021.628693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982902PMC
March 2021

Morbidity and Mortality of Patients Who Underwent Minimally Invasive Esophagectomy After Neoadjuvant Chemoradiotherapy vs Neoadjuvant Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: A Randomized Clinical Trial.

JAMA Surg 2021 May;156(5):444-451

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), The First Department of Thoracic Surgery, Peking University Cancer Hospital and Institute, Peking University School of Oncology, Beijing, China.

Importance: Safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) vs neoadjuvant chemotherapy (nCT) for treatment of locally advanced esophageal squamous cell carcinoma (ESCC) remain uncertain given lack of high-level clinical evidence.

Objective: To compare safety and long-term survival of nCRT followed by minimally invasive esophagectomy (MIE) with that of nCT followed by MIE for patients with locally advanced ESCC.

Design, Setting, And Participants: A prospective, multicenter, open-label, randomized clinical trial that compared safety and efficacy of nCRT vs nCT followed by MIE for patients with locally advanced ESCC. From January 1, 2017, to December 31, 2018, 264 patients with ESCC of clinical stages from cT3 to T4aN0 to 1M0 were enrolled. Analysis was performed on an intention-to-treat basis from January 1, 2017, to August 30, 2020.

Interventions: Eligible patients were randomized to the nCRT group (n = 132) or the nCT group (n = 132) by a computer-generated random system. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while 40 Gy of concurrent radiotherapy was added for the nCRT group. At about 6 weeks after neoadjuvant therapy, MIE via thoracoscopy and laparoscopy was performed for the patients in both groups.

Main Outcomes And Measures: The primary outcome was 3-year overall survival. Secondary outcomes included postoperative complications, mortality, postoperative pathologic outcome, recurrence-free survival time, and quality of life.

Results: Among 264 patients (226 men [85.6%]; mean [SD] age, 61.4 [6.8] years), postoperative morbidity was 47.4% in the nCRT group (54 of 114) and 42.6% in the nCT group (46 of 108), with no significant difference between groups (difference, 4.8%; 95% CI, -8.2% to 17.5%; P = .48). Distribution of the severity of complications was similar between the 2 groups based on Clavien-Dindo classification. The 90-day perioperative mortality rate was 3.5% for the nCRT group (4 of 114) and 2.8% for the nCT group (3 of 108) (P = .94). The R0 resection rates were similar between groups (109 of 112 [97.3%] vs 100 of 104 [96.2%]; P = .92). However, patients in the nCRT group had a higher pathologic complete response (residual tumor, 0%) rate (40 of 112 [35.7%] vs 4 of 104 [3.8%]; P < .001) and a higher rate of negative lymph nodes (ypN0, 74 of 112 [66.1%] vs 48 of 104 [46.2%]; P = .03) than those in the nCT group. One-year overall survival using intention-to-treat analysis was 87.1% in the nCRT group (115 of 132) and 82.6% in the nCT group (109 of 132) (P = .30). Furthermore, deaths caused by tumor progression or recurrence were significantly less in the nCRT group than in the nCT group (9 of 132 [6.8%] vs 19 of 132 [14.4%]; P = .046); however, deaths from nontumor causes were similar (8 of 132 [6.1%] vs 4 of 132 [3.0%]; P = .24).

Conclusions And Relevance: Initial results of the trial showed that nCRT followed by MIE has similar safety to and better histopathologic outcome than nCT followed by MIE for treatment of locally advanced ESCC.

Trial Registration: ClinicalTrials.gov Identifier: NCT03001596.
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http://dx.doi.org/10.1001/jamasurg.2021.0133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970392PMC
May 2021

Pattern of No. 12a lymph node metastasis in gastric cancer.

Chin J Cancer Res 2021 Feb;33(1):61-68

Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Objective: The current standard D2 lymphadenectomy for gastric cancer (GC) includes dissection of lymph nodes (LNs) along the proper hepatic artery (No. 12a), however, the survival benefit remains controversial. The purpose of this study was to evaluate the pattern of No. 12a LN metastasis (LNM) in GC and explore the indications for No. 12a LN dissection.

Methods: Medical records of 413 consecutive GC patients who underwent curative surgery in Zhongshan Hospital, Fudan University between January 2015 and December 2018 were enrolled and reviewed retrospectively. The correlation between No. 12a LNM and clinicopathologic characteristics of patients was analyzed.

Results: The overall incidence of No. 12a LNM was 2.67% (11/413). Tumor location (P=0.012), depth of tumor infiltration (P<0.01) and N stage (P=0.018) were significant factors associated with No. 12a LNM. All the tumors with No. 12a LNM involved the lower third of the stomach and were in T3-4 stages. Patients with No. 12a LNM had extensive LNM than those without (20.91±4.25. 5.0±0.54, P<0.001). For advanced GC patients (stage III/IV) with tumors involving the lower third of the stomach, the incidence of No. 12a LNM increased to 10.7% (11/103). Patients with No. 12a LNM had a significantly poorer recurrence-free survival (RFS) (P=0.005) and overall survival (OS) (P=0.017). According to the result of multivariable Cox regression, No. 12a LNM was not an independent impact factor on RFS and OS.

Conclusions: The overall incidence of No. 12a LNM was low but it was much higher in GC patients who had very advanced tumors involving the lower third of the stomach. No. 12a LN dissection should be considered for these patients to improve the survival outcomes.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2021.01.07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941682PMC
February 2021

Soybean-derived gma-miR159a alleviates colon tumorigenesis by suppressing TCF7/MYC in mice.

J Nutr Biochem 2021 06 8;92:108627. Epub 2021 Mar 8.

College of Food Science and Engineering/Collaborative Innovation Center for Modern Grain Circulation and Safety/Key Laboratory of Grains and Oils Quality Control and Processing, Nanjing University of Finance and Economics, Nanjing, China. Electronic address:

Previous reports have shown that plant-derived microRNAs (miRNAs) regulate mammalian gene expression through dietary intake. Our prior study found that gma-miR159a, which is abundant in soybean, significantly inhibited the proliferation of colon cancer cells. In the current study, dietary gma-miR159a was utilized to study its anti-colon cancer function in azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon cancer mice. Under processing conditions, gma-miR159a exhibited excellent stability in cooked soybean. In vitro, gma-miR159a suppressed the expression of the oncogene MYC downstream of the Wnt signaling pathway by targeting the TCF7 gene, significantly inhibiting the growth of colon cancer cells. The in vivo experiments showed that gma-miR159a and soybean RNA (total RNA extracted from soybean) significantly reduced tumor growth in AOM/DSS-induced colon cancer mice by gavage. This effect disappeared when anti-miR159a was present. In addition, gma-miR159a and soybean RNA significantly attenuated inflammation in colon cancer mice. These results showed that long-term dietary intake of soybean-derived gma-miR159a effectively prevented the occurrence of colon cancer and colitis, which provides novel evidence for the prevention function of soybean.
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http://dx.doi.org/10.1016/j.jnutbio.2021.108627DOI Listing
June 2021

Novel green chitosan-pectin gel beads for the removal of Cu(II), Cd(II), Hg(II) and Pb(II) from aqueous solution.

Int J Biol Macromol 2021 Apr 11;176:217-225. Epub 2021 Feb 11.

College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing 210023, China.

Chitosan-pectin gel beads (CPBs) were synthesized via a facile and green method and applied to remove heavy metals from aqueous solution. The structural characteristics of CPBs were investigated by SEM and FTIR, the mechanical strength of CPBs was measured by Texture Analyzer and the stability of CPBs was evaluated in acidic solution. To study the adsorption characteristics, the effect of pH, contact time, initial heavy metals concentration, temperature, adsorption mechanism and regeneration were systematically investigated. The adsorption kinetics fitted well pseudo-second-order model, and the adsorption isotherms were well described by Langmuir model. The maximum adsorption capacities of Cu(II), Cd(II), Hg(II) and Pb(II) were 169.4, 177.6, 208.5 and 266.5 mg/g, respectively. The adsorption-desorption experiments revealed that the CPBs exhibited a great reusability. Thus, the synthesized CPBs in this study had the potential to be utilized as an environment-friendly and green adsorbent for the removal of heavy metals.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.037DOI Listing
April 2021

Measurement Matrix Optimization for Compressed Sensing System with Constructed Dictionary via Takenaka-Malmquist Functions.

Sensors (Basel) 2021 Feb 9;21(4). Epub 2021 Feb 9.

Department of Computer and Information Science, Faculty of Science and Technology, University of Macau, Macau 999078, China.

Compressed sensing (CS) has been proposed to improve the efficiency of signal processing by simultaneously sampling and compressing the signal of interest under the assumption that the signal is sparse in a certain domain. This paper aims to improve the CS system performance by constructing a novel sparsifying dictionary and optimizing the measurement matrix. Owing to the adaptability and robustness of the Takenaka-Malmquist (TM) functions in system identification, the use of it as the basis function of a sparsifying dictionary makes the represented signal exhibit a sparser structure than the existing sparsifying dictionaries. To reduce the mutual coherence between the dictionary and the measurement matrix, an equiangular tight frame (ETF) based iterative minimization algorithm is proposed. In our approach, we modify the singular values without changing the properties of the corresponding Gram matrix of the sensing matrix to enhance the independence between the column vectors of the Gram matrix. Simulation results demonstrate the promising performance of the proposed algorithm as well as the superiority of the CS system, designed with the constructed sparsifying dictionary and the optimized measurement matrix, over existing ones in terms of signal recovery accuracy.
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http://dx.doi.org/10.3390/s21041229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916195PMC
February 2021

Tomato Chlorosis Virus Infection Facilitates MED Reproduction by Elevating Expression.

Insects 2021 Jan 25;12(2). Epub 2021 Jan 25.

Department of Entomology, University of Kentucky, Lexington, KY 40546, USA.

Transmission of plant pathogenic viruses mostly relies on insect vectors. Plant virus could enhance its transmission by modulating the vector. Previously, we showed that feeding on virus infected plants can promote the reproduction of the sweet potato whitefly, MED (Q biotype). In this study, using a whitefly-Tomato chlorosis virus (ToCV)-tomato system, we investigated how ToCV modulates MED reproduction to facilitate its spread. Here, we hypothesized that ToCV-infected tomato plants would increase MED fecundity via elevated gene expression. As a result, fecundity and the relative expression of MED was measured on ToCV-infected and uninfected tomato plants on days 4, 8, 12, 16, 20 and 24. The role of on MED reproduction was examined in the presence and absence of ToCV using dietary RNAi. ToCV infection significantly increased MED fecundity on days 12, 16 and 20, and elevated expression on days 8, 12 and 16. Both ovarian development and fecundity of MED were suppressed when was silenced with or without ToCV infection. These combined results suggest that ToCV infection increases MED fecundity via elevated expression.
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http://dx.doi.org/10.3390/insects12020101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911321PMC
January 2021

Proprotein Convertase Subtilisin/Kexin Type 9 Promotes Gastric Cancer Metastasis and Suppresses Apoptosis by Facilitating MAPK Signaling Pathway Through HSP70 Up-Regulation.

Front Oncol 2020 7;10:609663. Epub 2021 Jan 7.

Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.

Objective: To examine the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) on gastric cancer (GC) progression and prognosis, and to explore the underlying mechanism.

Methods: PCSK9 expression levels in human GC tissues were determined by quantitative real-time PCR, western blotting, and immunohistochemical assay. PCSK9 serum levels were detected by enzyme-linked immunosorbent assay. The relationships of PCSK9 and GC progression and survival were analyzed using the Chi-square test, Kaplan-Meier analysis, and Cox proportional hazards model. The effect of PCSK9 on cell invasion, migration, and apoptosis were determined in human GC cell lines and mouse xenograft model separately using PCSK9 knockdown and overexpression strategies. The PCSK9 interacting molecules, screened by co-immunoprecipitation combined with LC-MS/MS, were identified by immunofluorescence localization and western blotting. Additionally, the mitogen-activated protein kinase (MAPK) pathway was assessed by western blotting.

Results: PCSK9 mRNA and protein levels were significantly elevated in GC tissues compared with the paired normal tissues at our medical center (P < 0.001). Notably, the up-regulation of PCSK9 expression in GC tissues was related to tumor progression and poor survival. GC patients had higher serum levels of PCSK9 than the age-matched healthy controls (P < 0.001); PCSK9 promoted invasive and migratory ability and inhibited apoptosis in GC cells with no apparent affection in cell proliferation. The silencing of PCSK9 reversed these effects, suppressing tumor metastasis and . Furthermore, PCSK9 maintained these functions through up-regulating heat shock protein 70 (HSP70), ultimately facilitating the mitogen-activated protein kinase (MAPK) pathway.

Conclusion: Collectively, our data revealed that high PCSK9 expression levels in GC tissue were correlated with GC progression and poor prognosis and that PCSK9 could promote GC metastasis and suppress apoptosis by facilitating MAPK signaling pathway through HSP70 up-regulation. PCSK9 may represent a novel potential therapeutic target in GC.
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http://dx.doi.org/10.3389/fonc.2020.609663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817950PMC
January 2021

Dual function of VvWRKY18 transcription factor in the β-aminobutyric acid-activated priming defense in grapes.

Physiol Plant 2021 Jan 22. Epub 2021 Jan 22.

College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, China.

Induction of phytoalexin production after invading pathogens is recognized as an essential aspect of the plant-induced resistance. The WRKY family includes plant-specific transcriptional factors associated with plant defense responses, but the comprehensive mechanisms are poorly understood. Here, we attempted to elaborate the regulatory function of VvWRKY18 from the group IIa of WRKY transcription factor (TF) from Vitis vinifera, in the regulation of β-aminobutyric acid (BABA)-activated stilbene phytoalexins biosynthesis and PATHOGENESIS-RELATED (PR) genes expressions in grapes. BABA at 10 mmol L triggered a priming protection in grapes and conferred a potentiation of the expression levels of VvWRKY18, VvNPR1, and several salicylic acid (SA)-responsive genes, which was accompanied by enhanced stilbene production upon Botrytis cinerea infection. In addition, a physical interaction between VvWRKY18 and the regulatory protein VvNPR1 was detected in vivo and in vitro by yeast-2-hybrid (Y2H), pull-down and co-immunoprecipitation assay (Co-IP) assays. Furthermore, yeast-1-hybrid (Y1H) and dual-luciferase reporter (DLR) assays indicated that VvWRKY18 activated the transcription of STILBENE SYNTHASE (STS) genes, including VvSTS1 and VvSTS2, by directly binding the W-box elements within the specific promoters and resultantly enhancing stilbene phytoalexins biosynthesis. Further investigation demonstrated that heterologous expression of VvWRKY18 elevated the transcriptions of STS and PR genes, thus contributing to potentiating the defense of transgenic Arabidopsis thaliana plants and resultantly inhibiting B. cinerea invasion. Hence, VvWRKY18 serves as a singular effector involved in the synthesis of stilbene phytoalexins in grapes and its interaction with VvNPR1 provided DNA binding ability required for VvNPR1 to initiate systemic acquired resistance (SAR) defense.
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http://dx.doi.org/10.1111/ppl.13341DOI Listing
January 2021

Electrocatalytically inactive copper improves the water adsorption/dissociation on NiS for accelerated alkaline and neutral hydrogen evolution.

Nanoscale 2021 Feb;13(4):2456-2464

Shenzhen Engineering Laboratory of Phosphorene and Optoelectronics, International Collaborative Laboratory of 2D Materials for Optoelectronics Science and Technology, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China.

Nickel dichalcogenides, especially Ni3S2, present inferior alkaline and neutral hydrogen evolution activity due to their sluggish water dissociation kinetics. Although these materials hold promise as non-noble metal-based electrocatalysts for the hydrogen evolution reaction (HER) in acidic media, developing efficient strategies to enhance the water dissociation processes of nickel dichalcogenides in alkaline and neutral solutions is also an important area of research. The present work discloses an electrocatalytically inactive copper doping strategy to promote the water adsorption and dissociation process of Ni3S2 (Cu-Ni3S2) nanoparticles supported on nickel foam (NF) towards improving the alkaline and neutral hydrogen evolution reactions. Based on combined density functional theory calculations and electrochemical characterizations, the doping of Cu can accelerate the Volmer step and therefore strengthen the water adsorption/dissociation on the respective Ni sites and S sites during the HER process. As a result, the electrocatalyst exhibits superior and stable HER performance in both 1 M KOH and 1 M phosphate-buffered saline (PBS) solutions, with much lower overpotentials of 121 and 228 mV at a current density of 10 mA cm-2, respectively, in comparison to bare Ni3S2. We therefore conclude that the tailored control of the water adsorption/dissociation capability of Ni3S2 will open significant opportunities for the rational design of alkaline and neutral electrocatalysts from earth-abundant and stable materials.
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http://dx.doi.org/10.1039/d0nr07275cDOI Listing
February 2021

Circular RNA circSDHC serves as a sponge for miR-127-3p to promote the proliferation and metastasis of renal cell carcinoma via the CDKN3/E2F1 axis.

Mol Cancer 2021 01 20;20(1):19. Epub 2021 Jan 20.

Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan road II, Guangzhou, 510080, People's Republic of China.

Background: There is increasing evidence that circular RNAs (circRNAs) have significant regulatory roles in cancer development and progression; however, the expression patterns and biological functions of circRNAs in renal cell carcinoma (RCC) remain largely elusive.

Method: Bioinformatics methods were applied to screen for circRNAs differentially expressed in RCC. Analysis of online circRNAs microarray datasets and our own patient cohort indicated that circSDHC (hsa_circ_0015004) had a potential oncogenic role in RCC. Subsequently, circSDHC expression was measured in RCC tissues and cell lines by qPCR assay, and the prognostic value of circSDHC evaluated. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of circSDHC on RCC proliferation and metastasis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between circSDHC, miR-127-3p and its target genes.

Results: Clinically, high circSDHC expression was correlated with advanced TNM stage and poor survival in patients with RCC. Further, circSDHC promoted tumor cell proliferation and invasion, both in vivo and in vitro. Analysis of the mechanism underlying the effects of circSDHC in RCC demonstrated that it binds competitively to miR-127-3p and prevents its suppression of a downstream gene, CDKN3, and the E2F1 pathway, thereby leading to RCC malignant progression. Furthermore, knockdown of circSDHC caused decreased CDKN3 expression and E2F1 pathway inhibition, which could be rescued by treatment with an miR-127-3p inhibitor.

Conclusion: Our data indicates, for the first time, an essential role for the circSDHC/miR-127-3p/CDKN3/E2F1 axis in RCC progression. Thus, circSDHC has potential to be a new therapeutic target in patients with RCC.
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http://dx.doi.org/10.1186/s12943-021-01314-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816303PMC
January 2021

Inhibition of immunotoxicity of Pb-induced RAW264.7 macrophages by selenium species in selenium-enriched rice.

Food Chem Toxicol 2021 Feb 28;148:111943. Epub 2020 Dec 28.

College of Food Science and Engineering, Nanjing University of Finance and Economics/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing, PR China.

Previous studies have revealed that Selenium-enriched rice protein hydrolysates (SPHs) could alleviate Pb-induced apoptosis in RAW264.7 macrophages. The purpose of the current study was to detect the effect of different selenium (Se) species on immunotoxicity of the Pb-induced RAW264.7 macrophages and explore the potential immunomodulatory mechanism. Herein, SPHs, an isolated SPHs fraction (SPHs-2), selenomethionine (SeMet), selenite (Se) were used to investigate their inhibitory effect and the impacts on the expression of cytokines and related protein kinases in immunomodulatory pathways. The results showed that, compared with Pb-only group, Se-containing components significantly enhanced the cell viability and effectively decrease nitric oxide (NO) content in Pb-induced RAW264.7 cells. Furthermore, compared with other Se species, SPHs-2 markedly decreased the secretion levels of pro-inflammatory cytokines TNF-α, NF-κB, IL-1β, MyD88, IL-6 and IL-8. Western blot results demonstrated that SPHs-2 effectively downregulated the expressions of IκB, IKKα, p38, and Erk1/2, and also successfully blocked the phosphorylation of these protein kinases. Our findings suggested that SPHs-2 effectively attenuate inflammatory response and inhibit the immunotoxicity of Pb on RAW264.7 macrophages via regulating NF-κB/MAPK signaling pathways.
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http://dx.doi.org/10.1016/j.fct.2020.111943DOI Listing
February 2021

[Chemical profiling and tissue distribution study of Jingyin Granules in rats using UHPLC-Q-Exactive Orbitrap HR-MS].

Zhongguo Zhong Yao Za Zhi 2020 Nov;45(22):5537-5554

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine Shanghai 201203, China.

In this study, the chemical profiling of Jingyin Granules and the tissue distribution of nine major constituents in this Chinese medicine were performed after oral administration of Jingyin Granules to rats, by using UHPLC-Q-Exactive Orbitrap HR-MS. An Acquity UPLC BEH C_(18) chromatographic column(2.1 mm×100 mm, 1.7 μm) was used as solid phase, while the mobile phase was methanol and 0.1% formic acid water for gradient elution. The major constituents in this Chinese medicine were quickly and accurately identified, via comparison with the retention times and MS/MS spectra of the standards. A total of 106 chemicals were identified from Jingyin Granules, including 24 kinds of organic acids, 47 kinds of flavonoids, 10 kinds of iridoids, and 21 kinds of saponins and 4 kinds of other compounds. After oral administered Jingyin Granules to rats, 48, 30, 25, 23, 45, 34, 39, 26, 19 prototype compounds were identified in serum, heart, liver, spleen, lung, kidney, brain, fat, and testicles, respectively. Meanwhile, an LC-MS based analytical method was established for simultaneous determination of chlorogenic acid, swertiamarin, caffeic acid, sweroside, liquiritin, prim-O-glucosylcimifugin, arctiin, 5-O-methylvisammioside and arctigenin in biological samples. The tissue distribution(serum, liver and lung) of these nine aim constituents in rats after oral administration of Jingyin Granules were investigated. It was found that these nine constituents could be quickly absorbed into circulation system and then distributed to liver and lung tissues. Except arctigenin, the exposure of other eight aim constituents to serum and lung was peaked at 1 h. At 1 h, the exposure of these components to lung tissue were ranked as follows: swertiamarin [(75 191.0±3 483.21) ng·g~(-1)]>arctiin [(2 716.5±36.06) ng·g~(-1)]>5-O-methylvisammioside [(585.1±0.71) ng·g~(-1)]>arctigenin [(437.45±3.18) ng·g~(-1)]>chlorogenic acid [(308.1±5.66) ng·g~(-1)]>prim-O-glucosylcimifugin [(211.35±2.19) ng·g~(-1)]>sweroside [(184.3±9.05) ng·g~(-1)]>caffeic acid [(175.95±2.05) ng·g~(-1)]>liquiritin [(174.78±153.34) ng·g~(-1)]. In summary, an UHPLC-Q-Exactive Orbitrap HR-MS method has been established for rapid and accurate identification of the constituents in Jingyin Granules, while the tissue distribution of nine major absorpted constituents were investigated in rats following oral administration of Jingyin Granules. These findings provided key information and guidance for further studies on pharmacodynamic substances and clinical applications of Jingyin Granules.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200903.201DOI Listing
November 2020

CT-guided percutaneous minimally invasive radiofrequency ablation for the relief of cancer related pain from metastatic non-small cell lung cancer patients: a retrospective study.

Ann Palliat Med 2021 Feb 24;10(2):1494-1502. Epub 2020 Nov 24.

Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.

Background: Radiofrequency ablation (RFA) is the current gold standard for palliative care of non-small cell lung cancer (NSCLC). Pain relief for advanced metastases of NSCLC is notoriously difficult. Combined RFA therapy may be more effective than palliating therapy alone in management of painful metastatic disease. The effects of RFA on quality of life, particularly pain, as well as long-term outcome studies are not well studied. To study the effectiveness of percutaneous minimal invasive RFA in pain management of NSCLC patients with metastatic chest wall, vertebral bodies and rib, and periphery lung nodule.

Methods: Forty patients with 59 tumors underwent percutaneous computed tomography (CT) or ultrasound-guided RFA for pain management over a 4-week observation. Forty patients were referred to ablation because of persistent severe pain despite using analgesics, chemotherapy or radiotherapy. The tumors were located in the periphery lung, or metastatic to chest wall, rib or vertebral body. Quantitative pain scale values were quantified on a 0-10 scale before, 24 hours, 72 hours, and 4 weeks after RFA. On the basis of changes in pain score and pain medication use, pain was reported with a composite measure as complete, partial, or no pain response. The overall survival (OS) rate was also collected and calculated with Kaplan-Meier method.

Results: After 4-week follow-up, complete pain relief (pain scale score ≤1) was observed in 12 patients (30%) and partial pain relief (pain scale score ≤3) in 15 (37.5%) patients; pain relief did not occur in 13 patients (32.5%). There was a significant decrease in pain at 24-hour, 72-hour, and 4-week follow-up compared with pain level at baseline (P<0.01). Opiate use was decreased in 92.5% (37/40) patients, remained unchanged in 7.5% (3/40) at 4 weeks follow-up. There are minor adverse events caused by RFA therapy, including pleural effusion (5/40), post procedural infections (3/40), pneumothorax (2/40) which resolved spontaneously. The OS rates at 6 months in the percutaneous RFA group were 60%, with average OS of 6.5 months in the further follow-up.

Conclusions: Percutaneous RFA resulted in sustained pain relief from in most advanced NSCLC patients with intractable pain and resistant to chemotherapy or radiotherapy. The effect of RFA was satisfactory, and patients can obtain a better life quality with less pain and complications.
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http://dx.doi.org/10.21037/apm-19-474DOI Listing
February 2021

A Cross Entropy Based Deep Neural Network Model for Road Extraction from Satellite Images.

Entropy (Basel) 2020 May 9;22(5). Epub 2020 May 9.

School of Information Engineering, Chang'an University, Xi'an 710064, China.

This paper proposes a deep convolutional neural network model with encoder-decoder architecture to extract road network from satellite images. We employ ResNet-18 and Atrous Spatial Pyramid Pooling technique to trade off between the extraction precision and running time. A modified cross entropy loss function is proposed to train our deep model. A PointRend algorithm is used to recover a smooth, clear and sharp road boundary. The augmentated DeepGlobe dataset is used to train our deep model and the asynchronous training method is applied to accelerate the training process. Five salellite images covering Xiaomu village are taken as input to evaluate our model. The proposed E-Road model has fewer number of parameters and shorter training time. The experiments show E-Road outperforms other state-of-the-art deep models with 5.84% to 59.09% improvement, and can give the accurate predictions for the images with complex environment.
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http://dx.doi.org/10.3390/e22050535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517028PMC
May 2020

Application of endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis and treatment of mediastinal lymph node tuberculous abscess: a case report and literature review.

J Cardiothorac Surg 2020 Nov 23;15(1):331. Epub 2020 Nov 23.

Clinic and Research Center for Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, P.R. China.

Background: This study aimed to report the experience of diagnosis and treatment of one rare case of mediastinal lymph node tuberculous abscess (MLNTA) using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA).

Case Presentation: An 18-year-old female patient was hospitalized in the Affiliated Hospital of Xuzhou Medical University in November 2017, due to intermittent left chest pain. She was suspected of infecting tuberculosis (TB) and thus received anti-TB treatment. Since April 1, 2018, she began to exhibit symptoms of chest distress. The patient was then admitted to Shanghai Pulmonary Hospital and continued receiving systemic anti-TB treatment during the whole course. On April 11, 2018, she received EBUS-TBNA to puncture pus and inject isoniazid. Simultaneously, the pus was sent for cytopathological and bacteriological examination, both supporting the diagnosis of TB in the patient. On April 24 and May 10, she received two times of EBUS-TBNA treatment. The symptoms of chest distress were relieved, but granulomatous neoplasm occurred at the EBUS-TBNA site on the trachea wall. The patient then received local clamp removal and cryotherapy on May 29 and Jul 19, respectively. Chest computed tomography (CT) reexamination on September 28 revealed that the MLNTA lesion had been completely absorbed, and electronic bronchoscopic reexamination on September 30 demonstrated that the granulomatous neoplasm on the trachea wall was entirely invisible.

Conclusions: Using EBUS-TBNA to puncture and aspirate pus and inject drugs can be effectively used to diagnose and treat MLNTA, which provides a new, less invasive, safe and reliable method for diagnosis and treatment of MLNTA.
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http://dx.doi.org/10.1186/s13019-020-01360-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681963PMC
November 2020

Pemetrexed-based chemotherapy for non-small-cell lung cancer patients with exon 20 insertion mutation: a multicenter study.

Transl Lung Cancer Res 2020 Oct;9(5):1853-1861

Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

Background: Chemotherapy is the major choice for advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor exon 20 insertion (EGFR ex20ins). The efficacy of pemetrexed-based with other chemotherapy regimens and EGFR ex20ins subtypes in this population has not been well studied.

Methods: We screened patients with EGFR ex20ins by next-generation sequencing (NGS) from a large cohort. The clinicopathologic and medical information were collected in advanced NSCLC patients with EGFR ex20ins. We also compared the clinical outcomes among patients with different subtypes of EGFR ex20ins.

Results: We retrospectively collected 119 stage IIIB/IV NSCLC patients with EGFR ex20ins from 9142 NSCLC patients across China from June 2013 to December 2018. The subtypes of EGFR ex20ins included A767_V769dupASV (33/119, 27.73%), S768_D770dupSVD (19/119, 15.97%), N771_H773dupNPH (11/119, 9.24%), A763_Y764insFQEA (2/119, 1.68%) and others (54/119, 45.38%). A total of 64.7% (77/119) of patients received pemetrexed-based first-line chemotherapy and 13.45% (16/119) of patients received pemetrexed-based second-line chemotherapy. Pemetrexed-based chemo-treated patients had longer median progression-free survival (PFS) than patients without pemetrexed-based chemo-treated (5.5 3.0 months, P=0.0026). Survival data was available for 66 patients and the median overall survival (OS) was 24.7 months. Pemetrexed-based chemo-treated patients had longer OS tendency than patients without pemetrexed-based chemo-treated (25.0 19.6 months, P=0.0769). Patients harboring A767_V769dupASV had better OS than other subtypes of EGFR ex20ins but without statistical significance (P=0.0676). Multivariate analysis revealed that histological type of NSCLC and bone-metastasis before treatment were independent prognostic factors for OS in all patients after adjusting all characteristic and treatment factors (P<0.05).

Conclusions: To the best of our knowledge, it is the largest cohort study of advanced NSCLC patients with EGFR ex20ins across China. Pemetrexed-based treatment could have better control of disease than non-pemetrexed-based chemotherapies in this population. Furthermore, more effective agents are expected for patients harboring EGFR ex20ins.
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http://dx.doi.org/10.21037/tlcr-20-382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653161PMC
October 2020

Immune Cell Infiltration and the Expression of PD-1 and PD-L1 in Primary PDGFRA-Mutant Gastrointestinal Stromal Tumors.

J Gastrointest Surg 2020 Nov 9. Epub 2020 Nov 9.

Department of General Surgery, Zhongshan Hospital, Fudan University School of Medicine, #180 Fenglin Road, Shanghai, 200032, China.

Purpose: To characterize the immune cell profile and expression of PD-1, PD-L1, and IDO in PDGFRA-mutant gastrointestinal stromal tumors (GISTs).

Methods: The clinicopathological data of PDGFRA-mutant GIST patients who received surgical resection in Zhongshan Hospital between January 2013 and August 2019 were reviewed retrospectively. The specimens of tissue chips were detected for immune cell infiltration and the expression of PD-1, PD-L1, and IDO by immunohistochemical staining.

Results: CD3, CD8, and CD68 cells were the main infiltrating immune cells in the 42 patients included in this study. In addition, CD4, CD56, Foxp3, and CD20 cells were also observed. A higher CD8 T cell count was associated with smaller tumor size and PDGFRA D842V mutation (P = 0.047, P = 0.005). A higher CD3 and CD68 cell count was associated with a higher mitotic index (P = 0.022, P = 0.006). CD4 and CD20 cell count was associated with tumor morphology (P = 0.002, P = 0.045). PD-1 expression was present in 37 (88%) samples. Eighteen samples were positive for PD-L1 expression, and it was higher in small vs. large tumors (P = 0.012) and epithelioid and mixed cell type vs. spindle cell type GISTs (P = 0.046). IDO expression was positive in all 42 patients. The number of CD4 cells was significantly greater in the specimens with high IDO expression (P = 0.012).

Conclusion: There were abundant infiltrating immune cells in PDGFRA-mutant GISTs. PD-L1 expression was negatively associated with tumor size. The immunotherapy targeting PD-1/PD-L1 checkpoint and IDO may be valuable.
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http://dx.doi.org/10.1007/s11605-020-04860-8DOI Listing
November 2020

Camrelizumab Plus Apatinib in Extensive-Stage SCLC (PASSION): A Multicenter, Two-Stage, Phase 2 Trial.

J Thorac Oncol 2021 02 6;16(2):299-309. Epub 2020 Nov 6.

Department of Medical Oncology, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, People's Republic of China. Electronic address:

Introduction: Treatment options in the second-line extensive-stage SCLC (ED-SCLC) setting are limited. The PASSION study (ClinicalTrials.gov identifier: NCT03417895) was a phase 2 study of camrelizumab plus apatinib in ED-SCLC after platinum-based chemotherapy.

Methods: In stage I of the study, patients were randomized (1:1:1) to receive camrelizumab 200 mg every 2 weeks plus apatinib 375 mg once daily (QD), 5 days on and 2 days off, or 7 days on and 7 days off (six patients each cohort). On the basis of tolerability during the first 28-day cycle and efficacy data at stage I, one cohort was chosen to expand to 45 patients at stage II. The primary end point was objective response rate (ORR).

Results: From April 20, 2018 to March 12, 2019, a total of 59 patients were enrolled, with 47 patients in the QD cohort. In the QD cohort, confirmed ORR reached 34.0% (95% confidence interval: 20.9‒49.3), the median progression-free survival was 3.6 months, and the median overall survival was 8.4 months. Chemotherapy-sensitive and chemotherapy-resistant patients (defined as patients with disease relapse at ≥90 and <90 d after platinum-based chemotherapy, respectively) had comparable confirmed ORR (37.5% versus 32.3%), median progression-free survival (3.6 versus 2.7 mo), and median overall survival (9.6 versus 8.0 mo). Treatment-related adverse events of grade 3 or higher were reported in 43 of 59 patients (72.9%). Five patients (8.5%) discontinued because of treatment-related adverse events.

Conclusions: Camrelizumab plus apatinib exhibited potential antitumor activity in patients with both chemotherapy-sensitive and chemotherapy-resistant ED-SCLC who had failed platinum-based chemotherapy with an acceptable toxicity profile. This phase 2 data warrant further clinical studies of camrelizumab plus apatinib in SCLC.
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http://dx.doi.org/10.1016/j.jtho.2020.10.002DOI Listing
February 2021