Publications by authors named "Xiaorong Sun"

67 Publications

Isoorientin Affects Markers of Alzheimer's Disease via Effects on the Oral and Gut Microbiota in APP/PS1 Mice.

J Nutr 2021 Oct 12. Epub 2021 Oct 12.

Beijing Agro-Biotechnology Research Center, Beijing Academy of Agriculture and Forestry Sciences, Beijing, China.

Background: There is growing evidence of strong associations between the pathogenesis of Alzheimer's disease (AD) and dysbiotic oral and gut microbiota. Recent studies demonstrated that isoorientin (ISO) is anti-inflammatory and alleviates markers of AD, which were hypothesized to be mediated by the oral and gut microbiota.

Objectives: We studied the effects of oral administration of ISO on AD-related markers and the oral and gut microbiota in mice.

Methods: Eight-month-old amyloid precursor protein/presenilin-1 (AP) transgenic male mice were randomly allocated to 3 groups of 15 mice each: vehicle (AP) alone or with a low dose of ISO (AP + ISO-L; 25 mg/kg) or a high dose of ISO (AP + ISO-H; 50 mg/kg). Age-matched wild-type (WT) C57BL/6 male littermates were used as controls. The 4 groups were treated intragastrically with ISO or sterilized ultrapure water for 2 months. AD-related markers in the brain, serum, colon, and liver were analyzed with immunohistochemical and histochemical staining, Western blotting, and ELISA. Oral and gut microbiotas were analyzed using 16S ribosomal RNA gene sequencing.

Results: The high-dose ISO treatment significantly decreased amyloid beta 42-positive deposition by 38.1% and 45.2% in the cortex and hippocampus, respectively, of AP mice (P < 0.05). Compared with the AP group, both ISO treatments reduced brain phospho-Tau, phosphor-p65, phosphor-inhibitor of NF-κB, and brain and serum LPS and TNF-α by 17.9%-72.5% and increased brain and serum IL-4 and IL-10 by 130%-210% in the AP + ISO-L and AP + ISO-H groups (P < 0.05). Abundances of 26, 25, and 23 microbial taxa in oral, fecal and cecal samples, respectively, were increased in both the AP + ISO-L and AP + ISO-H groups relative to the AP group [linear discriminant analysis (LDA) >3.0; P < 0.05]. Gram-negative bacteria, Alteromonas, Campylobacterales, and uncultured Bacteroidales bacterium were positively correlated (rho = 0.28-0.59; P < 0.05) with the LPS levels and responses of inflammatory cytokines.

Conclusions: The microbiota-gut-brain axis is a potential mechanism by which ISO reduces AD-related markers in AP mice.
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http://dx.doi.org/10.1093/jn/nxab328DOI Listing
October 2021

A preclinical study: correlation between PD-L1 PET imaging and the prediction of therapy efficacy of MC38 tumor with Ga-labeled PD-L1 targeted nanobody.

Aging (Albany NY) 2021 04 27;13(9):13006-13022. Epub 2021 Apr 27.

Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250017, P.R. China.

Although immunotherapy has achieved great clinical success in clinical outcomes, especially the anti-PD-1 or anti-PD-L1 antibodies, not all patients respond to anti-PD-1 immunotherapy. It is urgently required for a clinical diagnosis to develop non-invasive imaging meditated strategy for assessing the expression level of PD-L1 in tumors. In this work, a Ga-labeled single-domain antibody tracer, Ga-NOTA-Nb109, was designed for specific and noninvasive imaging of PD-L1 expression in an MC38 tumor-bearing mouse model. Comprehensive studies including Positron Emission Tomography (PET), biodistribution, blocking studies, immunohistochemistry, and immunotherapy, have been performed in differences PD-L1 expression tumor-bearing models. These results revealed that Ga-NOTA-Nb109 specifically accumulated in the MC38-hPD-L1 tumor. The content of this nanobody in MC38 hPD-L1 tumor and MC38 Mixed tumor was 8.2 ± 1.3, 7.3 ± 1.2, 3.7 ± 1.5, 2.3 ± 1.2%ID/g and 7.5 ± 1.4, 3.6 ± 1.7, 1.7 ± 0.6, 1.2 ± 0.5%ID/g at 0.5, 1, 1.5, 2 hours post-injection, respectively. Ga-NOTA-Nb109 has the potential to further noninvasive PET imaging and therapy effectiveness assessments based on the PD-L1 status in tumors. To explore the possible synergistic effects of immunotherapy combined with chemotherapy, MC38 xenografts with different sensitivity to PD-L1 blockade were established. In addition, we found that PD-1 blockade also had efficacy on the PD-L1 knockout tumors. RT-PCR and immunofluorescence analysis were used to detect the expression of PD-L1. It was observed that both mouse and human PD-L1 expressed among three types of MC38 tumors. These results suggest that PD-L1 on tumor cells affect the efficacy, but it on host myeloid cells might be essential for checkpoint blockade. Moreover, anti-PD-1 treatment activates tumor-reactive CD103 CD39 CD8+T cells (TILs) in tumor microenvironment.
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http://dx.doi.org/10.18632/aging.202981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148448PMC
April 2021

Functionalizing DNA nanostructures with natural cationic amino acids.

Bioact Mater 2021 Sep 27;6(9):2946-2955. Epub 2021 Feb 27.

Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, 183 Xinqiao Street, Chongqing, 400037, China.

Complexing self-assembled DNA nanostructures with various functional guest species is the key to unlocking new and exciting biomedical applications. Cationic guest species not only induce magnesium-free DNA to self-assemble into defined structures but also endow the final complex nanomaterials with new properties. Herein, we propose a novel strategy that employs naturally occurring cationic amino acids to induce DNA self-assembly into defined nanostructures. Natural l-arginine and l-lysine can readily induce the assembly of tile-based DNA nanotubes and DNA origami sheets in a magnesium-free manner. The self-assembly processes are demonstrated to be pH- and concentration-dependent and are achieved at constant temperatures. Moreover, the assembled DNA/amino acid complex nanomaterials are stable at a physiological temperature of 37 °C. Substituting l-arginine with its D form enhances its serum stability. Further preliminary examination of this complex nanomaterial platform for biomedical applications indicates that DNA/amino acids exhibit distinct cellular uptake behaviors compared with their magnesium-assembled counterparts. The nanomaterial mainly clusters around the cell membrane and might be utilized to manipulate molecular events on the membrane. Our study suggests that the properties of DNA nanostructures can be tuned by complexing them with customized guest molecules for a designed application. The strategy proposed herein might be promising to advance the biomedical applications of DNA nanostructures.
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http://dx.doi.org/10.1016/j.bioactmat.2021.02.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930363PMC
September 2021

Stage-Specific PET Radiomic Prediction Model for the Histological Subtype Classification of Non-Small-Cell Lung Cancer.

Cancer Manag Res 2021 12;13:307-317. Epub 2021 Jan 12.

Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, People's Republic of China.

Purpose: To investigate the impact of staging on differences in glucose metabolic heterogeneity between lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) by F-fluorodeoxyglucose positron emission tomography (F-FDG PET) textural analysis and to develop a stage-specific PET radiomic prediction model to distinguish lung ADC from SCC.

Patients And Methods: Patients who were histologically diagnosed with lung ADC or SCC and underwent pretreatment F-FDG PET/CT scans were retrospectively identified. Radiomic features were extracted from a semiautomatically outlined tumor region in the Chang-Gung Image Texture Analysis (CGITA) software package. The differences in radiomic parameters between lung ADC and SCC were compared stage-by-stage in 253 consecutive NSCLC patients with stages I to III disease. The least absolute shrinkage and selection operator (LASSO) algorithm was used for feature selection. A radiomic signature for each stage was subsequently constructed and evaluated. Then, an individual nomogram incorporating the radiomic signature and clinical risk factors was established and evaluated. The performance of the constructed models was assessed by receiver operating characteristic (ROC) curve analysis, and the nomogram was further validated by calibration curve analysis.

Results: The performance of the radiomic signature for distinguishing lung ADC and SCC in both the training and validation cohorts was good, with AUCs of 0.883, 0.854, and 0.895 in the training cohort and 0.932, 0.944, and 0.886 in the validation cohort for stages I, II, and III NSCLC, respectively. The radiomic-clinical nomogram integrating radiomic features with independent clinical predictors exhibited more favorable discriminative performance, with AUCs of 0.982, 0.963, and 0.979 in the training cohort and 0.989, 0.984, and 0.978 in the validation cohort for stages I, II, and III, respectively.

Conclusion: Differences in PET radiomic features between lung ADC and SCC varied in different stages. Stage-specific PET radiomic prediction models provided more favorable performance for discriminating the histological subtype of NSCLC.
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http://dx.doi.org/10.2147/CMAR.S287128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811450PMC
January 2021

Characterization and phylogenetic analysis of the complete mitochondrial genome of sp. (Entomophthorales: Ancylistaceae).

Mitochondrial DNA B Resour 2019 Dec 12;5(1):121-122. Epub 2019 Dec 12.

Chengdu Bio-HT Company Limited, Chengdu, China.

In the present study, we presented the complete mitochondrial genome of an entomophthoroid fungus sp. The mitogenome of sp. has a total length of 26,612 bp, with the base composition as follows: A (44.22%), T (27.10%), C (10.99%) and G (17.68%). The mitogenome contains 19 protein-coding genes, 2 ribosomal RNA genes (rRNA), and 23 transfer RNA (tRNA) genes. The taxonomic status of the sp. mitogenome exhibited a close relationship with the mitogenome of .
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http://dx.doi.org/10.1080/23802359.2019.1698340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721048PMC
December 2019

Characterization and phylogenetic analysis of the complete mitochondrial genome of the human pathogenic fungus sp. (Tremellales: Cryptococcaceae).

Mitochondrial DNA B Resour 2019 Nov 21;4(2):4200-4201. Epub 2019 Nov 21.

Chengdu Bio-HT Company Limited, Chengdu, China.

In the present study, the complete mitogenome of sp. were sequenced and assembled. The complete mitogenome of sp. was composed of circular DNA molecules, with a total length of 30,029 bp. The base composition of this mitochondrial genome is as follows: A (31.94%), T (34.89%), G (15.97%), and C (17.21%). The mitogenome contains 20 protein-coding genes, 2 ribosomal RNA genes (rRNA), and 22 transfer RNA (tRNA) genes. Phylogenetic analysis showed that the mitogenome of the sp. exhibited a closest relationship with .
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http://dx.doi.org/10.1080/23802359.2019.1693295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707753PMC
November 2019

Radiomics Nomogram for Predicting Locoregional Failure in Locally Advanced Non-small Cell Lung Cancer Treated with Definitive Chemoradiotherapy.

Acad Radiol 2020 Dec 8. Epub 2020 Dec 8.

Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan, Shandong 250117, China. Electronic address:

Rationale And Objectives: To develop and validate a computed tomography (CT)-based radiomics nomogram for predicting locoregional failure (LRF) in patients with locally advanced non-small cell lung cancer (NSCLC) treated with definitive chemoradiotherapy (CRT).

Materials And Methods: A total of 141 patients with locally advanced NSCLC treated with definitive CRT from January 2014 to December 2017 were included and divided into testing cohort (n = 100) and validation (n = 41) cohort. Radiomics features were extracted from pretreatment contrast enhanced CT. The least absolute shrinkage and selection operator logistic regression was processed to select predictive features from the testing cohort and constructed a radiomics signature. Clinical characteristics and the radiomics signature were analyzed using univariable and multivariate Cox regression. The radiomics nomogram was established with the radiomics signature and independent clinical factors. Harrell's C-index, calibration curves and decision curves were used to assess the performance of the radiomics nomogram.

Results: The radiomics signature, which consisted of eight selected features, was an independent factor of LRF. The clinical predictors of LRF were the histologic type and clinical stage. The radiomics nomogram combined with the radiomics signature and clinical prognostic factors showed good performance with C-indexes of 0.796 (95% confidence interval [CI]: 0.709-0.883) and 0.756 (95% CI: 0.674-0.838) in the testing and validation cohorts respectively. Additionally, the combined nomogram resulted in better performance (p < 0.001) for the estimation of LRF than the nomograms with the radiomics signature (C-index: 0.776; 95% CI: 0.686-0.866) or clinical predictors (C-index: 0.641; 95% CI: 0.542-0.740) alone.

Conclusion: The radiomics nomogram provided the best performance for LRF prediction in patients with locally advanced NSCLC, which may help optimize individual treatments.
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http://dx.doi.org/10.1016/j.acra.2020.11.018DOI Listing
December 2020

CT-based radiomics for predicting brain metastases as the first failure in patients with curatively resected locally advanced non-small cell lung cancer.

Eur J Radiol 2021 Jan 12;134:109411. Epub 2020 Nov 12.

School of Clinical Medicine, Weifang Medical University, Weifang, Shandong, China; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, Shandong, China; Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Department of Graduate, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. Electronic address:

Purpose: Brain metastasis (BM) is the primary first failure pattern in patients with curatively resected locally advanced non-small cell lung cancer (LA-NSCLC). It is not yet possible to accurately predict the occurrence of BM. The purpose of the research is to develop and validate a prediction model of BM-free survival based on radiomics characterising the primary lesions combined with clinical characteristics in patients with curatively resected LA-NSCLC.

Methods: This study consisted of 124 patients with curatively resected stage IIB-IIIB NSCLC in our institution between January 2014 and June 2018. Patients were randomly divided into training and validation cohorts using a 4:1 ratio. Radiomics features were selected from the chest CT images before surgery. A radiomics signature was constructed using the LASSO algorithm based on the training cohort. Clinical model was developed using the Cox proportional hazards model. The clinical, radiomics, and integrated nomograms were constructed. The prediction performance of the models was assessed based on its discrimination, calibration, and clinical utility.

Results: The radiomics signature is significantly associated with BM-free survival in the overall cohort. The discrimination performance of the integrated nomogram, with the C-indexes 0.889 (0.872-0.906, 95 % CI) and 0.853 (0.788-0.918, 95 % CI) in the training and validation cohorts, respectively, is significantly better than the clinical nomogram (p < 0.0001 for the training cohort, p = 0.0008 for the validation cohort). Compared with the radiomics nomogram, the integrated nomogram is also improved to varying degrees, but not apparent in the validation cohort (p = 0.0007 for the training cohort, p = 0.0554 for the validation cohort). The calibration curve and decision curve analysis demonstrated that the integrated nomogram exceeded the clinical or radiomics nomograms in predicting BM-free survival.

Conclusions: Compared with the clinical or radiomics nomograms, the predictive performance of the integrated nomogram is significantly improved. The integrated nomogram is most suitable for predicting BM-free survival in patients with curatively resected LA-NSCLC.
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http://dx.doi.org/10.1016/j.ejrad.2020.109411DOI Listing
January 2021

Fine Mapping of the Gene Conferring Resistance to Late Blight () in Tomato.

Plant Dis 2021 Apr 3;105(4):851-858. Epub 2021 Mar 3.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Late blight is a devastating tomato disease. Breeding new varieties with multiple resistance () genes is highly effective for preventing late blight. The gene mediates resistance to race T in tomato. In this study, we used an F population derived from a cross between Moboline (resistant) and LA3988 (susceptible) cultivars for the fine mapping of . Two flanking markers, CAPS-1 and CC-Ase, mapped to a 141-kb genomic region containing 21 projected genes, 5 of which were identified as putative genes. The coding sequence varied significantly between the parents. The markers developed and candidate genes identified in this study shall be useful for the molecular breeding of tomato exhibiting increased late blight resistance and for the cloning of the gene.
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http://dx.doi.org/10.1094/PDIS-03-19-0679-REDOI Listing
April 2021

F-RGD PET/CT imaging reveals characteristics of angiogenesis in non-small cell lung cancer.

Transl Lung Cancer Res 2020 Aug;9(4):1324-1332

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

Background: The objective of this study was to explore the benefit of F-AlF-NOTA-PRGD2 positron emission tomography/computed tomography (denoted as F-RGD PET/CT) imaging for determining the clinical pathologic features of non-small cell lung cancer (NSCLC).

Methods: Seventy-two patients with NSCLC (37 cases of adenocarcinoma and 35 cases of squamous carcinoma) were enrolled to receive F-RGD PET/CT scanning pretreatment. The peak standard uptake value (SUV), mean standard uptake value (SUV), angiogenic tumor volume (ATV) and total lesion angiogenesis (TLA) of tumors were determined using an automated contouring program. Cases were classified according to the tumor, lymph node, metastasis (TNM) stage.

Results: Significant differences in ATV and TLA were observed among T1, T2, T3 and T4 cases (ATV, P=0.000; TLA, P=0.000). ATV and TLA also differed significantly among cases of clinical stage I, II, III and IV (ATV, P=0.002; TLA, P=0.011). However, no significant differences in any values were observed between stage III and IV NSCLC cases (SUV, P=0.675; SUV, P=0.668; ATV, P=0.52; TLA, P=0.634). All assessed values were higher in squamous cell carcinoma cases than in adenocarcinoma cases (SUV, P=0.045; SUV, P=0.014; ATV, P=0.003; TLA, P=0.001). For clinical stage III and IV cases specifically, SUV, SUV, and TLA were higher for squamous cell carcinoma than for adenocarcinoma (SUV, P=0.015; SUV, P=0.009; TLA, P=0.036).C F-RGD PET/CT imaging revealed the presence of increased angiogenesis in the tumor microenvironment of NSCLC, especially squamous cell carcinoma, and thus may be valuable in planning therapeutic regimens for individual patients.
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http://dx.doi.org/10.21037/tlcr-20-187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481644PMC
August 2020

Long noncoding RNA DUXAP8 regulates proliferation and apoptosis of ovarian cancer cells via targeting miR-590-5p.

Hum Cell 2020 Oct 4;33(4):1240-1251. Epub 2020 Aug 4.

Department of Pathology, Jinan Maternity and Child Care Hospital, No.2 Xiaojing 3rd Jianguo Road, Jinan, 250002, China.

The aim of this study is to investigate the effect of lncRNA DUXAP8 on proliferation and apoptosis of ovarian cancer cells, and to explore its potential mechanism. DUXAP8 interfering and overexpressing cell lines were constructed and the cell proliferation and apoptosis were tested. Hematoxylin-eosin, TdT-mediated dUTP nick end labeling, and immunohistochemistry were used to detect the effect of DUXAP8 on the ability of tumor formation. Quantitative real-time polymerase chain reaction and western blot were used to detect the mRNA and protein expression of miR-590-5p and YAP1, respectively. Dual luciferase assay was used to determine the target relationship between DUXAP8, miR-590-5p, and YAP1. DUXAP8 interference and miR-590-5p down-regulated cell lines were further constructed. Compared with normal ovarian cells, the expression of DUXAP8 in ovarian cancer cells was significantly increased, while the expression of miR-590-5p was decreased (p < 0.05). After DUXAP8 interference, cell proliferation and colony formation were decreased, and apoptosis was increased. The results of in vivo experiment are consistent with the in vitro experiments. The expression of miR-590-5p was up-regulated and the expression of YAP1 was decreased after DUXAP8 interference. Moreover, miR590-5p inhibitor can attenuate the effect of DUXAP8 interference on ovarian cancer cells. Taken together, lncRNA DUXAP8 can regulate the proliferation and apoptosis of ovarian cancer cells, and its mechanism may be related to the regulation of YAP1 gene by targeting miR-590-5p.
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http://dx.doi.org/10.1007/s13577-020-00398-8DOI Listing
October 2020

The artificial intelligence-assisted cytology diagnostic system in large-scale cervical cancer screening: A population-based cohort study of 0.7 million women.

Cancer Med 2020 09 22;9(18):6896-6906. Epub 2020 Jul 22.

Landing Cloud Medical Laboratory Co., Wuhan, China.

Background: Adequate cytology is limited by insufficient cytologists in a large-scale cervical cancer screening. We aimed to develop an artificial intelligence (AI)-assisted cytology system in cervical cancer screening program.

Methods: We conducted a perspective cohort study within a population-based cervical cancer screening program for 0.7 million women, using a validated AI-assisted cytology system. For comparison, cytologists examined all slides classified by AI as abnormal and a randomly selected 10% of normal slides. Each woman with slides classified as abnormal by either AI-assisted or manual reading was diagnosed by colposcopy and biopsy. The outcomes were histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+).

Results: Finally, we recruited 703 103 women, of whom 98 549 were independently screened by AI and manual reading. The overall agreement rate between AI and manual reading was 94.7% (95% confidential interval [CI], 94.5%-94.8%), and kappa was 0.92 (0.91-0.92). The detection rates of CIN2+ increased with the severity of cytology abnormality performed by both AI and manual reading (P  < 0.001). General estimated equations showed that detection of CIN2+ among women with ASC-H or HSIL by AI were significantly higher than corresponding groups classified by cytologists (for ASC-H: odds ratio [OR] = 1.22, 95%CI 1.11-1.34, P < .001; for HSIL: OR = 1.41, 1.28-1.55, P < .001). AI-assisted cytology was 5.8% (3.0%-8.6%) more sensitive for detection of CIN2+ than manual reading with a slight reduction in specificity.

Conclusions: AI-assisted cytology system could exclude most of normal cytology, and improve sensitivity with clinically equivalent specificity for detection of CIN2+ compared with manual cytology reading. Overall, the results support AI-based cytology system for the primary cervical cancer screening in large-scale population.
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http://dx.doi.org/10.1002/cam4.3296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520355PMC
September 2020

Letter to the editor: Is it reasonable to prescribe RAI for all DTC patients with a primary tumor diameter exceeding 1 cm?

Eur J Nucl Med Mol Imaging 2020 10 13;47(11):2505-2506. Epub 2020 May 13.

Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

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http://dx.doi.org/10.1007/s00259-020-04858-zDOI Listing
October 2020

Nimotuzumab, an EGFR‑targeted antibody, promotes radiosensitivity of recurrent esophageal squamous cell carcinoma.

Int J Oncol 2020 04 12;56(4):945-956. Epub 2020 Feb 12.

Department of Nuclear Medicine, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China.

Local tumor recurrence is one of the main causes for the failure of esophageal cancer treatment following radiotherapy. Previous studies have demonstrated that epidermal growth factor receptor (EGFR)‑targeted therapy combined with radiotherapy is expected to become an effective means to control tumor recurrence. The aim of the present study was to investigate the effect and mechanism of nimotuzumab (an EGFR‑targeted antibody) in the treatment of recurrent esophageal carcinoma. The radiation responses of two esophageal squamous carcinoma cell lines, EC109 and TE‑1, with or without nimotuzumab, were first evaluated by CCK‑8 assay. Colony formation and apoptosis were used to measure anti‑proliferation effects. It was demonstrated that nimotuzumab arrested the cell cycle at the G2 phase in vitro. Western blotting and immunofluorescence analysis were used to determine signaling pathway changes. It was observed that nimotuzumab inhibited phosphorylation of EGFR in EC109 cells. Furthermore, recurrent tumor models were established and it was identified that the degree of tumor hypoxia was positively associated with EGFR overexpression. In EC109 cell xenografts, nimotuzumab combined with radiation led to a significant delay in recurrent tumor growth compared with that of radiation alone (P<0.001 for 0 Gy pre‑irradiation, P=0.005 for 20 Gy pre‑irradiation, P=0.005 for 10 Gy pre‑irradiation). These results suggest that nimotuzumab combined with radiation may be an effective means to control recurrent esophageal squamous cell carcinoma with EGFR overexpression.
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http://dx.doi.org/10.3892/ijo.2020.4981DOI Listing
April 2020

Cone-beam CT radiomics features might improve the prediction of lung toxicity after SBRT in stage I NSCLC patients.

Thorac Cancer 2020 04 15;11(4):964-972. Epub 2020 Feb 15.

School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, China.

Background: Stereotactic body radiotherapy (SBRT) is the standard care for inoperable early stage non-small cell lung cancer (NSCLC). The purpose of our study was to investigate whether a prediction model based on cone-beam CT (CBCT) plus pretreatment CT radiomics features could improve the prediction of tumor control and lung toxicity after SBRT in comparison to a model based on pretreatment CT radiomics features alone.

Methods: A total of 34 cases of stage I NSCLC patients who received SBRT were included in the study. The pretreatment planning CT and serial CBCT radiomics features were analyzed using the imaging biomarker explorer (IBEX) software platform. Multivariate logistic regression was conducted for the association between progression-free survival (PFS), lung toxicity and features. The predictive capabilities of the models based on CBCT and CT features were compared using receiver operating characteristic (ROC) curves.

Results: Five CBCT features and two planning CT features were correlated with disease progression. Six CBCT features and two planning CT features were related to lung injury. The ROC curves indicated that the model based on the CBCT plus planning CT features might be better than the model based on the planning CT features in predicting lung injury. The other ROC curves indicated that the model based on the planning CT features was similar to the model based on the CBCT plus planning CT features in predicting disease progression.

Conclusions: Both pretreatment CT and CBCT radiomics features could predict disease progression and lung injury. A model with CBCT plus pretreatment CT radiomics features might improve the prediction of lung toxicity in comparison with a model with pretreatment CT features alone.

Key Points: Significant findings of the study: A model with cone-beam CT radiomics features plus pre-treatment CT radiomics features might improve the prediction of lung toxicity after SBRT in stage I NSCLC patients.

What This Study Adds: In the prediction of PFS and lung toxicity in early-stage NSCLC patients treated with SBRT, CBCT radiomics could be another effective method.
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http://dx.doi.org/10.1111/1759-7714.13349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113065PMC
April 2020

Prognostic Role Of Computed Tomography Textural Features In Early-Stage Non-Small Cell Lung Cancer Patients Receiving Stereotactic Body Radiotherapy.

Cancer Manag Res 2019 25;11:9921-9930. Epub 2019 Nov 25.

Department of Radiation Oncology, Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People's Republic of China.

Purpose: The imaging features of patients with early-stage non-small cell lung cancer (NSCLC) receiving stereotactic body radiotherapy (SBRT) are crucial for the decision-making process to establish a treatment plan. The purpose of this study was to predict the clinical outcomes of SBRT from the textural features of pretreatment computed tomography (CT) images.

Patients And Methods: Forty-one early-stage NSCLC patients who received SBRT were included in this retrospective study. In total, 72 textural features were extracted from the pretreatment contrast-enhanced CT images. Survival analysis was used to identify high-risk groups for progression-free survival (PFS) and disease-specific survival (DSS). Receiver operating characteristic (ROC) curve analysis was utilized to estimate the diagnostic abilities of the textural parameters. Univariable and multivariable Cox regression analyses were performed to evaluate the predictors of PFS and DSS.

Results: Four parameters, including entropy (P=0.003), second angular moment (SAM) (P=0.04), high-intensity long-run emphasis (HILRE) (P=0.046) and long-run emphasis (LRE) (P=0.042), were significant prognostic features for PFS. In addition, contrast (P=0.008), coarseness (P=0.017), low-intensity zone emphasis (LIZE) (P=0.01) and large number emphasis (LNE) (P=0.046) were significant prognostic factors for DSS. In the ROC analysis, the area under the curve (AUC) of coarseness for local recurrence (LR) was 0.722 (0.528-0.916), and the AUC of entropy for lymph node metastasis (LNM) was 0.771 (0.556-0.987). The four highest AUCs for distant metastasis (DM) were 0.885 (0.784-0.985) for LNE, 0.846 (0.733-0.959) for SAM, 0.731 (0.500-0.961) for LRE and 0.731 (0.585-0.876) for contrast. In the multivariable analysis, smoking and entropy were independent prognostic factors for PFS.

Conclusion: This exploratory study reveals that textual features derived from pretreatment CT scans have prognostic value in early-stage NSCLC patients treated with SBRT.
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http://dx.doi.org/10.2147/CMAR.S220587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883938PMC
November 2019

Association of radiomic features with epidermal growth factor receptor mutation status in non-small cell lung cancer and survival treated with tyrosine kinase inhibitors.

Nucl Med Commun 2019 Nov;40(11):1091-1098

School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences.

Since the discovery of the fact that tyrosine kinase inhibitors could improve progression-free survival for patients with advanced non-small cell lung cancer compared with traditional chemotherapy, it has been extremely important to identify epidermal growth factor receptor mutation status in treatment stratification. Although lack of sufficient biopsy samples limit the precise detection of epidermal growth factor receptor mutation status in clinical practice, and it is difficult to identify the sensitive patients who confer favorable response to tyrosine kinase inhibitors. An increasing number of scholars tried to deal with these problems using methods based on the non-invasive imaging including computed tomography and PET to find the association with epidermal growth factor receptor mutation status and survival treated with tyrosine kinase inhibitor in non-small cell lung cancer. Although the conclusions have not reached a consensus, quantitative and high-throughput radiomics have brought us a new direction and might successfully help identify patients undergoing tyrosine kinase inhibitors who could get significant benefits.
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http://dx.doi.org/10.1097/MNM.0000000000001076DOI Listing
November 2019

PET Imaging of Tumor PD-L1 Expression with a Highly Specific Nonblocking Single-Domain Antibody.

J Nucl Med 2020 01 28;61(1):117-122. Epub 2019 Jun 28.

Key Laboratory of Nuclear Medicine of Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, China

Although immunotherapy through programmed death 1/programmed death ligand 1 (PD-1/PD-L1) checkpoint blockade has shown impressive clinical outcomes, not all patients respond to it. Recent studies have demonstrated that the expression level of PD-L1 in tumors is one of the factors that correlate with PD-1/PD-L1 checkpoint blockade therapy. Herein, a Ga-labeled single-domain antibody tracer, Ga-NOTA-Nb109, was designed and developed for specific and noninvasive imaging of PD-L1 expression in a melanoma-bearing mouse model. The single-domain antibody Nb109 was labeled with the radionuclide Ga through a NOTA chelator. An in vitro binding assay was performed to assess the affinity and binding epitope of Nb109 to PD-L1. The clinical application value of Ga-NOTA-Nb109 was evaluated by a stability assay; by biodistribution and pharmacokinetics studies; and by PET imaging, autoradiography, and immunohistochemical staining studies on tumor-bearing models with differences in PD-L1 expression. Ga-NOTA-Nb109 was obtained with a radiochemical yield of more than 95% and radiochemical purity of more than 98% in 10 min. It showed a highly specific affinity for PD-L1, with an equilibrium dissociation constant of 2.9 × 10 M. A competitive binding assay indicated Nb109 to have a binding epitope different from that of PD-1 and PD-L1 antibody. All biodistribution, PET imaging, autoradiography, and immunohistochemical staining studies revealed that Ga-NOTA-Nb109 specifically accumulated in A375-hPD-L1 tumor, with a maximum uptake of 5.0% ± 0.35% injected dose/g at 1 h. Ga-NOTA-Nb109 holds great potential for noninvasive PET imaging of the PD-L1 status in tumors and for timely evaluation of the effect of immune checkpoint targeting treatment.
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http://dx.doi.org/10.2967/jnumed.119.226712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954462PMC
January 2020

Identification and Characterization of () Gene in Tomato ().

Int J Mol Sci 2019 May 5;20(9). Epub 2019 May 5.

Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops, Ministry of Agriculture, 12 Zhongguancun Nandajie Street, Beijing 100081, China.

Internode length is an important agronomic trait affecting plant architecture and crop yield. However, few genes for internode elongation have been identified in tomato. In this study, we characterized an elongated internode inbred line P502, which is a natural mutant of the tomato cultivar 05T606. The mutant P502 exhibits longer internode and higher bioactive GA concentration compared with wild-type 05T606. Genetic analysis suggested that the elongated internode trait is controlled by quantitative trait loci (QTL). Then, we identified a major QTL on chromosome 2 based on molecular markers and bulked segregant analysis (BSA). The locus was designated as (), which explained 73.6% genetic variance. The was further mapped to a 75.8-kb region containing 10 genes in the reference Heinz 1706 genome. One single nucleotide polymorphism (SNP) in the coding region of was identified, which encodes gibberellin 2-beta-dioxygenase 7 (SlGA2ox7). SlGA2ox7, orthologous to AtGA2ox7 and AtGA2ox8, is involved in the regulation of GA degradation. Overexpression of the wild gene in mutant P502 caused a dwarf phenotype with a shortened internode. The difference of expression levels was not significant in the P502 and wild-type, but the expression levels of GA biosynthetic genes including , , , , , , , , , , and , were upregulated in mutant P502. Our results may provide a better understanding of the genetics underlying the internode elongation and valuable information to improve plant architecture of the tomato.
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http://dx.doi.org/10.3390/ijms20092204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540210PMC
May 2019

Trientine selectively delivers copper to the heart and suppresses pressure overload-induced cardiac hypertrophy in rats.

Exp Biol Med (Maywood) 2018 10 24;243(14):1141-1152. Epub 2018 Nov 24.

Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, China.

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http://dx.doi.org/10.1177/1535370218813988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327367PMC
October 2018

Integrated texture parameter of 18F-FDG PET may be a stratification factor for the survival of nonoperative patients with locally advanced non-small-cell lung cancer.

Nucl Med Commun 2018 Aug;39(8):732-740

Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University.

Objective: This study explored whether integrated texture parameter (ITP) of the fluorine-18-fluorodeoxyglucose PET (F-FDG PET) is a stratification factor for the survival of nonoperative patients with locally advanced non-small-cell lung cancer (LA-NSCLC).

Patients And Methods: Thirty-five patients with LA-NSCLC treated with chemoradiotherapy or radiotherapy were included in the retrospective study. Eight principal components (PCs) were extracted from 72 F-FDG PET texture features (TFs) using PC analysis. The survival rates between PC subgroups (group by median value) were compared using Kaplan-Meier method. Seventy-two factor loadings for PC7 were evaluated using t-test. Standardized values of the TFs with significant factor loading were multiplied by the corresponding PC7 component coefficient, and the products were added together to obtain ITP. The survival rates between ITP subgroups (group by median value) were compared using Kaplan-Meier method. Patient characteristics between ITP subgroups were compared using χ -test, Mann-Whitney U-test, or t-test.

Results: The median follow-up time was 20.7 months. The median overall survival (OS) and progression-free survival (PFS) were 32.5 and 14.4 months, respectively. The patients with high PC7 value had lesser OS (P=0.006) and PFS (P=0.010) than those with lower value. Factor loadings of standardized uptake value kurtosis, run percentage, and zone percentage were significant for PC7 (P<0.01). The patients with high ITP value had lesser OS (P=0.001) and PFS (P=0.002) than those with lower value. There were no significant differences in patient characteristics between ITP subgroups (P>0.2).

Conclusion: This study demonstrated that ITP might be a stratification factor for the survival of nonoperative patients with LA-NSCLC.
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http://dx.doi.org/10.1097/MNM.0000000000000860DOI Listing
August 2018

Correlation of hypoxia status with radiosensitizing effects of sodium glycididazole: A preclinical study.

Oncol Lett 2018 May 21;15(5):6481-6488. Epub 2018 Feb 21.

Department of Radiation Oncology, Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Science, Jinan, Shandong 250117, P.R. China.

The correlation of pretreatment hypoxia status with the radiosensitization effect of sodium glycididazole (CMNa) was not previously defined. The purpose of the present study was to evaluate the tumor hypoxia status in various cancer xenografts and to investigate the correlation between tumor hypoxia status and radiosensitizing effects of CMNa based on the pharmacokinetic and pharmacodynamic parameters. Human esophageal cancer (EC109), head and neck cancer (FaDu) and lung cancer (A549) nude mice xenografts were used. The concentrations of CMNa and its metabolites in the tumors and normal tissues were determined by high-performance liquid chromatography following intravenous injection of 171.9, 57.3 or 19.1 mg/kg CMNa. The tumors were irradiated with 30 Gy in 6 fractions with CMNa administration prior to each irradiation. The tumor growth delay values were calculated for each treatment group and compared with groups treated with radiation alone. Tumor hypoxia status was verified by immunohistostaining of tissues for hypoxia inducible factor 1α (HIF-1α) staining, and the concentration of plasma osteopontin (OPN) was determined using ELISA. The correlation between OPN concentration and tumor growth delay was subsequently analyzed. It was observed that the drug concentration in the tumor was 1.6-2.8 times higher compared with adjacent muscle, particularly at high and medium doses. CMNa was able to sensitize tumors to irradiation, particularly for EC109 and FaDu xenografts at high dose (P<0.05). Furthermore, there was markedly increased expression of HIF-1α and plasma OPN levels in FaDu and EC109 xenografts compared with A549. Additionally, it was indicated that pretreatment hypoxia status might be correlated with the radiosensitizing effects of CMNa. The present data demonstrated that tumor hypoxia status might be correlated with the radiosensitizing effects of CMNa in different tumor models.
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http://dx.doi.org/10.3892/ol.2018.8096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876462PMC
May 2018

F-fluorodeoxyglucose positron emission computed tomography for monitoring tumor response in esophageal carcinoma treated with concurrent chemoradiotherapy.

Oncol Lett 2018 Feb 5;15(2):1845-1852. Epub 2017 Dec 5.

Department of Nuclear Medicine, Shandong Tumor Hospital, Jinan, Shandong 250117, P.R. China.

The aim of the present study was to explore the value of fluorodeoxyglucose positron emission tomography (F-FDG PET) in monitoring the early tumor response of esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiotherapy (CRT). A total of 48 patients with pathologically proven ESCC were retrospectively analyzed. All patients underwent two serial F-FDG PET scans at baseline (pre-CRT) and 40 Gy/4 weeks of starting radiation therapy (inter-CRT). All patients received intensity-modulated radiotherapy (with a total radiation dose of 59.6 Gy) concurrently with cisplatin-based chemotherapy. The maximum standardized uptake value (SUV) and metabolic tumor volume (MTV) were measured using F-FDG PET. The percentage changes (Δ) in SUV and MTV between two serial scans were calculated and were revealed to be associated with the objective tumor response (oTR), according to the Response Evaluation Criteria in Solid Tumors 1.1. Among the 48 patients, 20.8% achieved a complete response, 68.8% exhibited a partial response and the oTR rate was 89.6%. On the pre-CRT PET scans, the mean SUV and MTV were 14.1±5.8 and 58.2±25.4 cm, respectively. Following 40 Gy irradiation over 4 weeks, the mean SUV and MTV significantly decreased to 4.3±3.5 and 19.0±12.1 cm, respectively (P<0.001). A significantly higher ΔSUV and ΔMTV was observed in the responders compared with that in the non-responders [0.71±0.16 vs. 0.51±0.26 (P=0.015); and 0.64±0.13 vs. 0.42±0.09 (P=0.001), respectively]. Univariate analysis revealed that ΔSUV and ΔMTV were significantly associated with oTR (P=0.010 and P=0.001, respectively). ΔMTV was used as a predictor and a cut-off value of 54% discriminated responders from non-responders with a sensitivity of 69.8% and a specificity of 100% (P=0.001). The area under the receiver operating characteristic curve was 0.837 (95% confidence interval, 0.702-0.928). The results of the present study indicated that interim F-FDG PET scans may provide early prognostic value for determining oTR in patients with ESCC undergoing treatment with CRT.
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http://dx.doi.org/10.3892/ol.2017.7528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5776923PMC
February 2018

Accuracy of Xpert Clostridium difficile assay for the diagnosis of Clostridium difficile infection: A meta analysis.

PLoS One 2017 9;12(10):e0185891. Epub 2017 Oct 9.

Department of Pathology, Jinan Women and Children's Health Hospital, Jinan, PR China.

Background: There is an urgent need for rapid and accurate microbiological diagnostic assay for detection of Clostridium difficile infection (CDI). We assessed the diagnostic accuracy of the Xpert Clostridium difficile assay (Xpert CD) for the diagnosis of CDI.

Methods: We searched PubMed, EMBASE, and Cochrane Library databases to identify studies according to predetermined criteria. STATA 13.0 software was used to analyze the tests for sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curves (AUC). QUADAS-2 was used to assess the quality of included studies with RevMan 5.2. Heterogeneity in accuracy measures was tested with Spearman correlation coefficient and Chi-square.

Results: A total of 22 studies were included in the meta-analysis. The pooled sensitivity (95% confidence intervals [CI]) was 0.97 (0.95-0.99) and specificity was 0.95 (0.94-0.96). The AUC was 0.99 (0.97-0.99). Significant heterogeneity was observed when we pooled most of the accuracy measures of selected studies.

Conclusions: The Xpert CD assay is a useful diagnostic tool with high sensitivity and specificity in diagnosing toxigenic CDI, and this method has excellent usability due to its rapidity and simplicity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0185891PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5633177PMC
October 2017

Enhanced radiosensitizing by sodium glycididazole in a recurrent esophageal carcinoma tumor model.

Oncotarget 2017 Sep 10;8(38):63871-63880. Epub 2017 Jul 10.

Department of Radiation Oncology, Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academic of Medicine Science, Jinan 250117, Shandong, China.

Re-irradiation is challenging for esophageal cancer patients with local-regional recurrence after initial radiotherapy. The purpose of this study is to establish a recurrent esophageal tumor model and investigate radiosensitizing effects of sodium glycididazole (CMNa). Tumor models were established by pre-irradiation (0 Gy, 10 Gy or 20 Gy) to the right hind leg of the nude mice 24 hours before tumor transplantation (ECA109 human esophageal carcinoma cells). Tumor growth curves were analyzed. Hypoxic microenvironment was exhibited in tumor frozen slides stained for pimonidazole, Hoechst 33342, hematoxylin-eosin and CD34. Mice bearing primary (0 Gy pre-irradiation) and recurrent (10 Gy pre-irradiation) tumors were randomized into control (no treatment), radiation (30 Gy in 3 weekly fractionations), or radiation combined with CMNa (1 mmol/kg . injected 60 min before radiation) respectively. The data showed tumors from 10 Gy and 20 Gy pre-irradiated sites grew significantly slower than those in the 0 Gy pre-irradiated group. The recurrent xenograft tumors showed increased necrotic fractions, decreased micro-vascular density, increased pimonidazole-positive fraction, and decreased Hoechst-positive fraction. In the primary xenograft tumors, CMNa adding to radiation did not lead to significant tumor growth delay than radiation alone. However, for the recurrent tumor model, the growth rate was remarkably reduced as CMNa combined with radiation as comparison with radiation alone. In conclusion, the recurrent esophageal xenograft model with tumor bed effect was successfully established characterized by slow growth, increased hypoxia fraction and decreased blood flow. Significant radiosensitization by CMNa was demonstrated in the recurrent model.
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http://dx.doi.org/10.18632/oncotarget.19151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609968PMC
September 2017

Plasma fibrinogen level may be a possible marker for the clinical response and prognosis of patients with breast cancer receiving neoadjuvant chemotherapy.

Tumour Biol 2017 Jun;39(6):1010428317700002

2 Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, P.R. China.

Neoadjuvant chemotherapy has been established as standard treatments for advanced breast cancer among multidisciplinary therapies. A simple and instructive biomarker for the postoperative recurrence and metastasis is needed to evaluate the therapeutic effect. Plasma fibrinogen level has been shown to be associated with tumor progression and poor outcomes in breast cancer patients. This study aims to further evaluate the clinical and prognostic value of plasma fibrinogen level as a biomarker in breast cancer patients receiving neoadjuvant chemotherapy. In this study, data of 67 patients were retrospectively collected and analyzed to identify the relationship between the plasma fibrinogen level and the clinical progression and outcome of these patients. Patients with increased plasma fibrinogen level after neoadjuvant chemotherapy had significantly shorter disease-free survival and overall survival (p < 0.001 and p = 0.001, respectively). In a univariate survival analysis, molecular type (p = 0.0004/p = 0.005), clinical response (p = 0.008/p = 0.015), and changes in plasma fibrinogen level (p = 0.012/p = 0.007) were associated with disease-free survival and overall survival, and all of them, molecular type (p = 0.0003/p = 0.005), clinical response (p = 0.027/p = 0.021), and changes in plasma fibrinogen level (p = 0.035/p = 0.025), were associated with disease-free survival and overall survival in a multivariate survival analysis, respectively. The plasma fibrinogen level was found to be a possible biomarker for clinical response to chemotherapy and postoperative metastasis or death in advanced breast cancer patients who received neoadjuvant chemotherapy.
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http://dx.doi.org/10.1177/1010428317700002DOI Listing
June 2017

Agronomic Trait Variations and Ploidy Differentiation of Kiwiberries in Northwest China: Implication for Breeding.

Front Plant Sci 2017 11;8:711. Epub 2017 May 11.

Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of SciencesWuhan, China.

Polyploid plants often have higher biomass and superior crop qualities. Breeders therefore search for crop germplasm with higher ploidy levels; however, whether higher ploidy levels are associated with better performance remains unclear. and related species, whose commercialized fruit are referred to as kiwiberries, harbor a series of ploidy races in nature, offering an opportunity to determine the link between ploidy levels and agronomic traits. In the present study, we determined the ploidy levels of var. var. , and in 16 natural populations using flow cytometry, and examined 31 trait variations in fruits, leaves and flowers by field observations, microscopic examination and laboratory analyses. Our results showed that octaploid and decaploid var. had larger dimension of leaves than tetraploid var. and , but their fruits were significantly smaller. In addition, var. (8 and 10) had higher contents of nutrients such as ascorbic acid and amino acids; however, some important agronomic traits, including the content of total sugar and total acid, were significantly lower in the octaploids and decaploids. Moreover, octaploids and decaploids did not result in greater ecological adaptability for the challenging environments and climates. In conclusion, the differentiation of ecological adaptability and traits among natural kiwiberries' cytotypes suggested that higher ploidy levels are not inevitably advantageous in plants. The findings of and related taxa in geographical distribution and agronomic trait variations will facilitate their germplasm domestication.
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http://dx.doi.org/10.3389/fpls.2017.00711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426280PMC
May 2017

18F-deoxyglucose positron emission tomography/computed tomography to predict local failure in esophageal squamous cell carcinoma.

Oncotarget 2017 May;8(21):34498-34506

Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China.

Esophageal squamous cell carcinoma (ESCC) patients are at risk for local failure (LF) following treatment. Predicting tumor regions at high risk for local failure before radiotherapy may increase treatment efficacy by permitting an escalated radiation dose specifically to those regions critical for tumor control. Forty-one patients with non-resectable locally advanced ESCC underwent 18F-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging before concurrent chemoradiotherapy (CCRT). After CCRT, a second (failure) FDG PET/CT was performed in cases of relapse. Failure FDG PET/CT scans were fused to pre-treatment scans to identify tumor regions at high risk for LF. Within a median follow-up time of 26 months, 20 patients (48.8%) had LF. In 19 patients, the failure occurred within a pre-treatment high FDG uptake region; the failure occurred outside these regions in only one patient. Pre-treatment metabolic tumor volume (MTV) was independently associated with LF (P<0.001, HR 1.128, 95% CI: 1.061-1.198). LF was more likely in patients with MTVs ≥27 cm3. In initial PET/CT images, when 50% maximum standardized uptake value (SUVmax) was used as the threshold, delineated subvolumes overlapped LF regions. These results confirm that LF occurs most commonly within pre-treatment high FDG uptake regions.
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http://dx.doi.org/10.18632/oncotarget.15606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470985PMC
May 2017

Prognositc significance of SUV on pretreatment F-FDG PET/CT in early-stage non-small cell lung cancer treated with stereotactic body radiotherapy: A meta-analysis.

J Med Imaging Radiat Oncol 2017 Oct 7;61(5):652-659. Epub 2017 Mar 7.

Department of Radiation Oncology, Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academic of Medicine Science, Jinan, Shandong, China.

Introduction: The prognostic importance of the F-FDG PET maximum standardized uptake value (SUV ) for early stage non-small cell lung cancer (NSCLC) patients receiving stereotactic body radiotherapy (SBRT) is not well defined. The purpose of this meta-analysis is to evaluate the efficacy of SUV on pretreatment F-FDG PET imaging to predict prognosis after SBRT.

Methods: All published English-language studies that assessed the treatment response after SBRT in patients with early-stage NSCLC using F-FDG PET were collected from the EMBASE and MEDLINE databases. All the included studies were published between January 2000 and June 2015 and limited to NSCLC, PET/CT, SBRT, and the impact of SUV on survival. The necessary data for the calculation of individual hazard ratios (HRs) were extracted from each publication. All the results were independently verified and examined by two reviewers to ensure accuracy.

Results: After evaluating the original articles, 11 retrospective studies (1008 patients) were included into the meta-analysis. Data were available in 11 studies for pre-SBRT primary tumour SUV . Seven studies (798 patients) were included for the overall survival (OS) analysis with a combined HR of 1.10 (95% CI, 1.05-1.15). Five studies (487 patients) were included for the local control analysis with a combined HR of 1.13 (95% CI, 1.06-1.21). Three studies (365 patients) were analysed for distant metastasis with a combined HR of 1.09 (95% CI, 1.03-1.16).

Conclusion: Patients with high levels of pre-SBRT SUV had poorer overall survival and local control and higher distant metastases. Further prospective studies are warranted to confirm the prognostic value of FDG uptake in early-stage NSCLC patients receiving SBRT.
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http://dx.doi.org/10.1111/1754-9485.12599DOI Listing
October 2017

The impact of intratumoral metabolic heterogeneity on postoperative recurrence and survival in resectable esophageal squamous cell carcinoma.

Oncotarget 2017 Feb;8(9):14969-14977

Department of Radiation Oncology, Shandong Cancer Hospital, Shandong University, Jinan, Shandong, China.

Objective: To evaluate the impact of intratumoral metabolic heterogeneity measured by 18F-FDG PET imaging on postoperative recurrence and survival for patients with esophageal squamous cell carcinoma (ESCC).

Results: AUC-CSH, metabolic tumor volume and pN-stage were significant prognostic factors for RFS. Additionally, tumor recurrence of the low AUC-CSH group (≤ 0.478) was 3 times higher than high group (P = 0.015). The median OS of patients with advanced AJCC stage or low AUC-CSH was also significantly shorter than that of patients with stage I & II or high AUC-CSH (P = 0.021, 0.009). Multivariate analysis identified the AUC-CSH to be the only significant risk factor for postoperative recurrence and overall survival in whole-group and stage III patients.

Materials And Methods: 116 ESCC patients who underwent staging 18F-FDG PET-CT scan and surgical resection were reviewed. The metabolic parameters were assessed as follows: maximum standardized uptake value (SUVmax), metabolic tumor volume, and the area under the curve of the cumulative SUV-volume histogram (AUC-CSH), which is known to reflect the intratumoral metabolic heterogeneity. Regression analyses were used to identify clinicopathological and imaging variables associated with relapse-free survival (RFS) and overall survival (OS).

Conclusions: Intratumoral metabolic heterogeneity characterized by AUC-CSH can predict postoperative recurrence and survival in patients with resectable ESCC.
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http://dx.doi.org/10.18632/oncotarget.14743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362458PMC
February 2017
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