Publications by authors named "Yingyi Wang"

103 Publications

Circulating activated immune cells as a potential blood biomarkers of non-small cell lung cancer occurrence and progression.

BMC Pulm Med 2021 Sep 6;21(1):282. Epub 2021 Sep 6.

Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China.

Background: Treatment for non-small cell lung cancer (NSCLC) has greatly improved in recent years. However, noninvasive early screening for carcinogenesis and progression unclear. The aim of this study was to explore the predictive value of peripheral blood immune cells in untreated NSCLC patients.

Methods: We retrospectively enrolled 305 untreated NSCLC patients and 132 healthy participants from February 2016 to August 2019 in Peking Union Medical College Hospital. Immune cell levels were determined by flow cytometry and routine blood tests.

Results: NSCLC patients had lower levels of T lymphocytes, NK cells, CD8+ T cells, naïve CD4+/CD4+, naïve CD4+ T cells and higher levels of CD4+ T cells, memory CD4+/CD4+ T cells, memory CD4+ T cells, CD4+CD28+/CD4+ T cells, CD4+CD28+ T cells, CD8+CD28+/CD8+ T cells, CD8+HLA-DR+/CD8+ T cells, CD8+HLA-DR+ T cells T cells, CD8+CD38+/CD8+ T cells, CD8+CD38+ T cells and CD4+/CD8+ T cells than those in controls. The percentages of specific lymphocyte subtypes were significantly different in cancer patients versus healthy individuals. For instance, cancer patients had lower levels of B cells, CD4+ T cells, naïve CD4+/CD4+ T cells, naïve CD4+ T cells, CD4+CD28+ T cells, CD8+CD28+ T cells and higher levels of NK cells, white blood cells (WBC), monocytes, neutrophils, eosinophils, basophils, monocytes to lymphocyte ratio (MLR), neutrophils to lymphocyte ratio (NLR), eosinophil to lymphocyte ratio (ELR), basophil to lymphocyte ratio (BLR), and blood platelet to lymphocyte ratio (PLR).

Conclusions: Abnormal T cell levels can be used as an independent predictive biomarker for noninvasive early screening in NSCLC occurrence and progression.
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http://dx.doi.org/10.1186/s12890-021-01636-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420051PMC
September 2021

Prognostic value of a modified Immunoscore in patients with stage IIII resectable colon cancer.

Chin J Cancer Res 2021 Jun;33(3):379-390

Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.

Objective: The Immunoscore method has proved fruitful for predicting prognosis in patients with colon cancer. However, there is still room for improvement in this scoring method to achieve further advances in its clinical translation. This study aimed to develop and validate a modified Immunoscore (IS-mod) system for predicting overall survival (OS) in patients with stage I-III colon cancer.

Methods: The IS-mod was proposed by counting CD3+ and CD8+ immune cells in regions of the tumor core and its invasive margin by drawing two lines of interest. A discovery cohort (N=212) and validation cohort (N=103) from two centers were used to evaluate the prognostic value of the IS-mod.

Results: In the discovery cohort, 5-year survival rates were 88.6% in the high IS-mod group and 60.7% in the low IS-mod group. Multivariate analysis confirmed that the IS-mod was an independent prognostic factor for OS [adjusted hazard ratio (HR)=0.36, 95% confidence interval (95% CI): 0.20-0.63]. With less annotation and computation cost, the IS-mod achieved performance comparable to that of the Immunoscore-like (IS-like) system (C-index, 0.676 . 0.661, P=0.231). The 2-category IS-mod using 47.5% as the threshold had a better prognostic value than that using a fixed threshold of 25% (C-index, 0.653 . 0.573, P=0.004). Similar results were confirmed in the validation cohort.

Conclusions: Our method simplifies the annotation and accelerates the calculation of Immunoscore method, thus making it easier for clinical implementation. The IS-mod achieved comparable prognostic performance when compared to the IS-like system in both cohorts. Besides, we further found that even with a small reference set (N≥120), the IS-mod still demonstrated a stable prognostic value. This finding may inspire other institutions to develop a local reference set of an IS-mod system for more accurate risk stratification of colon cancer.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2021.03.09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286894PMC
June 2021

Humidity-Insensitive NO Sensors Based on SnO/rGO Composites.

Front Chem 2021 28;9:681313. Epub 2021 May 28.

Department of Health and Environmental Sciences, Xi'an Jiaotong-Liverpool University, Suzhou, China.

This study reported a novel humidity-insensitive nitrogen dioxide (NO) gas sensor based on tin dioxide (SnO)/reduced graphene oxide (rGO) composites through the sol-gel method. The sensor demonstrated ppb-level NO detection in p-type sensing behaviors (13.6% response to 750 ppb). Because of the synergistic effect on SnO/rGO p-n heterojunction, the sensing performance was greatly enhanced compared to that of bare rGO. The limit of detection of sensors was as low as 6.7 ppb under dry air. Moreover, benefited from the formed superhydrophobic structure of the SnO/rGO composites (contact angle: 149.0°), the humidity showed a negligible influence on the dynamic response (S) of the sensor to different concentration of NO when increasing the relative humidity (RH) from 0 to 70% at 116°C. The relative conductivity of the sensor to 83% relative humidity was 0.11%. In addition, the response ratio (S/S) between 750 ppb NO and 83% RH was 649.0, indicating the negligible impaction of high-level ambient humidity on the sensor. The as-fabricated humidity-insensitive gas sensor can promise NO detection in real-world applications such as safety alarm, chemical engineering, and so on.
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http://dx.doi.org/10.3389/fchem.2021.681313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193670PMC
May 2021

ZNF280A promotes lung adenocarcinoma development by regulating the expression of EIF3C.

Cell Death Dis 2021 01 4;12(1):39. Epub 2021 Jan 4.

Department of Medical Oncology, Peking Union Medical College Hospital, Beijing, China.

Lung adenocarcinoma (LUAD) is the most common histological subtype in non-small cell lung cancer, which is the malignant tumor with the highest mortality and morbidity in the world. Herein, ZNF280A, a member of the zinc finger protein family carrying two consecutive Cys2His2 zinc finger domains, was shown by us to act as a tumor driver in LUAD. The immunohistochemical analysis of ZNF280A in LUAD indicated its positive correlation with tumor grade, pathological stage and lymphatic metastasis, and negative relationship with patients' survival. A loss-of-function study revealed the inhibition of LUAD development by ZNF280A in vitro and in vivo, whereas ZNF280A overexpression induced opposite effects. Statistical analysis of gene expression profiling in LUAD cells with or without ZNF280A knockdown identified EIF3C as a potential downstream of ZNF280A, which possesses similar regulatory effects on phenotypes of LUAD cells with ZNF280A. Moreover, downregulation of EIF3C in ZNF280A-overexpressed cells could attenuate neutralize the ZNF280A-induced promotion of LUAD. In summary, our study demonstrated that ZNF280A may promote the development of LUAD by regulating cell proliferation, apoptosis, cell cycle, and cell migration and probably via interacting EIF3C.
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http://dx.doi.org/10.1038/s41419-020-03309-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791122PMC
January 2021

A one-step electrochemically reduced graphene oxide based sensor for sensitive voltammetric determination of furfural in milk products.

Anal Methods 2021 01 9;13(1):56-63. Epub 2020 Dec 9.

College of Chemistry and Life Sciences, Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Zhejiang Normal University, Jinhua 321004, P. R. China.

Designing of fast, inexpensive and sensitive furfural determination methods for dairy milk is crucial in analytical and food chemistry. In this study, an electrochemical sensor was developed for the cathodic determination of furfural using a one-step electrochemically reduced graphene oxide (ErGO) modified glassy carbon electrode (GCE). The morphology and chemical constituents of the obtained ErGO/GCE were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Raman and X-ray photoelectron spectroscopy (XPS). The results showed that the fast and green electrochemical reduction process effectively eliminated the oxygen-containing groups in GO and produced reduced graphene with a high surface area and improved electron transfer kinetics. In addition, the ErGO based sensor displayed excellent responses for furfural in a NaHPO-NaHPO solution (pH = 9.18) with a wide linear range from 2 to 2015 μM and a low detection limit of 0.4 μM (S/N = 3). The reduction mechanism of furfural was also discussed. Furthermore, the feasibility of the sensor was confirmed by the determination of furfural in three milk samples which generated acceptable outputs.
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http://dx.doi.org/10.1039/d0ay01789bDOI Listing
January 2021

Effects and mechanism of gating modifier spider toxins on the hERG channel.

Toxicon 2021 Jan 17;189:56-64. Epub 2020 Nov 17.

Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Key Laboratory of Psychiatric Disorders, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic address:

Jingzhaotoxin-I, -III, -IV, -XIII, and -35 (JZTX-I, -III, -IV, -XIII, and -35), gating modifier toxins isolated from the venom of the Chinese tarantula Chilobrachys Jingzhao, were reported to act on cardiac sodium channels and Kv channels. JZTX-I and JZTX-XIII inhibited the hERG channel with the IC value of 626.9 nM and 612.6 nM, respectively. JZTX-III, -IV, and -35 share high sequence similarity with JZTX-I and JZTX-XIII, but they showed much lower affinity on the hERG channel compared with JZTX-I and JZTX-XIII. The inhibitory potency of the above five toxins on the hERG channel was not in accordance with their affinity on the Nav1.5 and Kv2.1 channels, indicating that the bioactive surfaces of the five toxins interacting with hERG, Nav1.5 and Kv2.1 are at least in part different. Structure-function analysis of the gating modifier toxins suggested that the functional bioactive surface binding to the hERG channel consists of a conserved hydrophobic patch, surrounding acidic residues (Glu10 in JZTX-XIII, Glu11 in JZTX-I), and basic residues which may be different from residues binding to the Kv2.1 channel.
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http://dx.doi.org/10.1016/j.toxicon.2020.11.008DOI Listing
January 2021

Flammulina velutipes polysaccharide improves C57BL/6 mice gut health through regulation of intestine microbial metabolic activity.

Int J Biol Macromol 2021 Jan 14;167:1308-1318. Epub 2020 Nov 14.

Shunde Hospital of Southern Medical University (The First People's Hospital of Shunde), No.1 of Jiazi Road, Lunjiao, Shunde District, Foshan City, Guangdong Province, China. Electronic address:

Flammulina velutipes polysaccharides (FVP) can improve gut health through gut microbiota and metabolism regulation. In this study, the 28-days fed experiment was used to investigate gut microbime and metabolic profiling induced by FVP. After treatment, intestinal tissue section showed the higher villus height and villus height/crypt depth (V/C) value in FVP-treated group. The 16 s rRNA gene sequencing revealed microbiota composition alteration caused by FVP, as the Firmicutes phylum increased while Bacteroidetes phylum slightly decreased. The metabolic profiling was detected by LC/MS and results showed 56 and 99 compounds were dramatically changed after FVP treatment in positive and negative ion mode, respectively. Annotation in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways displayed the adjustment of energy metabolism, amino acid metabolism, nucleotide metabolism and other related basic pathways after FVP treatment. Our study suggested that FVP can be developed as a dietary supplement for intestine health promotion.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.11.085DOI Listing
January 2021

Hist-Immune signature: a prognostic factor in colorectal cancer using immunohistochemical slide image analysis.

Oncoimmunology 2020 10 30;9(1):1841935. Epub 2020 Oct 30.

Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Computerized image analysis for whole-slide images has been shown to improve efficiency, accuracy, and consistency in histopathology evaluations. We aimed to assess whether immunohistochemistry (IHC) image quantitative features can reflect the immune status and provide prognostic information for colorectal cancer patients. A fully automated pipeline was designed to extract histogram features from IHC digital images in a training set (N = 243). A Hist-Immune signature was generated with selected features using the LASSO Cox model. The results were validated using internal (N = 147) and external (N = 76) validation sets. The five-feature-based Hist-Immune signature was significantly associated with overall survival in training (HR 2.72, 95% CI 1.68-4.41, < .001), internal (2.86, 1.28-6.39, 0.010), and external (2.30, 1.02-6.16, 0.044) validation sets. The full model constructed by integrating the Hist-Immune signature and clinicopathological factors had good discrimination ability (C-index 0.727, 95% CI 0.678-0.776), confirmed using internal (0.703, 0.621-0.784) and external (0.756, 0.653-0.859) validation sets. Our findings indicate that the Hist-Immune signature constructed based on the quantitative features could reflect the immune status of patients with colorectal cancer, which might advocate change in risk stratification and consequent precision medicine.
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http://dx.doi.org/10.1080/2162402X.2020.1841935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605350PMC
October 2020

Prognostic Nomogram That Predicts Overall Survival of Patients with Distal Cholangiocarcinoma After Pancreatoduodenectomy.

Cancer Manag Res 2020 20;12:10303-10310. Epub 2020 Oct 20.

Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

Purpose: We aimed to develop a nomogram for predicting the prognosis of patients with distal cholangiocarcinoma (DCC) and to compare its performance with that of the American Joint Committee on Cancer (AJCC) TNM system.

Patients And Methods: To develop a nomogram, we collected the clinical data of 147 patients diagnosed with DCC who underwent pancreatoduodenectomy. Predictive accuracy and discriminative ability were determined using a concordance index and a calibration curve. Predictive performance was compared with that of a current staging systems for DCC.

Results: Multivariate analysis revealed that jaundice, alcohol consumption, high fibrinogen, poorly differentiated tumor cells, positive lymph nodes, and positive margins were significantly associated with overall survival. These variables were incorporated into the nomogram. The concordance index of the nomogram for predicting overall survival was 0.737 (P<0.001), which is significantly higher than the concordance index values (concordance index = 0.586) acquired using the AJCC TNM system (eighth edition). The calibration curve agreed well with predicted prediction and observed overall survival.

Conclusion: We developed a nomogram for predicting the prognoses of patients with distal cholangiocarcinoma, which had superior practical clinical value compared with that of the AJCC TNM system.
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http://dx.doi.org/10.2147/CMAR.S276393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585820PMC
October 2020

Artificial intelligence quantified tumour-stroma ratio is an independent predictor for overall survival in resectable colorectal cancer.

EBioMedicine 2020 Nov 8;61:103054. Epub 2020 Oct 8.

Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou 510080, China. Electronic address:

Background: An artificial intelligence method could accelerate the clinical implementation of tumour-stroma ratio (TSR), which has prognostic relevance in colorectal cancer (CRC). We, therefore, developed a deep learning model for the fully automated TSR quantification on routine haematoxylin and eosin (HE) stained whole-slide images (WSI) and further investigated its prognostic validity for patient stratification.

Methods: We trained a convolutional neural network (CNN) model using transfer learning, with its nine-class tissue classification performance evaluated in two independent test sets. Patch-level segmentation on WSI HE slides was performed using the model, with TSR subsequently derived. A discovery (N=499) and validation cohort (N=315) were used to evaluate the prognostic value of TSR for overall survival (OS).

Findings: The CNN-quantified TSR was a prognostic factor, independently of other clinicopathologic characteristics, with stroma-high associated with reduced OS in the discovery (HR 1.72, 95% CI 1.24-2.37, P=0.001) and validation cohort (2.08, 1.26-3.42, 0.004). Integrating TSR into a Cox model with other risk factors showed improved prognostic capability.

Interpretation: We developed a deep learning model to quantify TSR based on histologic WSI of CRC and demonstrated its prognostic validity for patient stratification for OS in two independent CRC patient cohorts. This fully automatic approach allows for the objective and standardised application while reducing pathologists' workload. Thus, it can potentially be of significant aid in clinical prognosis prediction and decision-making.

Funding: National Key Research and Development Program of China, National Science Fund for Distinguished Young Scholar, and National Science Foundation for Young Scientists of China.
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http://dx.doi.org/10.1016/j.ebiom.2020.103054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648125PMC
November 2020

Targeting the gut microbial metabolic pathway with small molecules decreases uremic toxin production.

Gut Microbes 2020 11;12(1):1-19

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine , Nanjing, China.

Uremic toxins are a class of toxins that accumulate in patients with chronic kidney disease (CKD). Indoxyl sulfate (IS), a typical uremic toxin, is not efficiently removed by hemodialysis. Modulation of IS production in the gut microbiota may be a promising strategy for decreasing IS concentration, thus, delaying CKD progression. In the present study, we identified isoquercitrin (ISO) as a natural product that can perturb microbiota-mediated indole production without directly inhibiting the growth of microbes or the indole-synthesizing enzyme TnaA. ISO inhibits the establishment of H proton potential by regulating the gut bacteria electron transport chain, thereby inhibiting the transport of tryptophan and further reducing indole biosynthesis. This non-microbiocidal mechanism may enable ISO to be used as a therapeutic tool, specifically against pathologies triggered by the accumulation of the microbial-produced toxin IS, as in CKD. Herein, we have shown that it is possible to inhibit gut microbial indole production using natural components. Therefore, targeting the uremic toxin metabolic pathway in gut bacteria may be a promising strategy to control host uremic toxin production.
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http://dx.doi.org/10.1080/19490976.2020.1823800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577114PMC
November 2020

Rodent Models of Amyloid-Beta Feature of Alzheimer's Disease: Development and Potential Treatment Implications.

Aging Dis 2020 Oct 1;11(5):1235-1259. Epub 2020 Oct 1.

1School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide and causes severe financial and social burdens. Despite much research on the pathogenesis of AD, the neuropathological mechanisms remain obscure and current treatments have proven ineffective. In the past decades, transgenic rodent models have been used to try to unravel this disease, which is crucial for early diagnosis and the assessment of disease-modifying compounds. In this review, we focus on transgenic rodent models used to study amyloid-beta pathology in AD. We also discuss their possible use as promising tools for AD research. There is still no effective treatment for AD and the development of potent therapeutics are urgently needed. Many molecular pathways are susceptible to AD, ranging from neuroinflammation, immune response, and neuroplasticity to neurotrophic factors. Studying these pathways may shed light on AD pathophysiology as well as provide potential targets for the development of more effective treatments. This review discusses the advantages and limitations of these models and their potential therapeutic implications for AD.
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http://dx.doi.org/10.14336/AD.2019.1026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505263PMC
October 2020

Identification of WDFY3 Neoantigens as Prognostic Markers in Longterm Survivors of Extrahepatic Cholangiocarcinoma.

Curr Cancer Drug Targets 2020 ;20(11):875-886

Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Background: Neoantigens are newly formed antigens that have not been previously recognized by the immune system. They may arise from altered tumor proteins that form as a result of mutations. Although neoantigens have recently been linked to antitumor immunity in long-term survivors of cancers, such as melanoma and colorectal cancer, their prognostic and immune-modulatory role in many cancer types remains undefined.

Objective: The purpose of this study is to identify prognostic markers for long-term extrahepatic cholangiocarcinoma (EHCC) survival.

Methods: We investigated neoantigens in EHCC, a rare, aggressive cancer with a 5-year overall survival rate lower than 10%, using a combination of whole-exome sequencing (WES), RNA sequencing (RNA-seq), computational biophysics, and immunohistochemistry.

Results: Our analysis revealed a decreased neutrophil infiltration-related trend of high-quality neoantigen load with IC50 <500 nM (r=-0.445, P=0.043). Among 24 EHCC patients examined, we identified four long-term survivors with WDFY3 neoantigens and none with WDFY3 neoantigens in the short-term survivors. The WDFY3 neoantigens are associated with a lower infiltration of neutrophils (p=0.013), lower expression of CCL5 (p=0.025), CXCL9 (p=0.036) and TIGIT (p=0.016), and less favorable prognosis (p=0.030). In contrast, the prognosis was not significantly associated with tumor mutation burden, neoantigen load, or immune cell infiltration.

Conclusion: We suggest that the WDFY3 neoantigens may affect prognosis by regulating antitumor immunity and that the WDFY3 neoantigens may be harnessed as potential targets for immunotherapy of EHCC.
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http://dx.doi.org/10.2174/1568009620999200918121456DOI Listing
January 2020

Antioncogenic Effect of MicroRNA-206 on Neck Squamous Cell Carcinoma Through Inhibition of Proliferation and Promotion of Apoptosis and Autophagy.

Hum Gene Ther 2020 12 8;31(23-24):1260-1273. Epub 2020 Dec 8.

Departments of Otorhinolaryngology-Head and Neck Surgery ,Peking University First Hospital, Beijing, P.R. China.

Recent studies have reported the crucial role of stanniocalcin-2 (STC2) in hepatocellular carcinoma; however, its role in head and neck squamous cell carcinoma (HNSCC) remains elusive. In this study, microRNA-206 (miR-206) was predicted to target STC2 gene. The study herein aimed to elucidate the effect of miR-206 on HNSCC by targeting STC2. STC2 was highly expressed in HNSCC tissues and cells. By targeting STC2, miR-206 decreased mRNA and protein expression of STC2. Importantly, our study showed that miR-206 blocked the Akt signaling pathway by inhibiting STC2. Intriguingly, our data from and experiments suggested that miR-206 overexpression led to decreased cell proliferation and increased cell apoptosis and autophagy, as well as suppressed tumor growth; whereas, STC2 silencing reversed the effects of miR-206 inhibitor on those biological behaviors. In this study, we investigated the antioncogenic effect of miR-206 on HNSCC by targeting STC2, and highlighted miR-206/STC2 aixs as potential therapeutic targets for HNSCC.
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http://dx.doi.org/10.1089/hum.2020.090DOI Listing
December 2020

TGF-β1 modulates temozolomide resistance in glioblastoma via altered microRNA processing and elevated MGMT.

Neuro Oncol 2021 03;23(3):435-446

Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China.

Background: Our previous studies have indicated that miR-198 reduces cellular methylguanine DNA methyltransferase (MGMT) levels to enhance temozolomide sensitivity. Transforming growth factor beta 1 (TGF-β1) switches off miR-198 expression by repressing K-homology splicing regulatory protein (KSRP) expression in epidermal keratinocytes. However, the underlying role of TGF-β1 in temozolomide resistance has remained unknown.

Methods: The distribution of KSRP was detected by western blotting and immunofluorescence. Microarray analysis was used to compare the levels of long noncoding RNAs (lncRNAs) between TGF-β1-treated and untreated cells. RNA immunoprecipitation was performed to verify the relationship between RNAs and KSRP. Flow cytometry and orthotopic and subcutaneous xenograft tumor models were used to determine the function of TGF-β1 in temozolomide resistance.

Results: Overexpression of TGF-β1 contributed to temozolomide resistance in MGMT promoter hypomethylated glioblastoma cells in vitro and in vivo. TGF-β1 treatment reduced cellular MGMT levels through suppressing the expression of miR-198. However, TGF-β1 upregulation did not affect KSRP expression in glioma cells. We identified and characterized 2 lncRNAs (H19 and HOXD-AS2) that were upregulated by TGF-β1 through Smad signaling. H19 and HOXD-AS2 exhibited competitive binding to KSRP and prevented KSRP from binding to primary miR-198, thus decreasing miR-198 expression. HOXD-AS2 or H19 upregulation strongly promoted temozolomide resistance and MGMT expression. Moreover, KSRP depletion abrogated the effects of TGF-β1 and lncRNAs on miR-198 and MGMT. Finally, we found that patients with low levels of TGF-β1 or lncRNA expression benefited from temozolomide therapy.

Conclusions: Our results reveal an underlying mechanism by which TGF-β1 confers temozolomide resistance. Furthermore, our findings suggest that a novel combination of temozolomide with a TGF-β inhibitor may serve as an effective therapy for glioblastomas.
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http://dx.doi.org/10.1093/neuonc/noaa198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992894PMC
March 2021

Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: a Randomized, Double-Blind, Phase 3 Study (Oncology pRogram by InnovENT anti-PD-1-11).

J Thorac Oncol 2020 10 8;15(10):1636-1646. Epub 2020 Aug 8.

Medical Science and Strategy Oncology, Innovent Biologics, Inc., Shanghai, People's Republic of China.

Introduction: Sintilimab, an anti-programmed death 1 antibody, plus pemetrexed and platinum had revealed promising efficacy for nonsquamous NSCLC in a phase 1b study. We conducted a randomized, double-blind, phase 3 study to compare the efficacy and safety of sintilimab with placebo, both in combination with such chemotherapy (ClinicalTrials.gov: NCT03607539).

Methods: A total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC without sensitizing EGFR or anaplastic lymphoma kinase genomic aberration were randomized (2:1 ratio) to receive either sintilimab 200 mg or placebo plus pemetrexed and platinum once every 3 weeks for four cycles, followed by sintilimab or placebo plus pemetrexed therapy. Crossover or treatment beyond disease progression was allowed. The primary end point was progression-free survival (PFS) as judged by an independent radiographic review committee.

Results: As of November 15, 2019, the median follow-up was 8.9 months. The median PFS was significantly longer in the sintilimab-combination group than that in the placebo-combination group (8.9 versus 5.0 mo; hazard ratio, 0.482, 95% confidence interval [CI]: 0.362-0.643; p < 0.00001). The confirmed objective response rate was 51.9% (95% CI: 45.7%-58.0%) in the sintilimab-combination group and 29.8% (95% CI: 22.1%-38.4%) in placebo-combination group. The incidence of grade 3 or higher adverse events was 61.7% in sintilimab-combination group and 58.8% in placebo-combination group.

Conclusions: In Chinese patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC, the addition of sintilimab to chemotherapy with pemetrexed and platinum resulted in considerably longer PFS than with chemotherapy alone with manageable safety profiles.
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http://dx.doi.org/10.1016/j.jtho.2020.07.014DOI Listing
October 2020

MMP-9 Inhibitor GM6001 Prevents the Development of ssTBI-Induced Parkinson's Disease via the Autophagy Pathway.

Cell Mol Neurobiol 2020 Aug 7. Epub 2020 Aug 7.

Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

Concussion is a widely recognized environmental risk factor for neurodegenerative diseases, including Parkinson's disease (PD). Small-vessel disease of the brain has been reported to contribute to neurodegenerative diseases. In this study, we observed BBB disruption in wild-type (WT) mice, but not in matrix metalloproteinase 9 (MMP-9) knockout mice, subjected to single severe traumatic brain injury (ssTBI). Furthermore, treating ssTBI mice with the MMP-9 inhibitor GM6001 effectively maintained BBB integrity, promoted the elimination of damaged mitochondria via mitophagy, and then prevented neuronal death and progressive neurodegeneration. However, we did not observe this neuroprotective effect of MMP-9 inhibition in beclin-1 mice. Collectively, these findings revealed that concussion led to BBB disruption via MMP-9, and that GM6001 prevented the development of PD via the autophagy pathway.
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http://dx.doi.org/10.1007/s10571-020-00933-zDOI Listing
August 2020

High Cancer Susceptibility Candidate 8 Expression Is Associated With Poor Prognosis of Pancreatic Adenocarcinoma: Validated Analysis Based on Four Cancer Databases.

Front Cell Dev Biol 2020 4;8:392. Epub 2020 Jun 4.

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: The aim of this study was to explore the association between the expression of a long non-coding RNA (lncRNA), cancer susceptibility candidate 8 (CASC8), and pancreatic adenocarcinoma (PAAD).

Materials And Methods: starBase database was used to perform differential expression, survival, and competing endogenous RNA (ceRNA) network and H19/miR-671 correlation analyses for CASC8 in 178 PAAD samples. Using the cBioPortal database website, we analyzed the alteration in CASC8 expression and its correlation with the overall survival in PAAD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were also performed using the circlncRNAnet database. Analysis of CASC8 polymorphisms was performed using the UCSC Xena database. Finally, the expression of CASC8 in Chinese PAAD tissues was validated by qPCR.

Results: The expression of CASC8 was observed to be high in 178 PAAD samples [fold change = 8.71, = 0.0014, false discovery rate (FDR) = 0.04] and was related with poor prognosis, but not in pancreatic neuroendocrine tumor (pNET). CASC8 amplification was noted in 6% of the PAAD patients; however, the gene amplification did not affect the expression of CASC8 but was involved with the overall survival time of PAAD patients. Network analysis indicated that H19 is the ceRNA pair of CASC8 and that CASC8 competitively binds to miR-671 and might participate in the process of epithelial-to-mesenchymal transition (EMT). The correlation analysis showed that CASC8 was significantly negatively correlated with SMAD7. The analysis of CASC8 polymorphism showed that high copy number segment (CNS) of CASC8 is associated with low survival. Validation using PAAD tissues from Chinese patients was consistent with the findings.

Conclusion: CASC8 is specifically expressed at a high level in PAAD and associated with poor prognosis, which might be through its interaction with H19, miR-671, and SMAD7. These results indicate that CASC8 could serve as a novel marker for predicting the prognosis and as a potential target for the therapy of PAAD.
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http://dx.doi.org/10.3389/fcell.2020.00392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287184PMC
June 2020

Sex difference in cognitive impairment in drug-free schizophrenia: Association with miR-195 levels.

Psychoneuroendocrinology 2020 09 7;119:104748. Epub 2020 Jun 7.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Objective: There is evidence that microRNA-195 (miR-195) is associated with schizophrenia (SZ) and cognition, but the relationship between miR-195 and cognitive impairment in SZ is still unknown. Sex differences in both microRNA (miRNA) expression and cognition were found in SZ. We aim to investigate whether sex moderates the relationship between miR-195 levels and cognition in SZ.

Methods: We recruited 121 drug-free SZ patients and 129 healthy controls. miR-195 expression levels in peripheral blood mononuclear cells (PBMCs) were measured using qRT-PCR. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess cognitive function. MANCOVA, ANCOVA, correlation analysis and hierarchical linear regression analysis were used to test the effect of sex on the aforementioned variables.

Results: All RBANS scores significantly decreased in patients compared to healthy controls (all p < 0.001); ANCOVA analysis demonstrated female SZ patients had lower delayed memory score (F = 15.36, p < 0.001) and total score (F = 5.26, p = 0.024) than male patients. There was no diagnosis, sex or sex by diagnosis interaction effect on miR-195 levels (all p > 0.05). Interestingly, correlation analysis showed significant negative association between miR-195 and attention score (r = -0.389, p = 0.019), delayed memory score (r= -0.351, p = 0.036), and total score (r = -0.386, p = 0.020) only in female patients. Hierarchical regression analysis showed sex by miR-195 interaction was a significant predictor of the RBANS total score (ΔR2 = 0.042, F(1, 67) = 4.71, p = 0.033).

Conclusion: Our data indicate that miR-195 is associated with cognitive impairment in female SZ patients, and it may be involved in the underlying mechanism of sex differences in cognitive impairment in SZ.
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http://dx.doi.org/10.1016/j.psyneuen.2020.104748DOI Listing
September 2020

Evaluation of human epidermal growth factor receptor 2 status of breast cancer using preoperative multidetector computed tomography with deep learning and handcrafted radiomics features.

Chin J Cancer Res 2020 Apr;32(2):175-185

Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.

Objective: To evaluate the human epidermal growth factor receptor 2 (HER2) status in patients with breast cancer using multidetector computed tomography (MDCT)-based handcrafted and deep radiomics features.

Methods: This retrospective study enrolled 339 female patients (primary cohort, n=177; validation cohort, n=162) with pathologically confirmed invasive breast cancer. Handcrafted and deep radiomics features were extracted from the MDCT images during the arterial phase. After the feature selection procedures, handcrafted and deep radiomics signatures and the combined model were built using multivariate logistic regression analysis. Performance was assessed by measures of discrimination, calibration, and clinical usefulness in the primary cohort and validated in the validation cohort.

Results: The handcrafted radiomics signature had a discriminative ability with a C-index of 0.739 [95% confidence interval (95% CI): 0.661-0.818] in the primary cohort and 0.695 (95% CI: 0.609-0.781) in the validation cohort. The deep radiomics signature also had a discriminative ability with a C-index of 0.760 (95% CI: 0.690-0.831) in the primary cohort and 0.777 (95% CI: 0.696-0.857) in the validation cohort. The combined model, which incorporated both the handcrafted and deep radiomics signatures, showed good discriminative ability with a C-index of 0.829 (95% CI: 0.767-0.890) in the primary cohort and 0.809 (95% CI: 0.740-0.879) in the validation cohort.

Conclusions: Handcrafted and deep radiomics features from MDCT images were associated with HER2 status in patients with breast cancer. Thus, these features could provide complementary aid for the radiological evaluation of HER2 status in breast cancer.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2020.02.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219093PMC
April 2020

Preoperative Prediction of Ki-67 Status in Breast Cancer with Multiparametric MRI Using Transfer Learning.

Acad Radiol 2021 02 8;28(2):e44-e53. Epub 2020 Apr 8.

Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No.106, Zhongshan 2nd road, Guangzhou 510080 Guangdong, PR China. Electronic address:

Rationale And Objectives: Ki-67 is one of the most important biomarkers of breast cancer traditionally measured invasively via immunohistochemistry. In this study, deep learning based radiomics models were established for preoperative prediction of Ki-67 status using multiparametric magnetic resonance imaging (mp-MRI).

Materials And Methods: Total of 328 eligible patients were retrospectively reviewed [training dataset (n = 230) and a temporal validation dataset (n = 98)]. Deep learning imaging features were extracted from T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and contrast enhanced T1-weighted imaging (T1+C). Transfer learning techniques constructed four feature sets based on the individual three MR sequences and their combination (i.e., mp-MRI). Multilayer perceptron classifiers were trained for final prediction of Ki-67 status. Mann-Whitney U test compared the predictive performance of individual models.

Results: The area under curve (AUC) of models based on T2WI,T1+C,DWI and mp-MRI were 0.727, 0.873, 0.674, and 0.888 in the training dataset, respectively, and 0.706, 0.829, 0.643, and 0.875 in the validation dataset, respectively. The predictive performance of mp-MRI classification model in the AUC value was significantly better than that of the individual sequence model (all p< 0.01).

Conclusion: In clinical practice, a noninvasive approach to improve the performance of radiomics in preoperative prediction of Ki-67 status can be provided by extracting breast cancer specific structural and functional features from mp-MRI images obtained from conventional scanning sequences using the advanced deep learning methods. This could further personalize medicine and computer aided diagnosis.
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http://dx.doi.org/10.1016/j.acra.2020.02.006DOI Listing
February 2021

Novel anilino quinazoline-based EGFR tyrosine kinase inhibitors for treatment of non-small cell lung cancer.

Biomater Sci 2021 Jan 1;9(2):443-455. Epub 2020 Apr 1.

NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics, Molecular Imaging Research Center (MIRC), Harbin Medical University, Harbin, Heilongjiang 150028, China.

The epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). EGFR-TKI positron emission tomography (PET) probes based on the central quinazoline core show great potential for NSCLC diagnosis, and pre-clinical and clinical therapy monitoring. In our previous research, anilino quinazoline based PET probe, N-(3-chloro-4-fluorophenyl)-7-(2-(2-(2-(2-F-fluoroethoxy) ethoxy) ethoxy) ethoxy)-6-methoxyquinazolin-4-amine (F-MPG), have been developed, and it has been successfully demonstrated to be a powerful non-invasive imaging tool for differentiating EGFR mutation status and stratifying NSCLC patients for EGFR-TKI treatment in a clinical study (n = 75 patients). Moreover, it has been found that F-MPG shows excellent tumor targeting performance and good pharmacokinetic characteristics in NSCLC patients. These results motivate us to investigate the cancer treatment efficacy of non-radioactive F-MPG and its analogue N-(3-chloro-4-fluorophenyl)-7-(2-(2-(2-(2-hydroxyethoxy)ethoxy) ethoxy) ethoxy)-6-methoxyquinazolin-4-amine (OH-MPG) in vitro and in small animal models. Our studies revealed that both F-MPG and OH-MPG displayed high therapeutic effect to NSCLC cells (IC = 5.3 nM and 2.0 nM to HCC827 cells for F-MPG and OH-MPG, respectively). More importantly, compared with a standard EGFR-TKI, 4-(3-bromoanilino)-6,7-dimethoxyquinazoline (PD153035), F-MPG and OH-MPG showed stronger tumor inhibition in preclinical models. Furthermore, the treatment efficacy of F-MPG or OH-MPG monitored by F-FDG-PET indicated that tumor uptake in treated groups was significantly decreased. Ex vivo experiments showed that the levels of serum biomarkers and pathological changes in the liver were significantly reduced in the F-MPG and OH-MPG group, compared to PD153035 treated group. In conclusion, EGFR targeted F-MPG and OH-MPG exhibit promising anti-tumor activity with limited liver damage, thus representing promising drug candidates for further investigation for combating the deadly NSCLC.
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http://dx.doi.org/10.1039/d0bm00293cDOI Listing
January 2021

Clinical Analysis of 15 Cases of Gallbladder Neuroendocrine Carcinoma and Comparison with Gallbladder Adenocarcinoma Using a Propensity Score Matching.

Cancer Manag Res 2020 26;12:1437-1446. Epub 2020 Feb 26.

Department of Hepatobiliary Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

Purpose: This study aimed to investigate the clinicopathological features and prognosis of gallbladder neuroendocrine carcinoma (GB-NEC).

Patients And Methods: Fifteen patients with GB-NEC and 171 patients with gallbladder adenocarcinoma (GB-ADC) treated in two tertiary medical centers between 2009 and 2015 were included. The clinicopathological features and prognostic risk factors of GB-NEC were analyzed retrospectively. A propensity score matching in a 1:2 ratio was used to compare the prognosis of GB-NEC and GB-ADC.

Results: For patients with GB-NEC, the median age of patients was 58.4 years (range 26-75), with a M:F ratio of 7:8. Based on 2010 WHO classification, ten cases were pathologically confirmed as NECs and five cases as MANECs. For TNM staging, eleven patients were stage III or above; while for Nevin staging, seven patients were stage IV or above. The 1-, 2-, and 3-year overall survival (OS) of GB-NEC were 60.0%, 38.8% and 31.1%, respectively, and the median survival time was 20.4 months. Patients with lymph node metastasis had significantly shorter survival than those without (OS: 10.4 vs 26.0 months, p<0.05). Accordingly, patients of Nevin stage III had better OS than those of Nevin stage IV (p<0.05), but other potential risk factors including gender, age, clinical symptoms, TNM stage, histopathologic subtype and treatment showed no significance. After the propensity score matching, the baseline variables had no significant difference between 15 patients with GB-NEC and 30 patients with GB-ADC, survival analysis showed GB-NEC had worse prognosis (3-year overall survival rate: 31.1% vs 63.8%, p<0.01).

Conclusion: Nevin staging helps classify patients of GB-NEC with different prognosis and the lymph node metastasis is a strong negative prognostic factor for OS. The propensity score analysis revealed even with the similar stage and treatment, GB-NEC still had worse OS than GB-ADC.
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http://dx.doi.org/10.2147/CMAR.S227501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049775PMC
February 2020

Preoperative Bilirubin-Adjusted Carbohydrate Antigen 19-9 as a Prognostic Factor for Extrahepatic Cholangiocarcinoma Patients at a Single Center.

Cancer Manag Res 2020 20;12:411-417. Epub 2020 Jan 20.

Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People's Republic of China.

Purpose: The aims of our study were to investigate the prognostic impact of the rate of preoperative serum carbohydrate antigen 19-9/bilirubin (CA19-9/BR) on patients with extrahepatic bile duct cancer.

Patients And Methods: We collected clinical data from 89 patients who underwent surgery for extrahepatic cholangiocarcinoma (ECC) at Peking Union Medical College Hospital between January 2012 and December 2017. The Kaplan-Meier analysis for univariate analysis and the Cox proportional hazards models for multivariate analysis were used to determine possible independent prognostic factors.

Results: CA19-9/BR was classified as elevated compared with normal based on the upper serum normal values of CA19-9 (37 U/mL) and bilirubin (1.5 mg/dL), which gives a cut-off at 25 U/mL/mg/dL. Univariate analysis showed that the overall survival of patients with a high CA19-9/BR ratio was significantly worse compared with patients with a low CA19-9/BR ratio (Hazard Ratio [HR] 2.149; 95% Confidence Interval [95% CI] 1.027-4.495; P=0.042). Multivariate analysis revealed that a high CA19-9/BR ratio (HR 3.250; 95% CI 1.165-9.067; P=0.024), low differentiation (HR 3.551; 95% CI 1.231-10.244; P=0.019), and positive margin (HR 2.555; 95% CI 1.111-5.875; P=0.027) remained independent prognostic factors after adjusting for age at diagnosis, maximal diameters, and other possible factors.

Conclusion: The preoperative CA19-9/BR ratio is a good prognostic factor in predicting survival in ECC patients and closer follow-up is recommended in patients with a higher CA19-9/BR ratio before surgery.
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http://dx.doi.org/10.2147/CMAR.S229329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980863PMC
January 2020

Disturbance of Oxidative Stress Parameters in Treatment-Resistant Bipolar Disorder and Their Association With Electroconvulsive Therapy Response.

Int J Neuropsychopharmacol 2020 04;23(4):207-216

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objective: Electroconvulsive therapy (ECT) is an effective option for treatment-resistant bipolar disorder (trBD). However, the mechanisms of its effect are unknown. Oxidative stress is thought to be involved in the underpinnings of BD. Our study is the first, to our knowledge, to report the association between notable oxidative stress parameters (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], catalase [CAT], and malondialdehyde [MDA]) levels and ECT response in trBD patients.

Methods: A total 28 trBD patients and 49 controls were recruited. Six-week ECT and naturalistic follow-up were conducted. SOD, GSH-Px, CAT, and MDA levels were measured by enzyme-linked immunosorbent assay, and the 17-item Hamilton Depression Rating Scale and Young Mania Rating Scale were administered at baseline and the end of the 6th week. MANCOVA, ANCOVA, 2 × 2 ANCOVA, and a multiple regression model were conducted.

Results: SOD levels were lower in both trBD mania and depression (P = .001; P = .001), while GSH-Px (P = .01; P = .001) and MDA (P = .001; P = .001) were higher in both trBD mania and depression compared with controls. CAT levels were positively associated with 17-item Hamilton Depression Rating Scale scores in trBD depression (radjusted  = 0.83, P = .005). MDA levels in trBD decreased after 6 weeks of ECT (P = .001). Interestingly, MDA levels decreased in responders (P = .001) but not in nonresponders (P > .05).

Conclusions: Our study indicates that decreased SOD could be a trait rather than a state in trBD. Oxidative stress levels are associated with illness severity and ECT response. This suggests that the mechanism of oxidative stress plays a crucial role in the pathophysiology of trBD.
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http://dx.doi.org/10.1093/ijnp/pyaa003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177162PMC
April 2020

MicroRNA-940 inhibits epithelial-mesenchymal transition of glioma cells via targeting ZEB2.

Am J Transl Res 2019 15;11(12):7351-7363. Epub 2019 Dec 15.

Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University Nanjing, China.

MicroRNAs have been found ectopically expressed in many cancers and play essential roles in tumor EMT progress. Recent studies identified decreased miR-940 expression in glioma cells and may serve as a tumor-suppressor. However, whether miR-940 involve in glioma EMT remain poorly understood. Here we confirmed that miR-940 was significantly reduced in glioma cells and tissues. Introduction of miR-940 dramatically suppressed invasion and migration of glioma cells. Gain-of-function experiments showed ZEB2 as a direct target of miR-940, knockdown of ZEB2 evidently repressed invasive capacity of glioma cells through EMT. Moreover, reintroduction of ZEB2 effectively reversed the tumor suppressive effect of miR-940 treatment. In vivo study showed reduced tumor cell motion in miR-940-injected groups. Spearman's correlation analysis indicated inversely correlated expression of ZEB2 and miR-940 in gliomas and NBTs. Altogether, miR-940-ZEB2 cascade may play important roles in glioma cells invasion and EMT progression, and might provide new therapeutic approaches for better outcomes of GBM patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943459PMC
December 2019

Deep Learning Signature Based on Staging CT for Preoperative Prediction of Sentinel Lymph Node Metastasis in Breast Cancer.

Acad Radiol 2020 09 7;27(9):1226-1233. Epub 2019 Dec 7.

School of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, China; Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.

Rationale And Objectives: To evaluate the noninvasive predictive performance of deep learning features based on staging CT for sentinel lymph node (SLN) metastasis of breast cancer.

Materials And Methods: A total of 348 breast cancer patients were enrolled in this study, with their SLN metastases pathologically confirmed. All patients received contrast-enhanced CT preoperative examinations and CT images were segmented and analyzed to extract deep features. After the feature selection, deep learning signature was built with the selected key features. The performance of the deep learning signatures was assessed with respect to discrimination, calibration, and clinical usefulness in the primary cohort (184 patients from January 2016 to March 2017) and then validated in the independent validation cohort (164 patients from April 2017 to December 2018).

Results: Ten deep learning features were automatically selected in the primary cohort to establish the deep learning signature of SLN metastasis. The deep learning signature shows favorable discriminative ability with an area under curve of 0.801 (95% confidence interval: 0.736-0.867) in primary cohort and 0.817 (95% confidence interval: 0.751-0.884) in validation cohort. To further distinguish the number of metastatic SLNs (1-2 or more than two metastatic SLN), another deep learning signature was constructed and also showed moderate performance (area under curve 0.770).

Conclusion: We developed the deep learning signatures for preoperative prediction of SLN metastasis status and numbers (1-2 or more than two metastatic SLN) in patients with breast cancer. The deep learning signature may potentially provide a noninvasive approach to assist clinicians in predicting SLN metastasis in patients with breast cancer.
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http://dx.doi.org/10.1016/j.acra.2019.11.007DOI Listing
September 2020

In Situ Growth of [email protected] Hierarchical Nanostructures for High Performance HS Sensing.

ACS Appl Mater Interfaces 2019 Nov 18;11(47):44829-44836. Epub 2019 Nov 18.

Xi'an Jiaotong-Liverpool University , Department of Health and Environmental Sciences , 111 Renai Road , Suzhou , Jiangsu 215123 , P. R. China.

Heterostructured metal oxides with large specific surface area are crucial for constructing gas sensors with high performance. However, using slurry-coating and screen-printing methods to fabricate gas sensors cannot result in high uniformity and reproducibility of the sensors. Here, NiO nanowalls decorated by SnO nanoneedles ([email protected]) were in situ grown on ceramic microchips via a chemical bath deposition method to detect HS instead of print-coating and slurry-coating methods. The morphologies and compositions of the [email protected] hierarchical nanostructures (HNSs) were well tuned by varying the growth time of the [email protected] HNSs to optimize the sensing performance. The response of the [email protected] HNSs (2 h) to 1 ppm of HS was over 23-fold higher than that of the pure NiO nanowalls and 17-fold higher than that of the pure SnO nanosheets. This dramatic enhancement is attributed to the large surface area of the [email protected] HNSs and the p-n heterojunction at the heterointerface of SnO and NiO. The variation in the depletion layers ( and ) at the heterointerface of SnO and NiO greatly depends on the properties of the target gases (e.g., electron-withdrawing property (NO) or electron-donating property (HS)).
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http://dx.doi.org/10.1021/acsami.9b13001DOI Listing
November 2019

Thorough survey and analysis of pulmonary lymphoepithelioma-like carcinoma in Macau and multimodality treatment for advanced disease.

Lung Cancer 2019 12 11;138:116-123. Epub 2019 Oct 11.

Department of oncology, Centro Hospitalar Conde de Sao Januario, Estrada do Visconde de S. Januario, Macau, China. Electronic address:

Objective: Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer. The clinical course and prognosis of advanced LELC are largely unknown. Few reports have discussed multimodality treatment for LELC.

Materials And Methods: This retrospective study identified records from 2007 to 2018 of pulmonary LELCs and other lung cancer subtypes from hospital information systems and collected demographic, treatment, and survival data.

Results: In this cohort of 69 LELCs (median age: 55.4), more female, non-smokers, and fewer right upper lobe tumors (4.3%) were observed in the LELC subgroup compared with others. The median overall survival (OS) of LELCs was 40 months, superior to other subtypes (p < 0.05), except adenocarcinoma (p = 0.062). Patients with early stage disease and primary tumor resection tended to have better OS in univariate analysis, but surgery was the independent predictor in multivariate analysis (0.042). The median OS of 52 advanced LELCs was 22.7 months. Platinum-based chemotherapy and radiotherapy with curative purpose were independent predictors for OS of advanced LELCs (p = 0.004 and 0.003, respectively). For patients who received multimodality treatment in advanced setting, the median line of treatments was two. The overall response and disease-control rates were 61.8% and 80.6%, respectively. There were no differences in response or survival between patients receiving taxane-combined and non-taxane-combined chemotherapy. However, patients treated with radiotherapy in upfront settings had significantly favorable response and progression-free survival compared with those without. One case with PD-L1 positivity had pembrolizumab in the 4 line and achieved tumor shrinkage and stable disease for 12 months.

Conclusion: Patients who underwent radical resection of primary tumors had better prognoses. Patients with advanced LELC could achieve satisfactory survival by receiving multimodality treatment, including platinum-based chemotherapy and/or radiotherapy. Immune checkpoint inhibitors may be part of future therapies. A well-organized clinical trial should be performed to determine the optimal treatment regimen.
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http://dx.doi.org/10.1016/j.lungcan.2019.10.004DOI Listing
December 2019
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