Publications by authors named "Yalun Li"

64 Publications

Tumor-targeted hyaluronic acid-mPEG modified nanostructured lipid carriers for cantharidin delivery: An in vivo and in vitro study.

Fitoterapia 2021 Sep 10:105033. Epub 2021 Sep 10.

College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China. Electronic address:

Aim: Cantharidin (CTD), the major component of the anti-cancer medicine obtained from Mylabris cichorii, exerts good inhibitory effects on several cancers, such as liver and breast cancer. However, owing to its toxicity, its oral administration can cause various adverse effects, limiting its clinical applications. Therefore, the development of a novel nano-drug delivery system for CTD would be highly beneficial.

Methods: A nanostructured lipid carrier (NLC) was designed to actively target CTD to tumor cells using a hyaluronic acid (HA)-decorated copolymer (mPEG-NH); the NLCs were called HA-mPEG-CTD-NLC. HA-mPEG was synthesized using amidation, and HA-mPEG-CTD-NLC was generated through ultrasonic emulsification in water. The mean hydrodynamic diameter of the particles was approximately 119.3 nm.

Results: Pharmacokinetic studies revealed that the half-life of HA-mPEG-CTD-NLC and its area under the curve were higher than those of a CTD solution. Further, the plasma clearance rate of HA-mPEG-CTD-NLC was 0.41 times that of the CTD solution, implying a significantly prolonged drug retention time in vivo. Fluorescence in vivo endo-microscopy and optical in vivo imaging revealed that HA-mPEG-CTD-NLC had superior cytotoxicity and targeting efficacy against SMMC-7721 cells. An evaluation of the in vivo anti-tumor activity showed that HA-mPEG-CTD-NLC significantly inhibited tumor growth and prolonged survival in tumor-bearing mice, with a tumor inhibition rate of 65.96%.

Conclusions: Our results indicate that HA-mPEG-CTD-NLC may have great potential in liver cancer-targeted therapy.
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http://dx.doi.org/10.1016/j.fitote.2021.105033DOI Listing
September 2021

Identification of Target PTEN-Based miR-425 and miR-576 as Potential Diagnostic and Immunotherapeutic Biomarkers of Colorectal Cancer With Liver Metastasis.

Front Oncol 2021 19;11:657984. Epub 2021 Aug 19.

Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.

A major complication of colorectal cancer (CRC), one of the most common and fatal types of cancers, is secondary liver metastasis. For patients with this fate, there are very few biomarkers available in clinical application, and the disease remains incurable. Recently, increasing studies demonstrated that tumorigenesis and development are closely related to immune escape, indicating that the roles of immune-related indicators might have been neglected in the past in colorectal cancer liver metastases (CRLM). Here, we unveil that elevated miR-425 and miR-576 promote CRLM through inhibiting PTEN-mediated cellular immune function. Specifically, miR-425 and miR-576 were identified for their significant upregulation in CRLM compared with the primary CRC tissues based on GSE81581 ( = 8) and GSE44121 ( = 18) datasets. Besides, we determined that the two microRNAs (miRNAs) coparticipated in restraining P53 and transforming growth factor beta (TGF-β) signaling pathways associated with tumor metastasis, and both shortened the overall survival of the patients with metastatic susceptibility. Notably, hybridization on relatively large samples of paired CRC tissues ( = 157) not only substantiated that the expression of miR-425 and miR-576 was dramatically upregulated in CRLM but also revealed that they were closely related to tumor deterioration, especially liver metastases. Moreover, we further confirmed that the combination of miR-425 and miR-576 was an effective predictive model for liver metastases and poor clinical outcomes. Mechanically, downregulated PTEN (GSE81558, = 6) was verified to be a shared target of miR-425 and miR-576 acting as metastasis-related oncogenes, on account of the presence of binding sites (+2928-+2934 and +4371-+4378, respectively) and the collaborative suppression of P53/TGF-β signaling in CRLM, which was further confirmed in CRC cells (HCT116 and SW480) based on systematic molecular biology experiments. Importantly, the target was strongly associated with microsatellite instability, tumor microenvironment, and immune cell infiltration. Thus, we speculate that miR-425 and miR-576 are novel biomarkers for CRLM prevention and immunotherapy and upstream inhibitors of the PTEN-P53/TGF-β function axis.
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http://dx.doi.org/10.3389/fonc.2021.657984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418231PMC
August 2021

Case Report: Identification of Two Rare Fusions, and , That Coexist in a Lung Adenocarcinoma Patient and the Response to Alectinib.

Front Oncol 2021 13;11:722843. Epub 2021 Aug 13.

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China.

Several double fusions coexisting in one patient have been reported. However, few studies have reported the clinical efficacy of ALK inhibitors in rare double fusions. Here, we described a rare , double-fusion variant in a patient with metastatic lung adenocarcinoma. The patient responded well to alectinib (600 mg) twice daily. This case shows a promising treatment option for patients with rare double-fusion variants.
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http://dx.doi.org/10.3389/fonc.2021.722843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415000PMC
August 2021

The landscape of immune checkpoint inhibitor therapy in advanced lung cancer.

BMC Cancer 2021 Aug 28;21(1):968. Epub 2021 Aug 28.

Department of Respiratory and Critical Care Medicine, West China Medical School/West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.

Background: The advent of immune checkpoint inhibitors (ICIs) therapy has resulted in significant survival benefits in patients with non-small-cell lung cancer (NSCLC) without increasing toxicity. However, the utilisation of immunotherapy for small-cell lung cancer (SCLC) remains unclear, with a scarcity of systematic comparisons of therapeutic effects and safety of immunotherapy in these two major lung cancer subtypes. Herein, we aimed to provide a comprehensive landscape of immunotherapy and systematically review its specific efficacy and safety in advanced lung cancer, accounting for histological types.

Methods: We identified studies assessing immunotherapy for lung cancer with predefined endpoints, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAE), from PubMed, Embase, Medline, and Cochrane library. A random-effects or fixed-effect model was adopted according to different settings.

Results: Overall, 38 trials with 20,173 patients with lung cancer were included in this study. ICI therapy resulted in a significantly prolonged survival in both patients with NSCLC and SCLC when compared with chemotherapy (hazard ratio [HR] = 0.74; 95% confidence interval [CI], 0.70-0.79] and [HR = 0.82; 95% CI, 0.75-0.90], respectively). The magnitude of disease control and survival benefits appeared superior with ICI plus standard of care (SOC) when compared with SOC alone. OS and PFS advantages were observed only when immunotherapy was employed as the first-line treatment in patients with SCLC.

Conclusion: ICI therapy is a promising therapeutic option in patients with NSCLC and SCLC. ICI plus SOC can be recommended as the optimal first-line treatment for patients with SCLC, and double-target ICIs combined with SOC are recommended in patients with NSCLC as both the first and subsequent lines of treatment. Additionally, non-first-line immunotherapy is not recommended in patients with SCLC.
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http://dx.doi.org/10.1186/s12885-021-08662-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403352PMC
August 2021

Real-world efficacy of osimertinib in previously EGFR-TKI treated NSCLC patients without identification of T790M mutation.

J Cancer Res Clin Oncol 2021 Aug 26. Epub 2021 Aug 26.

Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ, USA.

Background: The efficacy of osimertinib in previously EGFR-TKI-treated NSCLC without identification of T790M mutational status remains unclear in real-world practice.

Patients And Methods: 417 patients had stage III-IV NSCLC harboring EGFR mutation and 154 out of 417 patients receiving osimertinib as ≥ second-line EGFR-TKI were identified. The time to treatment failure and risk of death were analyzed.

Results: Higher risk of death was found in EGFR-mutant patients with age ≥ 65 years, non-adenocarcinoma, no surgery or radiation, non-exon 19 deletion/exon 21 L858R, higher ECOG PS (2-4), PD-L1 expression ≥ 50%, and bone/liver/adrenal metastasis (all p < 0.05). Osimertinib as ≥ second-line TKI in patients with/without identification of T790M revealed lower risk of death compared to first-line first/second generation TKI without subsequent osimertinib (p = 0.0002; 0.0232, respectively). However, osimertinib-treated patients with T790M did not have superior survival than those without (p = 0.2803). A higher risk of treatment failure for osimertinib was found in males, patients with first-line TKI duration ≤ 12 months, BMI drop > 10%, and PD-L1 expression ≥ 50% (All p < 0.05). Nonetheless, osimertinib as ≥ second-line TKI in patients without identification of 790 M did not have higher risk of treatment failure than those with T790M (p = 0.1236).

Conclusions: This study demonstrates that osimertinib as second line or subsequent TKI in EGFR-TKI-treated patients without identification of T790M revealed lower risk of death compared to first-line first/second generation TKI without subsequent osimertinib, in real-world practice. Additionally, EGFR-mutant patients with PD-L1 expression ≥ 50% had a higher risk of treatment failure for osimertinib and worse overall survival than those with PD-L1 expression < 50%. These results suggest that osimertinib as second line or subsequent TKI may be a potential alternative option for the treatment of patients without identification of T790M and PD-L1 expression ≥ 50% is associated with a significantly poor outcome in patients receiving osimertinib.
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http://dx.doi.org/10.1007/s00432-021-03766-5DOI Listing
August 2021

Lung adenocarcinoma with ERBB2 exon 20 insertions: Comutations and immunogenomic features related to chemoimmunotherapy.

Lung Cancer 2021 Aug 3;160:50-58. Epub 2021 Aug 3.

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China. Electronic address:

Background: The genomic mutation and immune feature landscape of ERBB2 exon 20 insertion (ERBB2-ex20ins)-driven non-small cell lung cancer and the features associated with the response to chemoimmunotherapy are currently unknown.

Methods: The genomic landscape of ERBB2-ex20ins lung adenocarcinoma (LUAD) patients was characterized by next-generation sequencing (NGS) of 1021 cancer genes. The clinical outcomes of chemoimmunotherapy were evaluated among 13 patients with stage IV ERBB2-ex20ins LUAD, and potential biomarkers of the response to chemoimmunotherapy were explored using NGS and T cell receptor sequencing.

Results: Among 8247 LUAD patients, 207 (2.5%) had ERBB2-ex20ins, of whom 181 (87.4%) harbored more than one comutation. The most common comutations were in TP53. Patients with ERBB2-ex20ins had a low tumor mutational burden (TMB; median, 4.2 mutations/Mb), and most (66.7%) were PD-L1 negative. Thirteen of the 207 patients received chemoimmunotherapy, for whom the objective response rate, disease control rate, and median progression-free survival were 31%, 77%, and 8.0 months, respectively. Responders exhibited a higher TMB and a trend toward lower clonality in tumors compared with nonresponders (p = 0.0067 and p = 0.085, respectively). A high TMB combined with mutations in DNA damage repair pathways and SWI/SNF chromatin remodeling complexes was associated with a benefit from chemoimmunotherapy.

Conclusions: The efficacy and outcome of chemoimmunotherapy were encouraging among ERBB2-ex20ins LUAD patients, who were characterized by low TMB and negative PD-L1 expression. The combination of TMB and comutations is a potential biomarker to identify patients who will benefit from chemoimmunotherapy.
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http://dx.doi.org/10.1016/j.lungcan.2021.07.014DOI Listing
August 2021

NF-κB-activated SPRY4-IT1 promotes cancer cell metastasis by downregulating TCEB1 mRNA via Staufen1-mediated mRNA decay.

Oncogene 2021 Jul 23;40(30):4919-4929. Epub 2021 Jun 23.

Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China.

Previous study demonstrated that most long non-coding RNAs (lncRNAs) function as competing endogenous RNAs or molecular sponges to negatively modulate miRNA and regulate tumor development. However, the molecular mechanisms of lncRNAs in cancer are not fully understood. Our study describes the role of the lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) in cancer metastasis by mechanisms related to Staufen1 (STAU1)-mediated mRNA decay (SMD). Briefly, we found that, high SPRY4-IT1 expression was associated with aggressiveness and poor outcome in human colorectal, breast and ovarian cancer tissues. In addition, functional assays revealed that SPRY4-IT1 significantly promoted colorectal, breast and ovarian cancer metastasis in vitro and in vivo. Mechanistically, microarray analyses identified several differentially-expressed genes upon SPRY4-IT1 overexpression in HCT 116 colorectal cancer cells. Among them, the 3'-UTR of transcription elongation factor B subunit 1 (TCEB1) mRNA can base-pair with the Alu element in the 3'-UTR of SPRY4-IT1. Moreover, SPRY4-IT1 was found to bind STAU1, promote STAU1 recruitment to the 3'-UTR of TCEB1 mRNA, and affect TCEB1 mRNA stability and expression, resulting in hypoxia-inducible factor 1α (HIF-1α) upregulation, and thereby affecting cancer cell metastasis. In addition, STAU1 depletion abrogated TCEB1 SMD and alleviated the pro-metastatic effect of SPRY4-IT1 overexpression. Significantly, we revealed that SPRY4-IT1 is also transactivated by NF-κB/p65, which activates SPRY4-IT1 to inhibit TCEB1 expression, and subsequently upregulate HIF-1α. In conclusion, our results highlight a novel mechanism of cytoplasmic lncRNA SPRY4-IT1 in which SPRY4-IT1 affecting TCEB1 mRNA stability via STAU1-mediated degradation during cancer metastasis.
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http://dx.doi.org/10.1038/s41388-021-01900-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321898PMC
July 2021

Circulating exosomal miR-363-5p inhibits lymph node metastasis by downregulating PDGFB and serves as a potential noninvasive biomarker for breast cancer.

Mol Oncol 2021 Sep 25;15(9):2466-2479. Epub 2021 Jun 25.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Sentinel lymph node (LN) biopsy is currently the standard procedure for clinical LN-negative breast cancer (BC) patients but it is prone to false-negative results and complications. Thus, an accurate noninvasive approach for LN staging is urgently needed in clinical practice. Here, circulating exosomal microRNA (miRNA) expression profiles in peripheral blood from BC patients and age-matched healthy women were obtained and analyzed. We identified an exosomal miRNA, miR-363-5p, that was significantly downregulated in exosomes from plasma of BC patients with LN metastasis which exhibited a consistent decreasing trend in tissue samples from multiple independent datasets. Plasma exosomal miR-363-5p achieved high diagnostic performance in distinguishing LN-positive patients from LN-negative patients. The high miR-363-5p expression level was significantly correlated with improved overall survival. Functional assays demonstrated that exosomal miR-363-5p modulates platelet-derived growth factor (PDGF) signaling activity by targeting PDGFB to inhibit cell proliferation and migration. Our study revealed, for the first time, plasma exosomal miR-363-5p plays a tumor suppressor role in BC and has the potential for noninvasive LN staging and prognosis prediction of BC.
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http://dx.doi.org/10.1002/1878-0261.13029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410538PMC
September 2021

Efficacy of Combination Chemo-Immunotherapy as a First-Line Treatment for Advanced Non-Small-Cell Lung Cancer Patients With HER2 Alterations: A Case Series.

Front Oncol 2021 20;11:633522. Epub 2021 Apr 20.

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China.

Objective: Although the treatment of non-small-cell lung cancer (NSCLC) patients with human epidermal growth factor receptor 2 (HER2) alterations has been studied for years, the overall response rate (ORR) of these patients is still unsatisfactory, and more therapeutic strategies are needed. Little is known about the combination of chemo- and immunotherapy in HER2-altered lung cancer treatment.

Materials And Methods: We report five cases of advanced NSCLC with HER2 insertion mutation or amplification treated with immunotherapy combined with chemotherapy as the first-line treatment. The HER2 alteration type, duration of treatment and survival were also analyzed.

Results: The five advanced NSCLC patients, three with HER2 mutations and two with HER2 amplifications, received chemo-immunotherapy as the first-line treatment. The average patient age was 54.6 years. Three patients were females, and two were males. Among all the patients, only one had a smoking history. The immunotherapies used were as follows: two patients were treated with sintilimab, and three patients were treated with pembrolizumab. Only one patient had squamous carcinoma, and she was also the only patient with a complete response (CR). The progression-free survival (PFS) ranged from 2-12 months, with a median PFS of 8.0 months.

Conclusions: Chemo-immunotherapy may be a promising first-line treatment option for NSCLC patients with HER2 alterations. Further clinical trials are required to confirm this therapeutic option.
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http://dx.doi.org/10.3389/fonc.2021.633522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093620PMC
April 2021

Detection of SARS-CoV-2 and Its Mutated Variants via CRISPR-Cas13-Based Transcription Amplification.

Anal Chem 2021 02 29;93(7):3393-3402. Epub 2021 Jan 29.

Department of Respiratory and Critical Care Medicine, West China Medical School/West China Hospital, Sichuan University, Chengdu 610041, China.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global health emergency, and its gene mutation and evolution further posed uncertainty of epidemic risk. Herein, we reported a light-up CRISPR-Cas13 transcription amplification method, which enables the detection of SARS-CoV-2 and its mutated variants. Sequence specificity was ensured by both the ligation process and Cas13a/crRNA recognition, allowing us to identify viral RNA mutation. Light-up RNA aptamer allows sensitive output of amplification signals via target-activated ribonuclease activity of CRISPR-Cas13a. The RNA virus assay has been designed to detect coronavirus, SARS-CoV-2, Middle East respiratory syndrome (MERS), and SARS, as well as the influenza viruses such as, H1N1, H7N9, and H9N2. It was accommodated to sense as low as 82 copies of SARS-CoV-2. Particularly, it allowed us to strictly discriminate key mutation of the SARS-CoV-2 variant, D614G, which may induce higher epidemic and pathogenetic risk. The proposed RNA virus assays are promising for point-of-care monitoring of SARS-CoV-2 and its risking variants.
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http://dx.doi.org/10.1021/acs.analchem.0c04303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860141PMC
February 2021

Drive circuitry of an electric vehicle enabling rapid heating of the battery pack at low temperatures.

iScience 2021 Jan 10;24(1):101921. Epub 2020 Dec 10.

State Key Laboratory of Automotive Safety and Energy, Tsinghua University, Beijing 100084, China.

Heating battery at low temperatures is fundamental to avoiding the range anxiety and the time-consuming charging associated with electric vehicles (EVs). One method for achieving fast and uniform battery heating is to polarize the cell under pulse currents. However, the on-board implementation of this method leads to an increase in the cost and size. Therefore, in this study, an adapted EV circuitry compatible with the existing one and an optimized operating condition are proposed to enable rapid battery heating. With this circuit, electricity transfer between the cells can be realized through a motor, leading to remarkably higher battery currents than those of the conventional circuit. The increase in the maximum heating currents (from 1.41C to 4C) resulted in a battery temperature rise of 8.6°C/min at low temperatures. This heating method exhibits low cost, high efficiency, and negligible effects on battery degradation, practical and promising on battery heating of EVs.
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http://dx.doi.org/10.1016/j.isci.2020.101921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773877PMC
January 2021

miR-146a Enhances the Sensitivity of Breast Cancer Cells to Paclitaxel by Downregulating IRAK1.

Cancer Biother Radiopharm 2020 Dec 1. Epub 2020 Dec 1.

Department of Breast Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.

To investigate the effect of miR-146a on the sensitivity of breast cancer cells to paclitaxel (PTX). The mRNA expressions of miR-146a in normal breast cancer cells, MCF-7, and PTX-resistant breast cancer cells, MCF-7/PTX, were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). MTS was used to analyze the cytotoxicity treated with different concentrations of PTX. Overexpressed and silenced cell lines of miR-146a and interleukin-1 receptor-associated kinase 1 (IRAK1) were constructed, respectively. Cells were treated with PTX and observed the changes of cell morphology. Proliferation was detected by clone formation assay. Invasion and migration were measured by transwell. RT-PCR was applied to detect the expression of IRAK1 gene. Dual luciferase report was performed to validate the target relationship between miR-146a and IRAK1. Salvage experiments were used to further verify the relationship between miR-146a and IRAK1. PTX reduces the viability of MCF-7 and MCF-7/PTX cells in a dose-dependent manner. The IC of PTX in MCF-7 cells was significantly lower compared with MCF-7/PTX cells ( < 0.05). Compared with MCF-7/PTX cells, the expression of miR-146a gene in MCF-7 cells was significantly increased, while the expression of IRAK1 gene was significantly reduced ( < 0.05). Cell proliferation, invasion, and migration were decreased after miR-146a overexpression or IRAK1 silencing. Whereas, miR-146a silencing and IRAK1 overexpression can increase cell proliferation, invasion, and migration ability. Salvage experiments further verify that IRAK1 can weaken the role of miR-146a. miR-146a can enhance the sensitivity of breast cancer cells to PTX; the mechanism may be related to the downregulation of IRAK1.
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http://dx.doi.org/10.1089/cbr.2020.3873DOI Listing
December 2020

Low T790M relative allele frequency indicates concurrent resistance mechanisms and poor responsiveness to osimertinib.

Transl Lung Cancer Res 2020 Oct;9(5):1952-1962

Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China.

Background: T790M relative allele frequency (RAF) in plasma, calculated by the ratio of T790M to epidermal growth factor receptor (EGFR)-sensitizing mutation allele frequencies (AF), is associated with osimertinib response in patients with progressive non-small cell lung cancer (NSCLC) post 1 generation EGFR-tyrosine kinase inhibitor (TKI) treatment. However, which subgroup of patients carry concurrent resistance mechanisms and have poor responsiveness to osimertinib remains unknown.

Methods: Matched re-biopsy tissue and plasma samples obtained from 32 patients who had progression following 1 generation EGFR-TKI treatment were genotyped using next-generation sequencing (NGS) to investigate which subgroup of patients, classified by plasma position 790 (T790M) RAF, were more likely to carry concurrent resistance mechanisms. In another independent cohort, consisting of 21 T790M-positive patients, we validated whether these patients had a poor response to osimertinib treatment.

Results: In the discovery cohort, patients with T790M RAF less than 20% were more likely to harbor concurrent resistance mechanisms (P=0.018), such as MET or ERBB2 amplification, and small cell lung cancer transformation. In the validation cohort, we found that patients with low T790M RAF (<20%) had significantly lower objective response rates (ORRs) (0 68.8%, P=0.03) and disease control rates (DCRs) (60% 100%, P=0.048) in response to osimertinib compared to patients with high T790M RAF.

Conclusions: In patients with progressive NSCLC post 1 generation EGFR-TKI treatment, plasma T790M RAFs of less than 20% can be used to identify patients who carry concurrent resistance mechanisms, and can predict a poorer response to osimertinib.

Trial Registration: This study was registered on http://www.chictr.org.cn (registration number: ChiCTR-DDD-16007900).
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http://dx.doi.org/10.21037/tlcr-20-915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653156PMC
October 2020

Long non-coding RNA ZFAS1 promotes colorectal cancer tumorigenesis and development through DDX21-POLR1B regulatory axis.

Aging (Albany NY) 2020 11 16;12(22):22656-22687. Epub 2020 Nov 16.

Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, P. R. China.

Increasing evidence supports long non-coding RNA-ZFAS1 as master protein regulators involved in a variety of human cancers. However, the molecular mechanism is not fully understood in colorectal cancer (CRC) and remains to be elucidated. Here, we uncovered a previously unreported mechanism linking RNA helicase DDX21 regulated by lncRNA ZFAS1 in control of POLR1B expression in CRC initiation and progression. Specifically, ZFAS1 exerted its oncogenic functions and was significantly up-regulated accompanied by elevated DDX21, POLR1B expression in CRC cells and tissues, which further closely associated with poor clinical outcomes. Notably, ZFAS1 knockdown dramatically suppressed CRC cell proliferation, invasion, migration, and increased cell apoptosis, which were contrary to the effect caused by ZFAS1 up-regulation. We further revealed that the inhibitory effect caused by ZFAS1 knockdown could be reversed by DDX21 overexpression and . Mechanistically, our research found that ZFAS1 could directly recruit DDX21 protein by harboring the specific motif (AAGA or CAGA). Finally, POLR1B was identified as the downstream target of DDX21 regulated by ZFAS1, which was also up-regulated in CRC cells and tissues and closely related to poor prognosis. The unrecognized ZFAS1/DDX21/POLR1B signaling regulation axis may provide new biomarkers and targets for CRC treatment and prognostic evaluation.
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http://dx.doi.org/10.18632/aging.103875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746388PMC
November 2020

Thermal runaway of Lithium-ion batteries employing LiN(SOF)-based concentrated electrolytes.

Nat Commun 2020 Oct 9;11(1):5100. Epub 2020 Oct 9.

State Key Laboratory of Automotive Safety and Energy, Tsinghua University, 100084, Beijing, China.

Concentrated electrolytes usually demonstrate good electrochemical performance and thermal stability, and are also supposed to be promising when it comes to improving the safety of lithium-ion batteries due to their low flammability. Here, we show that LiN(SOF)-based concentrated electrolytes are incapable of solving the safety issues of lithium-ion batteries. To illustrate, a mechanism based on battery material and characterizations reveals that the tremendous heat in lithium-ion batteries is released due to the reaction between the lithiated graphite and LiN(SOF) triggered thermal runaway of batteries, even if the concentrated electrolyte is non-flammable or low-flammable. Generally, the flammability of an electrolyte represents its behaviors when oxidized by oxygen, while it is the electrolyte reduction that triggers the chain of exothermic reactions in a battery. Thus, this study lights the way to a deeper understanding of the thermal runaway mechanism in batteries as well as the design philosophy of electrolytes for safer lithium-ion batteries.
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http://dx.doi.org/10.1038/s41467-020-18868-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547674PMC
October 2020

Tim-3 promotes tube formation and decreases tight junction formation in vascular endothelial cells.

Biosci Rep 2020 10;40(10)

Cardiff China Medical Research Collaborative, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, U.K.

As a negative immune checkpoint molecule, T-cell immunoglobulin domain and mucin domain containing molecule-3 (Tim-3) has been found to serve a crucial role in immune escape and tumour progression. Previous studies have reported that Tim-3 is important to endothelial cells and it has also been demonstrated to be involved in numerous types of human diseases, including melanoma, lymphoma, rickettsial infection and atherosclerosis; however, its exact mechanism of action remains largely unknown. In the present study, Tim-3 was overexpressed in vascular endothelial human lung microvascular endothelial cells (HMVECs) and human umbilical vein endothelial cells (HUVECs), and in vitro assays were used to determine that Tim-3 promoted cell proliferation, migration, invasion and tube formation through activating cyclin D1 (CCND1), Ras homolog gene family member A and vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2). Additionally, Tim-3 decreased tight junction (TJ) formation and the transepithelial resistance (TER) of endothelial cells by decreasing the expression levels of TJ protein 2, Occludin and claudin 1 (CLND1). In conclusion, these findings suggested that Tim-3 may exert a positive role in angiogenesis and a negative role in TJ formation in vascular endothelial cells, which may provide novel strategies for the treatment of Tim-3-associated diseases.
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http://dx.doi.org/10.1042/BSR20202130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560514PMC
October 2020

Progress and Future Trends in PET/CT and PET/MRI Molecular Imaging Approaches for Breast Cancer.

Front Oncol 2020 12;10:1301. Epub 2020 Aug 12.

PET-CT Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Breast cancer is a major disease with high morbidity and mortality in women worldwide. Increased use of imaging biomarkers has been shown to add more information with clinical utility in the detection and evaluation of breast cancer. To date, numerous studies related to PET-based imaging in breast cancer have been published. Here, we review available studies on the clinical utility of different PET-based molecular imaging methods in breast cancer diagnosis, staging, distant-metastasis detection, therapeutic and prognostic prediction, and evaluation of therapeutic responses. For primary breast cancer, PET/MRI performed similarly to MRI but better than PET/CT. PET/CT and PET/MRI both have higher sensitivity than MRI in the detection of axillary and extra-axillary nodal metastases. For distant metastases, PET/CT has better performance in the detection of lung metastasis, while PET/MRI performs better in the liver and bone. Additionally, PET/CT is superior in terms of monitoring local recurrence. The progress in novel radiotracers and PET radiomics presents opportunities to reclassify tumors by combining their fine anatomical features with molecular characteristics and develop a beneficial pathway from bench to bedside to predict the treatment response and prognosis of breast cancer. However, further investigation is still needed before application of these modalities in clinical practice. In conclusion, PET-based imaging is not suitable for early-stage breast cancer, but it adds value in identifying regional nodal disease and distant metastases as an adjuvant to standard diagnostic imaging. Recent advances in imaging techniques would further widen the comprehensive and convergent applications of PET approaches in the clinical management of breast cancer.
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http://dx.doi.org/10.3389/fonc.2020.01301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435066PMC
August 2020

Decreased level of peripheral CD8CD28 T cells is associated with lymph node metastasis in patients with breast cancer.

Future Oncol 2020 Nov 21;16(32):2611-2617. Epub 2020 Aug 21.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, PR China.

Lymph node metastasis (LNM) is an independent risk factor for prognosis in patients with early breast cancer (EBC). Here we explored whether peripheral lymphocyte subtypes could be used as surrogate markers for LNM in patients with EBC. The lymphocyte subpopulations in peripheral blood were measured in 152 EBC patients and 43 patients with benign breast tumors. The cytotoxic T cell count was significantly lower in patients with EBC than in patients with benign tumors (244.17 ± 105.83 vs 289.97 ± 121.72; p = 0.02), especially in patients with LNM (218.36 ± 86.21; p = 0.04). A decreased level of peripheral CD8CD28 T lymphocytes is associated with LNM in patients with EBC and could be used as a potential therapeutic target for breast cancer.
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http://dx.doi.org/10.2217/fon-2020-0614DOI Listing
November 2020

LNC473 Regulating APAF1 IRES-Dependent Translation via Competitive Sponging miR574 and miR15b: Implications in Colorectal Cancer.

Mol Ther Nucleic Acids 2020 Sep 10;21:764-779. Epub 2020 Jul 10.

Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, P.R. China; Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang 110122, P.R. China. Electronic address:

A growing number of studies have focused on the involvement of non-coding RNAs (ncRNAs) in the internal ribosome entry site (IRES)-mediated translation in tumorigenesis; however, the underlying mechanisms in colorectal cancer (CRC) remain elusive. In this study, we show that LINC00473 (LNC473) exerted its functions as a tumor suppressor in promoting apoptotic protease-activating factor 1 (APAF1) IRES activity through competitively sponging miR574-5p and miR15b-5p in CRC initiation and pathogenesis. Specifically, LNC473 and its downstream target APAF1 were significantly downregulated accompanied by upregulated miR574-5p and miR15b-5p in CRC cells and tissues, which had a significant prognostic impact on clinical outcomes in our CRC cohort (n = 157). Furthermore, ectopic LNC473 significantly sponged endogenous miR574-5p or miR15b-5p and thereby inhibited cell proliferation and colony formation capacity, and it accelerated cell apoptosis through activating the APAF1-CASP9-CASP3 pathway. Notably, LNC473 overexpression resulted in dramatic promotion of APAF1 IRES activity and translation, whereas rescue experiments confirmed the recovery by the existence of LNC473 and miR574/15b-5p. Mechanistically, LNC473 overexpression promoted IRES binding domain exposure and removed the constraints controlling from miR574-5p and miR15b-5p, and subsequently enhanced IRES-mediated APAF1 expression in vitro and in vivo. Therefore, our results uncover a novel LNC473-miR574/miR15b-APAF1 signaling axis, which provides new targets and crosstalk regulation mechanism for CRC prevention and treatment.
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http://dx.doi.org/10.1016/j.omtn.2020.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419277PMC
September 2020

Identification of DGUOK-AS1 as a Prognostic Factor in Breast Cancer by Bioinformatics Analysis.

Front Oncol 2020 17;10:1092. Epub 2020 Jul 17.

Department of Breast Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Significant developments have been made in breast cancer diagnosis and treatment, yet the prognosis remains unsatisfactory. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play pivotal roles in the development and progression of human tumors. However, the regulatory mechanisms and clinical significance of most lncRNAs in breast cancer remain poorly understood. The lncRNA, miRNA, and mRNA expression profiles were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. A lncRNA-miRNA-mRNA regulatory network was constructed and visualized using Cytoscape. The protein-protein interaction (PPI) network was constructed using the STRING database and hub genes were extracted using the cytoHubba plugin. Gene Ontology and Kyoto Encyclopedia of Gene and Genomes analyses identified the functions and signaling pathways associated with these differentially expressed mRNAs (DEmRNAs). Expression of the key lncRNA and the relationship with prognosis of patients with breast cancer were evaluated. Six differentially expressed lncRNAs (DElncRNAs), 29 differentially expressed miRNAs (DEmiRNAs), and 253 DEmRNAs were selected to construct the regulatory network. A PPI network was established and seven hub genes were identified. A lncRNA-miRNA-hub gene regulatory sub-network was established containing two DElncRNAs, five DEmiRNAs, and seven DEmRNAs. Hub genes were associated with breast cancer onset and progression. The upregulated DGUOK-AS1 was identified as the key lncRNA in breast cancer based on the competing endogenous RNA network. High DGUOK-AS1 expression was associated with adverse prognosis in patients with breast cancer and a prognostic nomogram built on Grade, LN status, and DGUOK-AS1 expression shows significant prognostic value. Our results reveal the significant roles of lncRNA/miRNA/mRNA regulatory networks in breast cancer and identified a novel prognosis predictor and promising therapeutic target for patients with breast cancer.
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http://dx.doi.org/10.3389/fonc.2020.01092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379746PMC
July 2020

Melatonin Plays a Critical Protective Role in Nicotine-Related Abdominal Aortic Aneurysm.

Front Physiol 2020 17;11:866. Epub 2020 Jul 17.

Department of Vascular Surgery, The First Hospital of China Medical University, Key Laboratory of Pathogenesis, Prevention and Therapeutics of Aortic Aneurysm, Shenyang, China.

: Smoking is a major risk factor for abdominal aortic aneurysm (AAA). Among the components of smoke, nicotine is known to exert pro-atherosclerotic, prothrombotic, and proangiogenic effects on vascular smooth muscle cells (VSMCs). The current study was designed to investigate the mechanisms through which nicotine induces vascular wall dysfunction and to examine whether melatonin protects against nicotine-related AAA. : In this study, an enzyme-linked immunosorbent assay (ELISA) was used to measure melatonin and TNF-α levels, as well as total antioxidant status (TAS), in patients with AAA. We established a nicotine-related AAA model and explored the mechanisms underlying the therapeutic effects of melatonin. Tissue histopathology was used to assess vascular function, while western blotting (WB) and immunofluorescence staining were performed to detect protein expression. : We observed melatonin insufficiency in the serum from patients with AAA, particularly smokers. Moreover, melatonin level was positively correlated with antioxidant capacity. In the model, nicotine accelerated AAA expansion and destroyed vascular structure. Furthermore, OPN, LC3II, p62, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), NF-κB p65, TNF-α, phosphorylated AKT, and phosphorylated mTOR levels were increased, , following nicotine treatment, while SM22α and α-SMA levels were reduced. Additionally, melatonin attenuated the effects of nicotine on AAA and reversed changes in protein expression. Moreover, melatonin lost its protective effects following bafilomycin A1-mediated inhibition of autophagy. : Based on our data, melatonin exerts a beneficial effect on rats with nicotine-related AAA by downregulating the AKT-mTOR signaling pathway, improving autophagy dysfunction, and restoring the VSMC phenotype.
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http://dx.doi.org/10.3389/fphys.2020.00866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379742PMC
July 2020

LNC942 promoting METTL14-mediated mA methylation in breast cancer cell proliferation and progression.

Oncogene 2020 07 23;39(31):5358-5372. Epub 2020 Jun 23.

Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, PR China.

Increasing evidence supports that long noncoding RNAs (lncRNAs) act as master regulators involved in tumorigenesis and development at the N6-methyladenine (mA) epigenetic modification level. However, the underlying regulatory mechanism in breast cancer (BRCA) remains elusive. Here, we unveil that LINC00942 (LNC942) exerts its functions as an oncogene in promoting METTL14-mediated mA methylation and regulating the expression and stability of its target genes CXCR4 and CYP1B1 in BRCA initiation and progression. Specifically, LNC942 and METTL14 were significantly upregulated accompanied with the upregulation of mA levels in BRCA cells and our included BRCA cohorts (n = 150). Functionally, LNC942 elicits potent oncogenic effects on promoting cell proliferation and colony formation and inhibiting cell apoptosis, subsequently elevating METTL14-mediated mA methylation levels and its associated mRNA stability and protein expression of CXCR4 and CYP1B1 in BRCA cells. Mechanistically, LNC942 directly recruits METTL14 protein by harboring the specific recognize sequence (+176-+265), thereby stabilized the expression of downstream targets of LNC942 including CXCR4 and CYP1B1 through posttranscriptional mA methylation modification in vitro and in vivo. Therefore, our results uncover a novel LNC942-METTL14-CXCR4/CYP1B1 signaling axis, which provides new targets and crosstalk mA epigenetic modification mechanism for BRCA prevention and treatment.
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http://dx.doi.org/10.1038/s41388-020-1338-9DOI Listing
July 2020

Acquired BRAF N581S mutation mediated resistance to gefitinib and responded to dabrafenib plus trametinib.

Lung Cancer 2020 08 9;146:355-357. Epub 2020 Jun 9.

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

Objectives: BRAFG469A and V600E were reported as the mechanisms of acquired resistance to first-generation EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer patients. Here, we described a rare case of BRAF N581S after gefitinib resistance and response to BRAF inhibitor plus MEK inhibitor.

Materials And Methods: Next-generation sequencing (NGS) was performed on the tumor tissue and plasma samples of a patient with metastatic lung adenocarcinoma harboring EGFR exon 19 deletion (EGFR 19del).

Results: EGFR 19del and MET amplification was detected after resistance to the initial gefitinib therapy. After 9 months of treatment with gefitinib plus crizotinib, the disease progressed again. NGS revealed the known EGFR 19del and a BRAF N581S missense mutation after progression. The patient obtained durable clinical benefit upon treatment with dabrafenib plus trametinib, achieving a progression-free survival (PFS) of more than 33 months.

Conclusion: BRAF N581S mutation could be explored as one kind of mechanism of acquired resistance to EGFR-TKIs. Combined inhibition of BRAF and MEK is a potential therapeutic strategy.
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http://dx.doi.org/10.1016/j.lungcan.2020.06.004DOI Listing
August 2020

Long noncoding RNA ZFAS1 promoting small nucleolar RNA-mediated 2'-O-methylation via NOP58 recruitment in colorectal cancer.

Mol Cancer 2020 05 22;19(1):95. Epub 2020 May 22.

Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, People's Republic of China.

Background: Increasing evidence supports the role of small nucleolar RNAs (snoRNAs) and long non-coding RNAs (lncRNAs) as master gene regulators at the epigenetic modification level. However, the underlying mechanism of these functional ncRNAs in colorectal cancer (CRC) has not been well investigated.

Methods: The dysregulated expression profiling of lncRNAs-snoRNAs-mRNAs and their correlations and co-expression enrichment were assessed by GeneChip microarray analysis. The candidate lncRNAs, snoRNAs, and target genes were detected by in situ hybridization (ISH), RT-PCR, qPCR and immunofluorescence (IF) assays. The biological functions of these factors were investigated using in vitro and in vivo studies that included CCK8, trans-well, cell apoptosis, IF assay, western blot method, and the xenograft mice models. rRNA 2'-O-methylation (Me) activities were determined by the RTL-P assay and a novel double-stranded primer based on the single-stranded toehold (DPBST) assay. The underlying molecular mechanisms were explored by bioinformatics and RNA stability, RNA fluorescence ISH, RNA pull-down and translation inhibition assays.

Results: To demonstrate the involvement of lncRNA and snoRNAs in 2'-O-Me modification during tumorigenesis, we uncovered a previously unreported mechanism linking the snoRNPs NOP58 regulated by ZFAS1 in control of SNORD12C, SNORD78 mediated rRNA 2'-O-Me activities in CRC initiation and development. Specifically, ZFAS1 exerts its oncogenic functions and significantly up-regulated accompanied by elevated NOP58, SNORD12C/78 expression in CRC cells and tissues. ZFAS1 knockdown suppressed CRC cell proliferation, migration, and increased cell apoptosis, and this inhibitory effect could be reversed by NOP58 overexpression in vitro and in vivo. Mechanistically, the NOP58 protein could be recognized by the specific motif (AAGA or CAGA) of ZFAS1. This event accelerates the assembly of SNORD12C/78 to allow for further guiding of 2'-O-Me at the corresponding Gm3878 and Gm4593 sites. Importantly, silencing SNORD12C or 78 reduced the rRNAs 2'-O-Me activities, which could be rescued by overexpression ZFAS1, and this subsequently inhibits the RNA stability and translation activity of their downstream targets (e.g., EIF4A3 and LAMC2).

Conclusion: The novel ZFAS1-NOP58-SNORD12C/78-EIF4A3/LAMC2 signaling axis that functions in CRC tumorigenesis provides a better understanding regarding the role of lncRNA-snoRNP-mediated rRNAs 2'-O-Me activities for the prevention and treatment of CRC.
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http://dx.doi.org/10.1186/s12943-020-01201-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243338PMC
May 2020

Efficient and Accurate Extracting of Unstructured EHRs on Cancer Therapy Responses for the Development of RECIST Natural Language Processing Tools: Part I, the Corpus.

JCO Clin Cancer Inform 2020 05;4:383-391

Department of Health Sciences Research, Mayo Clinic, Scottsdale, AZ.

Purpose: Electronic health records (EHRs) are created primarily for nonresearch purposes; thus, the amounts of data are enormous, and the data are crude, heterogeneous, incomplete, and largely unstructured, presenting challenges to effective analyses for timely, reliable results. Particularly, research dealing with clinical notes relevant to patient care and outcome is seldom conducted, due to the complexity of data extraction and accurate annotation in the past. RECIST is a set of widely accepted research criteria to evaluate tumor response in patients undergoing antineoplastic therapy. The aim for this study was to identify textual sources for RECIST information in EHRs and to develop a corpus of pharmacotherapy and response entities for development of natural language processing tools.

Methods: We focused on pharmacotherapies and patient responses, using 55,120 medical notes (n = 72 types) in Mayo Clinic's EHRs from 622 randomly selected patients who signed authorization for research. Using the Multidocument Annotation Environment tool, we applied and evaluated predefined keywords, and time interval and note-type filters for identifying RECIST information and established a gold standard data set for patient outcome research.

Results: Key words reduced clinical notes to 37,406, and using four note types within 12 months postdiagnosis further reduced the number of notes to 5,005 that were manually annotated, which covered 97.9% of all cases (n = 609 of 622). The resulting data set of 609 cases (n = 503 for training and n = 106 for validation purpose), contains 736 fully annotated, deidentified clinical notes, with pharmacotherapies and four response end points: complete response, partial response, stable disease, and progressive disease. This resource is readily expandable to specific drugs, regimens, and most solid tumors.

Conclusion: We have established a gold standard data set to accommodate development of biomedical informatics tools in accelerating research into antineoplastic therapeutic response.
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http://dx.doi.org/10.1200/CCI.19.00147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265793PMC
May 2020

Prognostic evaluation of colorectal cancer using three new comprehensive indexes related to infection, anemia and coagulation derived from peripheral blood.

J Cancer 2020 6;11(13):3834-3845. Epub 2020 Apr 6.

Department of Anorectal Surgery, First Affiliated Hospital of China Medical University , Shenyang, Liaoning, China.

: Many indicators of peripheral blood in routine blood test (BRT) results of colorectal cancer (CRC) patients are related to prognosis. Currently, indexes such as NLR (Neutrophil-to- Lymphocyte Ratio), PLR (Platelet-to-Lymphocyte Ratio) and LMR (Lymphocyte-to-Monocyte ratio) evaluate the survival risk of patients by assessing the inflammatory - immune status of CRCs. These indexes are more comprehensive and accurate than independent estimates. We hope to design more effective indexes through fully considering the correlation and significance between BRT indicators and prognosis, so as to play a guiding role in clinical malignant estimation of CRCs. : 701 CRCs in training set and 256 CRCs in test set were included in the study samples, and their clinical data, tumor pathology results and peripheral blood routine results were collected. The prognosis, progression, and survival status of all patients were determined after follow-up. Above data were used for statistical analysis and designing new indexes. : It was found that high NE, MONO, RDW-CV/SD and PLT in peripheral blood indicated poor prognosis of DFS and OS. Conversely, CRCs with postoperative tumor progression or death had lower LY, EO, RBC, HGB, HCT, MCV, MCH, MCHC, PDW, and P-LCR. IRR, ARR and CRR related to infection, anemia and coagulation were designed respectively using the largest AUC indicators (P<0.05) selected by ROC curve. The formula: IRR= (NE*MONO)/(LY*EO); ARR= (HGB*MCHC)/RDW-CV; CRR=PLT/PDW. Results of Kaplan‑Meier survival analysis and multivariate COX proportional hazard analysis adjusted for age, gender, TNM stage, infiltration, adhesion showed IRR, ARR, CRR were all able to be used as the evaluation standard of survival of CRC. The result was also authenticated in the test set. : We designed three different prognostic indexes of colorectal cancer, IRR, ARR and CRR, which could be used as risk indicators of CRC prognosis, tumor progression and survival.
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http://dx.doi.org/10.7150/jca.42409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171501PMC
April 2020

Mutational landscape and genetic signatures of cell-free DNA in tumour-induced osteomalacia.

J Cell Mol Med 2020 05 11;24(9):4931-4943. Epub 2020 Apr 11.

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

Tumour-induced osteomalacia (TIO) is a very rare paraneoplastic syndrome with bone pain, fractures and muscle weakness, which is mostly caused by phosphaturic mesenchymal tumours (PMTs). Cell-free DNA (cfDNA) has been regarded as a non-invasive liquid biopsy for many malignant tumours. However, it has not been studied in benign tumours, which prompted us to adopt the targeted next-generation sequencing approach to compare cfDNAs of 4 TIO patients, four patients with bone metastasis (BM) and 10 healthy controls. The mutational landscapes of cfDNA in TIO and BM groups were similar in the spectrum of allele frequencies and mutation types. Markedly, deleterious missense mutations in FGFR1 and loss-of-function mutations in MED12 were found in 3/4 TIO patients but none of BM patients. The gene ontology analysis strongly supported that these mutated genes found in TIOs would play a potential role in PMTs' process. The genetic signatures and corresponding change in expression of FGFR1 and FGF23 were further validated in PMT tissues from a test cohort of another three TIO patients. In summary, we reported the first study of the mutational landscape and genetic signatures of cfDNA in TIO/PMTs.
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http://dx.doi.org/10.1111/jcmm.14991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205804PMC
May 2020

Identification of functional circRNA/miRNA/mRNA regulatory network for exploring prospective therapy strategy of colorectal cancer.

J Cell Biochem 2020 Mar 1. Epub 2020 Mar 1.

Department of Pharmacology, School of Pharmacy, Liaoning Key Laboratory of Molecular Targeted Antitumor Drug Development and Evaluation, China Medical University, Shenyang, China.

Circular RNA (circRNA) has been reported to have great scientific significance and clinical value in multiple cancers including colorectal cancer (CRC). However, the biological function of most circRNAs in CRC is still in its infancy. Herein, we discovered the differential expressed circRNAs (DECs) between CRC tissues and matched adjacent using deep RNA sequencing and further confirmed the DECs expression by combining with another Gene Expression Omnibus dataset. Furthermore, we validated the expression of the top four upregulated circRNAs (hsa_circ_0030632, hsa_circ_0004887, hsa_circ_0001550, and hsa_circ_0001681) in both of paired CRC tissues and CRC cell lines. Then, a circRNA/microRNA/messenger RNA regulatory network was established and the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed these four circRNAs participated in various biological processed including apoptotic process and multiple metabolic processes. Moreover, based on the regulatory network, three bioactive compounds (pergolide, pivampicillin, and methylergometrine) for the treatment of CRC were also found. In conclusion, this study improved our understanding of circRNAs and may also facilitate the finding of promising targets and biomarkers in CRC.
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http://dx.doi.org/10.1002/jcb.29703DOI Listing
March 2020

Correction to "Thermal Runaway Triggered by Plated Lithium on the Anode after Fast Charging".

ACS Appl Mater Interfaces 2020 02 22;12(5):6793. Epub 2020 Jan 22.

State Key Laboratory of Automotive Safety and Energy , Tsinghua University , Beijing 100084 , China.

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http://dx.doi.org/10.1021/acsami.9b22722DOI Listing
February 2020
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