Publications by authors named "Yang Shao"

380 Publications

Risk assessment and its influencing factors of involuntary admission in patients with mental disorders in Shanghai, China.

Int J Soc Psychiatry 2021 Apr 16:207640211007154. Epub 2021 Apr 16.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai, P. R. China.

Background: The 'risk criterion' for involuntary admission (IA) has been adopted by Mental Health Law of the People's Republic of China since 2013. How the new legal regulation influences daily practices in psychiatric institutes are still unclear.

Aims: The present study sought to explore the application of risk criterion in IA cases; especially risk assessed by psychiatrists at admission and its influencing factors.

Method: Socio-demographic and clinical data including risk assessment for admission of 3,529 involuntary admitted patients from two typical hospitals in Shanghai from 2013 to 2014 were consecutively collected. Personal information of psychiatrists who made admission assessment was collected separately.

Results: Among the 3,529 cases, 1,890 (53.6%) were admitted because of actual harmful behaviors to self or others, while 1,639 (46.4%) were admitted with some kinds of risk, but 265 (7.5%) were admitted without any records on risk assessment checklists. Patients who were unemployed, of younger age, single status, diagnosed with schizophrenia were more likely to be admitted without any records on the checklist. Male gender, older age, and lower professional title are influencing factors that psychiatrists made no risk assessment records.

Conclusions: The vast majority (92.5%) of risk assessment in IA patients were qualified in our study. In order to protect the legal rights of patients better, operational and reasonable procedures of risk assessment should be developed, such include more detailed rules to IA, systematic training of psychiatrists on IA assessment, mechanism improving doctor-patient relationship, and alternative mental health services for patients and so on.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/00207640211007154DOI Listing
April 2021

Association of Mutation With Clinical Benefits of Anti-PD-1 Inhibitors in Non-small Cell Lung Cancer.

Front Oncol 2021 22;11:596542. Epub 2021 Mar 22.

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

Although anti-PD-1 inhibitors exhibit impressive clinical results in non-small cell lung cancer (NSCLC) cases, a substantial percentage of patients do not respond to this treatment. Moreover, the current recommended biomarkers are not perfect. Therefore, it is essential to discover novel molecular determinants of responses to anti-PD-1 inhibitors. We performed Whole Exome Sequencing (WES) in a cohort of 33 Chinese NSCLC patients. Patients were classified into the durable clinical benefit (DCB) and no durable benefit (NDB) groups. Infiltrating CD8 cells in the tumor microenvironment (TME) were investigated by immunohistochemistry. We also used public datasets to validate our results. In our cohort, good clinical responses to anti-PD-1 inhibitors were more pronounced in younger patients with lower Eastern Cooperative Oncology Group (ECOG) scores and only extra-pulmonary metastasis. More importantly, we identified a novel mutation, which was significantly enriched in DCB patients ( = 0.015), and mutated patients had a longer progression-free survival (PFS) (hazard ratio = 0.3, 95% CI 0.1-0.9; = 0.026). Immunohistochemistry results indicated that the mutation was associated with increased infiltration by CD8 T cells in the TME ( = 0.0313). When combining mutation with ECOG scores and intra-pulmonary metastasis status, patients with more positive predictors had longer PFS ( = 0.003). Furthermore, mutation was involved in immune responses and associated with a longer PFS in the Memorial Sloan-Kettering Cancer Center (MSKCC) cohort. Collectively, we identified that mutations were involved in immune responses, and NSCLC tumors harboring mutated exhibited good responses to anti-PD-1 inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.596542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019943PMC
March 2021

The genomic landscape of young and old lung cancer patients highlights age-dependent mutation frequencies and clinical actionability in young patients.

Int J Cancer 2021 Apr 2. Epub 2021 Apr 2.

The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

The aim of the study was to investigate age-dependent tendency of genomic alterations in lung cancer, and also to examine mutational profiles and its association with clinical treatment outcomes in young adenocarcinoma patients. By studying 7858 lung cancer samples using targeted-gene sequencing, we investigated genomic differences and clinical on-treatment time (OTT) to different therapies between young (≤ 45 years) and old (> 45 years) patients. The age-dependent trend test for genomic alterations in all patients revealed steady increases in tumor mutation burden and alterations in a number of genes with age, including KRAS, MET, CDKN2A, PIK3CA and MDM2, while the frequencies of ALK, ROS1 and RET fusions and ERBB2 mutations were decreasing. The highest rate of EGFR alterations was observed in the 45 ~ 50 years age group. Comparisons of young and old adenocarcinoma patients found that young patients were characterized by a higher prevalence of ALK, ROS1 and RET fusions, and ERBB2 exon-20 insertions and EGFR exon-19 deletions. Actionable mutations were highly prevalent in young adenocarcinoma patients, with 88% of patients harboring at least one actionable genetic alteration. First-line therapies in EGFR-positive patients (n = 979) by EGFR tyrosine kinase inhibitors or chemotherapy resulted in similar OTT between young and old patients. Somatic interaction analyses implied that young EGFR-positive patients were more likely to also have PIK3CA, MET, TP53 and RB1 mutations than old patients. Lung cancer in young patients, and especially those with adenocarcinoma, exhibited different clinical features and genomic attributes compared to old patients, which should be considered for therapeutic decision-making purposes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33583DOI Listing
April 2021

Salinity Effects on Morpho-Physiological and Yield Traits of Soybean ( L.) as Mediated by Foliar Spray with Brassinolide.

Plants (Basel) 2021 Mar 13;10(3). Epub 2021 Mar 13.

Department of Soil Science, Faculty of Agriculture, Forestry and Wildlife Resources Management, University of Calabar, Calabar P.M.B. 1115, Nigeria.

Salinity episodes that are common in arid regions, characterized by dryland, are adversely affecting crop production worldwide. This study evaluated the effectiveness of brassinolide (BL) in ameliorating salinity stress imposed on soybean at four levels (control (1.10), 32.40, 60.60 and 86.30 mM/L NaCl) in factorial combination with six BL application frequency (control (BL), application at seedling (BL), flowering (BL), podding (BL), seedling + flowering (BL) and seedling + flowering + podding (BL)) stages. Plant growth attributes, seed yield, and N, P, K, Ca and Mg partitioning to leaves, stems and roots, as well as protein and seed-N concentrations, were significantly ( ≤ 0.05) reduced by salinity stress. These trends were ascribed to considerable impairments in the photosynthetic pigments, photosynthetically active radiation, leaf stomatal conductance and relative water content in the leaves of seedlings under stress. The activity of peroxidase and superoxidase significantly ( ≤ 0.05) increased with salinity. Foliar spray with BL significantly ( ≤ 0.05) improved the photosynthetic attributes, as well as nutrient partitioning, under stress, and alleviated ion toxicity by maintaining a favourable K/Na ratio and decreasing oxidative damage. Foliar spray with brassinolide could sustain soybean growth and seed yield at salt concentrations up to 60.60 mM/L NaCl.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/plants10030541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000651PMC
March 2021

Identification of Novel Alectinib-Resistant Mutation G1202K with Sensitization to Lorlatinib: A Case Report and in silico Structural Modelling.

Onco Targets Ther 2021 25;14:2131-2138. Epub 2021 Mar 25.

Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, People's Republic of China.

Background: Drug resistance caused by G1202R/G1202del mutation in anaplastic lymphoma kinase () represents a great challenge in the clinic. The effect of other mutation(s) at G1202 on the available tyrosine kinase inhibitors (TKIs) in the clinic remains unknown.

Case Presentation: A 50-year-old Chinese male non-smoker with lung adenocarcinoma progressed with spinal metastasis after receiving chest radiation together with Pemetrexed and Cisplatin as adjuvant chemotherapy. Targeted next generation sequencing (NGS) identified gene fusion in the resected left lung tissue. Local radiation followed by Crizotinib were used in the following treatment and the spinal metastasis was found to shrink, but the progression free survival (PFS) only lasted for 2 months with the appearance of brain metastasis. Afterwards, the patient benefited from the therapy of Alectinib with a PFS of 8 months. Then he progressed with metastases in right lung and pleural, and did not show response to the chemotherapy with Docetaxel plus Bevacizumab. The targeted sequencing consistently identified gene fusion in both plasma and pleural effusion (PE), as well as a novel G1202K mutation (c.3604_3605delGGinsAA). Given the lack of established or known drug treatment for this novel mutation, we implemented molecular dynamics (MD) simulation-guided drug sensitivity prediction, which results suggested Lorlatinib remains potent against G1202K mutant ALK. Therefore, Lorlatinib was used as the fourth-line therapy, which lead to the considerable efficacy with improved performance status (PS) score and reduced lung metastases. The structural mechanism underlying G1202K-induced drug resistance to different ALK-TKIs was also discussed.

Conclusion: Our case suggested the -G1202K mutation may serve as a novel mechanism underlying the resistance to Alectinib, and provide direct evidence to support its sensitization to Lorlatinib. Our work represented an example of integrating in silico predictions into clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OTT.S293901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007639PMC
March 2021

OPCML Methylation and the Risk of Ovarian Cancer: A Meta and Bioinformatics Analysis.

Front Cell Dev Biol 2021 11;9:570898. Epub 2021 Mar 11.

Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China.

The association of opioid binding protein cell adhesion molecule-like (OPCML) gene methylation with ovarian cancer risk remains unclear. We identified eligible studies by searching the PubMed, Web of Science, ScienceDirect, and Wanfang databases. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to determine the association of OPCML methylation with ovarian cancer risk. Meta-regression and subgroup analysis were used to assess the sources of heterogeneity. Additionally, we analyzed the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets to validate our findings. Our study included 476 ovarian cancer patients and 385 controls from eight eligible studies. The pooled OR was 33.47 (95% CI = 12.43-90.16) in the cancer group vs. the control group under the random-effects model. The association was still significant in subgroups according to sample type, control type, methods, and sample sizes (all < 0.05). Sensitivity analysis showed that the finding was robust. No publication bias was observed in Begg's ( = 0.458) and Egger's tests ( = 0.261). We further found that OPCML methylation was related to III/IV (OR = 4.20, 95% CI = 1.59-11.14) and poorly differentiated grade (OR = 4.37; 95% CI = 1.14-16.78). Based on GSE146552 and GSE155760, we validated that three CpG sites (cg16639665, cg23236270, cg15964611) in OPCML promoter region were significantly higher in cancer tissues compared to normal tissues. However, we did not observe the associations of OPCML methylation with clinicopathological parameters and overall survival based on TCGA ovarian cancer data. Our findings support that OPCML methylation is associated with an increased risk of ovarian cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.570898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990783PMC
March 2021

Comparative efficacy and safety of topical hemostatic agents in primary total knee arthroplasty: A network meta-analysis of randomized controlled trials.

Medicine (Baltimore) 2021 Mar;100(12):e25087

Department of Traumatology & Orthopedics, Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine, Wuxi, China.

Background: Topical hemostatic agents are commonly used for reducing perioperative blood loss and transfusion requirement in primary total knee arthroplasty (TKA), although the optimal option has yet to be defined. This study aimed to evaluate the efficacy and safety of topical hemostatic agents and rank the best intervention using the network meta-analysis (NMA) method.

Methods: We searched Web of science, PubMed, and Cochrane Library database up to April 2020, for randomized controlled trials (RCTs) on topical hemostatic agents in primary TKA. The quality of included studies was assessed using the Cochrane "risk of bias" tool. Direct and indirect comparisons were performed for the result of network meta-analysis followed by consistency test.

Results: Thirty seven RCTs with 3792 patients were included in this NMA and the pooled results indicated that tranexamic acid plus diluted epinephrine (TXA+DEP) displayed the highest efficacy in reducing total blood loss, hemoglobin drop and transfusion requirement. None of the included treatments was found to increase risk of thromboembolic events compared to placebo. According to the results of ranking probabilities, TXA+DEP had the highest possibility to be the best topical hemostatic agent with regard to the greatest comparative efficacy and a relatively high safety level.

Conclusion: Current evidence supports that administration of TXA+DEP may be the optimal topical hemostatic agent to decrease blood loss and transfusion requirement in primary TKA. More direct studies that focused on the topical application of TXA+DEP versus other treatments are needed in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000025087DOI Listing
March 2021

Genomic Mutation Profile of Primary Gastrointestinal Diffuse Large B-Cell Lymphoma.

Front Oncol 2021 5;11:622648. Epub 2021 Mar 5.

State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, China.

Primary gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) is the most common gastrointestinal lymphoma, but its genetic features are poorly understood. We performed whole-exome sequencing of 25 primary tumor samples from patients with GI-DLBCL and 23 matched normal tissue samples. Oncogenic mutations were screened, and the correlations between genetic mutations and clinicopathological characteristics were analyzed. Twenty-five patients with GI-DLBCL were enrolled in the genetic mutation analysis with a median of 184 (range 79-382) protein-altering variants per patient. We identified recurrent oncogenic mutations in GI-DLBCL, including those in , and . Compared with nodal DLBCL, GI-DLBCL exhibited an increased mutation frequency of and reduced mutation frequencies of , and . Moreover, GI-DLBCL exhibited fewer and mutations than DLBCL in the testis and central nervous system. GI-DLBCLs with , and mutations exhibited a tendency toward a high proliferation index. and mutations often occurred in tumors with early clinical staging. Our data provide a comprehensive understanding of the landscape of mutations in a small subset of GI-DLBCLs. The genetic mutation profiles of GI-DLBCL differ from those of nodal DLBCL and DLBCL in immune-privileged sites. The different mutated genes are related to the NF-κB and JAK-STAT pathways, and the different pathogenetic mechanisms leading to the development of DLBCL may be influenced by the tissue microenvironment. Differences in genetic alterations might influence the clinicopathological characteristics of GI-DLBCL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.622648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973209PMC
March 2021

Genomic Profiling Identified Novel Prognostic Biomarkers in Chinese Midline Glioma Patients.

Front Oncol 2020 3;10:607429. Epub 2021 Mar 3.

Department of Pathology, Guangdong Provincial People's Hospital, Guangzhou, China.

Background: Molecular characteristics are essential for the classification and grading of gliomas. However, diagnostic classification of midline glioma is still debatable and substantial molecular and clinical heterogeneity within each subgroup suggested that they should be further stratified. Here, we studied the mutation landscape of Chinese midline glioma patients in hope to provide new insights for glioma prognosis and treatment.

Methods: Tissue samples from 112 midline glioma patients underwent next-generation sequencing targeting 425 cancer-relevant genes. Gene mutations and copy number variations were investigated for their somatic interactions and prognostic effect using overall survival data. Pathway-based survival analysis was performed for ten canonical oncogenic pathways.

Results: We identified several currently established diagnostic and prognostic biomarkers of glioma, including (33%), (26%), (24%), (21%), (14%) (14%), (13%), and (6%). Among all genetic aberrations with more than 5% occurrence rate, six mutations and three copy number gains were greatly associated with poor overall survival (univariate, P < 0.1). Of these, mutations (hazard ratio [HR], 3.00; 95% confidence interval [CI], 1.37-6.61; P = 0.01) and mutations (HR, 2.04; 95% CI, 1.08-3.84; P = 0.02) remained significant in multivariate analyses. Additionally, we have also identified a novel amplification (found in 31% patients) as a potential independent biomarker for glioma (multivariate HR, 2.78; 95% CI, 1.53-5.08; P < 0.001), which was seldom reported in public databases. Pathway analyses revealed significantly worse prognosis with abnormal PI3K (HR, 1.81; 95% CI, 1.12-2.95; P = 0.01) and cell cycle pathways (HR, 1.97; 95% CI, 1.15-3.37; P = 0.01), both of which stayed meaningful after multivariate adjustment.

Conclusions: In this study, we discovered shorter survival in midline glioma patients with PIK3CA and TERT mutations and with abnormal PI3K and cell cycle pathways. We also revealed a novel prognostic marker, amplification that collectively provided new insights and opportunities in understanding and treating midline gliomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.607429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968371PMC
March 2021

Copy number loss in granzyme genes confers resistance to immune checkpoint inhibitor in nasopharyngeal carcinoma.

J Immunother Cancer 2021 Mar;9(3)

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

Background: Anti-programmed death (PD)-1 therapy has recently been used in recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC). The long-term survival and its biomarkers responding to anti-PD-1 treatment in patients with R/M NPC remain unclear.

Methods: Patients with R/M NPC were enrolled between March 2016 and January 2018 from two phase I clinical trials. The median follow-up period was 24.7 months. Eligible patients progressed on standard chemotherapy had measurable disease by Response Evaluation Criteria in Solid Tumor V.1.1. Non-obligatory contemporaneous tumor samples were collected for whole-exome sequencing. The primary outcome was objective response rate (ORR). Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were secondary outcomes assessed in all patients.

Results: Among 124 evaluable patients, anti-PD-1 therapy achieved an ORR of 29.8% and a durable clinical benefit rate of 60.5%. The median OS (mOS) was 17.1 months (95% CI 14.2 to 24.7), median PFS (mPFS) was 3.8 months (95% CI 3.4 to 6.0), and median DOR was 9.5 months. Significant OS benefit from treatment was observed in patients without liver metastasis (23.8 vs 13.3 months, p=0.006). Copy number deletion in genes encoding granzyme B or granzyme H () was associated with poor treatment outcome (mPFS altered vs wildtype: 1.7 vs 3.6 months, p=0.03; mOS altered vs wildtype: 10.1 vs 18 months, p=0.012).

Conclusions: Anti-PD-1 treatment provided promising clinical benefit in pretreated patients with R/M NPC. Copy number loss in either or genes was associated with reduced survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jitc-2020-002014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978327PMC
March 2021

Timing and Origins of Local and Distant Metastases in Lung Cancer.

J Thorac Oncol 2021 Mar 13. Epub 2021 Mar 13.

Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China; Southern Medical University, Guangzhou, People's Republic of China. Electronic address:

Introduction: Metastasis is the primary cause of lung cancer-related death. Nevertheless, the underlying molecular mechanisms and evolutionary patterns of lung cancer metastases are still elusive.

Methods: We performed whole-exome sequencing for 40 primary tumors (PTs) and 61 metastases from 47 patients with lung cancer, of which 40 patients had paired PTs and metastases. The PT-metastasis genomic divergence, metastatic drivers, timing of metastatic dissemination, and evolutionary origins were analyzed using appropriate statistical tools and mathematical models.

Results: There were various degrees of genomic heterogeneity when comparing the paired primary and metastatic lesions or comparing metastases of different sites. Multiple metastasis-selected/enriched genetic alterations were found, such as MYC amplification, NKX2-1 amplification, RICTOR amplification, arm 20p gain, and arm 11p loss, and these results were were also featured in a meta-analysis cross-validated using an independent cohort from Memorial Sloan-Kettering Cancer Center database. To elucidate the metastatic seeding time, we applied a metastatic model and found 61.1% of the tumors were late dissemination, in which the metastatic seeding happened approximately 2.74 years before clinical detection. One exception was lymph node metastases whose dissemination time was relatively early. By analyzing the evolutionary origins, we reported that nonlymph node metastases were mainly seeded by the PT (87.5%) rather than the earlier colonized lymph node metastases.

Conclusions: Our results shed light on the molecular features that potentially drive lung cancer metastases. The distinct temporospatial pattern of disease progression revealed that lung cancer was susceptible to either late dissemination or indolent early lymph node metastases, leaving a potential time window to minimize metastases by early cancer detection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtho.2021.02.023DOI Listing
March 2021

Tumor mutation burden estimated by a 69-gene-panel is associated with overall survival in patients with diffuse large B-cell lymphoma.

Exp Hematol Oncol 2021 Mar 15;10(1):20. Epub 2021 Mar 15.

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

Background: Tumor mutation burden (TMB) as estimated by cancer gene panels (CGPs) has been confirmed to be associated with prognosis and is effective in predicting clinical benefit from immune checkpoint blockade (ICB) in solid tumors. However, whether the TMB calculated by CGPs is associated with overall survival (OS) for patients with diffuse large B-cell lymphoma (DLBCL) is worth exploring.

Methods: The prognostic value of panel-TMB, calculated by a panel of 69 genes (GP69), for 87 DLBCL patients in our clinical center (GDPH dataset) was explored. The results were further validated using 37 DLBCL patients from the Cancer Genome Atlas (TCGA) database (TCGA dataset).

Results: Spearman correlation analysis suggested that panel-TMB is positively correlated with the TMB calculated by whole-exome sequencing (wTMB) in the TCGA dataset (R = 0.76, P < 0.0001). Both GDPH and TCGA results demonstrated that higher panel-TMB is significantly associated with a poor OS for DLBCL patients (P < 0.05) where a panel of 13 genes was associated with poor OS, and another panel of 26 genes was correlated with a favorable OS for DLBCL patients. Further subgroup analysis indicated that higher panel-TMB had shorter OS in DLBCL patients with younger than 60 years, elevated LDH, greater than one extranodal involvement, stage III/IV, an IPI score of 3-5, or HBsAg, anti-HBc, or HBV-DNA negativity (P < 0.05). Interestingly, the nomogram model constructed by panel-TMB, stage, and IPI could individually and visually predict the 1-, 2- and 3-year OS rates of DLBCL patients.

Conclusions: We established GP69 for the evaluation of OS for Chinese DLBCL patients. panel-TMB might be a potential predictor for prognostic stratification of DLBCL patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40164-021-00215-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962318PMC
March 2021

Anlotinib has good efficacy and low toxicity: a phase II study of anlotinib in pre-treated HER-2 negative metastatic breast cancer.

Cancer Biol Med 2021 Mar 12. Epub 2021 Mar 12.

Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

Objective: Anlotinib is a novel tyrosine kinase inhibitor blocking angiogenesis. This study was performed to assess the efficacy and safety of anlotinib in patients with metastatic breast cancer.

Methods: Patients with HER2-negative breast cancer, who were pre-treated with anthracycline or taxanes in a neoadjuvant, adjuvant, or metastatic setting, and had treatment failure after at least one prior chemotherapy regimen in the metastatic setting were enrolled. Anlotinib was administered at 12 mg daily for 14 days in a 21-day cycle until disease progression or unacceptable toxicity occurred. Simultaneously, 5-10 mL of venous blood was collected to perform circulating tumor DNA (ctDNA) testing every 2 treatment cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), progression-free survival (PFS), overall survival, safety, and biomarkers.

Results: Twenty-six eligible patients were enrolled, with a median age of 56 (30-75) years. The median follow-up time was 10.5 months. The ORR was 15.4%, the DCR was 80.8%, and the median PFS was 5.22 months (95% confidence interval 2.86-6.24). Fourteen (53.8%) patients survived for more than 10 months. The changes in the detectable ctDNA variant allele frequency were consistent with the tumor response. The most common treatment-related adverse events were hypertension (57.7%), thyroidstimulating hormone elevation (34.6%), and hand-foot syndrome (23.1%).

Conclusions: Anlotinib showed objective efficacy with tolerable toxicity in heavily pre-treated, metastatic HER2-negative breast cancer. The dynamic changes in the ctDNA variant allele fraction may be predictive of the tumor response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0463DOI Listing
March 2021

Targeting FGFR in non-small cell lung cancer: implications from the landscape of clinically actionable aberrations of FGFR kinases.

Cancer Biol Med 2021 Mar 12. Epub 2021 Mar 12.

Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin 150086, China.

Objective: Dysfunction in fibroblast growth factor receptor (FGFR) signaling has been reported in diverse cancer types, including non-small cell lung cancer (NSCLC). The frequency of aberrations in Chinese NSCLC patients is therefore of great clinical significance.

Methods: A total of 10,966 NSCLC patients whose tumor specimen and/or circulating cell-free DNA (cfDNA) underwent hybridization capture-based next-generation sequencing were reviewed. Patients' clinical characteristics and treatment histories were also evaluated.

Results: aberrations, including mutations, fusions, and gene amplifications, were detected in 1.9% (210/10,966) of the population. abnormalities were more frequently observed in lung squamous cell carcinomas (6.8%, 65/954) than lung adenocarcinomas (1.3%, 128/9,596). oncogenic mutations were identified in 19 patients (~0.17%), of which, 68% were male lung squamous cell carcinoma patients. Eleven out of the 19 patients (58%) had concurrent altered PI3K signaling, thus highlighting a potential combination therapeutic strategy of dual-targeting FGFR and PI3K signaling in such patients. Furthermore, fusions retaining the intact kinase domain were identified in 12 patients (0.11%), including 9 , 1 , 1 novel , and 1 novel fusion between the and 5'-untranslated regions, which may have caused overexpressions. Concomitant mutations or amplifications were observed in 6 patients, and 4 patients received anti-EGFR inhibitors, in whom fusions may have mediated resistance to anti-EGFR therapies. amplification was detected in 24 patients, with the majority being amplifications. Importantly, oncogenic mutations, fusions, and gene amplifications were almost always mutually exclusive events.

Conclusions: We report the prevalence of anomalies in a large NSCLC population, including mutations, gene amplifications, and novel fusions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0120DOI Listing
March 2021

Bromodomain-containing protein 4 silencing by microRNA-765 produces anti-ovarian cancer cell activity.

Aging (Albany NY) 2021 03 3;13(6):8214-8227. Epub 2021 Mar 3.

Obstetrics and Gynecology Department, The Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, China.

Bromodomain-containing protein 4 (BRD4) overexpression promotes ovarian cancer progression, and represents an important therapeutic oncotarget. This current study identified microRNA-765 (miR-765) as a novel BRD4-targeting miRNA. We showed that miR-765 directly associated with and silenced BRD4. In primary ovarian cancer cells and established cell lines (SKOV3 and CaOV3), ectopic overexpression of miR-765 inhibited cancer cell proliferation, migration and invasion, and induced apoptosis activation. In contrast, miR-765 inhibition by its anti-sense induced BRD4 upregulation to promote ovarian cancer cell proliferation, migration and invasion. Significantly, miR-765 overexpression-induced anti-ovarian cancer cell activity was largely attenuated by restoring BRD4 expression through an UTR-null BRD4 construct. Moreover, CRISPR/Cas9-induced BRD4 knockout (KO)inhibited proliferation and activated apoptosis in ovarian cancer cells. BRD4 KO in ovarian cancer cells abolished the functional impact of miR-765. miR-765 expression levels were downregulated in human ovarian cancer tissues and cells, correlating with the upregulation of mRNA. Collectively, BRD4 silencing by miR-765produces significant anti-ovarian cancer cell activity. miR-765 could be further tested for its anti-ovarian cancer potential.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034896PMC
March 2021

The Cancer-Testis Long Non-coding RNA PCAT6 Facilitates the Malignant Phenotype of Ovarian Cancer by Sponging miR-143-3p.

Front Cell Dev Biol 2021 4;9:593677. Epub 2021 Feb 4.

Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China.

It has been reported that long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis. However, their roles in ovarian cancer (OC) remain to be elucidated. The aim of this study was to uncover the function and underlying mechanisms of PCAT6 in OC. The expression pattern of PCAT6 in OC was analyzed in the GSE137238, GSE143897 and Gene Expression Profile Interactive Analysis (GEPIA) datasets. Kaplan-Meier Plotter online software was used for survival analysis. Loss-of-function assays and gain-of-function assays were used to assess the function of PCAT6 in OC development. Moreover, small-RNA sequencing, bioinformatic analysis, luciferase assays and rescue experiments were carried out to clarify the potential mechanism of PCAT6 in OC. PCAT6 expression was significantly increased in OC tissues and positively correlated with advanced stages and with poor overall survival, progression-free survival and post-progression survival. Knockdown of PCAT6 in A2780 and SKOV3 cells inhibited OC cell proliferation, migration and invasion. In contrast, Overexpression of PCAT6 exerted the opposite effects on OC cells. Notably, PCAT6 bound to miR-143-3p and affected the expression of transforming growth factor (TGF)-β-activated kinase 1 (TAK1). Subsequent rescue assays confirmed that upregulation of miR-143-3p decreased the PCAT6 overexpression-induced promotion of proliferation, migration and invasion. Moreover, downregulation of miR-143-3p reversed the PCAT6 knockdown-induced inhibition of proliferation, migration, and invasion. Our findings demonstrate that PCAT6 plays an oncogenic role in OC and may be useful as a therapeutic target for OC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.593677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902004PMC
February 2021

Effects of repetitive submergence on the accumulation and release of nutrient elements in Pinus elliottii seedlings.

Environ Sci Pollut Res Int 2021 Jan 28. Epub 2021 Jan 28.

Key Laboratory of Forest Ecology and Environment of National Forestry and Grassland Administration, Research Institute of Forest Ecology, Environment and Protection, Chinese Academy of Forestry, Beijing, 100091, China.

Pinus elliottii is an evergreen coniferous tree. It is considered a potential species for ecological restoration in the Three Gorges Reservoir Area (TGRA). To classify the effects of different degrees of flooding stress in winter on nutrient accumulation in Pinus elliottii after experiencing early drought stress in summer, simulated water treatments of deep submergence (DS) and moderate submergence (MS) were imposed after the summer drought period. The results indicated that the survival rate of seedlings was 95.3%, and the accumulation trend of the flooded plants was rapid at an average rate of 1.99 ± 0.33% in the early stage of flooding (stage I: 0-7 days), a rapid release rate in the second stage (stage II: 7-60 days), and an average rate of only 0.07 ± 0.04% in the later stage (stage III: 60-150 days). After 150 days of flooding, the leaves of Pinus elliottii released an average of 7.156 ± 0.4 g kg of organic carbon, 8.839 ± 0.6 g kg of nitrogen, 0.781 ± 0.1 g kg of phosphorus, and 2.985 ± 0.3 g kg of potassium of macroelement content, and an average of 0.201 ± 0.03 g kg manganese, 0.147 ± 0.04 g kg iron, 0.002 g kg copper, and 0.023 g kg of zinc of microelement contents. Our results also demonstrated that after 150 days of flooding, the C/N, N/P, and C/P ratios of the nutrient element content of Pinus elliottii in the water-level fluctuation zone of the TGRA were 0.810%, 11.32%, and 9.16%, respectively. The absorption and release of nutrients under water flooding are generally divided into three stages: first, the early storage stage (the first stage: 0 to 7 days, optional), then the rapid release (the second stage: 7 to 60 days), and the later stage slow release phase (third stage: 60 to 150 days). Water flooding reduced the contents of C, N, P, and K and affected the absorption of nutrient elements in the plant. At the same time, soluble Mn and Fe over absorbed during flooding could cause toxicity to leaf tissues. At the same time, Pinus elliottii selected to reduce Cu in leaves to ensure that the root has a strong redox capacity and improve nitrogen utilization, thereby preventing the long-term flooding of toxic cations and acid substances. Taken together, our results conclude that increased drought stress can reduce the ability of Pinus elliottii seedlings to withstand flooding stress; the seedlings of Pinus elliottii can maintain their growth by accumulating certain nutrient elements under submerged conditions, which implies that this species would be a suitable candidate for reforestation in the TGRA because of its tolerance to submergence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-021-12528-2DOI Listing
January 2021

Genomic Profiling and Prognostic Value Analysis of Genetic Alterations in Chinese Resected Lung Cancer With Invasive Mucinous Adenocarcinoma.

Front Oncol 2020 11;10:603671. Epub 2021 Jan 11.

Department of Thoracic Surgery, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.

Background: Invasive mucinous adenocarcinoma (IMA) of the lung is a distinct histological subtype with unique clinical and pathological features. Despite previous genomic studies on lung IMA, the genetic characteristics and the prognosis-related biomarkers in Chinese surgically resected lung IMA remain unclear.

Methods: We collected 76 surgically resected primary tumors of invasive lung adenocarcinoma, including 51 IMA and 25 non-mucinous adenocarcinomas (non-IMA). IMA was further divided into pure-IMA (mucinous features≥90%) and mixed-IMA subgroups. Comprehensive genomic profiling based on targeted next-generation sequencing (NGS) of 425 genes was explored and genomic characteristics were evaluated for the correlation with postoperative disease-free survival (DFS).

Results: IMA had a unique genetic profile, with more diverse driver mutations and more tumor drivers/suppressors co-occurrence than that of non-IMA. The frequency of (72.0% vs. 40.0% vs. 23.1%, p=0.002) and (undetected vs. 20.0% vs. 26.9%, p=0.015) alterations showed a trend of gradual decrease and increase from non-IMA to mixed-IMA to pure-IMA, respectively. The frequency of mutations in pure-IMA was higher than that in mixed-IMA, albeit statistically insignificant (23.1% vs. 4.0%, p=0.10). mutation was significantly less in pure-IMA compared to mixed-IMA and non-IMA (23.1% vs. 52.0% vs. 56.0%, p=0.03). Besides, IMA exhibited less arm-level amplifications (p=0.04) and more arm-level deletions (p=0.004) than non-IMA, and the frequency of amplification and deletion also showed a trend of gradual decrease and increase from non-IMA to mixed-IMA to pure-IMA, respectively. Furthermore, prognosis analysis in stage III IMA patients showed that patients harboring alterations in (mDFS=30.3 vs. 16.0 months, HR=0.19, P=0.027) and PI3K pathway (mDFS=36.0 vs. 16.0 months, HR=0.12, P=0.023) achieved prolonged DFS, while patients with poorly differentiated tumors (mDFS=14.1 vs. 28.0 months, HR=3.75, p=0.037) or with mutations (mDFS=13.0 vs. 20.0 months, HR=6.95, p=0.027) had shorter DFS. Multivariate analysis showed that mutations, PI3K pathway alterations, and tumor differentiation status were independent factors that have statistically significant influences on clinical outcomes of IMA patients.

Conclusion: Our study provided genomic insights into Chinese surgically resected lung IMA. We also identified several genomic features that may serve as potential biomarkers on postoperative recurrence in IMA patients with stage III disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.603671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829865PMC
January 2021

Understanding the relationship between land use and land cover and malaria in Nepal.

Geospat Health 2020 12 29;15(2). Epub 2020 Dec 29.

Department of Geography, Virginia Tech, Blacksburg.

Malaria is a leading cause of mortality and morbidity globally. Land Use and Land Cover (LULC) change have been found to affect the transmission of malaria in other regions, but no study has examined such relationships in Nepal. Therefore, this study has three aims: first, to analyze the spatial and temporal trend of Malaria Incidence Rate (MIR) between 1999 and 2015, second to assess LULC change between 2000 and 2010, and finally to understand the relationship between LULC and malaria in Nepal. The land cover types examined are forest, water bodies, agriculture, grassland, shrubland, barren areas, built-up areas, and rice paddies. The temporal trend of MIR and the relationship between MIR and LULC were evaluated using Poisson and negative binomial regression. Forest, water bodies, and built-up area increased in Nepal by 0.8%, 8.2%, and 28.4% respectively, while other LULC variables decreased between 2000 and 2010. MIR decreased significantly in 21 districts; however, four districts, namely Pyuthan, Kaski, Rupandehi, and Siraha, had a significantly increasing MIR trend between 1999 and 2015. MIR was positively related to water bodies and rice paddies during 2001, 2002, and 2003 but negatively related to grassland during 2010. However, there was no relationship between LULC and MIR during 2000, 2011, 2012 and 2013. This information will be helpful for public health officials to increase control efforts in those districts and in areas near water bodies and rice paddies to aid in their effort to eliminate malaria from Nepal.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4081/gh.2020.855DOI Listing
December 2020

Nanostructured Black Aluminum Prepared by Laser Direct Writing as a High-Performance Plasmonic Absorber for Photothermal/Electric Conversion.

ACS Appl Mater Interfaces 2021 Jan 11;13(3):4305-4315. Epub 2021 Jan 11.

Collaborative Innovation Center of Technology and Equipment for Biological Diagnosis and Therapy in Universities of Shandong, Institute for Advanced Interdisciplinary Research (iAIR), University of Jinan, Ji'nan 250022, P. R. China.

Utilizing the abundant and renewable solar energy to address the global energy shortage and water scarcity is promising. Great effort has been devoted to photothermal conversion for its typically full-spectrum utilization and high efficiency. Here, the coral-like micro/nanostructure was fabricated on an aluminum sheet by a facile laser direct writing technology. The nanocluster and microscale branches of corals endowed this black aluminum with broad-band plasmonic absorption and rapid heat transfer from the light absorption region to substrate. The black aluminum achieved ultrahigh solar absorbance of over 92.6% (>95.1% in the visible range) and excellent light heating ability (>90.6 °C under 1.0 sun). With good photothermal properties, this plasmonic absorber was used in a state-of-the-art eight-layer membrane distillation system, producing a water yield of up to 2.40 kg m h and a high solar conversion efficiency of 166.5% under 1-sun irradiation. Photothermal electricity was also achieved based on this system with a thermoelectric generator, with a water yield of 0.89 kg m h and a maximum electrical power output of 7.21 μW cm under 1.0 sun. Considering the excellent performance of the plasmon-enhanced black aluminum, this work provides an alternative and feasible route toward high-efficient utilization of the solar energy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c17584DOI Listing
January 2021

Morphological, immunohistochemical, and genetic analyses of bronchiolar adenoma and its putative variants.

J Pathol Clin Res 2021 May 5;7(3):287-300. Epub 2021 Jan 5.

Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, PR China.

We collected 26 cases of bronchiolar adenoma (BA) and its variants, and performed a comprehensive characterization using a combination of morphological, immunohistochemical, and genetic assessments. Of these 26, 13 were classic bilayered cases, including 10 proximal and 3 distal-type BAs. Of note, we also identified 13 cases that lacked a continuous basal cell layer. In five cases, the adenomas were partially classic bilayered, leaving a single layer of columnar or cuboidal epithelial cells in some areas of the lesion (BA with monolayered cell lesions). In the other eight cases, the glandular or papillary structures were entirely composed of monolayered columnar or cuboidal epithelial cells, which were morphologically identical to the luminal epithelial cells of classic BA (monolayered BA-like lesions). Immunohistochemical analysis revealed thyroid transcription factor 1 expression by ciliated columnar epithelial cells, basal cells, and nonciliated columnar and cuboidal epithelial cells. Basal cells also expressed p40 and p63. Twenty-five cases underwent next-generation sequencing using a 422-cancer-gene panel (GeneseeqPrime). Oncogenic driver mutations were detected in 23 cases, including 13 (52%) with EGFR mutations, 4 (16%) with KRAS G12D/V mutations, 3 (12%) with BRAF V600E mutations, 2 (8%) with ERBB2 exon 20 insertions, and 1 (4%) with a RET fusion. EGFR exon 20 insertions were present in 100% of BAs with monolayered cell lesions, 37.5% of monolayered BA-like lesions, and 8% of classic BA (Fisher's exact test, p = 0.002, false discovery rate = 0.014). Collectively, our study revealed a gradual morphological transition between BA and its variants. The genetic composition of BAs with monolayered structures differed significantly from those of classic BAs or lung adenocarcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cjp2.197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072999PMC
May 2021

Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid for the Diagnosis of External Ventricular and Lumbar Drainage-Associated Ventriculitis and Meningitis.

Front Microbiol 2020 14;11:596175. Epub 2020 Dec 14.

Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Metagenomic next-generation sequencing (mNGS) has become a widely used technology that can accurately detect individual pathogens. This prospective study was performed between February 2019 and September 2019 in one of the largest clinical neurosurgery centers in China. The study aimed to evaluate the performance of mNGS on cerebrospinal fluid (CSF) from neurosurgical patients for the diagnosis of external ventricular and lumbar drainage (EVD/LD)-associated ventriculitis and meningitis (VM). We collected CSF specimens from neurosurgical patients with EVD/LD for more than 24 h to perform conventional microbiological studies and mNGS analyses in a pairwise manner. We also investigated the usefulness of mNGS of CSF for the diagnosis of EVD/LD-associated VM. In total, 102 patients were enrolled in this study and divided into three groups, including confirmed VM (cVM) (39), suspected VM (sVM) (49), and non-VM (nVM) (14) groups. Of all the patients, mNGS detected 21 Gram-positive bacteria, 20 Gram-negative bacteria, and five fungi. The three primary bacteria detected were (9), (5), and (3). The mNGS-positive coincidence rate of confirmed EVD/LD-associated VM was 61.54% (24/39), and the negative coincidence rate of the nVM group was 100% (14/14). Of 15 VM pathogens not identified by mNGS in the cVM group, eight were negative with mNGS and seven were inconsistent with the conventional microbiological identification results. In addition, mNGS identified pathogens in 22 cases that were negative using conventional methods; of them, 10 patients received a favorable clinical treatment; thus, showing the benefit of mNGS-guided therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2020.596175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767851PMC
December 2020

Clinical implications of plasma ctDNA features and dynamics in gastric cancer treated with HER2-targeted therapies.

Clin Transl Med 2020 Dec;10(8):e254

Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China.

Background: Gastric cancer (GC) is confronted with limited options for precision medicine. Human epidermal growth factor receptor 2 (HER2) is the principal druggable target of GC, yet proper biomarkers for response/resistance prediction remain unveiled.

Methods: From 40 GC patients received HER2-targeted therapy, a total of 327 peripheral blood plasma specimens was collected including baseline and treatment time points. Circulating tumor DNA (ctDNA) was extracted and sequenced with a target panel of 425 genes. Experimental validation of resistant mutations was carried out in NIH-3T3 cell line.

Results: Genomic features, including ERBB2 copy number variation (CNV), total copy number load, and tumor mutation burdens (TMBs), dynamically changed along with the treatment process and correlated with disease progression. Plasma ctDNA-based diagnosis was more sensitive than conventional computed tomography scanning in 40% of investigated patients, gaining additional time for clinical management. Compared to baseline, new gene alterations were emerged in 12 patients who developed drug resistance during treatment. ERBB2 mutations potentially related to Pyrotinib resistance were identified in plasma ctDNA of one patient and functional analysis of their downstream signaling pathways was carried out in NIH-3T3 cell line. TMB exhibited more power than ERBB2 CNV in predicting treatment responses and prognosis for HER2-targeted therapy in GC patients. Interestingly, survival analysis indicated that patients harboring both HER2 (ERBB2) positivity and high TMB might gain more therapeutic benefits from immune checkpoint inhibitors instead of HER2-targeted regimens that required further studies and validations CONCLUSIONS: Our work showed that the dynamic surveillance of plasma ctDNA genomic features provided instructive information for the precision medication of GC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ctm2.254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737756PMC
December 2020

The Effects of Temperature on Dynamics of Psychiatric Outpatients.

Front Psychiatry 2020 7;11:523059. Epub 2020 Dec 7.

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

Climate changes affect mental states and alter the risk for psychiatric diseases. Seasonal changes in temperature lead to dynamics in the occurrence of psychiatric conditions and pose challenges in the administration of clinical psychiatry services. The present study aims to retrospectively analyze outpatient data with weather reports from January 2014 to March 2019 at Shanghai Mental Health Center, one of the largest psychiatric hospitals in the world, in order to provide policy insights into the administration of psychiatric clinics. The results show steady increases in the number of overall patients over the past 5 years with several peaks within each year. Temperature changes and weather information reliably predict the increased number of psychiatric patients. We conclude that mental health hospitals should prepare for patient dynamics based on the weather forecast.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2020.523059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750496PMC
December 2020

Complex ALK Fusions Are Associated With Better Prognosis in Advanced Non-Small Cell Lung Cancer.

Front Oncol 2020 11;10:596937. Epub 2020 Dec 11.

Division of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Background: Echinoderm microtubule-associated protein-like 4 () is the canonical anaplastic lymphoma kinase () fusion partner in non-small cell lung cancer (NSCLC), and -positive patients showed promising responses to ALK tyrosine kinase inhibitors (TKIs). However, studies that comprehensively investigate ALK TKI treatment in patients with different fusion patterns are still lacking.

Methods: Ninety-eight -positive patients with advanced NSCLC were retrospectively studied for their response to crizotinib and subsequent treatments. Comprehensive genomic profiling (CGP) was conducted to divide patients into different groups based on their fusion patterns. Non-canonical fusions were validated using RNA-sequencing.

Results: 54.1% of patients had pure canonical fusions, 19.4% carried only non-canonical fusions, and 26.5% harbored complex fusions with coexisting canonical and non-canonical fusions. The objective response rate and median progression-free survival to crizotinib treatment tended to be better in the complex fusion group. Notably, patients with complex fusions had significantly improved overall survival after crizotinib treatment (p = 0.012), especially when compared with the pure canonical fusion group (p = 0.010). The complex fusion group also tended to respond better to next-generation ALK TKIs, which were used as later-line therapies. Most identified non-canonical fusions were likely to be expressed in tumors, and some of them formed canonical transcripts during mRNA maturation.

Conclusion: Our results suggest NSCLC patients with complex fusions could potentially have better treatment outcomes to ALK TKIs therapy. Also, diagnosis using CGP is of great value to identify novel fusions and predict prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.596937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759679PMC
December 2020

Genetic aberrations in Chinese pancreatic cancer patients and their association with anatomic location and disease outcomes.

Cancer Med 2021 02 22;10(3):933-943. Epub 2020 Dec 22.

Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Objectives: Pancreatic cancer (PC) is one of the most lethal malignancies with an increasing death rate over the years. We performed targeted sequencing and survival analyses on 90 Chinese pancreatic cancer patients, hoping to identify genomic biomarkers associated with clinical outcomes and therapeutic options.

Method: Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue specimens of 90 pancreatic cancer patients and sequenced. The associations with clinicopathological factors were analyzed.

Result: High prevalence of driver mutations in KRAS, TP53, CDKN2A, SMAD4, and ARID1A genes were found. Most mutated genes in PC belonged to cell cycle and DNA damage repair pathways. Tumors that arise from the pancreas' body and tail (BT tumors) displayed a higher ratio of mutated KRAS and TP53 than those that arise from the pancreas' head and neck (HN tumors), who showed less diverse KRAS subtypes. Patients with a KRAS p.G12R mutated tumor tended to have a prolonged disease-free survival (DFS) and overall survival (OS) than other KRAS subtypes. Those with an altered ARID1A gene and more than two mutated driver genes tended to have a shorter DFS and OS.

Conclusion: HN and BT tumors of the pancreas displayed different mutational profiles, which had prognostic significances and indicated different potential therapeutic options.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.3679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897942PMC
February 2021

Fusion in Lung Adenocarcinoma with Excellent Response Upon Alectinib Treatment: A Case Report and Literature Review.

Onco Targets Ther 2020 4;13:12515-12519. Epub 2020 Dec 4.

Department of Respiratory Oncology, Guangxi Medical University Affiliated Tumor Hospital, Nanning, China.

Non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase () rearrangement benefit from treatment with ALK inhibitors. Therefore, the identification of druggable fusions is necessary for NSCLC treatment. More than 90 fusion partners of have been reported in NSCLC patients, but the striatin gene () fusion has rarely been reported. Moreover, the response of - fusion patients treated with ALK inhibitors remains to be explored. A 64-year-old Chinese male with no history of smoking or alcohol consumption was diagnosed as stage IVB lung adenocarcinoma (LADC) (cT4N3M1c) in October 2018. Next-generation sequencing (NGS) targeting 425 cancer-related genes was performed on the plasma and supernatant of pleural effusion samples and revealed an - fusion. The patient received alectinib (600 mg, twice daily) as the first-line treatment with an excellent response exceeding 19 months. This is the first report of a NSCLC patient harboring an - fusion and exhibiting an excellent response to alectinib treatment. This case provides valuable information for therapeutic decision-making of patients with - fusions. Furthermore, this case also highlighted the advantage of performing targeted NGS on circulating tumor DNA for the identification and analysis of rare, druggable genomic alterations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OTT.S282933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727031PMC
December 2020

Profiling Analysis Reveals the Crucial Role of the Endogenous Peptides in Bladder Cancer Progression.

Onco Targets Ther 2020 3;13:12443-12455. Epub 2020 Dec 3.

Department of Nephrology and Urology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People's Republic of China.

Background: Peptide drugs provide promising regimes in bladder cancer. In order to identify potential bioactive peptides involved in bladder cancer, we performed the present study.

Methods: Liquid chromatography/mass spectrometry assay was used to compare the endogenous peptides between bladder cancer and normal control. The potential biological functions of these dysregulated peptides are assessed by GO analysis and KEGG pathway analysis of their precursors. The SMART and UniProt databases are used to identify the sequences of the dysregulated peptides located in the functional domains. The Open Targets Platform database was used to investigate the precursors related to metabolic diseases.

Results: A total of 9 up-regulated peptides and 110 down-regulated peptides in bladder cancer compared with normal control were identified (fold change > 1.2, < 0.05). The MW of these dysregulated peptides ranged from 500 Da to 2500 Da and the MW of all identified peptides was below 3500 Da. The GO and KEGG pathway analysis indicated that these dysregulated peptides could play an important role in bladder cancer. Our further analysis revealed that HFNPRFNAHGDAN derived from LGALS1 and those peptides derived from P4HB and SERPINA1 might be the promising diagnostic biomarkers and therapeutic targets of bladder cancer.

Conclusion: In the present study, we have identified the profile of the peptides significantly dysregulated in bladder cancer. Moreover, using bioinformatic analysis, we found the peptides derived from LGALS1, P4HB and SERPINA1 could be the promising diagnostic biomarkers and therapeutic targets of bladder cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OTT.S281713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725083PMC
December 2020

Acquired rare recurrent mutations as mechanisms of resistance to Osimertinib in lung cancer and structural modelling.

Am J Cancer Res 2020 1;10(11):4005-4015. Epub 2020 Nov 1.

Department of Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital Nanjing, Jiangsu, China.

A growing number of progression on Osimertinib among -mutated lung cancers represents a great challenge clinically. Our study aims to gain insights into novel mechanisms of acquired resistance to Osimertinib. We performed genomic studies on 2 large independent cohorts of lung cancer patients with progressed diseases on different tyrosine kinase inhibitors (TKIs). modeling was used to study the structural mechanism of selected EGFR mutations. Compared with the 1-TKIs-resistant group, mutations C797S/G, L718Q/V, L792F/H were significantly more enriched in the Osimertinib-resistant cohort, whose sensitivities to Osimertinib were successfully predicted. Importantly, a total of 14 low-frequency mutations were exclusively or significantly observed in the Osimertinib-resistant group, 7 were predicted to dramatically reduce the binding affinity of EGFR to Osimertinib (G796S, V802F, T725M, Q791L/H, P794S/R). Analysis of pre-Osimertinib treatment samples of two patients supported that V802F and G796S were acquired during the treatment. In addition, G796S was predicted to be susceptible to gefitinib. This study represented the largest real-world data so far investigating Osimertinib resistance in -mutated lung cancer. We identified a collection of coexistent EGFR rare mutations and provided possible guidance for those patients who progressed on the first-line treatment of Osimertinib.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716156PMC
November 2020