Publications by authors named "Qing Lan"

573 Publications

Genomic and evolutionary classification of lung cancer in never smokers.

Nat Genet 2021 Sep 6;53(9):1348-1359. Epub 2021 Sep 6.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

Lung cancer in never smokers (LCINS) is a common cause of cancer mortality but its genomic landscape is poorly characterized. Here high-coverage whole-genome sequencing of 232 LCINS showed 3 subtypes defined by copy number aberrations. The dominant subtype (piano), which is rare in lung cancer in smokers, features somatic UBA1 mutations, germline AR variants and stem cell-like properties, including low mutational burden, high intratumor heterogeneity, long telomeres, frequent KRAS mutations and slow growth, as suggested by the occurrence of cancer drivers' progenitor cells many years before tumor diagnosis. The other subtypes are characterized by specific amplifications and EGFR mutations (mezzo-forte) and whole-genome doubling (forte). No strong tobacco smoking signatures were detected, even in cases with exposure to secondhand tobacco smoke. Genes within the receptor tyrosine kinase-Ras pathway had distinct impacts on survival; five genomic alterations independently doubled mortality. These findings create avenues for personalized treatment in LCINS.
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http://dx.doi.org/10.1038/s41588-021-00920-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432745PMC
September 2021

Household air pollution from, and fuel efficiency of, different coal types following local cooking practices in Xuanwei, China.

Environ Pollut 2021 Aug 12;290:117949. Epub 2021 Aug 12.

Institute for Risk Assessment Sciences, Utrecht University, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.

The domestic combustion of smoky (bituminous) coal in the Chinese counties of Xuanwei and Fuyuan, are responsible for some of the highest rates of lung cancer in the world. Cancer rates vary between coal producing regions (deposits) in the area, with coals from Laibin exhibiting particularly high risks and smokeless (anthracite) coal exhibiting lower risks. However, little information is available on the specific burning characteristics of coals from throughout the area. We conducted an extensive controlled burning experiment using coal from multiple deposits in either a traditional firepit or ventilated stove, accompanied by a detailed examination of time-weighted and real-time size-aggregated particle concentrations. Smoky coal caused higher particle concentrations of all sizes than smokeless coal, with variations observed by geological source. Virtually all particle emissions were in the PM fraction (98% - mass based), and 75% and 46% were in the PM and PM fraction respectively. Real-time concentrations of PM and PM peaked after coal was added and declined afterwards. Ventilation reduced particle concentrations by up to 15-fold and increased the coal burning rate by 1.9-fold. These findings may provide valuable insight for reducing exposure and adverse health effects associated with domestic coal combustion.
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http://dx.doi.org/10.1016/j.envpol.2021.117949DOI Listing
August 2021

Elevated urinary mutagenicity among those exposed to bituminous coal combustion emissions or diesel engine exhaust.

Environ Mol Mutagen 2021 Jul 31. Epub 2021 Jul 31.

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.

Urinary mutagenicity reflects systemic exposure to complex mixtures of genotoxic/carcinogenic agents and is linked to tumor development. Coal combustion emissions (CCE) and diesel engine exhaust (DEE) are associated with cancers of the lung and other sites, but their influence on urinary mutagenicity is unclear. We investigated associations between exposure to CCE or DEE and urinary mutagenicity. In two separate cross-sectional studies of nonsmokers, organic extracts of urine were evaluated for mutagenicity levels using strain YG1041 in the Salmonella (Ames) mutagenicity assay. First, we compared levels among 10 female bituminous (smoky) coal users from Laibin, Xuanwei, China, and 10 female anthracite (smokeless) coal users. We estimated exposure-response relationships using indoor air concentrations of two carcinogens in CCE relevant to lung cancer, 5-methylchrysene (5MC), and benzo[a]pyrene (B[a]P). Second, we compared levels among 20 highly exposed male diesel factory workers and 15 unexposed male controls; we evaluated exposure-response relationships using elemental carbon (EC) as a DEE-surrogate. Age-adjusted linear regression was used to estimate associations. Laibin smoky coal users had significantly higher average urinary mutagenicity levels compared to smokeless coal users (28.4 ± 14.0 SD vs. 0.9 ± 2.8 SD rev/ml-eq, p = 2 × 10 ) and a significant exposure-response relationship with 5MC (p = 7 × 10 ). DEE-exposed workers had significantly higher urinary mutagenicity levels compared to unexposed controls (13.0 ± 10.1 SD vs. 5.6 ± 4.4 SD rev/ml-eq, p = .02) and a significant exposure-response relationship with EC (p-trend = 2 × 10 ). Exposure to CCE and DEE is associated with urinary mutagenicity, suggesting systemic exposure to mutagens, potentially contributing to cancer risk and development at various sites.
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http://dx.doi.org/10.1002/em.22455DOI Listing
July 2021

Modeling of pre-transplantation liver viability with spatial-temporal smooth variable selection.

Comput Methods Programs Biomed 2021 Sep 3;208:106264. Epub 2021 Jul 3.

Grado Department of Industrial and Systems Engineering, Virginia Tech, Blacksburg, VA 24061, USA.

Background And Objective: Liver viability assessment plays a critical role in liver transplantation, and the accuracy of the assessment directly determines the success of the transplantation surgery and patient's outcomes. With various factors that affect liver viability, including pre-existing medical conditions of donors, the procurement process, and preservation conditions, liver viability assessment is typically subjective, invasive or inconsistent in results among different surgeons and pathologists. Motivated by these challenges, we aimed to create a non-invasive statistical model utilizing spatial-temporal infrared image (IR) data to predict the binary liver viability (acceptable/unacceptable) during the preservation.

Methods: The spatial-temporal features of liver surface temperature, monitored by IR thermography, are significantly correlated with the liver viability. A spatial-temporal smooth variable selection (STSVS) method is proposed to define the smoothness of model parameters corresponding to different liver surface regions at different times.

Results: A case study, using porcine livers, has been performed to validate the efficacy of the STSVS method. The comparison results show that STSVS has the better overall prediction performance compared to the past state-of-the-art predictive models, including generalized linear model (GLM), support vector machine (SVM), LASSO, and Fused LASSO. Moreover, the significant predictors identified by the STSVS method indicate the importance of edges of lobes in predicting liver viability during the pre-transplantation preservation.

Conclusions: The proposed method has the best performance in predicting liver viability. This 'real-time' prediction method may increase the utilization of donors' livers without damaging tissues and time-consuming, yet imprecise feature assessment.
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http://dx.doi.org/10.1016/j.cmpb.2021.106264DOI Listing
September 2021

The Emerging Roles of RNA mA Methylation and Demethylation as Critical Regulators of Tumorigenesis, Drug Sensitivity, and Resistance.

Cancer Res 2021 Jul 5;81(13):3431-3440. Epub 2021 Mar 5.

Children's Cancer Institute Australia, Sydney, New South Wales, Australia.

RNA -methyladenosine (mA) modification occurs in approximately 25% of mRNAs at the transcriptome-wide level. RNA mA is regulated by the RNA mA methyltransferases methyltransferase-like 3 (METTL3), METTL14, and METTL16 (writers), demethylases FTO and ALKBH5 (erasers), and binding proteins YTHDC1-2, YTHDF1-3, IGF2BP1-3, and SND1 (readers). These RNA mA modification proteins are frequently upregulated or downregulated in human cancer tissues and are often associated with poor patient prognosis. By modulating pre-mRNA splicing, mRNA nuclear export, decay, stability, and translation of oncogenic and tumor suppressive transcripts, RNA mA modification proteins regulate cancer cell proliferation, survival, migration, invasion, tumor initiation, progression, metastasis, and sensitivity to anticancer therapies. Importantly, small-molecule activators of METTL3, as well as inhibitors of METTL3, FTO, ALKBH5, and IGF2BP1 have recently been identified and have shown considerable anticancer effects when administered alone or in combination with other anticancer agents, both and in mouse models of human cancers. Future compound screening and design of more potent and selective RNA mA modification protein inhibitors and activators are expected to provide novel anticancer agents, appropriate for clinical trials in patients with cancer tissues harboring aberrant RNA mA modification protein expression or RNA mA modification protein-induced resistance to cancer therapy.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-4107DOI Listing
July 2021

Doxorubicin Delivered via ApoE-Directed Reduction-Sensitive Polymersomes Potently Inhibit Orthotopic Human Glioblastoma Xenografts in Nude Mice.

Int J Nanomedicine 2021 15;16:4105-4115. Epub 2021 Jun 15.

Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People's Republic of China.

Purpose: Glioblastoma multiforme (GBM) poorly responds to chemotherapy owing to the existence of blood-brain barriers (BBB). It has been a long desire to develop BBB-permeable vehicles to facilitate drug targeting to GBM.

Method And Results: Here, we report that doxorubicin hydrochloride loaded in ApoE peptide-functionalized reduction-sensitive polymersomes (ApoE-PS-DOX) induces potent therapy of orthotopic U-87 MG model in nude mice. ApoE-PS-DOX with varying amount of ApoE (10~30 mol%) all had stable DOX loading and small sizes (< 90 nm). As revealed by flow cytometry, confocal microscopy, apoptosis and MTT assays, ApoE-PS-DOX with 20 mol.% ApoE induced the best cellular uptake and inhibitory effect to U-87 MG cells, which were much better than the non-targeted PS-DOX and liposomal doxorubicin (Lipo-DOX) used in the clinic. ApoE-PS-DOX revealed a pharmacokinetic profile comparable to PS-DOX but induced considerably better growth inhibition of orthotopically xenografted U-87 MG tumors in nude mice than PS-DOX and Lipo-DOX, leading to significant survival benefits with a median survival time of 44 days, which was almost doubled relative to the phosphate-buffered saline (PBS) group. Moreover, in contrast to mice treated with Lipo-DOX and PS-DOX, ApoE-PS-DOX group exhibited little body weight loss, signifying that ApoE-PS-DOX not only has low side effects but also can effectively inhibit glioblastoma invasion.

Conclusion: This ApoE-docked multifunctional polymersomal doxorubicin induces potent and safe chemotherapy of orthotopic U-87 MG model in nude mice offering an alternative treatment modality for GBM.
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http://dx.doi.org/10.2147/IJN.S314895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214541PMC
June 2021

Commute patterns, residential traffic-related air pollution, and lung cancer risk in the prospective UK Biobank cohort study.

Environ Int 2021 10 15;155:106698. Epub 2021 Jun 15.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20850, USA.

Introduction: Commuting exposes millions of people to carcinogens from traffic-related air pollution (TRAP) but is seldomly considered in epidemiologic studies of lung cancer. In the prospective United Kingdom (UK) Biobank cohort study, we investigated associations between commute patterns, residential nitrogen dioxide concentrations (NO; a surrogate for TRAP), and lung cancer risk.

Methods: We analyzed 234,124 employed participants at baseline (2006-2010). There were 493 incident lung cancer cases diagnosed over an average 7-year follow-up. Subjects were cross-classified into exclusive categories of commute mode (automobile, public transportation, walking, cycling, active mixture, and other mixture) and frequency (regular: 1-4, often: ≥5 work-bound trips/week). Annual average residential NO concentrations in 2005-2007 were estimated with land use regression. Multivariable Cox regression was used to estimate associations between commute patterns, NO quartiles, and incident lung cancer. We conducted analyses stratified by NO (>, ≤median = 28.3 µg/m) and potential confounders such as sex and smoking.

Results: Compared to regular automobile use, commuting often by public transportation was associated with increased lung cancer risk (hazard ratio (HR) = 1.58, 95% confidence intervals (CI):1.08-2.33). Additionally, we found a positive exposure-response relationship with residential NO (HR = 1.21, 95 %CI: 0.90-1.62; HR = 1.48, 95 %CI: 1.10-1.99; HR = 1.58, 95 %CI: 1.13-2.23; p-trend = 3.1 × 10). The public transportation association was observed among those with higher NO (p-interaction = 0.02). Other commute categories were not associated with risk.

Conclusions: Commuters residing in high-NO areas who often use public transportation could have elevated lung cancer risk compared to regular automobile users. These results warrant investigations into which component(s) of public transportation contribute to the observed association with increased lung cancer risk.
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http://dx.doi.org/10.1016/j.envint.2021.106698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292218PMC
October 2021

Integrative analysis of TP73 profile prognostic significance in WHO grade II/III glioma.

Cancer Med 2021 07 13;10(13):4644-4657. Epub 2021 Jun 13.

Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Due to the extremely intrinsic heterogeneity among glioma patients, the outcomes of these patients are tremendously different. Therefore, the exploitation of novel biomarker classification of glioma is vitally important for deep insight into the essence and predicting the prognosis of glioma. We aim to analyze the correlation between TP73 mRNA expression, DNA methylated alteration and the prognosis of WHO grade II/III glioma, utilizing bioinformatics to evaluate its significance as a risk-factor in predicting the prognosis of these glioma patients. The analysis found that TP73 expression was positively correlated with the grade of glioma, and showed a strong correlation with glioma molecular classification, which revealed significantly higher TP73 expression in IDH-wildtype than in IDH-mutant subtype of WHO grade II/III glioma. Cox regression analysis indicated that high expression of TP73 shared an independent high-risk factor impacting the prognosis of WHO grade II/III glioma. We discovered 8 DNA promoter methylation sites with prognostic significance, which were negatively associated with TP73 expression, and positively associated with beneficial overall survival (OS) and progression-free survival (PFS). Integrating with four independent glioma datasets, subsequent Meta-analysis verified that low expression of TP73 was closely related to favorable OS, especially in IDH-mutant subtype. Moreover, we found that 1p/19q /TP73 subgroup shared the most favorable OS, 1p/19q /TP73 subgroup suffered the worst OS. Meanwhile, the enrichment analysis of TP73-related differential mRNAs demonstrated that TP73 aberration in WHO grade II/III glioma might be closely related to cell cycle and P53 signaling pathways. Finally, TP73 expression of 53 glioma specimens was measured by qRT-PCR, which was consistent with the previous analytical result, and TP73 high-expression subgroup suffered worse PFS than TP73 low-expression subgroup. In summary, our funding supports that TP73 gene can perform as a reliable biomarker to evaluate the survival outcome of patients diagnosed with WHO grade II/III glioma.
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http://dx.doi.org/10.1002/cam4.4016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267133PMC
July 2021

Single-Nucleus Chromatin Accessibility Landscape Reveals Diversity in Regulatory Regions Across Distinct Adult Rat Cortex.

Front Mol Neurosci 2021 17;14:651355. Epub 2021 May 17.

BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China.

Rats have been widely used as an experimental organism in psychological, pharmacological, and behavioral studies by modeling human diseases such as neurological disorders. It is critical to identify and characterize cell fate determinants and their regulatory mechanisms in single-cell resolutions across rat brain regions. Here, we applied droplet-based single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq) to systematically profile the single-cell chromatin accessibility across four dissected brain areas in adult (SD) rats with a total of 59,023 single nuclei and identified 16 distinct cell types. Interestingly, we found that different cortex regions exhibit diversity in both cellular compositions and gene regulatory regions. Several cell-type-specific transcription factors (TFs), including SPI1, KLF4, KLF6, and NEUROD2, have been shown to play important roles during the pathogenesis of various neurological diseases, such as Alzheimer's disease (AD), astrocytic gliomas, autism spectrum disorder (ASD), and intellectual disabilities. Therefore, our single-nucleus atlas of rat cortex could serve as an invaluable resource for dissecting the regulatory mechanisms underlying diverse cortex cell fates and further revealing the regulatory networks of neuropathogenesis.
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http://dx.doi.org/10.3389/fnmol.2021.651355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166204PMC
May 2021

Elevated Alu retroelement copy number among workers exposed to diesel engine exhaust.

Occup Environ Med 2021 May 26. Epub 2021 May 26.

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.

Background: Millions of workers worldwide are exposed to diesel engine exhaust (DEE), a known genotoxic carcinogen. Alu retroelements are repetitive DNA sequences that can multiply and compromise genomic stability. There is some evidence linking altered Alu repeats to cancer and elevated mortality risks. However, whether Alu repeats are influenced by environmental pollutants is unexplored. In an occupational setting with high DEE exposure levels, we investigated associations with Alu repeat copy number.

Methods: A cross-sectional study of 54 male DEE-exposed workers from an engine testing facility and a comparison group of 55 male unexposed controls was conducted in China. Personal air samples were assessed for elemental carbon, a DEE surrogate, using NIOSH Method 5040. Quantitative PCR (qPCR) was used to measure Alu repeat copy number relative to albumin (Alb) single-gene copy number in leucocyte DNA. The unitless Alu/Alb ratio reflects the average quantity of Alu repeats per cell. Linear regression models adjusted for age and smoking status were used to estimate relations between DEE-exposed workers versus unexposed controls, DEE tertiles (6.1-39.0, 39.1-54.5 and 54.6-107.7 µg/m) and Alu/Alb ratio.

Results: DEE-exposed workers had a higher average Alu/Alb ratio than the unexposed controls (p=0.03). Further, we found a positive exposure-response relationship (p=0.02). The Alu/Alb ratio was highest among workers exposed to the top tertile of DEE versus the unexposed controls (1.12±0.08 SD vs 1.06±0.07 SD, p=0.01).

Conclusion: Our findings suggest that DEE exposure may contribute to genomic instability. Further investigations of environmental pollutants, Alu copy number and carcinogenesis are warranted.
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http://dx.doi.org/10.1136/oemed-2021-107462DOI Listing
May 2021

PSMD12 promotes glioma progression by upregulating the expression of Nrf2.

Ann Transl Med 2021 Apr;9(8):700

Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, China.

Background: Glioma is the most common and aggressive primary brain tumor in adults. Proteasome 26S subunit, non-ATPase 12 (PSMD12), an important subunit in the 26S proteasome, is known to be involved in the growth and apoptosis of breast cancer cells. However, its exact function and underlying molecular mechanisms in glioma remain unknown.

Methods: PSMD12 expression was detected in glioma tissue specimens by immunohistochemistry (IHC) and TCGA database. Overexpression and down-regulation of PSMD12 and Nrf2 were induced in glioma cell lines, and CCK-8 and Transwell assays were used to detect cell proliferation and invasion evaluation, respectively. Xenograft model was used to observe the effect of knockdown of PSMD12 on tumor growth. Immunohistochemical assays and TCGA database were conducted to reveal the relationships between PSMD12 expression and Nrf2. Finally, Western blot and related biological function experiments were used to explore the mechanism of PSMD12 regulating the glioma progression and Nrf2.

Results: We revealed that PSMD12 is upregulated in glioma, especially in high-grade glioma, by analyzing bioinformatics data and clinical specimens. PSMD12 upregulation was associated with poor prognosis in glioma patients. Knockdown of PSMD12 inhibited the growth of glioma cells and and decreased their invasion ability, whereas PSMD12 overexpression had the opposite effect. Mechanistic analysis revealed that PSMD12 increased the expression of nuclear factor E2-related factor 2 (Nrf2), which functions as a tumor promoter in the development of glioma. Similar to PSMD12, Nrf2, which exhibited a strong positive correlation with PSMD12, was abnormally elevated in glioma tissues and contributed to worse overall survival (OS). Nrf2 overexpression reversed the inhibitory effects induced by PSMD12 knockdown. Finally, PSMD12 enhanced the proliferation and invasion of glioma cells via Akt signaling-mediated Nrf2 expression.

Conclusions: These results suggest that PSMD12 is considered to be a crucial regulator of the development and progression of glioma and may serve as a potential biomarker or therapeutic target for the treatment of glioma.
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http://dx.doi.org/10.21037/atm-21-1481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106014PMC
April 2021

Early prone positioning therapy for patients with mild COVID-19 disease.

Med Clin (Engl Ed) 2021 Apr 17;156(8):386-389. Epub 2021 Apr 17.

Orthopedics, The Central Hospital of Dazhou, Dazhou, Sichuan, PR China.

Objective: In December 2019, Wuhan, China, experienced an outbreak of coronavirus disease 2019 (COVID-19). Some patients admitted to our hospital were treated with early prone positioning (PP). Here, we analyzed its clinical significance.

Methods: This was a retrospective observational study. We defined the early PP group as mild COVID-19 patients who were placed into a prone position within 24 h of admission; others served as the control group. We recorded basic data and outcomes of early PP and compared the results to those of controls.

Results: After 1 day of treatment, oxygenation was greater in the early PP group than in the control group (P/F: 421.6 ± 39.74 vs. 382.1 ± 38.84 mmHg [1 mmHg = 0.133 kPa],  < 0.01). And early PP group spent less total time in prone position (11.1 ± 4.17 vs. 16.9 ± 5.20 days,  < 0.01), and required shorter hospitalization duration (12.2 ± 4.49 vs. 23.2 ± 4.83 days,  < 0.001).

Conclusions: Early PP treatment can improve hypoxia and shorten the prone position time and hospitalization duration in mild COVID-19 patients. It is a potential clinically applicable intervention.
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http://dx.doi.org/10.1016/j.medcle.2020.11.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052860PMC
April 2021

A Prospective Investigation of Circulating Metabolome Identifies Potential Biomarkers for Gastric Cancer Risk.

Cancer Epidemiol Biomarkers Prev 2021 Sep 1;30(9):1634-1642. Epub 2021 Apr 1.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.

Background: Metabolomics is widely used to identify potential novel biomarkers for cancer risk. No investigation, however, has been conducted to prospectively evaluate the role of perturbation of metabolome in gastric cancer development.

Methods: 250 incident cases diagnosed with primary gastric cancer were selected from the Shanghai Women's Health and the Shanghai Men's Health Study, and each was individually matched to one control by incidence density sampling. An untargeted global profiling platform was used to measure approximately 1,000 metabolites in prediagnostic plasma. Conditional logistic regression was utilized to generate ORs and values.

Results: Eighteen metabolites were associated with gastric cancer risk at < 0.01. Among them, 11 metabolites were lysophospholipids or lipids of other classes; for example, 1-(1-enyl-palmitoyl)-GPE (P-16:0) (OR = 1.56; = 1.89 × 10). Levels of methylmalonate, a suggested biomarker of vitamin B12 deficiency, was correlated with increased gastric cancer risk (OR = 1.42; = 0.004). Inverse associations were found for three biomarkers for coffee/tea consumption (3-hydroxypyridine sulfate, quinate and N-(2-furoyl) glycine), although the associations were only significant when comparing cases that were diagnosed within 5 years after the blood collection to matched controls. Most of the identified associations were more profound in women and never smokers than their male or ever smoking counterparts and some with notable significant interactions.

Conclusions: Our study identified multiple potential risk biomarkers for gastric cancer independent of infection and other major risk factors.

Impact: New risk-assessment tools to identify high-risk population could be developed to improve prevention of gastric cancer..
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419074PMC
September 2021

Electrochemically Regulated Li Deposition by Crown Ether.

ACS Appl Mater Interfaces 2021 Apr 24;13(13):15872-15880. Epub 2021 Mar 24.

Hubei Key Lab of Electrochemical Power Sources, College of Chemistry and Molecular Science, Wuhan University, Wuhan 430072, China.

The lithium-secondary battery is considered to be the most prospective electrochemical energy storage in the upcoming decades. However, its real application still much depends on the effective strategy toward Li dendrite growth. After years of effort, many successful works have been reported on improving the solid-electrolyte interphase (SEI), either via electrolyte optimization or building artificial SEI while intrinsically adjusting the electrochemical reduction of Li has been rarely mentioned. Inspired by the successful works in the electroplating industry, in this paper, a Li-chelating agent, benzo-15-crown-5 (B15C5) was used to regulate Li-reduction kinetics from an electrochemical view. Owing to the coordination with Li, Li + complex + e → Li[complex] is generated and proved by a decreased value. B15C5 confined within the PVC matrix has been coated on a Li anode. With thus-obtained B15C5-PVC-Li, dendrite growth has been significantly reduced and prolonged cycling has been observed in Li|Li symmetric cells. Electrochemically modulated Li deposition has been further accessed by the full cell of LiFePO|Li, and 163 mA h/g capacity is stably released after 400 cycles at 1.0 mA/cm. This study provides an alternate approach to address the dendrite growth issue and sheds more light on the Li-deposition kinetics.
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http://dx.doi.org/10.1021/acsami.1c01476DOI Listing
April 2021

Genetically Inferred Telomere Length and Testicular Germ Cell Tumor Risk.

Cancer Epidemiol Biomarkers Prev 2021 06 18;30(6):1275-1278. Epub 2021 Mar 18.

Division of Cancer Epidemiology and Genetics, NCI, Rockville, Maryland.

Background: Studies evaluating the association between peripheral blood leukocyte telomere length (LTL) and testicular germ cell tumor (TGCT) risk have produced conflicting results.

Methods: Using available genotype data from the Testicular Cancer Consortium (TECAC), polygenic risk score and Mendelian randomization analyses of genetic variants previously associated with LTL were used to assess potential etiologic associations between telomere length and TGCT risk.

Results: Genetically inferred telomere length was not associated with TGCT risk among 2,049 cases and 6,921 controls with individual-level genotype data (OR, 1.02; 95% confidence interval, 0.97-1.07). Mendelian randomization analyses using summary statistic data further indicated no evidence for an association between telomere length and TGCT risk among all available TECAC participants (3,558 cases and 13,971 controls).

Conclusions: Our analyses in the largest molecular genetic testicular cancer study to date provide no evidence for an association between genetically inferred peripheral blood LTL and TGCT risk.

Impact: The lack of evidence for an overall association indicates that peripheral blood LTL is likely not a strong biomarker for TGCT risk.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172526PMC
June 2021

Tracing Lung Cancer Risk Factors Through Mutational Signatures in Never-Smokers.

Am J Epidemiol 2021 06;190(6):962-976

Epidemiologic studies often rely on questionnaire data, exposure measurement tools, and/or biomarkers to identify risk factors and the underlying carcinogenic processes. An emerging and promising complementary approach to investigate cancer etiology is the study of somatic "mutational signatures" that endogenous and exogenous processes imprint on the cellular genome. These signatures can be identified from a complex web of somatic mutations thanks to advances in DNA sequencing technology and analytical algorithms. This approach is at the core of the Sherlock-Lung study (2018-ongoing), a retrospective case-only study of over 2,000 lung cancers in never-smokers (LCINS), using different patterns of mutations observed within LCINS tumors to trace back possible exposures or endogenous processes. Whole genome and transcriptome sequencing, genome-wide methylation, microbiome, and other analyses are integrated with data from histological and radiological imaging, lifestyle, demographic characteristics, environmental and occupational exposures, and medical records to classify LCINS into subtypes that could reveal distinct risk factors. To date, we have received samples and data from 1,370 LCINS cases from 17 study sites worldwide and whole-genome sequencing has been completed on 1,257 samples. Here, we present the Sherlock-Lung study design and analytical strategy, also illustrating some empirical challenges and the potential for this approach in future epidemiologic studies.
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http://dx.doi.org/10.1093/aje/kwaa234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316614PMC
June 2021

GBP5 drives malignancy of glioblastoma via the Src/ERK1/2/MMP3 pathway.

Cell Death Dis 2021 02 19;12(2):203. Epub 2021 Feb 19.

Central Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.

Guanylate binding proteins (GBPs), a family of interferon-inducible large GTPase, play a pivotal role in cell-autonomous immunity and tumor malignant transformation. Glioblastoma (GBM) is the most prevalent and lethal primary brain tumor in adults. Here we show that GBP5 was highly expressed in GBM cell lines and in clinical samples, especially in the mesenchymal subtype. The expression levels of GBP5 were negatively correlated with the prognosis of GBM patients. Overexpression of GBP5 promoted the proliferation, migration, and invasion of GBM cells in vitro and in vivo. In contrast, silencing GBP5 by RNA interference exhibited the opposite effects. Consequently, targeting GBP5 in GBM cells resulted in impaired tumor growth and prolonged survival time of mice with GBM tumors. We further identified that the Src/ERK1/2/MMP3 axis was essential for GBP5-promoted GBM aggressiveness. These findings suggest that GBP5 may represent a novel target for GBM intervention.
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http://dx.doi.org/10.1038/s41419-021-03492-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896088PMC
February 2021

Early prone positioning therapy for patients with mild COVID-19 disease.

Med Clin (Barc) 2021 04 26;156(8):386-389. Epub 2020 Dec 26.

Orthopedics, The Central Hospital of Dazhou, Dazhou, Sichuan, PR China. Electronic address:

Objective: In December 2019, Wuhan, China, experienced an outbreak of coronavirus disease 2019 (COVID-19). Some patients admitted to our hospital were treated with early prone positioning (PP). Here, we analyzed its clinical significance.

Methods: This was a retrospective observational study. We defined the early PP group as mild COVID-19 patients who were placed into a prone position within 24h of admission; others served as the control group. We recorded basic data and outcomes of early PP and compared the results to those of controls.

Results: After 1 day of treatment, oxygenation was greater in the early PP group than in the control group (P/F: 421.6±39.74 vs. 382.1±38.84mmHg [1mmHg=0.133kPa], p<0.01). And early PP group spent less total time in prone position (11.1±4.17 vs. 16.9±5.20 days, p<0.01), and required shorter hospitalization duration (12.2±4.49 vs. 23.2±4.83 days, p<0.001).

Conclusions: Early PP treatment can improve hypoxia and shorten the prone position time and hospitalization duration in mild COVID-19 patients. It is a potential clinically applicable intervention.
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http://dx.doi.org/10.1016/j.medcli.2020.11.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834567PMC
April 2021

Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia.

Environ Int 2021 02 29;147:105975. Epub 2020 Dec 29.

Department of Internal Medicine, Kaohsiung Medical University Hospital, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.
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http://dx.doi.org/10.1016/j.envint.2020.105975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378844PMC
February 2021

A Prospective Study of Circulating Chemokines and Angiogenesis Markers and Risk of Multiple Myeloma and Its Precursor.

JNCI Cancer Spectr 2020 Apr 16;4(2):pkz104. Epub 2019 Dec 16.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

Background: Experimental and clinical studies have implicated certain chemokines and angiogenic cytokines in multiple myeloma (MM) pathogenesis. To investigate whether systemic concentrations of these markers are associated with future MM risk and progression from its precursor, monoclonal gammopathy of undetermined significance (MGUS), we conducted a prospective study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Methods: We measured concentrations of 45 immunologic and pro-angiogenic markers in sera from 241 MM case patients, 441 participants with nonprogressing MGUS, and 258 MGUS-free control participants using Luminex-based multiplex assays and enzyme-linked immunosorbent assays. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. We also evaluated absolute risk of progression using weighted Kaplan-Meier estimates. All statistical tests were two-sided.

Results: Prediagnostic levels of six markers were statistically significantly elevated among MM case patients compared with MGUS-free control participants using a false discovery rate of 10% (EGF, HGF, Ang-2, CXCL12, CCL8, and BMP-9). Of these, three angiogenesis markers were associated with future progression from MGUS to MM: EGF (fourth vs first quartile: OR = 3.01, 95% CI = 1.61 to 5.63, = .00028), HGF (OR = 2.59, 95% CI = 1.33 to 5.03, = .015), and Ang-2 (OR = 2.14, 95% CI = 1.15 to 3.98, = .07). A composite angiogenesis biomarker score substantially stratified risk of MGUS progression to MM beyond established risk factors for progression, particularly during the first 5 years of follow-up (areas under the curve of 0.71 and 0.64 with and without the angiogenesis marker score, respectively).

Conclusions: Our prospective findings provide new insights into mechanisms involved in MM development and suggest that systemic angiogenesis markers could potentially improve risk stratification models for MGUS patients.
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http://dx.doi.org/10.1093/jncics/pkz104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083234PMC
April 2020

Associations of coffee and tea consumption with lung cancer risk.

Int J Cancer 2020 Dec 16. Epub 2020 Dec 16.

Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, South Korea.

Associations of coffee and tea consumption with lung cancer risk have been inconsistent, and most lung cancer cases investigated were smokers. Included in this study were over 1.1 million participants from 17 prospective cohorts. Cox regression analyses were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Potential effect modifications by sex, smoking, race, cancer subtype and coffee type were assessed. After a median 8.6 years of follow-up, 20 280 incident lung cancer cases were identified. Compared with noncoffee and nontea consumption, HRs (95% CIs) associated with exclusive coffee drinkers (≥2 cups/d) among current, former and never smokers were 1.30 (1.15-1.47), 1.49 (1.27-1.74) and 1.35 (1.15-1.58), respectively. Corresponding HRs for exclusive tea drinkers (≥2 cups/d) were 1.16 (1.02-1.32), 1.10 (0.92-1.32) and 1.37 (1.17-1.61). In general, the coffee and tea associations did not differ significantly by sex, race or histologic subtype. Our findings suggest that higher consumption of coffee or tea is associated with increased lung cancer risk. However, these findings should not be assumed to be causal because of the likelihood of residual confounding by smoking, including passive smoking, and change of coffee and tea consumption after study enrolment.
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http://dx.doi.org/10.1002/ijc.33445DOI Listing
December 2020

Variation in oral microbiome is associated with future risk of lung cancer among never-smokers.

Thorax 2021 03 14;76(3):256-263. Epub 2020 Dec 14.

National Cancer Institute, Bethesda, Maryland, USA.

Objective: To prospectively investigate whether diversity in oral microbiota is associated with risk of lung cancer among never-smokers.

Design And Setting: A nested case-control study within two prospective cohort studies, the Shanghai Women's Health Study (n=74 941) and the Shanghai Men's Health Study (n=61 480).

Participants: Lifetime never-smokers who had no cancer at baseline. Cases were subjects who were diagnosed with incident lung cancer (n=114) and were matched 1:1 with controls on sex, age (≤2 years), date (≤30 days) and time (morning/afternoon) of sample collection, antibiotic use during the week before sample collection (yes/no) and menopausal status (for women).

Main Outcomes And Measures: Metagenomic shotgun sequencing was used to measure the community structure and abundance of the oral microbiome in pre-diagnostic oral rinse samples of each case and control. Multivariable logistic regression models were used to estimate the association of lung cancer risk with alpha diversity metrics and relative abundance of taxa. The Microbiome Regression-Based Kernel Association Test (MiRKAT) evaluated the association between risk and the microbiome beta diversity.

Results: Subjects with lower microbiota alpha diversity had an increased risk of lung cancer compared with those with higher microbial alpha diversity (Shannon: p=0.05; Simpson: p=0.04; Observed Species: p=0.64). No case-control differences were apparent for beta diversity (p=0.30). After accounting for multiple comparisons, a greater abundance of Spirochaetia (OR 1.00 (reference), OR 0.61 (95% CI 0.32 to 1.18), OR 0.42 (95% CI 0.21 to 0.85)) and Bacteroidetes (OR 1.00 (reference), OR 0.66 (95% CI 0.35 to 1.25), OR 0.31 (95% CI 0.15 to 0.64)) was associated with a decreased risk of lung cancer, while a greater abundance of the Bacilli class (OR 1.00 (reference), OR 1.49 (95% CI 0.73 to 3.08), OR 2.40 (95% CI 1.18 to 4.87)) and Lactobacillales order (OR 1.00 (reference), OR 2.15 (95% CI 1.03 to 4.47), OR 3.26 (95% CI 1.58 to 6.70)) was associated with an increased risk of lung cancer.

Conclusions: Our prospective study of never-smokers suggests that lower alpha diversity was associated with a greater risk of lung cancer and the abundance of certain specific taxa was associated with altered risk, providing further insight into the aetiology of lung cancer in the absence of active tobacco smoking.
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http://dx.doi.org/10.1136/thoraxjnl-2020-215542DOI Listing
March 2021

White Blood Cell Count and Risk of Incident Lung Cancer in the UK Biobank.

JNCI Cancer Spectr 2020 Apr 12;4(2):pkz102. Epub 2019 Dec 12.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.

Background: The contribution of measurable immunological and inflammatory parameters to lung cancer development remains unclear, particularly among never smokers. We investigated the relationship between total and differential white blood cell (WBC) counts and incident lung cancer risk overall and among subgroups defined by smoking status and sex in the United Kingdom (UK).

Methods: We evaluated 424 407 adults aged 37-73 years from the UK Biobank. Questionnaires, physical measurements, and blood were administered and collected at baseline in 2006-2010. Complete blood cell counts were measured using standard methods. Lung cancer diagnoses and histological classifications were obtained from cancer registries. Multivariable Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence intervals of incident lung cancer in relation to quartiles (Q) of total WBC and subtype-specific counts, with Q1 as the reference.

Results: There were 1493 incident cases diagnosed over an average 7-year follow-up. Overall, the highest quartile of total WBC count was statistically significantly associated with elevated lung cancer risk (HR = 1.67, 95% CI = 1.41 to 1.98). Among women, increased risks were found in current smokers ( /  = 244 / 19 464, HR = 2.15, 95% CI = 1.46 to 3.16), former smokers ( /  = 280 / 69 198, HR = 1.75, 95% CI = 1.24 to 2.47), and never smokers without environmental tobacco smoke exposure (n / n = 108 / 111 294, HR = 1.93, 95% CI = 1.11 to 3.35). Among men, stronger associations were identified in current smokers (n /  = 329 / 22 934, HR = 2.95, 95% CI = 2.04 to 4.26) and former smokers ( /  = 358/71 616, HR = 2.38, 95% CI = 1.74 to 3.27) but not in never smokers. Findings were similar for lung adenocarcinoma and squamous cell carcinoma and were driven primarily by elevated neutrophil fractions.

Conclusions: Elevated WBCs could potentially be one of many important markers for increased lung cancer risk, especially among never-smoking women and ever-smoking men.
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http://dx.doi.org/10.1093/jncics/pkz102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083262PMC
April 2020

Single-Cell Sequencing of Glioblastoma Reveals Central Nervous System Susceptibility to SARS-CoV-2.

Front Oncol 2020 16;10:566599. Epub 2020 Nov 16.

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

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the recent global COVID-19 outbreak, which led to a public health emergency. Entry of SARS-CoV-2 into human cells is dependent on the SARS-CoV receptor, angiotensin converting enzyme 2 (ACE2) receptor, and cathepsin. Cathepsin degrades the spike protein (S protein), which results in the entry of viral nucleic acid into the human host cell.

Methods: We explored the susceptibility of the central nervous system (CNS) to SARS-CoV-2 infection using single-cell transcriptome analysis of glioblastoma.

Results: The results showed that ACE2 expression is relatively high in endothelial cells (ECs), bone marrow mesenchymal stem cells (BMSCs), and neural precursor cells (NPCs). Cathepsin B (Cat B) and cathepsin (Cat L) were also strongly expressed in various cell clusters within the glioblastoma microenvironment. Immunofluorescence staining of glioma and normal brain tissue chips further confirmed that ACE2 expression co-localized with CD31, CD73, and nestin, which confirmed the susceptibility to SARS-CoV-2 of nervous system cells, including ECs, BMSCs, and NPCs, from clinical specimens.

Conclusions: These findings reveal the mechanism of SARS-CoV-2 neural invasion and suggest that special attention should be paid to SARS-CoV-2-infected patients with neural symptoms, especially those who suffered a glioma.
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http://dx.doi.org/10.3389/fonc.2020.566599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703438PMC
November 2020

Targeted Therapy of -Rearranged Neuroblastoma with BET Bromodomain Inhibitor and Proteasome Inhibitor Combination Therapy.

Clin Cancer Res 2021 Mar 11;27(5):1438-1451. Epub 2020 Dec 11.

Department of Pathology, School of Medical Sciences, UNSW Sydney, Sydney, New South Wales, Australia.

Purpose: gene rearrangement with transcriptional superenhancers leads to overexpression and neuroblastoma. No targeted therapy is available for clinical trials in patients with -rearranged neuroblastoma.

Experimental Design: Anticancer agents exerting the best synergistic anticancer effects with BET bromodomain inhibitors were identified by screening an FDA-approved oncology drug library. The synergistic effects of the BET bromodomain inhibitor OTX015 and the proteasome inhibitor carfilzomib were examined by immunoblot and flow cytometry analysis. The anticancer efficacy of OTX015 and carfilzomib combination therapy was investigated in mice xenografted with -rearranged neuroblastoma cell lines or patient-derived xenograft (PDX) tumor cells, and the role of TERT reduction in the anticancer efficacy was examined through rescue experiments in mice.

Results: The BET bromodomain protein BRD4 promoted -rearranged neuroblastoma cell proliferation through upregulating TERT expression. Screening of an approved oncology drug library identified the proteasome inhibitor carfilzomib as the agent exerting the best synergistic anticancer effects with BET bromodomain inhibitors including OTX015. OTX015 and carfilzomib synergistically reduced TERT protein expression, induced endoplasmic reticulum stress, and induced -rearranged neuroblastoma cell apoptosis which was blocked by TERT overexpression and endoplasmic reticulum stress antagonists. In mice xenografted with -rearranged neuroblastoma cell lines or PDX tumor cells, OTX015 and carfilzomib synergistically blocked TERT expression, induced tumor cell apoptosis, suppressed tumor progression, and improved mouse survival, which was largely reversed by forced TERT overexpression.

Conclusions: OTX015 and carfilzomib combination therapy is likely to be translated into the first clinical trial of a targeted therapy in patients with -rearranged neuroblastoma.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3044DOI Listing
March 2021

Patterns of Human Leukocyte Antigen Class I and Class II Associations and Cancer.

Cancer Res 2021 02 3;81(4):1148-1152. Epub 2020 Dec 3.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.

Human leukocyte antigen (HLA) gene variation is associated with risk of cancers, particularly those with infectious etiology or hematopoietic origin, given its role in immune presentation. Previous studies focused primarily on HLA allele/haplotype-specific associations. To answer whether associations are driven by HLA class I (essential for T-cell cytotoxicity) or class II (important for T-cell helper responses) genes, we analyzed GWAS from 24 case-control studies and consortia comprising 27 cancers (totaling >71,000 individuals). Associations for most cancers with infectious etiology or of hematopoietic origin were driven by multiple HLA regions, suggesting that both cytotoxic and helper T-cell responses are important. Notable exceptions were observed for nasopharyngeal carcinoma, an EBV-associated cancer, and CLL/SLL forms of non-Hodgkin lymphomas; these cancers were associated with HLA class I region only and HLA class II region only, implying the importance of cytotoxic T-cell responses for the former and CD4 T-cell helper responses for the latter. Our findings suggest that increased understanding of the pattern of HLA associations for individual cancers could lead to better insights into specific mechanisms involved in cancer pathogenesis. SIGNIFICANCE: GWAS of >71,000 individuals across 27 cancer types suggest that patterns of HLA Class I and Class II associations may provide etiologic insights for cancer.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2292DOI Listing
February 2021

Synthesis and biological evaluation of camptothecin substituted norcantharimide derivatives.

Nat Prod Res 2020 Oct 20:1-5. Epub 2020 Oct 20.

Department of Medicinal Chemistry, Zunyi Medical University, Zunyi City, China.

In this paper, a series of novel derivatives of camptothecin substituted norcantharimide was designed by mimic strategy. These compounds were synthesized in moderate yields by directly coupling CPT with N-amino acid norcantharimides. Their cytotoxicity to four human tumour cell lines (HepG2, BGC-803, SW480 and PANC-1) and normal human cell lines L-O2 and HIEC was evaluated. The synthesized CPT substituted norcantharimide analogs ( and ) showed better anti-hepatocarcinoma activity than CPT. Compounds , , , and also showed strong inhibition activity against BGC803.
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http://dx.doi.org/10.1080/14786419.2020.1834546DOI Listing
October 2020

Sequencing dropout-and-batch effect normalization for single-cell mRNA profiles: a survey and comparative analysis.

Brief Bioinform 2021 Jul;22(4)

Faculty of Engineering and IT in the University of Technology Sydney.

Single-cell mRNA sequencing has been adopted as a powerful technique for understanding gene expression profiles at the single-cell level. However, challenges remain due to factors such as the inefficiency of mRNA molecular capture, technical noises and separate sequencing of cells in different batches. Normalization methods have been developed to ensure a relatively accurate analysis. This work presents a survey on 10 tools specifically designed for single-cell mRNA sequencing data preprocessing steps, among which 6 tools are used for dropout normalization and 4 tools are for batch effect correction. In this survey, we outline the main methodology for each of these tools, and we also compare these tools to evaluate their normalization performance on datasets which are simulated under the constraints of dropout inefficiency, batch effect or their combined effects. We found that Saver and Baynorm performed better than other methods in dropout normalization, in most cases. Beer and Batchelor performed better in the batch effect normalization, and the Saver-Beer tool combination and the Baynorm-Beer combination performed better in the mixed dropout-and-batch effect normalization. Over-normalization is a common issue occurred to these dropout normalization tools that is worth of future investigation. For the batch normalization tools, the capability of retaining heterogeneity between different groups of cells after normalization can be another direction for future improvement.
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http://dx.doi.org/10.1093/bib/bbaa248DOI Listing
July 2021
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