The biology and management of non-small cell lung cancer

Nature, Journal Year: 2018, Volume and Issue: 553(7689), P. 446 - 454

Published: Jan. 1, 2018

Language: Английский

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Lung Cancer 2020

Clinics in Chest Medicine, Journal Year: 2020, Volume and Issue: 41(1), P. 1 - 24

Published: Jan. 31, 2020

Language: Английский

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Annual Report to the Nation on the Status of Cancer, part I: National cancer statistics

Cancer, Journal Year: 2018, Volume and Issue: 124(13), P. 2785 - 2800

Published: May 22, 2018

BACKGROUND The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), National Institute (NCI), North Association of Central Registries (NAACCR) collaborate to provide annual updates on cancer occurrence trends in United States. METHODS Incidence data were obtained from CDC‐funded NCI‐funded population‐based registry programs compiled by NAACCR. Data deaths Center Health Statistics Vital System. Trends age‐standardized incidence death rates all cancers combined leading types sex, race, ethnicity estimated joinpoint analysis expressed as percent change. Stage distribution 5‐year survival stage at diagnosis calculated breast cancer, colon rectum (colorectal) lung bronchus melanoma skin. RESULTS Overall 2008 2014 decreased 2.2% per year among men but stable women. 1999 2015 1.8% 1.4% Among men, during most recent period (2010‐2014) 7 17 common types, (2011‐2015) 11 18 types. women, declined cancers, 14 20 cancers. Death sites, including (men women), colorectal female breast, prostate. increased liver women); pancreas brain other nervous system oral cavity pharynx only); soft tissue, heart nonmelanoma skin uterus. higher than women racial ethnic groups. For sites combined, black white had highest compared with groups, Non‐Hispanic mortality those Hispanic ethnicity. Five‐year cases diagnosed 2007 through 2013 ranged 100% (stage I) 26.5% IV) 88.1% 12.6% 55.1% 4.2% 99.5% 16% children, overall 0.8% 2010 2014, 1.5% 2011 2015. CONCLUSIONS Overall, there continue be significant declines both Differences race group remain. Progress reducing has not occurred sites. Examining highlights potential benefits associated early detection treatment. 2018;124:2785‐2800 . © 2018

Language: Английский

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Annual report to the nation on the status of cancer, part I: National cancer statistics

Cancer, Journal Year: 2020, Volume and Issue: 126(10), P. 2225 - 2249

Published: March 12, 2020

Background The American Cancer Society, the Centers for Disease Control and Prevention, National Institute, North Association of Central Registries collaborate to provide annual updates on cancer occurrence trends in United States. Methods Data new diagnoses during 2001 through 2016 were obtained from Prevention‐funded Institute‐funded population‐based registry programs compiled by Registries. deaths 2017 Center Health Statistics' Vital Statistics System. Trends incidence death rates all cancers combined leading types sex, racial/ethnic group, age estimated joinpoint analysis characterized average percent change most recent 5 years (2012‐2016 2013‐2017 mortality). Results Overall, decreased 0.6% per year 2012 2016, but differed type. Among males, stable overall among non‐Hispanic white males other groups; increased 17 common cancers, 7 (including prostate), lung bronchus [lung] colorectal). females, groups, increasing 0.2% year; 8 18 breast), 6 colorectal), 4 lung). 1.5% 2013 2017, decreasing 1.8% 1.4% females. During both females each 11 19 14 20 lung, colorectal, breast). largest declines observed melanoma skin (decreasing 6.1% 6.3% females) 4.8% 3.7% females). children younger than 15 years, an 0.8% 2017. adolescents young adults aged 39 0.9% 1.0% Conclusions Although continue decline, are leveling off slightly These reflect population changes risk factors, screening test use, diagnostic practices, treatment advances. Many can be prevented or treated effectively if they found early. Population‐based mortality data used inform efforts decrease burden States regularly monitor progress toward goals.

Language: Английский

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Anticancer, antimicrobial and photocatalytic activities of green synthesized magnesium oxide nanoparticles (MgONPs) using aqueous extract of Sargassum wightii

Journal of Photochemistry and Photobiology B Biology, Journal Year: 2018, Volume and Issue: 190, P. 86 - 97

Published: Nov. 23, 2018

Language: Английский

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Downregulation of GSDMD attenuates tumor proliferation via the intrinsic mitochondrial apoptotic pathway and inhibition of EGFR/Akt signaling and predicts a good prognosis in non‑small cell lung cancer

Oncology Reports, Journal Year: 2018, Volume and Issue: unknown

Published: Aug. 7, 2018

Gasdermin D (GSDMD) is a newly discovered pyroptosis executive protein, which can be cleaved by inflammatory caspases and essential for secretion of IL‑1β, making it critical mediator inflammation. However, the precise role GSDMD in carcinogenesis remains nearly unknown. Considering vital inflammation tumorigenesis, we investigated biological function non‑small cell lung cancer (NSCLC). Our study demonstrated that protein levels were significantly upregulated NSCLC compared to these matched adjacent tumor specimens. Higher expression was associated with aggressive traits including larger size more advanced tumor-node-metastasis (TNM) stages. In addition, high indicated poor prognosis adenocarcinoma (LUAD), but not squamous carcinoma (LUSC). Knockdown restricted growth vitro vivo. Notably, intrinsic extrinsic activation pyroptotic (NLRP3/caspase‑1) signaling GSDMD‑deficient cells induced another type programmed death (apoptosis), instead pyroptosis. depletion activated cleavage caspase‑3 PARP, promoted via mitochondrial apoptotic pathways. co‑expression analyses correlation between EGFR/Akt signaling. Collectively, our results revealed crosstalk apoptosis cells. attenuated proliferation promoting inhibiting NSCLC. conclution, an independent prognostic biomarker LUAD.

Language: Английский

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The superior efficacy of anti-PD-1/PD-L1 immunotherapy in KRAS-mutant non-small cell lung cancer that correlates with an inflammatory phenotype and increased immunogenicity

Cancer Letters, Journal Year: 2019, Volume and Issue: 470, P. 95 - 105

Published: Oct. 20, 2019

Immune checkpoint inhibitors against PD-1/PD-L1 yield improved survival rates of KRAS-mutant NSCLC patients, who conferred a poor prognosis without effective targeted therapy until now. Yet, the underlying association between KRAS mutations and immune responses remains unclear. We performed an integrated analysis data from publicly available repositories clinical center cohorts to explore mutation status tumor immunity-associated features, including PD-L1 expression, CD8+ tumor-infiltrating lymphocytes (TILs) mutational burden (TMB). Our results revealed that are correlated with inflammatory microenvironment immunogenicity, resulting in superior patient response inhibitors. Meanwhile, three-pool further confirmed patients show remarkable benefit anti-PD-1/PD-L1 immunotherapy. In addition, lung adenocarcinoma mouse model was established estimate relative efficacy anti-PD-L1 monoclonal antibody monotherapy or combination treatment docetaxel versus alone. Most surprisingly, we found blockade combined did not promote anti-tumor response. These findings uncover may be optimal therapeutic schedule harboring mutations.

Language: Английский

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KRAS G12C NSCLC Models Are Sensitive to Direct Targeting of KRAS in Combination with PI3K Inhibition

Clinical Cancer Research, Journal Year: 2018, Volume and Issue: 25(2), P. 796 - 807

Published: Oct. 16, 2018

Abstract Purpose: KRAS-mutant lung cancers have been recalcitrant to treatments including those targeting the MAPK pathway. Covalent inhibitors of KRAS p.G12C allele allow for direct and specific inhibition mutant in cancer cells. However, as other targeted therapies, therapeutic potential these can be impaired by intrinsic resistance mechanisms. Therefore, combination strategies are likely needed improve efficacy. Experimental Design: To identify maximally leverage we defined response a panel NSCLC models bearing G12C–activating mutation vitro vivo. We used second-generation G12C inhibitor, ARS1620 with improved bioavailability over first generation. analyzed downstream effectors signaling mechanisms underlying differential response. candidate strategies, performed high-throughput drug screening across 112 drugs ARS1620. validated top hits vivo patient-derived xenograft models. Results: Response was heterogeneous Adaptive involving reactivation pathway failure induce PI3K–AKT inactivation were identified events. several model-specific effective combinations well broad-sensitizing effect PI3K-AKT–mTOR inhibitors. The G12Ci+PI3Ki on resistant single-agent xenografts Conclusions: Our findings suggest that adaptation some instances limit efficacy but PI3K overcome this resistance.

Language: Английский

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Machine learning of serum metabolic patterns encodes early-stage lung adenocarcinoma

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: July 16, 2020

Abstract Early cancer detection greatly increases the chances for successful treatment, but available diagnostics some tumours, including lung adenocarcinoma (LA), are limited. An ideal early-stage diagnosis of LA large-scale clinical use must address quick detection, low invasiveness, and high performance. Here, we conduct machine learning serum metabolic patterns to detect LA. We extract direct by optimized ferric particle-assisted laser desorption/ionization mass spectrometry within 1 s using only 50 nL serum. define a range 100–400 Da with 143 m/z features. diagnose sensitivity~70–90% specificity~90–93% through sparse regression patterns. identify biomarker panel seven metabolites relevant pathways distinguish from controls ( p < 0.05). Our approach advances design analysis early holds promise as an efficient test low-cost rollout clinics.

Language: Английский

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Polymyxin B hemoperfusion in endotoxemic septic shock patients without extreme endotoxemia: a post hoc analysis of the EUPHRATES trial

Intensive Care Medicine, Journal Year: 2018, Volume and Issue: 44(12), P. 2205 - 2212

Published: Nov. 23, 2018

The EUPHRATES trial examined the impact of polymyxin B hemoperfusion (PMX) on mortality in patients with septic shock and endotoxemia, defined as EAA ≥ 0.60. No difference was found 28-day all-cause mortality. However, showed that some burden endotoxin activity extreme (EAA 0.9). In a post hoc analysis, we evaluated PMX use measured between 0.6–0.89. Post-hoc analysis for 194 0.6–0.89 who completed two treatments (PMX or sham). primary end point at 28 days adjusted APACHE II score baseline mean arterial pressure (MAP). Additional points included changes MAP, cumulative vasopressor index (CVI), median reduction, ventilator-free (VFD), dialysis-free (DFD) hospital length stay. Subpopulations analyzed were site type infection those norepinephrine dose > 0.1 mcg/kg/min baseline. At days, 23 88 (26.1%) group died versus 39 106 (36.8%) sham [risk 10.7%, OR 0.52, 95% CI (0.27, 0.99), P = 0.047]. When unadjusted variables, 0.11. survival time longer than [HR 0.56 (95% 0.33, 0.95) 0.03]. treatment compared greater change MAP [median (IQR) 8 mmHg (− 0.5, 19.5) vs. 4 4.0, 11) 0.04] VFD 20 (0.5, 23.5) 6 (0, 20), 0.004]. There no significant differences other points. PMX-treated bacterial growth culture [PMX, 6/30 (20%) sham, 13/31 (41.9%), 0.005]. population − 12.9% (range: increase 49.2%–reduction 86.3%). above PMX: 6/38 (15.7%) 15/49 (30.6%), 0.08. These hypothesis-generating results, based an exploratory trial, suggest measurable responses 0.6 to 0.89 pressure, Clinicaltrials.gov Identifier: NCT01046669. Funding Spectral Medical Incorporated.

Language: Английский

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