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2.
Medicine (Baltimore) ; 100(35): e27138, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477165

RESUMO

RATIONALE: The emergence of immune checkpoint inhibitors has brought new breakthroughs in the treatment of small cell lung cancer (SCLC). Programmed cell death-ligand 1 inhibitors combined with chemotherapy have been approved for the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC). However, programmed death 1 inhibitors have limited efficacy in the treatment of SCLC. The reason may be related to the abnormal vascular state in the tumor microenvironment. PATIENT CONCERNS: A 55-year-old male patient, presenting cough and sputum for 1 month. DIAGNOSES: The patient was clinically diagnosed with SCLC and staged as ES-SCLC. INTERVENTIONS: Etoposide combined with lobaplatin treatment every 3 weeks for 4 cycles, evaluate as progressive disease. On the basis of the original plan, combined with camrelizumab for 2 cycles, evaluation as progressive disease. Then, the patient was treated with intravenous infusion of camrelizumab plus oral anlotinib. After 4 cycles, evaluation as partial response. Then we continued to use camrelizumab combined with anlotinib treatment for the patient. At the end of 26 cycles, the chest computed tomography examination revealed that the patient had achieved complete remission. OUTCOMES: After treated with carrelizumab combined with anlotinib for 26 cycles, the curative effect was evaluated as complete remission, progression-free survival was 24 months and there was no immune-related adverse reaction during treatment period. Besides, the patient developed complicated hand-foot syndrome, but this symptom was significantly relieved after reducing the dosage of anlotinib. LESSONS: In this case, antiangiogenesis combined with programmed death 1 inhibitors significantly inhibited tumor progression. It also indicated that anlotinib concurrent carrelizumab may be a superior choice for ES-SCLC. Further clinical trials required to confifirm its effificacy and safety.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Indóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Quinolinas/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Humanos , Neoplasias Pulmonares/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Radiografia Torácica , Carcinoma de Pequenas Células do Pulmão/induzido quimicamente , Tomografia Computadorizada por Raios X
3.
Ann Glob Health ; 87(1): 73, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395196

RESUMO

Asbestos is a known human carcinogen and the chief known cause of mesothelioma. In 1997, a group of experts developed the Helsinki Criteria, which established criteria for attribution of mesothelioma to asbestos. The criteria include two methods for causation attribution: 1) a history of significant occupational, domestic, or environmental exposure and/or 2) pathologic evidence of exposure to asbestos. In 2014, the Helsinki Criteria were updated, and these attribution criteria were not changed. However, since the Helsinki Criteria were first released in 1997, some pathologists, cell biologists, and others have claimed that a history of exposure cannot establish causation unless the lung asbestos fiber burden exceeds "the background range for the laboratory in question to attribute mesothelioma cases to exposure to asbestos." This practice ignores the impact on fiber burden of clearance/translocation over time, which in part is why the Helsinki Criteria concluded that a history of exposure to asbestos was independently sufficient to attribute causation to asbestos. After reviewing the Helsinki Criteria, we conclude that their methodology is fatally flawed because a quantitative assessment of a background lung tissue fiber level cannot be established. The flaws of the Helsinki Criteria are both technical and substantive. The 1995 paper that served as the scientific basis for establishing background levels used inconsistent methods to determine exposures in controls and cases. In addition, historic controls cannot be used to establish background fiber levels for current cases because ambient exposures to asbestos have decreased over time and control cases pre-date current cases by decades. The use of scanning electron microscope (SEM) compounded the non-compatibility problem; the applied SEM cannot distinguish talc from anthophyllite because it cannot perform selected area electron diffraction, which is a crucial identifier in ATEM for distinguishing the difference between serpentine asbestos, amphibole asbestos, and talc.


Assuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Asbestos/toxicidade , Neoplasias Pulmonares/induzido quimicamente , Pulmão/patologia , Mesotelioma Maligno/induzido quimicamente , Fibras Minerais/análise , Exposição Ocupacional/efeitos adversos , Humanos , Neoplasias Pulmonares/epidemiologia , Mesotelioma Maligno/epidemiologia , Fibras Minerais/toxicidade , Exposição Ocupacional/análise , Material Particulado/análise , Material Particulado/química
4.
Environ Health Prev Med ; 26(1): 80, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34388980

RESUMO

High levels (> 100 ug/L) of arsenic are known to cause lung cancer; however, whether low (≤ 10 ug/L) and medium (10 to 100 ug/L) doses of arsenic will cause lung cancer or other lung diseases, and whether arsenic has dose-dependent or threshold effects, remains unknown. Summarizing the results of previous studies, we infer that low- and medium-concentration arsenic cause lung diseases in a dose-dependent manner. Arsenic trioxide (ATO) is recognized as a chemotherapeutic drug for acute promyelocytic leukemia (APL), also having a significant effect on lung cancer. The anti-lung cancer mechanisms of ATO include inhibition of proliferation, promotion of apoptosis, anti-angiogenesis, and inhibition of tumor metastasis. In this review, we summarized the role of arsenic in lung disease from both pathogenic and therapeutic perspectives. Understanding the paradoxical effects of arsenic in the lungs may provide some ideas for further research on the occurrence and treatment of lung diseases.


Assuntos
Arsênio , Neoplasias Pulmonares , Pulmão , Animais , Arsênio/efeitos adversos , Arsênio/uso terapêutico , Arsênio/toxicidade , Relação Dose-Resposta a Droga , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Camundongos
5.
Toxicology ; 460: 152890, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34364923

RESUMO

Arsenic is a naturally occurring metalloid strongly associated with the incidence of lung cancer. Understanding the mechanisms of arsenic-induced carcinogenesis favors the development of effective interventions to reduce the incidence and mortality of lung cancer. In this study, we investigated the role of activating transcription factor 3 (ATF3) in arsenic-induced transformation of human bronchial epithelial cells. ATF3 was upregulated during chronic exposure to 0.25 µM arsenic, and loss of ATF3 promoted arsenic-induced transformation. Moreover, arsenic-transformed ATF3 knockout (ATF3 KO-AsT) cells exhibited more aggressive characteristics, including acceleration in proliferation, resistance to chemotherapy and increase in migratory capacity. RNA-seq revealed that pathways involved in inflammation, cell cycle, EMT and oncogenesis were affected due to ATF3 deficiency during chronic arsenic exposure. Further experiments confirmed the overproduction of IL-6, IL-8 and TNFα as well as enhanced phosphorylation of AKT and STAT3 in ATF3 KO-AsT cells. Our results demonstrate that ATF3 upregulated by chronic low-dose arsenic exposure represses cell transformation and acquisition of malignant characteristics through inhibiting the production of proinflammatory cytokines and activation of downstream proteins AKT and STAT3, providing a new strategy for the prevention of carcinogen-induced lung cancer.


Assuntos
Fator 3 Ativador da Transcrição/deficiência , Arsênio/toxicidade , Brônquios/metabolismo , Mediadores da Inflamação/metabolismo , Neoplasias Pulmonares/metabolismo , Mucosa Respiratória/metabolismo , Fator 3 Ativador da Transcrição/genética , Animais , Linhagem Celular Transformada , Feminino , Técnicas de Inativação de Genes/métodos , Células HEK293 , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
6.
Front Public Health ; 9: 678040, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354974

RESUMO

Biodurability is one of the main determinants of asbestos hazardousness for human health. Very little is known about the actual persistence of asbestos in lungs and its clearance, nor about differences in this regard between the different mineralogical types of asbestos. The aim of the present study was to evaluate the amount, the dimensional characteristics and the mineralogic kinds of asbestos in lungs (measured using SEM-EDS) of a series of 72 deceased subjects who were certainly exposed to asbestos (mainly crocidolite and chrysotile) during their life. Moreover, we investigated possible correlations between the lung burden of asbestos (in general and considering each asbestos type), as well as their dimension (length, width, and l/w ratio) and the duration of exposure, the latency- in case of malignant mesothelioma (MM), the survival and the time since the end of exposure. In 62.5% of subjects, asbestos burden in lungs was lower that the threshold considered demonstrative for occupational exposure. In 29.1% of cases no asbestos was found. Chrysotile was practically not detected. The mean length of asbestos fibers and the length to width ratio were significantly related to the duration of exposure to asbestos. No other statistically significant correlations were found between the amount and dimensional characteristics of asbestos (nor with the relative amount of each asbestos type) and the other chronological variables considered. In conclusion, it was pointed out that chrysotile can be completely removed from human lungs in <8 years and, instead, amphiboles persist much more time. The present results suggest, as well, that the finding of no asbestos in lungs cannot rule out the attribution of MM to asbestos (in particular, chrysotile) inhaled in an occupational setting. This point is of crucial importance from a legal point of view.


Assuntos
Asbestos , Neoplasias Pulmonares , Asbestos/efeitos adversos , Amiantos Anfibólicos/efeitos adversos , Asbestos Serpentinas/efeitos adversos , Humanos , Pulmão , Neoplasias Pulmonares/induzido quimicamente
7.
Biomed Pharmacother ; 139: 111658, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243627

RESUMO

According to recent statistics, Lung Cancer (LC) is one of the most frequently diagnosed tumor types, representing nearly 12% of all global cancer cases. Moreover, in recent years, an increased mortality rate and incidence of this cancer were observed, especially among nonsmokers. Lung cancer patients are often characterized by poor prognosis and low survival rates, which encourages the scientific community to investigate the biochemical and molecular processes leading to the development of this malignancy. Furthermore, the mechanisms of LC formation and progression are not yet fully elucidated due to their high complexity, as well as a multitude of environmental, genetic, and molecular factors involved. Even though LC's association with exposure to cigarette smoke is indisputable, current research provides evidence that the development of this cancer can also be affected by the presence of estrogens and their interaction with several tobacco smoke components. Hence, the main goal of this brief review was to investigate reports of a possible synergy between 17ß estradiol (E2), the most biologically active estrogen, and benzo(a)pyrene (BaP), a strongly carcinogenic compound produced as a result of incomplete tobacco combustion. The literature sources demonstrate a possible carcinogenic synergy between estrogens, especially E2, and BaP, a toxic tobacco smoke component. Therefeore, the combined effect of disturbed estrogen production in cancer cells, as well as the molecular influence exerted by BaP, could explain the increased aggressiveness and rate of LC development. Summarizing, the synergistic effect of these risk factors is an interesting area of further research.


Assuntos
Benzo(a)pireno/toxicidade , Estrogênios/metabolismo , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/metabolismo , Fumar/efeitos adversos , Animais , Carcinógenos/toxicidade , Estradiol/metabolismo , Humanos , Fumaça/efeitos adversos , Tabaco/toxicidade
8.
Life Sci ; 282: 119827, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34273373

RESUMO

AIMS: We aimed to investigate the effect of PBDEs (47, 99, 209) on cellular events involved in epigenetic modification, inflammation, and epithelial mesenchymal transition (EMT). MATERIALS AND METHODS: We studied: 1) ERK1/2 phosphorylation; 2) Enhancer of Zester Homolog 2 (EZH2); 3) Histone H3 tri-methylated in lysine 27 (H3K27me3); 4) K-RAS; 5) silencing disabled homolog 2-interacting protein gene (DAB2IP), 6) let-7a; 7) Muc5AC/Muc5B, and 8) IL-8 in a 3D in vitro model of epithelium obtained with primary Normal Human Bronchial Epithelial cells (pNHBEs) or A549 cell line, chronically exposed to PBDEs (47, 99, 209). KEY FINDINGS: PBDEs (10 nM, 100 nM and 1 µM) increased ERK1/2 phosphorylation, and EZH2, H3K27me3, and K-RAS protein expression, while decreased DAB2IP and Let-7a transcripts in pNHBEs ALI culture. Furthermore PBDEs (47, 99) (100 nM) increased Muc5AC and Muc5B mRNA, and PBDE 47 (100 nM) IL-8 mRNA via EZH2 in pNHBEs. Finally, PBDEs (100 nM) affected EZH2, H3K27me3, K-RAS protein expression, and DAB2IP, Let-7a transcripts and cell invasion in A549 cells. Gsk343 (methyltransferase EZH2 inhibitor) (1 mM) and U0126 (inhibitor of MEK1/2) (10 µM) were used to show the specific effect of PBDEs. SIGNIFICANCE: PBDE inhalation might promote inflammation/cancer via EZH2 methyltransferase activity and H3K27me3, k-RAS and ERk1/2 involvement, generating adverse health outcomes of the human lung.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Células Epiteliais , Retardadores de Chama/administração & dosagem , Éteres Difenil Halogenados/efeitos adversos , Neoplasias Pulmonares , Proteínas de Neoplasias/metabolismo , Mucosa Respiratória , Células A549 , Idoso , Células Epiteliais/enzimologia , Células Epiteliais/patologia , Feminino , Retardadores de Chama/farmacologia , Éteres Difenil Halogenados/farmacologia , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mucosa Respiratória/enzimologia , Mucosa Respiratória/patologia
9.
Int J Mol Sci ; 22(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299130

RESUMO

Although cisplatin is one of most effective chemotherapeutic drugs that is widely used to treat various types of cancer, it can cause undesirable damage in immune cells and normal tissue because of its strong cytotoxicity and non-selectivity. This study was conducted to investigate the cytoprotective effects of Cudrania tricuspidata fruit-derived polysaccharides (CTPS) against cisplatin-induced cytotoxicity in macrophages, lung cancer cell lines, and a mouse model, and to explore the possibility of application of CTPS as a supplement for anticancer therapy. Both cisplatin alone and cisplatin with CTPS induced a significant cytotoxicity in A549 and H460 lung cancer cells, whereas cytotoxicity was suppressed by CTPS in cisplatin-treated RAW264.7 cells. CTPS significantly attenuated the apoptotic and necrotic population, as well as cell penetration in cisplatin-treated RAW264.7 cells, which ultimately inhibited the upregulation of Bcl-2-associated X protein (Bax), cytosolic cytochrome c, poly (adenosine diphosphateribose) polymerase (PARP) cleavage, and caspases-3, -8, and -9, and the downregulation of B cell lymphoma-2 (Bcl-2). The CTPS-induced cytoprotective action was mediated with a reduction in reactive oxygen species production and mitochondrial transmembrane potential loss in cisplatin-treated RAW264.7 cells. In agreement with the results obtained above, CTPS induced the attenuation of cell damage in cisplatin-treated bone marrow-derived macrophages (primary cells). In in vivo studies, CTPS significantly inhibited metastatic colonies and bodyweight loss as well as immunotoxicity in splenic T cells compared to the cisplatin-treated group in lung metastasis-induced mice. Furthermore, CTPS decreased the level of CRE and BUN in serum. In summation, these results suggest that CTPS-induced cytoprotective action may play a role in alleviating the side effects induced by chemotherapeutic drugs.


Assuntos
Cisplatino/toxicidade , Frutas/química , Macrófagos/efeitos dos fármacos , Melanoma Experimental/tratamento farmacológico , Moraceae/química , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Animais , Antineoplásicos/toxicidade , Apoptose , Proliferação de Células , Feminino , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Macrófagos/patologia , Melanoma Experimental/induzido quimicamente , Melanoma Experimental/patologia , Potencial da Membrana Mitocondrial , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Substâncias Protetoras/farmacologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Artigo em Inglês | MEDLINE | ID: mdl-34207798

RESUMO

The Serine and Arginine-Rich Splicing Factor 1 (SRSF1) has a proto-oncogenic function, being associated with angiogenesis and frequently overexpressed in many human malignant neoplasms. Its immunohistochemical expression has never been investigated in malignant pleural mesothelioma (MPM). We evaluated SRSF1 immunoexpression and its possible relation to angiogenesis in a selected cohort of 10 fluoro-edenite(FE)-induced MPM cases. METHODS: Immunohistochemical analyses with an anti-SRSF1 antibody were performed. We interpreted the cases as positive if tumor cell nuclei were stained; a semi-quantitative analysis of the cases was performed by evaluating the intensity of staining and the percentage of tumor positive cells. A microvessel density (MVD) count was also performed. RESULTS: High and low immunoexpressions of SRSF1 were seen in six and four MPMs, respectively. A trend of shorter overall survival was found in FE-induced MPM patients with SRSF1 overexpression. In addition, a significant association between high-MVD and high SRSF1 immunoexpression (p = 0.0476) was found. CONCLUSIONS: SRSF1 appears to be involved in MPM pathogenesis and its immunoexpression may represent a prognostic biomarker capable of identifying subgroups of patients with different prognosis. However, given the preliminary nature of the present study, further investigations on larger series, and additional in vitro studies, are required to validate our findings.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Arginina , Amiantos Anfibólicos , Biomarcadores Tumorais/genética , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Mesotelioma/induzido quimicamente , Fatores de Processamento de RNA , Serina , Fatores de Processamento de Serina-Arginina/genética
11.
BMC Cancer ; 21(1): 711, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34134640

RESUMO

BACKGROUND: This study aims to provide new insights on the role of smoking patterns and cigarette dependence in female lung cancer, and to examine differences by histological subtype. METHODS: We conducted a population-based case-control study in the great Paris area among women including 716 incident cases diagnosed between 2014 and 2017 and 757 age-matched controls. Detailed data on smoking history was collected during in-person interviews to assess intensity and duration of tobacco smoking, time since cessation, smoking habits (depth of smoke inhalation, use of filter, type of tobacco, and type of cigarettes) and Fagerström test for cigarette dependence. The comprehensive smoking index (CSI), a score modelling the combined effects of intensity, duration and time since quitting smoking was determined for each subject. Multivariable logistic regression models were fitted to calculate odds ratios (ORs) and their confidence intervals (95%CI) of lung cancer associated with smoking variables. RESULTS: Lung cancer risk increased linearly with intensity and duration of tobacco smoking while it decreased with time since cessation, to reach the risk in never-smokers after 20 years of abstinence. The combined effect of intensity and duration of tobacco smoking was more than multiplicative (p-interaction 0.012). The OR in the highest vs the lowest quartile of CSI was 12.64 (95%CI 8.50; 18.80) (p-trend < 0.001). The risk of small cell or squamous cell carcinomas increased with the CSI more sharply than the risk of adenocarcinomas. Deep smoke inhalation, dark vs blond tobacco, conventional vs light cigarettes, and unfiltered vs filtered cigarettes, as well as having mixed smoking habits, were found to be independent risk factors. Having high cigarette addiction behaviours also increased the risk after adjusting for CSI. CONCLUSION: This study provides additional insights on the effects of tobacco smoking patterns on lung cancer risk among women.


Assuntos
Neoplasias Pulmonares/induzido quimicamente , Fumar/efeitos adversos , Idoso , Estudos de Casos e Controles , Feminino , França , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo
12.
Environ Int ; 155: 106698, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34139591

RESUMO

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 (NO2; 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 NO2 concentrations in 2005-2007 were estimated with land use regression. Multivariable Cox regression was used to estimate associations between commute patterns, NO2 quartiles, and incident lung cancer. We conducted analyses stratified by NO2 (>, ≤median = 28.3 µg/m3) 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 NO2 (HRQ2 = 1.21, 95 %CI: 0.90-1.62; HRQ3 = 1.48, 95 %CI: 1.10-1.99; HRQ4 = 1.58, 95 %CI: 1.13-2.23; p-trend = 3.1 × 10-3). The public transportation association was observed among those with higher NO2 (p-interaction = 0.02). Other commute categories were not associated with risk. CONCLUSIONS: Commuters residing in high-NO2 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.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Neoplasias Pulmonares , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Bancos de Espécimes Biológicos , Estudos de Coortes , Exposição Ambiental/análise , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/epidemiologia , Material Particulado , Estudos Prospectivos , Transportes , Reino Unido/epidemiologia
13.
Ecotoxicol Environ Saf ; 220: 112378, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34082244

RESUMO

Circular RNAs (circRNAs) have been demonstrated to play critical roles in the pathogenesis of human cancers and carcinogenesis of several environmental pollutants. Nevertheless, the function of circRNAs in cadmium carcinogenesis is unclear. circ-SHPRH is down-regulated in many cancers including non-small cell lung cancer. In our present study, during cadmium-induced transformation of human bronchial epithelial BEAS-2B cells, epithelial-mesenchymal transition (EMT) was induced. Meanwhile, at the middle and late stages of cell transformation, cadmium down-regulated the expression of circ-SHPRH, as well as QKI, a tumor suppressor protein known to prevent the proliferation and EMT during progression of human cancers, compared with passage-matched control BEAS-2B cells. Overexpression of circ-SHPRH in cadmium-transformed BEAS-2B cells promoted the expression of QKI and significantly inhibited proliferation, EMT, invasion, migration and anchorage-independent growth in soft agar of the cells. Mechanistic studies showed that circ-SHPRH functioned as a sponge of miR-224-5p to regulate QKI expression. Interestingly, QKI and circ-SHPRH could form a positive-feedback loop that perpetuated circ-SHPRH/miR-224-5p/QKI axis. Collectively, our results demonstrated that circ-SHPRH inhibited cadmium-induced transformation of BEAS-2B cells through sponging miR-224-5p to regulate QKI expression under cadmium treatment. Our study uncovered a novel molecular mechanism involved in circRNAs in the development of lung cancer due to cadmium exposure.


Assuntos
Cádmio/toxicidade , DNA Helicases/metabolismo , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares/induzido quimicamente , MicroRNAs/metabolismo , RNA Circular/metabolismo , Proteínas de Ligação a RNA/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Carcinogênese/induzido quimicamente , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células , Regulação para Baixo , Poluentes Ambientais/toxicidade , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia
14.
Toxicol Appl Pharmacol ; 426: 115633, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34166680

RESUMO

Chronic exposure to environmental arsenic promotes lung cancer. Emerging evidence indicates that compromised host immunity, particularly T cell anti-tumor immunity, may play a critical role in cancer development. However, there is a knowledge gap in terms of the effects of arsenic exposure on T cell anti-tumor immunity and how that may contribute to arsenic lung carcinogenicity. Immunosuppression has been known as a risk factor for many types of cancer, including lung cancer. The development of cancer indicates the success of immunosuppression and escape of cancer cells from host anti-tumor immunity in which T cells are the major component. The anti-tumor immunity is mainly executed by CD8 cytotoxic T cells through their anti-tumor effector function, which can be regulated by immune checkpoint pathways. Some inhibitory receptors on the T cell membrane and their ligands form these pathways, among which programmed death-1 (PD-1), a T cell inhibitory receptor, and its ligand, programmed death-ligand 1 (PD-L1), are best characterized. A/J mice are naturally sensitive to pulmonary carcinogens, prone to develop spontaneous lung tumors later in life and have been frequently used as an animal model for lung tumorigenesis research. Chronic arsenic administration through drinking water has been shown to enhance tumor formation in the lungs of A/J mice. In the current study, using this mouse model we want to determine whether PD-1/PD-L1 plays a role in arsenic-enhanced lung tumorigenesis. The results showed that prolonged arsenic exposure up-regulated PD-1/PD-L1, increased regulatory T cells (Tregs), decreased CD8/Treg ratio, inhibited T cell antitumor function in the lungs and enhanced lung tumor formation, while inhibition of PD-1/PD-L1 restored CD8/Treg ratio and T cell anti-tumor effector function, and mitigated arsenic-enhanced lung tumorigenesis. In addition, inhibition of PD-1/PD-L1 could be a potential preventive strategy to mitigate the tumorigenic action of chronic arsenic exposure.


Assuntos
Arsênio/toxicidade , Antígeno B7-H1/imunologia , Carcinogênese/imunologia , Neoplasias Pulmonares/induzido quimicamente , Receptor de Morte Celular Programada 1/imunologia , Animais , Linfócitos T CD8-Positivos/imunologia , Carcinogênese/efeitos dos fármacos , Feminino , Imunoglobulina G/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Masculino , Camundongos , Linfócitos T Reguladores/imunologia
15.
Toxicol Lett ; 348: 40-49, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34052308

RESUMO

BACKGROUND: Circular RNAs (circRNAs) have an important role in the development and progression of human tumors, including lung cancer. Yet, their role in lung cancer induced by benzo(a)pyrene (B[a]P) remains unclear. In this study, circRNA chips and qRT-PCR were used to examine downregulated circRNAs in malignantly transformed 16HBE cells (16HBE-T) induced by B[a]P. Five down-regulated circRNAs were found, among which hsa_circ_0004552 (circ_CARM1) had the most significant downregulation. Consequently, the role of circ_CARM1 on 16HBE-T cells biological behavior was further examined using several in vitro experiments. MATERIALS AND METHODS: Detecting RNA expression via qRT-PCR. Fluorescence in situ hybridization (FISH) was used to identify the localization of circ_CARM1 in 16HBE-T. The effect of circ_CARM1 on cell behavior (cell migration, proliferation, and apoptosis) was explored by transfecting cells with a vector carrying an overexpression and then using wound healing, transwell migration assay, and flow cytometry. Also, the regulation mechanism for circ_CARM1, miR-1288-3p, and CTNNBIP1 was studied by Dual-Luciferase® Reporter (DLR™) Assay System and western blotting. RESULTS: Reduced expression of circ_CARM1 is observed in 16HBE-T. The overexpression of circ_CARM1 further inhibited the migration of 16HBE-T cells but did not affect cell proliferation and apoptosis. Furthermore, bioinformatic analysis and Dual-Luciferase® Reporter (DLR™) Assay System showed that the competitive binding of circ_CARM1 and miR-1288-3p enhanced the expression of CTNNBIP1, thereby inhibiting the migration of 16HBE-T cells. CONCLUSION: Downregulation of circ_CARM1 can stimulate the expression of miR-1288-3p, thereby reducing the expression of CTNNBIP1, spurring cell migration.


Assuntos
7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido/toxicidade , Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Pulmonares/patologia , RNA Circular/fisiologia , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Transformação Celular Neoplásica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/induzido quimicamente , MicroRNAs/fisiologia
16.
Environ Res ; 198: 111214, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33974841

RESUMO

Although outdoor air pollution including particulate matter (PM) was classified as carcinogenic to humans based on accumulating epidemiological evidence, these findings were suggested mostly from low-dose environments in North America and Europe. We aimed to examine the association of long-term exposure to PM ≤ 10 and 2.5 µm in diameter (PM10 and PM2.5) and nitrogen dioxide (NO2) with lung cancer incidence using a population-based cohort in the Seoul Metropolitan Area (SMA), South Korea. Our study included 83,478 people residing in the SMA and followed up for 2007-2015 from the National Health Insurance Service-National Sample Cohort. This cohort was constructed based on the National Health Insurance database that contains sociodemographic and medical information under universal health coverage. Individual long-term concentrations of PM10, PM2.5, and NO2 were estimated at people's district-level and annually-updated residential addresses for the previous 5 years by using previously-validated prediction models. We applied a time-dependent Cox proportional hazards model and estimated hazard ratios (HRs) per 10 µg/m3 and 10 ppb increases in PM and NO2, respectively, after adjusting for individual characteristics. During 9 years of follow-up, 489 lung cancer new cases occurred (714,012 person-year). The adjusted HRs for PM10 were greater than 1 but statistically non-significant (HR = 1.15; 95% CI = 0.88-1.52). We also did not find associations for PM2.5 and NO2. Despite null associations for the total population, our subgroup analysis suggested associations with PM in family members with cancer (PM10: HR = 2.59, 95% CI = 1.26-5.32; PM2.5: 5.55, 1.09-27.91) and in those who have smoked more than 1 pack per day (1.77, 0.96-3.25; 3.81, 1.00-14.44) or for less than 20 years (2.81; 1.13-7.07; 2.02, 0.21-19.23). Our study based on a highly urbanized population exposed to relatively high air pollution provides no evidence of the association between PM and lung cancer incidence in the total population but indicates the potential susceptibility in heavy smokers for relatively short periods and family members of cancer patients. Future studies should re-examine the association using improved exposure assessment and extended population.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Neoplasias Pulmonares , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Europa (Continente) , Humanos , Incidência , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/epidemiologia , América do Norte , Material Particulado/análise , Material Particulado/toxicidade , República da Coreia/epidemiologia , Seul/epidemiologia
17.
PLoS One ; 16(4): e0249790, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33831090

RESUMO

Despite the use of large amounts of asbestos in the 1990s, few studies have been conducted in Korea on occupational and environmental asbestos exposure and lung cancer risk. The main aim of this study was to estimate the risk of lung cancer development caused by occupational and environmental asbestos exposures in residents of South Chungcheong Province, where about half of the asbestos mines in Korea operated. We conducted a case-control study, for which the information on asbestos exposure history and demographic characteristics was provided by the Environmental Health Center for asbestos of Soonchunhyang University Cheonan Hospital. After adjusting for all covariates, the odds ratios for lung cancer tended to increase with higher exposure probability for both occupational as well as environmental asbestos. The relative risk of occupational asbestos exposure was higher than that of environmental exposure; the interaction of co-exposure was not statistically significant. The estimated means of the latency period were significantly shorter in participants who were engaged in the production of asbestos-containing products and in those who lived near asbestos industries as compared to other groups.


Assuntos
Asbestos/efeitos adversos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/etiologia , Doenças Profissionais/induzido quimicamente , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Pulmão/efeitos dos fármacos , Masculino , República da Coreia
18.
Am J Epidemiol ; 190(9): 1784-1792, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33847736

RESUMO

The evidence for styrene's being a human lung carcinogen has been inconclusive. Occupational cohorts within the reinforced-plastics industry are an ideal population in which to study this association because of their relatively high levels of exposure to styrene and lack of concomitant exposures to other known carcinogens. However, healthy worker survivor bias (HWSB), where healthier workers stay employed longer and thus have higher exposure potential, is a likely source of confounding bias for exposure-response associations, in part due to styrene's acute effects. Through December 31, 2016, we studied a cohort of 5,163 boatbuilders exposed to styrene in Washington State who were employed between 1959 and 1978; prior regression analyses had demonstrated little evidence for an exposure-response relationship between styrene exposure and lung cancer mortality. Based on estimates of necessary components of HWSB, we found evidence for a potentially large HWSB. Using g-estimation of a structural nested model to account for HWSB, we estimated that 1 year of styrene exposure at more than 30 parts per million accelerated time to lung cancer death by 2.29 years (95% confidence interval: 1.53, 2.94). Our results suggest possibly strong HWSB in our small cohort and indicate that large, influential studies of styrene-exposed workers may suffer from similar biases, warranting a reassessment of the evidence of long-term health effects of styrene exposure.


Assuntos
Neoplasias Pulmonares/induzido quimicamente , Indústria Manufatureira , Exposição Ocupacional/efeitos adversos , Plásticos/toxicidade , Navios , Estireno/toxicidade , Idoso , Viés , Relação Dose-Resposta a Droga , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Indústria Manufatureira/estatística & dados numéricos , Pessoa de Meia-Idade , Modelos Estatísticos , Análise de Regressão , Sobreviventes/estatística & dados numéricos , Washington/epidemiologia
19.
J Hazard Mater ; 416: 125839, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-33887567

RESUMO

Benzo[a]pyrene (B[a]P) is a typical carcinogen associated with increased lung cancer risk, but the underlying mechanisms remain unclear. This study aimed to investigate epigenome-wide DNA methylation associated with B[a]P exposure and their mediation effects on B[a]P-lung cancer association in two lung cancer case-control studies of 462 subjects. Their plasma levels of benzo[a]pyrene diol epoxide-albumin (BPDE-Alb) adducts and genome-wide DNA methylations were separately detected in peripheral blood by using enzyme-linked immunosorbent assay (ELISA) and genome-wide methylation arrays. The epigenome-wide meta-analysis was performed to analyze the associations between BPDE-Alb adducts and DNA methylations. Mediation analysis was applied to assess effect of DNA methylation on the B[a]P-lung cancer association. We identified 15 CpGs associated with BPDE-Alb adducts (P-meta < 1.0 × 10-5), among which the methylation levels at five loci (cg06245338, cg24256211, cg15107887, cg02211741, and cg04354393 annotated to UBE2O, SAMD4A, ACBD6, DGKZ, and SLFN13, respectively) mediated a separate 38.5%, 29.2%, 41.5%, 47.7%, 56.5%, and a joint 58.2% of the association between BPDE-Alb adducts and lung cancer risk. Compared to the traditional factors [area under the curve (AUC) = 0.788], addition of these CpGs exerted improved discriminations for lung cancer, with AUC ranging 0.828-0.861. Our results highlight DNA methylation alterations as potential mediators in lung tumorigenesis induced by B[a]P exposure.


Assuntos
Benzo(a)pireno , Neoplasias Pulmonares , 7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido , Transportadores de Cassetes de Ligação de ATP , Benzo(a)pireno/toxicidade , Adutos de DNA , Metilação de DNA , Epigenoma , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Enzimas de Conjugação de Ubiquitina
20.
Environ Sci Pollut Res Int ; 28(32): 43515-43527, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33834342

RESUMO

The study examines the prophylactic action of artichoke leaf hydroethanolic extract (ALE) and artichoke flower head hydroethanolic extract (AFE) against diethylnitrosamine (DEN)/acetylaminofluorene (AAF)-induced lung cancer in Wistar rats. To chemically induce lung cancer, DEN was injected intraperitoneally twice a week for a fortnight at a dose of 150 mg/kg body weight (b.w.), followed by oral supplementation of AAF four times a week for 3 weeks at a dose of 20 mg/kg b.w. The DEN/AAF-administered rats were orally supplemented with ALE or AFE at a dose of 100 mg/kg b.w. for 17 weeks starting from the 1st week of DEN injection to the 17th week of the experiment. The lung cancerous injuries resulting from DEN/AAF-administration were significantly improved by the treatment with ALE and AFE as observed in histological examination. In addition, there was a significant reduction in lung lipid peroxidation, with resultant elevation in antioxidant enzymatic activity of glutathione-S-transferase, glutathione peroxidase, glutathione reductase, and superoxide dismutase as well as glutathione content in DEN/AAF-supplemented rats treated with ALE and AFE as compared to DEN/AAF-administered control. The lung tumor suppressor protein (p53) and B-cell lymphoma-2 (Bcl-2) mRNA expression significantly increased in the rats treated with ALE and AFE. In conclusion, the finding showed that ALE and AFE produced anti-cancer prophylactic effects against DEN/AAF-induced lung cancer in rats via suppression of oxidative stress and improved apoptotic signal induction.


Assuntos
Cynara scolymus , Neoplasias Pulmonares , Animais , Dietilnitrosamina/toxicidade , Flores , Fígado/metabolismo , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/prevenção & controle , Estresse Oxidativo , Extratos Vegetais/metabolismo , Folhas de Planta , Ratos , Ratos Wistar
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