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1.
Cell Signal ; 101: 110525, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36400383

RESUMO

MicroRNAs (miRNAs), small non-coding RNAs approximately 20-25 nt in length, play important roles via directly binding to the corresponding 3' UTR of target mRNAs. Recent research has shown that miRNAs cover a wide range of diseases, including several types of cancer. It is interesting to note that miR-206 operates as a tumor suppressor and is downregulated in abundant cancer types, such as breast cancer, lung cancer, colorectal cancer, and so forth. Interestingly, a growing number of studies have also reported that miR-206 could function as an oncogene and promote tumor cell proliferation. Thereby, miR-206 may act as either oncogenes or tumor suppressors under certain conditions. In addition, it was widely acknowledged that restoring tumor-suppressor miR-206 has emerged as an unconventional cancer therapy strategy. Therefore, miR-206 might be a newfangled procedure for achieving a more significant treatment outcome for cancer patients. This review summarizes the role of miR-206 in several cancer types and the contributions made between miR-206 and the diagnosis, treatment, and drug resistance of solid tumors.


Assuntos
Neoplasias da Mama , Neoplasias Pulmonares , MicroRNAs , Humanos , Feminino , Oncogenes , MicroRNAs/genética , Proliferação de Células/genética
2.
Cell Signal ; 101: 110486, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36208704

RESUMO

Melanoma is one of the most consequential skin cancer with a rising death incidences. Silent but belligerent nature of metastatic sprouting is the leading cause of melanoma related mortality. Invasion of metastatic cells and re-expression of E-Cadherin play the crucial role in the establishment of secondary tumor at distal sites. Thus, manipulation of tumor cell invasion in parallel to regulation of E-Cadherin expression can be considered as potential anti-metastatic strategy. Evidences suggested key role of reactive oxygen species associated ROCK activities in the modulation of metastatic invasion via F-actin stabilization. Here, we first-time report Decylubiquinone, a dietary Coenzyme Q10 analog, as an effective attenuator of pulmonary metastatic melanoma in C57BL/6 mice. Current study depicted detailed molecular interplay associated with Decylubiquinone mediated phosphorylation of ROCKII at Tyr722 along with reduced phosphorylation of ROCKII Ser1366 leading to suppression of Limk1/2-Cofilin-F-actin stabilization axis that finally restricted B16F10 melanoma cell invasion at metastatic site. Analysis further deciphered the role of HNF4α as its nuclear translocation modulated E-Cadherin expression, the effect of reactive oxygen species dependent ROCKII activity in secondarily colonized B16F10 melanoma cells at lungs. Thus unbosoming of related signal orchestra represented Decylubiquinone as a potential remedial agent against secondary lung melanoma.


Assuntos
Neoplasias Pulmonares , Melanoma Experimental , Melanoma , Camundongos , Animais , Actinas , Espécies Reativas de Oxigênio , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Caderinas/metabolismo , Melanoma/metabolismo , Pulmão/metabolismo , Neoplasias Pulmonares/metabolismo , Metástase Neoplásica/patologia , Melanoma Experimental/patologia , Movimento Celular
3.
Int J Cancer ; 152(1): 7-14, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35362560

RESUMO

We aimed to determine participation in low-dose computed tomography (LDCT) of individuals with a family history of common cancers in a population-based screening program to provide timely evidence in high-risk populations in China. The analysis was conducted using data from the Cancer Screening Program in Urban China (CanSPUC), which recruited 282 377 participants aged 40 to 74 years from eight cities in the Henan province. Using the CanSPUC risk score system, 55 428 participants were evaluated to have high risk for lung cancer and were recommended for LDCT. We calculated the overall and group-specific participation rates using family history of common cancers and compared differences in participation rates between different groups. Odds ratios (ORs) and 95% confidence intervals were derived by multivariable logistic regression. Of the 55 428 participants, 22 260 underwent LDCT (participation rate, 40.16%). Family history of lung, esophageal, stomach, liver and colorectal cancer was associated with increased participation in LDCT screening. The odds of participants with a family history of one, two, three and four or more cancer cases undergoing LDCT screening were 1.9, 2.7, 2.8 and 3.5 times, respectively, than those without a family history of cancer. Compared to those without a history of cancer, participation in LDCT gradually increased as the number of cancer cases in the family increased (P < .001). Our findings suggest that there is room for improvement in lung cancer screening given the relatively low participation rate. Lung cancer screening in populations with a family history of cancer may improve efficiency and cost-effectiveness; however, this requires further verification.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Tomografia Computadorizada por Raios X/métodos , Programas de Rastreamento , China/epidemiologia
4.
Int J Cancer ; 152(1): 15-23, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35579989

RESUMO

Global phase 3 trials have demonstrated the priority of several next-generation anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs). However, clinical studies are conducted with specific populations that differ from the real world. The study aimed to evaluate the clinical outcomes of alectinib in real-world settings. Patients with advanced nonsmall-cell lung cancer (NSCLC) and EML4-ALK fusion were enrolled from two medical centers between June 2018 and June 2020. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS) to alectinib. The secondary endpoint was response of brain metastases. The risk factors for disease progression were also investigated. In total, 127 patients with advanced NSCLC were enrolled into this study. Of them, 54.3% received first-line alectinib. The 1- and 2-year PFS rates were 77.4% and 68.3%, respectively. ORR and disease control rate (DCR) were 53.5% and 91.3%, respectively. Among patients with brain metastases, intracranial ORR and DCR were 63.6% and 88.6%, respectively. In addition, we found that "crizotinib pretreatment", "liver metastasis" and "TP53 co-mutation" were individually associated with shorter PFS in alectinib treatment. In conclusion, this study confirms the salient clinical outcomes of alectinib for ALK-fusion-driven NSCLC patients with or without brain metastases, adding real-world evidence to the priority of alectinib in clinical practice.


Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Quinase do Linfoma Anaplásico/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/farmacologia
5.
J Ethnopharmacol ; 302(Pt A): 115814, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36240975

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Kanglaite injection (KLTi), a Chinese herbal medicine, is used as an adjuvant treatment for non-small-cell lung cancer (NSCLC). AIMS OF THE STUDY: To provide an evidence-based endorsement for the clinical application and selection of KLTi by evaluating the reporting quality, methodological quality, risk of bias, and evidence quality of systemic reviews (SRs). MATERIALS AND METHODS: SRs of KLTi adjuvant therapy of NSCLC were searched by using 12 databases, consulting experts, and retrieving relevant conference papers until 2022.03.24. The treatment group received KLTi in combination with other therapies, regardless of dosage, duration, or the therapy combined. Network meta-analyses and SRs using repeated data were excluded. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines 2009, A MeaSurement Tool to Assess systematic Reviews, Risk of Bias in Systematic Review, and the Grading of Recommendations Assessment, Development and Evaluation were used to assess the quality of reports, methodological quality, risk of bias, and level of evidence; R was used for visual analysis of the relevant contents. RESULTS: Twenty SRs (13 Chinese and 7 English articles), all authored by Chinese authors as the first author, were included. The reporting information of most included studies was relatively complete (21-27 points), accounting for three-fourths of the total literature. The quality of the methods used in all studies was critically low. The risk of bias was mostly high. Results of the evidence summary showed that among the "moderate" evidence, KLTi combined with chemotherapy had benefits of 9.7-16.4% for objective response rate (ORR) (11 SRs), 8.1-14% for disease control rate (four SRs), and 20.1-28.6% for quality of life (12 SRs) compared with those of chemotherapy alone. The incidence of gastrointestinal symptoms (five SRs) was reduced by 11.5%-23.2%, while that of leukopenia (four SRs) improved by 19.5-29.2%. Combined radiotherapy and targeted therapy had benefits of 25.9% and 16.8%, respectively, in ORR and 31.3% and 22.8%, respectively, in quality of life (the quality of evidence was "low"). The results depicted that treatment with two courses of KLTi produce the best results. CONCLUSION: Our results suggest that KLTi, whether combined with chemotherapy, radiotherapy, or targeted therapy, has an effect on ORR and quality of life and induces adverse reactions, such as leukopenia, nausea, and vomiting. It may improve patient survival; however, the impact of its low-grade quality on the immune function remains undetermined. Owing to the low reporting quality and methodological quality and high risk of bias of the SRs and the included studies, clinical application of KLTi remains unelucidated; higher-quality SRs and randomized controlled trials are necessary in the future.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Leucopenia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , China , Neoplasias Pulmonares/tratamento farmacológico , Medicamentos sem Prescrição/uso terapêutico , Qualidade de Vida , Revisões Sistemáticas como Assunto
6.
J Ethnopharmacol ; 300: 115748, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36162545

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: With high mortality and morbidity rates, lung cancer (LC) has become one of the major threats to human health. The treatment strategies for LC currently face issues, such as drug resistance and body tolerance. Traditional Chinese medicine (TCM) is characterized by novel pharmacological mechanisms, low toxicity, and limited side effects. TCM includes a substantial number of biologically active ingredients, several of which are effective monomeric agents against LC. An increasing number of researchers are focusing their efforts on the discovery of active anti-cancer ingredients in TCM. AIM OF THE REVIEW: In this review, we summarized the anti-LC mechanisms of five types of TCM monomeric compounds. Our goal is to provide research ideas for the identification of new prospective medication candidates for the treatment of LC. MATERIALS AND METHODS: We collected reports on the anti-LC effects of TCM monomers from web databases, including PubMed, Science Direct, Web of Science, and Europe PubMed Central. Among the keywords used were "lung cancer," "traditional Chinese medicine," "pharmacology," and their combinations thereof. Then, we systematically summarized the anti-LC efficacy and related mechanisms of TCM monomers. RESULTS: Based on the available literature, this paper reviewed the therapeutic effects and mechanisms of five types of TCM monomers on LC. The characteristics of TCM monomers include the capabilities to suppress the tumor cell cycle, inhibit proliferation, induce apoptosis, promote autophagy, inhibit tumor cell invasion and metastasis, and enhance efficacy or reduce drug resistance when combined with cytotoxic agents and other methods to arrest the progression of LC and prolong the survival of patients. CONCLUSIONS: TCM contains numerous flavonoids, alkaloids, terpenoids, polyphenols, and other active compounds that are effective against LC. Given their chemical structure and pharmacological properties, these monomers are suitable as candidate drugs for the treatment of LC.


Assuntos
Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Citotoxinas , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Flavonoides , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Medicina Tradicional Chinesa , Estudos Prospectivos , Terpenos
7.
J Hazard Mater ; 442: 130077, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36209608

RESUMO

This work reviews the bio-chemical mechanisms leading to adverse effects produced when mineral fibres are inhaled and transported in the lungs from the perspective of a mineralogist. The behaviour of three known carcinogenic mineral fibres (crocidolite, chrysotile, and fibrous-asbestiform erionite) during their journey through the upper respiratory tract, the deep respiratory tract and the pleural cavity is discussed. These three fibres have been selected as they are the most socially and economically relevant mineral fibres representative of the classes of chain silicates (amphiboles), layer silicates (serpentine), and framework silicates (zeolites), respectively. Comparison of the behaviour of these fibres is made according to their specific crystal-chemical assemblages and properties. Known biological and subsequent pathologic effects which lead and contribute to carcinogenesis are critically reviewed under the mineralogical perspective and in relation to recent progress in this multidisciplinary field of research. Special attention is given to the understanding of the cause-effect relationships for lung cancer and malignant mesothelioma. Comparison with interstitial pulmonary fibrosis, or "asbestosis", will also be made here. This overview highlights open issues, data gaps, and conflicts in the literature for these topics, especially as regards relative potencies of the three mineral fibres under consideration for lung cancer and mesothelioma. Finally, an attempt is made to identify future research lines suitable for a general comprehensive model of the carcinogenicity of mineral fibres.


Assuntos
Amianto , Neoplasias Pulmonares , Zeolitas , Humanos , Fibras Minerais/toxicidade , Asbesto Crocidolita , Asbestos Serpentinas , Zeolitas/química , Amiantos Anfibólicos/toxicidade , Pulmão , Neoplasias Pulmonares/induzido quimicamente , Amianto/toxicidade
8.
J Enzyme Inhib Med Chem ; 38(1): 1-11, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36305251

RESUMO

The effect of the combination of 10-Hydroxycamptothecin (HCPT) and crizotinib (CRI) on EGFR- and KRAS-mutant lung cancer cells was investigated and the conjugates of the two drugs were synthesised. HCPT combined with CRI synergistically inhibited the cell growth and proliferation of H1975, HCC827, and H460 without aggravating adverse effect on the normal cells. The combination synergistically enhanced the cell apoptosis rate through releasing Cyto-C by activation of Bcl-2 family-mediated mitochondrial signalling, which was associate with inactivating of EGFR related downstream signalling pathways including AKT, ERK, JNK, and p38 MAPK. Based on this synergy, the conjugates of HCPT and CRI (compounds CH-1 and CH-2) with different chemical bonds were synthesised. Compound CH-1 exhibited stronger cytotoxicity than HCPT and CRI alone or in combination. The combination of HCPT and CRI might be a promising therapeutic regimen and the conjugate CH-1was a potential target drug for the treatment of lung cancer.


Assuntos
Neoplasias Pulmonares , Humanos , Crizotinibe/farmacologia , Crizotinibe/uso terapêutico , Linhagem Celular Tumoral , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Apoptose , Receptores ErbB
9.
Oncol Rep ; 49(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36382661

RESUMO

Lung cancer (LC) is the leading cause of cancer­related death, with high incidence and mortality rate. Early diagnosis and treatment of LC are imperative to improve the 5­year survival rate for patients with LC. In recent years, miRNAs as promising biomarkers with high sensitivity and specificity for LC have been studied increasingly. In LC regulatory networks, miRNAs play crucial roles in the occurrence, development and metastasis of non­small cell lung cancer (NSCLC), such as oncogenic factors, tumor suppressors and regulators. Dysfunctional miRNAs perform tumor­suppressive or oncogenic functions in the regulation of cell proliferation, invasion, apoptosis, cell cycle disorder and angiogenesis by negatively regulating target genes. In the present review, the biological process of miRNAs was firstly summarized and recent advances in the mechanism of miRNAs involved in tumor formation and development were described. In addition, the present review concentrated on the latest findings on the miRNAs related with circulating free and extracellular vesicles in the early diagnosis of NSCLC. Additionally, the diagnostic performances of circulating free and extracellular vesicles­associated miRNAs in NSCLC were contrasted. Owing to the increased stability and wide­ranging practical applicability, miRNA may be one promising biomarker for NSCLC diagnosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Biomarcadores Tumorais/genética , Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica
10.
Cancer Lett ; 552: 215958, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36252816

RESUMO

Since lung cancer remains the leading cause of cancer death globally, there is an urgent demand for novel therapeutic targets. We carried out a CRISPR interference (CRISPRi) loss-of-function screen for human lung adenocarcinoma (LUAD) targeting 2098 deregulated genes using a customized algorithm to comprehensively probe the functionality of every resolvable transcriptional start site (TSS). CASP8AP2 was identified as the only hit that significantly affected the viability of all eight screened LUAD cell lines while the viability of non-transformed lung cells was only moderately impacted. Knockdown (KD) of CASP8AP2 induced both autophagy and apoptotic cell death pathways. Systematic expression profiling linked the AP-1 transcription factor to the CASP8AP2 KD-induced cancer cell death. Furthermore, inhibition of AP-1 reverted the CASP8AP2 silencing-induced phenotype. Overall, the tailored CRISPRi screen profiled the impact of over 2000 genes on the survival of eight LUAD cell lines and identified the CASP8AP2 - AP-1 axis mediating lung cancer viability.


Assuntos
Adenocarcinoma de Pulmão , Proteínas Reguladoras de Apoptose , Proteínas de Ligação ao Cálcio , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Apoptose/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Detecção Precoce de Câncer , Pulmão/patologia , Neoplasias Pulmonares/metabolismo , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo
11.
J Enzyme Inhib Med Chem ; 38(1): 176-191, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36317648

RESUMO

Herein, a set of pyridine and pyrimidine derivatives were assessed for their impact on the cell cycle and apoptosis. Human breast cancer (MCF7), hepatocellular carcinoma (HEPG2), larynx cancer (HEP2), lung cancer (H460), colon cancers (HCT116 and Caco2), and hypopharyngeal cancer (FADU), and normal Vero cell lines were used. Compounds 8 and 14 displayed outstanding effects on the investigated cell lines and were further tested for their antioxidant activity in MCF7, H460, FADU, HEP2, HEPG2, HCT116, Caco2, and Vero cells by measuring superoxide dismutase (SOD), malondialdehyde content (MDA), reduced glutathione (GSH), and nitric oxide (NO) content. Besides, Annexin V-FITC apoptosis detection and cell cycle DNA index using the HEPG-2 cell line were established on both compounds as well. Furthermore, compounds 8 and 14 were assessed for their EGFR kinase (Wild and T790M) inhibitory activities, revealing eligible potential. Additionally, molecular docking, ADME, and SAR studies were carried out for the investigated candidates.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Animais , Chlorocebus aethiops , Humanos , Receptores ErbB/metabolismo , Inibidores de Proteínas Quinases/metabolismo , Simulação de Acoplamento Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Células Vero , Células CACO-2 , Neoplasias Pulmonares/patologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células , Relação Estrutura-Atividade , Mutação , Pirimidinas/farmacologia , Piridinas/farmacologia , Estrutura Molecular
12.
Sci Total Environ ; 855: 158899, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36165824

RESUMO

Bedrock U has been used as a proxy for local indoor radon exposure. A preliminary assessment of cancer incidence rate in a cohort of 809,939 adult males living in 9 different Swedish counties in 1986 has been used to correlate the cumulative lung cancer and total cancer (excluding lung) incidence rates between 1986 and 2020, respectively with the municipality average value of bedrock U concentration obtained from Swedish geological Survey (SGU). To control for regional difference in tobacco smoking, data on county average smoking prevalence, obtained from a survey conducted by the Public Health Agency of Sweden from 2001 to 2004, was used. Regression analysis shows that there is a significant positive correlation between smoking prevalence adjusted lung cancer incidence rate in males and the municipality bedrock U concentration (R2 = 0.273 with a slope 5.0 ±â€¯0.87·10-3 ppm-1). The correlation is even more significant (R2 = 0.759 with a slope = 4.8 ±â€¯0.25·10-3 ppm-1) when assessed on population weighted cancer incidence data binned in nine intervals of municipality average bedrock U concentration (ranging from 0.97 to 4.9 ppm). When assessing the corresponding correlations for total cancer incidence rate (excluding cancer of the lung) with adjustment for smoking prevalence, there appears to be no or little correlation with bedrock U concentration (R2 = 0.031). We conclude that an expanded future study needs age-standardized cancer incidence data to obtain a more consistent exposure-response model. Such model could be used to predict future lung cancer cases based on geological survey maps of bedrock U as an alternative to laborious indoor radon measurements, and to discern what future lung cancer rates can be expected for a population nearing zero smoking prevalence, with and without radon prevention.


Assuntos
Neoplasias Pulmonares , Neoplasias Induzidas por Radiação , Radônio , Urânio , Humanos , Adulto , Masculino , Radônio/análise , Incidência , Urânio/análise , Suécia/epidemiologia , Cidades , Fumar , Neoplasias Pulmonares/epidemiologia , Fumar Tabaco , Neoplasias Induzidas por Radiação/epidemiologia
13.
Environ Res ; 216(Pt 1): 114485, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36206924

RESUMO

BACKGROUND: The new WHO air quality guidelines indicate that the air pollution disease burden is greater than previously reported. We aimed to estimate the air pollution disease burden and its economic cost in Barcelona to inform local action. METHODS: We used a quantitative health impact assessment to estimate the non-accidental mortality and incidence of childhood asthma and lung cancer attributable to long-term air pollution exposure in the city of Barcelona (Spain) in 2018-2019. We used the population weighted mean of PM2.5 and NO2 assigned at the geocoded address during the study period and the 2021 WHO air quality guidelines as counterfactual scenario to estimate new annual cases attributable to each pollutant separately and combined. We estimated the social cost of attributable deaths and the health care cost of childhood asthma and lung cancer attributable cases. We also estimated attributable mortality by city district and the mortality avoidable by achieving the WHO air quality interim targets. RESULTS: Mean exposure was 17 µg/m3 for PM2.5 and 39 µg/m3 for NO2. Total combined air pollution attributable mortality was 13% (95%CI = 9%-17%), corresponding to 1,886 deaths (95%CI = 1,296-2,571) and a social cost of €1,292 million (95%CI = 888-1,762) annually. Fifty-one percent (95%CI = 21%-71%) and 17% (95%CI = 7%-29%) of new cases of childhood asthma and lung cancer were attributable to air pollution with a health care cost of €4.3 and €2.7 million, respectively. Achieving the first unmet WHO air quality interim targets for PM2.5 and for NO2 would avoid 410 deaths and €281 million annually. CONCLUSION: Air pollution in Barcelona represents a huge disease and economic burden, which is greater than previous estimates. Much stronger measures to reduce PM2.5 and NO2 levels are urgently needed. Until the WHO air quality guidelines are met in the city, achieving each WHO air quality interim targets would avoid hundreds of deaths each year.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Asma , Neoplasias Pulmonares , Humanos , Poluentes Atmosféricos/análise , Material Particulado , Dióxido de Nitrogênio , Poluição do Ar/análise , Efeitos Psicossociais da Doença , Asma/epidemiologia , Neoplasias Pulmonares/epidemiologia , Exposição Ambiental/análise
14.
Environ Res ; 216(Pt 1): 114471, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36208787

RESUMO

BACKGROUND: Industrial complex (IC) residence is associated with higher cancer incidence in adults and children. However, the effect on young adults and the residence duration are not well described. Since the beginning of the 20th century, the Haifa bay area (HBA) has a major IC area with petrochemical industry complex and many other industries. The objectives of the current study were to estimate the association between IC residence and cancer incidence and to evaluate the effect of the residence duration. METHODS: This study is a registry-based cohort (N = 1,022,637) with a follow-up of 21 years. Cox regression models were used to evaluate the associations (hazards ratios (HR) and its 95% confidence intervals (CIs)) between HBA residence and incidence of all cancer sites (n = 62,049) and for site-specific cancer types including: lung cancer (n = 5398), bladder cancer (n = 3790), breast cancer (n = 11,310), prostate cancer (n = 6389) skin cancer (n = 4651), pancreatic cancer (n = 2144) and colorectal cancer (n = 8675). We evaluated the effect of the duration of exposure as categories of 7 years for those with 15 years of follow-up. RESULTS: IC residence was associated with higher risk for all cancer sites (HR:1.09, 95% CI: 1.06-1.12), for site-specific cancer incidence including: lung cancer (HR:1.14, 95% CI: 1.04-1.23), bladder cancer (HR:1.11, 95% CI: 1.01-1.23), breast cancer (HR:1.04, 95% CI: 0.98-1.10), prostate cancer (HR:1.07, 95% CI: 0.99-1.16), skin cancer (HR:1.22, 95% CI: 1.12-1.33) and colorectal cancer (HR:1.10, 95%CI: 1.03-1.17). Similar risk was also observed among young adults (HR: 1.10, 95% CI: 1.00-1.20). In the analyses for the duration of exposure, IC residence was associated with higher risk for all cancer site for the longest residence duration (15-21 years: HR: 1.08, 95% CI: 1.04-1.13). CONCLUSIONS: Harmful associations were found between IC residence and incidence of all cancer sites and site-specific cancers types. Our findings add to the limited evidence of associations between IC residence and cancer in young adults.


Assuntos
Neoplasias da Mama , Neoplasias Colorretais , Neoplasias Pulmonares , Neoplasias , Neoplasias da Próstata , Neoplasias Cutâneas , Neoplasias da Bexiga Urinária , Adulto Jovem , Criança , Masculino , Humanos , Seguimentos , Neoplasias da Bexiga Urinária/epidemiologia , Israel/epidemiologia , Neoplasias/epidemiologia , Incidência , Sistema de Registros , Neoplasias da Mama/epidemiologia , Neoplasias Pulmonares/epidemiologia , Fatores de Risco
15.
Oncol Rep ; 49(1)2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36367180

RESUMO

Lung cancer is the most common type of cancer and the leading cause of cancer­associated death worldwide. Despite the availability of various treatments such as surgery, chemoradiotherapy, targeted drugs and immunotherapy, treatment is expensive and the prognosis remains poor. At present, lung cancer drugs and treatment programs remain in a state of continuous exploration and research to improve the prognosis, and to reduce the pain and economic burden for the patients. Type 2 diabetes is a common chronic disease in middle­aged and elderly patients, leading to significantly increased complications of cardiovascular and cerebrovascular diseases. Epidemiology shows that type 2 diabetes also increases the incidence of malignant tumors, including lung, liver, colorectal and pancreatic cancer. Metformin is a biguanide, widely used as a first­line oral drug in treating type 2 diabetes. Metformin has a hypoglycemic effect and a biological antitumor impact, reducing the incidence of various tumors, including lung cancer, and improving the prognosis of patients with tumors. The anti­lung cancer effect of metformin involves a variety of mechanisms that can improve the therapeutic effect and prognosis of lung cancer, as a single drug or in combination with other therapies. The present study aims to review the associated literature and the therapeutic effects of metformin on lung cancer.


Assuntos
Diabetes Mellitus Tipo 2 , Neoplasias Pulmonares , Metformina , Neoplasias Pancreáticas , Idoso , Humanos , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/induzido quimicamente , Metformina/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico
16.
Sci Total Environ ; 856(Pt 1): 159118, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36181805

RESUMO

The health risk and burden of disease induced by exposure to inorganic arsenic (iAs) through drinking water and foodstuffs in Iran were assessed. The iAs levels in drinking water and foodstuffs (15 food groups) in the country were determined through systematic review of three international databases (PubMed, Scopus, and Web of Science) and meta-analysis. Based on the results of the systematic review and meta-analysis, the average iAs levels in drinking water and all the food groups at the national level were lower than the maximum permissible levels. The total average non-carcinogenic risk of dietary exposure to iAs in terms of hazard index (HI) was 3.4. The average incremental lifetime cancer risk (ILCR) values of dietary exposure to iAs were determined to be 1.5 × 10-3 for skin cancer, 1.0 × 10-3 for lung cancer, and 4.0 × 10-4 for bladder cancer. Over two-thirds of the non-carcinogenic and carcinogenic risk of dietary exposure to iAs was attributed to bread and cereals, drinking water, and rice. The total annual cancer incidence, deaths, disability-adjusted life years (DALYs), death rate, and DALY rate (per 100,000 people) were assessed to be 3347 (95 % uncertainty interval: 1791 to 5999), 1302 (697 to 2336), 72,606 (38,833 to 130,228), 1.6 (0.87 to 2.9), and 91 (49 to 160). The contribution of mortality in the attributable burden of disease was 95.1 %. The contributions of the causes in the attributable burden of disease were 72 % for lung cancer, 16 % for bladder cancer, and 12 % for skin cancer. Due to the significant attributable burden of disease, national and subnational action plans consisting of multi-disciplinary approaches for risk management of dietary exposure to iAs, especially for the higher arsenic-affected areas and high-risk population groups in the country are recommended.


Assuntos
Arsênio , Água Potável , Neoplasias Pulmonares , Neoplasias Cutâneas , Neoplasias da Bexiga Urinária , Humanos , Água Potável/análise , Arsênio/efeitos adversos , Arsênio/análise , Irã (Geográfico)/epidemiologia , Anos de Vida Ajustados pela Incapacidade , Causas de Morte , Medição de Risco , Exposição Ambiental/análise
17.
J Exp Med ; 220(1)2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36305874

RESUMO

Current understanding of tumor immunosuppressive mechanisms forms the basis for modern day immunotherapies. Immunoregulatory role of platelets in cancer remains largely elusive. Platelets from non-small cell lung cancer (NSCLC) patients revealed a distinct activation phenotype. TREM-like transcript 1 (TLT-1), a platelet protein, was increased along with enhanced extracellular release from NSCLC platelets. The increased platelet TLT-1 was also evident in humanized mice with patient-derived tumors. In immunocompetent mice with syngeneic tumors, TLT-1 binding to T cells, in vivo, led to suppression of CD8 T cells, promoting tumor growth. We identified direct interaction between TLT-1 and CD3ε on T cells, implicating the NF-κB pathway in CD8 T cell suppression. Anti-TLT-1 antibody rescued patients' T cells from platelet-induced suppression ex vivo and reduced tumors in mice in vivo. Clinically, higher TLT-1 correlated with reduced survival of NSCLC patients. Our findings thus identify TLT-1 as a platelet-derived immunosuppressor that suppresses CD8 T cells and demonstrate its therapeutic and prognostic significance in cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Camundongos , Animais , Receptores Imunológicos/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Plaquetas/metabolismo , Linfócitos T CD8-Positivos
18.
J Enzyme Inhib Med Chem ; 38(1): 51-66, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36305287

RESUMO

ARS-interacting multifunctional proteins 2 (AIMP2) is known to be a powerful tumour suppressor. However, the target AIMP2-DX2, AIMP2-lacking exon 2, is often detected in many cancer patients and cells. The predominant approach for targeting AIMP-DX2 has been attempted via small molecule mediated inhibition, but due to the lack of satisfactory activity against AIMP2-DX2, new therapeutic strategies are needed to develop a novel drug for AIMP2-DX2. Here, we report the use of the PROTAC strategy that combines small-molecule AIMP2-DX2 inhibitors with selective E3-ligase ligands with optimised linkers. Consequently, candidate compound 45 was found to be a degrader of AIMP2-DX2. Together, these findings demonstrate that our PROTAC technology targeting AIMP2-DX2 would be a potential new strategy for future lung cancer treatment.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Humanos , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Pulmão , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Proteínas Nucleares/metabolismo , Proteólise
19.
Thorac Surg Clin ; 33(1): 109-116, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36372527

RESUMO

Pulmonary nodules (lesions <3 cm in size) are commonly identified on computed tomographic scans, but radiographic features alone are inadequate to reliably differentiate between benign and malignant etiologies. Therefore, tissue biopsy remains the standard approach to determine the appropriate treatment course for many patients with pulmonary nodules. Although percutaneous biopsy is highly accurate, it poses substantial risks of procedural complications, including pneumothorax and bleeding. Robotic bronchoscopy has recently been developed to overcome many of the limitations of previous navigational platforms. Here, we explore the currently available systems for robotic bronchoscopy-in particular, electromagnetic-navigation robotic-assisted bronchoscopy and shape-sensing robotic-assisted bronchoscopy.


Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Procedimentos Cirúrgicos Robóticos , Humanos , Broncoscopia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Fenômenos Eletromagnéticos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia
20.
Thorac Surg Clin ; 33(1): 43-49, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36372532

RESUMO

Pulmonary segmentectomy is a parenchymal-sparing alternative approach to lobectomy for the surgical management of stage I NSCLC. Segmentectomy is an anatomical resection that requires meticulous dissection and exposure of the segmental pulmonary artery, vein, and bronchus. The open thoracotomy approach has been gradually replaced by video-assisted thoracoscopy (VATS) and robotic-assisted minimally invasive approaches for performing segmentectomy for surgical resection for early-stage lung cancer. There are 2 recent randomized studies that demonstrated that pulmonary segmentectomy is equivalent to lobectomy for the surgical management of NSCLC tumors 2 cm or smaller. This article will review robotic-assisted segmentectomy techniques that are performed for the surgical management of stage I nonsmall cell lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Procedimentos Cirúrgicos Robóticos , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida/métodos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos
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