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1.
J Exp Med ; 220(1)2023 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-36305874

RESUMEN

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.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Ratones , Animales , Receptores Inmunológicos/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Plaquetas/metabolismo , Linfocitos T CD8-positivos
2.
J Enzyme Inhib Med Chem ; 38(1): 1-11, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36305251

RESUMEN

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.


Asunto(s)
Neoplasias Pulmonares , Humanos , Crizotinib/farmacología , Crizotinib/uso terapéutico , Línea Celular Tumoral , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Apoptosis , Receptores ErbB
3.
Thorac Surg Clin ; 33(1): 109-116, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36372527

RESUMEN

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.


Asunto(s)
Neoplasias Pulmonares , Nódulos Pulmonares Múltiples , Procedimientos Quirúrgicos Robotizados , Humanos , Broncoscopía/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Fenómenos Electromagnéticos , Pulmón/diagnóstico por imagen , Pulmón/patología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología
4.
Thorac Surg Clin ; 33(1): 43-49, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36372532

RESUMEN

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.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Procedimientos Quirúrgicos Robotizados , Humanos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/patología , Neumonectomía/métodos , Cirugía Torácica Asistida por Video/métodos , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Estudios Retrospectivos
5.
Thorac Surg Clin ; 33(1): 51-60, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36372533

RESUMEN

Performing robotic thoracic lung resection is becoming an option for patients with complex thoracic disease. The robotic-assisted approach has similar survival with decreased postoperative pain, morbidity, and hospital length of stay compared with the open approach in pneumonectomy, bronchoplasty, and arterioplasty. Appropriate patient selection based on medical and surgical history combined with surgeon experience is imperative for an excellent outcome. This article will discuss the use of the robot in pneumonectomy, arterioplasty, and bronchoplasty to provide information about the technical approach and postoperative management.


Asunto(s)
Neoplasias Pulmonares , Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Neoplasias Pulmonares/cirugía , Estudios Retrospectivos , Neumonectomía , Pulmón , Cirugía Torácica Asistida por Video , Resultado del Tratamiento
6.
Oncol Rep ; 49(1)2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36367180

RESUMEN

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.


Asunto(s)
Diabetes Mellitus Tipo 2 , Neoplasias Pulmonares , Metformina , Neoplasias Pancreáticas , Anciano , Humanos , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inducido químicamente , Metformina/farmacología , Neoplasias Pancreáticas/tratamiento farmacológico
7.
J Enzyme Inhib Med Chem ; 38(1): 239-245, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36373202

RESUMEN

EGFR is a protein kinase whose aberrant activity is frequently involved in the development of non-small lung cancer (NSCLC) drug resistant forms. The allosteric inhibition of this enzyme is currently one among the most attractive approaches to design and develop anticancer drugs. In a previous study, we reported the identification of a hit compound acting as type III allosteric inhibitor of the L858R/T790M double mutant EGFR. Herein, we report the design, synthesis and in vitro testing of a series of analogues of the previously identified hit with the aim of exploring the structure-activity relationships (SAR) around this scaffold. The performed analyses allowed us to identify two compounds 15 and 18 showing improved inhibition of double mutant EGFR with respect to the original hit, as well as interesting antiproliferative activity against H1975 NSCLC cancer cells expressing double mutant EGFR. The newly discovered compounds represent promising starting points for further hit-to-lead optimisation.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Receptores ErbB/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Inhibidores de Proteínas Quinasas , Mutación , Relación Estructura-Actividad , Línea Celular Tumoral , Resistencia a Antineoplásicos
8.
J Hazard Mater ; 442: 130077, 2023 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-36209608

RESUMEN

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.


Asunto(s)
Amianto , Neoplasias Pulmonares , Zeolitas , Humanos , Fibras Minerales/toxicidad , Asbesto Crocidolita , Asbestos Serpentinas , Zeolitas/química , Asbestos Anfíboles/toxicidad , Pulmón , Neoplasias Pulmonares/inducido químicamente , Amianto/toxicidad
9.
Spectrochim Acta A Mol Biomol Spectrosc ; 285: 121839, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36191438

RESUMEN

According to the limited molecular information reflected by single spectroscopy, and the complementarity of FTIR spectroscopy and Raman spectroscopy, we propose a novel diagnostic technology combining multispectral fusion and deep learning. We used serum samples from 45 healthy controls, 44 non-small cell lung cancer (NSCLC), 38 glioma and 37 esophageal cancer patients, and the Raman spectra and FTIR spectra were collected respectively. Then we performed low-level fusion and feature fusion on the spectral, and used SVM, Convolutional Neural Network-Long-Short Term Memory (CNN-LSTM) and the multi-scale convolutional fusion neural network (MFCNN). The accuracy of low-level fusion and feature fusion models are improved by about 10% compared with single spectral models.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Aprendizaje Profundo , Neoplasias Pulmonares , Humanos , Espectrometría Raman/métodos , Espectroscopía Infrarroja por Transformada de Fourier , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Tecnología
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 285: 121940, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36208576

RESUMEN

INTRODUCTION: We analyzed the expression of PD-L1 in human lymphomas using hyperspectral imaging (HSI) compared to visual assessment (VA) and conventional digital image analysis (DIA) to strengthen further the value of HSI as a tool for the evaluation of brightfield-based immunohistochemistry (IHC). In addition, fluorescent multiplex immunohistochemistry (mIHC) was used as a second detection method to analyze the impact of a different detection method. MATERIAL AND METHODS: 18 cases (6 follicular lymphomas and 12 diffuse large B-cell lymphomas) were stained for PD-L1 by IHC and for PD-L1, CD3, and CD8 by fluorescent mIHC. The percentage of positively stained cells was evaluated with VA, HSI, and DIA for IHC and VA and DIA for mIHC. Results were compared between the different methods of detection and analysis. RESULTS: An overall high concordance was found between VA, HSI, and DIA in IHC (Cohens Kappa = 0.810VA/HSI, 0.710 VA/DIA, and 0.516 HSI/DIA) and for VAmIHCversus DIAmIHC (Cohens Kappa = 0.894). Comparing IHC and mIHC general agreement differed depending on the methods compared but reached at most a moderate agreement (Cohens Kappa between 0.250 and 0.483). This is reflected by the significantly higher percentage of PD-L1+ cells found with mIHC (pFriedman = 0.014). CONCLUSION: Our study shows a good concordance for the different analysis methods. Compared to VA and DIA, HSI proved to be a reliable tool for assessing IHC. Understanding the regulation of PD-L1 expression will further enlighten the role of PD-L1 as a biomarker. Therefore it is necessary to develop an instrument, such as HSI, which can offer a reliable and objective evaluation of PD-L1 expression.


Asunto(s)
Neoplasias Pulmonares , Linfoma , Humanos , Antígeno B7-H1/análisis , Antígeno B7-H1/metabolismo , Inmunohistoquímica , Imágenes Hiperespectrales , Biomarcadores de Tumor/metabolismo , Neoplasias Pulmonares/diagnóstico
11.
J Enzyme Inhib Med Chem ; 38(1): 176-191, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36317648

RESUMEN

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.


Asunto(s)
Antineoplásicos , Neoplasias Pulmonares , Animales , Chlorocebus aethiops , Humanos , Receptores ErbB/metabolismo , Inhibidores de Proteínas Quinasas/metabolismo , Simulación del Acoplamiento Molecular , Ensayos de Selección de Medicamentos Antitumorales , Células Vero , Células CACO-2 , Neoplasias Pulmonares/patología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Proliferación Celular , Relación Estructura-Actividad , Mutación , Pirimidinas/farmacología , Piridinas/farmacología , Estructura Molecular
12.
Oncol Rep ; 49(1)2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36382661

RESUMEN

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.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Biomarcadores de Tumor/genética , Carcinogénesis/genética , Regulación Neoplásica de la Expresión Génica
13.
Cancer Lett ; 552: 215958, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36252816

RESUMEN

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.


Asunto(s)
Adenocarcinoma del Pulmón , Proteínas Reguladoras de la Apoptosis , Proteínas de Unión al Calcio , Neoplasias Pulmonares , Humanos , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Apoptosis/genética , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Detección Precoz del Cáncer , Pulmón/patología , Neoplasias Pulmonares/metabolismo , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismo , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo
14.
Int J Cancer ; 152(2): 203-213, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36043555

RESUMEN

Opium use was recently classified as a human carcinogen for lung cancer by the International Agency for Research on Cancer. We conducted a large, multicenter case-control study evaluating the association between opium use and the risk of lung cancer. We recruited 627 cases and 3477 controls from May 2017 to July 2020. We used unconditional logistic regression analyses to estimate the odds ratios (OR) and 95% confidence intervals (CI) and measured the association between opium use and the risk of lung cancer. The ORs were adjusted for the residential place, age, gender, socioeconomic status, cigarettes, and water pipe smoking. We found a 3.6-fold risk of lung cancer for regular opium users compared to never users (95% CI: 2.9, 4.6). There was a strong dose-response association between a cumulative count of opium use and lung cancer risk. The OR for regular opium use was higher for small cell carcinoma than in other histology (8.3, 95% CI: 4.8, 14.4). The OR of developing lung cancer among opium users was higher in females (7.4, 95% CI: 3.8, 14.5) than in males (3.3, 95% CI: 2.6, 4.2). The OR for users of both opium and tobacco was 13.4 (95% CI: 10.2, 17.7) compared to nonusers of anything. The risk of developing lung cancer is higher in regular opium users, and these results strengthen the conclusions on the carcinogenicity of opium. The association is stronger for small cell carcinoma cases than in other histology.


Asunto(s)
Carcinoma de Células Pequeñas , Neoplasias Pulmonares , Adicción al Opio , Carcinoma Pulmonar de Células Pequeñas , Humanos , Femenino , Masculino , Adicción al Opio/epidemiología , Estudios de Casos y Controles , Opio/efectos adversos , Irán/epidemiología , Carcinoma Pulmonar de Células Pequeñas/epidemiología , Carcinoma Pulmonar de Células Pequeñas/etiología , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/epidemiología
15.
Ann Lab Med ; 43(1): 82-85, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36045060

RESUMEN

Cytokeratin 19 fragment antigen 21-1 (CYFRA 21-1) is useful for predicting and monitoring non-small cell lung cancer prognosis. We established reference intervals (RIs) of CYFRA 21-1 in Korean adults, including those older than 60 years. Data of 4,098 apparently healthy subjects (age range, 20-87 years) were analyzed after excluding those with a history of malignancy, high tumor marker concentrations (except CYFRA 21-1), and/or abnormal findings on a chest computed tomography scan through medical chart review. After removing two outliers, RIs of CYFRA 21-1 were determined using data of 4,096 subjects based on the non-parametric method (2.5th and 97.5th percentiles) according to CLSI guidelines EP28-A3c. The subjects were divided into two and four groups according to sex and age (20-40, 41-50, 51-60, and >60 years), respectively, and the median CYFRA 21-1 concentration was compared between the groups. The RI of CYFRA 21-1 was 0.66-3.84 ng/mL, applicable to both men and women. Regardless of sex, the CYFRA 21-1 concentration increased with age, suggesting that age-dependent RIs of CYFRA 21-1 should be applied. Rather than using a single RI provided by the manufacturer, the RI of CYFRA 21-1 should be continually verified and established in each clinical laboratory.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias , Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Queratina-19 , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , República de Corea , Adulto Joven
16.
J Ethnopharmacol ; 300: 115748, 2023 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-36162545

RESUMEN

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.


Asunto(s)
Medicamentos Herbarios Chinos , Neoplasias Pulmonares , Citotoxinas , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Flavonoides , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Medicina Tradicional China , Estudios Prospectivos , Terpenos
17.
Int J Cancer ; 152(1): 15-23, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-35579989

RESUMEN

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.


Asunto(s)
Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Quinasa de Linfoma Anaplásico/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Inhibidores de Proteínas Quinasas/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética
18.
Int J Cancer ; 152(1): 79-89, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36062503

RESUMEN

Immune checkpoint inhibitors (ICIs), which represent the new standard of care for advanced nonsmall cell lung cancer (NCSLC), are not effective in many patients. Biomarkers are needed to guide treatment. Sequencing data of an ICI-treated cohort were analyzed to identify genomic signatures predicting ICI efficacy, followed by validation using multiple independent cohorts. Their predictive mechanism was explored by evaluating the tumor immune microenvironment and tumor mutational burden (TMB). In the discovery cohort, patients carrying FGFR4 alterations (FGFR4altered ) had a better objective response rate (ORR) (50.0% vs 19.4%; P = .057) and improved median progression-free survival (mPFS) (13.17 vs 3.17 months; HR 0.37; 95% CI 0.14-1; P = .04) than wild-type patients (FGFR4wt ). In the publicly available validation cohorts, FGFR4 alterations correlated with higher ORR (100% vs 31%; P = .028), longer median overall survival (mOS) (not reached [NR] vs 11 months; HR 0.28, 95% CI 0.09-0.89, P = .02), and mPFS (NR vs 6.07 months; HR 0.05, 95% CI 0-3.94, P = .039). FGFR4 alterations were confirmed as an independent predictor of superior PFS (P = .014) and OS (P = .005). FGFR4altered patients also exhibited a significantly improved disease control rate (100% vs 60%, P = .045) and prolonged mPFS (9.70 vs 3.16 months; P = .095) compared to FGFR4wt patients in our Shanghai Pulmonary Hospital cohort. FGFR4 alterations associated with a higher TMB levels, more CD8+ T cells in the tumor stroma, and a higher M1/M2 ratio for tumor-associated macrophages in the tumor center and stroma. Thus, FGFR4 alterations may serve as a potential independent predictor of ICI efficacy in NSCLC.


Asunto(s)
Antineoplásicos Inmunológicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Linfocitos T CD8-positivos , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/farmacología , Mutación , China , Biomarcadores de Tumor/genética , Microambiente Tumoral , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/genética
19.
Sci Total Environ ; 855: 158899, 2023 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-36165824

RESUMEN

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.


Asunto(s)
Neoplasias Pulmonares , Neoplasias Inducidas por Radiación , Radón , Uranio , Humanos , Adulto , Masculino , Radón/análisis , Incidencia , Uranio/análisis , Suecia/epidemiología , Ciudades , Fumar , Neoplasias Pulmonares/epidemiología , Fumar Tabaco , Neoplasias Inducidas por Radiación/epidemiología
20.
Sci Total Environ ; 856(Pt 1): 159118, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36181805

RESUMEN

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.


Asunto(s)
Arsénico , Agua Potable , Neoplasias Pulmonares , Neoplasias Cutáneas , Neoplasias de la Vejiga Urinaria , Humanos , Agua Potable/análisis , Arsénico/efectos adversos , Arsénico/análisis , Irán/epidemiología , Años de Vida Ajustados por Discapacidad , Causas de Muerte , Medición de Riesgo , Exposición a Riesgos Ambientales/análisis
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