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1.
J Transl Med ; 20(1): 404, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064415

RESUMO

Microparticles (MPs) are 100-1000 nm heterogeneous submicron membranous vesicles derived from various cell types that express surface proteins and antigenic profiles suggestive of their cellular origin. MPs contain a diverse array of bioactive chemicals and surface receptors, including lipids, nucleic acids, and proteins, which are essential for cell-to-cell communication. The tumour microenvironment (TME) is enriched with MPs that can directly affect tumour progression through their interactions with receptors. Liquid biopsy, a minimally invasive test, is a promising alternative to tissue biopsy for the early screening of lung cancer (LC). The diverse biomolecular information from MPs provides a number of potential biomarkers for LC risk assessment, early detection, diagnosis, prognosis, and surveillance. Remodelling the TME, which profoundly influences immunotherapy and clinical outcomes, is an emerging strategy to improve immunotherapy. Tumour-derived MPs can reverse drug resistance and are ideal candidates for the creation of innovative and effective cancer vaccines. This review described the biogenesis and components of MPs and further summarised their main isolation and quantification methods. More importantly, the review presented the clinical application of MPs as predictive biomarkers in cancer diagnosis and prognosis, their role as therapeutic drug carriers, particularly in anti-tumour drug resistance, and their utility as cancer vaccines. Finally, we discussed current challenges that could impede the clinical use of MPs and determined that further studies on the functional roles of MPs in LC are required.


Assuntos
Vacinas Anticâncer , Micropartículas Derivadas de Células , Neoplasias Pulmonares , Micropartículas Derivadas de Células/metabolismo , Humanos , Biópsia Líquida , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Prognóstico , Microambiente Tumoral
2.
Contrast Media Mol Imaging ; 2022: 2471039, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072634

RESUMO

The clinical efficacy, serum tumor markers, and miR-34 expression levels of bronchial artery embolization (BAE) in patients with lung cancer with hemoptysis are investigated. 92 patients with lung cancer hemoptysis treated in our hospital from January 2019 to December 2021 are randomly selected, and 92 patients are randomly divided into the conservative group and the BAE group according to the number table method, with 46 patients in each group. The efficacy, overall survival (OS) rate, coagulation function, hemoptysis volume, serum tumor markers, and miR-34 expression are compared among all groups at different time points. The experimental results show that the BAE treatment can promote the expression of miR-34 and inhibit the expression of tumor markers, so it can improve the efficacy of patients with lung cancer hemoptysis, improve the symptoms of hemoptysis and coagulation function, and prolong the life cycle of patients.


Assuntos
Neoplasias Pulmonares , MicroRNAs , Biomarcadores Tumorais , Artérias Brônquicas , Hemoptise/terapia , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/terapia , MicroRNAs/genética , Estudos Retrospectivos
3.
Dis Markers ; 2022: 1479246, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072895

RESUMO

Commensal microbiome is a key factor of lung cancer immunotherapy efficacy. Elucidating the role of specific strains as bacterial markers in immunotherapy has drawn great attention from the academia. At present, most preclinical studies about the relationship between bacterial markers and immunotherapy rely on the syngeneic mouse models. However, mice differ greatly from humans in immune system and tumor characteristics. In this study, humanized mouse models based on peripheral blood mononuclear cells (PBMCs) immune reconstitution and lung cancer cell line-derived xenograft (CDX) or patient-derived xenograft (PDX) were constructed. The PBMC-PDX model was shown to be superior to the PBMC-CDX model in preserving tumor heterogeneity and construction time-saving. Through optimizing the experimental process, the time it took for humanized models to evaluate the effect of cancer treatment was reduced to 42 days. Next, by utilizing PBMC-PDX mice treated with antibiotics (ATB), the role of Bifidobacterium longum in lung cancer immunotherapy was studied. It was found that although both Bifidobacterium longum and immunotherapy drug pembrolizumab alone showed suppressing tumor growth, the efficacy of pembrolizumab was attenuated when administrated to mice colonized with Bifidobacterium longum. Further exploration revealed that Bifidobacterium longum caused significant changes in the proportion of human CD45+ cells in the PBMC-PDX model. The PBMC-PDX model has the potential to be applied as an efficient platform to support evaluation of bacterial markers in immunotherapy research and facilitate development of precision medicine targeting human commensal bacteria.


Assuntos
Leucócitos Mononucleares , Neoplasias Pulmonares , Animais , Bactérias , Biomarcadores , Modelos Animais de Doenças , Humanos , Fatores Imunológicos , Imunoterapia , Neoplasias Pulmonares/terapia , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Pathol Oncol Res ; 28: 1610555, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110249

RESUMO

The biological macromolecule Nocardia rubra cell-wall skeleton (Nr-CWS) has well-established immune-stimulating and anti-tumor activities. However, the role of Nr-CWS on natural killer (NK) cells remains unclear. Here, we explore the function and related mechanisms of Nr-CWS on NK cells. Using a tumor-bearing model, we show that Nr-CWS has slightly effect on solid tumor. In addition, using a tumor metastasis model, we show that Nr-CWS suppresses the lung metastasis induced by B16F10 melanoma cells in mice, which indicates that Nr-CWS may up-regulate the function of NK cells. Further investigation demonstrated that Nr-CWS can increase the expression of TRAIL and FasL on spleen NK cells from Nr-CWS treated B16F10 tumor metastasis mice. The spleen index and serum levels of TNF-α, IFN-γ, and IL-2 in B16F10 tumor metastasis mice treated with Nr-CWS were significantly increased. In vitro, the studies using purified or sorted NK cells revealed that Nr-CWS increases the expression of CD69, TRAIL, and FasL, decreases the expression of CD27, and enhances NK cell cytotoxicity. The intracellular expression of IFN-γ, TNF-α, perforin (prf), granzyme-B (GrzB), and secreted TNF-α, IFN-γ, IL-6 of the cultured NK cells were significantly increased after treatment with Nr-CWS. Overall, the findings indicate that Nr-CWS could suppress the lung metastasis induced by B16F10 melanoma cells, which may be exerted through its effect on NK cells by promoting NK cell terminal differentiation (CD27lowCD11bhigh), and up-regulating the production of cytokines and cytotoxic molecules.


Assuntos
Neoplasias Pulmonares , Melanoma , Animais , Citocinas , Granzimas , Imunoterapia , Interleucina-2/farmacologia , Interleucina-6 , Células Matadoras Naturais , Neoplasias Pulmonares/terapia , Camundongos , Perforina , Rhodococcus , Fator de Necrose Tumoral alfa
5.
Front Immunol ; 13: 938269, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059450

RESUMO

Background: An open, observational, three-arm clinical study aimed at investigating the efficacy of different neoadjuvant therapies (neoadjuvant immunotherapy with(out) chemotherapy, neoadjuvant chemotherapy, and neoadjuvant targeted therapy) in operable locally advanced non-small cell lung cancer (NSCLC) was conducted (NCT04197076). We report an interim analysis of 49 of 53 evaluable patients. Methods: This study was conducted at Shanghai Chest Hospital and included eligible NSCLC patients who were 18 years old and had clinical stage IIB-IIIB disease. All 49 patients had surgical resection within 4-6 weeks after 2-3 cycles of neoadjuvant treatment consisting of immunotherapy (24 patients), chemotherapy (16 patients), and a targeted therapy (9 patients) regimen starting on the first day of each 21-day cycle. Pathologic complete response (pCR) was evaluated as the primary endpoint. Major pathological response (MPR) and tumor regression rate (TRR) were also evaluated. Results: An improved pathologic complete response was achieved in the neoadjuvant immunotherapy arm compared with the neoadjuvant chemotherapy arm and neoadjuvant targeted therapy arm [20.8% (5/24) vs. 6.3% (1/16) vs. 0.0% (0/9); P = 0.089, 95% CI 0.138-0.151]. More importantly, we found that the curative effect of the neoadjuvant immunotherapy arm in pCR+MPR was better than that of the neoadjuvant chemotherapy arm and neoadjuvant targeted therapy arm [45.8% (11/24) vs. 18.8% (3/16) vs. 0.0% (0/9); P = 0.006, 95% confidence interval, 0.008-0.012]. Different neoadjuvant therapies had a statistically significant effect on postoperative pathological tumor downstaging (P = 0.017). Conclusions: Neoadjuvant immunotherapy was associated with a trend toward better pCR than the neoadjuvant chemotherapy arm and neoadjuvant targeted therapy. Curative effect (pCR + MPR) was significantly better with neoadjuvant immunotherapy (P = 0.006, 95% confidence interval, 0.008-0.012). Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04197076?recrs=a&cond=NCT04197076&draw=2&rank=1.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adolescente , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , China , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Terapia Neoadjuvante , Estadiamento de Neoplasias
6.
Front Endocrinol (Lausanne) ; 13: 970269, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060936

RESUMO

Background: Cuproptosis is a recently found non-apoptotic cell death type that holds promise as an emerging therapeutic modality in lung adenocarcinoma (LUAD) patients who develop resistance to radiotherapy and chemotherapy. However, the Cuproptosis' role in the onset and progression of LUAD remains unclear. Methods: Cuproptosis-related genes (CRGs) were identified by a co-expression network approach based on LUAD cell line data from radiotherapy, and a robust risk model was developed using deep learning techniques based on prognostic CRGs and explored the value of deep learning models systematically for clinical applications, functional enrichment analysis, immune infiltration analysis, and genomic variation analysis. Results: A three-layer artificial neural network risk model was constructed based on 15 independent prognostic radiotherapy-related CRGs. The risk model was observed as a robust independent prognostic factor for LUAD in the training as well as three external validation cohorts. The patients present in the low-risk group were found to have immune "hot" tumors exhibiting anticancer activity, whereas the high-risk group patients had immune "cold" tumors with active metabolism and proliferation. The high-risk group patients were more sensitive to chemotherapy whereas the low-risk group patients were more sensitive to immunotherapy. Genomic variants did not vary considerably among both groups of patients. Conclusion: Our findings advance the understanding of cuproptosis and offer fresh perspectives on the clinical management and precision therapy of LUAD.


Assuntos
Adenocarcinoma de Pulmão , Aprendizado Profundo , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/terapia , Regulação Neoplásica da Expressão Gênica , Humanos , Imunoterapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Prognóstico
7.
Immunotherapy ; 14(14): 1121-1131, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36047777

RESUMO

Background: PD-L1 and VISTA are important checkpoint control stations and play an immunomodulatory role in patients with non-small-cell lung cancer. Method: The expression levels of PD-L1 and VISTA between pre- and post-treatment tumor tissue were compared. Results: While PD-L1 expression was >1% in 35% of patients before neoadjuvant therapy, PD-L1 expression was >1% in 65% of patients after treatment (p = 0.004). VISTA expression was >1% in 41% of patients before treatment, and this rate was 65% after treatment (p = 0.025). Conclusion: Chemotherapy and chemoradiotherapy can be used as immunizers by increasing PD-L1 and VISTA expression levels.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Terapia Neoadjuvante
8.
Front Immunol ; 13: 970879, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003386

RESUMO

Symptomatic colon metastasis from primary lung cancer is rare in clinical practice. We report the case of a 58-year-old patient with advanced lung adenocarcinoma who developed abdominal symptoms, including abdominal distention and difficulty defecating, after immunotherapy and chemotherapy. The patient was diagnosed with lung adenocarcinoma, and systemic positron emission tomography-computed tomography confirmed multiple lymph node, pleural, and adrenal metastases. Molecular detection indicated BRAF V600E mutation and high programmed death-ligand 1 (PD-L1) expression. After first-line anti-programmed cell death protein 1 immunotherapy combined with chemotherapy, the nodes in the chest remarkably diminished. However, it was followed by colon obstruction, incomplete ileus, and bone metastasis. Endoscopic histological examination confirmed adenocarcinoma but could not identify primary or secondary tumors due to insufficient tissue. We performed colon resection to remove the obstruction, and postoperative tissue pathological microscopy confirmed metastasis from the lung adenocarcinoma. We corroborated the BRAF V600E mutation and high PD-L1 expression and supported the molecular features of lung adenocarcinoma. During hospitalization, the patient presented with unbearable pain in the bone metastases, and palliative radiotherapy was administered. Then, the patient received dabrafenib plus trametinib as the second-line therapy. This report discusses the clinical characteristics, pathology, imaging, molecular profile assessments, and treatment of primary lung adenocarcinoma with colon metastasis.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias do Colo , Neoplasias Pulmonares , Neoplasias Retais , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/genética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/terapia , Humanos , Imidazóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Mutação , Oximas/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Piridonas/uso terapêutico , Pirimidinonas/uso terapêutico , Neoplasias Retais/tratamento farmacológico
9.
Front Immunol ; 13: 957751, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003401

RESUMO

Tumoral heterogeneity has proven to be a leading cause of difference in prognosis and acquired drug resistance. High intratumor heterogeneity often means poor clinical response and prognosis. Histopathological subtypes suggest tumor heterogeneity evolved during the progression of lung adenocarcinoma, but the exploration of its molecular mechanisms remains limited. In this work, we first verified that transcriptional patterns of a set of differentially expressed genes profoundly revealed the histologic progression of lung adenocarcinoma. Next, a predictive model based on the transcriptional patterns was established to accurately distinguish histologic subtypes. Two crucial genes were identified and used to construct a tumor heterogeneous scoring model (L2SITH) to stratify patients, and we found that patients with low heterogeneity score had better prognosis. Low L2SITH scores implied low tumor purity and beneficial tumor microenvironment. Moreover, L2SITH effectively identified cohorts with better responses to anti-PD-1 immunotherapy.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/terapia , Humanos , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/terapia , Prognóstico , Microambiente Tumoral/genética
10.
Nanotechnology ; 33(45)2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35917695

RESUMO

Killing tumor cells efficiently with photothermal therapy remains a huge challenge. In this study, we successfully prepared a novel polymer with photothermal conversion capability via a condensation reaction, and then subjected it to Polyethylene glycol (PEG) modification and ultrasonic nanocrystalline treatment to make it suitable forin vivophotothermal therapy applications. The conjugated polymer demonstrated good biocompatibility and photothermal conversion ability and was shown in cell experiments to be effective in killing tumor cells after laser irradiation. In addition, the conjugated polymer-based photothermal therapy, guided by photoacoustic real-time imaging and mediated by laser irradiation, of a tumor-bearing mouse model could effectively inhibit the growth of tumor tissue and demonstrated goodin vivobiosafety. Thus, photothermal therapy based on the conjugated polymer synthesized in this study provides a new idea and strategy for the treatment of lung cancer.


Assuntos
Neoplasias Pulmonares , Nanopartículas , Técnicas Fotoacústicas , Animais , Linhagem Celular Tumoral , Neoplasias Pulmonares/terapia , Camundongos , Nanopartículas/química , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Terapia Fototérmica , Polietilenoglicóis/química , Polímeros
11.
J Bras Pneumol ; 48(5): e20220064, 2022.
Artigo em Inglês, Português | MEDLINE | ID: mdl-36000688

RESUMO

OBJECTIVE: To evaluate the process of diagnosing patients with malignant pleural mesothelioma (MPM) at a tertiary care hospital. METHODS: This was a retrospective study involving patients referred to a tertiary-care cancer center in Brazil between 2009 and 2020. The diagnostic process was divided into four steps: onset of symptoms, referral to a specialist visit, histopathological diagnosis, and beginning of treatment. The intervals between each phase and the factors for delays were evaluated. Data including clinical status, radiological examinations, staging, treatment modalities, and survival outcomes were collected. RESULTS: During the study period, 66 patients (mean age = 64 years) were diagnosed with MPM and underwent treatment. Only 27 (41%) of the patients had knowledge of prior exposure to asbestos. The median number of months (IQR) between the onset of symptoms and the first specialist visit, between the specialist visit and histopathological characterization, and between definite diagnosis and beginning of treatment was, respectively, 6.5 (2.0-11.4), 1.5 (0.6-2.1), and 1.7 (1.2-3.4). The knowledge of prior asbestos exposure was associated with a shorter time to referral to a specialist (median: 214 vs. 120 days; p = 0.04). A substantial number of nondiagnostic procedures and false-negative biopsy results (the majority of which involved the use of Cope needle biopsy) were found to be decisive factors for the length of waiting time. The mean overall survival was 11.9 months. CONCLUSIONS: The unfamiliarity of health professionals with MPM and the patient's lack of knowledge of prior asbestos exposure were the major factors to cause a long time interval between the onset of symptoms and beginning of treatment. An overall survival shorter than 1 year is likely to have been due to the aforementioned delays.


Assuntos
Amianto , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Amianto/toxicidade , Países em Desenvolvimento , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Mesotelioma/diagnóstico , Mesotelioma/etiologia , Mesotelioma/terapia , Pessoa de Meia-Idade , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/terapia , Estudos Retrospectivos
12.
Inn Med (Heidelb) ; 63(7): 717-723, 2022 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-35925268

RESUMO

Treatment concepts for patients with localized and locally advanced non-small cell lung cancer (NSCLC) are based on local treatment, surgery and/or radiotherapy, with curative intent. An adjuvant systemic treatment is added after primary resection of an operable NSCLC primarily to reduce the systemic risk of relapse. Locally advanced stages with mediastinal lymph node involvement carry a substantial risk of local and distant recurrence and require multimodal treatment strategies in an interdisciplinary approach. Recently, immunotherapy with programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) checkpoint inhibitors is increasingly being integrated into adjuvant, neoadjuvant or perioperative treatment concepts.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Imunoterapia , Neoplasias Pulmonares/terapia , Terapia Neoadjuvante , Recidiva Local de Neoplasia
13.
Zhonghua Jie He He Hu Xi Za Zhi ; 45(8): 826-834, 2022 Aug 12.
Artigo em Chinês | MEDLINE | ID: mdl-35927054

RESUMO

With the application of high-resolution chest imaging system and lung cancer screening program, patients with multiple primary lung cancer (MPLC) are becoming a growing population in clinical practice. However, the diagnostic criteria of MPLC and its differentiation from intrapulmonary metastasis of lung cancer (IM) are still controversial, especially in cases with similar histology. On the basis of reviewing the existing literature, this paper discusses the changes of the diagnostic criteria of MPLC and the differential diagnosis methods of imaging, histology and molecular genetics of MPLC and IM, and briefly introduces the application of multidisciplinary diagnosis, algorithm, predictive model and artificial intelligence in the differential diagnosis of MPLC. In addition, we also discuss the latest progress in the treatment of MPLC. Radical surgery is the main method for the treatment of MPLC. Stereotactic body radiation therapy (SBRT) is safe and feasible for inoperable MPLC patients, and targeted therapy and immunotherapy can also be used in MPLC after appropriate patient selection.


Assuntos
Neoplasias Pulmonares , Neoplasias Primárias Múltiplas , Inteligência Artificial , Detecção Precoce de Câncer , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/terapia , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia
14.
BMC Cancer ; 22(1): 939, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36045330

RESUMO

BACKGROUND: This analysis presents the outcomes of the operations of the National Cancer Network (NCN) pilot project in Lower Silesian Voivodeship, Poland, for lung cancer for the period of 2019-2021. The results concerning measures of the quality of medical processes were analysed. METHODS: Twenty-one measures used to gauge the quality of oncological care for lung cancer were assessed. Data collection and processing for the purpose of calculating the measures were carried out as part of the NCN pilot project based on the Regulation of the Ministry of Health enacted on 13 December 2018. The measures were calculated at the Voivodeship Coordination Center, and the data were derived from the centres included in the network in the area of the analysed voivodeship. RESULTS: A total of 3,638 patients diagnosed with lung cancer were enrolled in the NCN pilot program during the analysed period. For 3 measures, out of 21, target values were obtained. For 2 measures, the values differed significantly from the assumed target value. CONCLUSION: In our opinion, the NCN pilot study, as a test of the network's functioning, meets the assumed goal. The NCN assessment is based on, inter alia, analysis of the outcomes of oncological quality of care measures for lung cancer, and facilitates monitoring of the quality of medical services provided and the identification of areas for improvement. In addition, the pilot program, which will last until the end of 2022, will allow for further in-depth analysis regarding the network's limitations before implementing the system on a national scale in Poland. This will be the subject of further investigation.


Assuntos
Neoplasias Pulmonares , Indicadores de Qualidade em Assistência à Saúde , Coleta de Dados , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Projetos Piloto , Polônia/epidemiologia
15.
Cancer Control ; 29: 10732748221124519, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36039467

RESUMO

PURPOSE: The aim of the present study was to develop a nomogram for prognostic prediction of patients with lung cancer in hospice. METHODS: The data was collected from 1106 lung cancer patients in hospice between January 2008 and December 2018. The data were split into a training set, which was used to identify the most important prognostic factors by the least absolute shrinkage and selection operator (LASSO) and to build the nomogram, while the testing set was used to validate the nomogram. The performance of the nomogram was assessed by c-index, calibration curve and the decision curve analysis (DCA). RESULTS: A total of 1106 patients, including 835 (75%) from the training set and 271 (25%) from testing set, were retrospectively analyzed in this study. Using the LASSO regression, 5 most important prognostic predictors that included sex, Karnofsky Performance Scale (KPS), quality-of-life (QOL), edema and anorexia, were selected out of 28 variables. Validated c-indexes of training set at 15, 30, and 90 days were .778 [.737-.818], .776 [.743-.809], and .751 [.713-.790], respectively. Similarly, the validated c-indexes of testing set at 15, 30, and 90 days were .789 [.714-.864], .748 [.685-.811], and .757 [.691-.823], respectively. The nomogram-predicted survival was well calibrated, as the predicted probabilities were close to the expected probabilities. Moreover, the DCA curve showed that nomogram received superior standardized net benefit at a broad threshold. CONCLUSIONS: The study built a non-lab nomogram with important predictor to analyze the clinical parameters using LASSO. It may be a useful tool to allow clinicians to easily estimate the prognosis of the patients with lung cancer in hospice.


Assuntos
Cuidados Paliativos na Terminalidade da Vida , Hospitais para Doentes Terminais , Neoplasias Pulmonares , Algoritmos , Humanos , Neoplasias Pulmonares/terapia , Qualidade de Vida , Estudos Retrospectivos
16.
Sci Rep ; 12(1): 13646, 2022 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-35953696

RESUMO

Lung squamous cell carcinoma (LUSC) comprises 20-30% of all lung cancers. Immunotherapy has significantly improved the prognosis of LUSC patients; however, only a small subset of patients responds to the treatment. Therefore, we aimed to develop a novel multi-gene signature associated with the immune phenotype of the tumor microenvironment for LUSC prognosis prediction. We stratified the LUSC patients from The Cancer Genome Atlas dataset into hot and cold tumor according to a combination of infiltration status of immune cells and PD-L1 expression level. Kaplan-Meier analysis showed that hot tumors were associated with shorter overall survival (OS). Enrichment analyses of differentially expressed genes (DEGs) between the hot and cold tumors suggested that hot tumors potentially have a higher immune response ratio to immunotherapy than cold tumors. Subsequently, hub genes based on the DEGs were identified and protein-protein interactions were constructed. Finally, we established an immune-related 13-gene signature based on the hub genes using the least absolute shrinkage and selection operator feature selection and multivariate cox regression analysis. This gene signature divided LUSC patients into high-risk and low-risk groups and the former inclined worse OS than the latter. Multivariate cox proportional hazard regression analysis showed that the risk model constructed by the 13 prognostic genes was an independent risk factor for prognosis. Receiver operating characteristic curve analysis showed a moderate predictive accuracy for 1-, 3- and 5-year OS. The 13-gene signature also performed well in four external cohorts (three LUSC and one melanoma cohorts) from Gene Expression Omnibus. Overall, in this study, we established a reliable immune-related 13-gene signature that can stratify and predict the prognosis of LUSC patients, which might serve clinical use of immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/terapia , Regulação Neoplásica da Expressão Gênica , Humanos , Imunoterapia , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Prognóstico , Microambiente Tumoral/genética
17.
Int J Mol Sci ; 23(15)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35955516

RESUMO

Liposome modification by targeting ligands has been used to mediate specific interactions and drug delivery to target cells. In this study, a new peptide ligand, CP7, was found to be able to effectively bind to FGFR1 through reverse molecular docking and could cooperate with VEGFR3 to achieve targeting of A549 cells. CP7 was modified on the surface of the liposome to construct a targeted and safe nanovehicle for the delivery of a therapeutic gene, Mcl-1 siRNA. Due to the specific binding between CP7 and A549 cells, siRNA-loaded liposome-PEG-CP7 showed increased cellular uptake in vitro, resulting in significant apoptosis of tumor cells through silencing of the Mcl-1 gene, which is associated with apoptosis and angiogenesis. This gene delivery system also showed significantly better antitumor activity in tumor-bearing mice in vivo. All of these suggested that siRNA-loaded liposome-PEG-CP7 could be a promising gene drug delivery system with good bioavailability and minimal side effects for treatment.


Assuntos
Lipossomos , Neoplasias Pulmonares , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Lipossomos/química , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Camundongos , Simulação de Acoplamento Molecular , Proteína de Sequência 1 de Leucemia de Células Mieloides , Peptídeos/química , Peptídeos/genética , RNA Interferente Pequeno/metabolismo
18.
Int J Mol Sci ; 23(15)2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-35955652

RESUMO

Lung cancer is the leading cause of cancer death worldwide. miR-199a, which has two mature molecules: miR-199a-3p and miR-199a-5p, plays an important biological role in the genesis and development of tumors. We collected recent research results on lung cancer and miR-199a from Google Scholar and PubMed databases. The biological functions of miR-199a in lung cancer are reviewed in detail, and its potential roles in lung cancer diagnosis and treatment are discussed. With miR-199a as the core point and a divergence outward, the interplay between miR-199a and other ncRNAs is reviewed, and a regulatory network covering various cancers is depicted, which can help us to better understand the mechanism of cancer occurrence and provide a means for developing novel therapeutic strategies. In addition, the current methods of diagnosis and treatment of lung cancer are reviewed. Finally, a conclusion was drawn: miR-199a inhibits the development of lung cancer, especially by inhibiting the proliferation, infiltration, and migration of lung cancer cells, inhibiting tumor angiogenesis, increasing the apoptosis of lung cancer cells, and affecting the drug resistance of lung cancer cells. This review aims to provide new insights into lung cancer therapy and prevention.


Assuntos
Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , MicroRNAs/genética , RNA não Traduzido
19.
J Transl Med ; 20(1): 349, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918758

RESUMO

Lung cancer is the second cancer and the leading cause of tumor-related mortality worldwide. Angiogenesis is a crucial hallmark of cancer development and a promising target in lung cancer. However, the anti-angiogenic drugs currently used in the clinic do not achieve long-term efficacy and are accompanied by severe adverse reactions. Therefore, the development of novel anti-angiogenic therapeutic approaches for lung cancer is urgently needed. Non-coding RNAs (ncRNAs) participate in multiple biological processes in cancers, including tumor angiogenesis. Many studies have demonstrated that ncRNAs play crucial roles in tumor angiogenesis. This review discusses the regulatory functions of different ncRNAs in lung cancer angiogenesis, focusing on the downstream targets and signaling pathways regulated by these ncRNAs. Additionally, given the recent trend towards utilizing ncRNAs as cancer therapeutics, we also discuss the tremendous potential applications of ncRNAs as biomarkers or novel anti-angiogenic tools in lung cancer.


Assuntos
Neoplasias Pulmonares , RNA Longo não Codificante , Biomarcadores Tumorais/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , RNA Longo não Codificante/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Transdução de Sinais/genética
20.
Zhongguo Fei Ai Za Zhi ; 25(8): 609-614, 2022 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-36002198

RESUMO

Small cell lung cancer (SCLC) is a malignant tumor with strong invasiveness and high mortality. It has the characteristics of easy metastasis, fast growth, high degree of malignancy and strong invasiveness. The prognosis of patients is generally poor. The current clinical diagnosis of SCLC is mainly based on tissue biopsy, which is invasive, long cycle time and high cost. In recent years, liquid biopsy has been gradually applied because of its non-invasive, comprehensive and real-time characteristics that traditional tissue biopsy does not have. The main detection objects of liquid biopsy include circulating tumor DNA (ctDNA), circulating tumor cells (CTCs) and exosomes in peripheral blood. The application of liquid biopsy in the clinical treatment of SCLC will help clinicians to improve the detailed diagnosis of SCLC patients, as well as the timely control and response to the treatment response of patients.
.


Assuntos
DNA Tumoral Circulante , Neoplasias Pulmonares , Células Neoplásicas Circulantes , Carcinoma de Pequenas Células do Pulmão , Biomarcadores Tumorais , Humanos , Biópsia Líquida , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Células Neoplásicas Circulantes/metabolismo , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/terapia
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