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1.
J Coll Physicians Surg Pak ; 34(4): 461-467, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38576291

RESUMO

The role of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC) has been questioned in the era of magnetic resonance imaging (MRI). The purpose of this study was to re-evaluate the efficacy of PCI in patients with LS-SCLC. Three electronic databases were searched, including PubMed, Embase, and the Cochrane Library from January 2012 to April 2022. All relevant publications were included based on the inclusion criteria, and survival data and brain metastasis (BM) rates were extracted and pooled. Ten studies were selected which involved 532 patients who received PCI and 613 patients who did not receive PCI. In pooled estimates, PCI significantly improved overall survival (OS) and progression-free survival (PFS) [hazard ratio (HR) = 0.71, 95% confidence interval (CI): 0.61-0.82, p <0.001; HR = 0.68, 95% CI: 0.48-0.97, p = 0.03, respectively]. Additionally, the use of PCI was associated with a significant reduction in the risk of brain metastasis (BM, risk ratio = 0.64, 95% CI: 0.46-0.90, p = 0.009). In subgroup analyses. The authors found that the PCI effects on OS were independent of region and the use of brain imaging after initial treatment. These findings demonstrate that PCI improves OS and PFS while decreasing the risk of BM in patients with LS-SCLC, implying that PCI remains necessary even in the MRI era. Key Words: Prophylactic cranial irradiation, Small cell lung cancer, Magnetic resonance imaging, Brain metastasis.


Assuntos
Irradiação Craniana , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Encefálicas/prevenção & controle , Neoplasias Encefálicas/secundário , Irradiação Craniana/métodos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/radioterapia
2.
BMJ Open Respir Res ; 11(1)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589197

RESUMO

BACKGROUND: Diagnosing mediastinal tumours, including incidental lesions, using low-dose CT (LDCT) performed for lung cancer screening, is challenging. It often requires additional invasive and costly tests for proper characterisation and surgical planning. This indicates the need for a more efficient and patient-centred approach, suggesting a gap in the existing diagnostic methods and the potential for artificial intelligence technologies to address this gap. This study aimed to create a multimodal hybrid transformer model using the Vision Transformer that leverages LDCT features and clinical data to improve surgical decision-making for patients with incidentally detected mediastinal tumours. METHODS: This retrospective study analysed patients with mediastinal tumours between 2010 and 2021. Patients eligible for surgery (n=30) were considered 'positive,' whereas those without tumour enlargement (n=32) were considered 'negative.' We developed a hybrid model combining a convolutional neural network with a transformer to integrate imaging and clinical data. The dataset was split in a 5:3:2 ratio for training, validation and testing. The model's efficacy was evaluated using a receiver operating characteristic (ROC) analysis across 25 iterations of random assignments and compared against conventional radiomics models and models excluding clinical data. RESULTS: The multimodal hybrid model demonstrated a mean area under the curve (AUC) of 0.90, significantly outperforming the non-clinical data model (AUC=0.86, p=0.04) and radiomics models (random forest AUC=0.81, p=0.008; logistic regression AUC=0.77, p=0.004). CONCLUSION: Integrating clinical and LDCT data using a hybrid transformer model can improve surgical decision-making for mediastinal tumours, showing superiority over models lacking clinical data integration.


Assuntos
Neoplasias Pulmonares , Neoplasias do Mediastino , Humanos , Neoplasias Pulmonares/patologia , Inteligência Artificial , Neoplasias do Mediastino/diagnóstico por imagem , Estudos Retrospectivos , Detecção Precoce de Câncer , Tomografia Computadorizada por Raios X/métodos
3.
Arkh Patol ; 86(2): 37-41, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38591905

RESUMO

Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion is an extremely rare tumor. Its clinical manifestation is unspecific and only molecular genetic method can proof this diagnosis. This paper describes an unusual clinical presentation of primary pulmonary myxoid sarcoma in a 68-year-old patient with involvement of both lungs.


Assuntos
Neoplasias Pulmonares , Sarcoma , Humanos , Idoso , Sarcoma/genética , Sarcoma/diagnóstico , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas de Fusão Oncogênica/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína EWS de Ligação a RNA/genética
4.
Artigo em Inglês | MEDLINE | ID: mdl-38569836

RESUMO

PURPOSE: This study evaluated the Controlling Nutritional Status (CONUT) score as a prognostic predictor in elderly non-small cell lung cancer (NSCLC) patients with surgical resection. METHODS: Overall, 114 patients over 80 years old undergoing curative resection for NSCLC were retrospectively analyzed. Receiver operating characteristic (ROC) analysis was conducted to evaluate the capacity of immune-inflammatory markers to predict overall survival (OS). Cox-proportional hazards regression analysis was implemented to investigate prognostic markers for OS. RESULTS: Based on ROC curves, the CONUT score was found to be the most valuable prognostic marker (area under the curve = 0.716). The high CONUT (≥2) group included 54 patients, and the low CONUT (0 or 1) group included 60 patients. The high CONUT group had poorer prognosis rates compared to the low CONUT group with regard to OS (5-year OS: 46.3% vs. 86.0%, p = 0.0006). In the multivariate data analysis, histology, lymphatic invasion, and CONUT score (hazard ratio: 4.23, p = 0.0003) were found to be exclusive and independent prognostic markers for OS. CONCLUSION: Preoperatively, the CONUT score can be used as a novel prognostic marker in elderly NSCLC patients. CONUT evaluations can also be used to design nutritional interventions to improve patient outcomes.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Idoso , Idoso de 80 Anos ou mais , Prognóstico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Resultado do Tratamento , Estudos Retrospectivos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Estado Nutricional
5.
Front Immunol ; 15: 1364506, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38571938

RESUMO

Introduction: Tertiary lymphoid structures (TLSs) are ectopic lymphoid formations that arise in non-lymphoid tissues due to chronic inflammation. The pivotal function of TLSs in regulating tumor invasion and metastasis has been established across several cancers, such as lung cancer, liver cancer, and melanoma, with a positive correlation between increased TLS presence and improved prognosis. Nevertheless, the current research about the clinical significance of TLSs in breast cancer remains limited. Methods: In our investigation, we discovered TLS-critical genes that may impact the prognosis of breast cancer patients, and categorized breast cancer into three distinct subtypes based on critical gene expression profiles, each exhibiting substantial differences in prognosis (p = 0.0046, log-rank test), with Cluster 1 having the best prognosis, followed by Cluster 2, and Cluster 3 having the worst prognosis. We explored the impact of the heterogeneity of these subtypes on patient prognosis, the differences in the molecular mechanism, and their responses to drug therapy and immunotherapy. In addition, we designed a machine learning-based classification model, unveiling highly consistent prognostic distinctions in several externally independent cohorts. Results: A notable marker gene CXCL13 was identified in Cluster 3, potentially pivotal in enhancing patient prognosis. At the single-cell resolution, we delved into the adverse prognosis of Cluster 3, observing an enhanced interaction between fibroblasts, myeloid cells, and basal cells, influencing patient prognosis. Furthermore, we identified several significantly upregulated genes (CD46, JAG1, IL6, and IL6R) that may positively correlate with cancer cells' survival and invasive capabilities in this subtype. Discussion: Our study is a robust foundation for precision medicine and personalized therapy, presenting a novel perspective for the contemporary classification of breast cancer.


Assuntos
Neoplasias da Mama , Neoplasias Hepáticas , Neoplasias Pulmonares , Estruturas Linfoides Terciárias , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Estruturas Linfoides Terciárias/patologia , Prognóstico , Neoplasias Pulmonares/patologia
6.
PLoS One ; 19(4): e0294227, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38564630

RESUMO

Current evidence suggests that DEP domain containing 1 (DEPDC1) has an important effect on non-small-cell lung cancer (NSCLC). However, the diagnostic value and the regulatory function within NSCLC are largely unclear. This work utilized publicly available databases and in vitro experiments for exploring, DEPDC1 expression, clinical features, diagnostic significance and latent molecular mechanism within NSCLC. According to our results, DEPDC1 was remarkably upregulated in the tissues of NSCLC patients compared with non-carcinoma tissues, linked with gender, stage, T classification and N classification based on TCGA data and associated with smoking status and stage according to GEO datasets. Meanwhile, the summary receiver operating characteristic (sROC) curve analysis result showed that DEPDC1 had a high diagnostic value in NSCLC (AUC = 0.96, 95% CI: 0.94-0.98; diagnostic odds ratio = 99.08, 95%CI: 31.91-307.65; sensitivity = 0.89, 95%CI: 0.81-0.94; specificity = 0.92, 95%CI: 0.86-0.96; positive predictive value = 0.94, 95%CI: 0.89-0.98; negative predictive value = 0.78, 95%CI: 0.67-0.90; positive likelihood ratio = 11.77, 95%CI: 6.11-22.68; and negative likelihood ratio = 0.12, 95%CI: 0.06-0.22). Subsequently, quantitative real-time PCR (qRT-PCR) and western blotting indicated that DEPDC1 was high expressed in NSCLC cells. According to the in vitro MTS and apoptotic assays, downregulated DEPDC1 expression targeting P53 signaling pathway inhibited the proliferation of NSCLC cells while promoting apoptosis of NSCLC cells. Moreover, DEPDC1 was significantly correlated with immune cell infiltrating levels in NSCLC based on TCGA data, which were primarily associated with T cells CD4 memory activated, macrophages M1, B cells memory, mast cells resting, T cells regulatory, monocytes, and T cells CD4 memory resting. Compared with the group with high expression of DEPDC1, the group with low expression level had higher scores for immune checkpoint inhibitors (ICIs) treatment. GSEA confirmed that DEPDC1 was involved in gene expression and tumor-related signaling pathways. Finally, DEPDC1 and its associated immune-related genes were shown to be enriched in 'receptor ligand activity', 'external side of plasma membrane', 'regulation of innate immune response', and 'Epstein-Barr virus infection' pathways. The present study demonstrates that DEPDC1 may contribute to NSCLC tumorigenesis and can be applied as the biomarker for diagnosis and immunology.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Infecções por Vírus Epstein-Barr , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Herpesvirus Humano 4/metabolismo , Transdução de Sinais , Proteínas de Neoplasias/genética , Proteínas Ativadoras de GTPase/metabolismo
7.
BMC Cancer ; 24(1): 408, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566039

RESUMO

BACKGROUND: Accumulating evidence indicates that aberrant non-SMC condensin II complex subunit D3 (NCAPD3) is associated with carcinogenesis of various cancers. Nevertheless, the biological role of NCAPD3 in the pathogenesis of non-small cell lung cancer (NSCLC) remains unclear. METHODS: Immunohistochemistry and Western blot were performed to assess NCAPD3 expression in NSCLC tissues and cell lines. The ability of cell proliferation, invasion, and migration was evaluated by CCK-8 assays, EdU assays, Transwell assays, and scratch wound healing assays. Flow cytometry was performed to verify the cell cycle and apoptosis. RNA-sequence and rescue experiment were performed to reveal the underlying mechanisms. RESULTS: The results showed that the expression of NCAPD3 was significantly elevated in NSCLC tissues. High NCAPD3 expression in NSCLC patients was substantially associated with a worse prognosis. Functionally, knockdown of NCAPD3 resulted in cell apoptosis and cell cycle arrest in NSCLC cells as well as a significant inhibition of proliferation, invasion, and migration. Furthermore, RNA-sequencing analysis suggested that NCAPD3 contributes to NSCLC carcinogenesis by regulating PI3K/Akt/FOXO4 pathway. Insulin-like growth factors-1 (IGF-1), an activator of PI3K/Akt signaling pathway, could reverse NCAPD3 silence-mediated proliferation inhibition and apoptosis in NSCLC cells. CONCLUSION: NCAPD3 suppresses apoptosis and promotes cell proliferation via the PI3K/Akt/FOXO4 signaling pathway, suggesting a potential use for NCAPD3 inhibitors as NSCLC therapeutics.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinogênese/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica , Neoplasias Pulmonares/patologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA
8.
Cell Commun Signal ; 22(1): 201, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566083

RESUMO

Lung cancer is a deeply malignant tumor with high incidence and mortality. Despite the rapid development of diagnosis and treatment technology, abundant patients with lung cancer are still inevitably faced with recurrence and metastasis, contributing to death. Lymphatic metastasis is the first step of distant metastasis and an important prognostic indicator of non-small cell lung cancer. Tumor-induced lymphangiogenesis is involved in the construction of the tumor microenvironment, except promoting malignant proliferation and metastasis of tumor cells, it also plays a crucial role in individual response to treatment, especially immunotherapy. Thus, this article reviews the current research status of lymphatic metastasis in non-small cell lung cancer, in order to provide some insights for the basic research and clinical and translational application in this field.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Vasos Linfáticos , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Metástase Linfática/patologia , Linfangiogênese/fisiologia , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patologia , Microambiente Tumoral
9.
Cancer Imaging ; 24(1): 47, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566150

RESUMO

PURPOSE: To investigate the computed tomography (CT) characteristics of air-containing space and its specific patterns in neoplastic and non-neoplastic ground glass nodules (GGNs) for clarifying their significance in differential diagnosis. MATERIALS AND METHODS: From January 2015 to October 2022, 1328 patients with 1,350 neoplastic GGNs and 462 patients with 465 non-neoplastic GGNs were retrospectively enrolled. Their clinical and CT data were analyzed and compared with emphasis on revealing the differences of air-containing space and its specific patterns (air bronchogram and bubble-like lucency [BLL]) between neoplastic and non-neoplastic GGNs and their significance in differentiating them. RESULTS: Compared with patients with non-neoplastic GGNs, female was more common (P < 0.001) and lesions were larger (P < 0.001) in those with neoplastic ones. Air bronchogram (30.1% vs. 17.2%), and BLL (13.0% vs. 2.6%) were all more frequent in neoplastic GGNs than in non-neoplastic ones (each P < 0.001), and the BLL had the highest specificity (93.6%) in differentiation. Among neoplastic GGNs, the BLL was more frequently detected in the larger (14.9 ± 6.0 mm vs. 11.4 ± 4.9 mm, P < 0.001) and part-solid (15.3% vs. 10.7%, P = 0.011) ones, and its incidence significantly increased along with the invasiveness (9.5-18.0%, P = 0.001), whereas no significant correlation was observed between the occurrence of BLL and lesion size, attenuation, or invasiveness. CONCLUSION: The air containing space and its specific patterns are of great value in differentiating GGNs, while BLL is a more specific and independent sign of neoplasms.


Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Humanos , Feminino , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/patologia , Tomografia Computadorizada por Raios X/métodos , Diagnóstico Diferencial
10.
J Transl Med ; 22(1): 329, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570798

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs), administered alone or combined with chemotherapy, are the standard of care in advanced non-oncogene addicted Non-Small Cell Lung Cancer (NSCLC). Despite these treatments' success, most long-term survival benefit is restricted to approximately 20% of patients, highlighting the need to identify novel biomarkers to optimize treatment strategies. In several solid tumors, immune soluble factors, the activatory CD137+ Tcells, and the immunosuppressive cell subsets Tregs and MDSCs (PMN(Lox1+)-MDSC and M-MDSCs) correlated with responses to ICIs and clinical outcomes thus becoming appealing predictive and prognostic factors. This study investigated the role of distinct CD137+ Tcell subsets, Tregs, MDSCs, and immune-soluble factors in NSCLC patients as possible biomarkers. METHODS: The levels of T cells, MDSCs and soluble factors were evaluated in 89 metastatic NSCLC patients who underwent ICIs as first- or second-line treatment. T cell analysis was performed by cytoflurimetry evaluating Tregs and different CD137+ Tcell subsets also combined with CD3+, CD8+, PD1+, and Ki67+ markers. Circulating cytokines and immune checkpoints were also evaluated by Luminex analysis. All these parameters were correlated with several clinical factors (age, sex, smoking status, PS and TPS), response to therapy, PFS , and OS . The analyses were conducted in the overall population and in patients treated with ICIs as first-line (naïve patients). RESULTS: In both groups of patients, high levels of circulating CD137+ and CD137+PD1+ T cells (total, CD4 and CD8) and the soluble factor LAG3 positively correlated with response to therapy. In naïve patients, PMN(Lox1+)-MDSCs negatively correlated with clinical response, and a high percentage of Tregs was associated with favorable survival. Moreover, the balance between Treg/CD137+ Tcells or PMN(Lox1+)-MDSC/CD137+ Tcells was higher in non-responding patients and was associated with poor survival. CD137+ Tcells and Tregs resulted as two positive independent prognostic factors. CONCLUSION: High levels of CD137+, CD137+PD1+ Tcells and sLAG3 could predict the response to ICIs in NSCLC patients independently by previous therapy. Combining the evaluation of CD137+ Tcells and Tregs also as Treg/CD137+ T cells ratio it is possible to identify naive patients with longer survival.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Linfócitos T Reguladores , Neoplasias Pulmonares/patologia , Prognóstico , Biomarcadores , Imunoterapia/métodos
11.
J Exp Clin Cancer Res ; 43(1): 103, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570866

RESUMO

BACKGROUND: Brain metastasis (BM) is common among cases of advanced non-small cell lung cancer (NSCLC) and is the leading cause of death for these patients. Mesothelin (MSLN), a tumor-associated antigen expressed in many solid tumors, has been reported to be involved in the progression of multiple tumors. However, its potential involvement in BM of NSCLC and the underlying mechanism remain unknown. METHODS: The expression of MSLN was validated in clinical tissue and serum samples using immunohistochemistry and enzyme-linked immunosorbent assay. The ability of NSCLC cells to penetrate the blood-brain barrier (BBB) was examined using an in vitro Transwell model and an ex vivo multi-organ microfluidic bionic chip. Immunofluorescence staining and western blotting were used to detect the disruption of tight junctions. In vivo BBB leakiness assay was performed to assess the barrier integrity. MET expression and activation was detected by western blotting. The therapeutic efficacy of drugs targeting MSLN (anetumab) and MET (crizotinib/capmatinib) on BM was evaluated in animal studies. RESULTS: MSLN expression was significantly elevated in both serum and tumor tissue samples from NSCLC patients with BM and correlated with a poor clinical prognosis. MSLN significantly enhanced the brain metastatic abilities of NSCLC cells, especially BBB extravasation. Mechanistically, MSLN facilitated the expression and activation of MET through the c-Jun N-terminal kinase (JNK) signaling pathway, which allowed tumor cells to disrupt tight junctions and the integrity of the BBB and thereby penetrate the barrier. Drugs targeting MSLN (anetumab) and MET (crizotinib/capmatinib) effectively blocked the development of BM and prolonged the survival of mice. CONCLUSIONS: Our results demonstrate that MSLN plays a critical role in BM of NSCLC by modulating the JNK/MET signaling network and thus, provides a potential novel therapeutic target for preventing BM in NSCLC patients.


Assuntos
Benzamidas , Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Imidazóis , Neoplasias Pulmonares , Triazinas , Humanos , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Mesotelina , Neoplasias Pulmonares/patologia , Proteínas Ligadas por GPI/metabolismo , Crizotinibe , Linhagem Celular Tumoral , Neoplasias Encefálicas/patologia
12.
Cancer Med ; 13(7): e7158, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572933

RESUMO

BACKGROUND: Thoracic adenoid cystic carcinoma (ACC) is rare, and the differences between tracheal and lung lesions have not been fully understood. METHODS: Patients were identified from a Chinese cancer center (FUSCC) (2005-2022) and the Surveillance, Epidemiology, and End Results (SEER) database (2000-2019). Incidence was calculated and trends were quantified. Clinicopathological features and overall survival (OS) were analyzed. Nomograms predicting OS were constructed. RESULTS: Totally, 55 tracheal adenoid cystic carcinoma (TACC) and 25 lung and bronchus adenoid cystic carcinoma (LACC) were included in a Chinese cohort, 121 TACC and 162 LACC included in the SEER cohort. There were larger tumor sizes, more lymph nodes and distant metastases for LACC than TACC patients. TACC patients are more likely to get local treatments. Patients with LACC had significantly worse median OS than patients with TACC (SEER cohort: 68.0 months vs. 109.0 months, p = 0.001, Chinese cohort: 62.9 months vs. 124.8 months, p = 0.061). Age, lymph node metastasis, distant metastasis and local treatment were identified as independent prognostic factors for OS of TACC. Distant metastasis and local treatment were identified for LACC. Specifically, surgery alone or in combination with radiotherapy is crucial for improving survival in both TACC and LACC. Only TACC benefits from radiotherapy alone, while chemotherapy does not improve survival for either. The nomograms constructed using these factors revealed good prognostic accuracy. CONCLUSIONS: LACC is more aggressive and has a worse prognosis than TACC. TACC patients have more opportunities for local treatment, which is important for the prognosis of both TACC and LACC. Nomograms were created for TACC and LACC to aid in personalized survival predictions and clinical decisions.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias Pulmonares , Humanos , Carcinoma Adenoide Cístico/epidemiologia , Carcinoma Adenoide Cístico/terapia , Carcinoma Adenoide Cístico/patologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Prognóstico , Nomogramas , Pulmão/patologia
14.
Front Immunol ; 15: 1352615, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38558814

RESUMO

Introduction: Fibroblast activation protein (FAP) is predominantly upregulated in various tumor microenvironments and scarcely expressed in normal tissues. Methods: We analyzed FAP across 1216 tissue samples covering 23 tumor types and 70 subtypes. Results: Elevated FAP levels were notable in breast, pancreatic, esophageal, and lung cancers. Using immunohistochemistry and RNAseq, a correlation between FAP gene and protein expression was found. Evaluating FAP's clinical significance, we assessed 29 cohorts from 12 clinical trials, including both mono and combination therapies with the PD-L1 inhibitor atezolizumab and chemotherapy. A trend links higher FAP expression to poorer prognosis, particularly in RCC, across both treatment arms. However, four cohorts showed improved survival with high FAP, while in four others, FAP had no apparent survival impact. Conclusions: Our results emphasize FAP's multifaceted role in therapy response, suggesting its potential as a cancer immunotherapy biomarker.


Assuntos
Neoplasias Pulmonares , Serina Endopeptidases , Humanos , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Imunoterapia , Neoplasias Pulmonares/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Fibroblastos/metabolismo , Microambiente Tumoral/genética
15.
Oncol Res ; 32(4): 625-641, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560562

RESUMO

The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer (NSCLC). Although researchers have disclosed that interleukin 17 (IL-17) can increase matrix metalloproteinases (MMPs) induction causing NSCLC cell metastasis, the underlying mechanism remains unclear. In the study, we found that IL-17 receptor A (IL-17RA), p300, p-STAT3, Ack-STAT3, and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17. p300, STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3, Ack-STAT3 and MMP19 level as well as the cell migration and invasion. Mechanism investigation revealed that STAT3 and p300 bound to the same region (-544 to -389 nt) of MMP19 promoter, and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity, p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17. Meanwhile, p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact, synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion. Besides, the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300, STAT3 or MMP19 gene plus IL-17 treatment, the nodule number, and MMP19, Ack-STAT3, or p-STAT3 production in the lung metastatic nodules were all alleviated. Collectively, these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation, which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Camundongos , Animais , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Interleucina-17/genética , Interleucina-17/metabolismo , Fosforilação , Neoplasias Pulmonares/patologia , Acetilação , Camundongos Nus , Transcrição Gênica , Movimento Celular/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
16.
Oncol Res ; 32(4): 643-658, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560570

RESUMO

The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma (LUAD), and chemoresistance, however, usually results in treatment failure and limits its application in the clinic. It has been shown that microRNAs (miRNAs) play a significant role in tumor chemoresistance. In this study, miR-125b was identified as a specific cisplatin (DDP)-resistant gene in LUAD, as indicated by the bioinformatics analysis and the real-time quantitative PCR assay. The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time. MiR-125b decreased the A549/DDP proliferation, and the multiple drug resistance- and autophagy-related protein expression levels, which were all reversed by the inhibition of miR-125b. In addition, xenografts of human tumors in nude mice were suppressed by miR-125b, demonstrating that through autophagy regulation, miR-125b could reverse the DDP resistance in LUAD cells, both in vitro and in vivo. Further mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L, which in turn inhibited autophagy and reversed chemoresistance. Based on these findings, miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , MicroRNAs , Proteínas Supressoras de Tumor , Animais , Camundongos , Humanos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos Nus , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Apoptose/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Autofagia/genética , Regulação Neoplásica da Expressão Gênica , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/farmacologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas/genética
18.
Technol Cancer Res Treat ; 23: 15330338241242635, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562094

RESUMO

Background: One of the most frequently used methods for quantifying PD-L1 (programmed cell death-ligand 1) expression in tumor tissue is IHC (immunohistochemistry). This may predict the patient's response to anti-PD1/PD-L1 therapy in cancer. Methods: ImageJ software was used to score IHC-stained sections for PD-L1 and compare the results with the conventional manual method. Results: In diffuse large B cell lymphoma, no significant difference between the scores obtained by the conventional method and ImageJ scores obtained using the option "RGB" or "Brightness/Contrast." On the other hand, a significant difference was found between the conventional and HSB scoring methods. ImageJ faced some challenges in analyzing head and neck squamous cell carcinoma tissues because of tissue heterogenicity. A significant difference was found between the conventional and ImageJ scores using HSB or RGB but not with the "Brightness/Contrast" option. Scores obtained by ImageJ analysis after taking images using 20 × objective lens gave significantly higher readings compared to 40 × magnification. A significant difference between camera-captured images' scores and scanner whole slide images' scores was observed. Conclusion: ImageJ can be used to score homogeneous tissues. In the case of highly heterogeneous tissues, it is advised to use the conventional method rather than ImageJ scoring.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias de Cabeça e Pescoço , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Antígeno B7-H1/metabolismo , Projetos de Pesquisa , Ligantes , Biomarcadores Tumorais/análise
19.
Cell Adh Migr ; 18(1): 1-11, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38557441

RESUMO

We aimed to investigate galectin-1 overexpression induces normal fibroblasts (NFs) translates into cancer-associated fibroblasts (CAFs). Galectin-1 overexpression was conducted in Human embryonic lung fibroblasts (HFL1) cell. The motilities of H1299 and A549 cells were measured. Human umbilical vein endothelial cell (HUVEC) proliferation and tube formation ability were assessed. Tumor volume and tumor weight was recorded. Cells motilities were increased, while apoptosis rates were decreased after CMs co-cultured. B-cell lymphoma-2 (Bcl-2) expression level was increased, while Bcl2-associatedX (Bax) and cleaved-caspase3 decreased. CMs treatment enhanced HUVEC proliferation and tube formation. Tumor volume and weight in CMs treated mice were increased, and the sensitivity of anlotinib in co-cultured cells was decreased. Our results revealed that galectin-1 overexpression induced NFs translated into CAFs.


Assuntos
Fibroblastos Associados a Câncer , Indóis , Neoplasias Pulmonares , Quinolinas , Humanos , Camundongos , Animais , Fibroblastos Associados a Câncer/metabolismo , Neoplasias Pulmonares/patologia , Galectina 1/genética , Galectina 1/metabolismo , Fibroblastos/metabolismo , Proliferação de Células
20.
J Clin Invest ; 134(7)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557498

RESUMO

BACKGROUNDPrecise stratification of patients with non-small cell lung cancer (NSCLC) is needed for appropriate application of PD-1/PD-L1 blockade therapy.METHODSWe measured soluble forms of the immune-checkpoint molecules PD-L1, PD-1, and CTLA-4 in plasma of patients with advanced NSCLC before PD-1/PD-L1 blockade. A prospective biomarker-finding trial (cohort A) included 50 previously treated patients who received nivolumab. A retrospective observational study was performed for patients treated with any PD-1/PD-L1 blockade therapy (cohorts B and C), cytotoxic chemotherapy (cohort D), or targeted therapy (cohort E). Plasma samples from all patients were assayed for soluble immune-checkpoint molecules with a highly sensitive chemiluminescence-based assay.RESULTSNonresponsiveness to PD-1/PD-L1 blockade therapy was associated with higher concentrations of these soluble immune factors among patients with immune-reactive (hot) tumors. Such an association was not apparent for patients treated with cytotoxic chemotherapy or targeted therapy. Integrative analysis of tumor size, PD-L1 expression in tumor tissue (tPD-L1), and gene expression in tumor tissue and peripheral CD8+ T cells revealed that high concentrations of the 3 soluble immune factors were associated with hyper or terminal exhaustion of antitumor immunity. The combination of soluble PD-L1 (sPD-L1) and sCTLA-4 efficiently discriminated responsiveness to PD-1/PD-L1 blockade among patients with immune-reactive tumors.CONCLUSIONCombinations of soluble immune factors might be able to identify patients unlikely to respond to PD-1/PD-L1 blockade as a result of terminal exhaustion of antitumor immunity. Our data suggest that such a combination better predicts, along with tPD-L1, for the response of patients with NSCLC.TRIAL REGISTRATIONUMIN000019674.FUNDINGThis study was funded by Ono Pharmaceutical Co. Ltd. and Sysmex Corporation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Antígeno B7-H1 , Receptor de Morte Celular Programada 1 , Fatores Imunológicos/uso terapêutico
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