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Non-small cell lung cancer (NSCLC) remains an unsolved challenge in oncology, signifying a substantial global health burden. While considerable progress has been made in recent years through the emergence of immunotherapy modalities, such as immune checkpoint inhibitors (ICIs), monotherapies often yield limited clinical outcomes. The rationale behind combining various immunotherapeutic or other anticancer agents, the mechanistic underpinnings, and the clinical evidence supporting their utilization is crucial in NSCLC therapy. Regarding the synergistic potential of combination immunotherapies, this study aims to provide insights to help the landscape of NSCLC treatment and improve clinical outcomes. In addition, this review article discusses the challenges and considerations of combination regimens, including toxicity management and patient selection.
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Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/imunologia , Imunoterapia/métodos , Inibidores de Checkpoint Imunológico/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Animais , Terapia Combinada , Resultado do TratamentoRESUMO
Aim: This study aimed to investigate the functions of ZNF582-AS1 and ZNF582 in esophageal cancer (EC). Materials & methods: Bioinformatics analysis, qRT-PCR and western blot were used to analyze the expression levels. Biological functions were evaluated using cell-counting kit 8, colony formation, Transwell assays and flow cytometry. FISH was used to detect subcellular localization, and methylation-specific PCR determined gene methylation levels. Animal experiments validated the impact on tumor progression. Results: ZNF582-AS1 and ZNF582 were highly methylated and downregulated in EC. Overexpression of ZNF582-AS1 up-regulated the expression of ZNF582, thereby inhibiting EC cell viability and metastasis, promoting apoptosis and inhibiting tumor growth. Conclusion: Low expression of ZNF582-AS1/ZNF582 mediated by DNA hypermethylation facilitates the malignant progression of EC.
Promoter hypermethylation silences ZNF582-AS1 and ZNF582, driving esophageal cancer progression, which has the potential for novel therapeutic strategies. # Methylation # Esophageal Cancer.
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Metilação de DNA , Neoplasias Esofágicas , Regulação Neoplásica da Expressão Gênica , Regiões Promotoras Genéticas , RNA Longo não Codificante , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Humanos , RNA Longo não Codificante/genética , Animais , Linhagem Celular Tumoral , Camundongos , Progressão da Doença , Proliferação de Células , Apoptose/genética , Camundongos Nus , Masculino , FemininoRESUMO
BACKGROUND: Since COVID-19 became a global epidemic disease in 2019, pulmonary fibrosis (PF) has become more prevalent among persons with severe infections, with IPF being the most prevalent form. In traditional Chinese medicine, various disorders are treated using Sinomenine (SIN). The SIN's strategy for PF defense is unclear. METHODS: Bleomycin (BLM) was used to induce PF, after which inflammatory factors, lung histological alterations, and the TGF-/Smad signaling pathway were assessed. By administering various dosages of SIN and the TGF- receptor inhibitor SB-431,542 to human embryonic lung fibroblasts (HFL-1) and A549 cells, we were able to examine proliferation and migration as well as the signaling molecules implicated in Epithelial-Mesenchymal Transition (EMT) and Extra-Cellular Matrix (ECM). RESULTS: In vivo, SIN reduced the pathological changes in the lung tissue induced by BLM, reduced the abnormal expression of inflammatory cytokines, and improved the weight and survival rate of mice. In vitro, SIN inhibited the migration and proliferation by inhibiting TGF-ß1/Smad3, PI3K/Akt, and NF-κB pathways, prevented the myofibroblasts (FMT) of HFL-1, reversed the EMT of A549 cells, restored the balance of matrix metalloenzymes, and reduced the expression of ECM proteins. CONCLUSION: SIN attenuated PF by down-regulating TGF-ß/Smad3, PI3K/Akt, and NF-κB signaling pathways, being a potential effective drug in the treatment of PF.
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Morfinanos , Proteínas Proto-Oncogênicas c-akt , Fibrose Pulmonar , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Células A549 , Bleomicina , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Regulação para Baixo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Pulmão/patologia , Pulmão/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Morfinanos/farmacologia , Morfinanos/uso terapêutico , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
INTRODUCTION: Primary chest wall tumors account for 5% of all thoracic neoplasms and 1% of all primary tumors. Chondrosarcoma is a rare solid tumor, with an annual incidence of <0.5 per million people per year. It predominantly occurs in the pelvis and femur, occasionally occurs in flat bones such as the sternum and ribs, and rarely invades lung tissue. Chest wall chondrosarcomas represent only 5-15% of all chondrosarcomas. Radical surgery often leads to a large range of chest wall defects, especially when the range exceeds 6 cm × 6 cm and involves the sternum, spine, or multiple consecutive ribs. The reconstruction of the chest wall bone should be considered to restore the integrity and stability of the chest, prevent chest wall softening and abnormal breathing, and ensure the stability of respiratory circulation. Chest wall reconstruction can help restore thoracic hardness and integrity, prevent lung hernia and abnormal breathing, while also ensuring a positive aesthetic outcome. The chest wall reconstruction includes reconstruction of the pleura, bony structures, and soft tissues. CASE REPORT: In our case of an adult male, after the resection of the third and fourth anterior rib chondrosarcoma, the common anatomical plate was shaped and fixed to the stump of the third rib with screws to ensure the stability of the thorax while retaining the mobility of the thorax. After applying hernia mesh pruning, the chest wall defect was stitched to complete the pleural reconstruction of the defect area. This procedure can effectively maintain the stability of the pleural cavity, provide more effective support for the chest wall soft tissue, and promote the recovery of upper limb function and lung function. CONCLUSION: The radical surgery of giant chest wall chondrosarcoma often leads to a large range of chest wall defects. Chest wall reconstruction needs to be carried out at the same time to restore the integrity and stability of the chest wall, to avoid chest wall softening and abnormal breathing, and to ensure the stability of respiratory circulation. Using the "sandwich" method for chest wall reconstruction, in which an anatomical plate is combined with hernia mesh and muscle soft tissue, and during which pleura, bony structure, and soft tissues are reconstructed, can provide more effective support for chest wall soft tissue, effectively prevent postoperative muscle tissue collapse, avoid postoperative abnormal breathing, and promote the recovery of postoperative upper limb function and lung function. It is a very effective method for chest wall reconstruction.
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Neoplasias Ósseas , Condrossarcoma , Procedimentos de Cirurgia Plástica , Costelas , Neoplasias Torácicas , Parede Torácica , Humanos , Condrossarcoma/cirurgia , Parede Torácica/cirurgia , Masculino , Neoplasias Torácicas/cirurgia , Neoplasias Ósseas/cirurgia , Costelas/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Pessoa de Meia-IdadeAssuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Tomografia Computadorizada por Raios X , Progressão da DoençaRESUMO
Lung adenocarcinoma (LUAD) is one of the most lethal and common malignancies. The energy metabolism of LUAD is a critical factor affecting its malignant progression, and research on this topic can aid in the development of novel cancer treatment targets. Bioinformatics analysis of the expression of long non-coding RNA (lncRNA) LINC00665 in LUAD was performed. Downstream regulatory molecules of LINC00665 were predicted using the StarBase database. We used quantitative reverse transcription polymerase chain reaction and western blot to measure the expression at mRNA and protein levels, respectively. The effects of the LINC00665/let-7c-5p/HMMR axis on cell viability in vitro were tested by CCK-8 assay. The regulatory effects on glycolysis were analyzed by extracellular acidification rate, oxygen consumption rate, glucose uptake, adenosine triphosphate production, and lactate production. The predicted competitive endogenous RNA mechanism between LINC00665 and let-7c-5p/HMMR was verified by a dual-luciferase reporter gene assay. LINC00665 was upregulated in LUAD. Silencing LINC00665 inhibited tumor proliferation and reduced the glycolytic activity of tumor cells. Additionally, the expression of LINC00665 had a negative correlation with that of let-7c-5p, while the expression of HMMR was remarkably inhibited by let-7c-5p. HMMR could affect the development of LUAD by influencing glycolytic capacity. Mechanistically, LINC00665 acted as a molecular sponge to absorb let-7c-5p and targeted HMMR. Transfection of let-7c-5p inhibitor or overexpression of HMMR plasmid could reverse the inhibition in proliferation and glycolysis of LUAD cells induced by silencing of LINC00665. In summary, this study demonstrated that the LINC00665/let-7c-5p/HMMR regulatory axis promoted the tumorigenesis of LUAD by enhancing aerobic glycolysis, suggesting that this regulatory axis was an effective target for inhibiting LUAD progression and providing theoretical support for the development of new drugs for LUAD.
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Adenocarcinoma , MicroRNAs , Humanos , Glicólise , Metabolismo Energético , Sobrevivência Celular , Pulmão , MicroRNAs/genética , Proliferação de Células , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão GênicaRESUMO
OBJECTIVES: This study aimed to investigate whether adding glue injection to three-dimensional computed tomography bronchography and angiography (3D-CTBA) has extra benefits to facilitate anatomical segmentectomy for pulmonary nodules. METHODS: We conducted a randomized controlled trial. The patients undergoing thoracoscopic segmentectomy assisted with 3D-CTBA simulation were enrolled. Then, they were divided into the 3D-CTBA group and the glue-labelling group who received additional computed tomography-guided percutaneous glue (2-octyl cyanoacrylate) injection to label the nodules. The primary outcome was the resection rate of the nodules, and the secondary measures included the operation time, complications and thorax drainage. RESULTS: A total of 173 patients were randomized into the 3D-CTBA group (89 patients) and glue-labelling group (84 patients) between January 2018 and March 2019. Before the segmentectomy, the patients using glue labelling recorded 5 (6.0%) cases of pneumothorax, 2 (2.4%) cases of haemothorax and 1 (1.2%) case of severe chest pain. All the surgical procedure was performed fluently and safely. The resection rate of the nodules was 100% in both groups. Furthermore, these patients demonstrated similar operation time [(141.5 ± 41.9) vs (142.1 ± 38.9) min], estimated blood loss [(111.3 ± 74.0) vs (106.0 ± 63.8) ml], duration of chest tube duration [(5.1 ± 3.0) vs (5.0 ± 3.5) days] and total drainage volume [(872.3 ± 643.1) vs (826.7 ± 806.0) ml], with a P-value of >0.05 respectively. In addition, 6 (7.1%) patients in the glue-labelling group and 6 (6.7%) patients in the 3D-CTBA group reported air leakage (>5 days) and chylothorax. CONCLUSIONS: Noninvasive 3D-CTBA alone is probably sufficient to facilitate anatomical segmentectomy. The additional invasive glue labelling could be avoided in selected patients who undergo intentional segmentectomy. CLINICAL TRIAL REGISTRATION: The trial was registered under the Chinese Clinical Trial Registry (ChiCTR). Identifier: ChiCTR1800018293, https://www.chictr.org.cn/showproj.html?proj=29345.
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PURPOSE: Esophageal squamous cell carcinoma (ESCC) is characterized by early metastasis and late diagnosis. miR-29c-3p is confirmed to repress angiogenesis in multiple tumor types. Yet, the functions of miR-29c-3p in the mechanism of ESCC angiogenesis, which were not sufficiently explored previously, were exactly what we investigated here at the molecular level. METHODS: The mRNA level of miR-29c-3p and Serpin peptidase inhibitor clade H member 1 (SERPINH1) in ESCC tissues were assessed via bioinformatics analysis. Thereafter, miR-29c-3p and SERPINH1 (HSP47) mRNA level in ESCC cell lines was evaluated via quantitative real-time polymerase chain reaction. The effects of abnormal miR-29c-3p and SERPINH1 expression on ESCC cell viability, proliferation, migration, invasion, and HUVEC angiogenesis were examined via CCK8, colony formation, transwell, and angiogenesis assays, respectively. The protein levels of SERPINH1, vascular endothelial growth factor-A (VEGFA), Wnt-1, ?-catenin, and p-?-catenin were evaluated via Western blot. Expression of VEGFA secreted by ESCC cells was measured via enzyme-linked immunosorbent assay. Treatment with the Wnt activator BML-284 further revealed the way miR-29c-3p mediated the Wnt signaling pathway and its effects on angiogenesis. RESULTS: Herein, we revealed a decrease of miR-29c-3p expression in ESCC tissues and cells, while the overexpressed miR-29c-3p could remarkably suppress ESCC cell progression, as well as HUVEC angiogenesis. Meanwhile, overexpressed miR-29c-3p notably downregulated VEGFA and repressed the Wnt signaling pathway. Treatment with the Wnt activator BML-284 could reverse the inhibition of HUVEC angiogenesis caused by miR-29c-3p. SERPINH1 was a downstream target of miR-29c-3p. SERPINH1 knockdown suppressed the malignant phenotypes of ESCC cells and impeded the Wnt signaling activation, while such suppression was reversed through miR-29c-3p inhibitor. CONCLUSIONS: We confirmed the mechanism that miR-29c-3p targeted SERPINH1, thus regulating angiogenesis in ESCC through the Wnt signaling pathway. It improves the understanding of angiogenesis in ESCC and offers new ideas for the research of ESCC treatment strategies in the future.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , MicroRNAs , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Via de Sinalização Wnt , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Linhagem Celular Tumoral , Cateninas/metabolismo , RNA Mensageiro , Angiogênese , Proliferação de Células , Proteínas de Choque Térmico HSP47/metabolismoRESUMO
As part of the tumor microenvironment (TME), collagen plays a significant role in cancer fibrosis formation. However, the collagen family expression profile and clinical features in lung adenocarcinoma (LUAD) are poorly understood. The objective of the present work was to investigate the expression pattern of genes from the collagen family in LUAD and to develop a predictive signature based on collagen family. The Cancer Genome Atlas (TCGA) samples were used as the training set, and five additional cohort samples obtained from the Gene Expression Omnibus (GEO) database were used as the validation set. A predictive model based on five collagen genes, including COL1A1, COL4A3, COL5A1, COL11A1, and COL22A1, was created by analyzing samples from the TCGA cohort using LASSO Cox analysis and univariate/multivariable Cox regression. Using Collagen-Risk scores, LUAD patients were then divided into high- and low-risk groups. KM survival analysis showed that collagen signature presented a robust prognostic power. GO and KEGG analyses confirmed that collagen signature was associated with extracellular matrix organization, ECM-receptor interaction, PI3K-Akts and AGE-RAGE signaling activation. High-risk patients exhibited a considerable activation of the p53 pathway and cell cycle, according to GSEA analysis. The Collage-Risk model showed unique features in immune cell infiltration and tumor-associated macrophage (TAM) polarization of the TME. Additionally, we deeply revealed the association of collagen signature with immune checkpoints (ICPs), tumor mutation burden (TMB), and tumor purity. We first constructed a reliable prognostic model based on TME principal component-collagen, which would enable clinicians to treat patients with LUAD more individually.
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Lung adenocarcinoma (LUAD) is a common malignancy. Many studies have shown that LUAD is resistant to gemcitabine chemotherapy, resulting in poor treatment outcomes in patients. We designed this study to reveal influences of hsa-miR-195-5p/E2F7/CEP55 axis on gemcitabine resistance and autophagy of LUAD cells. The expression data of LUAD-related mRNAs were downloaded from TCGA-LUAD database for differential expression analysis. The bioinformatics databases (hTFtarget, starBase and TargetScan) were used to predict the upstream and downstream regulatory molecules of E2F7. Then the binding relationships between E2F7 and regulatory molecules were verified by ChIP and dual-luciferase reporter assay. qRT-PCR and western blot were used to detect the mRNA and protein levels of has-miR-195-5p, E2F7, and CEP55. CCK-8 assay was used to analyze the half-maximal inhibitory concentration (IC50) and cell proliferation ability of LUAD cells after gemcitabine treatment. Apoptosis was detected by flow cytometry. Apoptosis/autophagy markers and LC3 aggregation were detected by western blot and immunofluorescence, respectively. Finally, the mouse transplantation model was constructed to verify the regulation mechanism in vivo. In LUAD cells and tissues, E2F7 and CEP55 were highly expressed, while has-miR-195-5p was relatively less expressed. The ChIP or dual-luciferase assays demonstrated the binding relationships of E2F7 to the CEP55 promoter region and has-miR-195-5p to the 3'-UTR of E2F7. Cell experiments demonstrated that overexpression of hsa-miR-195-5p stimulated LUAD cell apoptosis and inhibited autophagy and gemcitabine resistance, while further overexpression E2F7/CEP55 could reverse the impact by hsa-miR-195-5p overexpression. In vivo experiments identified that hsa-miR-195-5p/E2F7/CEP55 axis constrained the growth of LUAD tumor. Hsa-miR-195-5p promoted apoptosis, repressed proliferation, and autophagy via E2F7/CEP55 and reduced gemcitabine resistance in LUAD, indicating that hsa-miR-195-5p/E2F7/CEP55 may be a novel target for LUAD.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , MicroRNAs , Animais , Camundongos , Gencitabina , Adenocarcinoma de Pulmão/genética , MicroRNAs/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Regiões 3' não Traduzidas , Autofagia , Proteínas de Ciclo Celular , Proliferação de Células , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica , Linhagem Celular TumoralRESUMO
Searching for differential genes in lung adenocarcinoma (LUAD) is vital for research. Hyaluronan mediated motility receptor (HMMR) promotes malignant progression of cancer patients. However, the molecular regulators of HMMR-mediated LUAD onset are unknown. This work aimed to study the relevance of HMMR to proliferation, migration and invasion of LUAD cells. Let-7c-5p and HMMR levels in LUAD cells and HLF-a cells were assessed, and their correlation was also detected. Their interaction was determined by dual-luciferase experiments and qRT-PCR. Cell proliferation, migration and invasion potentials in vitro were validated through cell counting kit-8 (CCK-8), colony formation, scratch healing, and transwell assays. The expression of HMMR was examined by qRT-PCR and western blot and the expression of let-7c-5p was assayed by qRT-PCR. It was found that HMMR level was increased in LUAD and negatively correlated with let-7c-5p level. Let-7c-5p directly targeted HMMR to repress LUAD cell proliferation, migration and invasion. The above data illustrated that the let-7c-5p/HMMR axis may provide certain therapeutic value for LUAD patients.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , MicroRNAs , Humanos , Adenocarcinoma de Pulmão/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , MicroRNAs/genéticaRESUMO
Purpose: Esophageal squamous cell carcinoma (ESCC) is characterized by early metastasis and late diagnosis. miR-29c-3p is confirmed to repress angiogenesis in multiple tumor types. Yet, the functions of miR-29c-3p in the mechanism of ESCC angiogenesis, which were not sufficiently explored previously, were exactly what we investigated here at the molecular level. Methods: The mRNA level of miR-29c-3p and Serpin peptidase inhibitor clade H member 1 (SERPINH1) in ESCC tissues were assessed via bioinformatics analysis. Thereafter, miR-29c-3p and SERPINH1 (HSP47) mRNA level in ESCC cell lines was evaluated via quantitative real-time polymerase chain reaction. The effects of abnormal miR-29c-3p and SERPINH1 expression on ESCC cell viability, proliferation, migration, invasion, and HUVEC angiogenesis were examined via CCK8, colony formation, transwell, and angiogenesis assays, respectively. The protein levels of SERPINH1, vascular endothelial growth factor-A (VEGFA), Wnt-1, ?-catenin, and p-?-catenin were evaluated via Western blot. Expression of VEGFA secreted by ESCC cells was measured via enzyme-linked immunosorbent assay. Treatment with the Wnt activator BML-284 further revealed the way miR-29c-3p mediated the Wnt signaling pathway and its effects on angiogenesis. Results: Herein, we revealed a decrease of miR-29c-3p expression in ESCC tissues and cells, while the overexpressed miR-29c-3p could remarkably suppress ESCC cell progression, as well as HUVEC angiogenesis. Meanwhile, overexpressed miR-29c-3p notably downregulated VEGFA and repressed the Wnt signaling pathway. Treatment with the Wnt activator BML-284 could reverse the inhibition of HUVEC angiogenesis caused by miR-29c-3p. SERPINH1 was a downstream target of miR-29c-3p. SERPINH1 knockdown suppressed the malignant phenotypes of ESCC cells and impeded the Wnt signaling activation, while such suppression was reversed through miR-29c-3p inhibitor. Conclusions: We confirmed the mechanism that miR-29c-3p targeted SERPINH1, thus regulating angiogenesis in ESCC through the Wnt signaling pathway. It improves the understanding of angiogenesis in ESCC and offers new ideas for the research of ESCC treatment strategies in the future.
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MicroRNAs , Proteínas Angiogênicas , Via de Sinalização Wnt , Carcinoma de Células Escamosas do EsôfagoRESUMO
The use of the white-light thoracoscopy is hampered by the low contrast between oncologic margins and surrounding normal parenchyma. As a result, many patients with in situ or micro-infiltrating adenocarcinoma have to undergo lobectomy due to a lack of tactile and visual feedback in the resection of solitary pulmonary nodules. Near-infrared (NIR) guided indocyanine green (ICG) fluorescence imaging technique has been widely investigated due to its unique capability in addressing the current challenges; however, there is no special consensus on the evidence and recommendations for its preoperative and intraoperative applications. This manuscript will describe the development process of a consensus on ICG fluorescence-guided thoracoscopic resection of pulmonary lesions and make recommendations that can be applied in a greater number of centers. Specifically, an expert panel of thoracic surgeons and radiographers was formed. Based on the quality of evidence and strength of recommendations, the consensus was developed in conjunction with the Chinese Guidelines on Video-assisted Thoracoscopy, and the National Comprehensive Cancer Network (NCCN) guidelines on the management of pulmonary lesions. Each of the statements was discussed and agreed upon with a unanimous consensus amongst the panel. A total of 6 consensus statements were developed. Fluorescence-guided thoracoscopy has unique advantages in the visualization of pulmonary nodules, and recognition and resection of the anterior plane of the pulmonary segment. The expert panel agrees that fluorescence-guided thoracoscopic surgery has the potential to become a routine operation for the treatment of pulmonary lesions.
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To evaluate the prognostic role of the preoperative plasma lipid profile, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in patients with lung squamous cell carcinoma (LUSC) who underwent complete resection. Clinical data, including preoperative plasma profile levels, were retrospectively collected and reviewed in 300 patients with LUSC who underwent radical lung resection between 2016 and 2017. The overall survival (OS) and disease-free survival (DFS) were assessed by the Kaplan-Meier method and the Cox proportional hazards regression model. TG ≤ 1.35, HDL-C ≤ 1.17, and LDL-C ≤ 2.32 were deemed as independent preoperative risk factors for OS, and HDL-C ≤ 1.17 was an independent preoperative risk factor for DFS. In the multivariate analyses involving OS and DFS, a decreased HDL-C level was significantly associated with worse OS (HR, 0.546; 95% CI, 0.380-0.784, P = 0.001) and DFS (HR, 0.644; 95% CI, 0.422-0.981, P = 0.041). Additionally, an increased TG (HR, 0.546; 95% CI, 0.366-0.814, P = 0.003) or LDL-C (HR, 0.652; 95% CI, 0.456-0.933, P = 0.019) level was significantly associated with better OS. In patients with LUSC, decreased levels of HDL-C may predict worse outcomes for both DFS and OS, while increased TG or LDL-C levels may predict better OS.
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Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Carcinoma de Células Escamosas/cirurgia , HDL-Colesterol , LDL-Colesterol , Humanos , Lipoproteínas HDL , Pulmão , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , TriglicerídeosRESUMO
To deliver doxorubicin (DOX) with enhanced efficacy and safety in vivo, fullerenol-modified micelles were prepared with the amphiphilic polymer DSPE-PEG-C60 as a carrier, which was synthesized by linking C60(OH)22 with DSPE-PEG-NH2. Studies of its particle size, PDI, zeta potential, and encapsulation efficiency were performed. DOX was successfully loaded into the micelles, exhibiting a suitable particle size [97 nm, 211 nm, 260 nm, vector: DOX = 5:1, 10:1; 15:1 (W/W)], a negative zeta potential of around -30 mv, and an acceptable encapsulation efficiency [86.1, 95.4, 97.5%, vector: DOX = 5:1, 10:1; 15:1 (W/W)]. The release behaviors of DOX from DSPE-PEG-C60 micelles were consistent with the DSPE-PEG micelles, and it showed sustained release. There was lower cytotoxicity of DSPE-PEG-C60 micelles on normal cell lines (L02, H9c2, GES-1) than free DOX and DSPE-PEG micelles. We explored the protective role of DSPE-PEG-C60 on doxorubicin-induced cardiomyocyte damage in H9c2 cells, which were evaluated with a reactive oxygen species (ROS) assay kit, JC-1, and an FITC annexin V apoptosis detection kit for cellular oxidative stress, mitochondrial membrane potential, and apoptosis. The results showed that H9c2 cells exposed to DSPE-PEG-C60 micelles displayed decreased intracellular ROS, an increased ratio of red fluorescence (JC-1 aggregates) to green fluorescence (JC-1 monomers), and a lower apoptotic ratio than the control and DSPE-PEG micelle cells. In conclusion, the prepared DOX-loaded DSPE-PEG-C60 micelles have great promise for safe, effective tumor therapy.
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BACKGROUND: Integrin ß (ITGB) superfamily plays an essential role in the intercellular connection and signal transmission. It was exhibited that overexpressing of ITGB family members promotes the malignant progression of lung adenocarcinoma (LUAD), but the relationship between ITGB superfamily and the LUAD prognosis remains unclear. METHODS: In this study, the samples were assigned to different subgroups utilizing non-negative matrix factorization clustering according to the expression of ITGB family members in LUAD. Kaplan-Meier (K-M) survival analysis revealed the significant differences in the prognosis between different ITGB subgroups. Subsequently, we screened differentially expressed genes among different subgroups and conducted univariate Cox analysis, random forest feature selection, and multivariate Cox analysis. 9-feature genes (FAM83A, AKAP12, PKP2, CYP17A1, GJB3, TMPRSS11F, KRT81, MARCH4, and STC1) in the ITGB superfamily were selected to establish a prognostic assessment model for LAUD. RESULTS: In accordance with the median risk score, LUAD samples were divided into high- and low-risk groups. The receiver operating characteristic (ROC) curve of LUAD patients' survival was predicted via K-M survival curve and principal component analysis dimensionality reduction. This model was found to have a favorable performance in LUAD prognostic assessment. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of differentially expressed genes between groups and Gene Set Enrichment Analysis (GSEA) of intergroup samples confirmed that the high- and low-risk groups had evident differences mainly in the function of extracellular matrix (ECM) interaction. Risk score and univariate and multivariate Cox regression analyses of clinical factors showed that the prognostic model could be applied as an independent prognostic factor for LUAD. Then, we draw the nomogram of 1-, 3-, and 5-year survival of LUAD patients predicted with the risk score and clinical factors. Calibration curve and clinical decision curve proved the favorable predictive ability of nomogram. CONCLUSION: We constructed a LUAD prognostic risk model based on the ITGB superfamily, which can provide guidance for clinicians on their prognostic judgment.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/patologia , Humanos , Integrinas/genética , Neoplasias Pulmonares/patologia , Proteínas de Neoplasias , Prognóstico , Medição de RiscoRESUMO
Esophageal squamous cell carcinoma (ESCC) is one of the malignant tumors with high mortality in humans, and there is a lack of effective and convenient early diagnosis methods. By analyzing the serum miRNA expression data in ESCC tumor samples and normal samples, on the basis of the maximal relevance and minimal redundancy (mRMR) feature selection and the incremental feature selection method, a random forest classifier constructed by five-feature miRNAs was acquired in our study. The receiver operator characteristic curve showed that the model was able to distinguish samples. Principal component analysis (PCA) and sample hierarchical cluster analysis showed that five-feature miRNAs could well distinguish ESCC patients from healthy individuals. The expression levels of miR-663a, miR-5100 and miR-221-3p all showed a higher expression level in ESCC patients than those in healthy individuals. On the contrary, miR-6763-5p and miR-7111-5p both showed lower expression levels in ESCC patients than those in healthy individuals. In addition, the collected clinical serum samples were used for qRT-PCR analysis. It was uncovered that the expression trends of the five-feature miRNAs followed a similar pattern with those in the training set. The above findings indicated that the five-feature miRNAs may be serum tumor markers of ESCC. This study offers new insights for the early diagnosis of ESCC.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , MicroRNAs , Biomarcadores Tumorais/genética , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Carcinoma de Células Escamosas do Esôfago/genética , Humanos , Aprendizado de Máquina , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
The role of anti-programmed cell death protein-1 (PD-1) antibody camrelizumab in brain metastases (BMs) from lung adenocarcinoma is uncertain. Herein, for the first time, we report the efficacy of camrelizumab in a patient with chemotherapy-refractory BMs from lung adenocarcinoma. A 49-year-old male non-smoker was admitted with cough and back pain. Primary lung adenocarcinoma with brain and spinal metastases was diagnosed. The specimen from CT-guided lung biopsy showed a positive expression of PD-L1 (~20%).The BMs were enlarged after first-line intravenous pemetrexed/cisplatin and zoledronic acid; whereas second-line camrelizumab demonstrated impressive complete remission of the BMs. The intracranial progression-free survival and overall survival of the patients since the start of the immunotherapy plan prolonged to more than 12 months and 20 months, respectively. In addition, we searched PubMed for relevant studies from inception to May 2020, and a total of 23 reports enrolling 1187 patients also indicated the promising efficacy of immunotherapy for BMs from lung cancer. However, more and better evidence is still needed before a definite conclusion could be drawn.
Assuntos
Adenocarcinoma de Pulmão/patologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Neoplasias Pulmonares/patologia , Neoplasias da Coluna Vertebral/tratamento farmacológico , Neoplasias da Coluna Vertebral/secundário , Ácido Zoledrônico/administração & dosagem , Neoplasias Encefálicas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Coluna Vertebral/mortalidadeRESUMO
BACKGROUND: To explore if the quantitative perfusion histogram parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) correlates with the expression of PTEN, P-Akt and m-TOR protein in lung cancer. METHODS: Thirty-three patients with 33 lesions who had been diagnosed with lung cancer were enrolled in this study. They were divided into three groups: squamous cell carcinoma (SCC, 15 cases), adenocarcinoma (AC, 12 cases) and small cell lung cancer (SCLC, 6 cases). Preoperative imaging (conventional imaging and DCE-MRI) was performed on all patients. The Exchange model was used to measure the phar- macokinetic parameters, including Ktrans, Vp, Kep, Ve and Fp, and then the histogram parameters meanvalue, skewness, kurtosis, uniformity, energy, entropy, quantile of above five parameters were analyzed. The expression of PTEN, P-Akt and m-TOR were assessed by immunohistochemistry. Spearman correlation analysis was used to compare the correlation between the quantitative perfusion histogram parameters and the expression of PTEN, P-Akt and m-TOR in different pathological subtypes of lung cancer. RESULTS: The expression of m-TOR (P = 0.013) and P-Akt (P = 0.002) in AC was significantly higher than those in SCC. Vp (uniformity) in SCC group, Ktrans (uniformity), Ve (kurtosis, Q10, Q25) in AC group, Fp (skewness, kurtosis, energy), Ve (Q75, Q90, Q95) in SCLC group was positively correlated with PTEN, and Fp (entropy) in the SCLC group was negatively correlated with PTEN (P < 0.05); Kep (Q5, Q10) in the SCLC group was positively correlated with P-Akt, and Kep (energy) in the SCLC group was negatively correlated with P-Akt (P < 0.05); Kep (Q5) in SCC group and Vp (meanvalue, Q75, Q90, Q95) in SCLC group was positively correlated with m-TOR, and Ve (meanvalue) in SCC group was negatively correlated with m-TOR (P < 0.05). CONCLUSIONS: The quantitative perfusion histogram parameters of DCE-MRI was correlated with the expression of PTEN, P-Akt and m-TOR in different pathological types of lung cancer, which may be used to indirectly evaluate the activation status of PI3K/Akt/mTOR signal pathway gene in lung cancer, and provide important reference for clinical treatment.
Assuntos
Adenocarcinoma/diagnóstico por imagem , Carcinoma de Células Escamosas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Adenocarcinoma/metabolismo , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/metabolismo , Meios de Contraste , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Imagem de Perfusão/métodos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Carcinoma de Pequenas Células do Pulmão/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
Esophageal squamous cell carcinoma (ESCC) turns out to be one of the most prevalent cancer types, leading to a relatively high mortality among worldwide sufferers. In this study, gene microarray data of ESCC patients were obtained from the GEO database, with the samples involved divided into a training set and a validation set. Based on the immune-related differential long non-coding RNAs (lncRNAs) we identified, a prognostic eight-lncRNA-based risk signature was constructed following regression analyses. Then, the predictive capacity of the model was evaluated in the training set and validation set using survival curves and receiver operation characteristic curves. In addition, univariate and multivariate regression analyses based on clinical information and the model-based risk score also demonstrated the ability of the risk score in independently determining the prognosis of patients. Besides, based on the CIBERSORT tool, the abundance of immune infiltrates in tumor samples was scored, and a significant difference was presented between the high- and low- risk groups. Correlation analysis with immune checkpoints (PD1, PDL1, and CTLA4) indicated that the eight-lncRNA signature-based risk score was negatively correlated with PD1 expression, suggesting that the eight-lncRNA signature may have an effect in immunotherapy for ESCC. Finally, GO annotation was performed for the differential mRNAs that were co-expressed with the eight lncRNAs, and it was uncovered that they were remarkably enriched in immune-related biological functions. These results suggested that the eight-lncRNA signature-based risk model could be employed as an independent biomarker for ESCC prognosis and might play a part in evaluating the response of ESCC to immunotherapy with immune checkpoint blockade.