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BACKGROUND: Models for predicting the survival outcomes of stage I non-small-cell lung cancer (NSCLC) defined by the newly released 8th edition TNM staging system are scarce. This study aimed to develop a nomogram for predicting the cancer-specific survival (CSS) of these patients and identifying individuals with a higher risk for CSS. METHODS: A total of 30,475 NSCLC cases were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We identified and integrated the risk factors to build a nomogram. The model was subjected to bootstrap internal validation with the SEER database, and external validation with a multicenter cohort of 1133 patients from China. The difference in the impact of adjuvant chemotherapy on model-defined high- and low-risk patients was examined using the National Cancer Database (NCDB). RESULTS: Eight independent prognostic factors were identified and integrated into the model. The calibration curves showed good agreement. The concordance index (C-index) of the nomogram was higher than that of the staging system (IA1, IA2, IA3, and IB) (internal validation set 0.63 vs. 0.56; external validation set 0.66 vs. 0.55; both p < 0.01). Specifically, 21.7% of stage IB patients (7.5% of all stage I) were categorized into the high-risk group (score > 30). There was a significant interaction effect between the adjuvant chemotherapy and risk groups in the NCDB cohort (p = 0.003). CONCLUSIONS: We established a practical nomogram to predict CSS for 8th edition stage I NSCLC. A prospective study is warranted to determine its role in identifying adjuvant chemotherapy candidates.
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Adenocarcinoma Bronquioloalveolar/mortalidade , Adenocarcinoma/mortalidade , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/mortalidade , Neoplasias Pulmonares/mortalidade , Estadiamento de Neoplasias/normas , Nomogramas , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adenocarcinoma Bronquioloalveolar/patologia , Adenocarcinoma Bronquioloalveolar/terapia , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Estudos de Coortes , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Programa de SEER , Taxa de SobrevidaRESUMO
Objective. Considering the demerits of a high-definition 2-dimensional (HD-2D) system, with its lack of stereopsis, and a conventional 3-dimensional (C-3D) system, which results in a dimmed image, we have recently developed a glasses-free 3-dimensional (GF-3D) display system for reconstruction surgeries such as video-assisted thoracic surgery (VATS) for tracheal reconstruction. Methods. Thoracic surgeons were invited to complete thoracoscopic continuous suture of a transected porcine trachea using the HD-2D, C-3D, and GF-3D systems on separate mornings in randomized order. The duration, numbers of stitches, and distance between every 2 stitches were recorded for every procedure. The surgeons' spontaneous eye blink rate was recorded for 5 minutes before the procedure and the last 5 minutes of the procedure. Results. Fifteen volunteers successfully completed the tracheal reconstruction procedures in this study. Both C-3D (0.403 ± 0.064 stitch/min, P < .001) and GF-3D (0.427 ± 0.079 stitch/min, P < .001) showed significant advantages in speed compared with HD-2D (0.289 ± 0.065 stitch/min). Both C-3D (2.536 ± 2.223 mm, P < .001) and GF-3D (2.603 ± 2.159 mm, P < .001) showed significant advantages in accuracy compared with HD-2D (3.473 ± 3.403 mm). Both HD-2D (1.240 ± 0.642, P < .001) and GF-3D (1.307 ± 0.894, P < .001) showed significant advantages in eye fatigue compared with C-3D (3.333 ± 1.44). Conclusions. All 3 available display systems are efficient for complex VATS. With the help of stereopsis, surgeons can achieve faster operation using C-3D and GF-3D systems in a thoracoscopic simulated setting. GF-3D may be a more effective display system for VATS reconstruction in terms of speed, accuracy, and eye fatigue during operations.
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Imageamento Tridimensional/métodos , Cirurgia Torácica Vídeoassistida/métodos , Animais , Piscadela/fisiologia , Desenho de Equipamento , Humanos , Duração da Cirurgia , Cirurgiões , Suínos , Cirurgia Torácica Vídeoassistida/instrumentação , Cirurgia Torácica Vídeoassistida/estatística & dados numéricosRESUMO
BACKGROUND: There have been no studies to systematically evaluate the two display (3D vs. 2D) systems regarding both laparoscopic and thoracoscopic surgeries in clinical settings; thus, we conducted one to evaluate the safety and efficacy of different visualization systems (two-dimensional and three-dimensional) during endoscopic surgery (laparoscopy or thoracoscopy) in clinical settings. METHODS: A comprehensive search of online databases was performed. Perioperative outcomes were synthesized. Cumulative meta-analysis was performed to evaluate the temporal trend of pooled outcomes. Specific subgroups (laparoscopy vs. thoracoscopy, prospective vs. retrospective study, malignant vs. benign diseases) were examined. Meta-regression was conducted to explore the source of heterogeneity. RESULTS: Twenty-three articles were considered in this analysis, of which 7 were thoracoscopic and 16 were laparoscopic surgeries. A total of 2930 patients were recorded, of which 1367 underwent 3D video-assisted surgery and 1563 underwent 2D display. Overall, significantly shorter operating time (SMD -0.69; p = <0.001), less blood loss (SMD -0.26; p = 0.028) and shorter hospital stays (SMD -0.16; p = 0.016) were found in the 3D display group. Meanwhile, the perioperative morbidity (OR 0.92; p = 0.487), retrieved lymph nodes (SMD 0.09; p = 0.081), drainage duration (SMD -0.15; p = 0.105) and drainage volume (SMD 0.00; p = 0.994) were similar between the two groups. Comparison of the overall outcomes in each subset showed consistency in all groups. CONCLUSIONS: This up-to-date meta-analysis reveals that the 3D display system is superior to the 2D system in clinical settings with significantly shorter operating time, less blood loss and shorter hospital stay. These findings suggest that, in laparoscopic or thoracoscopic surgeries, 3D endoscopic system is preferable when condition permits. Future efforts should be made on decreasing the side effects of 3D display and increasing its cost-effectiveness.
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Imageamento Tridimensional/métodos , Cirurgia Vídeoassistida/métodos , Adulto , Idoso , Feminino , Humanos , Laparoscopia/métodos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Toracoscopia/métodosRESUMO
OBJECTIVES: The investigation was aimed to evaluate the safety and efficacy of glasses-free 3-dimensional (3D) video-assisted thoracoscopic surgery (VATS) versus 2D VATS for radical resection of non-small cell lung cancer (NSCLC). METHODS: We reviewed the clinical data of patients with pathologically proven NSCLC who underwent glasses-free 3D (the 3D group) and 2D VATS radical lobectomy (the 2D group) with systematic lymph node dissection. The outcomes of this study included operative characteristics and safety of 2D and 3D VATS, and duration of lymphadenectomy of right stations 2 and 4. RESULTS: A total of 190 patients were eligible for the study. The 2D group consisted of 108 patients while the 3D group included 82 patients. The 2 groups were comparable in demographic and baseline variables ( P > .05). The median number of resected lymph nodes was 19 in both groups ( P = .583). The median length of hospital stay was comparable between the 2 groups (2D, 7 days vs 3D, 8 days; P = .167). No operative mortality was reported in either group. Complications developed in 21 (19.4%) patients in the 2D group and 14 (17.1%) in the 3D group ( P = .710). A subgroup analysis of patients who underwent right station 2 and 4 lymphadenectomy showed that the mean time for right station 2 and 4 lymph node dissection was significantly shorter in the 3D group than in the 2D group (3D, 430.9 ± 237.2 vs 2D, 648.6 ± 364.1 seconds; P < .001). CONCLUSIONS: Glasses-free 3D VATS and 2D VATS are comparable in operative characteristics and safety profile for radical resection of NSCLC. Glasses-free 3D visualization facilitates more rapid right-sided mediastinal lymphadenectomy.
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Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Cirurgia Torácica Vídeoassistida , Idoso , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Cirurgia Torácica Vídeoassistida/métodos , Cirurgia Torácica Vídeoassistida/estatística & dados numéricos , Resultado do TratamentoRESUMO
Advances in lung cancer research applying machine learning (ML) technology have generated many relevant literature. However, there is absence of bibliometric analysis review that aids a comprehensive understanding of this field and its progress. Present article for the first time performed a bibliometric analysis to clarify research status and focus from 2010 to 2021. In the analysis, a total of 2,312 relevant literature were searched and retrieved from the Web of Science Core Collection database. We conducted a bibliometric analysis and further visualization. During that time, exponentially growing annual publication and our model have shown a flourishing research prospect. Annual citation reached the peak in 2017. Researchers from United States and China have produced most of the relevant literature and strongest partnership between them. Medical image analysis and Nature appeared to bring more attention to the public. The computer-aided diagnosis, precision medicine, and survival prediction were the focus of research, reflecting the development trend at that period. ML did make a big difference in lung cancer research in the past decade.
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Lung cancer (LC) is the leading cause of cancer-associated deaths worldwide, among which non-small-cell lung cancer (NSCLC) accounts for 80%. Stromal cell-derived factor-1 (SDF-1) inhibition results in a significant depletion of NSCLC metastasis. Additionally, SDF-1 is the only natural chemokine known to bind and activate the receptor CXCR4. Thus, we attempted to clarify the molecular mechanism of SDF-1 underlying NSCLC progression. Transwell migration, adhesion, and G-LISA assays were used to assess megakaryocytic chemotaxis in vitro and in vivo in terms of megakaryocytic migration, adherence, and RhoA activation, respectively. Western blotting was used to assess PI3K/Akt-associated protein abundances in MEG-01 cells and primary megakaryocytes under the indicated treatment. A hematology analyzer and flow cytometry were used to assess platelet counts in peripheral blood and newly formed platelet counts in Lewis LC mice under different treatments. Immunochemistry and flow cytometry were used to measure CD41+ megakaryocyte numbers in Lewis LC mouse tissue under different treatments. ELISA was used to measure serum TPO levels, and H&E staining was used to detect NSCLC metastasis.SDF-1 receptor knockdown suppressed megakaryocytic chemotaxis in Lewis LC mice. SDF-1 receptor inhibition suppressed megakaryocytic chemotaxis via the PI3K/Akt pathway. SDF-1 receptor knockdown suppressed CD41+ megakaryocyte numbers in vivo through PI3K/Akt signaling. SDF-1 receptor inhibition suppressed CD41+ megakaryocytes to hinder NSCLC metastasis. SDF-1 facilitates NSCLC metastasis by enhancing the chemoattraction of megakaryocytes via the PI3K/Akt signaling pathway, which may provide a potential new direction for seeking therapeutic plans for NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Quimiocina CXCL12 , Quimiotaxia , Neoplasias Pulmonares , Megacariócitos , Transdução de Sinais , Animais , Humanos , Camundongos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Quimiocina CXCL12/metabolismo , Quimiocina CXCL12/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Megacariócitos/metabolismo , Megacariócitos/patologia , Metástase Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Receptores CXCR4/metabolismo , Receptores CXCR4/genéticaRESUMO
SCOPE: Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer (EOC) that is associated with higher interleukin-6 (IL-6) levels, and suppression of the Janus kinase 2/Signal transducer and activator of transription 3 (JAK2/STAT3) pathway may contribute to the suppression of this cancer. This study aims to compare the anti-cancer effect of pterostilbene (PSB) and 2'- and 3'-hydroxypterostilbene (2HPSB and 3HPSB, respectively) on the JAK2/STAT3 pathway. METHODS AND RESULTS: In vitro experiments with the OCCC cell line TOV21G and a xenograft nude mouse model are used to achieve the study aims. The results showed that 3HPSB has the greatest anti-proliferative and pro-apoptotic effects of the three compounds studied. Activation of the JAK2/STAT3 pathway and the nuclear translocation of STAT3 are effectively inhibited by 3HPSB and PSB. Both 3HPSB and PSB can effectively suppress tumor growth, which is mediated by the inhibition of JAK2/STAT3 phosphorylation. CONCLUSION: This is the first study to compare the efficacy of PSB, 3HPSB, and the newly identified compound 2HPSB regarding ovarian cancer. Moreover, targeting JAK2/STAT3 is shown to be a potentially effective strategy for OCCC treatment. This study is expected to provide new insights into the potential of the abovementioned phytochemicals for development as adjuvants for cancer treatment in the future.
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Carcinoma , Neoplasias Ovarianas , Feminino , Animais , Camundongos , Humanos , Janus Quinase 2/metabolismo , Janus Quinase 2/farmacologia , Linhagem Celular Tumoral , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Fator de Transcrição STAT3/metabolismo , Proliferação de CélulasRESUMO
RNA interference (RNAi) was first literaturally reported in 1998 and has become rapidly a promising tool for therapeutic applications in gene therapy. In a typical RNAi process, small interfering RNAs (siRNA) are used to specifically downregulate the expression of the targeted gene, known as the term "gene silencing." One key point for successful gene silencing is to employ a safe and efficient siRNA delivery system. In this context, dendrimers are emerging as potential nonviral vectors to deliver siRNA for RNAi purpose. Dendrimers have attracted intense interest since their emanating research in the 1980s and are extensively studied as efficient DNA delivery vectors in gene transfer applications, due to their unique features based on the well-defined and multivalent structures. Knowing that DNA and RNA possess a similar structure in terms of nucleic acid framework and the electronegative nature, one can also use the excellent DNA delivery properties of dendrimers to develop effective siRNA delivery systems. In this review, the development of dendrimer-based siRNA delivery vectors is summarized, focusing on the vector features (siRNA delivery efficiency, cytotoxicity, etc.) of different types of dendrimers and the related investigations on structure-activity relationship to promote safe and efficient siRNA delivery system.
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Dendrímeros/química , Interferência de RNA , RNA Interferente Pequeno/genética , Animais , Dendrímeros/classificação , Dendrímeros/uso terapêutico , Terapia Genética/métodos , Humanos , RNA Interferente Pequeno/metabolismoRESUMO
Several studies have demonstrated great potential implications for the gut-lung axis in lung disease etiology and treatment. The gut environment can be influenced by diet, metabolites, microbiotal composition, primary diseases, and medical interventions. These changes modulate the functions of alveolar macrophages (AMs) to shape the pulmonary immune response, which greatly impacts lung health. The immune modulation of AMs is implicated in the pathogenesis of various lung diseases. However, the mechanism of the gut-lung axis in lung diseases has not yet been determined. This mini-review aimed to shed light on the critical nature of communication between the gut and AMs during the development of pulmonary infection, injury, allergy, and malignancy. A better understanding of their crosstalk may provide new insights into future therapeutic strategies targeting the gut-AM interaction.
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Hipersensibilidade , Pneumopatias , Humanos , Macrófagos Alveolares , Pulmão , Hipersensibilidade/metabolismoRESUMO
Transplantation is an important life-saving therapeutic choice for patients with organ or tissue failure once all other treatment options are exhausted. However, most allografts become damaged over an extended period, and post-transplantation survival is limited. Ischemia reperfusion injury (IRI) tends to be associated with a poor prognosis; resultant severe primary graft dysfunction is the main cause of transplant failure. Targeting the cGAS-STING pathway has recently been shown to be an effective approach for improving transplantation outcomes, when activated or inhibited cGAS-STING pathway, IRI can be alleviated by regulating inflammatory response and programmed cell death. Thus, continuing efforts to develop selective agonists and antagonists may bring great hopes to post-transplant patient. In this mini-review, we reviewed the role of the cGAS-STING pathway in transplantation, and summarized the crosstalk between this pathway and inflammatory response and programmed cell death during IRI, aiming to provide novel insights into the development of therapies to improve patient outcome after transplantation.
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Transplante de Rim , Traumatismo por Reperfusão , Humanos , Traumatismo por Reperfusão/metabolismo , Apoptose , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Transplante de Rim/efeitos adversosRESUMO
Background: In the tumor immune microenvironment, the contribution of innate and adaptive immune cells to tumor progression has been consistently demonstrated. However, reliable prognostic biomarkers for lung adenocarcinoma (LUAD) have not yet been identified. We thus developed and validated an immunologic long noncoding RNA (lncRNA) signature (ILLS) to facilitate the classification of patients with high and low risk and provide potential "made-to-measure" treatment choices. Methods: The LUAD data sets were obtained and processed from public databases of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The abundance of immune infiltration and its related pathways were calculated through consensus clustering, weighted gene coexpression network analysis (WGCNA), and an integrated ImmLnc to identify immune-related lncRNAs and extract immune-related prognostic lncRNAs. Based on the integrative procedure, the best algorithm composition was least absolute shrinkage and selection operator (LASSO) and stepwise Cox regression in both directions to develop the ILLS in the TCGA-LUAD data set and validate the predictive power of 4 independent data sets, GSE31210, GSE37745, GSE30219, and GSE50081 through survival analysis, receiver operating characteristic (ROC) analysis, and multivariate Cox regression. The concordance index (C-index) analysis was transversely compared with 49 published signatures in the above 5 data sets to further confirm its stability and superiority. Finally, drug sensitivity analysis was conducted to explore potential therapeutic agents. Results: Patients from the high-risk groups consistently had worse overall survival (OS) compared to the low-risk groups. ILLS proved to be an independent prognostic factor with favorable sensitivity and specificity. Among the 4 GEO data sets, compared to those reported in the other literature, ILLS maintained stable prediction ability and was more suitable as a consensus risk-stratification tool. However, The Cancer Immunome Atlas and IMvigor210 data sets demonstrated practical utility in recognizing target populations with effective immunotherapy, while the high-risk group exhibited potential targets for certain chemotherapy drugs, such as carmustine, etoposide, arsenic trioxide, and alectinib. Conclusions: ILLS demonstrated superior and stable prognostic prediction ability and thus has potential as a tool for assisting in risk classification and clinical decision-making in patients with LUAD.
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The refractoriness of tumor cells to apoptosis represents the main mechanism of resistance to chemotherapy. Smac/DIABLO mimetics proved to be effective in overcoming cancer-acquired resistance to apoptosis as a consequence of overexpression of the anti-apoptotic proteins XIAP, cIAP1, and cIAP2. In this work, we describe a dual-targeting peptide capable of selectively activating apoptosis in cancer cells. The complex consists of a fluorescent periodic mesoporous organosilica nanoparticle that carries the short sequences of Smac/DIABLO bound to the αvß3-integrin ligand. The dual-targeting peptide @PMO shows significantly higher toxicity in αvß3-positive HeLa cells with respect to αvß3-negative Ht29 cells. @PMO exhibited synergistic effects in combination with oxaliplatin in a panel of αvß3-positive cancer cells, while its toxicity is overcome by XIAP overexpression or integrin ß3 silencing. The successful uptake of the molecule by αvß3-positive cells makes @PMO promising for the re-sensitization to apoptosis of many cancer types.
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BACKGROUND AND OBJECTIVES: microRNAs (miRNAs), small non-coding RNAs, are always aberrantly expressed in many diseases including human cancers. The aim of this study was to examine and determine the clinical significance of hsa-miR-31, hsa-miR-142-3p, hsa-miR-338-3p, and hsa-miR-1261 expression in esophageal squamous cell carcinoma (ESCC). METHODS: Expression levels of four selected miRNAs, initially evaluated by microarray, were validated by qRT-PCR. Various statistical methods were used to analyze the relationship between miRNA expression and clinicopathologic features and prognosis in 91 patients with ESCC. RESULTS: MiR-31 and miR-142-3p expression were correlated to histological differentiation in ESCC (P < 0.05, Student's t-test); high miR-142-3p expression was associated with a poor prognosis in all 91 ESCC patients (P = 0.014, log-rank) and identified as an independent prognostic factor in ESCC (P = 0.017, univariate Cox; P = 0.022, multivariate Cox). More importantly, stratified analysis indicated that high miR-142-3p expression was correlated to a poor prognosis within good-prognosis groups comprised of ESCC patients with small tumor size, negative lymph node metastasis, or early stage (all P < 0.05). CONCLUSION: The main findings suggest that miR-142-3p is involved in the progression of ESCC and is a potential prognostic biomarker for ESCC.
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Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , MicroRNAs/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Esôfago/metabolismo , Esôfago/patologia , Feminino , Seguimentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de SobrevidaRESUMO
Background: Lung transplantation is a treatment for end-stage lung disease. The optimal transplant strategy for patients with end-stage lung disease complicated by pulmonary hypertension (PH) is controversial. The aim of this study is to review this experience and analyze the outcomes of lung transplantation for PH. Methods: This retrospective study collected data on patients with PH undergoing lung transplantation between March 2016 and December 2019 at a single center in China. The perioperative features and short- and medium-term outcomes between single-lung transplantation (SLT) and double-lung transplantation (DLT) were compared. Kaplan-Meier methods were used to analyze overall survival across a variety of transplantation procedures, age, mean pulmonary artery pressure (mPAP), body mass index (BMI), and indications of transplantation. Results: A total of 63 patients with PH were finally included in the analysis. The mean age, mean BMI, and mPAP were 56.37 years, 19.56 kg/m2, and 35.4 mmHg respectively. The overall 1-, 2-, and 3-year survival was 70%, 63%, and 60%, respectively. Five (7.94%) patients died within 30 days after surgery and nine patients (14.3%) died from infection during the followed-up period. There were no significant differences in the short- and medium-term survival outcomes of SLT and DLT, but postoperative pulmonary function was better in DLT. Patients older than 60 years of age had worse survival (P=0.01). Conclusions: The short- and medium-term survival outcomes between SLT and DLT are similar in selected patients with PH. DLT provides better pulmonary function. Patients older than 60 years are associated with worse survival.
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BACKGROUND: Lung cancer is the most commonly diagnosed cancer and the major cause of cancer-related deaths worldwide. The increasing studies have demonstrated that circular RNA (circRNA) was involved in the progression of various cancers, including non-small-cell lung cancer (NSCLC). This study was designed to assess the expression, roles and functional mechanisms of circ_0000735 in NSCLC. MATERIALS AND METHODS: The expression levels of circ_0000735, miR-940 and bone morphogenetic protein binding endothelial cell precursor-derived regulator (BMPER) were estimated by the real-time quantitative polymerase chain reaction (RT-qPCR). The biological behaviors of NSCLC cells such as proliferation, migration and invasion were analyzed by cell counting kit-8 (CCK-8), colony-forming assays and transwell assay, respectively. Furthermore, extracellular acid ratio and lactate production were tested to assess glycolysis levels of NSCLC cells. The interaction relationship among circ_0000735, BMPER and miR-940 was analyzed by bioinformatics database and dual-luciferase reporter assay. The protein expression level of BMPER was assessed by Western blot assay. Tumorigenesis assay was established to clarify the functional roles of circ_0000735 in vivo. RESULTS: Circ_0000735 was upregulated and significantly correlated with overall survival in patients with NSCLC. In addition, the loss-of-functional experiments revealed that knockdown of circ_0000735 repressed proliferation, migration, invasion and glycolysis of NSCLC cells and tumor growth in vivo, which was overturned by overexpression of BMPER. Similarly, overexpression of circ_0000735 enhanced proliferation, migration, invasion, and glycolysis of NSCLC cells. In addition, we also confirmed that overexpression of miR-940 impeded proliferation, migration, invasion, and glycolysis of NSCLC cells. Furthermore, overexpression of BMPER abolished si-circ_0000735 induced effects on NSCLC cells. CONCLUSION: Circ_0000735 regulated proliferation, migration, invasion, and glycolysis in NSCLC cells by targeting miR-940/BMPER axis.
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BACKGROUND: Mediastinal restaging after induction treatment is still a difficult and controversial issue. We aimed to investigate the diagnostic accuracy of endobronchial ultrasound-guided transbronchial needle aspiration and endoscopic ultrasound-guided fine-needle aspiration for restaging the mediastinum after induction treatment in patients with lung cancer. METHODS: Embase and PubMed databases were searched from conception to March 2019. Data from relevant studies were analyzed to assess sensitivity and specificity of endobronchial ultrasound-guided transbronchial needle aspiration and endoscopic ultrasound-guided fine-needle aspiration, and to fit the hierarchical summary receiver operating characteristic curves. RESULTS: A total of 10 studies consisting of 558 patients fulfilled the inclusion criteria. All patients were restaged by endobronchial ultrasound-guided transbronchial needle aspiration, endoscopic ultrasound-guided fine-needle aspiration, or both. Negative results were confirmed by subsequent surgical approaches. There were no complications reported during any endosonography approaches reviewed. The pooled sensitivities of endobronchial ultrasound-guided transbronchial needle aspiration and endoscopic ultrasound-guided fine-needle aspiration were 65% (95% confidence interval [CI], 52-76) and 73% (95% CI, 52-87), respectively, and specificities were 99% (95% CI, 78-100) and 99% (95% CI, 90-100), respectively. The area under the hierarchical summary receiver operating characteristic curves were 0.85 (95% CI, 0.81-0.88) for endobronchial ultrasound-guided transbronchial needle aspiration and 0.99 (95% CI, 0.98-1) for endoscopic ultrasound-guided fine-needle aspiration. Moreover, for patients who received chemotherapy alone, the pooled sensitivity of endosonography with lymph node sampling for restaging was 66% (95% CI, 56-75), and specificity was 100% (95% CI, 34-100); for patients who received chemoradiotherapy, the results seemed similar with a sensitivity of 77% (95% CI, 47-92) and specificity of 99% (95% CI, 48-100). CONCLUSIONS: Endosonography with lymph node sampling is an accurate and safe technique for mediastinal restaging of lung cancer.
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Broncoscopia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Estadiamento de Neoplasias/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Feminino , Humanos , Neoplasias Pulmonares/terapia , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Pneumonectomia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto JovemRESUMO
BACKGROUND: Whether non-intubated spontaneous ventilation video-assisted thoracoscopic surgery (SV-VATS) is a safe procedure remains controversial for mediastinal tumor patients with impaired lung function. Herein, we assessed feasibility of SV-VATS in lung function deficiency patients underwent mediastinal tumor resection. METHODS: From December 2015 to February 2020, 32 mediastinal tumor patients with impaired lung function (preoperative forced expiratory volume in 1 second <70% of the predicted value) were retrospectively collected. Patients were divided into two groups: SV-VATS group and mechanical ventilation VATS (MV-VATS) group. Intraoperative and postoperative variables were compared between two cohorts. RESULTS: Fifteen patients (46.88%) underwent SV-VATS and 17 patients (53.12%) were performed with MV-VATS. The most common causes of lung function deficiency were smoking (81.25%) and COPD (71.88%). Patients in the SV-VATS group had similar blood loss (20.63 vs. 18.76 mL, P=0.417) with MV-VATS group. The anesthesia time (217.51 vs. 197.76 min; P=0.343) and surgery time (141.23 vs. 132.36 min; P=0.209) were also similar between groups. Five people suffered postoperative complications in each group, in which 1 patient underwent MV-VATS was transferred to intensive care unit (ICU) because of prolonged extubation owing to hypoxia. There was no difference on chest tube removal time (2.6 vs. 2.3 days; P=0.172) or hospital duration (5.03 vs. 4.74 days; P=0.297) in patients underwent SV-VATS and MV-VATS. CONCLUSIONS: SV-VATS is safe and provides similar short-term results to MV-VATS for mediastinal tumor resection in patients with limited pulmonary function.
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BACKGROUND: Lung is a reservoir for megakaryocytes (MKs). The relationship between intra-tumoral MKs and non-small cell lung cancer (NSCLC) is unknown. We investigate relationship between high intra-tumoral MKs with the recurrence of NSCLC. METHODS: The tissue sections of 629 patients with resected NSCLC were stained with hematoxylin, anti-CD61, anti-CD34 and stromal cell-derived factor-1 (SDF-1). CD61+ giant cells localized in CD34+ capillaries were identified as MKs. The impact of MKs and preoperative platelet count on disease-free survival (DFS) was investigated. RESULTS: Overall, 18.9% of patients were positive for the presence of MKs. In univariate analysis, the median DFS of the MK+ group was shorter than the median DFS of the MK- group (69.1 vs. 80.5 months; P=0.021). Multivariate analysis indicated that MKs in tumor tissue was an unfavorable prognostic factor for DFS (HR 1.351, P=0.065), the impact of which was more significant in non-squamous cell carcinoma (NSCC) (HR 1.710, P=0.008) and in patients with N0 (HR 1.883, P=0.009). Although systemic platelet count of the MK+ group was significantly higher than the MK- group (270.6×109 vs. 243.6×109/L, P=0.007), the stratified subgroup DFS curves (P=0.003) showed that the effect of MKs on prognosis was independent of the blood platelet count. CONCLUSIONS: Our results demonstrate that CD61+ MKs in tumor tissue predict unfavorable prognosis in NSCLC.
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Rational: LDCT screening can identify early-stage lung cancers yet introduces excessive false positives and it remains a great challenge to differentiate malignant tumors from benign solitary pulmonary nodules, which calls for better non-invasive diagnostic tools. Methods: We performed DNA methylation profiling by high throughput DNA bisulfite sequencing in tissue samples (nodule size < 3 cm in diameter) to learn methylation patterns that differentiate cancerous tumors from benign lesions. Then we filtered out methylation patterns exhibiting high background in circulating tumor DNA (ctDNA) and built an assay for plasma sample classification. Results: We first performed methylation profiling of 230 tissue samples to learn cancer-specific methylation patterns which achieved a sensitivity of 92.7% (88.3% - 97.1%) and a specificity of 92.8% (89.3% - 96.3%). These tissue-derived DNA methylation markers were further filtered using a training set of 66 plasma samples and 9 markers were selected to build a diagnostic prediction model. From an independent validation set of additional 66 plasma samples, this model obtained a sensitivity of 79.5% (63.5% - 90.7%) and a specificity of 85.2% (66.3% - 95.8%) for differentiating patients with malignant tumor (n = 39) from patients with benign lesions (n = 27). Additionally, when tested on gender and age matched asymptomatic normal individuals (n = 118), our model achieved a specificity of 93.2% (89.0% - 98.3%). Specifically, our assay is highly sensitive towards early-stage lung cancer, with a sensitivity of 75.0% (55.0%-90.0%) in 20 stage Ia lung cancer patients and 85.7% (57.1%-100.0%) in 7 stage Ib lung cancer patients. Conclusions: We have developed a novel sensitive blood based non-invasive diagnostic assay for detecting early stage lung cancer as well as differentiating lung cancers from benign pulmonary nodules.
Assuntos
DNA Tumoral Circulante/genética , Metilação de DNA/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer/métodos , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: The optimal treatment for stage IIIA-N2 non-small cell lung cancer (NSCLC) is controversial. We aimed to address this important issue through a Bayesian network meta-analysis. METHODS: We performed a search of electronic databases for randomized controlled trials comparing the following treatments: surgery, radiotherapy, chemotherapy, and their multiple combinations before March 25, 2018. Pooled data on overall survival and treatment-related deaths were analyzed within the Bayesian framework. RESULTS: Eighteen eligible trials reporting 13 treatments were included. In terms of overall survival, neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy or radiotherapy, which tended to be consistent (hazard ratio [HR] 1.14, 95% credible interval [CrI] 0.21 to 5.93), ranked superior to other treatments. Notably, neoadjuvant chemotherapy followed by surgery and adjuvant radiotherapy was significantly more effective in prolonging survival than surgery alone (HR 0.38, 95% CrI 0.18 to 0.81), surgery plus adjuvant radiotherapy (HR 0.51, 95% CrI 0.29 to 0.92) and potentially surgery plus adjuvant chemotherapy (HR 0.49, 95% CrI 0.23 to 1.05). Overall, with 29% as the highest possibility of causing the fewest treatment-related deaths, neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy or radiotherapy was the safest treatment option. CONCLUSIONS: Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy or radiotherapy has the greatest possibility to be the optimal treatment with the best overall survival and fewest treatment-related deaths for stage IIIA-N2 NSCLC.