RESUMO
Periostin is an extracellular matrix protein involved in tumorigenesis and metastasis. However, the role of serum periostin as a surrogate marker for treatment efficacy is still unknown. In 122 advanced non-small cell lung cancer cases, 37 patients with benign lung disease and 40 healthy controls, serum periostin was measured by enzyme-linked immunosorbent assays. The associations of serum periostin levels with the clinic-pathological parameters, chemotherapy response, and clinical outcomes of non-small cell lung cancer patients were analyzed. Serum periostin levels were significantly higher in non-small cell lung cancer patients, and it was related significantly to bone metastasis ( p = 0.021). Serum periostin of 65 non-small cell lung cancer patients were detected before and after two cycles of chemotherapy. The patients with and without periostin response had significant difference in objective response to chemotherapy ( p = 0.001). For the 122 non-small cell lung cancer patients, the median progression-free survival was 5 months. In a multivariate analysis, performance status (hazard ratio, 1.71; 95% confidence interval, 1.10-2.67), baseline periostin (hazard ratio, 1.01; 95% confidence interval, 1.00-1.01), and periostin response (hazard ratio, 0.50; 95% confidence interval, 0.29-0.86) were significantly correlated with prognosis. In conclusion, serum periostin was elevated in advanced non-small cell lung cancer patients. Baseline periostin and periostin responses appeared to be reliable surrogate markers to predict chemotherapy response and survival in patients with advanced non-small cell lung cancer.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Moléculas de Adesão Celular/sangue , Prognóstico , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
Long noncoding RNAs (lncRNAs), which refer to a group of RNAs with length more than 200 nucleotides and limited protein-coding potential, play a widespread role in regulating biological processes, such as cell differentiation, proliferation, apoptosis, and migration. LncRNAs are dysregulated in multiple cancers, playing an either oncogenic or tumor-suppressive role. LncRNA GAS5 is a recently identified tumor suppressor involved in several cancers, like breast cancer, prostate cancer, lung cancer, and colorectal cancer. The low-expression pattern confers tumor cells elevated capacity of proliferation and predicts poorer prognosis. Existing studies mirror that lncRNA GAS5 promises to be a novel diagnostic biomarker, therapy target, as well as prognostic biomarker. In this review, we will summarize the current knowledge about this vital lncRNA, from its discovery, characteristics, and biological function to molecular mechanism in various neoplasms.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias/genética , Neoplasias/patologia , RNA Longo não Codificante/fisiologia , Feminino , Genes Supressores de Tumor/fisiologia , Humanos , Masculino , PrognósticoRESUMO
In more recent years, long non-coding RNAs (lncRNAs) have been investigated as a new class of regulators of cellular processes, such as cell growth, apoptosis, and carcinogenesis. Although lncRNAs are dysregulated in numerous cancer types, limited data are available on the expression profile and functional role of lncRNAs in non-small cell lung cancer (NSCLC). In the present study, we determined the expression pattern of the growth arrest-specific transcript 5 (GAS5) in 72 NSCLC specimens by qRT-PCR and assess its biological functions in the development and progression of NSCLC. The results revealed that GAS5 expression was down-regulated in cancerous tissues compared to adjacent noncancerous tissues (P < 0.05) and was highly related to tumor size and TNM stage (P < 0.05). This correlation between GAS5 and clinicopathological parameters indicates that GAS5 might function as a tumor suppressor. Furthermore, GAS5 overexpression increased tumor cell growth arrest and induced apoptosis in vitro and in vivo. Meanwhile, siRNA-mediated knockdown of GAS5 promoted tumor cell growth. Importantly, through western blot analysis, we found that ectopic expression of GAS5 significantly up-regulated p53 expression and down-regulated transcription factor E2F1 expression. Taken together, these findings suggest that GAS5 is a tumor suppressor in NSCLC, and the action of GAS5 is mediated by p53-dependent and p53-independent pathways. GAS5 could serve as a potential diagnostic marker for NSCLC and may be a novel therapeutic target in patients with NSCLC.
Assuntos
Apoptose/genética , Biomarcadores Tumorais/fisiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/genética , Neoplasias Pulmonares/patologia , RNA Longo não Codificante/fisiologia , Idoso , Animais , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Feminino , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/genética , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , RNA Longo não Codificante/genéticaRESUMO
It is a great surprise that the genomes of mammals and other eukaryotes harbor many thousands of long noncoding RNAs (lncRNAs). Although these long noncoding transcripts were once considered to be simply transcriptional noise or cloning artifacts, multiple studies have suggested that lncRNAs are emerging as new players in diverse human diseases, especially in cancer, and that the molecular mechanisms of lncRNAs need to be elucidated. More recently, evidence has begun to accumulate describing the complex post-transcriptional regulation in which lncRNAs are involved. It was reported that lncRNAs can be implicated in degradation, translation, pre-messenger RNA (mRNA) splicing, and protein activities and even as microRNAs (miRNAs) sponges in both a sequence-dependent and sequence-independent manner. In this review, we present an updated vision of lncRNAs and summarize the mechanism of post-transcriptional regulation by lncRNAs, providing new insight into the functional cellular roles that they may play in human diseases, with a particular focus on cancers.
Assuntos
Neoplasias/genética , Processamento Pós-Transcricional do RNA/genética , Splicing de RNA/genética , RNA Longo não Codificante/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Neoplasias/patologiaRESUMO
INTRODUCTION: Comprehensively evaluating the efficacy and safety of high-frequency oscillatory ventilation (HFOV) is important to allow clinicians who are using or considering this intervention to make appropriate decisions. METHODS: To find randomized controlled trials (RCTs) comparing HFOV with conventional mechanical ventilation (CMV) as an initial treatment for adult ARDS patients, we searched electronic databases (including PubMed, MedLine, Springer Link, Elsevier Science Direct, ISI web of knowledge, and EMBASE) with the following terms: "acute respiratory distress syndrome", "acute lung injury", and "high frequency oscillation ventilation". Additional sources included reference lists from the identified primary studies and relevant meta-analyses. Two investigators independently screened articles and extracted data. Meta-analysis was conducted using random-effects models. RESULTS: We included 6 RCTs with a total of 1,608 patients in this meta-analysis. Compared with CMV, HFOV did not significantly reduce the mortality at 30 or 28 days. The pooled relative risk (RR) was 1.051 (95% confidence interval (CI) 0.813 to 1.358). ICU mortality was also not significantly reduced in HFOV group, with a pooled RR of 1.218 (95% CI 0.925 to 1.604). The pooled effect sizes of HFOV for oxygenation failure, ventilation failure and duration of mechanical ventilation were 0.557 (95% CI 0.351 to 0.884), 0.892 (95% CI 0.435 to 1.829) and 0.079 (95% CI -0.045 to 0.203), respectively. The risk of barotrauma and hypotension were similar between the CMV group and HFOV group, with a RR of 1.205 (95% CI 0.834 to 1.742) and a RR of 1.326 (95% CI 0.271 to 6.476), respectively. CONCLUSIONS: Although HFOV seems not to increase the risk of barotrauma or hypotension, and reduces the risk of oxygenation failure, it does not improve survival in adult acute respiratory distress syndrome patients.
Assuntos
Ventilação de Alta Frequência/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/terapia , Adulto , Ventilação de Alta Frequência/efeitos adversos , Humanos , Unidades de Terapia Intensiva/tendências , Mortalidade/tendências , Ensaios Clínicos Controlados Aleatórios como Assunto/mortalidade , Respiração Artificial/efeitos adversos , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/mortalidade , Resultado do TratamentoRESUMO
Cisplatin resistance significantly impacts the antitumor efficacy of cisplatin chemotherapy and contributes to poor prognosis, including metastasis. In this study, we present the utilization of metal-organic framework (MOF) nanoparticles as the therapeutic component and drug loading scaffold for implementing a ternary combination therapeutic strategy to combat cisplatin-resistant lung cancer and metastasis. Specifically, by engineering MOFs (Cis@MOF-siVEGF) through the self-assembly of THPP as photosensitizer for photodynamic therapy (PDT), along with the incorporation of cisplatin (DDP) and VEGF siRNA (siVEGF), we propose the leverage of photodynamic-induced oxidative damage and gene silencing of the angiogenic factor to reverse cisplatin resistance and sensitize therapeutic potency. Our findings demonstrated that the chemo/photodynamic/antiangiogenic triple combination therapy via Cis@MOF-siVEGF under irradiation effectively inhibits cisplatin-resistant tumor growth and induces abscopal effects. Importantly, molecular mechanistic exploration suggested that MUC4 exerted regulatory effects on governing cancer metastasis, thus representing a potential immunotherapeutic target for cancer intervention. Overall, our study creates a MOFs-based multicomponent delivery platform for complementary therapeutic modules with synergistically enhanced antitumor efficacy and sheds light on potential regulatory mechanisms on cisplatin-resistance cancers.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Cisplatino , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares , Estruturas Metalorgânicas , RNA Interferente Pequeno , Fator A de Crescimento do Endotélio Vascular , Cisplatino/farmacologia , Cisplatino/química , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Humanos , RNA Interferente Pequeno/química , RNA Interferente Pequeno/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/terapia , Mucina-4/metabolismo , Fotoquimioterapia , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Metástase Neoplásica , Camundongos Nus , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: Neutrophil to lymphocyte ratio (NLR) has been shown to be a prognosis indicator in different types of cancer. We aimed to investigate the association between NLR and therapy response, progression free survival (PFS) and overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients treated with first-line platinum-based chemotherapy. METHODS: Patients who were hospitalized between January 2007 and December 2010 were enrolled and eliminated according to the inclusion and exclusion criteria. The NLR was defined as the absolute neutrophil count divided by the absolute lymphocyte count. Logistic regression analysis was applied for response rate and Cox regression analysis was adopted for PFS and OS. A P value of ≤0.05 was considered to be statistically significant. RESULTS: A total of 182 patients were enrolled in the current study. The median PFS was 164.5 days and median OS was 439.5 days. The statistical analysis data indicated that low pretreatment NLR (≤ 2.63) (OR = 2.043, P = 0.043), decreased posttreatment NLR (OR = 2.368, P = 0.013), well and moderate differentiation (OR = 2.773, P = 0.021) and normal CEA level (≤ 9.6 ng/ml) (OR = 2.090, P = 0.046) were associated with response to first-line platinum-based chemotherapy. A high pretreatment NLR (HR = 1.807, P = 0.018 for PFS, HR = 1.761, P = 0.020 for OS) and distant metastasis (HR = 2.118, P = 0.008 for PFS, HR = 2.753, P = 0.000 for OS) were independent prognostic factors for PFS and OS. CONCLUSION: Elevated pretreatment NLR might be a potential biomarker of worse response to first-line platinum-based chemotherapy and shorter PFS and OS for advanced NSCLC patients. To confirm these findings, larger, prospective and randomized studies are needed.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/imunologia , Neoplasias Pulmonares/imunologia , Contagem de Linfócitos , Linfócitos/imunologia , Neutrófilos/imunologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cisplatino/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Contagem de Leucócitos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do TratamentoRESUMO
OBJECTIVE: To explore the protein-tyrosine-phosphatase 1B (PTP1B) expression and its prognostic significance in non-small-cell lung cancer (NSCLC). METHODS: Immunohistochemical method of EnVision was applied to investigate the expression of PTP1B in lung specimens from 63 cases with NSCLC and 9 cases with pneumonia confirmed by pathological examination after surgical removals at Jinling Hospital from June 2000 to October 2010. The data of PTP1B expression in different lung tissues and its relationship with clinicopathological features and prognostic value for survival were analyzed by chi-square test, Kaplan-Meire survival analysis, Log rank test and multivariable Cox regression analysis. RESULTS: The expression of PTP1B was negative in pneumonia group while positive in NSCLC tissues (32/63, 50.8%) (χ(2) = 8.229, P = 0.004). The expression of PTP1B in NSCLC tissue was not correlated with gender, age, smoking history, tumor size, pathological type, lymph node metastasis and chemotherapy, but significantly associated with pTNM staging (χ(2) = 6.426, P = 0.040). Kaplan-Meire survival analysis showed that the expression of PTP1B was significantly correlated with overall survival (Log-rank, P = 0.047). Multivariable Cox regression analysis indicated that both PTP1B (HR = 2.050, P = 0.044) and pTNM staging (HR = 3.631, P = 0.000) were independent prognostic factors for NSCLC. CONCLUSIONS: PTP1B may be a biomarker for differential diagnosis of malignant lung disease. And PTP1B and pTNM were independent prognostic factors for NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Pulmão/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Pneumonia/patologia , PrognósticoRESUMO
BACKGROUND: Although the treatment of ERBB2-altered non-small cell lung cancer (NSCLC) has been studied for many years, there are no comprehensive studies to evaluate the benefits of various therapies as first-line treatment. Through the development of immunotherapy, more and more different combination treatments were applicated in clinical practice, therefore, we conducted a multicenter retrospective study to evaluate the efficacy of different treatments. METHODS: We enrolled patients with ERBB2-altered NSCLC who had undergone at least one-line systemic anticancer treatment to evaluate the efficacy of first-line chemotherapy alone (Chemo), anti-ERBB2 tyrosine kinase inhibitor (TKI), chemotherapy plus immunotherapy (Chemo + Immuno), chemotherapy plus anti-angiogenesis therapy (Chemo + Antiangio) and chemotherapy combined with immunotherapy and anti-angiogenesis therapy (Chemo + Immuno + Antiangio). The clinical outcomes included objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), one-year and three-year survival rate. RESULTS: We enroll 36 patients harboring ERBB2 mutation and 29 with ERBB2 amplification. The overall ORR was 30.8%, DCR was 69.2% and mPFS was 5.7 months. Chemo + Immuno and Chemo + Antiangio both achieved longer mPFS than TKI (7.8 vs 3.6 months, HR: 0.24, 95 %CI: 0.09-0.64, P = 0.002; 5.9 vs 3.6 months, HR: 0.36, 95 %CI: 0.15-0.88, P = 0.019; respectively), while there was no significant difference in mPFS between Chemo + Immuno or Chemo + Antiangio and Chemo (both P > 0.05), the mPFS of the first two was longer. For ERBB2-mutant patients, the mPFS was 5.9 months, and Chemo + Immuno and Chemo + Antiangio both achieved longer mPFS than TKI (12.9 vs 2.9 months, HR: 0.15, 95 %CI: 0.03-0.68, P = 0.005; 7.1 vs 2.9 months, HR: 0.50, 95 %CI: 0.29-0.88, P = 0.009, respectively). In the same therapies, patients with ERBB2 mutation or ERBB2 amplification showed no statistical significance in PFS (both P > 0.05). CONCLUSIONS: In the first-line treatment of ERBB2-altered NSCLC, chemotherapy combined with immunotherapy or anti-angiogenesis therapy may have greater survival benefits than ERBB2-target therapy, but the efficacy may not be better than that of chemotherapy.
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 , Estudos Retrospectivos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/efeitos adversos , MutaçãoRESUMO
BACKGROUND: Studies have shown that the incidence and severity of corona virus disease 2019 (COVID-19) in patients with lung cancer are higher than those in healthy people. At present, the main anti-tumor treatments for lung cancer include surgery, immunotherapy, chemotherapy, radiotherapy, targeted therapy and anti-angiogenesis therapy. While the effects of different anti-tumor treatments on the occurrence and severity of COVID-19 pneumonia are not uniform. Therefore, we aimed to describe clinical characteristics and antitumor therapy of patients with lung cancer and COVID-19 pneumonia, and examined risk factors for severity in this population. METHODS: From December 1, 2022 to February 15, 2023, a retrospective study was conducted in 217 patients diagnosed with COVID-19 and pathologically confirmed lung cancer in the Jinling Hospital. We collected data about patients' clinical features, antitumor treatment regimen within 6 months, and the diagnosis and treatment of COVID-19. Risk factors for occurrence and severity of COVID-19 pneumonia were identified by univariable and multivariable Logistic regression models. RESULTS: (1) Among the 217 patients included, 51 (23.5%) developed COVID-19 pneumonia, of which 42 (82.4%) were classified as medium and 9 (17.6%) were classified as severe; (2) Univariate and multivariate analysis revealed overweight (OR=2.405, 95%CI: 1.095-5.286) and intrapulmonary focal radiotherapy (OR=2.977, 95%CI: 1.071-8.274) are risk factors for increasing occurrence of COVID-19 pneumonia, while other therapies are not; (3) Chronic obstructive pulmonary disease (COPD) history (OR=7.600, 95%CI: 1.430-40.387) was more likely to develop severe pneumonia and anti-tumor therapies such as intrapulmonary focal radiotherapy, chemotherapy, targeted therapy and immunotherapy did not increase severity. CONCLUSIONS: Intrapulmonary focal radiation therapy within 6 months increased the incidence of COVID-19 pneumonia, but did not increase the severity. However, there was no safety concern for chemotherapy, targeted therapy, surgery and immunotherapy.
Assuntos
COVID-19 , Neoplasias Pulmonares , Pneumonia , Humanos , Estudos Retrospectivos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Incidência , Pneumonia/etiologiaRESUMO
Background: Dynamic needle-tip positioning (DNTP) was shown to improve arterial cannulation efficiency with fewer complications than conventional palpation and ultrasound methods by some studies. However, this is still controversial, and we performed this meta-analysis to comprehensively assess its value in arterial cannulation. Methods: A literature search of randomized controlled trials was conducted, and 11 studies were finally included. Efficiency outcomes (first-attempt success, overall success, and total cannulation time) and complications (hematoma, thrombosis, posterior wall puncture, and vasospasm) were separately analyzed. Subgroup analyses in different populations under cannulation were also performed. Results: DNTP was associated with increased first-attempt success (pooled RR = 1.792, p < 0.001), overall success (pooled RR = 1.368, p = 0.001), and decreased cannulation time (pooled SMD = −1.758, p = 0.001) than palpation. DNTP gained even more advantage in small children and infants. No significant difference in these outcomes between DNTP and conventional ultrasound method was detected. Fewer hematoma occurred in DNTP than palpation (pooled RR = 0.265, p < 0.001) or traditional ultrasound (pooled RR = 0.348, p < 0.001). DNPT was also associated with fewer posterior wall punctures (pooled RR = 0.495, p = 0.001) and vasospasm (pooled RR = 0.267, p = 0.007) than traditional ultrasound. Conclusions: DNTP was a better choice in artery cannulation than conventional palpation and ultrasound method, especially in small children and infants.
RESUMO
OBJECTIVE: To explore the values of low-dose computed tomography (LDCT) in the screening of high-risk populations for early lung cancer through a meta-analysis of the relevant literature. METHODS: PubMed, EBSCO, Cochrane and other databases were searched with key words. And the studies were selected by the inclusion and exclusion criteria. The baseline data were collected and analyzed by statistical software. RESULTS: Ten random controlled trials (RCTs) were selected. Compared to the chest X ray (CXR) screening and no screening controls, LDCT screening had an odds ratio (OR) of 3.705, 95%CI 3.527 - 3.891. And in the subgroup analysis, a higher number of stage I lung cancer was detected (OR 4.464, 95%CI 2.860 - 6.969) by LDCT. Moreover, LDCT screening showed an increased detection of adenocarcinoma in lung cancer (OR 4.652, 95%CI 2.877 - 7.522). CONCLUSION: LDCT is superior to CXR in the early detection of lung cancer, especially stage I and adenocarcinoma.
Assuntos
Adenocarcinoma/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada Espiral/métodos , Adenocarcinoma de Pulmão , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: The number of lung cancer in the elderly is increasing. However, a disturbing number of elderly patients failed to get pathological diagnosis and therapeutic outcomes are worse than the young. This study is conducted to explore the diagnosis and treatment status of lung cancer in patients over 75 years old. METHODS: Patients diagnosed with lung cancer between September 1, 2010 and October 30, 2017 were continuously screened. The pathological diagnosis must be based on the cytology or histology diagnosis. The clinical diagnosis must be built on both typical imaging features and increased tumor markers. Clinical features and survival information were obtained and analyzed. RESULTS: A total of 338 primary lung cancer inpatients were finally included with an age of 78.02±2.94 years. The most frequent comorbidities were hypertension, chronic obstructive pulmonary disease (COPD) and cardiovascular disease; 290 of all these patients were pathologically diagnosed while the other 48 patients only got a clinical diagnosis. Among the pathological diagnosis, adenocarcinoma, squamous carcinoma and small cell lung cancer counted for 91.72%. Epidermal growth factor receptor (EGFR) detection was performed in 126 patients and 41 of them were sensitive mutated. Among all included patients, 150 were treated by the best supportive treatment (BST). Anti-cancer treatment is significantly associated with better survival than BST (P<0.001). Definite sensitive mutation is associated with improved survival than undetected patients in EGFR-tyrosine kinase inhibitors (TKIs) treatment patients (P=0.039). CONCLUSIONS: Pathological diagnosis of lung cancer in elderly patients is relatively deficient. Pathologic and molecular pathological diagnosis derived anti-cancer treatment is effective in improving survival.
RESUMO
Currently, in clinical settings, all TP53 mutations have been considered equally. However, numerous studies have demonstrated that the position and type of mutation have differential effects on prognosis. Such discrepancy can be partially due to the lack of unifying classification system for TP53 mutations. In the present study, two of the most frequently used systems were compared, according to the location of the mutation or its functional effects on p53 protein and the impact of TP53 mutations on the overall survival (OS) time of 379 Chinese patients with advanced lung cancer was analyzed. Capture-based ultra-deep targeted sequencing on plasma samples of 379 patients with advanced lung cancer was performed. The present results suggested that mutations occurring in exon 8 may be associated with shorter OS in tyrosine kinase inhibitor-naïve patients (P=0.013) and in patients previously treated with one line of treatment (P=0.032). The results of the present study provided solid evidence that not all TP53 mutations were associated with a similar prognosis. Mutations in exon 8 were found in a subgroup of patients with unfavorable prognosis across various treatment histories. To the best of our knowledge, the present study is the first to compare different TP53 mutation classification systems in a large cohort of patients with advanced lung cancer.
RESUMO
Metastasis of cancer cells is a key impediment to favorable outcomes of cancer treatment. Functional roles of long noncoding RNAs in several biological processes, including metastasis, have recently been discovered. In our previous work, we reported a positive correlation of increased expression of linc00673 in NSCLC tissues with tumor size, lymph node metastasis, TNM stage, and increased proliferation of NSCLC cells, both, in vitro and in vivo. In this study, we demonstrate that ectopic expression of linc00673 promotes migration and invasion of NSCLC cells. Furthermore, our results indicate that linc00673 could silence HOXA5 expression by recruiting epigenetic repressor, EZH2, at its promoter regions. HOXA5 was identified as a tumor suppressor gene, which inhibited NSCLC cell metastasis by regulating cytoskeletal remodeling. To summarize, we for the first time identified the role of lin00673 in promoting invasion and migration of NSCLC cells. Insights from this study may help to identify novel therapeutic targets for NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteínas de Homeodomínio/genética , Neoplasias Pulmonares/patologia , RNA Longo não Codificante/genética , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Metástase Linfática , Camundongos , Estadiamento de Neoplasias , Transplante de Neoplasias , Prognóstico , Regiões Promotoras Genéticas , Ligação ProteicaRESUMO
The number of patients diagnosed with pulmonary nodules increased as more patients with high risk of lung cancer choose low-dose computed tomography (CT) scans for the screening of cancer. Clinicians might get two questions from the patients: what is the definite diagnosis of the nodule? What should we do? We have already got many guidelines trying to solve these problems. There are also several prediction models for pulmonary nodules. However, guidelines are not suitable for all types of patients, and the reality of patients is more complicated. Here we reported a 58-year-old man with a lung nodule in the right upper lobe, which was occasionally found during a period of pneumonia. We suggested two periods of follow-up, and the patient was also admitted to a clinical trial about circulating tumor cells (CTCs). He finally accepted surgical excision with a pathologic diagnosis of adenocarcinoma. This case suggests that: we might suggest CT surveillance for patients with solid nodules about 8 mm maximum diameter; three-dimensional reconstruction of CT scans could provide more information about the details of nodules; CTCs counts of peripheral blood could be considered as a potential clue for malignancy.
RESUMO
OBJECTIVES: Can addition of neurokinin-1 receptor antagonists (NK1-RAs) be considered as an ideal strategy for the prevention of chemotherapy-induced nausea and vomiting (CINV)? Researchers differ on this question. MATERIALS AND METHODS: Electronic databases were searched for randomized control trials (RCTs) that evaluated the effectiveness and safety of NK1-RAs in preventing CINV. The primary end point was complete response (CR) in the acute, delayed, and overall phases after chemotherapy. Subgroup analyses evaluated the types of NK1-RAs, routines of administration, types of malignancies, regimens used in combination with NK1-RAs, and age of patients included in the studies. The incidences of different types of adverse events were also extracted to estimate the safety of NK1-RAs. RESULTS: A total of 38 RCTs involving 13,923 patients were identified. The CR rate of patients receiving NK-RAs was significantly higher than patients in the control groups during overall phase (70.8% vs 56.0%, <0.001), acute phase (85.1% vs 79.6%, <0.001), and delayed phase (71.4% vs 58.2%, <0.001). There were three studies including patients of children or adolescents, the CR rate was also significantly higher in the treatment group (overall phase: OR=2.807, <0.001; acute phase: OR=2.863, P =0.012; delayed phase: OR=2.417, <0.001). For all the other outcomes, patients in the NK1-RAs groups showed improvements compared to the control groups (incidence of nausea: 45.2% vs 45.9%, <0.001; occurrence of vomiting: 22.6% vs 38.9%, <0.001; usage of rescue drugs: 23.5% vs 34.1%, <0.001). The pooled side effects from NK1-RAs did not significantly differ from previous reports and the toxicity rates in patients less than eighteen years old also did not diff between the two groups (P=0.497). However, we found that constipation and insomnia were more common in the patients of control groups, whereas diarrhea and hiccups were more frequently detected in patients receiving NK1-RAs. CONCLUSIONS: NK1-RAs improved the CR rate of CINV. They are effective for both adults and children. The use of NK1-RAs might be associated with the appearance of diarrhea and hiccups, while decreasing the possibility of constipation and insomnia.
Assuntos
Antineoplásicos/efeitos adversos , Náusea/prevenção & controle , Neoplasias/tratamento farmacológico , Antagonistas dos Receptores de Neurocinina-1/uso terapêutico , Vômito/prevenção & controle , Adolescente , Adulto , Humanos , Náusea/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Vômito/induzido quimicamenteRESUMO
Bronchioloalveolar carcinoma (BAC) is a unique lung neoplasm with variable forms, such as single nodular, multifocal and lobar pneumonic types. The pneumonic type BAC is often difficult to differentiate from pneumonia. Here we present a case of 63-year-old Chinese male, who had recurrent cough, white sputum with pneumonic lesions in left lower lobe. He suffered from lung biopsies for three times, and finally diagnosed as high differentiated adenocarcinoma 8 years later. He was treated with four cycles of pemetrexed and cisplatin, and four cycles of docetaxel and nedaplatin. However, he did not achieve disease stabilization and is still under follow up. This case suggests that, pneumonic type adenocarcinoma may radiographically and clinically resemble infectious pneumonia. Lack of fever and leukocytosis, no response to antibiotics, air bronchogram, and accompanied nodules or patches in computed tomography (CT) scans should raise suspicion about the diagnosis of pneumonia. Lung biopsy might be the only means of ruling in a diagnosis of BAC.