Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
1.
J Mater Chem B ; 12(17): 4217-4231, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38596904

RESUMO

Numerous studies have shown that there are multiple neural activities involved in the process of bone resorption and bone regeneration, and promoting osteogenesis by promoting neural network reconstruction is an effective strategy for repairing critical size bone defects. However, traumatic bone defects often cause activation of the sympathetic nervous system (SNS) in the damaged area, releasing excess catecholamines (CAs), resulting in a decrease in the rate of bone formation. Herein, a 3D-printed scaffold loaded with propranolol (PRN) is proposed to reduce CA concentrations in bone defect areas and promote bone regeneration through drug release. For this purpose, PRN-loaded methacrylated gelatin (GelMA) microspheres were mixed with low-concentration GelMA and perfused into a 3D-printed porous hydroxyapatite (HAp) scaffold. By releasing PRN, which can block ß-adrenergic receptors, it hinders the activation of sympathetic nerves and inhibits the release of excess CA by the SNS. At the same time, the composite scaffold recruits bone marrow mesenchymal stem cells (BMSCs) and promotes the differentiation of BMSCs in the direction of osteoblasts, which effectively promotes bone regeneration in the rabbit femoral condyle defect model. The results of the study showed that the release of PRN from the composite scaffold could effectively hinder the activation of sympathetic nerves and promote bone regeneration, providing a new strategy for the treatment of bone defects.


Assuntos
Regeneração Óssea , Células-Tronco Mesenquimais , Impressão Tridimensional , Sistema Nervoso Simpático , Alicerces Teciduais , Regeneração Óssea/efeitos dos fármacos , Animais , Coelhos , Sistema Nervoso Simpático/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Alicerces Teciduais/química , Propranolol/farmacologia , Propranolol/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Gelatina/química , Osteogênese/efeitos dos fármacos , Durapatita/química , Durapatita/farmacologia
2.
PLoS One ; 18(3): e0282888, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36928232

RESUMO

Lung squamous cell carcinoma (LUSC) is the primary pathological type of lung cancer with a less favorable prognosis. This study attempts to construct a ferroptosis-associated signature associated with overall survival (OS) that can predict the prognosis of LUSC and explore its relationship with immune infiltration. A 5 ferroptosis-associated gene model was constructed by LASSO-penalized regression analysis to predict the prognosis of patients with LUSC in the TCGA database and validated in the GEO and TCGA databases. Patients were stratified into high-risk and low-risk groups by the median value of the risk scores, and the former prognosis was significantly worse (P<0.001). Additionally, we found a certain association between the two risk groups and immune infiltration through CIBERSORT. Meanwhile, the differentially expressed genes (DEGs) between normal and tumor tissue were used to perform functional analysis, which showed a significant association with leukocyte transendothelial migration pathways in the TCGA cohort. In addition, immune cell infiltration analysis confirmed that M2 macrophages were significantly highly expressed in the high-risk group. Overall, the model successfully established by ferroptosis-associated genes suggests that ferroptosis may be related to immune infiltration in LUSC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Ferroptose , Neoplasias Pulmonares , Humanos , Ferroptose/genética , Prognóstico , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , Pulmão
3.
J Cancer Res Clin Oncol ; 149(10): 6857-6873, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36809502

RESUMO

INTRODUCTION: A comprehensive appraisal of published meta-analyses incorporating Mendelian randomization studies was performed to map the different risk factors and assess the causality for lung cancer. METHODS: Systematic reviews and meta-analyses of observational and interventional studies were reviewed based on PubMed, Embase, Web of Science, and Cochrane Library. Mendelian randomization analyses were conducted to validate the causal associations of those various exposures with lung cancer using summary statistics from 10 genome-wide association studies (GWAS) consortia and other GWAS databases in MR-Base platform. RESULTS: In the review of meta-analyses, 105 risk factors associated with lung cancer were identified from 93 articles. It was found that 72 risk factors were nominally significant (P < 0.05) associated with lung cancer. Mendelian randomization analyses were performed to analyze 36 exposures based on 551 SNPs and 4,944,052 individuals, finding that 3 exposures had a consistent risk/protective effect on lung cancer with the results of the meta-analysis. In Mendelian randomization anaylses, smoking (OR 1.44, 95% CI 1.18-1.75; P = 0.001) and blood copper (OR 1.14, 95% CI 1.01-1.29; P = 0.039) significantly associated with increased risk of lung cancer, whereas aspirin use (OR 0.67, 95% CI 0.50-0.89; P = 0.006) showed protective effects. CONCLUSION: This study mapped putative associations of risk factors for lung cancer, revealing the causal hazard effect of smoking, blood copper, and the protective effect of aspirin use in the development of lung cancer. CLINICAL TRIAL REGISTRY: This study is registered with PROSPERO (CRD42020159082).


Assuntos
Neoplasias Pulmonares , Fumar , Humanos , Cobre , Estudo de Associação Genômica Ampla , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Metanálise como Assunto
4.
J Mater Chem B ; 11(4): 837-851, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36594635

RESUMO

The delayed healing of diabetic wounds is directly affected by the disturbance of wound microenvironment, resulting from persistent inflammation, insufficient angiogenesis, and impaired cell functions. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) showed considerable therapeutic potential in diabetic wound healing. However, the low retention rate of MSC-EVs at wound sites hampers their efficacy. For skin wounds exposed to the outer environment, using a hydrogel with tissue adhesiveness under a moist wound condition is a promising strategy for wound healing. In this study, we modified methacryloyl-modified gelatin (GelMA) hydrogel with catechol motifs of dopamine to fabricate a GelMA-dopamine hydrogel. EVs isolated from MSCs were applied in the synthesized GelMA-dopamine hydrogel to prepare a GelMA-dopamine-EV hydrogel. The results demonstrated that the newly formed GelMA-dopamine hydrogel possessed improved properties of softness, adhesiveness, and absorptive capacity, as well as high biocompatibility in the working concentration (15% w/v). In addition, MSC-EVs were verified to promote cell migration and angiogenesis in vitro. In the skin wound model of diabetic rats, the GelMA-dopamine-EV hydrogel exerted prominent wound healing efficacy estimated by collagen deposition, skin appendage regeneration, and the expression of IL-6, CD31, and TGF-ß. In conclusion, this combination of MSC-EVs and the modified hydrogel not only accelerates wound closure but also promotes skin structure normalization by rescuing the homeostasis of the healing microenvironment of diabetic wounds, which provides a potential approach for the treatment of diabetic wounds.


Assuntos
Diabetes Mellitus Experimental , Vesículas Extracelulares , Células-Tronco Mesenquimais , Ratos , Animais , Hidrogéis/química , Diabetes Mellitus Experimental/tratamento farmacológico , Adesivos/farmacologia , Adesivos/uso terapêutico , Dopamina/uso terapêutico , Cicatrização/fisiologia , Gelatina/química
5.
Front Oncol ; 13: 1268260, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38304028

RESUMO

Human epidermal growth factor 2 (HER2) mutations are uncommon in non-small cell lung cancer (NSCLC), and the lack of established, effective, targeted drugs has resulted in a persistently poor prognosis. Herein, we report the case of a non-smoking, 58-year-old man diagnosed with lung adenocarcinoma (cT3N0M1c, stage IVB) harboring a HER2 mutation (Y772_A775dupYVMA) and PD-L1 (-). The patient's Eastern Cooperative Oncology Group performance status (PS) score was assessed as 1. He commenced first-line treatment with chemotherapy, followed by immuno-chemotherapy, and with disease progression, he received HER2-targeted therapy and chemotherapy with an anti-angiogenic agent. However, HER2-targeted therapy, including pan-HER tyrosine kinase inhibitors (afatinib, pyrotinib, and pozitinib) and antibody-drug conjugate (T-DM1), produced only stable disease (SD) as the best response. After the previously described treatment, primary tumor recurrence and multiple brain metastases were observed. Despite the patient's compromised overall physical condition with a PS score of 3-4, he was administered T-DXd in addition to whole-brain radiotherapy (WBRT). Remarkably, both intracranial metastases and primary lesions were significantly reduced, he achieved a partial response (PR), and his PS score increased from 3-4 to 1. He was then treated with T-DXd for almost 9 months until the disease again progressed, and he did not discontinue the drug despite the occurrence of myelosuppression during this period. This is a critical case as it exerted an effective response to T-DXd despite multiple lines therapy, including T-DM1. Simultaneously, despite the occurrence of myelosuppression in the patient during T-DXd, it was controlled after aggressive treatment.

6.
Transl Lung Cancer Res ; 11(7): 1302-1314, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35958335

RESUMO

Background: Previous studies have shown that metabolites play important roles in phenotypic regulation, but the causal link between metabolites and tumors has not been examined adequately. Herein, we investigate the causality between metabolites and various cancers through a Mendelian randomization (MR) study. Methods: We carried out a two-sample MR analysis based on genetic instrumental variables as proxies for 486 selected human serum metabolites to evaluate the causal effects of genetically determined metabotypes (GDMs) on cancers. Summary data from various cancer types obtained from large consortia. Inverse variance weighted (IVW), MR-Egger and weighted-median methods were implemented to infer the causal effects, moreover, we particularly explored the presentence of horizontal pleiotropy through MR-Egger regression and MR-PRESSO Global test. Metabolic pathways analysis and subgroup analyses were further explored using available data. Statistical analyses were all performed in R. Results: In MR analysis, 202 significant causative relationship features were identified. 7-alpha-hydroxy-3-oxo-4-cholestenoate (ORIVW =1.45; 95% CI: 1.06-1.97; PIVW =0.018), gamma-glutamylisoleucine (ORIVW =1.40; 95% CI: 1.16-1.69; PIVW =0.0004), 1-oleoylglycerophosphocholine (ORIVW =1.22; 95% CI: 1.1-1.35; PIVW =0.0001), gamma-glutamylleucine (ORIVW =4.74; 95% CI: 1.18-18.93; PIVW =0.027) were the most dangerous metabolites for lung cancer, ovarian cancer, breast cancer, and glioma, respectively; while pseudouridine (ORIVW =0.50; 95% CI: 0.30-0.83; PIVW =0.007), 2-methylbutyroylcarnitine (ORIVW =0.77; 95% CI: 0.68-0.86; PIVW =2.9×10-6), 2-methylbutyroylcarnitine (ORIVW =0.77; 95% CI: 0.70-0.85; PIVW =3.4×10-7), glycylvaline (ORIVW =0.13; 95% CI: 0.02-0.75; PIVW =0.021) were associated with lower risk of lung cancer, ovarian cancer, breast cancer, and glioma, respectively. Interestingly, 2-methylbutyroylcarnitine was also associated with decreased risk of lung cancer (ORIVW =0.59; 0.50-0.70; P IVW =1.98×10-9) expect ovarian cancer and breast cancer. In subgroup analysis, 2-methylbutyroylcarnitine was associated with decreased risk of estrogen receptor (ER) positive breast cancer (ORIVW =0.72; 0.64-0.80; PIVW =3.55×10-9), lung adenocarcinoma (LAC) (ORIVW =0.60; 0.48-0.70; PIVW =1.14×10-5). Metabolic pathways analysis identified 4 significant pathways. Conclusions: Our study integrated metabolomics and genomics to explore the risk factors involved in the development of cancers. It is worth exploring whether metabolites with causality can be used as biomarkers to distinguish patients at high risk of cancer in clinical practice. More detailed studies are needed to clarify the mechanistic pathways.

7.
Front Endocrinol (Lausanne) ; 13: 1087965, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36733810

RESUMO

Purpose: This study aimed to investigate the causal association between unhealthy lifestyle factors and diabetic retinopathy (DR) risk and to determine better interventions targeting these modifiable unhealthy factors. Design: Two-sample Mendelian randomization (MR) analysis was performed in this study. The inverse variance-weighted method was used as the primary method. Method: Our study included 687 single-nucleotide polymorphisms associated with unhealthy lifestyle factors as instrumental variables. Aggregated data on individual-level genetic information were obtained from the corresponding studies and consortia. A total of 292,622,3 cases and 739,241,18 variants from four large consortia (MRC Integrative Epidemiology Unit [MRC-IEU], Genetic Investigation of Anthropometric Traits [GIANT], GWAS & Sequencing Consortium of Alcohol and Nicotine Use [GSCAN], and Neale Lab) were included. Result: In the MR analysis, a higher body mass index (BMI) (odds ratio [OR], 95% confidence interval [CI] = 1.42, 1.30-1.54; P < 0.001] and cigarettes per day (OR, 95% CI = 1.16, 1.05-1.28; P = 0.003) were genetically predicted to be causally associated with an increased risk of DR, while patients with higher hip circumference (HC) had a lower risk of DR (OR, 95% CI = 0.85, 0.76-0.95; P = 0.004). In the analysis of subtypes of DR, the results of BMI and HC were similar to those of DR, whereas cigarettes per day were only related to proliferative DR (PDR) (OR, 95% CI = 1.18, 1.04-1.33; P = 0.009). In the MR-PRESSO analysis, a higher waist-to-hip ratio (WHR) was a risk factor for DR and PDR (OR, 95% CI = 1.24, 1.02-1.50, P = 0.041; OR, 95% CI = 1.32, 1.01-1.73, P = 0.049) after removing the outliers. Furthermore, no pleiotropy was observed in these exposures. Conclusion: Our findings suggest that higher BMI, WHR, and smoking are likely to be causal factors in the development of DR, whereas genetically higher HC is associated with a lower risk of DR, providing insights into a better understanding of the etiology and prevention of DR.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/etiologia , Retinopatia Diabética/genética , Análise da Randomização Mendeliana , Fatores de Risco , Relação Cintura-Quadril , Índice de Massa Corporal
8.
Transl Lung Cancer Res ; 10(9): 3771-3781, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733627

RESUMO

BACKGROUND: The use of tyrosine kinase inhibitors (TKIs) is associated with incident creatine kinase (CK) elevation in the treatment of advanced non-small cell lung cancer (NSCLC) patients. However, whether higher CK levels are associated with better antitumor responses or survival remains to be explored. We intend to investigate the clinical correlation between CK levels and TKI efficacy in advanced NSCLC. METHODS: In this retrospective study, we enrolled 135 patients with stage IV NSCLC receiving TKI-based therapy in our center between June 2012 to July 2020. CK levels were monitored from the initiation of TKI medication and during the administration period. An X-tile analysis provided the optimal cutoff point for higher baseline CK. Patients were identified and grouped according to their baseline CK level and fold changes during TKI therapy. The primary endpoints included progression-free survival (PFS) and overall survival (OS), and the objective response rate (ORR) was calculated as the secondary endpoint. RESULTS: Among the 135 patients included in our study, those with higher baseline CK levels (≥70 U/L) had favorable PFS (15.2 vs. 8.8 months; P=0.028), while patients with significantly elevated CK (the highest CK value/baseline CK value ≥2 times) appeared to gain better PFS (14.6 vs. 10.0 months; P=0.139). The overall ORR was 67.4%. Patients with higher baseline CK levels had numerically higher ORR (74.6% vs. 60.3%; P=0.076). Similarly, patients with significant CK elevation had a superior 4-month PFS rate (77.6% vs. 59.7%; P=0.029). Results from the subgroup analyses were identical to the overall ones. For patients with higher baseline CK levels, those experiencing significant CK elevation had prolonged PFS (17.2 vs. 14.2 months; P=0.038); a same trend was obtained from the lower baseline CK group (<70 U/L) (9.4 vs. 7.9 months; P=0.038). In multivariable analysis, higher baseline CK level and significant CK elevation remained statistically associated with PFS, with hazard ratios of 0.48 and 0.59, respectively. CONCLUSIONS: Both higher baseline CK levels and significant CK elevation after treatment were correlated with prolonged PFS in NSCLC treated with TKIs, suggesting the potential prognostic and predictive impact of CK level on these patients.

9.
Ann Transl Med ; 9(15): 1265, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532402

RESUMO

Extramedullary plasmacytoma (EMP) is an uncommon monoclonal plasma cell malignancy that arises outside of the bone marrow. Rarely, EMPs can occur in the trachea, resulting in severe respiratory distress. Due to a small number of cases, the optimal management of tracheal EMP remains a topic of debate. Here, we report a rare case of solitary tracheal EMP causing symptoms of cough, sputum, paroxysmal nocturnal dyspnea, and progressive exertional dyspnea in a 65-year-old male patient. Computerized tomography and fibro bronchoscopy indicated a pedicled nodular mass on the anterior tracheal wall obstructing over 95% of the lumen. The patient was soon successfully managed with partial tracheal resection and reconstruction surgery under non-intubated anesthesia and was diagnosed as EMP by histopathology of the resected mass. Additional laboratory tests excluded the diagnosis of multiple myeloma (MM). There are no signs of recurrence after 6 months of follow-up. Although traditional intubated anesthesia with single-lung mechanical ventilation has been widely applied to radical surgery for tracheal tumors, it is associated with a higher incidence of intubation-related complications and thus prolongs the surgical procedure and postoperative recovery. In this article, we reported the application of tracheal resection and reconstruction under non-intubated anesthesia for the treatment of tracheal EMP, which was proved to be feasible and safe. Non-intubated anesthesia for tracheal resection and reconstruction is likely to be an alternative minimally invasive option for patients with tracheal EMP involving central airways.

10.
J Cancer Res Clin Oncol ; 147(10): 2837-2849, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34318357

RESUMO

BACKGROUND: Since little consensus has been reached on whether milder reduction in forced expiratory volume in 1 s (FEV1) increases lung cancer incidence, we conducted a meta-analysis and performed Mendelian randomization (MR) analysis to explore the association and causal relationship between FEV1 and lung cancer incidence. METHODS: We conducted a comprehensive search from PubMed, Medline, EMBASE, and Cochrane Library databases as of February 2020. MR analysis was performed using summary data obtained from two large consortia [International Lung Cancer Consortium (ILCCO) and Neale Lab] to assess the possible causality between FEV1 and lung cancer risk. RESULTS: Eight studies involving 88,743 cases were included. The incidence of lung cancer increased with decreasing FEV1.The combined odds ratio (OR) of decreased FEV1 for lung cancer incidence was 1.91 [95% confidence interval (CI) 1.67-2.19; P < 0.001]. Compared with the highest quintile of FEV1 (quintile 5, > 100% of predicted), the OR was 3.06 (95% CI 2.20-4.24; P < 0.001) for quintile 1 (< 70% of predicted), 1.89 (95% CI 1.50-2.38; P < 0.001) for quintile 2 (70-80% of predicted), 1.53 (95% CI 1.31-1.79; P < 0.001) for quintile 3 (80-90% of predicted), and 1.64 (95% CI 1.18-2.28; P = 0.003) for quintile 4 (90-100% of predicted). In subgroup meta-analysis, the correlation between FEV1 and lung cancer risk was different among men (OR = 1.74; 95% CI 1.49-2.03; P < 0.001) and women (OR = 2.80; 95% CI 1.87-4.19; P < 0.001). However, MR analysis showed no causality between the FEV1 and lung cancer risk (OR = 1.199; 95% CI 0.958-1.500; P = 0.114). CONCLUSION: FEV1 is likely to be a predictor of lung cancer, especially for women. However, genetically decreased FEV1 is not causally correlated with lung cancer incidence.


Assuntos
Predisposição Genética para Doença , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Pulmão/fisiopatologia , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Estudos de Coortes , Estudo de Associação Genômica Ampla , Humanos , Incidência , Metanálise como Assunto , Fatores de Risco
11.
Ann Transl Med ; 9(5): 372, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33842593

RESUMO

BACKGROUND: An increasing number and proportion of younger lung cancer patients have been observed worldwide, raising concerns on the optimal age to begin screening. This study aimed to investigate the association between age and findings in initial CT scans. METHODS: We searched for low-dose CT screening cohorts from electronic databases. Single-arm syntheses weighted by sample size were performed to calculate the detection rates of pulmonary nodules, lung cancers (all stages and stage I), and the proportion of stage I diseases in lung cancers. In addition, we included patients who underwent chest CT in our center as a supplementary cohort. The correlation between the detection rates and age was evaluated by the Pearson Correlation Coefficient. RESULTS: A total of 37 studies involving 163,442 participants were included. We found the detection rates of pulmonary nodules and lung cancers increased with age. However, the proportion of stage I diseases in lung cancers declined with increased starting age and was significantly higher in the 40-year group than in other groups (40 vs. 45, 50, 55, P<0.001). In addition, the ratio of early-stage lung cancer to the number of nodules declined with age. Similarly, in our center, the detection rates of nodules (R2=0.86, P≤0.001), all lung cancer (R2=0.99, P≤0.001) and stage I diseases (R2=0.87, P=0.001) increased with age, while the proportion of stage I diseases consistently declined with age (R2=0.97, P≤0.001). CONCLUSIONS: Starting lung cancer screening at an earlier age is associated with a higher probability of identifying a curable disease, urging future research to determine the optimal starting age.

12.
Transl Lung Cancer Res ; 10(12): 4380-4389, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35070748

RESUMO

BACKGROUND: Significantly rising plasma circulating C-reaction protein (CRP) concentrations are pervasive in lung cancer (LC) development, demonstrating a bidirectional relation. However, it remains uncertain whether the causation between them exists, and the degree to which the effect varies across different ethnic ancestries remains unknown. Therefore, we attempted to investigate the causal relationship between these two phenotypes. METHODS: With summary statistics of CRP-related single nucleotide polymorphisms (SNPs) identified by several large-scale genome-wide association studies (GWAS) datasets based on five ethnic ancestries coverage worldwide, we implemented bidirectional two-sample Mendelian randomization (MR) analyses. Genetic summary data of 11,348 LC cases and 15,861 controls from the International Lung Cancer Consortium (ILCCO) were applied. The inverse-variance weighted (IVW) approach was utilized as the principal analysis, supplemented by various complementary methods. RESULTS: MR study did not reveal the causal relationship shared across genetically predisposed CRP blood concentrations and LC risk (OR =1.022, 95% CI: 0.965-1.083, P=0.455) including pathological subtypes (OR =1.026, 95% CI: 0.947-1.112, P=0.534 for lung adenocarcinoma; OR =1.060, 95% CI: 0.970-1.158, P=0.201 for squamous cell lung cancer). Further analyses among East Asian, Hispanic/Latin American, European, African American/Afro-Caribbean, and South Asian populations revealed consistent null causation. Additionally, the causal effects of LC on CRP concentrations were not statically significant (OR =0.999, 95% CI: 0.977-1.021, P=0.923). CONCLUSIONS: We did not observe a bidirectional causal association between CRP blood concentrations on LC among East Asian, Hispanic/Latin American, European, African American/Afro-Caribbean, and South Asian ancestry individuals.

13.
Breast Cancer Res Treat ; 185(3): 799-806, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33128677

RESUMO

PURPOSE: The association between polycystic ovary syndrome (PCOS) and breast cancer remains inconclusive. Conventional observational studies are susceptible to inverse causality and potential confounders. With a Mendelian randomization (MR) approach, we aimed to investigate the causal relationship between genetically predicted PCOS and breast cancer risk. METHODS: Our study included 11 PCOS-associated single nucleotide polymorphisms as instrumental variables identified by the latest genome-wide association study. Individual-level genetic summary data of participants were obtained from the Breast Cancer Association Consortium, with a total of 122,977 cases and 105,974 controls. The inverse-variance weighted method was applied to estimate the causality between genetically predicted PCOS and breast cancer risk. To further evaluate the pleiotropy, the weighted median and MR-Egger regression methods were implemented as well. RESULTS: Our study demonstrated that genetically predicted PCOS was causally associated with an increased risk of overall breast cancer (odds ratio (OR) = 1.07; 95% confidence interval (CI) 1.02-1.12, p = 0.005). The subgroup analyses according to immunohistochemical type further illustrated that genetically predicted PCOS was associated with an increased risk of estrogen receptor (ER)-positive breast cancer (OR = 1.09; 95% CI 1.03-1.15, p = 0.002), while no causality was observed for ER-negative breast cancer (OR = 1.02; 95% CI 0.96-1.09, p = 0.463). In addition, no pleiotropy was found in our study. CONCLUSIONS: Our findings indicated that PCOS was likely to be a causal factor in the development of ER-positive breast cancer, providing a better understanding for the etiology of breast cancer and the prevention of breast cancer.


Assuntos
Neoplasias da Mama , Síndrome do Ovário Policístico , Mama , Neoplasias da Mama/etiologia , Neoplasias da Mama/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/genética , Polimorfismo de Nucleotídeo Único
14.
J Cancer Res Clin Oncol ; 147(1): 139-151, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32965542

RESUMO

PURPOSE: We aimed to elucidate the associations between aspirin use with risk of lung cancer, by conducting a meta-analysis and Mendelian randomization (MR) analyses from published Genome-Wide Association Studies (GWAS). METHODS: Cohort studies, nested case-control studies, and randomized controlled trials (RCTs) investigating the impact of aspirin exposure and lung cancer incidence were included. Relative risk (RR) and its 95% confidence interval (CI) were evaluated in eligible studies. Subgroup analyses regarding gender, pathologic subtypes and smoking status were also executed. MR analyses were conducted using summary statistics obtained from two large consortia [Neale Lab and International Lung Cancer Consortium (ILCCO)] to assess the possible causal relationship of aspirin on lung cancer incidence. RESULTS: Sixteen eligible studies involving 1,522,687 patients were included. The combined RR of aspirin use for the incidence of lung cancer was 0.95 (95% confidence interval (CI) 0.91-0.98). In subgroup meta-analyses, a significant protective effect was observed in squamous cell lung cancer (RR = 0.80; 95% CI 0.65-0.98). In terms of gender, the chemopreventive value was only observed among men (RR = 0.87; 95% CI 0.77-0.97). The MR risk analysis suggested a causal effect of aspirin on lung cancer incidence, with evidence of a decreased risk for overall lung cancer (OR = 0.042; 95% CI 0.003-0.564) and squamous cell lung cancer (OR = 0.002; 95% CI 1.21 × 10-5-0.301). CONCLUSION: Our study provided evidence for a causal protective effect of aspirin on the risk of lung cancer incidence among men, particularly on the squamous cell lung cancer risk.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Neoplasias Pulmonares/epidemiologia , Análise da Randomização Mendeliana , China/epidemiologia , Estudo de Associação Genômica Ampla , Humanos , Incidência , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Metanálise como Assunto , Prognóstico
16.
J Thorac Dis ; 12(8): 4427-4433, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32944356

RESUMO

As the computer processing technique and display technology evolved dramatically, the surgical approach to early-stage non-small cell lung cancer (NSCLC) has made a rapid progress within the past few years. Currently, the gold standard for NSCLC is lobectomy. After the introduction of video-assisted thoracoscopic surgery (VATS), lung resection can now be conducted mini-invasively, enabling better prognosis for patients and better operation condition for surgeons. At the very beginning, the conventional two-dimensional (2D) system enabled operators to have a closer, magnified and illuminated view inside the body cavity than open thoracotomy. With the introduction of the glasses-assisted three-dimensional (3D) and glasses-free 3D display system, multiple viewing angles were further enhanced, thus a more stable, easier to master and less invasive video-assisted thoracoscopic surgery (VATS) appeared. However, given that the standard VATS is associated with limited maneuverability and stereoscopy, it restricts the availability in more advanced cases. Hopefully, most of the limitations of standard VATS can be overcome with the robotic-assisted thoracic surgery (RATS). The RATS system consists of a remote console and a robotic unit with 3 or 4 arms that can duplicate surgeons' movements. Also, it provides a magnified, 3D and high definition (HD) operation field to surgeons, allowing them to perform more complicated procedures. Apart from these, some new technologies are also invented in combination with the existing surgery system to solve difficult problems. It is hoped that the higher costs of innovative surgical technique can be offset by the better patient outcomes and improved benefits in cost-effectiveness.

17.
Eur J Cardiothorac Surg ; 58(3): 605-612, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32447374

RESUMO

OBJECTIVES: The feasibility and safety of spontaneous ventilation (SV) video-assisted thoracoscopic surgery (VATS) for non-small-cell lung cancer (NSCLC) in patients with excess body weight [defined as body mass index (BMI) ≥ 25 kg/m2] remain unclear. METHODS: Patients with NSCLC with excess body weight who underwent SV-VATS or mechanical ventilation (MV) VATS (MV-VATS) between April 2012 and July 2018 were analysed retrospectively. Propensity score matching was applied to balance the distribution of demographic characteristics. The short-term outcomes between the SV-VATS group and MV-VATS group were compared. RESULTS: From April 2012 to July 2018, a total of 703 patients with excess body weight were included, 68 of whom underwent SV-VATS and 635 of whom underwent MV-VATS. After propensity score matching, the distribution of demographic characteristics was well balanced. BMIs (26.65 ± 1.74 vs 27.18 ± 2.36 kg/m2; P = 0.29) were similar between the groups. Patients who underwent SV-VATS had similar anaesthesia times (213 ± 57 vs 233 ± 67 min; P = 0.16) and similar operative times (122 ± 44 vs 142 ± 56 min; P = 0.086). The intraoperative bleeding volume, postoperative chest tube duration, volume of pleural drainage, number of dissected N1 and N2 station lymph nodes, length of hospitalization and incidence of complications were comparable between the 2 groups. CONCLUSIONS: Primary lung cancer resection is feasible and not associated with safety issues under SV-VATS in selected patients with NSCLC with excess body weight.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Peso Corporal , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA