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1.
Int Immunopharmacol ; 134: 112161, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38728878

RESUMO

Intervertebral disc degeneration (IVDD) is a leading cause of degenerative spinal disorders, involving complex biological processes. This study investigates the role of the kallikrein-kinin system (KKS) in IVDD, focusing on the protective effects of bradykinin (BK) on nucleus pulposus cells (NPCs) under oxidative stress. Clinical specimens were collected, and experiments were conducted using human and rat primary NPCs to elucidate BK's impact on tert-butyl hydroperoxide (TBHP)-induced oxidative stress and damage. The results demonstrate that BK significantly inhibits TBHP-induced NPC apoptosis and restores mitochondrial function. Further analysis reveals that this protective effect is mediated through the BK receptor 2 (B2R) and its downstream PI3K/AKT pathway. Additionally, BK/PLGA sustained-release microspheres were developed and validated in a rat model, highlighting their potential therapeutic efficacy for IVDD. Overall, this study sheds light on the crucial role of the KKS in IVDD pathogenesis and suggests targeting the B2R as a promising therapeutic strategy to delay IVDD progression and promote disc regeneration.


Assuntos
Apoptose , Bradicinina , Degeneração do Disco Intervertebral , Núcleo Pulposo , Estresse Oxidativo , Ratos Sprague-Dawley , terc-Butil Hidroperóxido , Animais , Núcleo Pulposo/efeitos dos fármacos , Núcleo Pulposo/patologia , Núcleo Pulposo/metabolismo , terc-Butil Hidroperóxido/toxicidade , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/patologia , Humanos , Masculino , Bradicinina/farmacologia , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Células Cultivadas , Receptor B2 da Bradicinina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Feminino , Microesferas , Transdução de Sinais/efeitos dos fármacos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Fosfatidilinositol 3-Quinases/metabolismo , Modelos Animais de Doenças
2.
Heliyon ; 10(9): e30214, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38707310

RESUMO

Background: Accumulating small unruptured intracranial aneurysms are detected due to the improved quality and higher frequency of cranial imaging, but treatment remains controversial. While surgery or endovascular treatment is effective for small aneurysms with a high risk of rupture, such interventions are unnecessary for aneurysms with a low risk of rupture. Consequently, it is imperative to accurately identify small aneurysms with a low risk of rupture. The purpose of this study was to develop a clinically practical model to predict small aneurysm ruptures based on a radiomics signature and clinical risk factors. Methods: A total of 293 patients having an aneurysm with a diameter of less than 5 mm, including 199 patients (67.9 %) with a ruptured aneurysm and 94 patients (32.1 %) without a ruptured aneurysm, were included in this study. Digital subtraction angiography or surgical treatment was required in all cases. Data on the clinical risk factors and the features on computed tomography angiography images associated with the aneurysm rupture status were collected simultaneously. We developed a clinical-radiomics model to predict aneurysm rupture status using multivariate logistic regression analysis. The combined clinical-radiomics model was constructed by nomogram analysis. The diagnostic performance, clinical utility, and model calibration were evaluated by operating characteristic curve analysis, decision curve analysis, and calibration analysis. Results: A combined clinical-radiomics model (Area Under Curve [AUC], 0.85; 95 % confidence interval [CI], 0.757-0.947) showed effective performance in the operating characteristic curve analysis. In the validation cohort, the performance of the combined model was better than that of the radiomics model (AUC, 0.75; 95 % CI, 0.645-0.865; Delong's test p-value = 0.01) and the clinical model (AUC, 0.74; 95 % CI, 0.625-0.851; Delong's test p-value <0.01) alone. The results of the decision curve, nomogram, and calibration analyses demonstrated the clinical utility and good fitness of the combined model. Conclusion: Our study demonstrated the effectiveness of a clinical-radiomics model for predicting rupture status in small aneurysms.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38780888

RESUMO

PURPOSE: To establish a pathomic model using histopathological image features for predicting indoleamine 2,3-dioxygenase 1 (IDO1) status and its relationship with overall survival (OS) in breast cancer. METHODS: A pathomic model was constructed using machine learning and histopathological images obtained from The Cancer Genome Atlas database to predict IDO1 expression. The model performance was evaluated based on the area under the curve, calibration curve, and decision curve analysis (DCA). Prediction scores (PSes) were generated from the model and applied to divide the patients into two groups. Survival outcomes, gene set enrichment, immune microenvironment, and tumor mutations were assessed between the two groups. RESULTS: Survival analysis followed by multivariate correction revealed that high IDO1 is a protective factor for OS. Further, the model was calibrated, and it exhibited good discrimination. Additionally, the DCA showed that the proposed model provided a good clinical net benefit. The Kaplan-Meier analysis revealed a positive correlation between high PS and improved OS. Univariate and multivariate Cox regression analyses demonstrated that PS is an independent protective factor for OS. Moreover, differentially expressed genes were enriched in various essential biological processes, including extracellular matrix receptor interaction, angiogenesis, transforming growth factor ß signaling, epithelial mesenchymal transition, cell junction, tryptophan metabolism, and heme metabolic processes. PS was positively correlated with M1 macrophages, CD8 + T cells, T follicular helper cells, and tumor mutational burden. CONCLUSION: These results indicate the potential ability of the proposed pathomic model to predict IDO1 status and the OS of breast cancer patients.

4.
Carbohydr Res ; 534: 108962, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37769377

RESUMO

It is of great significance to develop marine resources and study its potential biological activity by using alginate lyase produced by marine psychrophilic bacteria. In the previous study, a new marine psychrophilic bacterium (Cobetia marina HQZ08) was screened from the growth area of Laminaria japonica, and it was found that the strain could efficiently produce alginate-degrading enzyme (Aly30). In this paper, the ability of Aly30 to degrade alginate was optimized and the optimal degradation conditions were obtained. It was found that the main degradation product of alginate oligosaccharides was trisaccharide. In vitro cell experiments showed that the antitumor activity of low molecular weight alginate oligosaccharides was better than that of high molecular weight alginate oligosaccharides. In summary, Aly30 had the potential to produce alginate oligosaccharides with low degree of polymerization and antitumor activity, which provided a reference for the enzymatic preparation and application of alginate oligosaccharides.


Assuntos
Alginatos , Halomonadaceae , Alginatos/farmacologia , Alginatos/metabolismo , Oligossacarídeos/farmacologia , Oligossacarídeos/metabolismo , Polissacarídeo-Liases/metabolismo , Especificidade por Substrato , Concentração de Íons de Hidrogênio
5.
Clin Chem Lab Med ; 61(11): 2010-2016, 2023 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-37171227

RESUMO

OBJECTIVES: The clinical significance of serum pepsinogen (PG) for screening gastric cancer has been a controversial topic. Serum PG I levels have been demonstrated to be correlated with age, sex, and the Helicobacter pylori (HP) infection. However, the underlying factors that influence serum PG I variations remain to be fully elucidated. We aimed to evaluate the impacts of sex and body mass index (BMI) on PG I in Chinese population. METHODS: The cross-sectional study recruited 4,299 apparently healthy participants in Fujian Province. Serum PG levels were automatically measured using ELISA method. Serum H. pylori-IgG antibody was detected by the colloidal gold immunoassay. Clinical characteristics were obtained by questionnaire. RESULTS: Totally, 2,263 participants who had tests of serum PG and anti-HP IgG antibody were enrolled. Increased BMI and serum uric acid were observed in males with low PG I value (<70 µg/L). Multiple logistic regression showed the presence of overweight was the independent risk factor for male participants with low PG I level (odds ratio [OR] 1.519; p=0.017). However, the association was not found in females. CONCLUSIONS: Sex-specific association of serum low PG I with overweight was observed in the southeast coastal areas of China. Thus, effects of sexual dimorphism should not be ignored during the clinical utilization of serum PG I.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Feminino , Humanos , Masculino , Pepsinogênio A , Índice de Massa Corporal , Estudos Transversais , Sobrepeso , Ácido Úrico , Imunoglobulina G , Infecções por Helicobacter/diagnóstico
6.
Front Oncol ; 13: 860711, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36910668

RESUMO

Purpose: We evaluated he effects of molecular guided-targeted therapy for intractable cancer. Also, the epidemiology of druggable gene alterations in Chinese population was investigated. Materials and methods: The Long March Pathway (ClinicalTrials.gov identifier: NCT03239015) is a non-randomized, open-label, phase II trial consisting of several basket studies examining the molecular profiles of intractable cancers in the Chinese population. The trial aimed to 1) evaluate the efficacy of targeted therapy for intractable cancer and 2) identify the molecular epidemiology of the tier II gene alterations among Chinese pan-cancer patients. Results: In the first stage, molecular profiles of 520 intractable pan-cancer patients were identified, and 115 patients were identified to have tier II gene alterations. Then, 27 of these 115 patients received targeted therapy based on molecular profiles. The overall response rate (ORR) was 29.6% (8/27), and the disease control rate (DCR) was 44.4% (12/27). The median duration of response (DOR) was 4.80 months (95% CI, 3.33-27.2), and median progression-free survival (PFS) was 4.67 months (95% CI, 2.33-9.50). In the second stage, molecular epidemiology of 17,841 Chinese pan-cancer patients demonstrated that the frequency of tier II gene alterations across cancer types is 17.7%. Bladder cancer had the most tier-II alterations (26.1%), followed by breast cancer (22.4%), and non-small cell lung cancer (NSCLC; 20.2%). Conclusion: The Long March Pathway trial demonstrated a significant clinical benefit for intractable cancer from molecular-guided targeted therapy in the Chinese population. The frequency of tier II gene alterations across cancer types supports the feasibility of molecular-guided targeted therapy under basket trials.

7.
Thorac Cancer ; 14(1): 30-35, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36495040

RESUMO

BACKGROUND: To investigate the correlation between the preoperative systemic immune-inflammation index (pSII) and postoperative pneumonia (POP) in surgical non-small cell lung cancer patients. METHODS: Patients who underwent lung cancer surgery at West China Hospital of Sichuan University were retrospectively included. The indicators were collected, including basic information of patients, surgery-related variables and POP rate. The predictive value of the pSII in the occurrence of POP was analyzed. RESULTS: A total of 1486 patients (male: 748, 50.3%; female: 738, 49.7%; mean age: 58.2 ± 9.7 years; median age: 59 years old, interquartile range: 51-65 years old) were finally included in the study, of which 142 patients had POP with an incidence of 9.5% (142/1486), 9.2% (69/748) in males, and 9.9% (73/738) in females. The proportion of patients with diabetes in the pneumonia group was significantly higher than that in the nonpneumonia group (9.8%, 14/142 vs. 5.6%, 75/1344, p = 0.041). Compared with the nonpneumonia group, the level of the preoperative body mass index (24.2 [21.9, 26.1] vs. 23.1 [21.1, 25.2], p = 0.003) and SII (487 [350, 673] vs. 345 [230, 500], p < 0.001) in the pneumonia group were significantly higher. Multiple factor analysis showed that the pSII (odds ratio: 1.001, 95% confidence interval: 1.000-1.001, p < 0.001) was an independent risk factor for POP (487 [350, 673] vs. 345 [230, 500], p < 0.001); receiver operating characteristic curve analysis showed that the pSII was effective in predicting POP (area under curve: 0.751, p < 0.001). CONCLUSION: The pSII is closely related to and can effectively predict the occurrence of POP after lung cancer surgery.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumonia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/complicações , Estudos Retrospectivos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pneumonia/epidemiologia , Pneumonia/etiologia , Inflamação/complicações , Prognóstico
8.
J Cancer Res Clin Oncol ; 149(8): 4623-4628, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36171456

RESUMO

PURPOSE: Neoadjuvant therapy followed by surgical resection is one of the preferred treatment option for locally advanced non-small cell lung cancer (NSCLC). For patients with mesenchymal-epithelial transition (MET) factor exon 14 skipping (METex14) mutations, the use of MET-tyrosine kinase inhibitors (TKIs) showed high efficiency and reduced toxicity compared with first-line standard chemotherapy. However, it is unknown whether preoperative induction targeted therapy of MET-TKIs is feasible and safe. METHODS: Here, we reported 3 cases of locally advanced unresectable NSCLC with METex14 mutations receiving induction therapy of MET-TKI savolitinib as first-line therapy or second-line therapy when they experienced disease progression after preoperative chemotherapy. RESULTS: All these 3 patients achieved significant tumor size shrinkage and their unresectable tumors became resectable after the treatment of savolitinib. No serious adverse events were observed during the treatment. They recovered well postoperatively, and no significant events were identified. CONCLUSIONS: Preoperative induction treatment with MET-TKI savolitinib showed its safety and effectiveness and may be an alternative option for neoadjuvant therapy for NSCLC patients with METex14 mutations.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Estudos de Viabilidade , Quimioterapia de Indução , Proteínas Proto-Oncogênicas c-met/genética , Mutação , Éxons , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia
9.
Front Oncol ; 12: 790076, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372007

RESUMO

Background: The aim of this study was to explore the feasibility and efficacy of a non-invasive quantitative imaging evaluation model to assess the lymphatic metastasis of breast cancer based on a radiomics signature constructed using conventional T1-weighted image (T1WI) enhanced MRI and molecular biomarkers. Methods: Patients with breast cancer diagnosed via lymph biopsies between June 2015 and June 2019 were selected for the study. All patients underwent T1WI contrast-enhancement before treatment; lymph biopsy after surgery; and simultaneous Ki-67, COX-2, PR, Her2 and proliferating cell nuclear antigen detection. All images were imported into ITK-SNAP for whole tumor delineation, and AK software was used for radiomics feature extraction. Next, the radiomics signature Rad-score was constructed after reduction of specific radiomic features. A multiple regression logistic model was built by combining the Rad-score and molecular biomarkers based on the minimum AIC. Results: In all, 100 patients were enrolled in this study, including 45 with non-lymph node (LN) metastasis and 55 with LN metastasis. A total of 1,051 texture feature parameters were extracted, and LASSO was used to reduce the dimensionality of the radiomics features. The log(λ) was set to 0.002786, and 19 parameters were retained for the construction of the radiomics tag Rad-score. ROC was used to evaluate the diagnostic efficiency of Rad-score: the area under the ROC curve (AUC) of the Rad-score for identifying non-lymphatic and lymphatic metastases was 0.891 in the training cohort and 0.744 in the validation cohort. With the incorporation of tumor molecular markers, the AUCs of the training cohort and validation cohort of the nomogram were 0.936 and 0.793, respectively, which were notably higher than the AUCs of the clinical parameters in the training and validation cohorts (0.719 and 0.588, respectively). Conclusion: The combined model constructed using the Rad-score and molecular biomarkers can be used as an effective non-invasive method to assess LN metastasis of breast cancer. Furthermore, it can be used to quantitatively evaluate the risk of breast cancer LN metastasis before surgery.

10.
Colloids Surf B Biointerfaces ; 213: 112424, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35227993

RESUMO

Antibiotic bone cement filling technology has been widely used in the treatment of infectious bone defects for decades. However, the current treatment requires multiple complicated procedures, which would lead to pain and financial burden for patients. Repairing bone defects and control infection at the same time is the pain spot of orthopaedic area. In this study, we develop a composite scaffold that aiming at effectively repair infectious bone defects simultaneously. Vancomycin hydrochloride(Van) /Poly(lactic-co-glycolic) acid(PLGA) microspheres prepared by double emulsion method were successfully loaded into ß-tricalcium phosphate scaffold through electrostatic and physical crosslinking. Full characterization, including mechanical properties, biocompatibility, in vitro release profile and antibacterial properties of the composite scaffolds(CPSFs) were performed. The rabbit osteomyelitis model based on big hole and small hole methods was established. Pharmacodynamics study, including the local bacteriostatic and osteogenic ability were evaluated by X-ray, Micro-CT and histopathology at 4 months after surgery. These findings indicate that a reliable rabbit model of local bone defect infection successfully established by big hole approach. The CPSFs with significant histocompatibility and biocompatibility could sustained release vancomycin for extended duration. It exhibited great application potential in clinical aim at the indication of local infectious bone defects.


Assuntos
Fosfatos de Cálcio , Osteogênese , Animais , Regeneração Óssea , Fosfatos de Cálcio/farmacologia , Humanos , Microesferas , Dor , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos , Alicerces Teciduais , Vancomicina/farmacologia
11.
Zhongguo Fei Ai Za Zhi ; 25(1): 14-20, 2022 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-35078280

RESUMO

BACKGROUND: Chronic obstructive pulmonary diseases (COPD) affects 45%-63% of lung cancer patients worldwide. Lung cancer patients complicated with COPD have decreased cardiopulmonary function and increased perioperative risk, and their postoperative exercise endurance and lung function are significantly lower than those with conventional lung cancer. Previous studies have shown that postoperative exercise training can improve the exercise endurance of unselected lung cancer patients, but it is unclear whether lung cancer patients with COPD can also benefit from postoperative exercise training. This study intends to explore the effects of postoperative exercise training on exercise endurance, daily activity and lung function of lung cancer patients with COPD. METHODS: Seventy-four patients with non-small cell lung cancer (NSCLC) complicated with COPD who underwent pneumonectomy in the lung cancer center of West China Hospital of Sichuan University from August 5, 2020 to August 25, 2021 were prospectively analyzed. They were randomly divided into exercise group and control group; The patients in the two groups received routine postoperative rehabilitation in the first week after operation, and the control group was given routine nursing from the second week. On this basis, the exercise group received postoperative exercise rehabilitation training for two weeks. Baseline evaluation was performed 3 days before operation and endpoint evaluation was performed 3 weeks after operation. RESULTS: The exercise endurance, daily activity and pulmonary function test results of the two groups decreased from baseline to the end point. However, after the operation and intervention program, the maximum oxygen consumption of Cardiopulmonary Exercise Test and the walking distance of 6-Minute Walking Test in the exercise group were significantly better than those in the control group [(13.09±1.46) mL/kg/min vs (11.89±1.38) mL/kg/min, P=0.033; (297±46) m vs (243±43) m, P=0.041]. The average number of we-chat steps in the exercise group was also significantly better than that in the control group (4,381±397 vs 3,478±342, P=0.035). Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) in the exercise group were better than those in the control group, but the difference did not reach a statistically significant level [(1.76±0.19) L vs (1.60±0.28) L, P=0.084; (1.01±0.17) L vs (0.96±0.21) L, P=0.467]. CONCLUSIONS: Postoperative exercise rehabilitation training can improve exercise endurance and daily activity ability of patients with lung cancer complicated with COPD and promote postoperative rehabilitation.


Assuntos
Neoplasias Pulmonares , Doença Pulmonar Obstrutiva Crônica , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Exercício Físico , Volume Expiratório Forçado , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/cirurgia , Doença Pulmonar Obstrutiva Crônica/complicações
12.
ANZ J Surg ; 91(11): E696-E702, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34405519

RESUMO

BACKGROUND: Whether dissection of left lower paratracheal (4L) lymph node has any impact on survival of patients with left-sided non-small cell lung cancer (NSCLC) remains unclear. We conducted the first meta-analysis to compare the survival of patients treated with 4L lymph node dissection (LND) and those without for left-sided NSCLC. METHODS: We systematically searched relevant studies from PubMed, Embase, and Web of Science on February 6, 2020. Data for analysis included 5-year overall survival (OS) and disease-free survival (DFS) rates, OS, and DFS. We calculated risk ratio (RR) for pooling 5-year OS and DFS rates and extracted hazard ratio (HR) from multivariate analysis for pooling OS and DFS. RESULTS: We finally included three retrospective cohort studies with propensity score-matched analysis consisting of 2103 patients. Meta-analysis showed that patients treated with 4L LND yielded significantly higher 5-year OS (67.7% vs. 54.6%; fixed effects models: RR = 0.75; 95% confidence interval [CI] = [0.67, 0.84]; p < 0.001; I2  = 0%) and DFS (53.3% vs. 44.8%; fixed effects models: RR = 0.85; 95% CI = [0.76, 0.95]; p = 0.003; I2  = 41.7%) rates than patients without 4L LNDS. Moreover, dissection of 4L lymph node was significantly associated with better OS (fixed effects model: HR = 0.66; 95% CI = [0.57, 0.76]; p < 0.001; I2  = 45.7%) and DFS (fixed effects model: HR = 0.67; 95% CI = [0.52, 0.87]; p = 0.003; I2  = 0%). No significant heterogeneities were observed. CONCLUSIONS: Dissection of 4L lymph node could significantly improve both 5-year OS and DFS rates and 4L LND was a favorable prognostic factor for patients with left-sided NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Dissecação , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
13.
Nutrition ; 90: 111345, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34166897

RESUMO

OBJECTIVES: Sarcopenia is commonly encountered in patients with advanced cancer, but the role of sarcopenia in predicting prognosis in this group of patients receiving immune checkpoint inhibitors (ICIs) remains undetermined. The aim of this study was to performed the first meta-analysis focusing on the prognostic value of sarcopenia in patients with advanced cancer who were treated with ICIs comprehensively. METHODS: A systematic search for relevant studies in the Web of Science, PubMed, and Embase was conducted on August 19, 2020. Outcomes including response rate, 1-y progression-free survival (PFS) rate, 1-y overall survival (OS) rate, and hazard ratios (HRs) of PFS and OS were extracted. Meta-analysis was performed by using the STATA version 12 software package. RESULTS: Nine cohort studies consisting of 740 patients with advanced cancer receiving ICIs were finally included for analysis. Our meta-analysis found that patients with sarcopenia tended to have a lower response rate than those without the disease (30.5 versus 15.9%; P = 0.095). Furthermore, patients with sarcopenia yielded a significantly shorter 1-y PFS rate (32 versus 10.8%; risk ratio [RR], 1.31; P < 0.001) and 1-y OS rate (66 versus 43%; RR, 1.71; P < 0.001) than patients without sarcopenia. Moreover, sarcopenia was found to be an independent, unfavorable prognostic factor of PFS (HR, 1.79; P < 0.001) and OS (HR, 2.11; P < 0.001) in patients with advanced cancer receiving ICIs. Subgroup analysis further confirmed the unfavorable predictive value of sarcopenia in patients with advanced non-small cell lung cancer and those with melanoma receiving ICIs. CONCLUSIONS: Sarcopenia proved to be an independent, unfavorable prognostic factor in patients with advanced cancer receiving ICIs. Routine assessment of sarcopenia status and correction of sarcopenic status should be emphasized for patients treated with ICIs. Further research with sufficient adjustments for confounding factors are warranted to better elucidate the prognostic value of sarcopenia in these patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Sarcopenia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/tratamento farmacológico , Prognóstico , Sarcopenia/diagnóstico , Sarcopenia/etiologia
14.
World J Surg ; 45(8): 2610-2618, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33899137

RESUMO

BACKGROUNDS: Whether sex has any impact on the risk of lymph node (LN) metastasis (LNM) in patients with early-stage non-small cell lung cancer (NSCLC) remains controversial. Therefore, we aimed to objectively compared the risk of LNM between female and male patients with early-stage NSCLC so as to figure out whether sex-different extent of surgery may be justified for treating these patients. METHODS: We retrospectively collected clinical data of patients undergoing lobectomy or segmentectomy with systematic hilar and mediastinal LN dissection for clinical stage IA peripheral NSCLC from June 2014 to April 2019. Both multivariate logistic regression analysis and propensity score-matched(PSM) analysis were applied to compare the risk of LNM between female and male patients. RESULTS: We finally included a total of 660 patients for analysis. In the analysis of unmatched cohorts, there was no significant different rate of LNM (12.4% Vs 13.9%, P=0.556), hilar/intrapulmonary LNM (8.4% Vs 10.7%, P=0.318) and mediastinal LNM(7.9% Vs 7.5%, P=0.851) between female and male patients. In the multivariate analysis, sex was not found to be an independent predictor of LN in these patients. Moreover, in the analysis of well-matched cohorts generated by PSM analysis, there was still no significant different rate of LNM (13.8% Vs 13.4%, P=0.892), hilar/intrapulmonary LNM (9.1% Vs 11.2%, P=0.442) and mediastinal LNM (9.1% Vs 6.5%, P=0.289) between female and male patients. CONCLUSIONS: Sex was not an independent predictor of LNM in early-stage NSCLC and there is no sufficient evidence justifying for sex-different extent of surgical resection for these patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Estudos Retrospectivos
15.
Medicine (Baltimore) ; 100(15): e25447, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33847650

RESUMO

BACKGROUND: High pretreatment level of D-dimer in small cell lung cancer (SCLC) is commonly encountered, but the impact of high pretreatment D-dimer level on the prognosis of SCLC patients remains undetermined. Therefore, we conducted this meta-analysis focusing specifically on the prognostic value of high pretreatment D-dimer level in SCLC patients comprehensively. METHODS: We searched systematically in PubMed, Embase, and Web of Science for relevant studies published before January 28, 2019. Outcomes including 1-year overall survival (OS), progression-free survival (PFS) rates, and hazard ratios (HRs) of OS and PFS from multivariate analysis were extracted and analyzed. RESULTS: A total of 5 cohort studies consisting of 813 SCLC patients (473 patients with high pretreatment level of D-dimer and 340 with normal level of D-dimer) were finally included for meta-analysis. We found that patients with high pretreatment level of D-dimer had significantly shorter 1-year OS (47.6% vs 79.9%; fixed effects: risk ratio [RR] = 2.506; 95% confidence interval [CI] = [1.948, 3.224]; P < .001) and PFS (15.8% vs 34.0%; random effects: RR = 1.294; 95% CI = [1.060, 1.579]; P = .011) rates than those with normal level of D-dimer. Moreover, high pretreatment D-dimer level was further proved to remain as an unfavorable predictor of OS (fixed effects: HR = 1.865; 95% CI = [1.469, 2.367]; P < .001; I2 = 7.6%) and PFS (fixed effects: HR = 1.513; 95% CI = [1.183, 1.936]; P = .001; I2 = 0.0%) in patients with SCLC. CONCLUSION: High pretreatment level of D-dimer was found to be an independent unfavorable prognostic factor in SCLC patients. However, more studies with sufficient adjustment for confounding factors are encouraged to confirm our conclusions.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Estudos de Coortes , Feminino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Carcinoma de Pequenas Células do Pulmão/terapia , Taxa de Sobrevida
16.
J Int Med Res ; 49(2): 300060520986681, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33530793

RESUMO

A rare and highly malignant small round cell tumor, Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) usually occurs in the pelvis, long-axis bones, and femur. In contrast, extraosseous ES is more often found in the paraspinal region, limbs, and retroperitoneum, but is extremely rare in the stomach. We report a case of a 55-year-old woman who presented with fatigue, fever, and black stool. Preoperative computed tomography (CT) imaging showed a large ulcerative lesion of approximately 5.5 × 5.0 cm in the stomach and irregular thickening of the ulcer wall. Upper endoscopy revealed a large, irregular ulcer in the posterior wall of the stomach. Histopathological examination suggested that the mass with the largest diameter (7.5 cm) was ES. Immunohistochemistry indicated positivity for CD99. Enhanced CT of the whole body was performed but no definite masses were found in other organs, and the patient was diagnosed with primary gastric ES. The patient underwent radical distal gastrectomy with Roux-en-Y gastrojejunostomy, but refused chemoradiotherapy.


Assuntos
Tumores Neuroectodérmicos Primitivos Periféricos , Tumores Neuroectodérmicos Primitivos , Sarcoma de Ewing , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Sarcoma de Ewing/diagnóstico por imagem , Sarcoma de Ewing/cirurgia , Estômago
17.
World J Surg ; 45(3): 897-906, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33230587

RESUMO

BACKGROUND: Whether video-assisted thoracoscopic surgery (VATS) sleeve lobectomy could be an alternative to traditional thoracotomy sleeve lobectomy in treating centrally located non-small cell lung cancer (NSCLC) remains unclear. Therefore, we conducted the first meta-analysis to compare the effects of VATS sleeve lobectomy with thoracotomy sleeve lobectomy. METHODS: We systematically searched relevant studies from Pubmed, Embase, and Web of Science on May 12, 2020. Data for analysis included short-term outcomes (blood loss, lymph node dissected, operation time, hospital stay, complications) and long-term outcomes (3-year overall survival (OS) and progression-free survival (PFS) rates). We calculated the weighted mean differences (WMDs) for continuous data and risk ratio (RR) for pooling categorical data. RESULTS: We finally included 5 retrospective cohort study consisting of 436 patients. VATS sleeve lobectomy yielded significantly less blood loss (WMD = -37.83; 95% confidence intervals (CIs) = [-58.56, -17.11]; P < 0.001) than thoracotomy sleeve lobectomy and comparable total number of dissected lymph node to thoracotomy sleeve lobectomy (WMD = - 0.07; 95%CI = [-1.14, 0.99]; P = 0.89). However, VATS sleeve lobectomy consumed significantly more operation time than thoracotomy sleeve lobectomy (WMD = 49.00; 95%CI = [14.67, 83.34]; P = 0.005). VATS sleeve lobectomy yielded significantly less postoperative hospital stay time than thoracotomy sleeve lobectomy (WMD = -1.68; 95%CI = [-2.98, -0.39]; P = 0.011) and comparable postoperative complication rate to thoracotomy sleeve lobectomy (RR = 0.84; 95%CI = [0.49, 1.44]; P = 0.52). Moreover, VATS sleeve lobectomy yielded comparable 3-year OS (RR = 1.08; 95%CI = [0.95, 1.22]; P = 0.23) and PFS (RR = 1.15; 95%CI = [0.96, 1.37]; P = 0.13) rates to thoracotomy sleeve lobectomy. No significant heterogeneities were observed. CONCLUSIONS: VATS sleeve lobectomy yielded less surgical trauma than thoracotomy sleeve lobectomy and improved postoperative recovery without compromising oncological prognosis. Even though VATS sleeve lobectomy may consume more operation time, it could be recommended as an alternative to thoracotomy sleeve lobectomy for treating centrally located NSCLC in carefully selected cases.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida , Toracotomia
18.
Zhongguo Fei Ai Za Zhi ; 23(10): 883-888, 2020 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-32810974

RESUMO

T-box transcription factor gene (TBX) interferes with the origin and development of organs, and TBX5 is expressed highest in normal cardiac and pulmonary tissues. Lack of TBX5 may lead to thoracic malformation and abnormal diaphragmatic development, in which ectopic expression and overexpression may induce the apoptosis of cell and inhibit the development of cell. Previous studies demonstrated the potential role of TBX5 in the development and progression of esophageal adenocarcinoma, gastric cancer, colon cancer and breast cancer. We reviewed the association between the expression of TBX2 subfamily and the prognosis, and explore the research progress of TBX5 in regulating the development and progression of lung cancer. Even though the relationshihp the development of lung cancer and TBX5 are not clear, TBX5 could significantly inhibit in vivo tumor growth, and the level of TBX5 was negatively correlated with lung cancer progression. Therefore, the gene expression levels and methylation extent of TBX could be a potential biomarker to reveal the proliferation and metastasis of lung cancer, as well as a therapeutic target for lung cancer.
.


Assuntos
Neoplasias Pulmonares/metabolismo , Proteínas com Domínio T/metabolismo , Animais , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Metilação , Proteínas com Domínio T/genética
19.
Oncologist ; 25(10): e1552-e1561, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32663354

RESUMO

BACKGROUND: The predictive model of postsurgical recurrence for solitary early hepatocellular carcinoma (SE-HCC) is not well established. The aim of this study was to develop a novel model for prediction of postsurgical recurrence and survival for patients with hepatitis B virus (HBV)-related SE-HCC ≤10 cm. PATIENTS AND METHODS: Data from 1,081 patients with HBV-related SE-HCC ≤10 cm who underwent curative liver resection from 2003 to 2016 in our center were collected retrospectively and randomly divided into the derivation cohort (n = 811) and the internal validation cohort (n = 270). Eight hundred twenty-three patients selected from another four tertiary hospitals served as the external validation cohort. Postsurgical recurrence-free survival (RFS) and overall survival (OS) predictive nomograms were generated. The discriminatory accuracies of the nomograms were compared with six conventional hepatocellular carcinoma (HCC) staging systems. RESULTS: Tumor size, differentiation, microscopic vascular invasion, preoperative α-fetoprotein, neutrophil-to-lymphocyte ratio, albumin-to-bilirubin ratio, and blood transfusion were identified as the risk factors associated with RFS and OS. RFS and OS predictive nomograms based on these seven variables were generated. The C-index was 0.83 (95% confidence interval [CI], 0.79-0.87) for the RFS-nomogram and 0.87 (95% CI, 0.83-0.91) for the OS-nomogram. Calibration curves showed good agreement between actual observation and nomogram prediction. Both C-indices of the two nomograms were substantially higher than those of the six conventional HCC staging systems (0.54-0.74 for RFS; 0.58-0.76 for OS) and those of HCC nomograms reported in literature. CONCLUSION: The novel nomograms were shown to be accurate at predicting postoperative recurrence and OS for patients with HBV-related SE-HCC ≤10 cm after curative liver resection. IMPLICATIONS FOR PRACTICE: This multicenter study proposed recurrence or mortality predictive nomograms for patients with hepatitis B virus-related solitary early hepatocellular carcinoma ≤10 cm after curative liver resection. A close postsurgical surveillance protocol and adjuvant therapy should be considered for patients at high risk of recurrence.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trombose , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Vírus da Hepatite B , Humanos , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia , Nomogramas , Prognóstico , Estudos Retrospectivos
20.
Cancer Manag Res ; 12: 4899-4910, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606978

RESUMO

PURPOSE: Our objective was to investigate the effect of circSMARCC1 on the developmental and biological behavior of colorectal cancer (CRC). MATERIALS AND METHODS: The expression of circSAMRCC1 and miR-140-3p in CRC tissues and cell lines (SW620, HCT116, HT29 and SW480) and a normal cell line (NCM460) was detected using qRT-PCR. The expression levels of circSMARCC1 and its linear subtype were detected. Fluorescence in situ hybridization was performed for the evaluation of the localization of circSAMRCC1 and miR-140-3p in the SW620 cell line. The effects of circSAMRCC1 and miR-140-3p on cell proliferation were investigated using CCK8 and colony formation assays, respectively. The effects of circSAMRCC1 and miR-140-3p on cell migration and invasion were determined using Transwell assay. The binding relationship between circSMARCC1 and miR-140-3p was further assessed by bioinformatics, ChIRP analysis and double luciferase reporter assay. RESULTS: The expression of circSAMRCC1 in the CRC tissues and four cell lines is significantly increased, and circSMARCC1 and miR-140-3p are negatively correlated with expression level in the tissue. The downregulation of circSMARCC1 decreased CRC cell viability and suppressed metastasis in vitro and Inhibition of protein (MMP-2, MMP-9, VEGF) expression. miR-140-3p is downregulated in CRC tissues; miR-140-3p mimics inhibited SW620 cell viability, migration and invasion, and miR-140-3p inhibitors reversed the the effect of circSMARCC1 downregulation on cell proliferation, migration and invasion in CRC cells. CONCLUSION: circSMARCC1 competitively combined with miR-140-3p and functioned through a circSMARCC1/miR-140-3p/MMPs axis as a CRC carcinogen, demonstrating its potential as a biomarker for CRC treatment.

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