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1.
Int Immunopharmacol ; 142(Pt B): 113096, 2024 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-39288625

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is characterized by high invasiveness and poor prognosis. The role of Sorbin and SH3 domain-containing protein 2 (SORBS2) in ESCC remains largely unexplored. METHODS: The expression levels of SORBS2 in ESCC were detected using RNA-seq and proteomics data. The biological functions of SORBS2 in ESCC were investigated through in vivo and in vitro experiments. The mechanism of SORBS2 was explored using RIP-seq technology, which identified the key downstream molecule metalloproteinase-3 (TIMP3). The interaction between SORBS2 and TIMP3, including specific binding sites, was validated through RIP-qPCR and RNA pull-down assays. The impact of altered SORBS2 expression in ESCC on HUVECs was assessed using endothelial tube formation assays. RESULTS: SORBS2 expression was significantly downregulated in ESCC tissues, and its decreased expression was associated with poor prognosis. Overexpression of SORBS2 in ESCC cell lines inhibited cell proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, SORBS2 bound to the 3' UTR of TIMP3 mRNA, enhancing its stability and thereby regulating TIMP3 expression. Rescue experiments demonstrated that increased TIMP3 expression could reverse the promotive effects of SORBS2 knockdown on ESCC, confirming TIMP3 as a critical downstream molecule of SORBS2. Furthermore, downregulation of SORBS2 in ESCC cells was associated with activation of HUVEC functions, whereas upregulation of TIMP3 could reverse this effect. The SORBS2/TIMP3 axis may exert tumor suppressive effects by influencing extracellular matrix degradation. CONCLUSION: This study confirms that SORBS2 inhibits ESCC tumor progression by regulating extracellular matrix degradation through TIMP3, providing a potential therapeutic target for future treatment interventions.


Assuntos
Movimento Celular , Proliferação de Células , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Regulação Neoplásica da Expressão Gênica , Inibidor Tecidual de Metaloproteinase-3 , Humanos , Inibidor Tecidual de Metaloproteinase-3/genética , Inibidor Tecidual de Metaloproteinase-3/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Animais , Linhagem Celular Tumoral , Masculino , Camundongos Nus , Feminino , Camundongos , Células Endoteliais da Veia Umbilical Humana , Camundongos Endogâmicos BALB C , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Inibidores de Serinopeptidase do Tipo Kazal
2.
Asian J Surg ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39209634

RESUMO

To investigate whether the application of intravenous indocyanine green fluorescence imaging(ICG-FI) had advantage in intersegmental plane visualization and perioperative outcome than using traditional inflation-deflation method(control group) in thoracoscopic segmentectomy. We searched PubMed, Embase, Cochrane Library, EMBASE, Wanfang Database, VIP Database, and CNKI Database to include comparative studies focusing on the comparisons of ICG-FI and control, up to December 2022. We used standard mean differences (SMD, continuous variables) or risk ratios (RR, categorical variables) with their corresponding 95 % confidence interval (CI) were used to assess pooled effects. This analysis was conducted according to the PRISMA guideline. Total, seven published studies with 905 patients (ICG-FI group n = 428, control group n = 477) were included for further analysis. The ICG-FI group was significantly associated with less bleeding during the surgery (SMD = -0.23,95 % CI: -0.08∼-0.38, P < 0.05), shorter surgery time (SMD = -0.87, 95 % CI: -1.75∼-0.17, P < 0.05) and intersegmental boundary line (IBL) presentation time (SMD = -4.50, 95 % CI: -4.97∼-4.07, P < 0.01). The ICG-FI group had shorter postoperative hospitalization time (SMD = -0.18, 95 % CI: -0.34∼-0.03), P < 0.05), and the drainage duration (SMD = -0.18, 95 % CI: -0.34∼-0.03,P < 0.05) than that in the control group. The ICG-FI group also showed the less postoperative complications (RR = 0.75, 95 % CI: 0.64-0.88). There were no significant differences in the number of lymph node resection. No significant publication bias were found in this analysis. Compared with inflation-deflation method, application of ICG-FI in thoracoscopic segmentectomy could reduce operation time, IBL presentation time, length of hospital stay, intraoperative blood loss, and overall complication incidence.

3.
Nat Med ; 30(9): 2549-2557, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38956195

RESUMO

Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial aimed to further assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, compared to neoadjuvant chemotherapy alone. A total of 391 patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified by clinical stage (I/II, III or IVA) and randomized in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy. Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin (Cam+nab-TP group; n = 132); camrelizumab, paclitaxel and cisplatin (Cam+TP group; n = 130); and paclitaxel with cisplatin (TP group; n = 129), followed by surgical resection. Both the Cam+nab-TP and Cam+TP groups also received adjuvant camrelizumab. The dual primary endpoints were the rate of pathological complete response (pCR), as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators. This study reports the final analysis of pCR rates. In the intention-to-treat population, the Cam+nab-TP and Cam+TP groups exhibited significantly higher pCR rates of 28.0% and 15.4%, respectively, compared to 4.7% in the TP group (Cam+nab-TP versus TP: difference 23.5%, 95% confidence interval (CI) 15.1-32.0, P < 0.0001; Cam+TP versus TP: difference 10.9%, 95% CI 3.7-18.1, P = 0.0034). The study met its primary endpoint of pCR; however, EFS is not yet mature. The incidence of grade ≥3 treatment-related adverse events during neoadjuvant treatment was 34.1% for the Cam+nab-TP group, 29.2% for the Cam+TP group and 28.8% for the TP group; the postoperative complication rates were 34.2%, 38.8% and 32.0%, respectively. Neoadjuvant camrelizumab plus chemotherapy demonstrated superior pCR rates compared to chemotherapy alone for LA-ESCC, with a tolerable safety profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034 .


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Terapia Neoadjuvante , Paclitaxel , Humanos , Pessoa de Meia-Idade , Feminino , Masculino , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Paclitaxel/efeitos adversos , Adulto
4.
Sci Rep ; 14(1): 17720, 2024 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-39085347

RESUMO

Esophageal cancer, ranked as the seventh most common cancer globally, encompasses squamous cell carcinoma and adenocarcinoma. Despite advancements in treatment modalities like surgery, chemotherapy, radiotherapy, and immunotherapy, radiotherapy, while crucial for enhancing local control and survival, poses risks for long-term side effects and the development of second primary malignancies (SPM), notably Second primary lung cancer (SPLC). This study aims to analyze the incidence of second primary lung cancer (SPLC) among esophageal cancer survivors, with a focus on the influence of radiotherapy, analyze variations across different demographic and clinical subgroups, and assess patient survival outcomes. Using data from the Surveillance, epidemiology, and end results (SEER) program on 56,493 esophageal cancer patients (2000-2020), we compared SPLC incidence in those with and without prior radiotherapy. We applied a competing risks framework, propensity score matching (PSM), and survival analyses to assess SPLC risk and radiotherapy's impact. The study showed that patients treated with radiotherapy have a significantly higher long-term risk of SPLC compared to those without it. Radiotherapy significantly raised SPLC risk (HR 1.41, 95% CI 1.06-1.88), with higher SIRs particularly in younger patients and females. Post-PSM, there were significant differences in cancer-specific survival between esophageal cancer survivors with post-radiotherapy SPLC and those with only primary lung cancer. This cohort study shows that radiotherapy in esophageal cancer survivors increases SPLC risk but does not worsen survival compared to those with OPLC, highlighting the need for long-term monitoring and management.


Assuntos
Sobreviventes de Câncer , Neoplasias Esofágicas , Neoplasias Pulmonares , Segunda Neoplasia Primária , Programa de SEER , Humanos , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/mortalidade , Feminino , Masculino , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/epidemiologia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/epidemiologia , Pessoa de Meia-Idade , Idoso , Sobreviventes de Câncer/estatística & dados numéricos , Incidência , Radioterapia/efeitos adversos , Análise de Sobrevida
5.
Transl Oncol ; 47: 102050, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38981245

RESUMO

PURPOSE: Development and validation of a radiomics model for predicting occult locally advanced esophageal squamous cell carcinoma (LA-ESCC) on computed tomography (CT) radiomic features before implementation of treatment. METHODS: The study retrospectively collected 574 patients with esophageal squamous cell carcinoma (ESCC) from two medical centers, which were divided into three cohorts for training, internal and external validation. After delineating volume of interest (VOI), radiomics features were extracted and subjected to feature selection using three robust methods. Subsequently, 10 machine learning models were constructed, among which the optimal model was utilized to establish a radiomics signature. Furthermore, a predictive nomogram incorporating both clinical and radiomics signatures was developed. The performance of these models was evaluated through receiver operating characteristic curves, calibration curves, decision curve analysis as well as measures including accuracy, sensitivity, and specificity. RESULTS: A total of 19 radiomics features were selected. The multilayer perceptron (MLP), which was found to be optimal, achieved an AUC of 0.919, 0.864 and 0.882 in the training, internal and external validation cohorts, respectively. Similarly, MLP showed good accuracy in distinguish occult LA-ESCC in subgroup of cT1-2N0M0 diagnosed by clinicians with 0.803 and 0.789 in two validation cohorts respectively. By incorporating the radiomics signature with clinical signature, a predictive nomogram demonstrated superior prediction performance with an AUC of 0.877 and accuracy of 0.85 in external validation cohort. CONCLUSION: The radiomics and machine learning model can offers improved accuracy in prediction of occult LA-ESCC, providing valuable assistance to clinicians when choosing treatment plans.

7.
Epigenomics ; 16(10): 733-752, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38869483

RESUMO

Aim: This study aimed to investigate the functions of ZNF582-AS1 and ZNF582 in esophageal cancer (EC). Materials & methods: Bioinformatics analysis, qRT-PCR and western blot were used to analyze the expression levels. Biological functions were evaluated using cell-counting kit 8, colony formation, Transwell assays and flow cytometry. FISH was used to detect subcellular localization, and methylation-specific PCR determined gene methylation levels. Animal experiments validated the impact on tumor progression. Results: ZNF582-AS1 and ZNF582 were highly methylated and downregulated in EC. Overexpression of ZNF582-AS1 up-regulated the expression of ZNF582, thereby inhibiting EC cell viability and metastasis, promoting apoptosis and inhibiting tumor growth. Conclusion: Low expression of ZNF582-AS1/ZNF582 mediated by DNA hypermethylation facilitates the malignant progression of EC.


Promoter hypermethylation silences ZNF582-AS1 and ZNF582, driving esophageal cancer progression, which has the potential for novel therapeutic strategies. # Methylation # Esophageal Cancer.


Assuntos
Metilação de DNA , Neoplasias Esofágicas , Regulação Neoplásica da Expressão Gênica , Regiões Promotoras Genéticas , RNA Longo não Codificante , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Humanos , RNA Longo não Codificante/genética , Animais , Linhagem Celular Tumoral , Camundongos , Progressão da Doença , Proliferação de Células , Apoptose/genética , Camundongos Nus , Masculino , Feminino
9.
Sci Rep ; 14(1): 9818, 2024 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684769

RESUMO

Lung cancer, a global mortality leader, often necessitates Video-Assisted Thoracoscopic (VATS) surgery. However, post-operative nausea and vomiting (PONV) is common, highlighting a need for effective management and prevention strategies in this context. A retrospective case-control study at Fujian Medical University Union Hospital evaluated patients undergoing VATS radical resection of lung cancer between May and September 2022. Patients were categorized based on PONV prevention methods, and data encompassing demographics, surgical history, and postoperative adverse events s were analyzed to assess the association between prophylactic protocols and PONV incidence. The Netupitant and Palonosetron Hydrochloride (NEPA) group showed a significant reduction in PONV occurrences post-surgery compared to Ondansetron (ONDA) and Control groups, emphasizing NEPA's efficacy in alleviating PONV symptoms (P < 0.05). Furthermore, following VATS radical resection of lung cancer, NEPA markedly reduced the intensity of PONV symptoms in patients. Both univariate and multivariate logistic analyses corroborated that NEPA independently reduces PONV risk, with its protective effect also apparent in susceptible populations like females and non-smokers. NEPA utilization markedly reduced both the incidence and severity of PONV in patients undergoing VATS radical resection of lung cancer, serving as an independent protective factor in mitigating PONV risk post-surgery.


Assuntos
Neoplasias Pulmonares , Náusea e Vômito Pós-Operatórios , Cirurgia Torácica Vídeoassistida , Humanos , Feminino , Cirurgia Torácica Vídeoassistida/métodos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Masculino , Neoplasias Pulmonares/cirurgia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Náusea e Vômito Pós-Operatórios/etiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Estudos de Casos e Controles , Antieméticos/uso terapêutico , Antieméticos/administração & dosagem , Ondansetron/uso terapêutico , Ondansetron/administração & dosagem , Palonossetrom/uso terapêutico , Palonossetrom/administração & dosagem
10.
Cancer Lett ; 591: 216874, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38636894

RESUMO

Esophageal cancer ranks among the most prevalent malignant tumors, and esophageal squamous cell carcinoma (ESCC) constitutes its predominant histological form. Despite its impact, a thorough insight into the molecular intricacies of ESCC's development is still incomplete, which hampers the advancement of targeted molecular diagnostics and treatments. Recently, B-cell lymphoma-2-associated transcription factor 1 (BCLAF1) has come under investigation for its potential involvement in tumor biology, yet its specific role and mechanism in ESCC remain unclear. In this study, we observed a marked increase in BCLAF1 expression in ESCC tissues, correlating with advanced tumor stages and inferior patient outcomes. Our comprehensive in vitro and in vivo studies show that BCLAF1 augments glycolytic activity and the proliferation, invasion, and spread of ESCC cells. By employing mass spectrometry, we identified YTHDF2 as a key protein interacting with BCLAF1 in ESCC, with further validation provided by colocalization, co-immunoprecipitation, and GST pull-down assay. Further investigations involving MeRIP-seq and RIP-seq, alongside transcriptomic analysis, highlighted SIX1 mRNA as a molecule significantly upregulated and modified by N6-methyladenosine (m6A) in BCLAF1 overexpressing cells. BCLAF1 was found to reduce the tumor-suppressive activities of YTHDF2, and its effects on promoting glycolysis and cancer progression were shown to hinge on SIX1 expression. This research establishes that BCLAF1 fosters glycolysis and tumor progression in ESCC through the YTHDF2-SIX1 pathway in an m6A-specific manner, suggesting a potential target for future therapeutic intervention.


Assuntos
Proliferação de Células , Progressão da Doença , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio , Estabilidade de RNA , Proteínas de Ligação a RNA , Proteínas Repressoras , Animais , Feminino , Humanos , Masculino , Camundongos , Adenosina/análogos & derivados , Adenosina/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Glicólise/genética , Camundongos Nus , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo
11.
Front Oncol ; 14: 1279733, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38463231

RESUMO

Objective: This study investigates the prognostic significance of inflammatory nutritional scores in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) undergoing neoadjuvant chemoimmunotherapy. Methods: A total of 190 LA-ESCC patients were recruited from three medical centers across China. Pre-treatment laboratory tests were utilized to calculate inflammatory nutritional scores. LASSO regression and multivariate logistic regression analyses were conducted to pinpoint predictors of pathological response. Kaplan-Meier and Cox regression analyses were employed to assess disease-free survival (DFS) prognostic factors. Results: The cohort comprised 154 males (81.05%) and 36 females (18.95%), with a median age of 61.4 years. Pathological complete response (pCR) was achieved in 17.38% of patients, while 44.78% attained major pathological response (MPR). LASSO and multivariate logistic regression analyses identified that hemoglobin, albumin, lymphocyte, and platelet (HALP) (P=0.02) as an independent predictors of MPR in LA-ESCC patients receiving neoadjuvant chemoimmunotherapy. Kaplan-Meier and log-rank tests indicated that patients with low HALP, MPR, ypT1-2, ypN0 and, ypTNM I stages had prolonged DFS (P < 0.05). Furthermore, univariate and multivariate Cox regression analyses underscored HALP (P = 0.019) and ypT (P = 0.029) as independent predictive factors for DFS in ESCC. Conclusion: Our study suggests that LA-ESCC patients with lower pre-treatment HALP scores exhibit improved pathological response and reduced recurrence rate. As a comprehensive index of inflammatory nutritional status, pre-treatment HALP may be a reliable prognostic marker in ESCC patients undergoing neoadjuvant chemoimmunotherapy.

12.
Front Nutr ; 11: 1265878, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38439922

RESUMO

Background: Lung cancer is the most common global cancer in terms of incidence and mortality. Its main driver is tobacco smoking. The identification of modifiable risk factors isa public health priority. Green tea consumption has been examined in epidemiological studies, with inconsistent findings. Thus, we aimed to apply Mendelian randomization to clarify any causal link between green tea consumption and the risk of lung cancer. Methods: We utilized a two-sample Mendelian randomization (MR) approach. Genetic variants served as instrumental variables. The goal was to explore a causal link between green tea consumption and different lung cancer types. Green tea consumption data was sourced from the UK Biobank dataset, and the genetic association data for various types of lung cancer were sourced from multiple databases. Our analysis included primary inverse-variance weighted (IVW) analyses and various sensitivity test. Results: No significant associations were found between green tea intake and any lung cancer subtypes, including non-small cell lung cancer (adenocarcinoma and squamous cell carcinoma) and small cell lung cancer. These findings were consistent when applying multiple Mendelian randomization methods. Conclusion: Green tea does not appear to offer protective benefits against lung cancer at a population level. However, lung cancer's complex etiology and green tea's potential health benefitssuggest more research is needed. Further studies should include diverse populations, improved exposure measurements and randomized controlled trials, are warranted.

13.
Front Immunol ; 15: 1332492, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38375480

RESUMO

Purpose: The need for adjuvant therapy (AT) following neoadjuvant chemoimmunotherapy (nICT) and surgery in esophageal squamous cell cancer (ESCC) remains uncertain. This study aims to investigate whether AT offers additional benefits in terms of recurrence-free survival (RFS) for ESCC patients after nICT and surgery. Methods: Retrospective analysis was conducted between January 2019 and December 2022 from three centers. Eligible patients were divided into two groups: the AT group and the non-AT group. Survival analyses comparing different modalities of AT (including adjuvant chemotherapy and adjuvant chemoimmunotherapy) with non-AT were performed. The primary endpoint was RFS. Propensity score matching(PSM) was used to mitigate inter-group patient heterogeneity. Kaplan-Meier survival curves and Cox regression analysis were employed for recurrence-free survival analysis. Results: A total of 155 nICT patients were included, with 26 patients experiencing recurrence. According to Cox analysis, receipt of adjuvant therapy emerged as an independent risk factor(HR:2.621, 95%CI:[1.089,6.310], P=0.032), and there was statistically significant difference in the Kaplan-Meier survival curves between non-AT and receipt of AT in matched pairs (p=0.026). Stratified analysis revealed AT bring no survival benefit to patients with pathological complete response(p= 0.149) and residual tumor cell(p=0.062). Subgroup analysis showed no significant difference in recurrence-free survival between non-AT and adjuvant chemoimmunotherapy patients(P=0.108). However, patients receiving adjuvant chemotherapy exhibited poorer recurrence survival compared to non-AT patients (p= 0.016). Conclusion: In terms of recurrence-free survival for ESCC patients after nICT and surgery, the necessity of adjuvant therapy especially the adjuvant chemotherapy, can be mitigated.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/terapia , Terapia Neoadjuvante , Neoplasias Esofágicas/patologia , Estudos Retrospectivos , Pontuação de Propensão , Intervalo Livre de Doença
14.
JAMA ; 331(3): 201-211, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38227033

RESUMO

Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.


Assuntos
Anticorpos Monoclonais Humanizados , Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Compostos de Platina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Resposta Patológica Completa , Antineoplásicos/uso terapêutico , Terapia Combinada , Compostos de Platina/administração & dosagem , Compostos de Platina/uso terapêutico , Idoso
15.
BMC Pulm Med ; 23(1): 417, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37907906

RESUMO

BACKGROUND: We aimed to investigate the factors influencing the cure, recurrence, and metastasis rates of stage IA lung adenocarcinoma, using a mixed cure model. METHODS: A total of 1,064 patients who underwent video-assisted thoracoscopic pulmonectomy were included. Variable screening was performed using the random forest algorithm and least absolute shrinkage and selection operator approaches. The mixed cure model was used to identify factors affecting patient cure and survival, and a sequential analysis was performed on 5%, 10%, and 20% of the presentational subtype concurrently. A receiver operating characteristics curve was used to determine the best model and construct a nomogram to predict the cure rate. RESULTS: The median follow-up time was 58 (range: 3-115) months. Results from the cure part of the mixed model indicated that the predominant subtype, presentational subtype, and tumor diameter were the main prognostic factors affecting cure rate. Therefore, the nomogram to predict the cure rate was constructed based on these factors. The survival part indicated that the predominant subtype was the only factor that influenced recurrence and metastasis. A sequential analysis of the presentational subtype showed it had no significant effect on survival (P > 0.05). Regardless of the recording mode, no significant improvement was observed in the model's discriminative ability. Only a few postoperative pathological specimens showed lymphovascular invasion (LVI); however, the survival curve suggested a significant effect on patient survival. CONCLUSIONS: After excluding the existence of long-term survivors, the predominant tumor subtype was determined to be the only factor influencing recurrence and metastasis. Although LVI is rare in stage IA lung adenocarcinoma, its significance cannot be discounted in terms of determining patient prognosis.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Adenocarcinoma/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/patologia , Prognóstico
17.
JAMA Netw Open ; 6(10): e2337889, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37843862

RESUMO

Importance: It is currently unclear whether high-resolution computed tomography can preoperatively identify pathologic tumor invasion for ground-glass opacity lung adenocarcinoma. Objectives: To evaluate the diagnostic value of high-resolution computed tomography for identifying pathologic tumor invasion for ground-glass opacity featured lung tumors. Design, Setting, and Participants: This prospective, multicenter diagnostic study enrolled patients with suspicious malignant ground-glass opacity nodules less than or equal to 30 mm from November 2019 to July 2021. Thoracic high-resolution computed tomography was performed, and pathologic tumor invasion (invasive adenocarcinoma vs adenocarcinoma in situ or minimally invasive adenocarcinoma) was estimated before surgery. Pathologic nonadenocarcinoma, benign diseases, or those without surgery were excluded from analyses; 673 patients were recruited, and 620 patients were included in the analysis. Statistical analysis was performed from October 2021 to January 2022. Exposure: Patients were grouped according to pathologic tumor invasion. Main Outcomes and Measures: Primary end point was diagnostic yield for pathologic tumor invasion. Secondary end point was diagnostic value of radiologic parameters. Results: Among 620 patients (442 [71.3%] female; mean [SD] age, 53.5 [12.0] years) with 622 nodules, 287 (46.1%) pure ground-glass opacity nodules and 335 (53.9%) part-solid nodules were analyzed. The median (range) size of nodules was 12.1 (3.8-30.0) mm; 47 adenocarcinomas in situ, 342 minimally invasive adenocarcinomas, and 233 invasive adenocarcinomas were confirmed. Overall, diagnostic accuracy was 83.0% (516 of 622; 95% CI, 79.8%-85.8%), diagnostic sensitivity was 82.4% (192 of 233; 95% CI, 76.9%-87.1%), and diagnostic specificity was 83.3% (324 of 389; 95% CI, 79.2%-86.9%). For tumors less than or equal to 10 mm, 3.6% (8 of 224) were diagnosed as invasive adenocarcinomas. The diagnostic accuracy was 96.0% (215 of 224; 95% CI, 92.5%-98.1%), diagnostic specificity was 97.2% (210 of 216; 95% CI, 94.1%-99.0%); for tumors greater than 20 mm, 6.9% (6 of 87) were diagnosed as adenocarcinomas in situ or minimally invasive adenocarcinomas. The diagnostic accuracy was 93.1% (81 of 87; 95% CI, 85.6%-97.4%) and diagnostic sensitivity was 97.5% (79 of 81; 95% CI, 91.4%-99.7%). For tumors between 10 to 20 mm, the diagnostic accuracy was 70.7% (220 of 311; 95% CI, 65.3%-75.7%), diagnostic sensitivity was 75.0% (108 of 144; 95% CI, 67.1%-81.8%), and diagnostic specificity was 67.1% (112 of 167; 95% CI, 59.4%-74.1%). Tumor size (odds ratio, 1.28; 95% CI, 1.18-1.39) and solid component size (odds ratio, 1.31; 95% CI, 1.22-1.42) could each independently serve as identifiers of pathologic invasive adenocarcinoma. When the cutoff value of solid component size was 6 mm, the diagnostic sensitivity was 84.6% (95% CI, 78.8%-89.4%) and specificity was 82.9% (95% CI, 75.6%-88.7%). Conclusions and relevance: In this diagnostic study, radiologic analysis showed good performance in identifying pathologic tumor invasion for ground-glass opacity-featured lung adenocarcinoma, especially for tumors less than or equal to 10 mm and greater than 20 mm; these results suggest that a solid component size of 6 mm could be clinically applied to distinguish pathologic tumor invasion.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Prospectivos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Adenocarcinoma/patologia , Tomografia Computadorizada por Raios X/métodos
18.
Cancer Cell Int ; 23(1): 198, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37684619

RESUMO

Small nucleolar RNA host gene 1 (SNHG1) is an important member of the SNHG family. This family is composed of a group of host genes that can be processed into small nucleolar RNAs and play important biological functions. In an oncogenic role, the SNHG1 expression is increased in various cancers, which has immense application prospects in the diagnosis, treatment, and prognosis of malignant tumors. In this review, we have summarized the role and molecular mechanism of SNHG1 in the development of various cancers. In addition, we have emphasized the clinical significance of SNHG1 in cancers in our article. This molecule is expected to be a new marker for potential usage in the diagnosis, prognosis, and treatment of cancer.

19.
Front Oncol ; 13: 1247450, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37719012

RESUMO

Objective: The aim of this retrospective study was to investigate the safety and economic aspects of using the EasyEndo disposable endoscopic cutting and stapling device for video-assisted thoracoscopic surgery (VATS) lobectomy or segmentectomy in patients with lung cancer. The choice between the two staplers was influenced by changes in our hospital's procurement policy; Johnson EC45A was used before January 2022 and was then replaced by the EasyEndo stapler. Methods: We reviewed and analyzed consecutive patients with lung cancer who underwent VATS segmentectomy from March 2021 to December 2022. Inclusion criteria included patients with suspected non-small cell lung cancer (NSCLC) who were eligible for surgical resection. The surgical procedures were performed using either the EasyEndo or Johnson EC45A staplers. Intraoperative variables, postoperative outcomes, and cost analysis were compared between the two groups. Results: A total of 1556 patients were included in the study, with 775 patients in the Control group and 781 patients in the EasyEndo group. There were no significant differences in patient characteristics between the two groups. Intraoperative variables, including blood loss, blood transfusion, and operation time, showed no significant differences between the groups. Postoperative outcomes, such as hospital stay, drainage tube placement time, and incidence of complications, were also comparable between the two groups. However, there was a significant difference in the cost of stapler usage, with the EasyEndo group showing a lower cost compared to the Control group. Conclusion: The EasyEndo disposable endoscopic cutting and stapling device demonstrated comparable safety and effectiveness to the Johnson EC45A stapler in VATS segmentectomy for lung cancer patients. Moreover, the use of the EasyEndo stapler resulted in cost savings, indicating its potential economic benefits for healthcare institutions.

20.
World J Surg Oncol ; 21(1): 243, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37563730

RESUMO

BACKGROUND: Cancer stem cells may be the source of cancer-causing mutant cells and are closely related to the prognosis of cancer. Our study aimed to investigate the potential association between single-nucleotide polymorphisms (SNPs) of cancer stem cell-related genes and the prognosis of lung cancer patients. METHODS: The SNP loci were genotyped by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS), and the overall survival of subjects was analyzed by log-rank test after stratifying and adjusting their demographic data, clinical data, and genotypes. The correlation between survival time and quality of life of lung cancer under codominant, dominant, recessive, and additive genetic models was analyzed by the Cox regression model. The association between SNP polymorphism and the prognosis of lung cancer was analyzed by Stata16.0 software, and their heterogeneity was tested. Interaction analysis was performed using R software (version 4.2.0). RESULTS: Stratified analysis unveiled that rs3740535 had recessive AA genotype and additive GG genotype; Rs3130932 dominant GT + GG genotype, additive TT genotype; Rs13409 additive TT genotype; Rs6815391 recessive CC genotype and additional TT genotype were associated with increased risk of lung cancer death. Rs3130932 recessive GG genotype was associated with a reduced risk of lung cancer death. CONCLUSION: Rs3740535, rs3130932, rs13409, and rs6815391 are associated with the overall survival of lung cancer patients and may be valuable for the prognosis of lung cancer patients.


Assuntos
Neoplasias Pulmonares , Polimorfismo de Nucleotídeo Único , Humanos , Qualidade de Vida , Neoplasias Pulmonares/genética , Genótipo , Prognóstico , Predisposição Genética para Doença , Estudos de Casos e Controles
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