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1.
J Dig Dis ; 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850211

RESUMO

OBJECTIVE: We aimed to investigate the prevalence of vascular complications in acute pancreatitis (AP), to compare patient outcomes using various treatments, and to explore the related risk factors. METHODS: Consecutive AP patients admitted from January 2010 to July 2017 were retrospectively included. Demographics, vascular complications, laboratory indices, and imaging findings were collected. Univariate and multivariate analyses were used to explore potential risk factors of vascular complications. RESULTS: Of 3048 AP patients, 808 (26.5%) had vascular complications, including visceral vein thrombosis, sinistral portal hypertension, and arterial complications. And 38 (4.7%) patients received anticoagulant therapy and had a higher rate of recanalization (P < 0.001). Bleeding occurred in 95 (11.8%) patients, who received further treatment. Multivariate analysis identified male gender (odds ratio [OR] 1.650, 95% confidence interval [CI] 1.101-2.472), hyperlipidemia (OR 1.714, 95% CI 1.356-2.165), disease recurrence (OR 3.727, 95% CI 2.713-5.118), smoking (OR 1.519, 95% CI 1.011-2.283), hemoglobin level (OR 0.987, 95% CI 0.981-0.993), white blood cell (WBC) count (OR 1.094, 95% CI 1.068-1.122), non-vascular local complications (OR 3.018, 95% CI 1.992-4.573), computed tomography severity index (CTSI) (OR 1.425, 95% CI 1.273-1.596), and acute physiology and chronic health evaluation (APACHE) II score (OR 1.057, 95% CI 1.025-1.090) were related to vascular complications. CONCLUSIONS: Vascular complications in AP is prevalent and their treatment is challenging. Further investigations are warranted to determine the optimal treatment strategy. Independent risk factors included male gender, hyperlipidemia, disease recurrence, smoking, WBC count, non-vascular local complications, CTSI, and APACHE II score.

2.
Sci Rep ; 14(1): 5080, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429521

RESUMO

The polycyclic aromatic hydrocarbon (PAH) concentrations in total suspended particulate matter (TSP) samples collected from October, 2021 to September, 2022 were analyzed to clarify the pollution characteristics and sources of 16 PAHs in the atmospheric TSP in Bengbu City. The ρ(PAHs) concentrations ranged from 1.71 to 43.85 ng/m3 and higher concentrations were detected in winter, followed by spring, autumn, and summer. The positive matrix factorization analysis revealed that, in spring and summer, PAH pollution was caused mainly by industrial emissions, gasoline and diesel fuel combustion, whereas in autumn and winter, it was coal, biomass and natural gas combustion. The cluster and potential source factor analyses showed that long-range transport was a significant factor. During spring, autumn, and winter, the northern and northwestern regions had a significant impact, whereas the coastal area south of Bengbu had the greatest influence in summer. The health risk assessment revealed that the annual total carcinogenic equivalent concentration values for PAHs varied from 0.0159 to 7.437 ng/m3, which was classified as moderate. Furthermore, the annual incremental lifetime cancer risk values ranged from 1.431 × 10-4 to 3.671 × 10-3 for adults and from 6.823 × 10-5 to 1.749 × 10-3 for children, which were higher than the standard.


Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Adulto , Criança , Humanos , Material Particulado/análise , Poluentes Atmosféricos/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Monitoramento Ambiental , Medição de Risco , Gasolina , China
3.
Int J Biol Sci ; 20(5): 1871-1883, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481804

RESUMO

Radiotherapy (RT) stands as the primary treatment for tumors, but it inevitably causes damage to normal cells. Consequently, radiation injury is a crucial consideration for radiation oncologists during therapy planning. Cell death including apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis play significant roles in tumor treatment. While previous studies elucidated the induction of apoptosis and autophagy by ionizing radiation (IR), recent attention has shifted to pyroptosis, ferroptosis, and necroptosis, revealing their effects induced by IR. This review aims to summarize the strategies employed by IR, either alone or in combination therapy, to induce pyroptosis, ferroptosis, and necroptosis in radiation injury. Furthermore, we explore their effects and molecular pathways, shedding light on their roles in radiation injury. Finally, we summarize the regulative agents for these three types of cell death and their mechanisms. In summary, optimizing radiation dose, dose rate, and combined treatment plans to minimize radiation damage and enhance the killing effect of RT is a key focus.


Assuntos
Ferroptose , Lesões por Radiação , Humanos , Piroptose , Necroptose , Apoptose
5.
J Cancer Res Clin Oncol ; 150(2): 94, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38369644

RESUMO

BACKGROUND: The third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can penetrate blood-brain barrier and are effective for brain metastases (BMs). There is no consensus on the optimal sequence of local therapy (LT) and EGFR-TKIs for symptomatic BM patients because patients suffering neurological symptoms were not enrolled in most clinical trials. METHODS: Non-small cell lung cancer (NSCLC) patients with EGFR mutation (EGFRm) and symptomatic BM receiving first-line osimertinib and aumolertinib from two medical centers were collected. All participants were allocated into the third-generation EGFR-TKIs (TKIs) group and the upfront LT (uLT) plus third-generation EGFR-TKIs (TKIs + uLT) group. Demographic data, survival outcomes, treatment failure patterns, and adverse events were evaluated between the two groups. We also conducted subgroup analyses to explore the impact of BM number on survival outcomes. RESULTS: 86 patients were enrolled, 44 in the TKIs group and 42 in the TKIs + uLT group. There were no significant differences in the short-term response between the groups. TKIs + uLT was associated with significantly longer overall survival (OS) (43 vs. 28 months; hazard ratio [HR], 0.36, 95% confidence interval [CI], 0.17-0.77; p = .011). No differences in progression-free survival (PFS), intracranial PFS (iPFS), failure patterns, or safety were observed. In subgroup analyses of oligo-BM patients, TKIs + uLT could prolong OS (43 vs. 31 months; HR 0.22; 95% CI 0.05-0.92; p = .015). CONCLUSIONS: EGFRm NSCLC patients with symptomatic BM might benefit from uLT, particularly oligo-BM patients. However, larger prospective cohort studies should be carried out to confirm the responses of the TKIs + uLT scheme.


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 , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Estudos Prospectivos , Estudos Retrospectivos , /uso terapêutico
6.
Front Pharmacol ; 15: 1333128, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38375030

RESUMO

Background: Tumor treating fields (TTF) was first approved for treatment of glioblastoma. Recently, the LUNAR study demonstrated that TTF + standard therapy (ST) extended survival in patients with advanced non-small cell lung cancer (NSCLC). This primary objective of this study is to analyze the cost-effectiveness of this treatment from the United States healthcare payers' perspective. Methods: A 3-health-state Markov model was established to compare the cost-effectiveness of TTF + ST and that of ST alone. Clinical data were extracted from the LUNAR study, supplemented by additional cost and utility data obtained from publications or online sources. One-way sensitivity analysis, probabilistic sensitivity analysis, and scenario analysis were conducted. The willingness-to-pay (WTP) threshold per quality-adjusted life-years (QALYs) gained was set to $150,000. The main results include total costs, QALYs, incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (INMB). Subgroup analyses were conducted for two types of ST, including immune checkpoint inhibitor, and docetaxel. Results: During a 10-year time horizon, the costs of TTF + ST and ST alone were $431,207.0 and $128,125.9, and the QALYs were 1.809 and 1.124, respectively. The ICER of TTF + ST compared to ST was $442,732.7 per QALY, and the INMB was -$200,395.7 at the WTP threshold. The cost of TTF per month was the most influential factor in cost-effectiveness, and TTF + ST had a 0% probability of being cost-effective at the WTP threshold compared with ST alone. Conclusion: TTF + ST is not a cost-effective treatment for advanced NSCLC patients who progressed after platinum-based therapy from the perspective of the United States healthcare payers.

7.
ACS Omega ; 9(2): 2752-2757, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38250410

RESUMO

A catalyst with a simple synthetic process and good catalytic performance was prepared using Na2CO3 as the active component and ZSM-5 as the carrier for the resource utilization of waste cooking oil. The structure of Na2CO3/ZSM-5 was characterized by Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy, and the effects of parameters such as Na2CO3 loading, catalyst percentage, and reaction time on the yield of fatty acid methyl esters were investigated. The results showed that the conversion of waste cooking oil to fatty acid methyl esters yielded up to 96.89% when the Na2CO3 loading was 35%, the reaction temperature was 65 °C, the reaction time was 2 h, and the catalyst percentage was 1 wt %. The Na2CO3/ZSM-5 catalyst could be used to replace H2SO4 or NaOCH3 in the industrial treatment of waste cooking oil for its resource utilization.

8.
Int J Biol Sci ; 20(2): 765-783, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38169621

RESUMO

Brain metastases (BMs) frequently occur in primary tumors such as lung cancer, breast cancer, and melanoma, and are associated with notably short natural survival. In addition to surgical interventions, chemotherapy, targeted therapy, and immunotherapy, radiotherapy (RT) is a crucial treatment for BM and encompasses whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS). Validating the efficacy and safety of treatment regimens through preclinical models is imperative for successful translation to clinical application. This not only advances fundamental research but also forms the theoretical foundation for clinical study. This review, grounded in animal models of brain metastases (AM-BM), explores the theoretical underpinnings and practical applications of radiotherapy in combination with chemotherapy, targeted therapy, immunotherapy, and emerging technologies such as nanomaterials and oxygen-containing microbubbles. Initially, we provided a concise overview of the establishment of AM-BMs. Subsequently, we summarize key RT parameters (RT mode, dose, fraction, dose rate) and their corresponding effects in AM-BMs. Finally, we present a comprehensive analysis of the current research status and future directions for combination therapy based on RT. In summary, there is presently no standardized regimen for AM-BM treatment involving RT. Further research is essential to deepen our understanding of the relationships between various parameters and their respective effects.


Assuntos
Neoplasias Encefálicas , Neoplasias Pulmonares , Melanoma , Radiocirurgia , Humanos , Irradiação Craniana , Neoplasias Pulmonares/patologia , Neoplasias Encefálicas/secundário , Melanoma/terapia , Estudos Retrospectivos
9.
J Robot Surg ; 18(1): 1, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38175325

RESUMO

AIM: Robotic-assisted pancreatectomy has been widely used. Organ-preserving pancreatectomy (OPP) and parenchymal-sparing pancreatectomy (PSP) has been gradually adopted for pancreatic benign or low-grade malignant tumors. This study aimed to evaluate the safety and efficacy of robotic-assisted OPP/PSP in our institute. METHODS: Patients undergoing robotic-assisted OPS/PSP at First Affiliated Hospital of Sun Yat-sen University between July 2015 and October 2021 were included in this study. The short-term and long-term outcomes of patients were retrospectively analyzed. RESULTS: Seventy-two patients were enrolled, including spleen-preserving distal pancreatectomy, central pancreatectomy, duodenum-preserving pancreatic head resection, and enucleation. Patients included were more likely to be young female (female: 46/72, median age: 47 years old). The median intraoperative blood loss and operation time was 50 ml and 255 min, respectively. Clinically relevant postoperative pancreatic fistula was 20.8% (grade B: 15/72, 20.8%; no grade C). The overall complication rate was 22.2% with the median postoperative length-of-stay of 8 days. At a median follow-up time of 28.5 months, the 5-year overall survival and recurrence-free survival rate were 100.0% and 100.0%, respectively. CONCLUSION: The short-term and long-term outcomes of patients receiving robotic-assisted OPP/PSP were acceptable. Robotic-assisted OPP/PSP was a feasible and safe technique for pancreatic benign or low-grade malignant lesions.


Assuntos
Neoplasias , Procedimentos Cirúrgicos Robóticos , Humanos , Feminino , Pessoa de Meia-Idade , Pancreatectomia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Pâncreas/cirurgia , Complicações Pós-Operatórias/epidemiologia
10.
Eur J Haematol ; 112(2): 257-265, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37698159

RESUMO

OBJECTIVES: We aim to analyze the predictive value of thromboelastography on bleeding severity of patients with chimeric antigen receptor (CAR)-T cell therapy. METHODS: A total of 80 patients with refractory/relapsed hematological malignancy were enrolled and divided into two groups: the severe bleeding group and the non-severe bleeding group. The thromboelastography data was collected on the day of CAR-T infusion and the 3rd, 7th, 10th, 13th, 17th, and 20th day after CAR-T cell infusion. RESULTS: The patients of the severe bleeding group had lower platelet (p < .007), maximum amplitude (p = .002), coagulation index (p = .005), and longer coagulation time (p = .019). Increasing trend in reaction time and coagulation time and decreasing trend in Alpha, maximum amplitude, and coagulation index on Days 0-10, opposite on Days 10-20. Univariate logistic regression analysis and multivariable logistic regression analysis showed maximum amplitude on the 3rd day after CAR-T cell infusion (MA3) (OR = 0.9; 95% CI = 0.84-0.95; p < .001) and cytokine release syndrome grade (OR = 2.57; 95% CI = 1.35-5.32; p = .006) were significantly associated with high bleeding severity. CONCLUSIONS: Thromboelastography was considered to be a good predictor of bleeding severity.


Assuntos
Neoplasias Hematológicas , Receptores de Antígenos Quiméricos , Humanos , Tromboelastografia , Imunoterapia Adotiva/efeitos adversos , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Hemorragia/diagnóstico , Hemorragia/etiologia , Hemorragia/terapia , Terapia Baseada em Transplante de Células e Tecidos
11.
BMC Surg ; 23(1): 382, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38114974

RESUMO

AIM: Splenic vessel-preserving spleen-preserving distal pancreatectomy (SVP-SPDP) has a lower risk of splenic infarction than the splenicvessel-sacrificing SPDP, but it is more technically demanding. Learning curve of robotic-assisted SVP-SPDP (RSVP-SPDP) remains unreported. This study sought to analyze the perioperative outcomes and learning curve of RSVP-SPDP by one single surgeon. METHODS: Seventy-four patients who were intended to receive RSVP-SPDP at the First Affiliated Hospital of Sun Yat-sen University between May 2015 and January 2023 were included. The learning curve were retrospectively analyzed by using cumulative sum (CUSUM) analyses. RESULTS: Sixty-two patients underwent RSVP-SPDP (spleen preservation rate: 83.8%). According to CUSUM curve, the operation time (median, 318 vs. 220 min; P < 0.001) and intraoperative blood loss (median, 50 vs. 50 mL; P = 0.012) was improved significantly after 16 cases. Blood transfusion rate (12.5% vs. 3.4%; P = 0.202), postoperative major morbidity rate (6.3% vs. 3.4%; P = 0.524), and postoperative length-of-stay (median, 10 vs. 8 days; P = 0.120) improved after 16 cases but did not reach statistical difference. None of the patients had splenic infarction or abscess postoperatively. CONCLUSION: RSVP-SPDP was a safe and feasible approach for selected patients after learning curve. The improvement of operation time and intraoperative blood loss was achieved after 16 cases.


Assuntos
Laparoscopia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Infarto do Baço , Cirurgiões , Humanos , Pancreatectomia , Estudos Retrospectivos , Perda Sanguínea Cirúrgica , Infarto do Baço/etiologia , Infarto do Baço/cirurgia , Curva de Aprendizado , Resultado do Tratamento , Artéria Esplênica/cirurgia , Neoplasias Pancreáticas/cirurgia
12.
Cell Rep ; 42(11): 113430, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37963021

RESUMO

Macroautophagy/autophagy plays a pivotal role in immune regulation. Its significance is evident in modulation of immune cell differentiation and maturation, physiologically and pathologically. Here, we investigate the role of macrophage autophagy on the development of atopic dermatitis (AD). By employing an MC903-induced AD mice model, we observe reduced cutaneous inflammation in macrophage Atg5 cKO mice compared with WT mice. Notably, there is a decreased infiltration of M2 macrophages in lesional skin from Atg5 cKO mice. Furthermore, impaired STAT6 phosphorylation and diminished expression of M2 markers are detected in autophagy-deficient macrophages. Our mechanistic exploration reveals that CEBPB drives the transcription of SOCS1/3 and SQSTM1/p62-mediated autophagy degrades CEBPB normally. Autophagy deficiency leads to CEBPB accumulation, and further promotes the expression of SOCS1/3. This process inhibits JAK1-STAT6 pathway activation and M2 marker expression. Together, our study indicates that autophagy is required for M2 activation and macrophage autophagy may be a promising target for AD intervention.


Assuntos
Dermatite Atópica , Animais , Camundongos , Autofagia , Dermatite Atópica/metabolismo , Modelos Animais de Doenças , Ativação de Macrófagos , Macrófagos/metabolismo
13.
Magn Reson Imaging ; 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38035947

RESUMO

PURPOSE: To develop and validate a model based on MRI radiomics modals for predicting surgical high FIGO(IB3 and ≥ IIA2) and low FIGO(IB1, IB2, and IIA1) stages in patients with cervical carcinoma (CC) . METHODS: A total of 296 early-stage patients with CC (preoperative FIGO stages IB-IIA) confirmed by surgery and pathology were included in this retrospective study from two institutions For each patient,we extracted radiomics features from spectral attenuated inversion-recovery T2-weighted (SPAIR-T2W) and contrast-enhanced T1-weighted (CE-T1W) images.Manual segmentation was performed using the 3D Slicer software, while radiomics features were extracted, screened using the R software. A 2-stage feature extraction strategy involving univariate analysis and the Least Absolute Shrinkage Selection Operator technique was performed. A support vector machine-based model was eventually constructed. Predictive accuracy of the training and validation datasets was assessed in terms of area under the ROC curve (AUC). RESULTS: A total of 1130 features were extracted from SPAIR-T2WI and CET1WI images respectively, in which 8 and 7 features significantly were associated with FIGO staging. AUCs of the SPAIR-T2W and CE-T1W models were were 0.803 and 0.790, respectively, in the internal validation group. In the external validation group, the AUCs were 0.767 and 0.749, respectively, which increased to 0.771 in the combined model. CONCLUSION: Our study demonstrated the feasibility of radiomics features from SPAIR-T2W and CE-T1W images for the prediction of surgical FIGO stage in CC. Our proposed model thereby carries the potential as a non-invasive tool for the staging and treatment planning of this disease. ADVANCES IN KNOWLEDGE: A radiomics model provide a non-invasive and objective method for the detection of FIGO staging in patients with cervical cancer before surgery, thus providing a reference for the selection of treatment options for patients.

14.
Biomed Pharmacother ; 167: 115456, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37696085

RESUMO

Tumor metastasis is the leading cause of mortality among advanced cancer patients. Understanding its mechanisms and treatment strategies is vital for clinical application. Arginine methylation, a post-translational modification catalyzed by protein arginine methyltransferases (PRMTs), is implicated in diverse physiological processes and disease progressions. Previous research has demonstrated PRMTs' involvement in tumor occurrence, progression, and metastasis. This review offers a comprehensive summary of the relationship between PRMTs, prognosis, and metastasis in various cancers. Our focus centers on elucidating the molecular mechanisms through which PRMTs regulate tumor metastasis. We also discuss relevant clinical trials and effective PRMT inhibitors, including chemical compounds, long non-coding RNA (lncRNA), micro-RNA (miRNA), and nanomaterials, for treating tumor metastasis. While a few studies present conflicting results, the overall trajectory suggests that inhibiting arginine methylation exhibits promise in curtailing tumor metastasis across various cancers. Nonetheless, the underlying mechanisms and molecular interactions are diverse. The development of inhibitors targeting arginine methylation, along with the progression of clinical trials, holds substantial potential in the field of tumor metastasis, meriting sustained attention.

15.
Microbiol Spectr ; : e0106923, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37668384

RESUMO

Zinc excess is toxic to bacteria and, thus, represents an important innate defense mechanism of host cells, especially against mycobacterial infections. However, the signaling pathway triggered by zinc excess and its relationship with iron homeostasis remain poorly understood in mycobacteria. Here, we characterize a novel Zur-IdeR-iron homeostasis signaling pathway that modulates the growth of Mycobacterium bovis under zinc toxicity. We found that the regulator Zur interacts with the iron-homeostasis regulator IdeR, enhancing the DNA-binding ability of IdeR. Excess zinc disrupts this interaction and represses ideR transcription through Zur, which promotes the expression of iron uptake genes and leads to the accumulation of intracellular iron in M. bovis. The elevated iron levels lower the bacterial survival ability under excess zinc stress. Consistently, deleting zur hinders intracellular iron accumulation of M. bovis and enhances bacterial growth under stress, while silencing ideR impairs the growth of the wild-type and zur-deleted strains under the same conditions. Interestingly, both Zur and IdeR are conserved in bacteria facing zinc toxicity. Overall, our work uncovers a novel antimicrobial signal pathway whereby zinc excess disrupts iron homeostasis, which may deepen our understanding of the crosstalk mechanism between iron and zinc homeostasis in bacteria.IMPORTANCEAs a catalytic and structural cofactor of proteins, zinc is essential for almost all living organisms. However, zinc excess is toxic and represents a vital innate immunity strategy of macrophages to combat intracellular pathogens, especially against mycobacterial pathogens such as Mycobacterium tuberculosis, the causative agent of tuberculosis. Here, we first characterize an antibacterial signaling pathway of zinc excess and its relationship with iron homeostasis in M. bovis. We found that excess zinc inhibits the transcription of ideR and its DNA-binding activity through Zur, which, in turn, promotes the expression of iron uptake genes, causes intracellular iron accumulation, and finally impairs the bacterial growth. This study reveals the existence of the Zur-IdeR-iron homeostasis pathway triggered by zinc excess in M. bovis, which will shed light on the crosstalk mechanisms between zinc and iron homeostasis in bacteria and the antimicrobial mechanisms of host-mediated zinc toxicity.

16.
iScience ; 26(9): 107634, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37664612

RESUMO

Adenosquamous carcinoma (ASC) is frequently misdiagnosed or overlooked in clinical practice due to its dual histological components and potential transformation from either adenocarcinoma (ADC) or squamous cell carcinoma (SCC). Our study aimed to differentiate ASC from ADC and SCC by incorporating features of enhanced CTs and clinical characteristics to build radiomics and deep learning models. The classification models were trained in Xiangya Hospital and validated in two other independent hospitals. The areas under the receiver operating characteristic curves (AUC), accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were used to estimate the performance. The optimal three-class classification model achieved a maximum AUC of 0.89 and accuracy of 0.81 in external validation sets, AUC of 0.99 and accuracy of 0.99 in the internal test set. These findings highlight the efficacy of our models in differentiating ASC, providing a non-invasive, timely, and accurate diagnostic approach before and during the treatment.

17.
Biomed Pharmacother ; 166: 115260, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37633056

RESUMO

Lung cancer is the leading cause of cancer-related mortality worldwide. A major contributing factor to the poor survival rates in lung cancer is the high prevalence of metastasis at the time of diagnosis. To address this critical issue, it is imperative to investigate the mechanisms underlying lung cancer metastasis. Circular RNAs (circRNAs), a distinct type of ribonucleic acid characterized by their unique circular structure, have been implicated in the progression of various diseases. Recent studies have highlighted the close association between circRNAs and the occurrence and development of lung cancer, particularly in relation to metastasis. In this review, we provide a concise overview of the expression patterns and prognostic significance of circRNAs in lung cancer. Additionally, we summarized the current understanding of the clinical relevance of circRNAs in lung cancer metastasis. Furthermore, we systematically focused on the roles of circRNAs in each step of lung cancer metastasis, reflecting the sequential progression of this process. Notably, circRNAs exhibit dual functionality in lung cancer metastasis, acting both as facilitators and inhibitors of metastatic processes. Given their potential, circRNAs hold promise as novel biomarkers and therapeutic targets for lung cancer metastasis, warranting further investigation.


Assuntos
Neoplasias Pulmonares , RNA Circular , Humanos , RNA Circular/genética , Neoplasias Pulmonares/genética , RNA/genética , Relevância Clínica
18.
J Cancer Res Clin Oncol ; 149(16): 15027-15038, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37612388

RESUMO

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy has shown promising results in treating blood cancers, but it has limited efficacy against solid tumors that express mesothelin (MSLN). One of the reasons is the immunosuppressive tumor microenvironment, which consists of physical barriers, multiple mechanisms of immune evasion, and various biochemical factors that favor tumor growth and survival. These factors reduce the antitumor activity of MSLN-targeted CAR T cells in clinical trials. Therefore, new therapeutic strategies are needed to enhance the effectiveness of MSLN-targeted CAR T cell therapy. METHODS: To investigate whether the antitumor efficacy of anti-MSLN CAR-T cells depends on the epitopes they recognize, we generated MSLN-targeted CAR T cells that bind to different regions of MSLN (Region I, II, III and Full length). We then evaluated the antitumor activity of MSLN-targeted CAR T cells alone or in combination with the chemotherapeutic drug irinotecan or an anti-PD-1 antibody in vitro and in vivo. RESULTS: We found that MSLN-targeted CAR T cells effectively killed MSLN-positive cancer cells (H9, H226 and Panc-1), but not MSLN-negative cells (A431) in vitro. In a mouse model of H9 tumor xenografts, all CAR T cells showed similar tumor suppression, but an MSLN-targeted scFv with Region I epitope, R47, performed slightly better. Combining irinotecan with CAR_R47 T cells enhanced tumor control synergistically in both H9 xenograft mice and patient-derived xenograft mice. CONCLUSIONS: Our results suggest that irinotecan can enhance the antitumor activity of MSLN-targeted CAR T cells, and offer a promising combination therapy strategy for MSLN-positive solid tumors.


Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Animais , Camundongos , Mesotelina , Imunoterapia Adotiva/métodos , Irinotecano , Proteínas Ligadas por GPI/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Neoplasias/tratamento farmacológico
19.
Curr Med Sci ; 43(5): 855-868, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37558865

RESUMO

Smad ubiquitylation regulatory factor 1 (Smurf1) is an important homologous member of E6-AP C-terminus type E3 ubiquitin ligase. Initially, Smurf1 was reportedly involved in the negative regulation of the bone morphogenesis protein (BMP) pathway. After further research, several studies have confirmed that Smurf1 is widely involved in various biological processes, such as bone homeostasis regulation, cell migration, apoptosis, and planar cell polarity. At the same time, recent studies have provided a deeper understanding of the regulatory mechanisms of Smurf1's expression, activity, and substrate selectivity. In our review, a brief summary of recent important biological functions and regulatory mechanisms of E3 ubiquitin ligase Smurf1 is proposed.

20.
Gastroenterol Rep (Oxf) ; 11: goad042, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37502197

RESUMO

Background: Robotic-assisted pancreatoduodenectomy (RPD) has been routinely performed in a few of centers worldwide. This study aimed to evaluate the perioperative outcomes and the learning curves of resection and reconstruction procedures in RPD by one single surgeon. Methods: Consecutive patients undergoing RPD by a single surgeon at the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between July 2016 and October 2022 were included. The perioperative outcomes and learning curves were retrospectively analysed by using cumulative sum (CUSUM) analyses. Results: One-hundred and sixty patients were included. According to the CUSUM curve, the times of resection and reconstruction procedures were shortened significantly after 30 cases (median, 284 vs 195 min; P < 0.001) and 45 cases (median, 138 vs 120 min; P < 0.001), respectively. The estimated intraoperative blood loss (median, 100 vs 50 mL; P < 0.001) and the incidence of clinically relevant post-operative pancreatic fistula (29.2% vs 12.5%; P = 0.035) decreased significantly after 20 and 120 cases, respectively. There were no significant differences in the total number of lymph nodes examined, post-operative major complications, or post-operative length-of-stay between the two groups. Conclusions: Optimization of the resection procedure and the acquisition of visual feedback facilitated the performance of RPD. RPD was a safe and feasible procedure in the selected patients.

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