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1.
Quant Imaging Med Surg ; 12(5): 2709-2720, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35502374

RESUMO

Background: Angiographic computed tomography (CT) is useful in various medical contexts, but little research has been presented regarding the application of cone beam CT (CBCT) in airway stenting. This study set out to evaluate the clinical feasibility of using CBCT in airway stent placement in a single-center retrospective cohort. Methods: A total of 228 patients with stenosis or fistula diseases were treated with metallic airway stents in the First Affiliated Hospital of Zhengzhou University from January 1, 2015, to December 31, 2018. Of them, 128 patients underwent fluoroscopy-guided airway stenting. CBCT scanning was performed on the other 100 patients during and after treatment, and their images were compared with those from postoperative multidetector CT (MDCT). The outcomes and complications in the CBCT-guided and fluoroscopy-guided groups were also assessed via Pearson's χ2 test or Fisher's exact test. Results: Tracheal stenting was performed successfully on the first attempt for 90 patients in the CBCT-guided group and 123 patients in the fluoroscopy-guided group. The mean measured diameters of the central airway in the CBCT images and MDCT images were 18.2±2.81 and 19.0±2.33 mm, respectively, and the mean lengths were 58.7±16.82 and 58.5±17.06 mm, respectively. In the CBCT-guided group and the fluoroscopy-guided group, the mean scores for visibility of the distal bronchus were 3.7±0.49 and 3.9±0.34, respectively; the mean scores for the pulmonary parenchyma were 3.3±0.71 and 3.9±0.31, respectively; and the mean scores for the airway above the upper stent graft were 1.8±0.41 and 4.0±0.20, respectively. Two of the three anatomical areas were reproduced in a diagnostically relevant way. The major complications rate was 7% and 19% in the CBCT-guided and fluoroscopy-guided groups, respectively. Conclusions: CBCT produces images with sufficient quality to replace MDCT as a reasonable control measure after stent implantation, and its use during surgery reduces complications relating to airway stent placement.

2.
J Hematol Oncol ; 15(1): 58, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35551634

RESUMO

Cancer is a top-ranked life-threatening disease with intratumor heterogeneity. Tumor heterogeneity is associated with metastasis, relapse, and therapy resistance. These factors contribute to treatment failure and an unfavorable prognosis. Personalized tumor models faithfully capturing the tumor heterogeneity of individual patients are urgently needed for precision medicine. Advances in stem cell culture have given rise to powerful organoid technology for the generation of in vitro three-dimensional tissues that have been shown to more accurately recapitulate the structures, specific functions, molecular characteristics, genomic alterations, expression profiles, and tumor microenvironment of primary tumors. Tumoroids in vitro serve as an important component of the pipeline for the discovery of potential therapeutic targets and the identification of novel compounds. In this review, we will summarize recent advances in tumoroid cultures as an excellent tool for accurate cancer modeling. Additionally, vascularization and immune microenvironment modeling based on organoid technology will also be described. Furthermore, we will summarize the great potential of tumor organoids in predicting the therapeutic response, investigating resistance-related mechanisms, optimizing treatment strategies, and exploring potential therapies. In addition, the bottlenecks and challenges of current tumoroids will also be discussed in this review.

3.
Front Immunol ; 13: 827921, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35386715

RESUMO

The immune checkpoint pathway consisting of the cell membrane-bound molecule programmed death protein 1 (PD-1) and its ligand PD-L1 has been found to mediate negative regulatory signals that effectively inhibit T-cell proliferation and function and impair antitumor immune responses. Considerable evidence suggests that the PD-1/PD-L1 pathway is responsible for tumor immune tolerance and immune escape. Blockage of this pathway has been found to reverse T lymphocyte depletion and restore antitumor immunity. Antagonists targeting this pathway have shown significant clinical activity in specific cancer types. Although originally identified as membrane-type molecules, several other forms of PD-1/PD-L1 have been detected in the blood of cancer patients, including soluble PD-1/PD-L1 (sPD-1/sPD-L1) and exosomal PD-L1 (exoPD-L1), increasing the composition and functional complications of the PD-1/PD-L1 signaling pathway. For example, sPD-1 has been shown to block the PD-1/PD-L immunosuppressive pathway by binding to PD-L1 and PD-L2, whereas the role of sPD-L1 and its mechanism of action in cancer remain unclear. In addition, many studies have investigated the roles of exoPD-L1 in immunosuppression, as a biomarker for tumor progression and as a predictive biomarker for response to immunotherapy. This review describes the molecular mechanisms underlying the generation of sPD-1/sPD-L1 and exoPD-L1, along with their biological activities and methods of detection. In addition, this review discusses the clinical importance of sPD-1/sPD-L1 and exoPD-L1 in cancer, including their predictive and prognostic roles and the effects of treatments that target these molecules.


Assuntos
Neoplasias , Receptor de Morte Celular Programada 1 , Antígeno B7-H1/metabolismo , Humanos , Imunoterapia/métodos , Neoplasias/terapia , Prognóstico
4.
Quant Imaging Med Surg ; 12(1): 207-214, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34993072

RESUMO

BACKGROUND: The present study aimed to compare the clinical results and pathological diagnostic quality of percutaneous transhepatic cholangiobiopsy for biliary obstruction using biopsy forceps (BFs) of varying diameter. METHODS: A total of 57 patients with obstructive jaundice who underwent percutaneous transhepatic cholangiobiopsy and drainage with 1 of 2 BFs diameters (6.0-mm BFs, n=30; 4.5-mm BFs, n=27) between February 2018 and May 2019 were retrospectively assessed. BFs were compared in terms of their sample quality, diagnostic accuracy, sensitivity, specificity, number of passes, and complication rate. RESULTS: All 57 patients underwent the procedure successfully and the technical success rate was 100%. The 6.0- and 4.5-mm BFs demonstrated a diagnostic accuracy of 80% (24/30) and 85% (23/27), respectively (P=0.733), and a sensitivity of 78% (22/28) and 86% (22/26), respectively (P=0.729). The specificity of both the 6.0- and 4.5-mm BFs was 100%. The complication rate was 10% (3/30) with the 6.0-mm BFs and 19% (5/27) with the 4.5-mm BFs (P=0.456). The mean number of biopsies was 2.9±0.6 with the 6.0-mm BFs compared with 3.6±1.0 with the 4.5-mm BFs (P<0.001). The 6.0-mm BFs provided a larger biopsy size and a less crushed specimen compared with the 4.5-mm BFs. The overall tissue scores were 5.2±0.8 with 6.0-mm BFs and 4.5±1.0 with 4.5-mm BFs (P=0.012). CONCLUSIONS: There was no statistically significant difference in the clinical results between the 2 BFs in the context of percutaneous transhepatic cholangiobiopsy. Superior samples were obtained using the 6.0-mm BFs, with a fewer number of passes. The complication rate did not increase compared with the 4.5-mm BFs.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34978618

RESUMO

AIM: To evaluate dynamic tissue changes after airway stenting (AS) with a newly designed metal brachytherapy stent (BS) loaded with radioactive 125I seeds in normal rabbits. METHODS: Forty-five normal New Zealand white rabbits were divided into 3 groups (group A: stent without seeds; group B: stent with 0.4 mCi active seeds; group C: stent with 0.8 mCi active seeds) and underwent AS under C-arm guidance. Then, five rabbits were killed from each group at 2, 4, and 8 weeks for further examination. Laboratory tests (including routine blood tests, liver function, kidney function, and electrolytes), gross observations, and tissue changes of Masson/hematoxylin-eosin staining, plus immunohistochemistry of α-SMA, NOX4, and TGF-ß were performed at each time point. RESULTS: All animals underwent AS successfully without procedure-related death, but one animal died at 6 weeks due to severe pulmonary infection in group C. Apart from a transient increase in white blood cells (P < 0.05) and a gradual increase in ROS levels (P < 0.05), other blood test items showed no significant changes (P > 0.05). The brachytherapy injury score increased with irradiation dose accumulation (P < 0.05), but tissue hyperplasia at the stent end in group C was less severe than that in groups A and B (P < 0.05). Airway lateral fibrosis was observed in all groups by histopathologic analysis; however, fibrosis in group C was more severe than that in groups A and B (P < 0.05). CONCLUSION: The brachytherapy injury score increased with irradiation dose accumulation, while granulation tissue hyperplasia at the stent end was inhibited by 125I brachytherapy within 8 weeks.

6.
Acad Radiol ; 29(1): 42-50, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33158706

RESUMO

PURPOSE: To evaluate the clinical benefit of simultaneous percutaneous microwave ablation (PMA) and percutaneous cementoplasty (PC) for patients with painful osteolytic bone metastases under flat-detector C-arm computed tomography (CACT). METHODS AND MATERIALS: Thirty patients (17 men and 13 women) with 42 osteolytic metastatic tumors were prospectively treated with PMA and PC simultaneously under CACT guidance. Technical success, major complications, local tumor control status, and daily morphine consumption were recorded. Visual analog scale, Oswestry disability index, and the short-form 36 questionnaire (SF-36, 8 domains) were used to evaluate pain, functional status, and quality of life (QoL), respectively. RESULTS: The technical success rate was 100% without major complications, and local tumor control rates were 100% and 75% for lesion diameter ≤3 cm and >3 cm, respectively. Daily morphine consumption, visual analog scale, and Oswestry disability index improved significantly from the respective pretreatment values of 75 mg, 7.4, and 59.2 to 17.3 mg, 1.7, and 22.9 at 1 week; 8.5 mg, 1.4, and 6.7 at 4 weeks; and 5.3 mg, 1.3, and 9.2 at 12 weeks, respectively (p< 0.01). The QoL assessments at 4 weeks showed significant improvements in physical function, role physical, bodily pain, general health and vitality (p < 0.05). CONCLUSION: Simultaneous PMA and PC under CACT guidance is effective to control pain and improve QoL in selective patients with painful osteolytic bone metastases.


Assuntos
Neoplasias Ósseas , Ablação por Cateter , Cementoplastia , Neoplasias Ósseas/complicações , Neoplasias Ósseas/diagnóstico por imagem , Terapia Combinada , Feminino , Humanos , Masculino , Micro-Ondas/uso terapêutico , Dor/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
7.
Cancer Lett ; 524: 29-41, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34656689

RESUMO

125I seeds can effectively inhibit the growth of a variety of cancer cells. It has been used in the treatment of a variety of cancers, and has achieved certain curative effect. However, to the best of our knowledge, no report has described the effects of 125I seeds on the biological functions of cholangiocarcinoma (CCA) and the mechanisms underlying the effects of the seeds on this cancer. In this study, we demonstrated that 125I seeds could inhibit the proliferation, migration and invasion of CCA cells, as well as promoting apoptosis and blocking the cell cycle in these cells. Moreover, 125I seeds inhibited the growth of CCA xenografts and promoted the apoptosis of CCA cells in vivo. Furthermore, transcriptome sequencing showed that 125I seeds could inhibit the growth of CCA by inhibiting the expression of AGR2 and regulating p38 MAPK pathway. Finally, this finding indicated that 125I seeds can inhibit proliferation and promote apoptosis in CCA cells by inhibiting the expression of AGR2 and DUSP1 and increasing the expression of p-p38 MAPK and p-p53. This study provides a new research direction for studies investigating the mechanisms underlying the effects of 125I seeds on CCA.


Assuntos
Colangiocarcinoma/radioterapia , Radioisótopos do Iodo/farmacologia , Mucoproteínas/genética , Proteínas Oncogênicas/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Animais , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Movimento Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Fosfatase 1 de Especificidade Dupla/genética , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Xenoenxertos , Humanos , Camundongos , Transdução de Sinais/efeitos da radiação , Proteína Supressora de Tumor p53/genética
8.
Bioact Mater ; 9: 266-280, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34820570

RESUMO

Anti-inflammatory and antihyperplasia activities are essential requirements for the successful use of airway stents. In this work, silver nanoparticles (AgNPs) and cisplatin (DDP) were combined in a synergistic modification strategy to improve the surface function of airway stents. Using polycaprolactone (PCL) as a drug carrier, a dual-functional PCL-AgNPs-DDP fiber film-coated airway stent was fabricated by electrospinning. The physicochemical and biological properties of the obtained fiber films were examined. The ATR-FTIR, XPS, SEM-EDS and TEM results suggested that AgNPs and DDP could be successfully immobilized onto the airway stent surface. The drug release and surface degradation results revealed that AgNPs and DDP can undergo sustained release from films for 30 d, and the weight loss was approximately 50% after 35 d. In addition, the dual-functional fiber film suppressed human embryonic lung fibroblast growth and exhibited excellent antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. Furthermore, the effectiveness of the dual-functional fiber film-coated airway stent was evaluated by application to the trachea of New Zealand rabbits. The in vivo results indicated that PCL-AgNPs-DDP fiber film-coated airway stent can significantly inhibit granulation tissue formation and collagen deposition, reduced the expression of IL-8, TNF-α, IL-1α, PCNA, α-SMA and CD68, and ultimately achieved anti-inflammatory and antihyperplasia effects. Hence, this study provides a dual-functional surface-coated airway stent to address the clinical complications associated with respiratory tract inflammation and granulation tissue hyperplasia, thus inhibiting tracheal stenosis.

9.
Front Cell Infect Microbiol ; 11: 730091, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746022

RESUMO

We investigated the effects of gut microbiota and serum metabolite levels in patients with Budd-Chiari syndrome (B-CS) and their importance for guiding clinical management strategies. In total, 214 B-CS patients (93 untreated and 121 treated) and 41 healthy controls were enrolled. Gut microbiota and serum metabolome were analysed using shotgun metagenomics and liquid chromatography-mass spectrometry. The gut microbiota of the patients showed abundance of Campylobacter and low levels of Saccharomyces, Deinococcus, and Thiomonas (P < 0.05). Thirty metabolites, including taurocholate and (R)-3-hydroxybutyric acid, were identified in the patients (VIP > 1, P < 0.05 and FC > 1.2 or FC < 0.83). Random forest (RF) models showed that serum metabolome could effectively identify B-CS from healthy controls and RF-metabolomics exhibited perfect discrimination (AUC = 100%, 95% CI: 100% - 100%), which was significantly higher than that achieved by RF-metagenomics (AUC = 58.48%, 95% CI: 38.46% - 78.5%). Campylobacter concisus and taurocholate showed significant positive correlation in patients with clinical manifestations (P < 0.05). Actinobacteria levels were significantly higher in untreated patients than in treated patients (P < 0.05). Campylobacter and Veillonella levels were significantly higher in treated patients than in healthy controls (P < 0.05). We identified major alterations in the gut microbiota and serum metabolome of patients with B-CS. Faecal metagenomics- and serum metabolomics-guided management strategies are required for patients with B-CS.


Assuntos
Síndrome de Budd-Chiari , Campylobacter , Humanos , Metabolômica , Metagenômica
10.
Surg Endosc ; 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34845555

RESUMO

AIM: To evaluate the efficacy and safety of brachytherapy with double-strand 125I seeds and biliary drainage for malignant obstructive jaundice. METHODS AND MATERIALS: 42 patients with obstructive jaundice because of extrahepatic cholangiocarcinoma were enrolled. 22 patients (group A) received a biliary stent with common drainage tube implantation, and 20 patients (group B) received a biliary stent with double-strand 125I seeds radiotherapy drainage tube placement. The length, location and pathological stage of biliary stricture were recorded in the two groups. Total bilirubin (TBIL), direct bilirubin (DBIL), IgA, IgG, IgM, alanine aminotransferase and white blood cell (WBC) count were measured before and after percutaneous transhepatic cholangial drainage (PTCD). Tumor diameter was measured before and three months after PTCD, and the difference were calculated. Stent patency time, survival time, and complications were recorded. RESULTS: There was no significant difference in the length, location and pathological stage of biliary stenosis between the two groups. There was no significant difference in TBIL, DBIL, IgA, IgG, IgM, alanine aminotransferase and WBC count between the two groups before or after PTCD (P > 0.05). Three months after PTCD, tumors growth in group A and tumors shrinkage in group B. The difference in tumor size between the two groups before and after PTCD was statistically significant (P < 0.05). The average stent patency times in groups A and B were 3.55 ± 0.76 months and 8.76 ± 1.85 months, respectively (P < 0.05). The average survival times in groups A and B were 133.5 ± 27.8 days and 252.5 ± 114.5 days, respectively (P < 0.05). There was no statistically significant difference in the incidence of complications between the two groups (P > 0.05). CONCLUSION: Double-strand 125I seeds radiotherapy biliary drainage tubes can safely and effectively control tumors, prolong the patency of biliary stents, and prolong patient survival.

11.
Front Bioeng Biotechnol ; 9: 764531, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692667

RESUMO

Radioisotopes have long been leveraged for internal radiotherapy-mediated cancer treatment. However, such therapeutic approaches are associated with serious side effects, and their efficacy is limited by intratumoral hypoxia. Herein, we prepared a folic acid-decorated palladium decahedral platform capable of enhancing the radiotherapeutic efficacy of iodine-125 (125I) seed treatment. This decahedral nanoenzyme was able to target tumor regions and catalyze the conversion of intracellular H2O2 to O2, thereby alleviating hypoxia within the tumor microenvironment. In addition, palladium was hypoxia can be alleviated, on the other hand, palladium was able to enhance the radiotherapeutic energy deposition within tumor tissues. The results of this analysis indicated that synthesized decahedral constructs can efficiently target and modify the hypoxic tumor microenvironment while simultaneously enhancing radiation energy deposition therein. Relative to palladium nanodots, the prolonged in vivo circulation of these decahedral constructs better enabled them to facilitate sustained radiosensitization. Overall, the results of this study highlight a novel approach to improving the therapeutic utility of 125I seed interstitial implantation, thus underscoring an important direction for future clinical research.

12.
Front Immunol ; 12: 702594, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394098

RESUMO

Background: A considerable number of patients with stage II/III colorectal cancer (CRC) will relapse within 5 years after surgery, which is a leading cause of death in early-stage CRC. The current TNM stage system is limited due to the heterogeneous clinical outcomes displayed in patients of same stage. Therefore, searching for a novel tool to identify patients at high recurrence-risk for improving post-operative individual management is an urgent need. Methods: Using four independent public cohorts and qRT-PCR data from 66 tissues, we developed and validated a recurrence-associated immune signature (RAIS) based on global immune genes. The clinical and molecular features, tumor immune microenvironment landscape, and immune checkpoints profiles of RAIS were also investigated. Results: In five independent cohorts, this novel scoring system was proven to be an independent recurrent factor and displayed excellent discrimination and calibration in predicting the recurrence-risk at 1~5 years. Further analysis revealed that the high-risk group displayed high mutation rate of TP53, while the low-risk group had more abundance of activated CD4+/CD8+ T cells and high expression of PD-1/PD-L1. Conclusions: The RAIS model is highly predictive of recurrence in patients with stage II/III CRC, which might serve as a powerful tool to further optimize decision-making in adjuvant chemotherapy and immunotherapy, as well as tailor surveillance protocol for individual patients.


Assuntos
Biomarcadores Tumorais/imunologia , Neoplasias Colorretais/patologia , Recidiva Local de Neoplasia/imunologia , Adulto , Idoso , Neoplasias Colorretais/imunologia , Feminino , Humanos , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Microambiente Tumoral/imunologia
13.
J Immunol Res ; 2021: 5518908, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34426790

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) remains an important cause of cancer death. The molecular mechanism of hepatocarcinogenesis and prognostic factors of HCC have not been completely uncovered. METHODS: In this study, we screened out differentially expressed lncRNAs (DE lncRNAs), miRNAs (DE miRNAs), and mRNAs (DE mRNAs) by comparing the gene expression of HCC and normal tissue in The Cancer Genome Atlas (TCGA) database. DE mRNAs were used to perform Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Then, the miRNA and lncRNA/mRNA modules that were most closely related to the survival time of patients with HCC were screened to construct a competitive endogenous RNA (ceRNA) network by weighted gene coexpression network analysis (WGCNA). Moreover, univariable Cox regression and Kaplan-Meier curve analyses of DE lncRNAs and DE mRNAs were conducted. Finally, the lasso-penalized Cox regression analysis and nomogram model were used to establish a new risk scoring system and predict the prognosis of patients with liver cancer. The expression of survival-related DE lncRNAs was verified by qRT-PCR. RESULTS: A total of 1896 DEmRNAs, 330 DElncRNAs, and 76 DEmiRNAs were identified in HCC and normal tissue samples. Then, the turquoise miRNA and turquoise lncRNA/mRNA modules that were most closely related to the survival time of patients with HCC were screened to construct a ceRNA network by WGCNA. In this ceRNA network, there were 566 lncRNA-miRNA-mRNA regulatory pairs, including 30 upregulated lncRNAs, 16 downregulated miRNAs, and 75 upregulated mRNAs. Moreover, we screened out 19 lncRNAs and 14 hub mRNAs related to prognosis from this ceRNA network by univariable Cox regression and Kaplan-Meier curve analyses. Finally, a new risk scoring system was established by selecting the optimal risk lncRNAs from the 19 prognosis-related lncRNAs through lasso-penalized Cox regression analysis. In addition, we established a nomogram model consisting of independent prognostic factors to predict the survival rate of HCC patients. Finally, the correlation between the risk score and immune cell infiltration and gene set enrichment analysis were determined. CONCLUSIONS: In conclusion, the results may provide potential biomarkers or therapeutic targets for HCC and the establishment of the new risk scoring system and nomogram model provides the new perspective for predicting the prognosis of HCC.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , RNA Longo não Codificante/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/metabolismo , Biologia Computacional/métodos , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Prognóstico , Modelos de Riscos Proporcionais , Mapeamento de Interação de Proteínas , RNA Mensageiro/genética , Curva ROC , Microambiente Tumoral
14.
Can J Gastroenterol Hepatol ; 2021: 5565793, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34458205

RESUMO

Purpose: The goal of this study was to assess the clinical efficacy and safety of the arsenic trioxide (ATO)/lipiodol emulsion in the transcatheter arterial chemoembolization (TACE) combined with apatinib in the treatment of advanced hepatocellular carcinoma (HCC). Methods: From December 2015 to February 2017, a total of 87 patients were consecutively enrolled and underwent ATO-TACE (aTACE) combined with apatinib in the treatment of advanced HCC. The treatment response and adverse events were assessed at the first month and third month after aTACE therapy. Progression-free survival (PFS), overall survival (OS), and treatment-related adverse events were also analyzed. Results: 87 patients (57 men; 30 women) were enrolled in the present study. Compared to that at the pre-aTACE examination, the levels of AST and ALT were elevated at the first week after procedure (65.84 U/L ± 22.93 U/L vs. 54.15 U/L ± 19.60 U/L, p=0.032; 63.44 U/L ± 22.50 U/L vs. 51.60 U/L ± 13.89 U/L, p=0.027, respectively). Most of the adverse events were grade 1 or 2 according to National Cancer Institute Common Terminology Criteria for Adverse Event (CTCAE). Of the exception, 4 persons (2%) did have grade 3 hand-foot skin reactions, 1 (1%) had grade 3 diarrhea, 1 (1%) had grade 3 hypertension, and 3 (3%) had grade 3 proteinuria and forced to reduce the dose of apatinib by half. The survival analysis of the combination with aTACE and apatinib therapy found that the median PFS was 10.2 months (95% CI: 8.543-11.857), and the median OS was 23.300 months (95% CI: 20.833-25.767). Additionally, both univariate and multivariate Cox regression revealed that the tumor burden (≤50%) and the patients without portal vein tumor thrombus (PVTT) significantly impacted the patient's PFS and OS and were related to better survival. Conclusion: aTACE combined with apatinib is a safe and promising treatment approach for patients with advanced HCC. Additionally, tumor burden (≤50%) and the patients without PVTT are associated with better PFS and OS.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Trióxido de Arsênio , Carcinoma Hepatocelular/tratamento farmacológico , Quimioembolização Terapêutica/efeitos adversos , Emulsões , Óleo Etiodado , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Piridinas , Resultado do Tratamento
15.
J Cell Mol Med ; 25(15): 7559-7574, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34288370

RESUMO

CUGBP Elav-like family member 2(CELF2) plays crucial roles in the development and activation of T cell. However, the impacts of CELF2 on tumour-infiltrating immune cells (TIICs) and clinical outcomes of tumours remain unclear. In this study, we found that elevated CELF2 expression was markedly correlated with prolonged survival in multiple tumours, particularly in breast and lung cancers. Notably, CELF2 only impacted the prognosis of triple-negative breast cancer (TNBC) with lymph node metastasis. Further investigation showed CELF2 expression was positively correlated with the infiltration abundance of dendritic cells (DCs), CD8+ T cells and neutrophils in breast invasive carcinoma (BRCA) and DCs in lung squamous cell carcinoma (LUSC). CELF2 also had strong correlations with markers of diverse TIICs such as T cells, tumour-associated macrophages and DCs in BRCA and LUSC. Importantly, CELF2 was significantly associated with plenty of immune checkpoint molecules (ICMs) and outperformed five prevalent biomarkers including PD-1, PD-L1, CTLA-4, CD8 and tumour mutation burden in predicting immunotherapeutic responses. Immunohistochemistry also revealed lower protein levels of CELF2 in TNBC and LUSC compared to normal tissues, and patients with high expression showed significantly prolonged prognosis. In conclusion, we demonstrated that increased CELF2 expression was closely related to better prognosis and superior TIIC infiltration and ICM expression, particularly in BRCA and LUSC. CELF2 also performed well in evaluating the immunotherapeutic efficacy, suggesting CELF2 might be a promising biomarker.


Assuntos
Biomarcadores Tumorais/genética , Proteínas CELF/genética , Carcinoma de Células Escamosas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas do Tecido Nervoso/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Biomarcadores Tumorais/metabolismo , Proteínas CELF/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Biologia Computacional , Feminino , Humanos , Imunoterapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Proteínas do Tecido Nervoso/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia
16.
Cancer Cell Int ; 21(1): 359, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233675

RESUMO

BACKGROUND: A large number of patients with stage II/III colorectal cancer (CRC) have a high recurrence rate after radical resection. We aimed to develop a novel tool to stratify patients with different recurrence-risk for optimizing decision-making in post-operative surveillance and therapeutic regimens. METHODS: We retrospectively enrolled four independent cohorts from the Gene Expression Omnibus and 66 CRC tissues from our hospital. The initial signature discovery was conducted in GSE143985 (n = 91). This was followed by independent validation of this signature in GSE17536 (n = 111), GSE29621 (n = 40), and GSE92921 (n = 59). Further experimental validation using qRT-PCR assays (n = 66) was performed to ensure the robustness and clinical feasible of this signature. RESULTS: We developed a novel recurrence-related signature consisting of six genes. This signature was validated to be significantly associated with dismal recurrence-free survival in five cohorts GSE143985 (HR: 4.296 [2.612-7.065], P < 0.0001), GSE17536 (HR: 2.354 [1.662-3.334], P < 0.0001), GSE29621 (HR: 3.934 [1.622-9.539], P = 0.0024), GSE92921 (HR: 7.080 [2.011-24.924], P = 0.0023), and qPCR assays (HR: 3.654 [2.217-6.020], P < 0.0001). This signature was also proven to be an independent recurrent factor. More importantly, this signature displayed excellent discrimination and calibration in predicting the recurrence-risk at 1-5 years, with most AUCs were above 0.9, average C-index for the five cohorts was 0.8795, and near-perfect calibration. CONCLUSIONS: We discovered and experimental validated a novel gene signature with stable and powerful performance for identifying patients at high recurrence-risk in stage II/III CRC.

17.
Onco Targets Ther ; 14: 4077-4086, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262293

RESUMO

PURPOSE: The purpose of this study was to compare the safety and effectiveness of a self-expandable metallic stent (SEMs) with a novel brachytherapy biliary drainage catheter (BBDC, double 125I seeds strands) or a single 125I seeds strand in the treatment of advanced perihilar cholangiocarcinoma (pCCA) with malignant obstructive jaundice (MOJ). METHODS: From September 2016 to December 2018, we retrospectively enrolled patients with biliary stent implantation after receiving either BBDC loaded with 125I seeds (double-strands irradiation group) or an 125I seed strand treatment (single-strand irradiation group, control group). The outcomes were analyzed regarding the relief of obstructive jaundice, and interventional-related complications. Moreover, the Kaplan-Meier method was used to analyze stent patency and survival. RESULTS: The success rate of interventional therapy in both groups was 100%, and all patients with MOJ were alleviated. According to the Common Terminology Criteria for Adverse Events (CTCAE 4.02), the grade 3 or 4 complications in the BBDC group and in the control group were 6/34 (17.65%) and 7/39 (17.95%), respectively (P > 0.05). The median and mean overall stent patency of the BBDC group and the control group were 207 days versus 180 days, 204.212 days versus 186.278 days (P = 0.043). The median and mean overall survivals in the BBDC group were higher than those in the control group (245 days versus 212 days, 244.883 days versus 221.844 days, P = 0.030). CONCLUSION: This interim analysis showed that BBDC (double-stranded irradiation) can prolong the stent patency time compared with 125I seed strand treatment (single-stranded irradiation) and had the advantage of reducing jaundice, which seemed to extend the survival period of advanced pCCA.

18.
Colloids Surf B Biointerfaces ; 206: 111949, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34216848

RESUMO

Antibacterial and antihyperplasia airway stents are highly desirable for tracheal stenosis. Herein, a series of polylactic acid (PLA) and silver nanoparticles (AgNPs) nanofiber membranes (PLA, PLA-4 %AgNPs and PLA-6 % AgNPs) were prepared by electrospinning. The physicochemical and biological properties of the resultant nanofiber membranes were examined. The SEM and drug release results indicated that the AgNPs were successfully introduced into PLA, and could be sustained to be released from membranes. The membranes showed antibacterial activity against S. aureus and P. aeruginosa, and cytocompatibility towards CCC-HPF-1 and NHBE cells. Furthermore, the membranes were used to cover a self-expandable metallic stent for use in the treatment of rabbit tracheal stenosis. The in vivo results revealed that the membranes, especially the AgNPs-coated airway stent could suppress tracheal stenosis by reducing inflammation and collagen deposition. Additionally, the study further confirmed that the inhibition of bacterial content in the trachea could be positively correlated with the reduction in tracheal granulation tissue hyperplasia. Conclusively, the PLA/AgNPs nanofiber membrane-coated airway stent has practical value for patients with clinical tracheal stenosis.


Assuntos
Nanopartículas Metálicas , Nanofibras , Estenose Traqueal , Animais , Antibacterianos/farmacologia , Humanos , Poliésteres , Coelhos , Prata , Staphylococcus aureus , Stents
20.
Front Genet ; 12: 669694, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079583

RESUMO

Background: Esophageal adenocarcinoma (EAC) remains a leading cause of cancer-related deaths worldwide and demonstrates a predominant rising incidence in Western countries. Recently, immunotherapy has dramatically changed the landscape of treatment for many advanced cancers, with the benefit in EAC thus far been limited to a small fraction of patients. Methods: Using somatic mutation data of The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium, we delineated the somatic mutation landscape of EAC patients from US and England. Based on the expression data of TCGA cohort, multiple bioinformatics algorithms were utilized to perform function annotation, immune cell infiltration analysis, and immunotherapy response assessment. Results: We found that RYR2 was a common frequently mutated gene in both cohorts, and patients with RYR2 mutation suggested higher tumor mutation burden (TMB), better prognosis, and superior expression of immune checkpoints. Moreover, RYR2 mutation upregulated the signaling pathways implicated in immune response and enhanced antitumor immunity in EAC. Multiple bioinformatics algorithms for assessing immunotherapy response demonstrated that patients with RYR2 mutation might benefit more from immunotherapy. In order to provide additional reference for antitumor therapy of different RYR2 status, we identified nine latent antitumor drugs associated with RYR2 status in EAC. Conclusion: This study reveals a novel gene whose mutation could be served as a potential biomarker for prognosis, TMB, and immunotherapy of EAC patients.

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