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  • 1
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    Serum TNFRII: A promising biomarker for predicting the risk of subcentimetre lung adenocarcinoma
    Wiley ; 2020
    In:  Journal of Cellular and Molecular Medicine Vol. 24, No. 7 ( 2020-04), p. 4150-4156
    Details
    In: Journal of Cellular and Molecular Medicine, Wiley, Vol. 24, No. 7 ( 2020-04), p. 4150-4156
    Kurzfassung: Early diagnosis of lung adenocarcinoma requires effective risk predictors. TNFRII was reported to be related to tumorigenesis, but remained unclear in lung cancer. This research set out to investigate the relationship between the sTNFRII (serum TNFRII) level and the risk of lung adenocarcinoma less than 1 cm in diameter. Seventy‐one pairs of subcentimetre lung adenocarcinoma patients and healthy controls were analysed through multiplex bead‐based Luminex assay and found a significantly lower expression of sTNFRII in patients with subcentimetre lung adenocarcinoma than that in the healthy controls ( P   〈  .001), which was further verified through ONCOMINE database analysis. Increased levels of sTNFRII reduced the risk of subcentimetre lung adenocarcinoma by 89% ( P   〈  .001). Patients with a higher level of BLC had a 2.70‐fold ( P   〈  .01) higher risk of subcentimetre adenocarcinoma. Furthermore, a higher BLC/TNFRII ratio was related to a 35‐fold higher risk of subcentimetre adenocarcinoma. TNFRII showed good specificity, sensitivity and accuracy (0.72, 0.75 and 0.73, respectively), with an AUC of 0.73 ( P   〈  .001). In conclusion, the present study assessed the value of sTNFRII as a potential biomarker to predict the risk of subcentimetre lung adenocarcinoma and provided evidence for the further use of TNFRII as an auxiliary marker in the diagnosis of subcentimetre lung adenocarcinoma.
    Materialart: Online-Ressource
    ISSN: 1582-1838 , 1582-4934
    URL: Issue
    URL: Article
    DOI: 10.1111/jcmm.v24.7
    DOI: 10.1111/jcmm.15071
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2020
    ZDB Id: 2076114-4
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
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    Table_3.xlsx
    Frontiers Media SA ; 2023
    In:  Frontiers in Cellular and Infection Microbiology Vol. 13 ( 2023-9-12)
    Details
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 13 ( 2023-9-12)
    Kurzfassung: Clonorchiasis is an important foodborne parasitic disease. However, eggs of Clonorchis sinensis (C. sinensis) cannot be detected in feces during biliary obstruction. Moreover, many diseases can cause biliary obstruction, such as gallstones, adenocarcinoma, cholangiocarcinoma and Ascaris lumbricoides infection. Therefore, it is of great significance to distinguish between patients of biliary obstruction and biliary obstruction with C. sinensis infection. Methods A total of 48 biliary obstruction patients were enrolled, including 23 infected with C. sinensis (C. sinensis) (OB+C.s) and 25 non-infected subjects (OB). The bile samples were collected by endoscopic retrograde cholangiopancreatography and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS). Additionally, multivariate statistical analysis methods were employed to identify differential metabolites. Next, bile amino acid levels were determined by targeted metabolomics analysis. Result A total of 146 and 132 significant metabolites were identified in electrospray ionization (ESI)+ and ESI− modes, respectively. The levels of amino acids (asparagine, glutamate, ornithine) and polyamines (spermidine and spermine) were significantly changed. Targeted analysis showed that the levels of amino acids (such as L-arginine, L-glutamine, L-lysine, L-propionic, and L-tyrosine) were lower in OB+C.s patients compared to those in OB patients. Marked metabolic pathways were involved in “Glutathione metabolism”, “Caffeine metabolism”, “Alanine, aspartate and glutamate metabolism”, “Arginine and proline metabolism”, “Purine metabolism”, “Beta-Alanine metabolism”, and “D-glutamine and D-glutamate metabolism”. Conclusion These results show that there were significant differences between OB+C.s and OB patients, especially in amino acids. The metabolic signature and perturbations in metabolic pathways may help to better distinguish OB+C.s and OB patients.
    Materialart: Online-Ressource
    ISSN: 2235-2988
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fcimb.2023.1254016
    DOI: 10.3389/fcimb.2023.1254016.s001
    DOI: 10.3389/fcimb.2023.1254016.s002
    DOI: 10.3389/fcimb.2023.1254016.s003
    DOI: 10.3389/fcimb.2023.1254016.s004
    DOI: 10.3389/fcimb.2023.1254016.s005
    DOI: 10.3389/fcimb.2023.1254016.s006
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2023
    ZDB Id: 2619676-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
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    Identification of Active Bronchioalveolar Stem Cells as the Cell of Origin in Lung Adenocarcinoma
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 6 ( 2022-03-15), p. 1025-1037
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 6 ( 2022-03-15), p. 1025-1037
    Kurzfassung: While initiation is established as a critical step in tumorigenesis, the identity of the cell of origin for lung adenocarcinoma and the mechanism controlling susceptibility to initiation remain elusive. Here we show that lung tumor suppressor Gprc5a-knockout (KO) mice are susceptible to initiation of lung tumorigenesis. Bronchioalveolar stem cells (BASC) and alveolar type 2 (AT2) cells were aberrantly expanded in Gprc5a-KO mouse lungs compared with those in wild-type (WT) mice, suggesting that Gprc5a-KO might confer susceptibility to initiation by increasing the cell of origin in mouse lungs. BASCs from Gprc5a-KO mice (KO-BASC) exhibited significantly increased stemness and self-renewal potential and reduced differentiation capacity compared with BASCs from WT mice (WT-BASC). AT2 cells did not possess self-renewal potential regardless of Gprc5a status. KO-BASCs expressed a stem-like gene profile with upregulated Abcg2, EGFR, and NF-κB signaling compared with WT-BASCs. Blockade of EGFR and NF-κB signaling inhibited both expansion of BASC and AT2 cells and lung tumorigenesis. Abcg2 was expressed in active KO-BASCs as well as in lung tumor cells but not in quiescent WT-BASCs or AT2 cells, supporting that lung adenocarcinoma cells are derived from Abcg2-positive KO-BASCs (active). Taken together, Gprc5a deletion leads to expansion of active BASCs via dysregulated EGFR and NF-κB signaling that confers susceptibility to initiation of lung tumorigenesis, marking Abcg2-positive BASCs as candidate cell of origin for lung adenocarcinoma. Significance: Identification of active bronchioalveolar stem cells as lung adenocarcinoma cells of origin provides insights into mechanisms of lung tumorigenesis and could facilitate development of effective strategies for cancer prevention and therapy. See related commentary by Osborne and Minna, p. 972
    Materialart: Online-Ressource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-21-2445
    RVK:
    XA 36000
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2022
    ZDB Id: 2036785-5
    ZDB Id: 1432-1
    ZDB Id: 410466-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
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    Irregular pulsation of aneurysmal wall is associated with symptomatic and ruptured intracranial aneurysms
    BMJ ; 2023
    In:  Journal of NeuroInterventional Surgery Vol. 15, No. 1 ( 2023-01), p. 91-96
    Details
    In: Journal of NeuroInterventional Surgery, BMJ, Vol. 15, No. 1 ( 2023-01), p. 91-96
    Kurzfassung: Irregular pulsation of aneurysmal wall detected by four-dimensional CT angiography (4D-CTA) has been described as a novel imaging feature of aneurysm vulnerability. Our study aimed to investigate whether irregular pulsation is associated with symptomatic and ruptured intracranial aneurysms (IAs). Methods This retrospective study included consecutive patients with IAs who underwent 4D-CTA from January 2018 to July 2021. IAs were categorized as asymptomatic, symptomatic or ruptured. The presence of irregular pulsation (defined as a temporary focal protuberance ≥1 mm on more than three successive frames) was identified on 4D-CTA movies. Univariate and multivariate analyses were used to identify the parameters associated with aneurysm symptomatic or ruptured status. Results Overall, 305 patients with 328 aneurysms (37 ruptured, 60 symptomatic, 231 asymptomatic) were included. Ruptured and symptomatic IAs were significantly larger in size compared with asymptomatic IAs (median (IQR) 6.5 (5.1–8.3) mm, 7.0 (5.5–9.7) mm vs 4.7 (3.8–6.3) mm, p=0.001 and p 〈 0.001, respectively) and had more irregular pulsations (70.3%, 78.3% vs 28.1%, p 〈 0.05). Irregular pulsation (OR 5.03, 95% CI 2.83 to 8.92; p 〈 0.001) was independently associated with aneurysm symptomatic/ruptured status in the whole population. With unruptured IAs, both irregular pulsation (OR 6.31, 95% CI 3.02 to 13.20; p 〈 0.001) and size (OR 1.17, 95% CI 1.03 to 1.32; p=0.015) were independently associated with the symptoms. The combination of irregular pulsation and size increased the accuracy over size alone in identifying symptomatic aneurysms (AUC 0.81 vs 0.77, p=0.007) in unruptured IAs. Conclusion In a large cohort of patients with IAs detected by 4D-CTA, the presence of irregular pulsation was independently associated with aneurysm symptomatic and ruptured status.
    Materialart: Online-Ressource
    ISSN: 1759-8478 , 1759-8486
    URL: Article
    DOI: 10.1136/neurintsurg-2021-018381
    Sprache: Englisch
    Verlag: BMJ
    Publikationsdatum: 2023
    ZDB Id: 2506028-4
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
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    Extracellular vesicle long RNA markers of early‐stage lung adenocarcinoma
    Wiley ; 2023
    In:  International Journal of Cancer Vol. 152, No. 7 ( 2023-04), p. 1490-1500
    Details
    In: International Journal of Cancer, Wiley, Vol. 152, No. 7 ( 2023-04), p. 1490-1500
    Kurzfassung: Lung cancer screening by low‐dose computed tomography (LDCT) can improve mortality rates among high‐risk individuals, especially adenocarcinoma cases with characteristically poor prognosis, although high false‐positive rates have limited its clinical application. The objective of our study was to identify biomarkers for early‐stage lung adenocarcinoma (ie, tumor diameter  〈 2 cm) through extracellular vesicle long RNA (evlRNA) sequencing. High throughput evlRNA sequencing and support vector machine (SVM) identification of candidate diagnostic marker transcripts were performed using serum samples obtained before lung surgery. A total of 145 upregulated and 363 downregulated differential genes ( P value 〈 .05, fold change 〉 1.5) were identified between lung adenocarcinoma (LUAD) patients and benign controls. An SVM model based on a 23‐gene signature could distinguish EV samples of LUAD patients from those of control subjects with 86.49% sensitivity, 95.00% specificity and 92.31% accuracy in the training set and 93.75% sensitivity, 85.71% specificity and 88.24% accuracy in the validation set. A 17‐gene signature was then identified that could distinguish AIS patient samples from those of MIA/IAD patients with 93.33% sensitivity, 98.00% specificity, and 96.25% accuracy in the trainingset and 83.33% sensitivity, 96.55% specificity, and 94.29% accuracy in the validation set. EvlRNAs in serum show considerable diagnostic value for screening LUAD patients with tumor sizes 〈 2 cm in conjunction with LDCT, potentially reducing false positive rates while improving mortality rates.
    Materialart: Online-Ressource
    ISSN: 0020-7136 , 1097-0215
    URL: Issue
    URL: Article
    DOI: 10.1002/ijc.v152.7
    DOI: 10.1002/ijc.34386
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2023
    ZDB Id: 218257-9
    ZDB Id: 1474822-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
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    Degradation of SARS-CoV-2 receptor ACE2 by the E3 ubiquitin ligase Skp2 in lung epithelial cells
    Springer Science and Business Media LLC ; 2021
    In:  Frontiers of Medicine Vol. 15, No. 2 ( 2021-04), p. 252-263
    Details
    In: Frontiers of Medicine, Springer Science and Business Media LLC, Vol. 15, No. 2 ( 2021-04), p. 252-263
    Materialart: Online-Ressource
    ISSN: 2095-0217 , 2095-0225
    URL: Article
    DOI: 10.1007/s11684-021-0837-6
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2021
    ZDB Id: 2617113-2
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
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    PTGES/PGE2 signaling links immunosuppression and lung metastasis in Gprc5a-knockout mouse model
    Springer Science and Business Media LLC ; 2020
    In:  Oncogene Vol. 39, No. 15 ( 2020-04-09), p. 3179-3194
    Details
    In: Oncogene, Springer Science and Business Media LLC, Vol. 39, No. 15 ( 2020-04-09), p. 3179-3194
    Kurzfassung: Chronic inflammation has been linked to promotion of tumorigenesis and metastasis in lung. However, due to lack of a relevant animal model for characterization, the underlying mechanism remains elusive. Lung tumor suppressor gene Gprc5a -knockout (ko) mice are susceptible to lung inflammation, tumorigenesis and metastasis, which resembles the pathological features in human patients. Here, we showed that PTGES/PGE 2 signaling was highly associated with lung tumorigenesis and metastasis in Gprc5a -ko mice. Interestingly, Ptges-knockout in mouse lung tumor cells, although reduced their stemness and EMT-like features, still formed tumors and lung metastasis in immune-deficient nude mice, but not in immune-competent mice. This suggests that the major role of PTGES/PGE 2 signaling in tumorigenicity and lung metastasis is through immunosuppression. Mechanistically, PTGES/PGE 2 signaling intrinsically endows tumor cells resistant to T-cell cytotoxicity, and induces cytokines extrinsically for MDSC recruitment, which is crucial for suppression of T-cell immunity. Importantly, targeting PGE 2 signaling in Gprc5a -ko mice by PTGES inhibitor suppressed MDSC recruitment, restored T cells, and significantly repressed lung metastasis. Thus, PTGES/PGE 2 signaling links immunosuppression and metastasis in an inflammatory lung microenvironment of Gprc5a -ko mouse model.
    Materialart: Online-Ressource
    ISSN: 0950-9232 , 1476-5594
    URL: Article
    DOI: 10.1038/s41388-020-1207-6
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2020
    ZDB Id: 2008404-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
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    Morphological and Compositional Features of Chronic Internal Carotid Artery Occlusion in MR Vessel Wall Imaging Predict Successful Endovascular Recanalization
    MDPI AG ; 2023
    In:  Diagnostics Vol. 13, No. 1 ( 2023-01-01), p. 147-
    Details
    In: Diagnostics, MDPI AG, Vol. 13, No. 1 ( 2023-01-01), p. 147-
    Kurzfassung: Background: We sought to determine if the morphological and compositional features of chronic internal carotid artery occlusion (CICAO), as assessed by MR vessel wall imaging (MR-VWI), initially predict successful endovascular recanalization. Methods: Consecutive patients with CICAO scheduled for endovascular recanalization were recruited. MR-VWI was performed within 1 week prior to surgery for evaluating the following features: proximal stump morphology, extent of occlusion, occlusion with collapse, arterial tortuosity, the presence of hyperintense signals (HIS) and calcification in the occluded C1 segment. Multivariate logistic regression was used to identify features associated with technical success and construct a prediction model. Results: Eighty-three patients were recruited, of which fifty-seven (68.7%) were recanalized successfully. The morphological and compositional characteristics of CICAO were associated with successful recanalization, including occlusions limited to C1 and extensive HIS, as well as the absence of extensive calcification, absence of high tortuosity, and absence of artery collapse. The MR CICAO score that comprised the five predictors showed a high predictive ability (area under the curve: 0.888, p 〈 0.001). Conclusion: the MR-VWI characteristics of CICAO predicted the technical success of endovascular recanalization and may be leveraged for identifying patients with a high probability of successful recanalization.
    Materialart: Online-Ressource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics13010147
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2023
    ZDB Id: 2662336-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
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    Treatment of allergic eosinophilic asthma through engineered IL-5-anchored chimeric antigen receptor T cells
    Springer Science and Business Media LLC ; 2022
    In:  Cell Discovery Vol. 8, No. 1 ( 2022-08-16)
    Details
    In: Cell Discovery, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2022-08-16)
    Kurzfassung: Severe eosinophilic asthma (SEA) is a therapy-resistant respiratory condition with poor clinical control. Treatment efficacy and patient compliance of current therapies remain unsatisfactory. Here, inspired by the remarkable success of chimeric antigen receptor-based cellular adoptive immunotherapies demonstrated for the treatment of a variety of malignant tumors, we engineered a cytokine-anchored chimeric antigen receptor T (CCAR-T) cell system using a chimeric IL-5-CD28-CD3ζ receptor to trigger T-cell-mediated killing of eosinophils that are elevated during severe asthma attacks. IL-5-anchored CCAR-T cells exhibited selective and effective killing capacity in vitro and restricted eosinophil differentiation with apparent protection against allergic airway inflammation in two mouse models of asthma. Notably, a single dose of IL-5-anchored CCAR-T cells resulted in persistent protection against asthma-related conditions over three months, significantly exceeding the typical therapeutic window of current mAb-based treatments in the clinics. This study presents a cell-based treatment strategy for SEA and could set the stage for a new era of precision therapies against a variety of intractable allergic diseases in the future.
    Materialart: Online-Ressource
    ISSN: 2056-5968
    URL: Article
    DOI: 10.1038/s41421-022-00433-y
    Sprache: Englisch
    Verlag: Springer Science and Business Media LLC
    Publikationsdatum: 2022
    ZDB Id: 2842548-0
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
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    IL6/STAT3 Signaling Orchestrates Premetastatic Niche Formation and Immunosuppressive Traits in Lung
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 4 ( 2020-02-15), p. 784-797
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 4 ( 2020-02-15), p. 784-797
    Kurzfassung: Cancer cells that succeed in forming metastasis need to be reprogrammed to evade immune surveillance and survive in a new microenvironment. This is facilitated by metastatic niches that are either postformed through reciprocal signaling between tumor cells and local stromal cells or preformed as premetastatic niches before tumor cell arrival. IL6/STAT3 signaling is aberrantly activated in lung tumorigenesis and metastasis, however, the roles and mechanisms of action of IL6 remain controversial. Here, we showed that blockade of intrinsic STAT3 signaling in lung tumor cells suppressed lung metastasis in immune-competent syngeneic mice, but not in immune-deficient nude mice. Consistently, repression of STAT3 signaling in tumor cells made them susceptible to T-cell–mediated cytotoxicity. Thus, STAT3-mediated immunosuppression is crucial for metastasis. Noticeably, lung metastasis was greatly increased in Gprc5a-knockout (ko; 5a−/−) mice compared with wild-type mice, which correlated with upregulated IL6 in the tumor microenvironment. Depletion of IL6 via combined deletion of Il6 and Gprc5a genes almost completely eliminated lung metastasis in Gprc5a-ko/Il6-ko (5a−/−;Il6−/−) mice. Mechanistically, dysregulated IL6 reprogrammed the STAT3 pathway in metastatic tumor cells, and induced recruitment of myeloid-derived suppressor cells and polarized macrophages to evade host immunity. Consistently, IHC staining showed that activated STAT3 correlated with repressed infiltration of CD8+ T cells in non–small cell lung cancer. Therefore, IL6/STAT3 signaling is crucial for orchestrating premetastatic niche formation and immunosuppression in lung. Significance: IL6 plays important roles not only in cell autonomous propensity for metastasis, but also in establishing the metastatic niche.
    Materialart: Online-Ressource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-19-2013
    RVK:
    XA 36000
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2020
    ZDB Id: 2036785-5
    ZDB Id: 1432-1
    ZDB Id: 410466-3
    Standort Signatur Einschränkungen Verfügbarkeit
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