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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Hui, Zhixuan, et al.
(författare)
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TGFβ-induced EN1 promotes tumor budding of adenoid cystic carcinoma in patient-derived organoid model
- 2024
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 154:10, s. 1814-1827
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Tidskriftsartikel (refereegranskat)abstract
- Adenoid cystic carcinoma (ACC) and basal cell adenoma (BCA) share many histological characteristics and often need a differential diagnosis in clinical pathology. Recently, we found homeobox protein engrailed-1 (EN1) was a potential diagnostic marker for ACC in an organoids library of salivary gland tumors (SGTs). Here we aim to confirm EN1 as a differential diagnostic marker for ACC, and further investigate the regulatory mechanism and biological function of EN1 in tumor progression. The transcriptional analysis, quantitative polymerase chain reaction, Western blot and immunohistochemistry staining were performed and revealed that EN1 was specifically and highly expressed in ACC, and accurately differentiated ACC from BCA. Furthermore, TGFβ signaling pathway was found associated with ACC, and the regulation of EN1 through TGFβ was detected in the human ACC cell lines and patient-derived organoids (PDOs). TGFβ-induced EN1 was important in promoting tumor budding in the PDOs model. Interestingly, a high level of EN1 and TGFβ1 in the budding tips was observed in ACC clinical samples, and the expression of EN1 and TGFβ1 in ACC was significantly associated with the clinical stage. In summary, our study verified EN1 is a good diagnostic marker to differentiate ACC from BCA. TGFβ-induced EN1 facilitates the tumor budding of ACC, which might be an important mechanism related to the malignant phenotype of ACC.
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| 3. |
- Wang, Bo, et al.
(författare)
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An organoid library of salivary gland tumors reveals subtype-specific characteristics and biomarkers
- 2022
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Ingår i: Journal of Experimental & Clinical Cancer Research. - : BioMed Central (BMC). - 1756-9966. ; 41:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Salivary gland tumors (SGTs) include a large group of rare neoplasms in the head and neck region, and the heterogeneous and overlapping features among the subtypes frequently make diagnostic difficulties. There is an urgent need to understand the cellular mechanisms underlying the heterogeneity and overlap among the subtypes, and explore the subtype-specific diagnostic biomarkers.Methods: The tumor tissue and the adjacent normal tissue from the 6 most common types of SGTs were processed for organoid culture which only maintained tumor epithelial cells. Organoids were histologically evaluated based on phenotype markers, followed by transcriptional profiling using RNA-sequencing. The transcriptomic similarities and differences among the subtypes were analyzed by subtype consensus clustering and hierarchical clustering. Furthermore, by comparative transcriptional analysis for these 6 types of SGTs and the matched organoids, the potential diagnostic biomarkers from tumor epithelium were identified, in which two selected biomarkers were evaluated by qPCR and confirmed by immunohistochemistry staining using a tissue microarray.Results: We generated a biobank of patient-derived organoids (PDOs) with 6 subtypes of SGTs, including 21 benign and 24 malignant SGTs. The PDOs recapitulated the morphological and transcriptional characteristics of the parental tumors. The overlap in the cell types and the heterogenous growth patterns were observed in the different subtypes of organoids. Comparing the bulk tissues, the cluster analysis of the PDOs remarkably revealed the epithelial characteristics, and visualized the intrinsic relationship among these subtypes. Finally, the exclusive biomarkers for the 6 most common types of SGTs were uncovered by comparative analysis, and PTP4A1 was demonstrated as a useful diagnostic biomarker for mucoepidermoid carcinoma.Conclusions: We established the first organoid biobank with multiple subtypes of SGTs. PDOs of SGTs recapitulate the morphological and transcriptional characteristics of the original tumors, which uncovers subtype-specific biomarkers and reveals the molecular distance among the subtype of SGTs.
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| 4. |
- Wang, Gang, et al.
(författare)
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Mixed-flow design for microfluidic printing of two-component polymer semiconductor systems
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 117:30, s. 17551-17557
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Tidskriftsartikel (refereegranskat)abstract
- The rational creation of two-component conjugated polymer sys-tems with high levels of phase purity in each component is challenging but crucial for realizing printed soft-matter electronics. Here, we report a mixed-flow microfluidic printing (MFMP) approach for two-component pi-polymer systems that significantly elevates phase purity in bulk-heterojunction solar cells and thin-film transistors. MFMP integrates laminar and extensional flows using a specially microstructured shear blade, designed with fluid flow simulation tools to tune the flow patterns and induce shear, stretch, and pushout effects. This optimizes polymer conformation and semi-conducting blend order as assessed by atomic force microscopy (AFM), transmission electron microscopy (TEM), grazing incidence wide-angle X-ray scattering (GIWAXS), resonant soft X-ray scattering (R-SoXS), photovoltaic response, and field effect mobility. For printed all-polymer (poly[(5,6-difluoro-2-octyl-2H-benzotriazole-4,7-diyl)-2,5-thiophenediyl[4,8-bis[5-(2-hexyldecyl)-2-thienyl]benzo[1,2-b:4,5-b ]dithiophene-2,6-diyl]-2,5-thiophenediyl]) [J51]:(poly{[N,N -bis(2-octyldodecyl) naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5 -(2,2 -bithio-phene)}) [N2200]) solar cells, this approach enhances short-circuit currents and fill factors, with power conversion efficiency increasing from 5.20% for conventional blade coating to 7.80% for MFMP. Moreover, the performance of mixed polymer ambipolar [poly(3-hexylthiophene-2,5-diyl) (P3HT):N2200] and semiconducting:insulat-ing polymer unipolar (N2200:polystyrene) transistors is similarly enhanced, underscoring versatility for two-component pi-polymer systems. Mixed-flow designs offer modalities for achieving high-performance organic optoelectronics via innovative printing methodologies.
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