433 results on '"Zhang, Xinna"'
Search Results
152. MALAT1 promoted invasiveness of gastric adenocarcinoma.
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Na Keum Lee, Jung Hwa Lee, Ivan, Cristina, Hui Ling, Xinna Zhang, Chan Hyuk Park, Calin, George A., Sang Kil Lee, Lee, Na Keum, Lee, Jung Hwa, Ling, Hui, Zhang, Xinna, Park, Chan Hyuk, and Lee, Sang Kil
- Subjects
ADENOCARCINOMA ,STOMACH cancer ,NON-coding RNA ,TRANSCRIPTION factors ,SMALL interfering RNA ,RNA metabolism ,RNA physiology ,APOPTOSIS ,BIOCHEMISTRY ,CANCER invasiveness ,CELL lines ,CELLULAR signal transduction ,GENES ,PHENOMENOLOGY ,RESEARCH funding ,RNA ,STOMACH tumors - Abstract
Background: Gastric cancer is the second leading cause of cancer globally, and the mechanism of its pathogenesis is still largely unknown. Recently, non-coding RNAs have been recognized to promote metastasis in various cancers, including gastric cancer.Methods: We found that metastasis associated lung adenocarcinoma transcript-1 (MALAT1) is upregulated in gastric cancer tissue compared to adjacent normal tissue, as determined by microarray and subsequent qRT-PCR, then investigated the impact of MALAT1 on apoptosis, cell proliferation, and the cell cycle to dissect the carcinogenesis of gastric cancer, and examined mechanisms of invasion and metastasis. Expression of MALAT1 and U6 was determined by SYBR qRT-PCR in nine-teen gastric cancer cell lines and fifty fresh samples of cancer tissue and adjacent tissues. Downregulation of MALAT1 was accomplished with two different siRNAs. Cell proliferation was determined after treatment with these siRNAs. FACS using PI/Annexin-V staining was carried out. To analyze the invasiveness, a scratch wound-healing assay and a Matrigel invasion assay were performed. Cancer related gene expression assay was done after transfection of siR- MALAT1.Results: The expression of MALAT1 was significantly elevated in various gastric cancer cell lines and gastric cancer tissues compared to normal cell lines and tissues (p < 0.01). siR-MALAT1 significantly reduced viable AGS cell numbers and induced apoptosis (p < 0.05). Deep invasion of tumor (advanced T stages) was more common in the high MALAT1-level group (p = 0.039). siR-MALAT1 significantly decreased AGS cell invasiveness and migration. siR-MALAT1 reduced expression of snail and N-cadherin, and elevated E-cadherin. The Wnt/β-catenin related genes were significantly decreased by transfection of siRNA MALAT1. MALAT1 is involved in gastric carcinogenesis via inhibition of apoptosis and promotes invasiveness via the epithelial-to-mesenchymal transition.Conclusions: In our study, we found that deregulation of MALAT1 could be involved in both tumorigenesis and invasiveness in gastric cancer cells. [ABSTRACT FROM AUTHOR]- Published
- 2017
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153. The Big Player Governs Small World Too
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Lu, Xiongbin, primary and Zhang, Xinna, additional
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- 2014
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154. N-BLR, a primate-specific non-coding transcript, modulates the epithelial-to-mesenchymal transition and leads to colorectal cancer invasion and migration
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Rigoutsos, Isidore, primary, Lee, Sang Kil, additional, Nam, Su Youn, additional, Ivkovic, Tina Catela, additional, Pichler, Martin, additional, Rossi, Simona, additional, Clark, Peter, additional, Yi, Jing, additional, Ling, Hui, additional, Shimizu, Masayoshi, additional, Redis, Roxana Simona, additional, Shah, Maitri Yogen, additional, Zhang, Xinna, additional, Jung, Eun Jung, additional, Tsirigos, Aristotelis, additional, Huang, Li, additional, Ferdin, Jana, additional, Gafa, Roberta, additional, Spizzo, Riccardo, additional, Nicoloso, Milena, additional, Shariati, Maryam, additional, Tiron, Aida, additional, Yeh, Jen Jen, additional, Teruel, Raul, additional, Melo, Sonia, additional, Xiao, Lianchun, additional, Flores, Elsa Renee, additional, Negrini, Massimo, additional, Bar Eli, Menashe, additional, Mani, Sendurai, additional, Liu, Chang-Gong, additional, Berindan-Neagoe, Ioana, additional, Esteller, Manel, additional, Keating, Michael, additional, Lanza, Giovanni, additional, and Calin, George, additional
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- 2014
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155. Noncoding RNAs in DNA Repair and Genome Integrity
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Wan, Guohui, primary, Liu, Yunhua, additional, Han, Cecil, additional, Zhang, Xinna, additional, and Lu, Xiongbin, additional
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- 2014
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156. In situ hybridization-based detection of microRNAs in human diseases
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Zhang, Xinna, primary, Lu, Xiongbin, additional, Lopez-Berestein, Gabriel, additional, Sood, Anil K., additional, and Calin, George, additional
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- 2014
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157. Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA CCAT2induce myeloid malignancies via unique SNP-specific RNA mutations
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Shah, Maitri Y., Ferracin, Manuela, Pileczki, Valentina, Chen, Baoqing, Redis, Roxana, Fabris, Linda, Zhang, Xinna, Ivan, Cristina, Shimizu, Masayoshi, Rodriguez-Aguayo, Cristian, Dragomir, Mihnea, Van Roosbroeck, Katrien, Almeida, Maria Ines, Ciccone, Maria, Nedelcu, Daniela, Cortez, Maria Angelica, Manshouri, Taghi, Calin, Steliana, Muftuoglu, Muharrem, Banerjee, Pinaki P., Badiwi, Mustafa H., Parker-Thornburg, Jan, Multani, Asha, Welsh, James William, Estecio, Marcos Roberto, Ling, Hui, Tomuleasa, Ciprian, Dima, Delia, Yang, Hui, Alvarez, Hector, You, M. James, Radovich, Milan, Shpall, Elizabeth, Fabbri, Muller, Rezvani, Katy, Girnita, Leonard, Berindan-Neagoe, Ioana, Maitra, Anirban, Verstovsek, Srdan, Fodde, Riccardo, Bueso-Ramos, Carlos, Gagea, Mihai, Manero, Guillermo Garcia, and Calin, George A.
- Abstract
The cancer-risk-associated rs6983267 single nucleotide polymorphism (SNP) and the accompanying long noncoding RNA CCAT2in the highly amplified 8q24.21 region have been implicated in cancer predisposition, although causality has not been established. Here, using allele-specific CCAT2transgenic mice, we demonstrate that CCAT2overexpression leads to spontaneous myeloid malignancies. We further identified that CCAT2is overexpressed in bone marrow and peripheral blood of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) patients. CCAT2induces global deregulation of gene expression by down-regulating EZH2 in vitro and in vivo in an allele-specific manner. We also identified a novel non-APOBEC, non-ADAR, RNA editing at the SNP locus in MDS/MPN patients and CCAT2-transgenic mice. The RNA transcribed from the SNP locus in malignant hematopoietic cells have different allelic composition from the corresponding genomic DNA, a phenomenon rarely observed in normal cells. Our findings provide fundamental insights into the functional role of rs6983267 SNP and CCAT2in myeloid malignancies.
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- 2018
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158. A miRNA signature associated with human metastatic medullary thyroid carcinoma
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Santarpia, Libero, primary, Calin, George A, additional, Adam, Liana, additional, Ye, Lei, additional, Fusco, Alfredo, additional, Giunti, Serena, additional, Thaller, Christina, additional, Paladini, Laura, additional, Zhang, Xinna, additional, Jimenez, Camilo, additional, Trimarchi, Francesco, additional, El-Naggar, Adel K, additional, and Gagel, Robert F, additional
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- 2013
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159. Therapeutic Synergy between microRNA and siRNA in Ovarian Cancer Treatment
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Nishimura, Masato, primary, Jung, Eun-Jung, additional, Shah, Maitri Y., additional, Lu, Chunhua, additional, Spizzo, Riccardo, additional, Shimizu, Masayoshi, additional, Han, Hee Dong, additional, Ivan, Cristina, additional, Rossi, Simona, additional, Zhang, Xinna, additional, Nicoloso, Milena S., additional, Wu, Sherry Y., additional, Almeida, Maria Ines, additional, Bottsford-Miller, Justin, additional, Pecot, Chad V., additional, Zand, Behrouz, additional, Matsuo, Koji, additional, Shahzad, Mian M., additional, Jennings, Nicholas B., additional, Rodriguez-Aguayo, Cristian, additional, Lopez-Berestein, Gabriel, additional, Sood, Anil K., additional, and Calin, George A., additional
- Published
- 2013
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160. CCAT2, a novel long non-coding RNA in breast cancer: expression study and clinical correlations
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Redis, Roxana S, primary, Sieuwerts, Anieta M, additional, Look, Maxime P, additional, Tudoran, Oana, additional, Ivan, Cristina, additional, Spizzo, Riccardo, additional, Zhang, Xinna, additional, de Weerd, Vanja, additional, Shimizu, Masayoshi, additional, Ling, Hui, additional, Buiga, Rares, additional, Pop, Victor, additional, Irimie, Alexandru, additional, Fodde, Riccardo, additional, Bedrosian, Isabella, additional, Martens, John WM, additional, Foekens, John A, additional, Berindan-Neagoe, Ioana, additional, and Calin, George A, additional
- Published
- 2013
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161. Tumour angiogenesis regulation by the miR-200 family
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Pecot, Chad V., primary, Rupaimoole, Rajesha, additional, Yang, Da, additional, Akbani, Rehan, additional, Ivan, Cristina, additional, Lu, Chunhua, additional, Wu, Sherry, additional, Han, Hee-Dong, additional, Shah, Maitri Y., additional, Rodriguez-Aguayo, Cristian, additional, Bottsford-Miller, Justin, additional, Liu, Yuexin, additional, Kim, Sang Bae, additional, Unruh, Anna, additional, Gonzalez-Villasana, Vianey, additional, Huang, Li, additional, Zand, Behrouz, additional, Moreno-Smith, Myrthala, additional, Mangala, Lingegowda S., additional, Taylor, Morgan, additional, Dalton, Heather J., additional, Sehgal, Vasudha, additional, Wen, Yunfei, additional, Kang, Yu, additional, Baggerly, Keith A., additional, Lee, Ju-Seog, additional, Ram, Prahlad T., additional, Ravoori, Murali K., additional, Kundra, Vikas, additional, Zhang, Xinna, additional, Ali-Fehmi, Rouba, additional, Gonzalez-Angulo, Ana-Maria, additional, Massion, Pierre P., additional, Calin, George A., additional, Lopez-Berestein, Gabriel, additional, Zhang, Wei, additional, and Sood, Anil K., additional
- Published
- 2013
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162. CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer
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Ling, Hui, primary, Spizzo, Riccardo, additional, Atlasi, Yaser, additional, Nicoloso, Milena, additional, Shimizu, Masayoshi, additional, Redis, Roxana S., additional, Nishida, Naohiro, additional, Gafà, Roberta, additional, Song, Jian, additional, Guo, Zhiyi, additional, Ivan, Cristina, additional, Barbarotto, Elisa, additional, De Vries, Ingrid, additional, Zhang, Xinna, additional, Ferracin, Manuela, additional, Churchman, Mike, additional, van Galen, Janneke F., additional, Beverloo, Berna H., additional, Shariati, Maryam, additional, Haderk, Franziska, additional, Estecio, Marcos R., additional, Garcia-Manero, Guillermo, additional, Patijn, Gijs A., additional, Gotley, David C., additional, Bhardwaj, Vikas, additional, Shureiqi, Imad, additional, Sen, Subrata, additional, Multani, Asha S., additional, Welsh, James, additional, Yamamoto, Ken, additional, Taniguchi, Itsuki, additional, Song, Min-Ae, additional, Gallinger, Steven, additional, Casey, Graham, additional, Thibodeau, Stephen N., additional, Le Marchand, Loïc, additional, Tiirikainen, Maarit, additional, Mani, Sendurai A., additional, Zhang, Wei, additional, Davuluri, Ramana V., additional, Mimori, Koshi, additional, Mori, Masaki, additional, Sieuwerts, Anieta M., additional, Martens, John W.M., additional, Tomlinson, Ian, additional, Negrini, Massimo, additional, Berindan-Neagoe, Ioana, additional, Foekens, John A., additional, Hamilton, Stanley R., additional, Lanza, Giovanni, additional, Kopetz, Scott, additional, Fodde, Riccardo, additional, and Calin, George A., additional
- Published
- 2013
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163. Abstract 3055: miR-495 functions as a novel regulator of the estrogen and progesterone receptorsin human breast cancers.
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Le, Xiao-Feng, primary, Ling, Hui, additional, Mao, Maggie, additional, Zhang, Xinna, additional, Zhang, Shu, additional, Calin, George A., additional, Wu, Yun, additional, and Bast, Robert C., additional
- Published
- 2013
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164. Abstract 4802: Metabolic distinctions in high grade epithelial ovarian cancer
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Zand, Behrouz, primary, Bottsford-Miller, Justin, additional, Hu, Wei, additional, Stone, Rebecca, additional, Nick, Alpa M., additional, Zhang, Xinna, additional, Geest, Koen De, additional, Lutgendorf, Susan K., additional, and Sood, Anil K., additional
- Published
- 2012
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165. Posttranscriptional regulation of miRNAs in the DNA damage response
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Zhang, Xinna, primary and Lu, Xiongbin, additional
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- 2011
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166. microRNA-10b: A New Marker or the Marker of Pancreatic Ductal Adenocarcinoma?
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Setoyama, Tetsuro, primary, Zhang, Xinna, additional, Natsugoe, Shoji, additional, and Calin, George A., additional
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- 2011
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167. Oncogenic Wip1 Phosphatase Is Inhibited by miR-16 in the DNA Damage Signaling Pathway
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Zhang, Xinna, primary, Wan, Guohui, additional, Mlotshwa, Sizolwenkosi, additional, Vance, Vicki, additional, Berger, Franklin G., additional, Chen, Hexin, additional, and Lu, Xiongbin, additional
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- 2010
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168. Phosphorylation and Degradation of MdmX Is Inhibited by Wip1 Phosphatase in the DNA Damage Response
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Zhang, Xinna, primary, Lin, Lin, additional, Guo, Huarong, additional, Yang, Jianhua, additional, Jones, Stephen N., additional, Jochemsen, Aart, additional, and Lu, Xiongbin, additional
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- 2009
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169. The Wip1 phosphatase and Mdm2: Cracking the "Wip" on p53 stability
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Lu, Xiongbin, primary, Nguyen, Thuy-Ai, additional, Zhang, Xinna, additional, and Donehower, Lawrence A., additional
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- 2008
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170. ABCC8 and ABCC9: ABC transporters that regulate K+ channels
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Bryan, Joseph, primary, Muñoz, Alvaro, additional, Zhang, Xinna, additional, Düfer, Martina, additional, Drews, Gisela, additional, Krippeit-Drews, Peter, additional, and Aguilar-Bryan, Lydia, additional
- Published
- 2006
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171. MicroRNA expression profiling identifies decreased expression of miR-205 in inflammatory breast cancer
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Huo, Lei, Wang, Yan, Gong, Yun, Krishnamurthy, Savitri, Wang, Jing, Diao, Lixia, Liu, Chang-Gong, Liu, Xiuping, Lin, Feng, Symmans, William F, Wei, Wei, Zhang, Xinna, Sun, Li, Alvarez, Ricardo H, Ueno, Naoto T, Fouad, Tamer M, Harano, Kenichi, Debeb, Bisrat G, Wu, Yun, Reuben, James, Cristofanilli, Massimo, and Zuo, Zhuang
- Abstract
Inflammatory breast cancer is the most aggressive form of breast cancer. Identifying new biomarkers to be used as therapeutic targets is in urgent need. Messenger RNA expression profiling studies have indicated that inflammatory breast cancer is a transcriptionally heterogeneous disease, and specific molecular targets for inflammatory breast cancer have not been well established. We performed microRNA expression profiling in inflammatory breast cancer in comparison with locally advanced noninflammatory breast cancer in this study. Although many microRNAs were differentially expressed between normal breast tissue and tumor tissue, most of them did not show differential expression between inflammatory and noninflammatory tumor samples. However, by microarray analysis, quantitative reverse transcription PCR, and in situhybridization, we showed that microRNA-205 expression was decreased not only in tumor compared with normal breast tissue, but also in inflammatory breast cancer compared with noninflammatory breast cancer. Lower expression of microRNA-205 correlated with worse distant metastasis-free survival and overall survival in our cohort. A small-scale immunohistochemistry analysis showed coexistence of decreased microRNA-205 expression and decreased E-cadherin expression in some ductal tumors. MicroRNA-205 may serve as a therapeutic target in advanced breast cancer including inflammatory breast cancer.
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- 2016
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172. Research on Leaf Area Index Inversion Based on LESS 3D Radiative Transfer Model and Machine Learning Algorithms.
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Jiang, Yunyang, Zhang, Zixuan, He, Huaijiang, Zhang, Xinna, Feng, Fei, Xu, Chengyang, Zhang, Mingjie, and Lafortezza, Raffaele
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LEAF area index , *RANDOM forest algorithms , *REMOTE-sensing images , *HYDROLOGIC cycle , *REMOTE sensing - Abstract
The Leaf Area Index (LAI) is a critical parameter that sheds light on the composition and function of forest ecosystems. Its efficient and rapid measurement is essential for simulating and estimating ecological activities such as vegetation productivity, water cycle, and carbon balance. In this study, we propose to combine high-resolution GF-6 2 m satellite images with the LESS three-dimensional RTM and employ different machine learning algorithms, including Random Forest, BP Neural Network, and XGBoost, to achieve LAI inversion for forest stands. By reconstructing real forest stand scenarios in the LESS model, we simulated reflectance data in blue, green, red, and near-infrared bands, as well as LAI data, and fused some real data as inputs to train the machine learning models. Subsequently, we used the remaining measured LAI data for validation and prediction to achieve LAI inversion. Among the three machine learning algorithms, Random Forest gave the highest performance, with an R2 of 0.6164 and an RMSE of 0.4109, while the BP Neural Network performed inefficiently (R2 = 0.4022, RMSE = 0.5407). Therefore, we ultimately employed the Random Forest algorithm to perform LAI inversion and generated LAI inversion spatial distribution maps, achieving an innovative, efficient, and reliable method for forest stand LAI inversion. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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173. Author Correction: TP53 loss creates therapeutic vulnerability in colorectal cancer.
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Liu, Yunhua, Zhang, Xinna, Han, Cecil, Wan, Guohui, Huang, Xingxu, Ivan, Cristina, Jiang, Dahai, Rodriguez-Aguayo, Cristian, Lopez-Berestein, Gabriel, Rao, Pulivarthi H., Maru, Dipen M., Pahl, Andreas, He, Xiaoming, Sood, Anil K., Ellis, Lee M., Anderl, Jan, and Lu, Xiongbin
- Published
- 2021
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174. Response of plant reflectance spectrum to simulated dust deposition and its estimation model.
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Zhu, Jiyou, Zhang, Xinna, He, Weijun, Yan, Xuemei, Yu, Qiang, Xu, Chengyang, Jiang, Qun'ou, Huang, Huaguo, and Wang, Ruirui
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COAL dust , *FOREST management , *HYPERGLYCEMIA , *POLLUTANTS , *MENTAL health - Abstract
To quantitatively reflect the relationship between dust and plant spectral reflectance. Dust from different sources in the city were selected to simulate the spectral characteristics of leaf dust. Taking Euonymus japonicus as the research object. Prediction model of leaf dust deposition was established based on spectral parameters. Results showed that among the three different dust pollutants, the reflection spectrum has 6 main reflection peaks and 7 main absorption valleys in 350–2500 nm. A steep reflection platform appears in the 692–763 nm band. In 760–1400 nm, the spectral reflectance gradually decreases with the increase of leaf dust coverage, and the variation range was coal dust > cement dust > pure soil dust. The spectral reflectance in 680–740 nm gradually decreases with the increase of leaf dust coverage. In the near infrared band, the fluctuation amplitude and slope of its first derivative spectrum gradually decrease with the increase of leaf dust. The biggest amplitude of variation was cement dust. With the increase of dust retention, the red edge position generally moves towards short wave direction, and the red edge slope generally decreases. The blue edge position moved to the short wave direction first and then to the long side direction, while the blue edge slope generally shows a decreasing trend. The yellow edge position moved to the long wave direction first and then to the short wave direction (coal dust, cement dust), and generally moved to the long side direction (pure soil dust). The yellow edge slope increases first and then decreases. The R2 values of the determination coefficients of the dust deposition prediction model have reached significant levels, which indicated that there was a relatively stable correlation between the spectral reflectance and dust deposition. The best prediction model of leaf dust deposition was leaf water content index model (y = 1.5019x − 1.4791, R2 = 0.7091, RMSE = 0.9725). [ABSTRACT FROM AUTHOR]
- Published
- 2020
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175. A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer
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Rodriguez-Aguayo, Cristian, Cooper, Laurence J. N., Ali-Fehmi, Rouba, Haemmerle, Monika, Pham, Elizabeth, Baggerly, Keith A., McGuire, Michael H., Ram, Prahlad T., Lee, Ju-Seog, Bar-Eli, Menashe, Zhang, Min, Rupaimoole, Rajesha, Hatakeyama, Hiroto, Sood, Anil K., Tucker, Sue, Olsen, Courtney, Kim, Ji Hoon, Lopez-Berestein, Gabriel, Hung, Mien-Chie, Armaiz-Pena, Guillermo N., Wu, Sherry Y., Filant, Justyna, Herbrich, Shelley M., Vidal-Anaya, Viviana, Seviour, Elena G., Huang, Li, Han, Hee-Dong, Pecot, Chad V., Pradeep, Sunila, Ehsanipour, Ehsan A., Maiti, Sourindra N., Yang, Da, Ivan, Cristina, Zhang, Xinna, Nagaraja, Archana S., Gharpure, Kshipra M., and Shen, Fangrong
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3. Good health - Abstract
A deeper mechanistic understanding of tumour angiogenesis regulation is needed to improve current anti-angiogenic therapies. Here we present evidence from systems-based miRNA analyses of large-scale patient data sets along with in vitro and in vivo experiments that miR-192 is a key regulator of angiogenesis. The potent anti-angiogenic effect of miR-192 stems from its ability to globally downregulate angiogenic pathways in cancer cells through regulation of EGR1 and HOXB9. Low miR-192 expression in human tumours is predictive of poor clinical outcome in several cancer types. Using 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) nanoliposomes, we show that miR-192 delivery leads to inhibition of tumour angiogenesis in multiple ovarian and renal tumour models, resulting in tumour regression and growth inhibition. This anti-angiogenic and anti-tumour effect is more robust than that observed with an anti-VEGF antibody. Collectively, these data identify miR-192 as a central node in tumour angiogenesis and support the use of miR-192 in an anti-angiogenesis therapy.
176. N-BLR, a primate-specific non-coding transcript leads to colorectal cancer invasion and migration
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Shah, Maitri Y., Lopez-Berestein, Gabriel, Liu, Chang Gong, Nam, Su Youn, Jing, Yi, Esteller, Manel, Ling, Hui, Yeh, Jen Jen, Gafà, Roberta, Ferdin, Jana, Rodriguez-Aguayo, Cristian, Pichler, Martin, Negrini, Massimo, Spizzo, Riccardo, Ivan, Cristina, Zhang, Xinna, Nicoloso, Milena S., Calin, George A., Telonis, Aristeidis G., Menter, David, Melo, Sonia A., Lanza, Giovanni, Tsirigos, Aristotelis, Kopetz, Scott, Rigoutsos, Isidore, Bar-Eli, Menashe, Clark, Peter M., Okugawa, Yoshinaga, Tiron, Aida, Catela Ivkovic, Tina, Jung, Eun Jung, Flores, Elsa R., Huang, Li, Mani, Sendurai A., Pasculli, Barbara, Paranjape, Anurag N., Anfossi, Simone, Lee, Sang Kil, Xiao, Lianchun, Shimizu, Masayoshi, Berindan-Neagoe, Ioana, Redis, Roxana S., Rossi, Simona, Goel, Ajay, Fabris, Linda, Shariati, Maryam, Jiang, Zhi-Qin, and Teruel-Montoya, Raul
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3. Good health - Abstract
Background Non-coding RNAs have been drawing increasing attention in recent years as functional data suggest that they play important roles in key cellular processes. N-BLR is a primate-specific long non-coding RNA that modulates the epithelial-to-mesenchymal transition, facilitates cell migration, and increases colorectal cancer invasion. Results We performed multivariate analyses of data from two independent cohorts of colorectal cancer patients and show that the abundance of N-BLR is associated with tumor stage, invasion potential, and overall patient survival. Through in vitro and in vivo experiments we found that N-BLR facilitates migration primarily via crosstalk with E-cadherin and ZEB1. We showed that this crosstalk is mediated by a pyknon, a short ~20 nucleotide-long DNA motif contained in the N-BLR transcript and is targeted by members of the miR-200 family. In light of these findings, we used a microarray to investigate the expression patterns of other pyknon-containing genomic loci. We found multiple such loci that are differentially transcribed between healthy and diseased tissues in colorectal cancer and chronic lymphocytic leukemia. Moreover, we identified several new loci whose expression correlates with the colorectal cancer patients’ overall survival. Conclusions The primate-specific N-BLR is a novel molecular contributor to the complex mechanisms that underlie metastasis in colorectal cancer and a potential novel biomarker for this disease. The presence of a functional pyknon within N-BLR and the related finding that many more pyknon-containing genomic loci in the human genome exhibit tissue-specific and disease-specific expression suggests the possibility of an alternative class of biomarkers and therapeutic targets that are primate-specific.
177. Ecological transformation is the key to improve ecosystem health for resource-exhausted cities: A case study in China based on future development scenarios.
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Jiang, Simin, Feng, Fei, Zhang, Xinna, Xu, Chengyang, Jia, Baoquan, and Lafortezza, Raffaele
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- 2024
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178. Size measurement based on a two-camera machine vision system for the bayonets of automobile brake pads.
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Xiang, Rong, He, Wenhui, Zhang, Xinna, Wang, Dong, and Shan, Yuekang
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COMPUTER vision , *MEASUREMENT , *BAYONETS , *AUTOMOBILE brakes , *EDGE detection (Image processing) , *CAMERAS - Abstract
This paper presents a measurement method based on a two-camera machine vision system and a relative measurement principle to realize the high-accuracy measurement of bayonet sizes of large automobile brake pads. This method used two cameras to capture the local images around the left and right standard edges of a specially designed standard and around the left- and right-detected edges of the measured bayonet. Then, the rectangle regions of the detected edges were set automatically. The measurement equation corresponding to the detected edges was derived after edge detection and linear fitting on the basis of the relative measurement principle. Finally, the bayonet sizes were determined using the measurement equation. Test results showed that repeatability was ±0.019 mm, the average of biases was 0.003 mm and average measurement time was 0.396 s per brake pad, all of which satisfied the requirements of online measurement. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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179. A T Cell‐Engaging Tumor Organoid Platform for Pancreatic Cancer Immunotherapy.
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Zhou, Zhuolong, Van der Jeught, Kevin, Li, Yujing, Sharma, Samantha, Yu, Tao, Moulana, Ishara, Liu, Sheng, Wan, Jun, Territo, Paul R., Opyrchal, Mateusz, Zhang, Xinna, Wan, Guohui, and Lu, Xiongbin
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DNA mismatch repair , *PANCREATIC cancer , *DRUG discovery , *T cells , *PANCREATIC duct , *THERAPEUTICS - Abstract
Pancreatic ductal adenocarcinoma (PDA) is a clinically challenging disease with limited treatment options. Despite a small percentage of cases with defective mismatch DNA repair (dMMR), PDA is included in the most immune‐resistant cancer types that are poorly responsive to immune checkpoint blockade (ICB) therapy. To facilitate drug discovery combating this immunosuppressive tumor type, a high‐throughput drug screen platform is established with the newly developed T cell‐incorporated pancreatic tumor organoid model. Tumor‐specific T cells are included in the pancreatic tumor organoids by two‐step cell packaging, fully recapitulating immune infiltration in the immunosuppressive tumor microenvironment (TME). The organoids are generated with key components in the original tumor, including epithelial, vascular endothelial, fibroblast and macrophage cells, and then packaged with T cells into their outside layer mimicking a physical barrier and enabling T cell infiltration and cytotoxicity studies. In the PDA organoid‐based screen, epigenetic inhibitors ITF2357 and I‐BET151 are identified, which in combination with anti‐PD‐1 based therapy show considerably greater anti‐tumor effect. The combinatorial treatment turns the TME from immunosuppressive to immunoactive, up‐regulates the MHC‐I antigen processing and presentation, and enhances the effector T cell activity. The standardized PDA organoid model has shown great promise to accelerate drug discovery for the immunosuppressive cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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180. Ultrasonic-driven degradation of organic pollutants using piezoelectric catalysts WS2/Bi2WO6 heterojunction composites.
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Chen, Haonan, Xi, Cuilu, Xu, Haibo, Zhang, Xinna, Xiao, Zhen, Xu, Shiqing, and Bai, Gongxun
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ENERGY levels (Quantum mechanics) , *RHODAMINE B , *ORGANIC dyes , *WATER pollution , *CHARGE carrier mobility - Abstract
Water pollution has been made worse by the widespread use of organic dyes and their discharge, which has coincided with the industry's rapid development. Piezoelectric catalysis, as an effective wastewater purification method with promising applications, can enhance the catalyst activity by collecting tiny vibrations in nature and is not limited by sunlight. In this work, we designed and synthesized intriguing WS 2 /Bi 2 WO 6 heterojunction nanocomposites, investigated their shape, structure, and piezoelectric characteristics using a range of characterization techniques, and used ultrasound to accelerate the organic dye Rhodamine B (RhB) degradation in wastewater. In comparison to the pristine monomaterials, the results demonstrated that the heterojunction composites demonstrated excellent degradation and stability of RhB under ultrasonic circumstances. The existence of heterojunctions and the internal piezoelectric field created by ultrasonic driving work in concert to boost catalytic performance, and the organic dye's rate of degradation is further accelerated by the carriers that are mutually transferred between the composites. [Display omitted] • RhB degradation with up to 95% degradation rate. • The material is easy to synthesize, green and stable. • Bi 2 WO 6 provides more active sites for heterojunction composites. • The presence of heterojunctions shifts carriers to lower energy levels. • Ultrasonic driving generates unique built-in electric field to enhance carrier mobility. [ABSTRACT FROM AUTHOR]
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- 2024
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181. Leaf functional traits differentiation in relation to covering materials of urban tree pits.
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Zhu, Jiyou, Cao, Yujuan, He, Weijun, Xu, Qing, Xu, Chengyang, and Zhang, Xinna
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SOIL porosity , *SOIL density , *LEAF area , *LEAF anatomy , *PLANTS , *URBAN trees , *POTTING soils - Abstract
Background: Understanding the ecological strategies of urban trees to the urban environment is crucial to the selection and management of urban trees. However, it is still unclear whether urban tree pit cover will affect plant functional traits. Here, we study the response of urban trees to different tree pit covers, analyzed the effects of different cover types on soil properties and their trade-off strategies based on leaf functional traits. Results: We found that there were obvious differences in the physical properties of the soil in different tree pit covers. Under the different tree pit cover types, soil bulk density and soil porosity reached the maximum under cement cover and turf cover, respectively. We found that tree pit cover significantly affected the leaf properties of urban trees. Leaf thickness, chlorophyll content index and stomatal density were mainly affected by soil bulk density and non-capillary porosity in a positive direction, and were affected by soil total porosity and capillary porosity in a negative direction. Leaf dry matter content and stomata area were mainly negatively affected by soil bulk density and non-capillary porosity, and positively affected by soil total porosity and capillary porosity. Covering materials of tree pits promoted the functional adjustment of plants and form the best combination of functions. Conclusion: Under the influence of tree pit cover, plant have low specific leaf area, stomata density, high leaf thickness, chlorophyll content index, leaf dry matter content, leaf tissue density and stomata area, which belong to "quick investment-return" type in the leaf economics spectrum. [ABSTRACT FROM AUTHOR]
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- 2021
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182. Leaf reflectance and functional traits as environmental indicators of urban dust deposition.
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Zhu, Jiyou, Xu, Jingliang, Cao, Yujuan, Fu, Jing, Li, Benling, Sun, Guangpeng, Zhang, Xinna, and Xu, Chengyang
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ENVIRONMENTAL indicators , *DUST , *REFLECTANCE , *DUST removal , *SPECTRAL reflectance , *SPECTRAL sensitivity - Abstract
Background: How to quickly predict and evaluate urban dust deposition is the key to the control of urban atmospheric environment. Here, we focus on changes of plant reflectance and plant functional traits due to dust deposition, and develop a prediction model of dust deposition based on these traits. Results: The results showed that (1) The average dust deposition per unit area of Ligustrum quihoui leaves was significantly different among urban environments (street (18.1001 g/m2), community (14.5597 g/m2) and park (9.7661 g/m2)). Among different urban environments, leaf reflectance curves tends to be consistent, but there were significant differences in leaf reflectance values (park (0.052–0.585) > community (0.028–0.477) > street (0.025–0.203)). (2) There were five major reflection peaks and five major absorption valleys. (3) The spectral reflectances before and after dust removal were significantly different (clean leaves > dust-stagnant leaves). 695 ~ 1400 nm was the sensitive range of spectral response. (4) Dust deposition has significant influence on slope and position of red edge. Red edge slope was park > community > street. After dust deposition, the red edge position has obviously "blue shift". The moving distance of the red edge position increases with the increase of dust deposition. The forecast model of dust deposition amount established by simple ratio index (y = 2.517x + 0.381, R2 = 0.787, RMSE (root-mean-square error) = 0.187. In the model, y refers to dust retention, x refers to simple ratio index.) has an average accuracy of 99.98%. (5) With the increase of dust deposition, the specific leaf area and chlorophyll content index decreased gradually. The leaf dry matter content, leaf tissue density and leaf thickness increased gradually. Conclusion: In the dust-polluted environment, L. quihoui generally presents a combination of characters with lower specific leaf area, chlorophyll content index, and higher leaf dry matter content, leaf tissue density and leaf thickness. Leaf reflectance spectroscopy and functional traits have been proved to be effective in evaluating the changes of urban dust deposition. [ABSTRACT FROM AUTHOR]
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- 2021
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183. Ferroelectric heterostructure nanocomposites based on Bi2MoO6 nanosheets and Bi2S3 nanorods for rapid piezocatalysis of organic dyes and antibiotics.
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Xi, Cuilu, Xu, Jiang, Chen, Haonan, Wang, Jiawen, Zhang, Xinna, Li, Yinyan, Bai, Gongxun, Xu, Hui, Xiao, Zhen, and Xu, Shiqing
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ORGANIC dyes , *NANORODS , *DYE-sensitized solar cells , *NANOSTRUCTURED materials , *ELECTRON-hole recombination , *PIEZOELECTRIC materials , *NANOCOMPOSITE materials , *SOLAR cells - Abstract
[Display omitted] • Type II heterojunction materials with good piezoelectric response were prepared. • Bi-based composites showed rapid degradation of organic pollutants. • The piezoelectric catalytic mechanism and polarity matching principle were revealed. Among numerous polluting compounds, the organic dyes and antibiotics are two servious factors causing water pollution. Hence, it is urgent to find a fast and safe way to degrade waste water in a sustainable approach. Here, ferroelectric heterostructure based on 2D Bi 2 MoO 6 nanosheets and Bi 2 S 3 nanorods has been prepared by a two-step solvothermal method for the reduction of organic dyes and antibiotics. Due to the energy band balance between Bi 2 S 3 and Bi 2 MoO 6 , the formed type-II heterostructure can populate charge transfer at the junction and effectively inhibit electron-hole recombination. Under ultrasonic stimulation, catalytic active sites of a Bi 2 MoO 6 /Bi 2 S 3 heterostructure for pollutant degradation can be generated through rapid charge transfer activation, thus enhancing the catalytic degradation effect of organic dyes and antibiotics. The Bi 2 MoO 6 /Bi 2 S 3 heterostructure not only has good degradation effect, but also shows better stability. This work opens up new avenues for designing highly-efficient catalysts, which is of importance for wastewater degradation and energy-saving applications. [ABSTRACT FROM AUTHOR]
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- 2024
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184. The unrelenting global expansion of the urban heat island over the last century.
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Ren, Yaxue, Lafortezza, Raffaele, Giannico, Vincenzo, Sanesi, Giovanni, Zhang, Xinna, and Xu, Chengyang
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- 2023
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185. Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA &ITCCAT2&IT induce myeloid malignancies via unique SNP-specific RNA mutations
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Mihnea P. Dragomir, Carlos E. Bueso-Ramos, Mustafa H. Badiwi, Cristian Rodriguez-Aguayo, Maitri Y. Shah, Daniela Nedelcu, James W. Welsh, Asha S. Multani, Riccardo Fodde, Valentina Pileczki, Srdan Verstovsek, Linda Fabris, Ioana Berindan-Neagoe, Guillermo Garcia Manero, Manuela Ferracin, Maria Angelica Cortez, Elizabeth J. Shpall, Maria Ciccone, Roxana S. Redis, Cristina Ivan, Anirban Maitra, Delia Dima, Masayoshi Shimizu, Héctor M. Alvarez, Xinna Zhang, Mihai Gagea, Pinaki P. Banerjee, Hui Ling, Leonard Girnita, Steliana Calin, M. James You, Jan Parker-Thornburg, Muharrem Muftuoglu, Katy Rezvani, Maria Inês Almeida, Hui Yang, Katrien Van Roosbroeck, Milan Radovich, Ciprian Tomuleasa, Muller Fabbri, Marcos R. Estecio, Baoqing Chen, George A. Calin, Taghi Manshouri, Pathology, Shah, Maitri Y., Ferracin, Manuela, Pileczki, Valentina, Chen, Baoqing, Redis, Roxana, Fabris, Linda, Zhang, Xinna, Ivan, Cristina, Shimizu, Masayoshi, Rodriguez-Aguayo, Cristian, Dragomir, Mihnea, Van Roosbroeck, Katrien, Almeida, Maria Ine, Ciccone, Maria, Nedelcu, Daniela, Cortez, Maria Angelica, Manshouri, Taghi, Calin, Steliana, Muftuoglu, Muharrem, Banerjee, Pinaki P., Badiwi, Mustafa H., Parker-Thornburg, Jan, Multani, Asha, Welsh, James William, Estecio, Marcos Roberto, Ling, Hui, Tomuleasa, Ciprian, Dima, Delia, Yang, Hui, Alvarez, Hector, You, M. Jame, Radovich, Milan, Shpall, Elizabeth, Fabbri, Muller, Rezvani, Katy, Girnita, Leonard, Berindan-Neagoe, Ioana, Maitra, Anirban, Verstovsek, Srdan, Fodde, Riccardo, Bueso-Ramos, Carlo, Gagea, Mihai, Manero, Guillermo Garcia, and Calin, George A.
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0301 basic medicine ,Myeloid ,RNA ,Single-nucleotide polymorphism ,Biology ,medicine.disease ,03 medical and health sciences ,genomic DNA ,030104 developmental biology ,medicine.anatomical_structure ,Genetic ,Myelodysplastic–myeloproliferative diseases ,SDG 3 - Good Health and Well-being ,RNA editing ,Gene expression ,Genetics ,medicine ,Cancer research ,SNP ,Genetics (clinical) - Abstract
The cancer-risk-associated rs6983267 single nucleotide polymorphism (SNP) and the accompanying long noncoding RNA CCAT2 in the highly amplified 8q24.21 region have been implicated in cancer predisposition, although causality has not been established. Here, using allele-specific CCAT2 transgenic mice, we demonstrate that CCAT2 overexpression leads to spontaneous myeloid malignancies. We further identified that CCAT2 is overexpressed in bone marrow and peripheral blood of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) patients. CCAT2 induces global deregulation of gene expression by down-regulating EZH2 in vitro and in vivo in an allele-specific manner. We also identified a novel non-APOBEC, non-ADAR, RNA editing at the SNP locus in MDS/MPN patients and CCAT2-transgenic mice. The RNA transcribed from the SNP locus in malignant hematopoietic cells have different allelic composition from the corresponding genomic DNA, a phenomenon rarely observed in normal cells. Our findings provide fundamental insights into the functional role of rs6983267 SNP and CCAT2 in myeloid malignancies.
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- 2018
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186. Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers
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Alessandra Ferrajoli, Katrien Van Roosbroeck, Massimo Negrini, Ioana Berindan-Neagoe, Dino Amadori, Hagop M. Kantarjian, Peter P. Ruvolo, Manuela Ferracin, Roxana S. Redis, Lianchun Xiao, Xuemei Wang, George A. Calin, Simona Rossi, Ivan Vannini, Antonino Neri, Robert Z. Orlowski, Steliana Calin, Vivian Ruvolo, Fortunato Morabito, Vianey Gonzalez-Villasana, Tara M. Lichtenberg, Gabriel Lopez-Berestein, Lynne V. Abruzzo, Ramana V. Davuluri, Michael J. Keating, Anil K. Sood, Rajesha Rupaimoole, M. James You, William Plunkett, Francesca Fanini, Chad V. Pecot, Tetsuro Setoyama, Xinna Zhang, Ignacio I. Wistuba, Muller Fabbri, Lucilla D’Abundo, Milena S. Nicoloso, Cristina Ivan, Enrique Fuentes-Mattei, Cristian Rodriguez-Aguayo, Van Roosbroeck, Katrien, Fanini, Francesca, Setoyama, Tetsuro, Ivan, Cristina, Rodriguez-Aguayo, Cristian, Fuentes-Mattei, Enrique, Xiao, Lianchun, Vannini, Ivan, Redis, Roxana S., D'Abundo, Lucilla, Zhang, Xinna, Nicoloso, Milena S., Rossi, Simona, Gonzalez-Villasana, Vianey, Rupaimoole, Rajesha, Ferracin, Manuela, Morabito, Fortunato, Neri, Antonino, Ruvolo, Peter P., Ruvolo, Vivian R., Pecot, Chad V., Amadori, Dino, Abruzzo, Lynne, Calin, Steliana, Wang, Xuemei, You, M. Jame, Ferrajoli, Alessandra, Orlowski, Robert, Plunkett, William, Lichtenberg, Tara M., Davuluri, Ramana V., Berindan-Neagoe, Ioana, Negrini, Massimo, Wistuba, Ignacio I., Kantarjian, Hagop M., Sood, Anil K., Lopez-Berestein, Gabriel, Keating, Michael J., Fabbri, Muller, and Calin, George A.
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0301 basic medicine ,Cancer Research ,therapy resistance ,medicine.medical_treatment ,Chronic lymphocytic leukemia ,chemotherapy, therapy resistance, miR-155 ,Socio-culturale ,Drug resistance ,Gene mutation ,chemotherapy ,miR-155 ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,medicine ,Doxorubicin ,Lung cancer ,Chemotherapy ,microRNA ,business.industry ,Cancer ,medicine.disease ,3. Good health ,lung cancer ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,business ,medicine.drug - Abstract
Purpose: The oncogenic miR-155 is upregulated in many human cancers, and its expression is increased in more aggressive and therapy-resistant tumors, but the molecular mechanisms underlying miR-155-induced therapy resistance are not fully understood. The main objectives of this study were to determine the role of miR-155 in resistance to chemotherapy and to evaluate anti-miR-155 treatment to chemosensitize tumors. Experimental Design: We performed in vitro studies on cell lines to investigate the role of miR-155 in therapy resistance. To assess the effects of miR-155 inhibition on chemoresistance, we used an in vivo orthotopic lung cancer model of athymic nude mice, which we treated with anti-miR-155 alone or in combination with chemotherapy. To analyze the association of miR-155 expression and the combination of miR-155 and TP53 expression with cancer survival, we studied 956 patients with lung cancer, chronic lymphocytic leukemia, and acute lymphoblastic leukemia. Results: We demonstrate that miR-155 induces resistance to multiple chemotherapeutic agents in vitro, and that downregulation of miR-155 successfully resensitizes tumors to chemotherapy in vivo. We show that anti-miR-155-DOPC can be considered non-toxic in vivo. We further demonstrate that miR-155 and TP53 are linked in a negative feedback mechanism and that a combination of high expression of miR-155 and low expression of TP53 is significantly associated with shorter survival in lung cancer. Conclusions: Our findings support the existence of an miR-155/TP53 feedback loop, which is involved in resistance to chemotherapy and which can be specifically targeted to overcome drug resistance, an important cause of cancer-related death. Clin Cancer Res; 23(11); 2891–904. ©2016 AACR.
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- 2017
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187. Metabolic interventions: A new insight into the cancer immunotherapy.
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Yu, Tao, Dong, Tianhan, Eyvani, Haniyeh, Fang, Yuanzhang, Wang, Xiyu, Zhang, Xinna, and Lu, Xiongbin
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CANCER cells , *T cells , *IMMUNOTHERAPY , *CELL metabolism , *TUMOR microenvironment - Abstract
Metabolic reprogramming confers cancer cells plasticity and viability under harsh conditions. Such active alterations lead to cell metabolic dependency, which can be exploited as an attractive target in development of effective antitumor therapies. Similar to cancer cells, activated T cells also execute global metabolic reprogramming for their proliferation and effector functions when recruited to the tumor microenvironment (TME). However, the high metabolic activity of rapidly proliferating cancer cells can compete for nutrients with immune cells in the TME, and consequently, suppressing their anti-tumor functions. Thus, therapeutic strategies could aim to restore T cell metabolism and anti-tumor responses in the TME by targeting the metabolic dependence of cancer cells. In this review, we highlight current research progress on metabolic reprogramming and the interplay between cancer cells and immune cells. We also discuss potential therapeutic intervention strategies for targeting metabolic pathways to improve cancer immunotherapy efficacy. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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188. Corrigendum to Exosomal miRNA confers chemo resistance via targeting Cav1/p-gp/M2-type macrophage axis in ovarian cancer.
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Kanlikilicer P, Bayraktar R, Denizli M, Rashed MH, Ivan C, Aslan B, Mitra R, Karagoz K, Bayraktar E, Zhang X, Rodriguez-Aguayo C, El-Arabey AA, Kahraman N, Baydogan S, Ozkayar O, Gatza ML, Ozpolat B, Calin GA, Sood AK, and Lopez-Berestein G
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- 2024
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189. Inhibitory DNA Aptamer Tools against SOCS3-gp130 Interactions.
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Zhang X, Hou Y, Chen W, Fu T, Wei Y, and Tan W
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- Humans, Signal Transduction drug effects, Protein Binding drug effects, Aptamers, Nucleotide chemistry, Aptamers, Nucleotide pharmacology, Aptamers, Nucleotide metabolism, Suppressor of Cytokine Signaling 3 Protein metabolism, Suppressor of Cytokine Signaling 3 Protein genetics, Cytokine Receptor gp130 metabolism
- Abstract
The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway plays a crucial role in transmembrane signal transduction, enabling cells to communicate with the extracellular environment, which requires precise regulation to prevent abnormal signaling outcomes. Within this complex pathway, suppressor of cytokine signaling 3 (SOCS3) acts as a pivotal negative regulator via binding to cytokine receptors. However, our understanding of the regulatory mechanisms governing SOCS3 interactions has been limited by the lack of suitable chemical probes. Aptamers, a notable category of chemical tools, have emerged as a viable avenue for the development of chemical inhibitors. In this study, we successfully identified specific inhibitory aptamers that bind to SOCS3 and effectively disrupt the interaction between SOCS3 and glycoprotein 130, a common cytokine receptor for interleukin-6 and leukemia inhibitory factor, which regulates the survival of normal human endometrial stromal cells. These aptamers not only provide a valuable chemical tool to advance our understanding of the regulatory dynamics of the JAK/STAT signaling pathway by SOCS3 but also hold great promise for the future development of therapeutic interventions.
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- 2024
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190. Inhibition of Glutamate-to-Glutathione Flux Promotes Tumor Antigen Presentation in Colorectal Cancer Cells.
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Yu T, Van der Jeught K, Zhu H, Zhou Z, Sharma S, Liu S, Eyvani H, So KM, Singh N, Wang J, Sandusky GE, Liu Y, Opyrchal M, Cao S, Wan J, Zhang C, and Zhang X
- Abstract
Colorectal cancer (CRC) cells display remarkable adaptability, orchestrating metabolic changes that confer growth advantages, pro-tumor microenvironment, and therapeutic resistance. One such metabolic change occurs in glutamine metabolism. Colorectal tumors with high glutaminase (GLS) expression exhibited reduced T cell infiltration and cytotoxicity, leading to poor clinical outcomes. However, depletion of GLS in CRC cells has minimal effect on tumor growth in immunocompromised mice. By contrast, remarkable inhibition of tumor growth is observed in immunocompetent mice when GLS is knocked down. It is found that GLS knockdown in CRC cells enhanced the cytotoxicity of tumor-specific T cells. Furthermore, the single-cell flux estimation analysis (scFEA) of glutamine metabolism revealed that glutamate-to-glutathione (Glu-GSH) flux, downstream of GLS, rather than Glu-to-2-oxoglutarate flux plays a key role in regulating the immune response of CRC cells in the tumor. Mechanistically, inhibition of the Glu-GSH flux activated reactive oxygen species (ROS)-related signaling pathways in tumor cells, thereby increasing the tumor immunogenicity by promoting the activity of the immunoproteasome. The combinatorial therapy of Glu-GSH flux inhibitor and anti-PD-1 antibody exhibited a superior tumor growth inhibitory effect compared to either monotherapy. Taken together, the study provides the first evidence pointing to Glu-GSH flux as a potential therapeutic target for CRC immunotherapy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
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- 2024
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191. DNA Hypomethylation-Mediated Transcription Dysregulation Participates in Pathogenesis of Polycystic Ovary Syndrome.
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Cao P, Li H, Wang P, Zhang X, Guo Y, Zhao K, Guo J, Li X, and Nashun B
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- Animals, Female, Mice, Disease Models, Animal, Transcription, Genetic, Epigenesis, Genetic, Gene Expression Regulation, Humans, Mice, Inbred C57BL, Polycystic Ovary Syndrome genetics, Polycystic Ovary Syndrome metabolism, Polycystic Ovary Syndrome pathology, DNA Methylation genetics
- Abstract
Polycystic ovary syndrome (PCOS) is a highly heterogeneous and genetically complex endocrine disorder. Although the etiology remains mostly elusive, growing evidence suggests that abnormal changes of DNA methylation correlate well with systemic and tissue-specific dysfunctions in PCOS. Herein, a dehydroepiandrosterone-induced PCOS-like mouse model which has a similar metabolic and reproductive phenotype as human patients with PCOS was generated. It was used to experimentally validate the potential role of aberrant DNA methylation in PCOS in this study. Integrated DNA methylation and transcriptome analysis revealed the potential role of genomic DNA hypomethylation in transcription regulation of PCOS and identified several key candidate genes, including BMP4, Adcy7, Tnfaip3, and Fas, which were regulated by aberrant DNA hypomethylation. Moreover, i.p. injection of S-adenosylmethionine increased the overall DNA methylation level of PCOS-like mice and restored expression of the candidate genes to similar levels as the control, alleviating reproductive and metabolic abnormalities in PCOS-like mice. These findings provide direct evidence showing the importance of normal DNA methylation in epigenetic regulation of PCOS and potential targets for diagnosis and treatment of the disease., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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192. Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer: Unravelling challenges and future directions.
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Sharma S, Singh N, Turk AA, Wan I, Guttikonda A, Dong JL, Zhang X, and Opyrchal M
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- Humans, Programmed Cell Death 1 Receptor antagonists & inhibitors, Programmed Cell Death 1 Receptor immunology, Immunotherapy methods, CTLA-4 Antigen antagonists & inhibitors, CTLA-4 Antigen immunology, Treatment Outcome, B7-H1 Antigen antagonists & inhibitors, B7-H1 Antigen immunology, Colorectal Neoplasms drug therapy, Colorectal Neoplasms immunology, Colorectal Neoplasms pathology, Colorectal Neoplasms genetics, Immune Checkpoint Inhibitors therapeutic use, Immune Checkpoint Inhibitors adverse effects, Clinical Trials as Topic
- Abstract
Colorectal cancer (CRC) is a complex disease with diverse etiologies and clinical outcomes. Despite considerable progress in development of CRC therapeutics, challenges remain regarding the diagnosis and management of advanced stage metastatic CRC (mCRC). In particular, the five-year survival rate is very low since mCRC is currently rarely curable. Over the past decade, cancer treatment has significantly improved with the introduction of cancer immunotherapies, specifically immune checkpoint inhibitors. Therapies aimed at blocking immune checkpoints such as PD-1, PD-L1, and CTLA-4 target inhibitory pathways of the immune system, and thereby enhance anti-tumor immunity. These therapies thus have shown promising results in many clinical trials alone or in combination. The efficacy and safety of immunotherapy, either alone or in combination with CRC, have been investigated in several clinical trials. Clinical trials, including KEYNOTE-164 and CheckMate 142, have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab, respectively, for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC. Unfortunately, these drugs benefit only a small percentage of patients, with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients. To this end, primary and secondary resistance to immunotherapy remains a significant issue, and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response. This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC. The underlying rationale, challenges faced, and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2024
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193. miR-543 regulates the epigenetic landscape of myelofibrosis by targeting TET1 and TET2.
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Fuentes-Mattei E, Bayraktar R, Manshouri T, Silva AM, Ivan C, Gulei D, Fabris L, Soares do Amaral N, Mur P, Perez C, Torres-Claudio E, Dragomir MP, Badillo-Perez A, Knutsen E, Narayanan P, Golfman L, Shimizu M, Zhang X, Zhao W, Ho WT, Estecio MR, Bartholomeusz G, Tomuleasa C, Berindan-Neagoe I, Zweidler-McKay PA, Estrov Z, Zhao ZJ, Verstovsek S, Calin GA, and Redis RS
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- 2024
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194. Prevalence of oral mucosal lesions in patients with systemic Lupus Erythematosus: a systematic review and meta-analysis.
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Du F, Qian W, Zhang X, Zhang L, and Shang J
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- Humans, Prevalence, Observational Studies as Topic, Oral Ulcer epidemiology, Candidiasis, Oral epidemiology, Lupus Erythematosus, Systemic complications, Lupus Erythematosus, Systemic epidemiology
- Abstract
Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can cause a range of symptoms, including oral mucosal lesions (OMLs). The prevalence of OMLs in SLE patients and their associated factors have been studied in various regions, but the results are inconsistent. This study aims to evaluate the prevalence of OMLs in patients with SLE., Methods: Observational studies of OML prevalence in SLE patients published before 2022 were retrieved from PubMed, Embase, Web of Science, Google Scholar, and the Cochrane Library without language restriction. The quality of the studies was assessed using the Newcastle-Ottawa Scale (NOS) and Agency for Healthcare Research and Quality (AHRQ)., Results: Our meta-analysis included 113 studies with a total of 53,307 SLE patients. We found that the prevalence of OMLs in SLE patients was 31% (95% CI: 28%, 35%), with oral ulcers being present in 30% of SLE patients (95% CI: 26%, 33%). Subgroup analysis showed that the prevalence of OMLs varied significantly by region, disease activity, and sample size (p ≤ 0.01). However, gender and year of publication had little effect on the prevalence of OMLs (p = 0.78 and 0.30, respectively). Oral ulcers were significantly associated with age of onset (p = 0.02), geographic location (p < 0.01), and race (p < 0.01). We also found that the prevalence of oral erythema was 9%, oral candidiasis was 9%, petechiae was 8%, cheilitis was 6%, and white plaque was 3%., Conclusions: Our analysis showed that the prevalence of OMLs varied significantly by region and disease activity, and child-onset patients of Indian, Malay, and Caucasian descent were more likely to have oral ulcers. The high prevalence of OML in SLE patients emphasizes the importance of regular oral examination and management in the comprehensive care of individuals with SLE., (© 2023. The Author(s).)
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- 2023
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195. Left Atrial and Ventricular Strain Differentiates Cardiac Amyloidosis and Hypertensive Heart Disease: A Cardiac MR Feature Tracking Study.
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Zhang X, Zhao R, Deng W, Li Y, An S, Qian Y, Liu B, Yu Y, and Li X
- Abstract
Rationale and Objectives: Strain measured by feature tracking technique represents the degree of deformation and reflects the systolic and diastolic function of the heart. Our purpose was to evaluate the differential diagnostic value and correlations of left atrial (LA) strain (LAS) and left ventricular (LV) strain (LVS) in cardiac amyloidosis (CA) and hypertensive heart disease (HHD) patients., Materials and Methods: We recruited 25 CA patients, 30 sex- and age-matched HHD patients and 20 healthy subjects totally. LAS and LVS were analyzed by CVI42 post-processing software. The efficiency of LAS and LVS in differentiating CA from HHD was compared by receiver operating characteristic curves analysis. Pearson or Spearman's analysis were used to assess the correlation between LAS and LV parameters., Results: Both HHD and CA patients had impaired LVS, the gradient of increasing absolute values of longitudinal strain (LS) and radial strain (RS) from the basal to the apical myocardium was most pronounced in the CA group, its relative apical sparing of LS (RAS
LS ) ratio reached 0.91 ± 0.02, significantly higher than other two groups (HHD: 0.72 ± 0.02; controls: 0.56 ± 0.01, all p <0.001). Additionally, except for the booster strain in the HHD group was preserved, all other LAS were reduced in patients' groups. The RASLS had the best differential diagnostic efficacy with an area under the curve (AUC) of 0.930 (p <0.001); The AUCs of LAS all greater than 0.850, above global LS (GLS) (AUC = 0.770, p = 0.001). LAS was notably correlated with LV ejection fraction (LVEF) and GLS, with reservoir strain having the greatest correlation with GLS (r = -0.828, p <0.001)., Conclusion: The RASLS has high efficiency in guiding the differential diagnosis of CA and HHD with similar degree and presentation of LVH. Moreover, LAS values can also provide some useful information and they are closely linked with LV function, CMR feature tracking may provide assistance in the evaluation of LA-LV coupling., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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196. Author Correction: An organoid-based screen for epigenetic inhibitors that stimulate antigen presentation and potentiate T-cell-mediated cytotoxicity.
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Zhou Z, Van der Jeught K, Fang Y, Yu T, Li Y, Ao Z, Liu S, Zhang L, Yang Y, Eyvani H, Cox ML, Wang X, He X, Ji G, Schneider BP, Guo F, Wan J, Zhang X, and Lu X
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- 2023
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197. 3D whole-heart noncontrast coronary MR angiography based on compressed SENSE technology: a comparative study of conventional SENSE sequence and coronary computed tomography angiography.
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Zhang Y, Zhang X, Jiang Y, Yang P, Hu X, Peng B, Yue X, Li Y, Ma P, Yuan Y, Yu Y, Liu B, and Li X
- Abstract
Objective: The relatively long scan time has hampered the clinical use of whole-heart noncontrast coronary magnetic resonance angiography (NCMRA). The compressed sensitivity encoding (SENSE) technique, also known as the CS technique, has been found to improve scan times. This study aimed to identify the optimal CS acceleration factor for NCMRA., Methods: Thirty-six participants underwent four NCMRA sequences: three sequences using the CS technique with acceleration factors of 4, 5, and 6, and one sequence using the conventional SENSE technique with the acceleration factor of 2. Coronary computed tomography angiography (CCTA) was considered as a reference sequence. The acquisition times of the four NCMRA sequences were assessed. The correlation and agreement between the visible vessel lengths obtained via CCTA and NCMRA were also assessed. The image quality scores and contrast ratio (CR) of eight coronary artery segments from the four NCMRA sequences were quantitatively evaluated., Results: The mean acquisition time of the conventional SENSE was 343 s, while that of CS4, CS5, and CS6 was 269, 215, and 190 s, respectively. The visible vessel length from the CS4 sequence showed good correlation and agreement with CCTA. The image quality score and CR from the CS4 sequence were not statistically significantly different from those in the other groups (p > 0.05). Moreover, the image score and CR showed a decreasing trend with the increase in the CS factor., Conclusions: The CS technique could significantly shorten the acquisition time of NCMRA. The CS sequence with an acceleration factor of 4 was generally acceptable for NCMRA in clinical settings to balance the image quality and acquisition time., (© 2023. The Author(s).)
- Published
- 2023
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198. An organoid-based screen for epigenetic inhibitors that stimulate antigen presentation and potentiate T-cell-mediated cytotoxicity.
- Author
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Zhou Z, Van der Jeught K, Fang Y, Yu T, Li Y, Ao Z, Liu S, Zhang L, Yang Y, Eyvani H, Cox ML, Wang X, He X, Ji G, Schneider BP, Guo F, Wan J, Zhang X, and Lu X
- Subjects
- Animals, CD8-Positive T-Lymphocytes, Epigenesis, Genetic, Female, Humans, Mice, Organoids, Antigen Presentation, Breast Neoplasms
- Abstract
In breast cancer, genetic heterogeneity, the lack of actionable targets and immune evasion all contribute to the limited clinical response rates to immune checkpoint blockade therapy. Here, we report a high-throughput screen based on the functional interaction of mouse- or patient-derived breast tumour organoids and tumour-specific cytotoxic T cells for the identification of epigenetic inhibitors that promote antigen presentation and potentiate T-cell-mediated cytotoxicity. We show that the epigenetic inhibitors GSK-LSD1, CUDC-101 and BML-210, identified by the screen, display antitumour activities in orthotopic mammary tumours in mice, that they upregulate antigen presentation mediated by the major histocompatibility complex class I on breast tumour cells and that treatment with BML-210 substantially sensitized breast tumours to the inhibitor of the checkpoint programmed death-1. Standardized measurements of tumour-cell killing activity facilitated by tumour-organoid-T-cell screens may help with the identification of candidate immunotherapeutics for a range of cancers., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2021
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199. Estimation model and its trade-off strategy of Mangifera persiciforma Colletotrichum gloeosporioides degree based on leaf reflection spectrum.
- Author
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Zhu J, Cao Y, Yao J, He W, Guo X, Zhao J, Xu Q, Zhang X, and Xu C
- Subjects
- Plant Leaves, Spectrum Analysis, Colletotrichum, Mangifera
- Abstract
Colletotrichum gloeosporioides is one of the most common and serious fungal diseases of the tree Mangifera persiciforma. Yet we lack an effective method to evaluate this ecological interaction accurately. Here, we measured the functional traits and leaf reflectance spectrum of the host plants under different disease degrees. The findings provide a fast and efficient method for large-scale and high-precision monitoring of C. gloeosporioides in M. persiciforma stands. Using the collected leaf reflection data, we set up a prediction model of the optimal disease degree. Firstly, we found that leaf functional traits of M. persiciforma generally consisted of low leaf thickness, low relative chlorophyll content, small specific leaf area, high leaf tissue density, high dry matter content, low stomatal density, and large stomatal area. Secondly, leaf reflectivity increases with damage of C. gloeosporioides, which corresponds to five main reflection peaks and five absorption valleys in the spectral reflectance curve of leaves at the same positions (350-1800 nm). Thirdly, with the increase of infection degree, red edge slope and yellow edge slope decrease, while green peak reflectance, red valley reflectance, and blue edge slope all increase. Blue shift was detected in the red edge, green peak, and red valley, while red shift appeared at the blue edge and yellow edge. Finally, the best predictive model was that based on green peak reflectance (y=3.6396-0.0693x, R
2 =0.5149, RMSE [root-mean-square error] =0.2735), with an R2 =0.92 and RMSE=0.0042 between its predicted vs. observed values. Because of its high inversion accuracy, the model can be used to predict the invasion conditions of M. persiciforma by C. gloeosporioides. Our study demonstrated that when plants are infected by C. gloeosporioides, there was a strong trade-off relationship between leaf functional traits. On the global leaf economics spectrum, the leaves tended toward the "slow investment-return" end when infected by C. gloeosporioides., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2021
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200. Atractylenolide I enhances responsiveness to immune checkpoint blockade therapy by activating tumor antigen presentation.
- Author
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Xu H, Van der Jeught K, Zhou Z, Zhang L, Yu T, Sun Y, Li Y, Wan C, So KM, Liu D, Frieden M, Fang Y, Mosley AL, He X, Zhang X, Sandusky GE, Liu Y, Meroueh SO, Zhang C, Wijeratne AB, Huang C, Ji G, and Lu X
- Subjects
- Animals, Antigens, Neoplasm genetics, HCT116 Cells, Humans, Immune Checkpoint Inhibitors pharmacokinetics, Immunity, Cellular genetics, Lactones pharmacokinetics, Mice, Mice, Inbred BALB C, Mice, Transgenic, Neoplasm Proteins genetics, Neoplasm Proteins immunology, Neoplasms, Experimental genetics, Neoplasms, Experimental immunology, RNA-Binding Proteins genetics, RNA-Binding Proteins immunology, Sesquiterpenes pharmacokinetics, Antigen Presentation drug effects, Antigens, Neoplasm immunology, CD8-Positive T-Lymphocytes immunology, Immune Checkpoint Inhibitors pharmacology, Immunity, Cellular drug effects, Immunotherapy, Lactones pharmacology, Neoplasms, Experimental therapy, Sesquiterpenes pharmacology
- Abstract
One of the primary mechanisms of tumor cell immune evasion is the loss of antigenicity, which arises due to lack of immunogenic tumor antigens as well as dysregulation of the antigen processing machinery. In a screen for small-molecule compounds from herbal medicine that potentiate T cell-mediated cytotoxicity, we identified atractylenolide I (ATT-I), which substantially promotes tumor antigen presentation of both human and mouse colorectal cancer (CRC) cells and thereby enhances the cytotoxic response of CD8+ T cells. Cellular thermal shift assay (CETSA) with multiplexed quantitative mass spectrometry identified the proteasome 26S subunit non-ATPase 4 (PSMD4), an essential component of the immunoproteasome complex, as a primary target protein of ATT-I. Binding of ATT-I with PSMD4 augments the antigen-processing activity of immunoproteasome, leading to enhanced MHC-I-mediated antigen presentation on cancer cells. In syngeneic mouse CRC models and human patient-derived CRC organoid models, ATT-I treatment promotes the cytotoxicity of CD8+ T cells and thus profoundly enhances the efficacy of immune checkpoint blockade therapy. Collectively, we show here that targeting the function of immunoproteasome with ATT-I promotes tumor antigen presentation and empowers T cell cytotoxicity, thus elevating the tumor response to immunotherapy.
- Published
- 2021
- Full Text
- View/download PDF
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