br Correspondence br Acknowledgments br The
The authors acknowledge the assistance of Chet Closson (Live Microscopy Core, University of Cincinnati). The authors thank Lisa McMillin (Cincinnati Children’s Hospital Medical Center, Pathology Research Core) for her assistance with organoid embedding and processing; Kathy McClinchey and the McClinchey Histology Lab Inc and Glenn Doerman (Cancer Biology, Graphic Design, Illustrations, Presentations and Desktop Publishing) for helping us prepare the figures for submission. The authors acknowledge Dr Joel Gabre for his insightful conversation. Finally, the authors thank the patients who consented to donate tissue and blood for the development of the gastric organoids. Without their willingness to participate in the study, this Pepstatin A work would not be possible.
N.S., J.W., J.C., L.H., J.B.: study concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; statistical analysis; technical or material support. J.C., L.M.N., J.H., M.M., N.S.: critical revision of the manuscript for important intellectual content; technical or material support. N.S., M.M., M.H., S.A.: study concept and design; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; technical or material support. Y.Z.: study concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; statistical analysis; obtained funding; study supervision.
Conflicts of interest The authors disclose no conflicts.
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An ssDNA aptamer selected by Cell-SELEX for the targeted imaging of poorly T differentiated gastric cancer tissue
Wanming Lia, Shuo Wanga,b, Linlin Zhoua, Yajie Chenga, Jin Fanga,
a Department of cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, PR China b Analytical Instrumentation Center, Shenyang Agricultural University, Shenyang 110001, PR China
Gastric cancer (GC) is associated with high morbidity and mortality rates worldwide. Poorly differentiated GC predicts a poor prognosis and is related to patients’ response to chemotherapy and targeted therapy. Therefore, it is very important to accurately evaluate the tumour differentiation status for the treatment of poorly differ-entiated GC. To develop a molecular probe to analyse poorly differentiated GC, we selected aptamers against poorly differentiated GC by subtractive Cell-SELEX using the poorly differentiated GC cell line BGC-823 as the target and the moderately differentiated GC cell line SGC-7901 as the negative control. After 15 rounds of selection, aptamer PDGC21 exhibited the highest affinity, and the Kd value of the truncated aptamer PDGC21-T was 35.2 ± 1.1 nM. Aptamer PDGC21-T not only specifically bound to the target cells but also bound to other poorly differentiated GC cells. When combined with fluorescent nanoparticle quantum dots (QDs), the PDGC21-T-QD probe could distinguish poorly differentiated GC cells in mixed culture cells and clinical specimens. Furthermore, in a tissue microarray containing 15 cases from patients, there was a higher positive rate in GC tissues compared with adjacent normal tissues; in poorly differentiated tissues, in particular, the fluorescence signal was significantly higher than that in well/moderately differentiated tissues. Therefore, aptamer PDGC21-T holds great potential for use as a molecular imaging probe for the detection of poorly differentiated GC, which is of great significance for diagnosis and treatment.
Gastric cancer (GC) is one of the most common malignant tumours and the third leading cause of cancer-related death worldwide, parti-cularly in East Asia, which accounts for more than half of the GC cases worldwide [1,2]. Because of the vague and nonspecific symptoms as-sociated with GC, the disease is often advanced upon diagnosis, after which chemotherapy is the primary treatment or post-operative treat-ment option . However, therapy is not effective for all patients with advanced GC, and the failure of therapy is related to the differentiation status of tumours in certain cases [4–7]. Sun et al. demonstrated that the clinical response rate of preoperative chemotherapy in the better differentiated group with advanced GC was significantly higher than that in the poorly differentiated group (100% versus 25%, P = 0.000) . Wang et al. reported that even the targeted therapy of advanced GC (Trastuzumab) is often effective for well-differentiated GC but in-effective for poorly differentiated GC [6,7]. In addition, previous data have indicated that the degree of tumour cellular differentiation is