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      Deconvolution of diffuse gastric cancer and the suppression of CD34 on the BALB/c nude mice model

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          Abstract

          Background

          Gastric cancer is a considerable burden for worldwide patients. And diffuse gastric cancer is the most insidious subgroup with poor survival. The phenotypic characterization of the diffuse gastric cancer cell line can be useful for gastric cancer researchers. In this article, we aimed to characterize the diffuse gastric cancer cells with MRI and transcriptomic data. We hypothesized that gene expression pattern is associated with the phenotype of the cells and that the heterogeneous enhancement pattern and the high tumorigenicity of SNU484 can be modulated by the perturbation of the highly expressed gene.

          Methods

          We evaluated the 9.4 T magnetic resonance imaging and transcriptomic data of the orthotopic mice models from diffuse gastric cancer cells such as SNU484, Hs746T, SNU668, and KATO III. We included MKN74 as an intestinal cancer control cell. After comprehensive analysis integrating MRI and transcriptomic data, we selected CD34 and validated the effect by shRNA in the BALB/c nude mice models.

          Results

          SNU484, SNU668, Hs746T, and MKN74 formed orthotopic tumors by the 5 weeks after cell injection. The diffuse phenotype was found in the SNU484 and Hs746T. SNU484 was the only tumor showing the heterogeneous enhancement pattern on T2 images with a high level of CD34 expression. Knockdown of CD34 decreased the round-void shape in the H&E staining ( P = 0.028), the heterogeneous T2 enhancement, and orthotopic tumorigenicity (100% vs 66.7%). The RNAseq showed that the suppressed CD34 is associated with the downregulated gene-sets of the extracellular matrix remodeling.

          Conclusion

          Suppression of CD34 in the human-originated gastric cancer cell suggests that it is important for the round-void histologic shape, heterogeneous enhancement pattern on MRI, and the growth of gastric cancer cell line.

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          Most cited references21

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          Predictive test for chemotherapy response in resectable gastric cancer: a multi-cohort, retrospective analysis

          Adjuvant chemotherapy after surgery improves survival of patients with stage II-III, resectable gastric cancer. However, the overall survival benefit observed after adjuvant chemotherapy is moderate, suggesting that not all patients with resectable gastric cancer treated with adjuvant chemotherapy benefit from it. We aimed to develop and validate a predictive test for adjuvant chemotherapy response in patients with resectable, stage II-III gastric cancer.
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            Fat and water magnetic resonance imaging.

            A wide variety of fat suppression and water-fat separation methods are used to suppress fat signal and improve visualization of abnormalities. This article reviews the most commonly used techniques for fat suppression and fat-water imaging including 1) chemically selective fat suppression pulses "FAT-SAT"; 2) spatial-spectral pulses (water excitation); 3) short inversion time (TI) inversion recovery (STIR) imaging; 4) chemical shift based water-fat separation methods; and finally 5) fat suppression and balanced steady-state free precession (SSFP) sequences. The basic physical background of these techniques including their specific advantages and disadvantages is given and related to clinical applications. This enables the reader to understand the reasons why some fat suppression methods work better than others in specific clinical settings.
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              Anesthesia and other considerations for in vivo imaging of small animals.

              The use of small animal imaging is increasing in biomedical research thanks to its ability to localize altered biochemical and physiological processes in the living animal and to follow these processes longitudinally and noninvasively. In contrast to human studies, however, imaging of small animals generally requires anesthesia, and anesthetic agents can have unintended effects on animal physiology that may confound the results of the imaging studies. In addition, repeated anesthesia, animal preparation for imaging, exposure to ionizing radiation, and the administration of contrast agents may affect the processes under study. We discuss this interplay of factors for small animal imaging in the context of four common imaging modalities for small animals: positron emission tomography (PET) and single photon emission computed tomography (SPECT), computed tomography (CT), magnetic resonance imaging (MRI), and optical imaging. We discuss animal preparation for imaging, including choice of animal strain and gender, the role of fasting and diet, and the circadian cycle. We review common anesthesias used in small animal imaging, such as pentobarbital, ketamine/xylazine, and isoflurane, and describe techniques for monitoring the respiration and circulation of anesthetized animals that are being imaged as well as developments for imaging conscious animals. We present current imaging literature exemplifying how anesthesia and animal handling can influence the biodistribution of PET tracers. Finally, we discuss how longitudinal imaging studies may affect animals due to repeated injections of radioactivity or other substrates and the general effect of stress on the animals. In conclusion, there are many animal handling issues to consider when designing an imaging experiment. Reproducible experimental conditions require clear, consistent reporting, in the study design and throughout the experiment, of the animal strain and gender, fasting, anesthesia, and how often individual animals were imaged.
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                Author and article information

                Contributors
                cyclomethane@yuhs.ac
                jungmion3@naver.com
                OMINI77@yuhs.ac
                gksmf589@naver.com
                SWPARK64@yuhs.ac
                SEOKGU9@yuhs.ac
                SHY916@yuhs.ac
                ymhuh@yuhs.ac
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                15 April 2020
                15 April 2020
                2020
                : 20
                : 314
                Affiliations
                [1 ]GRID grid.15444.30, ISNI 0000 0004 0470 5454, Department of Biochemistry and Molecular Biology, , Yonsei University College of Medicine, ; Seoul, South Korea
                [2 ]GRID grid.15444.30, ISNI 0000 0004 0470 5454, Brain Korea 21 PLUS Project for Medical Science, , Yonsei University, ; Seoul, South Korea
                [3 ]GRID grid.15444.30, ISNI 0000 0004 0470 5454, Department of Radiology, Severance Hospital, , Yonsei University College of Medicine, ; Seoul, Republic of Korea
                [4 ]GRID grid.15444.30, ISNI 0000 0004 0470 5454, Departments of Neurosurgery, , Severance Hospital, Yonsei University College of Medicine, ; Seoul, South Korea
                [5 ]GRID grid.15444.30, ISNI 0000 0004 0470 5454, Department of Medical Science, , Yonsei University Graduate School, ; Seoul, South Korea
                [6 ]GRID grid.15444.30, ISNI 0000 0004 0470 5454, Severance Biomedical Science Institute, , College of Medicine, Yonsei University, ; Seoul, South Korea
                [7 ]GRID grid.413046.4, ISNI 0000 0004 0439 4086, YUHS-KRIBB Medical Convergence Research Institute, ; Seoul, South Korea
                Article
                6814
                10.1186/s12885-020-06814-4
                7160933
                32293340
                e2b93a08-5ece-46d6-abe0-42232e5952a9
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 27 September 2019
                : 1 April 2020
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Oncology & Radiotherapy
                diffuse gastric cancer,cd34,knockdown,magnetic resonance imaging,histology,phenotype,balb/c nude mouse

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