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Journal articles on the topic 'ANTXR1'

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Author: Grafiati

Published: 10 December 2022

Last updated: 28 January 2023

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1

Go, Mandy Y., Edith M. C. Chow, and Jeremy Mogridge. "The Cytoplasmic Domain of Anthrax Toxin Receptor 1 Affects Binding of the Protective Antigen." Infection and Immunity 77, no. 1 (October 20, 2008): 52–59. http://dx.doi.org/10.1128/iai.01073-08.

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ABSTRACT The protective antigen (PA) component of anthrax toxin binds the I domain of the receptor ANTXR1. Integrin I domains convert between open and closed conformations that bind ligand with high and low affinities, respectively; this process is regulated by signaling from the cytoplasmic domains. To assess whether intracellular signals might influence the interaction between ANTXR1 and PA, we compared two splice variants of ANTXR1 that differ only in their cytoplasmic domains. We found that cells expressing ANTXR1 splice variant 1 (ANTXR1-sv1) bound markedly less PA than did cells expressing a similar level of the shorter splice variant ANTXR1-sv2. ANTXR1-sv1 but not ANTXR1-sv2 associated with the actin cytoskeleton, although disruption of the cytoskeleton did not affect binding of ANTXR-sv1 to PA. Introduction of a cytoplasmic domain missense mutation found in the related receptor ANTXR2 in a patient with juvenile hyaline fibromatosis impaired actin association and increased binding of PA to ANTXR1-sv1. These results suggest that ANTXR1 has two affinity states that may be modulated by cytoplasmic signals.

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2

Jayawardena, Nadishka, Laura N. Burga, Richard A. Easingwood, Yoshimasa Takizawa, Matthias Wolf, and Mihnea Bostina. "Structural basis for anthrax toxin receptor 1 recognition by Seneca Valley Virus." Proceedings of the National Academy of Sciences 115, no. 46 (October 31, 2018): E10934—E10940. http://dx.doi.org/10.1073/pnas.1810664115.

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Recently, the use of oncolytic viruses in cancer therapy has become a realistic therapeutic option. Seneca Valley Virus (SVV) is a newly discovered picornavirus, which has earned a significant reputation as a potent oncolytic agent. Anthrax toxin receptor 1 (ANTXR1), one of the cellular receptors for the protective antigen secreted by Bacillus anthracis, has been identified as the high-affinity cellular receptor for SVV. Here, we report the structure of the SVV-ANTXR1 complex determined by single-particle cryo-electron microscopy analysis at near-atomic resolution. This is an example of a shared receptor structure between a mammalian virus and a bacterial toxin. Our structure shows that ANTXR1 decorates the outer surface of the SVV capsid and interacts with the surface-exposed BC loop and loop II of VP1, “the puff” of VP2 and “the knob” of VP3. Comparison of the receptor-bound capsid structure with the native capsid structure reveals that receptor binding induces minor conformational changes in SVV capsid structure, suggesting the role of ANTXR1 as an attachment receptor. Furthermore, our results demonstrate that the capsid footprint on the receptor is not conserved in anthrax toxin receptor 2 (ANTXR2), thereby providing a molecular mechanism for explaining the exquisite selectivity of SVV for ANTXR1.

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3

Jiang, Qing, Xin Qin, Carolina Andrea Yoshida, Hisato Komori, Kei Yamana, Shinsuke Ohba, Hironori Hojo, Brad St Croix, Viviane K. S. Kawata-Matsuura, and Toshihisa Komori. "Antxr1, Which is a Target of Runx2, Regulates Chondrocyte Proliferation and Apoptosis." International Journal of Molecular Sciences 21, no. 7 (March 31, 2020): 2425. http://dx.doi.org/10.3390/ijms21072425.

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Antxr1/Tem8 is highly expressed in tumor endothelial cells and is a receptor for anthrax toxin. Mutation of Antxr1 causes GAPO syndrome, which is characterized by growth retardation, alopecia, pseudo-anodontia, and optic atrophy. However, the mechanism underlying the growth retardation remains to be clarified. Runx2 is essential for osteoblast differentiation and chondrocyte maturation and regulates chondrocyte proliferation through Ihh induction. In the search of Runx2 target genes in chondrocytes, we found that Antxr1 expression is upregulated by Runx2. Antxr1 was highly expressed in cartilaginous tissues and was directly regulated by Runx2. In skeletal development, the process of endochondral ossification proceeded similarly in wild-type and Antxr1–/– mice. However, the limbs of Antxr1–/– mice were shorter than those of wild-type mice from embryonic day 16.5 due to the reduced chondrocyte proliferation. Chondrocyte-specific Antxr1 transgenic mice exhibited shortened limbs, although the process of endochondral ossification proceeded as in wild-type mice. BrdU-uptake and apoptosis were both increased in chondrocytes, and the apoptosis-high regions were mineralized. These findings indicated that Antxr1, of which the expression is regulated by Runx2, plays an important role in chondrocyte proliferation and that overexpression of Antxr1 causes chondrocyte apoptosis accompanied by matrix mineralization.

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4

Jayawardena, Nadishka, Linde A. Miles, Laura N. Burga, Charles Rudin, Matthias Wolf, John T. Poirier, and Mihnea Bostina. "N-Linked Glycosylation on Anthrax Toxin Receptor 1 Is Essential for Seneca Valley Virus Infection." Viruses 13, no. 5 (April 28, 2021): 769. http://dx.doi.org/10.3390/v13050769.

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Seneca Valley virus (SVV) is a picornavirus with potency in selectively infecting and lysing cancerous cells. The cellular receptor for SVV mediating the selective tropism for tumors is anthrax toxin receptor 1 (ANTXR1), a type I transmembrane protein expressed in tumors. Similar to other mammalian receptors, ANTXR1 has been shown to harbor N-linked glycosylation sites in its extracellular vWA domain. However, the exact role of ANTXR1 glycosylation on SVV attachment and cellular entry was unknown. Here we show that N-linked glycosylation in the ANTXR1 vWA domain is necessary for SVV attachment and entry. In our study, tandem mass spectrometry analysis of recombinant ANTXR1-Fc revealed the presence of complex glycans at N166, N184 in the vWA domain, and N81 in the Fc domain. Symmetry-expanded cryo-EM reconstruction of SVV-ANTXR1-Fc further validated the presence of N166 and N184 in the vWA domain. Cell blocking, co-immunoprecipitation, and plaque formation assays confirmed that deglycosylation of ANTXR1 prevents SVV attachment and subsequent entry. Overall, our results identified N-glycosylation in ANTXR1 as a necessary post-translational modification for establishing stable interactions with SVV. We anticipate our findings will aid in selecting patients for future cancer therapeutics, where screening for both ANTXR1 and its glycosylation could lead to an improved outcome from SVV therapy.

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5

Alcalá, Sonia, Paola Martinelli, Patrick C. Hermann, Christopher Heeschen, and Bruno Sainz. "The Anthrax Toxin Receptor 1 (ANTXR1) Is Enriched in Pancreatic Cancer Stem Cells Derived from Primary Tumor Cultures." Stem Cells International 2019 (May 2, 2019): 1–13. http://dx.doi.org/10.1155/2019/1378639.

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Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of cancer-related mortality. Cancer stem cells (CSCs) have been shown to be the drivers of pancreatic tumor growth, metastasis, and chemoresistance, but our understanding of these cells is still limited by our inability to efficiently identify and isolate them. While a number of markers capable of identifying pancreatic CSCs (PaCSCs) have been discovered since 2007, there is no doubt that more markers are still needed. The anthrax toxin receptor 1 (ANTXR1) was identified as a functional biomarker of triple-negative breast CSCs, and PDAC patients stratified based on ANTXR1 expression levels showed increased mortality and enrichment of pathways known to be necessary for CSC biology, including TGF-β, NOTCH, Wnt/β-catenin, and IL-6/JAK/STAT3 signaling and epithelial to mesenchymal transition, suggesting that ANTXR1 may represent a putative PaCSC marker. In this study, we show that ANTXR1+ cells are not only detectable across a panel of 7 PDAC patient-derived xenograft primary cultures but ANTXR1 expression significantly increased in CSC-enriched 3D sphere cultures. Importantly, ANTXR1+ cells also coexpressed other known PaCSC markers such as CD44, CD133, and autofluorescence, and ANTXR1+ cells displayed enhanced CSC functional and molecular properties, including increased self-renewal and expression of pluripotency-associated genes, compared to ANTXR1- cells. Thus, this study validates ANTXR1 as a new PaCSC marker and we propose its use in identifying CSCs in this tumor type and its exploitation in the development of CSC-targeted therapies for PDAC.

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6

Stránecký, Viktor, Alexander Hoischen, Hana Hartmannová, Maha S. Zaki, Amit Chaudhary, Enrique Zudaire, Lenka Nosková, et al. "Mutations in ANTXR1 Cause GAPO Syndrome." American Journal of Human Genetics 92, no. 5 (May 2013): 792–99. http://dx.doi.org/10.1016/j.ajhg.2013.03.023.

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7

Dong, Zhiqiang, Jinglong Zhang, Liang Niu, Guokuo Hou, Zhenshan Gao, and Qiang Yang. "miR-381-3p Involves in Glioma Progression by Suppressing Tumor-Promoter Factor ANTXR1." Computational and Mathematical Methods in Medicine 2021 (December 16, 2021): 1–7. http://dx.doi.org/10.1155/2021/4883509.

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Accumulating studies revealed association between development of glioma and miRNA dysregulation. A case in point is miR-381-3p, but its mechanism in glioma is unclear yet. In this work, we confirmed that overexpressed miR-381-3p repressed biological functions of glioma cells. Additionally, we also discovered that upregulated anthrax toxin receptor 1 (ANTXR1) was negatively mediated by miR-381-3p. We further proved that miR-381-3p-targeted ANTXR1 was able to counteract the suppression of miR-381-3p on biological functions of glioma. We concluded that miR-381-3p and ANTXR1 were both important factors in modulating glioma progression. miR-381-3p/ANTXR1 axis is expected to be a molecular target for glioma.

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8

Cao, Lin, Ran Zhang, Tingting Liu, Zixian Sun, Mingxu Hu, Yuna Sun, Lingpeng Cheng, et al. "Seneca Valley virus attachment and uncoating mediated by its receptor anthrax toxin receptor 1." Proceedings of the National Academy of Sciences 115, no. 51 (December 4, 2018): 13087–92. http://dx.doi.org/10.1073/pnas.1814309115.

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Seneca Valley virus (SVV) is an oncolytic picornavirus with selective tropism for neuroendocrine cancers. SVV mediates cell entry by attachment to the receptor anthrax toxin receptor 1 (ANTXR1). Here we determine atomic structures of mature SVV particles alone and in complex with ANTXR1 in both neutral and acidic conditions, as well as empty “spent” particles in complex with ANTXR1 in acidic conditions by cryoelectron microscopy. SVV engages ANTXR1 mainly by the VP2 DF and VP1 CD loops, leading to structural changes in the VP1 GH loop and VP3 GH loop, which attenuate interprotomer interactions and destabilize the capsid assembly. Despite lying on the edge of the attachment site, VP2 D146 interacts with the metal ion in ANTXR1 and is required for cell entry. Though the individual substitution of most interacting residues abolishes receptor binding and virus propagation, a serine-to-alanine mutation at VP2 S177 significantly increases SVV proliferation. Acidification of the SVV–ANTXR1 complex results in a major reconfiguration of the pentameric capsid assemblies, which rotate ∼20° around the icosahedral fivefold axes to form a previously uncharacterized spent particle resembling a potential uncoating intermediate with remarkable perforations at both two- and threefold axes. These structures provide high-resolution snapshots of SVV entry, highlighting opportunities for anticancer therapeutic optimization.

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9

Jin, Tingting, Zhaojun Zhang, Yuanyuan Han, Di Li, Juan Liu, Minmin Jiang, Ryo Kurita, et al. "ANTXR1 Regulates Erythroid Cell Proliferation and Differentiation through wnt/β-Catenin Signaling Pathway In Vitro and in Hematopoietic Stem Cell." Disease Markers 2022 (August 27, 2022): 1–15. http://dx.doi.org/10.1155/2022/1226697.

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Erythropoiesis is a highly complex and sophisticated multistage process regulated by many transcription factors, as well as noncoding RNAs. Anthrax toxin receptor 1 (ANTXR1) is a type I transmembrane protein that binds the anthrax toxin ligands and mediates the entry of its toxic part into cells. It also functions as a receptor for the Protective antigen (PA) of anthrax toxin, and mediates the entry of Edema factor (EF) and Lethal factor (LF) into the cytoplasm of target cells and exerts their toxicity. Previous research has shown that ANTXR1 inhibits the expression of γ-globin during the differentiation of erythroid cells. However, the effect on erythropoiesis from a cellular perspective has not been fully determined. This study examined the role of ANTXR1 on erythropoiesis using K562 and HUDEP-2 cell lines as well as cord blood CD34+ cells. Our study has shown that overexpression of ANTXR1 can positively regulate erythrocyte proliferation, as well as inhibit GATA1 and ALAS2 expression, differentiation, and apoptosis in K562 cells and hematopoietic stem cells. ANTXR1 knockdown inhibited proliferation, promoted GATA1 and ALAS2 expression, accelerated erythrocyte differentiation and apoptosis, and promoted erythrocyte maturation. Our study also showed that ANTXR1 may regulate the proliferation and differentiation of hematopoietic cells, though the Wnt/β-catenin pathway, which may help to establish a possible therapeutic target for the treatment of blood disorders.

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10

Jin, Tingting, Zhaojun Zhang, Yuanyuan Han, Di Li, Juan Liu, Minmin Jiang, Junwei Zhu, et al. "Transmembrane Protein ANTXR1 Regulates γ-Globin Expression by Targeting the Wnt/β-Catenin Signaling Pathway." Journal of Immunology Research 2022 (July 30, 2022): 1–17. http://dx.doi.org/10.1155/2022/8440422.

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Reactivation of fetal hemoglobin (HbF, α2γ2) alleviates clinical symptoms in patients with β-thalassemia and sickle cell disease, although the regulatory mechanisms of γ-globin expression have not yet been fully elucidated. Recent studies found that interfering with the expression of the membrane protein ANTXR1 gene upregulated γ-globin levels. However, the exact mechanism by which ANTXR1 regulates γ-globin levels remains unclear. Our study showed that overexpression and knockdown of ANTXR1 in K562, cord blood CD34+, and HUDEP-2 cells decreased and increased γ-globin expression, respectively. ANTXR1 regulates the reactivation of fetal hemoglobin (HbF, α2γ2) in K562, cord blood CD34+, and adult peripheral blood CD34+ cells through interaction with LRP6 to promote the nuclear entry of β-catenin and activate the Wnt/β-catenin signaling pathway. The overexpression or knockdown of ANTXR1 on γ-globin and Wnt/β-catenin signaling in K562 cells was reversed by the inhibitor XAV939 and the activator LiCl, respectively, where XAV939 inhibits the transcription of β-catenin in the Wnt pathway, but LiCl inhibits GSK3-β. We also showed that the binding ability of the rank4 site in the transcriptional regulatory region of the SOX6 gene to c-Jun was significantly increased after overexpression of ANTXR1 in K562 cells. SOX6 protein expression was increased significantly after overexpression of the c-Jun gene, indicating that the transcription factor c-Jun initiated the transcription of SOX6, thereby silencing γ-globin. Our findings may provide a new intervention target for the treatment of β-hemoglobinopathies.

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11

Al-Ali, Zhara A., Rana K. Fallatah, Esra A. Aljaffer, Eman R. Albukhari, Neriman Sadek Al-Ali, Ziyad T. Al-Ghannam, Reem Sayeb Al-Atrash, Ahmed Alsuliman, and Chittibabu Vatte. "ANTXR1 Intronic Variants Are Associated with Fetal Hemoglobin in the Arab-Indian Haplotype of Sickle Cell Disease." Acta Haematologica 140, no. 1 (2018): 55–59. http://dx.doi.org/10.1159/000491688.

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Disease severity of sickle cell anemia is highly variable, and it is commonly accepted that fetal hemoglobin (HbF) levels play a major role as an ameliorating factor. Investigation of genetic variants have identified several genes to be the principal influencers of HbF regulation. Here, we further elucidated the association of rs4527238 and rs35685045 of ANTXR1 genes in the context of HbF level variance in sickle cell anemia patients of the Arab-Indian haplotype. Samples from 630 sickle cell anemia patients were analyzed for the mutations at 2 specific locations of the ANTXR1 gene by TaqMan®-based real-time PCR. The CC genotype (p = 0.018) of rs4527238 and the TT genotype (p = 0.048) of rs35685045 of ANTXR1 were found to be significantly associated with low HbF expression. The frequency of the CC genotype of rs4527238 was observed to be high in the low HbF patient group compared to the high HbF group (p = 0.009). Likewise, the frequency of the TT genotype of rs35685045 was also high among the low HbF group (p = 0.017). The ANTXR1 genetic mutations and the association with HbF expression in the Arab-Indian haplotype sickle cell patients revealed that the ANTXR1 gene may be a major HbF modulator leading to potential therapeutic options that should be further explored.

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12

Li, Yuanchun, Qingdong Wang, DongWei Wang, and Weihua Fu. "KLF7 Promotes Gastric Carcinogenesis Through Regulation of ANTXR1." Cancer Management and Research Volume 13 (July 2021): 5547–57. http://dx.doi.org/10.2147/cmar.s308071.

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13

Li, Yuanchun, Qingdong Wang, DongWei Wang, and Weihua Fu. "KLF7 Promotes Gastric Carcinogenesis Through Regulation of ANTXR1 [Corrigendum]." Cancer Management and Research Volume 13 (August 2021): 6113–14. http://dx.doi.org/10.2147/cmar.s331877.

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14

Herrmann, David, Anna Ferrer-Vaquer, Christian Lahsnig, Nicole Firnberg, Andreas Leibbrandt, and Annette Neubüser. "Expression and regulation of ANTXR1 in the chick embryo." Developmental Dynamics 239, no. 2 (December 23, 2009): 680–87. http://dx.doi.org/10.1002/dvdy.22194.

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15

Li, Yuanchun, Qingdong Wang, DongWei Wang, and Weihua Fu. "KLF7 Promotes Gastric Carcinogenesis Through Regulation of ANTXR1 [Retraction]." Cancer Management and Research Volume 14 (December 2022): 3417–18. http://dx.doi.org/10.2147/cmar.s399986.

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16

Petrovic, Kristina, Joseph Robinson, Katharine Whitworth, Elizabeth Jinks, Abeer Shaaban, and Steven P. Lee. "TEM8/ANTXR1-specific CAR T cells mediate toxicity in vivo." PLOS ONE 14, no. 10 (October 17, 2019): e0224015. http://dx.doi.org/10.1371/journal.pone.0224015.

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17

Vathipadiekal, Vinod, John Farrell, Zhang Shuai, Heather Edward, Heather Shappell, A. M. Al-Rubaish, Fahad Al-Muhanna, et al. "A Candidate Trans-Acting Modulator of Fetal Hemoglobin Gene Expression in the Arab-Indian Haplotype of Sickle Cell Anemia." Blood 126, no. 23 (December 3, 2015): 409. http://dx.doi.org/10.1182/blood.v126.23.409.409.

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Abstract In the Arab-Indian (AI) β-globin gene (HBB) haplotype of sickle cell anemia, fetal hemoglobin (HbF) levels are higher and the disease phenotype milder than in African HBB haplotypes. To study the genetic basis of HbF regulation in the AI haplotype, whole genome sequencing (WGS) was done in 14 unrelated Saudi AI haplotype HbS homozygotes; 7 selected for low HbF (7.9±1.9%) and 7 for high HbF (18.5±3.2%). WGS was also done in 3 Indians with the AI haplotype (HbF 26.0±4.5%), 3 African Americans with the Benin haplotype selected because of the uncommonly high HbF for this haplotype (19.8±0.4%) and 1 African American homozygote with the Senegal haplotype (HbF 16.0%). Association of SNPs with HbF was tested using simple linear regression with an additive genetic model, and the Sequence Kernel Association Test using sliding windows of 5 SNPs. We found 465 SNPs that were significantly associated with HbF in a single SNP analysis (p≤10-5). Following annotation using SNPper and ENCODE RegulomeDB, PLINK was employed to remove all SNPs in high linkage disequilibrium (r2>0.8) ending with 128 SNPs for follow-up analysis. These prioritized variants were further investigated using functional evaluation tools such as SCAN, Hembase, ErythronDB and the results of WGS were followed by genome-wide SNP analysis, imputation of genotypes to 1000genomes, and targeted direct genotyping in the following cohorts with sickle cell anemia: 110 AI haplotype cases (HbF 18.0±7.0%); 71 Saudi Benin haplotype cases (HbF 11.4±4.1%); 44 Indian AI haplotype homozygotes (HbF 23.0±4.8%); 894 African Americans with diverse HBB haplotypes (HbF 5.2±5.6%). All cases were examined when the HbF levels had stabilized. None of the patients were using hydroxyurea when HbF was measured. Based on WGS, 2 SNPs, rs4527238 and rs35685045 (D'=1) in intron 9 of ANTXR1 (anthrax toxin receptor 1, 2p13.1) remained associated with HbF after correction for multiple comparisons. This result was replicated in the cohort of 110 additional AI haplotype Saudi patients but not in cohorts with other HBB haplotypes. The alternative alleles of these 2 SNPs had nearly equal frequencies in Saudis with the Saudi AI haplotype and lower frequencies in Indians, Saudi Benin haplotype and African Americans with sickle cell anemia. The T allele of rs4527238 and the C allele of rs35685045 are associated with high HbF. ANTXR1 SNPs explained 10% of the HbF variability compared with 8% for BCL11A; these genes had independent, additive effects on HbF and explained about 15% of HbF variability. RNA sequencing and gene expression microarray analysis at 3 time points during the erythroid differentiation of CD34+ and iPSCs isolated from the same subjects showed that only the long splice variant of ANTXR1 was expressed. Expression increased over time in CD34+ erythroid cells and decreased over time in iPSC-derived erythroid progenitors in a pattern similar to BCL11A expression, with increasing expression as CD34+ cells matured and HbF expression fell and declining expression as iPSCs differentiated and HbF expression increased. Immunofluorescence co-staining for ANTXR1 and HbF during the erythroid differentiation of sickle iPSCs showed that reduced expression of ANTXR1 was paralleled by increased expression of HbF. By GTEx analysis, eQTLs at rs4527238 and rs35685045 showed a trend for increased expression according to genotype with rs4527238 T/T having the lowest level of expression and T/C and C/C genotypes, higher expression levels (p= 0.08) and for rs35685045, C/C the lowest expression levels and C/T and T/T higher expression levels (p= 0.07); rs4527238 and rs35685045 had no effect on the expression of BCL11A, a repressor of HbF expression located at 2p16 (p=0.8). STRING 9.1 predicted protein interactions of ANTXR1 directly with LRP6, HDAC2, BCLX and BRAC1 with the highest level of confidence (0.95) with LRP6. The HbF phenotype in AI haplotype sickle cell anemia is unique and ANTXR1 is the first trans-acting element associated with HbF whose effects appear to be limited to the Saudi AI haplotype. ANTXR1 might have dual effects on HbF, indirectly affecting hematopoiesis via interactions with LRP6 and Wnt signaling, and directly modulating HBG expression through its effects on HDAC2. A dual effect on HbF expression has been suggested for MYB. Whether targeting ANTXR1 is a therapeutic option will require further studies. Disclosures No relevant conflicts of interest to declare.

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18

Yildiz, Onur, Elifcan Taşdelen, Taner Karakaya, and Harun Taşdelen. "Two siblings with GAPO syndrome: a novel missense variant in ANTXR1." Clinical Dysmorphology 31, no. 4 (August 26, 2022): 191–95. http://dx.doi.org/10.1097/mcd.0000000000000430.

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19

Puvvada, Soham D., Cassandra L. Love, Vladimir Grubor, Jenny Zhang, Jason Smith, and Sandeep S. Dave. "Pharmacogenetic Approaches Identify ANTXR1 As a Potential Mediator of Response to Therapeutic NF-κB Inhibition in Diffuse Large B Cell Lymphoma." Blood 118, no. 21 (November 18, 2011): 234. http://dx.doi.org/10.1182/blood.v118.21.234.234.

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Abstract Abstract 234 Background: NF-κB is a family of transcription factors known to play an essential role in the development & survival of lymphocytes. In recent years, it has been clear that aberrant NF-κB activation is a hallmark of various lymphoid malignancies and appears to be associated with chemotherapy resistance and adverse prognosis. The canonical NF-κB pathway is frequently engaged in lymphoid malignancies wherein activated IKK phosphorylates IκB proteins inducing IκB polyubiquination and subsequent proteasomal proteolytic degradation; this allows for release and nuclear translocation of NF-κB dimers to activate target gene transcription. Gene Expression Profiling (GEP) has identified two distinct sub groups of Diffuse Large B cell Lymphoma (DLBCL). While the Activated B cell (ABC) type shows constitutive activation of NF-κB, the role for NF-κB activation in Germinal Center B Cell (GCB) DLBCL is currently unclear. Since NF-κB inhibition has been identified as a therapeutic possibility in DLBCLs, it is important to define the role of this pathway and its modulators. In this study, we sought to investigate key regulators of the NF-κB pathway that might mediate a therapeutic response to IKKβ inhibition of NF-κB in DLBCL including the GCB subtype. Through GEP and Exome Sequencing, we demonstrate that ANTXR1 is a key mediator of response to IKKβ inhibition in DLBCL. Methods/Results: We obtained a novel selective inhibitor of IKKβ, TLX-2001 that has been found to be safe in animal models. IC50 were obtained on 61 cell lines representing various lymphomas including DLBCL (N=25) using cell viability MTT assays. The drug showed efficacy in both ABC and GCB DLBCL cell lines at physiologically achievable concentrations. These results were unsurprising in ABC DLBCLs which are known to depend on NF-κB activation, but the lethality of this selective drug in GCB DLBCLs was unexpected. To better understand the role of individual genes in the response in GCB DLBCLs, gene expression profiling was performed on 61 cell lines using Human Gene 1.0 ST Array. We found that ANTXR1 expression significantly correlated with NF-κB resistance (p = 0.035). Additionally, we sequenced the exomes of DLBCL tumors (N=95) and matched normal tissue (N=34). 95 cases of DLBCLs consisted of 73 cases of primary human DLBCLs and 22 DLBCL cell lines. Whole exome sequencing was performed using the Agilent solution-based system of exon capture to sequence all protein coding exons in the CCDS database. We identified 465 recurrently somatically mutated genes in these DLBCL cases, and found that mutation status of ANTXR1 was associated with high sensitivity to IKKβ inhibition (p =0.015) of NF-κB. Cell lines with non-synonymous mutations in ANTXR1 had over 3-fold lower IC50 (mean= 2.39 μM) compared to cell lines with no mutation in ANTXR1 (mean IC50 = 8.72μM). Discussion/Conclusion: ANTXR1 is the docking receptor for bacillus anthracis toxin, and anti-tumor responses have been observed in mice injected with recombinant engineered anthrax toxin. It is also known as TEM8 and maps to chromosome 2p13.1. Increased levels of TEM8 (tumor endothelial marker 8) have been noted in various malignancies including melanoma. Our data suggest that pharmacogenetic approaches that combine gene expression profiling and whole exome sequencing are useful tools for identifying novel genes that modulate therapeutic responses in lymphoma. Disclosures: No relevant conflicts of interest to declare.

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Hu, Kai, Bjorn R. Olsen, and Tatiana Y. Besschetnova. "Cell autonomous ANTXR1-mediated regulation of extracellular matrix components in primary fibroblasts." Matrix Biology 62 (October 2017): 105–14. http://dx.doi.org/10.1016/j.matbio.2016.12.002.

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21

Baek, Jong Min, Sung Chul Kwak, Kwon-Ha Yoon, Ju-Young Kim, and Myeung Su Lee. "Role of ANTXR1 in the regulation of RANKL-induced osteoclast differentiation and function." Biochemical and Biophysical Research Communications 510, no. 2 (March 2019): 296–302. http://dx.doi.org/10.1016/j.bbrc.2019.01.094.

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22

Sotoudeh, Masoud, Ramin Shakeri, Sanford M. Dawsey, Bahareh Sharififard, Naser Ahmadbeigi, and Mahmood Naderi. "ANTXR1 (TEM8) overexpression in gastric adenocarcinoma makes the protein a potential target of immunotherapy." Cancer Immunology, Immunotherapy 68, no. 10 (September 14, 2019): 1597–603. http://dx.doi.org/10.1007/s00262-019-02392-y.

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23

Chaudhary, Amit, Mary Beth Hilton, Steven Seaman, Diana C. Haines, Susan Stevenson, Peter K. Lemotte, William R. Tschantz, et al. "TEM8/ANTXR1 Blockade Inhibits Pathological Angiogenesis and Potentiates Tumoricidal Responses against Multiple Cancer Types." Cancer Cell 21, no. 2 (February 2012): 212–26. http://dx.doi.org/10.1016/j.ccr.2012.01.004.

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24

Salas-Alanís, Julio C., Claire A. Scott, Oscar R. Fajardo-Ramírez, Carola Duran, María G. Moreno-Treviño, and David P. Kelsell. "New ANTXR1 Gene Mutation for GAPO Syndrome: A Case Report." Molecular Syndromology 7, no. 3 (2016): 160–63. http://dx.doi.org/10.1159/000446619.

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Dinckan, Nuriye, Renqian Du, Zeynep C. Akdemir, Yavuz Bayram, Shalini N. Jhangiani, Harsha Doddapaneni, Jianhong Hu, et al. "A biallelic ANTXR1 variant expands the anthrax toxin receptor associated phenotype to tooth agenesis." American Journal of Medical Genetics Part A 176, no. 4 (February 13, 2018): 1015–22. http://dx.doi.org/10.1002/ajmg.a.38625.

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Byrd, Tiara T., Kristen Fousek, Antonella Pignata, Christopher Szot, Heba Samaha, Steven Seaman, Lacey Dobrolecki, et al. "TEM8/ANTXR1-Specific CAR T Cells as a Targeted Therapy for Triple-Negative Breast Cancer." Cancer Research 78, no. 2 (November 28, 2017): 489–500. http://dx.doi.org/10.1158/0008-5472.can-16-1911.

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Tran, Vien The, BaoChi Bui, Anh Quynh Ngoc Phan, An Le Pham, Lien Kim Thi Ha, Minh Van Hoang, Vien The Tran, and Phung Kim Thi Ngo. "16194 A GAPO syndrome case report: Identification of novel biallenic ANTXR1 variants cause GAPO syndrome." Journal of the American Academy of Dermatology 83, no. 6 (December 2020): AB56. http://dx.doi.org/10.1016/j.jaad.2020.06.312.

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Salles, Isabelle I., Daniel E. Voth, Sabrina C. Ward, Kathleen M. Averette, Rodney K. Tweten, Kenneth A. Bradley, and Jimmy D. Ballard. "Cytotoxic activity of Bacillus anthracis protective antigen observed in a macrophage cell line overexpressing ANTXR1." Cellular Microbiology 8, no. 8 (August 2006): 1272–81. http://dx.doi.org/10.1111/j.1462-5822.2006.00708.x.

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Vargas, Micaela, Raghavendra Karamsetty, Stephen H. Leppla, and G. Jilani Chaudry. "Broad Expression Analysis of Human ANTXR1/TEM8 Transcripts Reveals Differential Expression and Novel Splizce Variants." PLoS ONE 7, no. 8 (August 17, 2012): e43174. http://dx.doi.org/10.1371/journal.pone.0043174.

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Backer, Marina V., Vimal Patel, Brian T. Jehning, Kevin P. Claffey, Vladimir A. Karginov, and Joseph M. Backer. "Inhibition of Anthrax Protective Antigen Outside and Inside the Cell." Antimicrobial Agents and Chemotherapy 51, no. 1 (October 30, 2006): 245–51. http://dx.doi.org/10.1128/aac.00983-06.

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ABSTRACT In the course of Bacillus anthracis infection, B. anthracis lethal factor (LF) and edema factor bind to a protective antigen (PA) associated with cellular receptors ANTXR1 (TEM8) or ANTXR2 (CMG2), followed by internalization of the complex via receptor-mediated endocytosis. A new group of potential antianthrax drugs, β-cyclodextrins, has recently been described. A member of this group, per-6-(3-aminopropylthio)-β-cyclodextrin (AmPrβCD), was shown to inhibit the toxicity of LF in vitro and in vivo. In order to determine which steps in lethal factor trafficking are inhibited by AmPrβCD, we developed two targeted fluorescent tracers based on LFn, a catalytically inactive fragment of LF: (i) LFn site specifically labeled with the fluorescent dye AlexaFluor-594 (LFn-Al), and (ii) LFn-decorated liposomes loaded with the fluorescent dye 8-hydroxypyrene-1,3,6-trisulfonic acid (LFn-Lip). Both tracers retained high affinity to PA/ANTXR complexes and were readily internalized via receptor-mediated endocytosis. Using fluorescent microscopy, we found that AmPrβCD inhibits receptor-mediated cell uptake but not the binding of LFn-Al to PA/ANTXR complexes, suggesting that AmPrβCD works outside the cell. Moreover, AmPrβCD and LFn-Al synergistically protect RAW 264.7 cells from PA-mediated LF toxicity, confirming that AmPrβCD did not affect the binding of LFn-Al to receptor-associated PA. In contrast, AmPrβCD did not inhibit PA-mediated internalization of LFn-Lip, suggesting that multiplexing of LFn on the liposomal surface overcomes the inhibiting effects of AmPrβCD. Notably, internalized LFn-Al and LFn-Lip protected cells that overexpressed anthrax receptor TEM8 from PA-induced, LF-independent toxicity, suggesting an independent mechanism for PA inhibition inside the cell. These data suggest the potential for the use of β-cyclodextrins in combination with LFn-Lip loaded with antianthrax drugs against intracellular targets.

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Chattopadhyay, Esita, Sandip Ghose, Anindita Ray, Nishat Anjum, Anjana Mazumdar, and Bidyut Roy. "A novel mutation at ANTXR1 in an Indian patient with growth retardation–alopecia–pseudoanodontia–optic atrophy syndrome." Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 124, no. 5 (November 2017): e261-e265. http://dx.doi.org/10.1016/j.oooo.2017.07.009.

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Abdel‐Hamid, Mohamed S., Samira Ismail, Maha S. Zaki, Ghada M. H. Abdel‐Salam, Ghada A. Otaify, Mahmoud Y. Issa, Mohamed Abdel‐Kader, et al. "GAPO syndrome in seven new patients: Identification of five novel ANTXR1 mutations including the first large intragenic deletion." American Journal of Medical Genetics Part A 179, no. 2 (December 21, 2018): 237–42. http://dx.doi.org/10.1002/ajmg.a.61021.

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Bagaria, Jaya, Kyung-Ok Kim, Eva Bagyinszky, Seong Soo A. An, and Jeong-Heum Baek. "Discriminating Potential Genetic Markers for Complete Response and Non-Complete Response Patients to Neoadjuvant Chemotherapy with Locally Advanced Rectal Cancer." International Journal of Environmental Research and Public Health 19, no. 7 (March 28, 2022): 4008. http://dx.doi.org/10.3390/ijerph19074008.

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Background: Neoadjuvant chemoradiotherapy (nCRT) prior to surgery is considered standard therapy for locally advanced rectal cancer. Unfortunately, most patients with rectal cancer are resistant to radiotherapy. This might be a genetic cause. The role of certain rectal cancer-causing genes has not been completely elucidated. This study aims to investigate the genes responsible for locally advanced rectal cancer patients not reacting to radiotherapy. Methods: Whole exome sequencing of the DNA samples was performed on the samples. Bioinformatic analysis on the subjects was established. Individual genetic information was screened to identify differently expressed genes that more frequently appeared in non-complete response (NCR) compared to complete response (CR) patients after nCRT. All variations were verified by Sanger sequencing. Results: Genotyping information and pathway analyses of the samples indicated genes such as FLCN, CALML5, and ANTXR1 to be commonly mutated in CR group, whereas genes such as GALNTL14, CNKSR1, ACD, and CUL3 were more commonly mutated in the NCR group. Chi-square test revealed some significant variants (<0.05) such as rs3744124 (FLCN), rs28365986 (ANTXR1), rs10904516 (CALML5), rs3738952 (CUL3), rs13394 and rs2293013 (PIH1D1), rs2274531 (GPA33), rs4963048 (BRSK2), rs17883366 (IL3RA), rs2297575 (PSMD5), rs2288101 (GALNT14), and rs11954652 (DCTN4). Conclusion: Identifying an array of genes that separate NCRs from CRs would lead to finding genetic biomarkers for early detection of rectal cancer patients that are resistant to nCRT. A further investigation to validate the significance of genetic biomarkers to segregate NCRs from CRs should be performed with a larger CRC dataset. Protein expression levels, as well as transcriptomic analysis, would also help us understand the mechanism of how these genes could play a role in preventing radiation therapy to patients. This would be essential to prevent redundant radiation therapy.

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Sotoudeh, Masoud, Seyed Iman Shirvani, Shahin Merat, Naser Ahmadbeigi, and Mahmood Naderi. "MSLN (Mesothelin), ANTXR1 (TEM8), and MUC3A are the potent antigenic targets for CAR T cell therapy of gastric adenocarcinoma." Journal of Cellular Biochemistry 120, no. 4 (September 27, 2018): 5010–17. http://dx.doi.org/10.1002/jcb.27776.

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Pietrzyk, Łukasz, Agnieszka Korolczuk, Małgorzata Matysek, Marcin B. Arciszewski, and Kamil Torres. "Clinical Value of Detecting Tumor Endothelial Marker 8 (ANTXR1) as a Biomarker in the Diagnosis and Prognosis of Colorectal Cancer." Cancer Management and Research Volume 13 (April 2021): 3113–22. http://dx.doi.org/10.2147/cmar.s298165.

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Chen, Daohong, Poornima Bhat-Nakshatri, Chirayu Goswami, Sunil Badve, and Harikrishna Nakshatri. "ANTXR1, a Stem Cell-Enriched Functional Biomarker, Connects Collagen Signaling to Cancer Stem-like Cells and Metastasis in Breast Cancer." Cancer Research 73, no. 18 (July 5, 2013): 5821–33. http://dx.doi.org/10.1158/0008-5472.can-13-1080.

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Xu, Yuqiang, Kuikui Ge, Junhao Lu, Jinjiang Huang, Wei Wei, and Qingshan Huang. "MicroRNA-493 suppresses hepatocellular carcinoma tumorigenesis through down-regulation of anthrax toxin receptor 1 (ANTXR1) and R-Spondin 2 (RSPO2)." Biomedicine & Pharmacotherapy 93 (September 2017): 334–43. http://dx.doi.org/10.1016/j.biopha.2017.06.047.

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Si, Tao, Xuejian Ning, Haihui Chen, Zhengguo Hu, Linglu Dun, Na Zheng, Ping Huang, Liu Yang, and Ping Yi. "ANTXR1 as a potential prognostic biomarker for hepatitis B virus-related hepatocellular carcinoma identified by a weighted gene correlation network analysis." Journal of Gastrointestinal Oncology 12, no. 6 (December 2021): 3079–92. http://dx.doi.org/10.21037/jgo-21-764.

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Robert, Smigiel, Rozensztrauch Anna, Walczak Anna, Rydzanicz Małgorzata, Stawinski Piotr, Berghausen-Mazur Marta, Kostrzewa Grażyna, Sasiadek Malgorzata, and Ploski Rafal. "Changing facial features in a child with GAPO syndrome caused by novel mutation in the ANTXR1 gene and uniparental disomy of chromosome 2." Clinical Dysmorphology 28, no. 4 (October 2019): 211–14. http://dx.doi.org/10.1097/mcd.0000000000000292.

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40

Barua, Soumitra, Janaki K. Iyer, Jason L. Larabee, Brent Raisley, Molly A. Hughes, K. Mark Coggeshall, and Jimmy D. Ballard. "Toxin Inhibition of Antimicrobial Factors Induced by Bacillus anthracis Peptidoglycan in Human Blood." Infection and Immunity 81, no. 10 (July 22, 2013): 3693–702. http://dx.doi.org/10.1128/iai.00709-13.

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ABSTRACTHere, we describe the capacity ofBacillus anthracispeptidoglycan (BaPGN) to trigger an antimicrobial response in human white blood cells (WBCs). Analysis of freshly isolated human blood cells found that monocytes and neutrophils, but not B and T cells, were highly responsive to BaPGN and produced a variety of cytokines and chemokines. This BaPGN-induced response was suppressed by anthrax lethal toxin (LT) and edema toxin (ET), with the most pronounced effect on human monocytes, and this corresponded with the higher levels of anthrax toxin receptor 1 (ANTXR1) in these cells than in neutrophils. The supernatant from BaPGN-treated cells altered the growth ofB. anthracisSterne, and this effect was blocked by LT, but not by ET. An FtsX mutant ofB. anthracisknown to be resistant to the antimicrobial effects of interferon-inducible Glu-Leu-Arg (ELR)-negative CXC chemokines was not affected by the BaPGN-induced antimicrobial effects. Collectively, these findings describe a system in which BaPGN triggers expression of antimicrobial factors in human WBCs and reveal a distinctive role, not shared with ET, in LT's capacity to suppress this response.

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Durie, Brian GM, Julia Beck, Sundar Jagannath, Howard B. Urnovitz, and Ekkehard Schutz. "Personalized Genetic Monitoring of myeloma using analytic multivariate analysis of total Fully-Sequenced Circulating DNA." Blood 112, no. 11 (November 16, 2008): 5120. http://dx.doi.org/10.1182/blood.v112.11.5120.5120.

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Abstract There is no single sequence or breakpoint region linked to all patients with myeloma. It was thus elected to extract, amplify and fully sequence all (total) DNA present in circulating blood (CNA) using pyrosequencing with the Roche/454 sequencer (GSFLX). The origin of circulating DNA was investigated by local alignment analyses using BLAST and compared with the circulating DNA of 47 healthy individuals, aged 18 to 64 years. Thirty-one samples were subjected to total CNA sequencing during the course of the disease for a patient with lambda Bence Jones myeloma sequentially monitored from relapse, through complete response for 38 months and then with development of subsequent relapse. Conventional monitoring included both serum free light chain analyses and whole body CT-PET imaging. For comparative purposes the CNA was categorized by origin, functionality, chromosomal localization and genes, based on public databases (human reference genome build 36.2 and corresponding annotation file seq_gene.md as downloaded from NCBI (ftp.ncbi.nih.gov). The average length of sequenced nucleotides was 185.7 nucleotides and the total number of nucleotides sequenced per sample was 1.2 – 2.6 million. CNA sequences occurring with a frequency significantly greater or less than those observed for healthy controls were evaluated in detail. The next steps were to examine correlations with initial active myeloma, response to treatment, the complete remission state off all therapy, and subsequent relapse. The presence of 10 DNA sequences was highly correlated with the disease course: ZMYM2; TSPAN5; TLL1; PRKD1; ANTXR1; SYT14; PRKCH; MBNL1; EGFR and EDG7. Of these ZYMYM2 was highly correlated with disease reactivation and relapse off therapy. TSPAN5 showed a clear pattern with reduction to background levels during remission, but increase at the very earliest sign of relapse evident on CT-PET. Conversely, other sequences (GRID1; KIF16B) increased substantially during the peak impact of successful therapy. Multivariate analyses were used to identify the best combinations of gene sequences predictive of disease course and outcome. The combination of four genes (GRID1; PRKD1; ANTXR1; GAB1) was sufficient to define the early active disease data points vs the normal controls (odds-ratio OR: 135 [10.6 to 172]; p<.0001). When the resulting model was kept and used as a search engine for the whole 2 years course, the time course followed the treatment success (OR: 54; p=.0017) and failure as well as the final relapse(OR: 13.3; p=.004) In conclusion: Total sequencing of DNA has proved promising in providing personalized molecular monitoring for myeloma. The details of associated DNA sequences provide insights to the underlying molecular pathophysiology linked to myeloma disease progression, response to successful therapy as well as subsequent relapse. Further testing is ongoing.

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Li, Yamin, Lintao Han, Chunhua Huang, Wangqiang Dai, Guangyu Tian, Fang Huang, Jingjing Li, Jinwei Liu, Qiong Wang, and Zhenxiang Zhou. "New Contributions to Asarum Powder on Immunology Related Toxicity Effects in Lung." Evidence-Based Complementary and Alternative Medicine 2018 (September 2, 2018): 1–14. http://dx.doi.org/10.1155/2018/1054032.

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Objective. Asarum is widely used in clinical practice of Chinese medicine in the treatment of respiratory diseases. Many toxic ingredients (safrole, etc.) had been found in Asarum that show multiple visceral toxicities. In this study, we performed systematic investigation of expression profiles of genes to take a new insight into unclear mechanism of Asarum toxicities in lung. Methods. mRNAs were extracted from lungs of rats after intragastric administration with/without Asarum powders, and microarray assays were applied to investigate gene expression profiles. Differentially expressed genes with significance were selected to carry out GO analysis. Subsequently, quantitative PCRs were performed to verify the differential expression of Tmprss6, Prkag3, Nptx2, Antxr11, Klk11, Rag2, Olr77, Cd7, Il20, LOC69, C6, Ccl20, LOC68, and Cd163 in lung. Changes of Ampk, Bcl2, Caspase 3, Il1, Il20, Matriptase2, Nfκb, Nptx2, and Rag2 in the lung on protein level were verified by western blotting and immunohistochemistry. Results. Compared with control group, the estimated organ coefficients were relatively increased in Asarum group. Results of GO analysis showed that a group of immune related genes in lung were expressed abnormally. The result of PCRs showed that Ccl20 was downregulated rather than other upregulated genes in the Asarum group. Western blotting and immunohistochemistry images showed that Asarum can upregulate the expression of Ampk, Caspase 3, Il1, Il20, Matriptase2, Nfκb, and Rag2 and downregulate the expression of Bcl2 in lung. Conclusion. Our data suggest that expressions of immune related genes in lung were selectively altered by Asarum. Therefore, inflammatory response was active, by regulating Caspase 3, Il1, Il20, Matriptase2, Nfκb, Rag2, Tmprss6, Prkag3, Nptx2, Antxr1, Klk11, Olr77, Cd7, LOC69, C6, LOC68, Cd163, Ampk, Bcl2, and Ccl20. Our study indicated that inflammatory factors take effect in lung toxicity caused by Asarum, which provides a new insight into molecular mechanism of Asarum toxicities in lung.

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Dang, Xuhong, Haipeng Lin, Yayi Yuan, Biao Yang, Juancong Dong, Zhongxin Zhang, Kai Yang, et al. "Quantitative Proteomics Analysis of Differentially Expressed Proteins in Serum of Former Uranium Miners by Isobaric Tags for the Relative and Absolute Quantitation." Dose-Response 19, no. 4 (October 2021): 155932582110561. http://dx.doi.org/10.1177/15593258211056190.

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The carcinogenicity of radon has been convincingly documented through epidemiological studies of underground miners. However, there is a lack of early warning indicators for radon radiation damage. In this study, mixed serum samples of 3 groups were collected from 27 underground uranium miners and seven aboveground miners according to the radiation exposure dose. The differentially expressed proteins in the serum were identified using the isobaric tags for the relative and absolute quantitation (iTRAQ)-based method. Some differentially expressed proteins were validated by enzyme-linked immunosorbent assay (ELISA) in 84 underground and 32 aboveground miners. A total of 25 co-differentially expressed proteins in 2 underground miner groups were screened, of which 9 were downregulated and 13 were upregulated. Biological process analysis of these proteins using Metascape showed that 5 GO terms were enriched, such as negative regulation of very-low-density lipoprotein particle clearance, endocytosis, and regulated exocytosis. The results of the ELISA for the expression levels of GCN1, CIP2A, and IGHV1-24 in the serum of 116 miners’ serum showed that the levels of GCN1 and CIP2A were consistent with the iTRAQ results. In conclusion, APOC1, APOC2, APOC3, ORM1, ORM2, ANTXR1, GCN1, and CIP2A may be potential early markers of radon radiation damage.

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Knight, Jason M., Eunji Kim, Ivan Ivanov, Laurie A. Davidson, Jennifer S. Goldsby, Meredith A. J. Hullar, Timothy W. Randolph, et al. "Comprehensive site-specific whole genome profiling of stromal and epithelial colonic gene signatures in human sigmoid colon and rectal tissue." Physiological Genomics 48, no. 9 (September 1, 2016): 651–59. http://dx.doi.org/10.1152/physiolgenomics.00023.2016.

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The strength of associations between various exposures (e.g., diet, tobacco, chemopreventive agents) and colorectal cancer risk may partially depend on the complex interaction between epithelium and stroma across anatomic subsites. Currently, baseline data describing genome-wide coding and long noncoding gene expression profiles in the healthy colon specific to tissue type and location are lacking. Therefore, colonic mucosal biopsies from 10 healthy participants who were enrolled in a clinical study to evaluate effects of lignan supplementation on gut resiliency were used to characterize the site-specific global gene expression signatures associated with stromal vs. epithelial cells in the sigmoid colon and rectum. Using RNA-seq, we demonstrate that tissue type and location patterns of gene expression and upstream regulatory pathways are distinct. For example, consistent with a key role of stroma in the crypt niche, mRNAs associated with immunoregulatory and inflammatory processes (i.e., CXCL14, ANTXR1), smooth muscle contraction (CALD1), proliferation and apoptosis (GLP2R, IGFBP3), and modulation of extracellular matrix (MMP2, COL3A1, MFAP4) were all highly expressed in the stroma. In comparison, HOX genes (HOXA3, HOXD9, HOXD10, HOXD11, and HOXD-AS2, a HOXD cluster antisense RNA 2), and WNT5B expression were also significantly higher in sigmoid colon compared with the rectum. These findings provide strong impetus for considering colorectal tissue subtypes and location in future observational studies and clinical trials designed to evaluate the effects of exposures on colonic health.

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Kundu, Paramita, Ruchi Jain, Arivazhagan Arimappamagan, Vani Santosh, and Paturu Kondaiah. "GENE-51. ROLE OF TUMOR ENDOTHELIAL MARKER 8 (TEM8) IN PRIMARY AND RECURRENT GLIOBLASTOMA." Neuro-Oncology 21, Supplement_6 (November 2019): vi108—vi109. http://dx.doi.org/10.1093/neuonc/noz175.453.

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Abstract Glioblastoma (GBM) is the most common primary malignant tumor of the adult central nervous system. It is highly invasive and almost inevitably recurs; leading to a median survival of 15 months. The recurrent tumor in most cases is radiotherapy and chemotherapy-resistant, making them quite challenging to treat. Several studies have elucidated key driver genes and molecular pathways involved in Gliomagenesis, but genes/pathways that might be involved in aiding relapse are not well elucidated. Interestingly, chemotherapy with Temozolomide and γ-irradiation have been documented to alter the DNA methylome of cells in vitro. A probable hypothesis could be that following surgical resection, therapy alters the epigenome of residual cancer cells giving rise to aggressively resistant recurrent tumors. To examine this possibility, 24 GBM biopsies (11 primary and 13 recurrent GBMs) were subjected to Methylation Bead Array to assess differential methylation of genes in recurrent GBM compared to primary tumors. This was correlated with RNA-seq data for recurrent tumors in TCGA database. A total of 1751 differentially methylated regions (DMRs) were identified, among which 205 differentially methylated genes (74 hypomethylated and 131 hypermethylated) were found to correlate with methylation and RNA-sequencing data of recurrent tumors in TCGA. Among these genes, ANTXR1/TEM8 (Tumor Endothelial Marker 8) was found to be overexpressed in recurrent tumors compared to primary tumors at both transcript and protein levels using RT-PCR and immunohistochemistry, respectively. When overexpressed in Glioma cell lines, TEM8 was found to upregulate phospho-GSK3β, phospho-AKT and lead to β-catenin translocation to the nucleus resulting in activation of Wnt signaling pathway. TEM8 overexpressing cells showed mild enhancement in proliferation and resistance to Temozolomide, Cisplatin and 5-fluoroUracil. Stem cells markers like Oct4 and Nanog are also upregulated. In conclusion, TEM8 may be involved in GBM recurrence and may have a role in conferring chemo- and radioresistance.

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Harahap, Rubyanata, Wulan Tri Gartanti, and Dadi Ahmadi. "Komunikasi Antar Pribadi Antara Reseller dengan Produsen Cantiqa Kemiri." Inter Komunika : Jurnal Komunikasi 3, no. 2 (December 9, 2018): 137. http://dx.doi.org/10.33376/ik.v3i2.213.

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Abstract. Interpersonal communication among business people is very interesting because every individual in each generation will be different in how to communicate. In business cooperation between producers and product resellers, the means of conveying the intent in the expressed communication message will differ depending on the purpose of the message delivery and the purpose of the contents of the message itself. So that the influence between the communication intentions conveyed will encourage the communicator to be able to provide added value.Communication is the sending of a message from someone and is received by another person with immediate effects and feedback, so that not only aims to build effective communication in interpersonal communication but also wants to create an effect. In relation to interpersonal communication, res-sellers and producers carry out communication with the aim of creating effective communication in order to carry out good cooperation. This study examines interpersonal communication between Cantiqa Kemiri producers and resellers. This research uses descriptive method with data collection techniques through interviews, literature studies, and observations. Key informants in this study were Cantiqa Kemiri producers and resellers. The results of this study indicate that interpersonal communication between Cantiqa Kemiri producers and resellers involves several aspects such as openness, empathy, support, positive feelings, and equality in maintaining relationships between each other so that product sales remain optimal.Keywords: Communication, Interpersonal Communication, Cooperation, Business, Manufacturer, ResellerAbstrak. Komunikasi antarpribadi diantara para pelaku bisnis menjadi sangat menarik diperhatikan karena setiap individu dalam setiap generasi akan berbeda cara berkomunikasinya. Dalam kerjasama bisnis diantara produsen dan reseller produk, cara penyampaian maksud dalam pesan komunikasi yang diutarakan akan berbeda tergantung dari tujuan penyampaian pesan serta maksud dari isi pesan itu sendiri. Sehingga pengaruh diantara maksud komunikasi yang disampaikan akan mendorong pelaku komunikasi tersebut untuk bias memberikan nilai tambah. Komunikasi merupakan pengiriman pesan dari seseorang dan diterima oleh orang lain dengan efek dan umpan balik yang langsung, sehingga bukan hanya bertujuan membangun komunikasi yang efektif dalam komunikasi antarpribadi tetapi juga ingin menciptakan efek. Dalam kaitannya dengan komunikasi antarpribadi, reseller dan produsen menjalankan komunikasi dengan tujuan untuk menciptakan komunikasi yang efektif agar dapat melaksanakan kerjasama yang baik. Penelitian ini meneliti mengenai komunikasi antarpribadi antara produsen dan reseller Cantiqa Kemiri. Penelitian ini menggunakan metode deskriptif dengan teknik pengumpulan data melalui wawancara, studi kepustakaan, dan observasi. Key informan dalam penelitian ini adalah produsen dan reseller Cantiqa Kemiri. Hasil dari penelitian ini menunjukan bahwa komunikasi antarpribadi antara produsen dan reseller Cantiqa Kemiri melibatkan beberapa aspek seperti keterbukaan, empati, dukungan, rasa positif, dan kesetaraan dalam menjaga hubungan antara satu sama lain sehingga penjualan produk tetap optimal.Kata Kunci: Komunikasi, KomunikasiAntarpribadi, Kerjasama, Bisnis, Produsen, Reseller

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Filandow, Elisabeth, Kezia Kanaya Clairine, Hasim Asyari, and Fikra Asyrafi. "KORELASI ANTARA BUDAYA SUSAH ANTRE TERHADAP PENYEBARAN COVID-19 DI INDONESIA." Jurnal Kewarganegaraan 5, no. 2 (December 2, 2021): 578–85. http://dx.doi.org/10.31316/jk.v5i2.1939.

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Muarifah, Alif, and Intan Puspitasari. "HUBUNGAN ANTARA POLA ASUH DEMOKRATIS DAN KECERDASAN EMOSI DENGAN PERSAINGAN ANTAR SAUDARA." JURNAL PSIKOLOGI INSIGHT 2, no. 1 (July 12, 2018): 1–10. http://dx.doi.org/10.17509/insight.v2i1.11919.

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This research aimed to know the correlation between democratic parenting style and emotional intelligence with sibling rivalry. Sibling rivalry triggered by individual internal or external factors. In this research, democratic parenting style serve as individual external factor and emotional intelligence serve as individual internal factor for sibling rivalry. Participants in this study were selected by purposive sampling technique which are parents who have children in age of 7-8 years old. Quntitative method was used by distributing Democratic Parenting Style Scale, Emotional Intelligence Scale and Persaingan antar saudara Scale to the participants. Regression was used to understand the correlation between variables and its correlational strength. This research showed that there is significant negative correlation between democratic parenting style and emotional intelligence with sibling rivalry. Partially, democratic parenting style and sibling rivalry results correlation coefficient r = -0.196 meanwhile emotional intelligence and sibling rivalry results correlation coefficient r = -0.293. Regression analysis between variables shows R square (R2) valued of 0.88 (8.8%). This result shows that democratic parenting style and emotionl intelligence can explain the variable variances of sibling rivalry valued of 8.8% together.

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Lufiana, Dita Veni, Rina Febriana, and Suci Rahayu. "HUBUNGAN ANTARA KUALITAS MAKANAN DENGAN KEPUASAN PELANGGAN PENGGUNA LAYANAN PESAN ANTAR OJEK ONLINE." Jurnal Sains Boga 2, no. 1 (November 26, 2020): 7–11. http://dx.doi.org/10.21009/jsb.002.1.02.

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HUBUNGAN ANTARA KUALITAS MAKANAN DENGAN KEPUASAN PELANGGAN PENGGUNA LAYANAN PESAN ANTAR OJEK ONLINE (STUDI KASUS DI KANTIN BUNDA, KARAWANG) ABSTRAK Penelitian ini bertujuan untuk mengetahui hubungan antara kualitas makanan dengan kepuasan pelanggan pengguna layanan ojek online. Jenis penelitian ini adalah penelitian survey untuk mencari hubungan kausal antara variabe melalui pengujian hipotesis. Penelitian ini dilakukan dengan jumlah responden sebanyak 67 orang pelanggan yang melakukan pembelian lebih dari 3 kali di Kantin Bunda Karawang. Penganmilan sampel menggunakan teknik sampel randoom dengan menyebarkan kuesioner menggunakan google ddocs. Metode analisis data yang digunakan dalam penelitian ini adalah menggunakan uji korelasi, sedangkan untuk menguji hipotesis menggunakan uji korelasi spearman. Berdasarkan penelitian taraf kesalahan yang digunakan adalah 0,05. Hasil model analisis korelasi menunjukan terdapat huungan antara kualitas makanan dengan kepuasan pelanggan pengguna layanan pesan antar ojek online dengan nilai rho hitung 0,57 lebih besar dari rho tabel 0,20. Berdasarkan hasil perhitungan karena rho hitung lebih besar dari rho tabel maka dapat disimpulkan bahwa terdapat hubungan antara kualitas makanan dengan kepuasan pelanggan pengguna layanan pean antar ojek online. Kata kunci : Kualitas Makanan, Kepuasan Pelanggan, Layanan Pesan Antar Online RELATIONSHIP BETWEEN FOOD QUALITY AND CUSTOMER SATISFACTION ON ONLINE OJEK MESSAGE SERVICE (CASE STUDY IN KANTIN BUNDA, KARAWANG) ABSTRACT This study aims to determine the relationship between food quality and customer satisfaction of users of online motorcycle taxi services. This type of research is survey research to find causal relationships between variables through hypothesis testing. This study conducted with a total of 67 respondents who made purchases more than three times at the Kunda Bunda Karawang. Sampling using the Random sample technique by distributing questionnaires using Google Docs. Data analysis method used in this study is to use a correlation test, while to test the hypothesis using the Spearman correlation test. Based on the research the error level used was 0.05. The results of the correlation analysis model show that there is a relationship between the quality of food and customer satisfaction of users of messaging services between online motorbike taxi drivers with assisted rho values â€‹â€‹of 0.57 higher than rho table 0.20. Based on the results of the calculation because rho counts are more significant than rho table, it can be concluded that there is a relationship between food quality and customer satisfaction among service users among online motorbikes. Keywords: Food Quality, Customer Satisfaction, Online Delivery Service

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Sujadi, Eko, A. Muri Yusuf, and Marjohan Marjohan. "Hubungan antara Locus Of Control dan Efektivitas Komunikasi antar Pribadi dengan Problem Focused Coping." Konselor 5, no. 1 (March 30, 2016): 24. http://dx.doi.org/10.24036/02016516490-0-00.

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Problem focused coping need to be possessed by every individual. The purposes of this research were to described locus of control, the effectiveness of interpersonal communication, problem focused coping,the correlation between locus of control with problem focused coping, andthe correlationbetween the effectiveness of interpersonal communication with problem focused coping.This research was descriptive & correlation research by using quantitative approach. Data were collected through a Likert scale questionaire and locus of controlby using inventory Rotters Internal-External Locus of Control (I-E Scale), which was the validity and reliability has been tested. The data were analyzed by percentage technique and product moment correlation. The finding of research are: 1)locus of control were in the middle range between internal locus of control and external locus of control with an average as big as 11.46, 2) the general level of effectiveness of interpersonal communication is in high category, 3) the general level of problem focused coping is in high category, 4) there is correlation between locus of control withproblem focused coping, and 5) there is correlation betweeneffectiveness of interpersonal communicationwithproblem focused coping.

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