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What Ginseng Can Do For You
Published in Joseph P. Hou, The Healing Power of Ginseng, 2019
The cellular and molecular targets of ginsenosides against cancer have also been studied. It appears that several molecular mechanisms exist and collectively converge on various signaling pathways. These pathways include regulation of cell cycle, induction of apoptosis, inhibition of angiogenesis, prohibition of invasion, and reduction of inflammatory response. A series of cell cycle proteins, apoptosis-related proteins, growth factors, protein kinases, and transcription factors are affected by ginsenosides. For example, Rh2 and Rg3 inhibit cancer cell proliferation by inducing gene and protein expression of the cell cycle regulatory protein p21, thus arresting tumor cell cycle progression by inducing cancer cell apoptosis through activation of caspase-3 protease via a bel-2-insensitive pathway and by sensitizing multidrug-resistant tumor cells to chemotherapy. To characterize further downstream genes targeted by ginseng saponins such as Rg3 in a human cancer cell line, the gene expression profiling was assayed, showing that the most affected pathway was the Ephrin receptor pathway.
Applications of imaging genomics beyond oncology
Published in Ruijiang Li, Lei Xing, Sandy Napel, Daniel L. Rubin, Radiomics and Radiogenomics, 2019
Xiaohui Yao, Jingwen Yan, Li Shen
GWAS has been performed in case-control studies to evaluate the associations of genetic variations such as SNPs with AD using categorical diagnosis as the phenotype. These studies have identified a number of susceptible loci, including complement C3b/C4b receptor 1 (CR1), clusterin (CLU), and phosphatidylinositol binding clathrin assembly protein (PICALM) [27], epistatic interaction between transferrin (TF) and hemochromatosis gene (HFE) [28], apolipoprotein E (APOE), and methylenetetrahydrofolate dehydrogenase (NADP + dependent) 1 like (MTHFD1L) [29], CR1 [30], membrane-spanning 4-domain family, subfamily A (MS4A) gene cluster [31], ATP binding cassette subfamily A member 7 (ABCA7), membrane spanning 4-domains A6A (MS4A6A)/membrane spanning 4-domains A4E (MS4A4E), Ephrin receptor A1 (EPHA1), CD33 molecule (CD33) and CD2 associated protein (CD2AP) [32], bridging integrator 1 (BIN1) [33], MS4A4/MS4A6E, CD2AP, CD33, and EPHA [34].
Imaging Angiogenesis
Published in George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos, Handbook of Small Animal Imaging, 2018
Several other potential avenues to assess angiogenic process in both the cardiovascular system and tumor have been recently proposed. These include the detection of HIF-1a activation, monitoring of the influx of blood-derived macrophages, monocytes, or circulating endothelial precursor cells, and expression of other markers involved in the maturation of developed neovasculature, such as ephrins, ephrin receptors, and semaphorins. Specifically, both monocytes and circulating endothelial precursor cells have been found to play pivotal roles in the stimulation of new vessel growth by releasing growth factors, proteases, and chemokines, which contribute not only to the angiogenesis but also to the collateral growth by recruiting other circulating cells such as T cells and bone-marrow-derived cells. Finally, tissue-derived stem cells and paracrine functions of other pluripotent progenitor cells also play an integral role in the cascade of events leading to both angiogenesis and arteriogenesis (Fam et al. 2003; Iagaru and Gambhir 2013).
Proteomic approaches to assist in diagnosis and prognosis of oral cancer
Published in Expert Review of Proteomics, 2021
Jamile De Oliveira Sá, Luciana Daniele Trino, Ana Karina Oliveira, Ariane Fidelis Busso Lopes, Daniela Campos Granato, Ana Gabriela Costa Normando, Erison Santana Santos, Leandro Xavier Neves, Carolina Moretto Carnielli, Adriana Franco Paes Leme
EVs isolated from the PE/CA-PJ49/E10 OSCC cell line were shown to highly express proteins involved in angiogenesis, proliferation, migration, and adhesion, especially EGFR and ITGB4 [69]. The proteome associated with angiogenesis was prioritized in EVs from 3 HNSCC cells, including two oral cancer cell lines – SCC61 and OSC19, and a pharynx cell line – Detroit 562 [70]. Label-free MS revealed 1,016 and 1,237 unique proteins in OSC19 and Detroit 562-EVs, respectively. The proteome from SCC61-derived EVs was retrieved from the literature [71]. Several ephrins and ephrin receptors (Eph) family proteins were detected in vesicles from the three cells, and analysis revealed EPHB2 as a promising candidate to have a role in EV-mediated angiogenesis. Further experiments confirmed that EPHB2 expression in HNSCC cells promotes tumor angiogenesis in an orthotopic mouse model and suggest that EPHB2 may recruit blood vessels into tumors, facilitating tumor survival and promoting metastasis.
Antitumor activity of the third generation EphA2 CAR-T cells against glioblastoma is associated with interferon gamma induced PD-L1
Published in OncoImmunology, 2021
Zhijing an, Yi Hu, Yue Bai, Can Zhang, Chang Xu, Xun Kang, Shoubo Yang, Wenbin Li, Xiaosong Zhong
Several GBM-CAR-T therapy candidate targets have been examined for evaluating their feasibility and reliability, such as IL-13 receptor subunit alpha 2 (IL13Ra2), human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor variant III (EGFRvIII), which have exhibited encouraging anti-tumor effects.12,20,21 Ephrin type-A receptor 2 (EphA2) is a member of the ephrin receptor family and plays important roles in a diverse array of developmental, physiological, and disease processes. Recent studies have indicated that EphA2 overexpression is associated with a poor prognosis in multiple types of tumors, such as esophageal, ovarian, and lung cancers.22,23 EphA2 is overexpressed in GBM, although poorly expressed in the normal brain, making it an attractive target for the development of novel therapeutic strategies.24–26 At present, at least two independent groups have developed different EphA2 specific CARs to treat GBM and obtained encouraging pre-clinical results.27–29
Lithium-induced gene expression alterations in two peripheral cell models of bipolar disorder
Published in The World Journal of Biological Psychiatry, 2019
Sarah Kittel-Schneider, Max Hilscher, Claus-Jürgen Scholz, Heike Weber, Lena Grünewald, Ricarda Schwarz, Andreas G. Chiocchetti, Andreas Reif
EPHB1 codes for a protein called Ephrin type B receptor 1. Ephrin receptors and their ligands, the ephrins, play a role in numerous developmental processes, also in the central nervous system. Ephrin receptors are part of the receptor tyrosine kinase family (Flanagan and Vanderhaeghen 1998). Furthermore, they seem to play a role in inflammatory and neuropathic pain (Cibert-Goton et al. 2013). Most interestingly, in our study, lithium treatment showed to have opposing effects in cells of bipolar patients and controls. EPHB1 expression was upregulated in control cells and downregulated in bipolar cells due to lithium treatment. In the GWAS data sets, a single-nucleotide polymorphism of EPBH1 gene (rs66745619) has been shown to be associated with BD and other single-nucleotide polymorphisms in EPHB1 (rs7635276, rs7613488 and rs35879719) were associated with lithium response in the ConLiGen GWAS dataset. To clarify the underlying molecular processes, further studies are needed.