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1

Du, Longhai, Yanlong Xu, Binxu Han, et al. "EGFR-targeting peptide conjugated polymer–lipid hybrid nanoparticles for delivery of salinomycin to osteosarcoma." Journal of Cancer Research and Therapeutics 19, no. 6 (2023): 1544–51. http://dx.doi.org/10.4103/jcrt.jcrt_2503_22.

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Context: Salinomycin (SAL) is a chemotherapeutic drug with anti-osteosarcoma efficacy, but its hydrophobic properties have hindered its application. Nanoparticles have been widely used as drug carriers to improve the solubility of hydrophobic drugs. The dodecapeptide GE11 has been shown to have great binding affinity to the epidermal growth factor receptor (EGFR), which is highly overexpressed in osteosarcoma. Materials and Methods: We designed novel SAL-loaded GE11-conjugated polymer–lipid hybrid nanoparticles (GE11-NPs-SAL) to target osteosarcoma. The characterization and antitumor activity of GE11-NPs-SAL were evaluated both in vitro and in vivo. Results: The results showed that GE11-NPs-SAL had a size of ~100 nm with a high encapsulation efficacy of ~80%. Compared with the non-targeted nanoparticles, GE11-NPs-SAL showed increased internalization in osteosarcoma cells and improved therapeutic efficacy in osteosarcoma both in vitro and in vivo. Conclusions: GE11-NPs-SAL is a promising treatment for osteosarcoma.
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2

Chiesa, Enrica, Silvia Pisani, Barbara Colzani, et al. "Intra-Articular Formulation of GE11-PLGA Conjugate-Based NPs for Dexamethasone Selective Targeting—In Vitro Evaluation." International Journal of Molecular Sciences 19, no. 8 (2018): 2304. http://dx.doi.org/10.3390/ijms19082304.

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Selectively targeted nanoscale drug delivery systems have recently emerged as promising intravenously therapeutic option for most chronic joint diseases. Here, a newly synthetized dodecapeptide (GE11)-polylactide-co-glycolide (PLGA)-based conjugate was used to prepare smart nanoparticles (NPs) intended for intra-articular administration and for selectively targeting Epidermal Growth Factor Receptor (EGFR). GE11-PLGA conjugate-based NPs are specifically uptaken by EGFR-overexpressed fibroblast; such as synoviocytes; which are the primarily cellular component involved in the development of destructive joint inflammation. The selective uptake could help to tune drug effectiveness in joints and to decrease local and systemic side effects. Dexamethasone (DXM) is a glucorticoid drug commonly used in joint disease treatment for both systemic and local administration route. In the present research; DXM was efficiently loaded into GE11-PLGA conjugate-based NPs through an eco-friendly nanoprecipitation method set up for this purpose. DXM loaded GE11-PLGA conjugate-based NPs revealed satisfactory ex vivo cytocompatibility; with proper size (≤150 nm) and good dimensional stability in synovial fluid. Intra-articular formulation was developed embedding DXM loaded GE11-PLGA conjugate-based NPs into thermosetting chitosan-based hydrogel; forming a biocompatible composite hydrogel able to quickly turn from liquid state into gel state at physiological temperature; within 15 min. Moreover; the use of thermosetting chitosan-based hydrogel extends the local release of active agent; DXM.
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3

Gaurav, Isha, Abhimanyu Thakur, Kui Zhang, et al. "Peptide-Conjugated Vascular Endothelial Extracellular Vesicles Encapsulating Vinorelbine for Lung Cancer Targeted Therapeutics." Nanomaterials 14, no. 20 (2024): 1669. http://dx.doi.org/10.3390/nano14201669.

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Lung cancer is one of the major cancer types and poses challenges in its treatment, including lack of specificity and harm to healthy cells. Nanoparticle-based drug delivery systems (NDDSs) show promise in overcoming these challenges. While conventional NDDSs have drawbacks, such as immune response and capture by the reticuloendothelial system (RES), extracellular vesicles (EVs) present a potential solution. EVs, which are naturally released from cells, can evade the RES without surface modification and with minimal toxicity to healthy cells. This makes them a promising candidate for developing a lung-cancer-targeting drug delivery system. EVs isolated from vascular endothelial cells, such as human umbilical endothelial-cell-derived EVs (HUVEC-EVs), have shown anti-angiogenic activity in a lung cancer mouse model; therefore, in this study, HUVEC-EVs were chosen as a carrier for drug delivery. To achieve lung-cancer-specific targeting, HUVEC-EVs were engineered to be decorated with GE11 peptides (GE11-HUVEC-EVs) via a postinsertional technique to target the epidermal growth factor receptor (EGFR) that is overexpressed on the surface of lung cancer cells. The GE11-HUVEC-EVs were loaded with vinorelbine (GE11-HUVEC-EVs-Vin), and then characterized and evaluated in in vitro and in vivo lung cancer models. Further, we examined the binding affinity of ABCB1, encoding P-glycoprotein, which plays a crucial role in chemoresistance via the efflux of the drug. Our results indicate that GE11-HUVEC-EVs-Vin effectively showed tumoricidal effects against cell and mouse models of lung cancer.
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4

Huang, Xueqin, Lingzhi Chen, Yuping Zhang, et al. "GE11 Peptide Conjugated Liposomes for EGFR-Targeted and Chemophotothermal Combined Anticancer Therapy." Bioinorganic Chemistry and Applications 2021 (March 31, 2021): 1–15. http://dx.doi.org/10.1155/2021/5534870.

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How to actively target tumor sites manipulating the controllable release of the encapsulated anticancer drugs and photosensitizers for synergistic anticancer therapy remains a big challenge. In this study, a cancer cell-targeted, near-infrared (NIR) light-triggered and anticancer drug loaded liposome system (LPs) was developed for synergistic cancer therapy. Photosensitizer indocyanine green (ICG) and chemotherapy drug Curcumin (CUR) were coencapsulated into the liposomes, followed by the surface conjugation of GE11 peptide for epidermal growth factor receptor (EGFR) targeting on the cancer cell surface. Strictly controlled by NIR light, GE11 peptide modified and CUR/ICG-loaded LPs (GE11-CUR/ICG-LPs) could introduce hyperthermia in EGFR overexpressed A549 cancer cells for photothermal therapy, which could also trigger the increased release of CUR for enhanced cancer cell inhibition. GE11-CUR/ICG-LPs synergized photochemotherapy could induce reactive oxygen species (ROS) generation and cytoskeleton disruption to activate stronger apoptotic signaling events than the photothermal therapy or chemotherapy alone by regulating Bax/Bcl-2 and PI3K/AKT pathways. This EGFR-targeted drug-delivery nanosystem with NIR sensitivity may potentially serve in more effective anticancer therapeutics with reduced off-target effects.
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5

Li, Kaichun, Liying Pang, Xiaorong Pan, et al. "GE11 Modified PLGA/TPGS Nanoparticles Targeting Delivery of Salinomycin to Breast Cancer Cells." Technology in Cancer Research & Treatment 20 (January 1, 2021): 153303382110049. http://dx.doi.org/10.1177/15330338211004954.

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Salinomycin (Sal) is a potent inhibitor with effective anti-breast cancer properties in clinical therapy. The occurrence of various side effect of Sal greatly limits its application. The epidermal growth factor receptor (EGFR) family is a family of receptors highly expressed in most breast cancer cells. GE11 is a dodecapeptide which shows excellent EGFR affinity. A series of nanoparticles derivatives with GE11 peptide conjugated PLGA/TPGS were synthesized. Nanoprecipitation method was used to prepare the Sal loaded nanoparticles at the optimized concentration. The characterization, targeting efficacy, and antitumor activity were detected both in vitro and in vivo. Encapsulation of Sal in GE11 modified PLGA/TPGS nanoparticles shows an improved therapy efficacy and lower systemic side effect. This represents the delivery system a promising strategy to enhance the therapeutic effect against EGFR highly expressed breast cancer.
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6

Gimond, Clotilde, Arjan van der Flier, Sanne van Delft та ін. "Induction of Cell Scattering by Expression of β1 Integrins in β1-Deficient Epithelial Cells Requires Activation of Members of the Rho Family of Gtpases and Downregulation of Cadherin and Catenin Function". Journal of Cell Biology 147, № 6 (1999): 1325–40. http://dx.doi.org/10.1083/jcb.147.6.1325.

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Adhesion receptors, which connect cells to each other and to the surrounding extracellular matrix (ECM), play a crucial role in the control of tissue structure and of morphogenesis. In this work, we have studied how intercellular adhesion molecules and β1 integrins influence each other using two different β1-null cell lines, epithelial GE11 and fibroblast-like GD25 cells. Expression of β1A or the cytoplasmic splice variant β1D, induced the disruption of intercellular adherens junctions and cell scattering in both GE11 and GD25 cells. In GE11 cells, the morphological change correlated with the redistribution of zonula occluden (ZO)-1 from tight junctions to adherens junctions at high cell confluency. In addition, the expression of β1 integrins caused a dramatic reorganization of the actin cytoskeleton and of focal contacts. Interaction of β1 integrins with their respective ligands was required for a complete morphological transition towards the spindle-shaped fibroblast-like phenotype. The expression of an interleukin-2 receptor (IL2R)-β1A chimera and its incorporation into focal adhesions also induced the disruption of cadherin-based adhesions and the reorganization of ECM–cell contacts, but failed to promote cell migration on fibronectin, in contrast to full-length β1A. This indicates that the disruption of cell–cell adhesion is not simply the consequence of the stimulated cell migration. Expression of β1 integrins in GE11 cells resulted in a decrease in cadherin and α-catenin protein levels accompanied by their redistribution from the cytoskeleton-associated fraction to the detergent-soluble fraction. Regulation of α-catenin protein levels by β1 integrins is likely to play a role in the morphological transition, since overexpression of α-catenin in GE11 cells before β1 prevented the disruption of intercellular adhesions and cell scattering. In addition, using biochemical activity assays for Rho-like GTPases, we show that the expression of β1A, β1D, or IL2R-β1A in GE11 or GD25 cells triggers activation of both RhoA and Rac1, but not of Cdc42. Moreover, dominant negative Rac1 (N17Rac1) inhibited the disruption of cell–cell adhesions when expressed before β1. However, all three GTPases might be involved in the morphological transition, since expression of either N19RhoA, N17Rac1, or N17Cdc42 reversed cell scattering and partially restored cadherin-based adhesions in GE11-β1A cells. Our results indicate that β1 integrins regulate the polarity and motility of epithelial cells by the induction of intracellular molecular events involving a downregulation of α-catenin function and the activation of the Rho-like G proteins Rac1 and RhoA.
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7

Gé, Lorraine Gaenaelle, Mathias Bogetoft Danielsen, Aaraby Yoheswaran Nielsen, et al. "Radiocobalt-Labeling of a Polypyridylamine Chelate Conjugated to GE11 for EGFR-Targeted Theranostics." Molecules 30, no. 2 (2025): 212. https://doi.org/10.3390/molecules30020212.

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The overexpression of the epidermal growth factor receptor (EGFR) in certain types of prostate cancers and glioblastoma makes it a promising target for targeted radioligand therapy. In this context, pairing an EGFR-targeting peptide with the emerging theranostic pair comprising the Auger electron emitter cobalt-58m (58mCo) and the Positron Emission Tomography-isotope cobalt-55 (55Co) would be of great interest for creating novel radiopharmaceuticals for prostate cancer and glioblastoma theranostics. In this study, GE11 (YHWYGYTPQNVI) was investigated for its EGFR-targeting potential when conjugated using click chemistry to N1-((triazol-4-yl)methyl)-N1,N2,N2-tris(pyridin-2-ylmethyl)ethane-1,2-diamine (TZTPEN). This chelator is suitable for binding Co2+ and Co3+. With cobalt-57 (57Co) serving as a surrogate radionuclide for 55/58mCo, the novel GE11-TZTPEN construct was successfully radiolabeled with a high radiochemical yield (99%) and purity (>99%). [57Co]Co-TZTPEN-GE11 showed high stability in PBS (pH 5) and specific uptake in EGFR-positive cell lines. Disappointingly, no tumor uptake was observed in EGFR-positive tumor-bearing mice, with most activity being accumulated predominantly in the liver, gall bladder, kidneys, and spleen. Some bone uptake was also observed, suggesting in vivo dissociation of 57Co from the complex. In conclusion, [57Co]Co-TZTPEN-GE11 shows poor pharmacokinetics in a mouse model and is, therefore, not deemed suitable as a targeting radiopharmaceutical for EGFR.
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8

Yang, Chengcheng, Xuan Mi, Huilan Su, et al. "GE11-PDA-Pt@USPIOs nano-formulation for relief of tumor hypoxia and MRI/PAI-guided tumor radio-chemotherapy." Biomaterials Science 7, no. 5 (2019): 2076–90. http://dx.doi.org/10.1039/c8bm01492b.

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9

Lee, Duhwan, Yeong Mi Lee, Jihoon Kim, Myung Kyu Lee, and Won Jong Kim. "Enhanced tumor-targeted gene delivery by bioreducible polyethylenimine tethering EGFR divalent ligands." Biomaterials Science 3, no. 7 (2015): 1096–104. http://dx.doi.org/10.1039/c5bm00004a.

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10

Gaugaz, Fabienne, Andrea Chicca, Mariano Redondo-Horcajo, Isabel Barasoain, J. Díaz, and Karl-Heinz Altmann. "Synthesis, Microtubule-Binding Affinity, and Antiproliferative Activity of New Epothilone Analogs and of an EGFR-Targeted Epothilone-Peptide Conjugate." International Journal of Molecular Sciences 20, no. 5 (2019): 1113. http://dx.doi.org/10.3390/ijms20051113.

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A new simplified, epoxide-free epothilone analog was prepared incorporating an N-(2-hydroxyethyl)-benzimidazole side chain, which binds to microtubules with high affinity and inhibits cancer cell growth in vitro with nM potency. Building on this scaffold, a disulfide-linked conjugate with the purported EGFR-binding (EGFR, epidermal growth factor receptor) peptide GE11 was then prepared. The conjugate retained significant microtubule-binding affinity, in spite of the size of the peptide attached to the benzimidazole side chain. The antiproliferative activity of the conjugate was significantly lower than for the parent scaffold and, surprisingly, was independent of the EGFR expression status of cells. Our data indicate that the disulfide-based conjugation with the GE11 peptide is not a viable approach for effective tumor-targeting of highly potent epothilones and probably not for other cytotoxics.
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11

Abourbeh, Galith, Alexei Shir, Eyal Mishani, et al. "PolyIC GE11 polyplex inhibits EGFR-overexpressing tumors." IUBMB Life 64, no. 4 (2012): 324–30. http://dx.doi.org/10.1002/iub.1002.

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12

Oertel, F., F. Starke, W. Sihver, J. Steinbach, and H. J. Pietzsch. "In vitro evaluation of 64Cu-labeled GE11-conjugates." Nuclear Medicine and Biology 41, no. 7 (2014): 634–35. http://dx.doi.org/10.1016/j.nucmedbio.2014.05.035.

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13

Judmann, Benedikt, Björn Wängler, Ralf Schirrmacher, Gert Fricker, and Carmen Wängler. "Towards Radiolabeled EGFR-Specific Peptides: Alternatives to GE11." Pharmaceuticals 16, no. 2 (2023): 273. http://dx.doi.org/10.3390/ph16020273.

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The human epidermal growth factor receptor (EGFR) is closely related to several cancer-promoting processes and overexpressed on a variety of tumor types, rendering it an important target structure for the imaging and therapy of several malignancies. To date, approaches to develop peptidic radioligands able to specifically address and visualize EGFR-positive tumors have been of limited success. Most of the attempts were based on the lead GE11, as this peptide was previously described to be a highly potent EGFR-specific agent. However, since it has recently been shown that GE11 exhibits an insufficient affinity to the EGFR in monomeric form to be suitable as a basis for the development of tracers based on it, in the present work we investigated which other peptides might be suitable as lead structures for the development of EGFR-specific peptidic radiotracers. For this purpose, we developed 68Ga-labeled radioligands based on the peptides D4, P1, P2, CPP, QRH, EGBP and Pep11, having been described before as EGFR-specific. In addition, we also tested three truncated versions of the endogenous EGFR ligand hEGF (human epidermal growth factor) with respect to their ability to specifically target the EGFR with high affinity. Therefore, chelator-modified labeling precursors of the mentioned peptides were synthesized, radiolabeled with 68Ga and the obtained radioligands were evaluated for their hydrophilicity/lipophilicity, stability against degradation by human serum peptidases, in vitro tumor cell uptake, and receptor affinity in competitive displacement experiments on EGFR-positive A431 cells. Although all NODA-GA-modified (NODA-GA: (1,4,7-triazacyclononane-4,7-diyl)diacetic acid-1-glutaric acid) labeling precursors could be obtained more or less efficient in yields between 5 and 74%, the 68Ga-radiolabeling proved to be unsuccessful for two of the three truncated versions of hEGF ([68Ga]Ga-8 and [68Ga]Ga-9), producing several side-products. For the other agents [68Ga]Ga-1–[68Ga]Ga-7, [68Ga]Ga-10 and [68Ga]Ga-11, high radiochemical yields and purities of ≥ 98% and molar activities of up to 114 GBq/µmol were obtained. In the assay investigating the radiopeptide susceptibilities against serum peptidase degradation, the EGBP-based agent demonstrated a limited stability with a half-life of only 66.4 ± 3.0 min, whereas the other tracers showed considerably higher stabilities of up to an 8000 min half-life. Finally, all radiotracer candidates were evaluated in terms of tumor cell internalization and receptor binding potential on EGFR-positive A431 cell. In these experiments, all developed agents failed to show an EGFR-specific tumor cell uptake or a relevant EGFR-affinity. By contrast, the positive controls tested under identical conditions, [125I]I-hEGF and hEGF demonstrated the expected high EGFR-specific tumor cell uptake (33.6% after 1 h, being reduced to 1.9% under blocking conditions) and affinity (IC50 value of 15.2 ± 3.3 nM). Thus, these results indicate that none of the previously described peptidic agents developed for EGFR targeting appears to be a reasonable choice as a lead structure for the development of radiopeptides for targeting of EGFR-positive tumors. Likewise, the tested truncated variants of the endogenous hEGF do not seem to be promising alternatives for this purpose.
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14

Luo, H. B., X. B. Li, Q. E. Zhang, M. D. Chen, and Y. K. Cheng. "A density functional theory study of germanium Ge11 clusters." Journal of Molecular Structure: THEOCHEM 674, no. 1-3 (2004): 83–86. http://dx.doi.org/10.1016/j.theochem.2004.01.010.

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15

Soleymani Abyaneh, Hoda, Amir Soleimani, Mohammad Vakili, et al. "Modulation of Hypoxia-Induced Chemoresistance to Polymeric Micellar Cisplatin: The Effect of Ligand Modification of Micellar Carrier Versus Inhibition of the Mediators of Drug Resistance." Pharmaceutics 10, no. 4 (2018): 196. http://dx.doi.org/10.3390/pharmaceutics10040196.

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Hypoxia can induce chemoresistance, which is a significant clinical obstacle in cancer therapy. Here, we assessed development of hypoxia-induced chemoresistance (HICR) against free versus polymeric cisplatin micelles in a triple negative breast cancer cell line, MDA-MB-231. We then explored two strategies for the modulation of HICR against cisplatin micelles: a) the development of actively targeted micelles; and b) combination therapy with modulators of HICR in MDA-MB-231 cells. Actively targeted cisplatin micelles were prepared through surface modification of acetal-poly(ethylene oxide)-poly(α-carboxyl-ε-caprolactone) (acetal-PEO-PCCL) micelles with epidermal growth factor receptor (EGFR)-targeting peptide, GE11 (YHWYGYTPQNVI). Our results showed that hypoxia induced resistance against free and cisplatin micelles in MDA-MB-231 cells. A significant increase in micellar cisplatin uptake was observed in MDA-MB-231 cells that overexpress EGFR, following surface modification of micelles with GE11. This did not lead to increased cytotoxicity of micellar cisplatin, however. On the other hand, the addition of pharmacological inhibitors of key molecules involved in HICR in MDA-MB-231 cells, i.e., inhibitors of hypoxia inducing factor-1 (HIF-1) and signal transducer and activator of transcription 3 (STAT3), substantially enhanced the cytotoxicity of free and cisplatin micelles. The results indicated the potential benefit of combination therapy with HIF-1 and STAT3 inhibitors in overcoming HICR to free or micellar cisplatin.
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16

Verwilligen, Piet. "GEM detectors for the CMS endcap muon system: status of three new detector stations." Journal of Instrumentation 18, no. 07 (2023): C07006. http://dx.doi.org/10.1088/1748-0221/18/07/c07006.

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Abstract The High-Luminosity LHC (HL-LHC, or Phase-2 LHC) will deliver proton-proton collisions at 5–7.5 times the nominal LHC luminosity, with an expected number of 140–200 pp-interactions per bunch crossing (Pile-up or PU). To maintain the performance of muon triggering and reconstruction under high background, the forward part of the Muon Spectrometer of the CMS experiment will be upgraded with Gas Electron Multipliers (GEM) and improved Resistive Plate Chambers (iRPC) detectors [1,2]. A first GEM station (GE1/1) was installed during Long Shutdown 2 (LS2, 2019–2021), a 2nd station (GE2/1) of Triple-GEM detectors will be installed in winter 2023–24 and 2024–25, while a new 6-layer station (ME0) will be installed in the third Long Shutdown (LS3, 2026–2028). GE11 is considered an early Phase-2 upgrade as it will reduce the pT threshold by combining GEM and Cathode Strip Chamber (CSC) hits in the forward muon system at twice the LHC design luminosity (ℒ = 2 · 1034 cm-2 s-1, 50 PU). After a successful start of Run-3 in 2022, with almost 40 fb-1 collected, the commissioning of the GE1/1 detector is nearly complete. Most chambers are operated stably with an efficiency in excess of 95%, next being the demonstration of the combined CSC-GEM trigger in 2023. The lessons learnt with the first large-area GEM station have lead to improvements in detector and electronics design for the Phase 2 detectors GE2/1 and ME0. This proceeding will discuss the progress made since last MPGD Conference (MPGD 2019) [3], discussing the commissioning and early performance of GE1/1; the design improvements and start of construction of GE2/1; and the R&D currently ongoing for ME0.
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17

Quinn, Jeffrey A., C. Thomas Graeber, A. Raymond Frackelton, Minsoo Kim, Jean E. Schwarzbauer, and Edward J. Filardo. "Coordinate Regulation of Estrogen-Mediated Fibronectin Matrix Assembly and Epidermal Growth Factor Receptor Transactivation by the G Protein-Coupled Receptor, GPR30." Molecular Endocrinology 23, no. 7 (2009): 1052–64. http://dx.doi.org/10.1210/me.2008-0262.

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Abstract Estrogen promotes changes in cytoskeletal architecture not easily attributed to the biological action of estrogen receptors, ERα and ERβ. The Gs protein-coupled transmembrane receptor, GPR30, is linked to specific estrogen binding and rapid estrogen-mediated release of heparin-bound epidermal growth factor. Using marker rescue and dominant interfering mutant strategies, we show that estrogen action via GPR30 promotes fibronectin (FN) matrix assembly by human breast cancer cells. Stimulation with 17β-estradiol or the ER antagonist, ICI 182, 780, results in the recruitment of FN-engaged integrin α5β1 conformers to fibrillar adhesions and the synthesis of FN fibrils. Concurrent with this cellular response, GPR30 promotes the formation of Src-dependent, Shc-integrin α5β1 complexes. Function-blocking antibodies directed against integrin α5β1 or soluble Arg-Gly-Asp peptide fragments derived from FN specifically inhibited GPR30-mediated epidermal growth factor receptor transactivation. Estrogen-mediated FN matrix assembly and epidermal growth factor receptor transactivation were similarly disrupted in integrin β1-deficient GE11 cells, whereas reintroduction of integrin β1 into GE11 cells restored these responses. Mutant Shc (317Y/F) blocked GPR30-induced FN matrix assembly and tyrosyl phosphorylation of erbB1. Interestingly, relative to recombinant wild-type Shc, 317Y/F Shc was more readily retained in GPR30-induced integrin α5β1 complexes, yet this mutant did not prevent endogenous Shc-integrin α5β1 complex formation. Our results suggest that GPR30 coordinates estrogen-mediated FN matrix assembly and growth factor release in human breast cancer cells via a Shc-dependent signaling mechanism that activates integrin α5β1.
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Biscaglia, Francesca, Senthilkumar Rajendran, Paolo Conflitti, et al. "Enhanced EGFR Targeting Activity of Plasmonic Nanostructures with Engineered GE11 Peptide." Advanced Healthcare Materials 6, no. 23 (2017): 1700596. http://dx.doi.org/10.1002/adhm.201700596.

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19

Abdulmalek, Shaymaa, Nouf Mostafa, Marwa Gomaa, Mohamed El‑Kersh, Ayman I. Elkady, and Mahmoud Balbaa. "Bee venom-loaded EGFR-targeting peptide-coupled chitosan nanoparticles for effective therapy of hepatocellular carcinoma by inhibiting EGFR-mediated MEK/ERK pathway." PLOS ONE 17, no. 8 (2022): e0272776. http://dx.doi.org/10.1371/journal.pone.0272776.

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Hepatocellular carcinoma (HCC) is one of the world’s most risky diseases due to the lack of clear and cost-effective therapeutic targets. Currently, the toxicity of conventional chemotherapeutic medications and the development of multidrug resistance is driving research into targeted therapies. The nano-biomedical field’s potential for developing an effective therapeutic nano-sized drug delivery system is viewed as a significant pharmaceutical trend for the encapsulation and release of numerous anticancer therapies. In this regard, current research is centered on the creation of biodegradable chitosan nanoparticles (CSNPs) for the selective and sustained release of bee venom into liver cancer cells. Furthermore, surface modification with polyethylene glycol (PEG) and GE11 peptide-conjugated bee venom-CSNPs allows for the targeting of EGFR-overexpressed liver cancer cells. A series of in vitro and in vivo cellular analyses were used to investigate the antitumor effects and mechanisms of targeted bee venom-CSNPs. Targeted bee venom-CSNPs, in particular, were found to have higher cytotoxicity against HepG2 cells than SMMC-7721 cells, as well as stronger cellular uptake and a substantial reduction in cell migration, leading to improved cancer suppression. It also promotes cancer cell death in EGFR overexpressed HepG2 cells by boosting reactive oxygen species, activating mitochondria-dependent pathways, inhibiting EGFR-stimulated MEK/ERK pathway, and elevating p38-MAPK in comparison to native bee venom. In hepatocellular carcinoma (HCC)-induced mice, it has anti-cancer properties against tumor tissue. It also improved liver function and architecture without causing any noticeable toxic side effects, as well as inhibiting tumor growth by activating the apoptotic pathway. The design of this cancer-targeted nanoparticle establishes GE11-bee venom-CSNPs as a potential chemotherapeutic treatment for EGFR over-expressed malignancies. Finally, our work elucidates the molecular mechanism underlying the anticancer selectivity of targeted bee venom-CSNPs and outlines therapeutic strategies to target liver cancer.
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Jiao, Honglei, Xinming Zhao, Jingya Han, Jingmian Zhang, and Jianfang Wang. "Synthesis of a novel 99mTc labeled GE11 peptide for EGFR SPECT imaging." International Journal of Radiation Biology 96, no. 11 (2020): 1443–51. http://dx.doi.org/10.1080/09553002.2020.1811419.

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Grataitong, Khwanthana, Wattana Weerachatyanukul, Krittalak Chakrabandhu, and Anne-Odile Hueber. "Modified MrNV viral capsids with GE11 peptide for binding colorectal cancer cells." FASEB Journal 34, S1 (2020): 1. http://dx.doi.org/10.1096/fasebj.2020.34.s1.09231.

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22

Dissoki, Samar, Aviv Hagooly, Smadar Elmachily, and Eyal Mishani. "Labeling approaches for the GE11 peptide, an epidermal growth factor receptor biomarker." Journal of Labelled Compounds and Radiopharmaceuticals 54, no. 11 (2011): 693–701. http://dx.doi.org/10.1002/jlcr.1910.

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23

Zain, Mohd Izani Mohd, and Mohd Daud Mat Din. "Democratic Dilemma of Malay Islamic Party: PAS, Coalition Pattern, and Rising Social Issues." Studia Islamika 29, no. 1 (2022): 83–109. http://dx.doi.org/10.36712/sdi.v29i1.16330.

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This article deliberates on how the Pan-Malaysian Islamic Party (PAS) embraces and weathers the challenges of democracy as a political culture beyond elections. The deliberation analyses the approach and behaviors of the party within a period of three general elections (GE), namely the GE12 in 2008, GE13 in 2013, and GE14 in 2018. Through qualitative approach and in-depth interviews with key PAS leaders, this article discusses PAS participation with the Pakatan Rakyat (PR), Muafakat Nasional (MN), and Perikatan Nasional (PN), which demonstrated the PAS’s unchartered undertaking to accept democracy as a political culture and not as a tool to achieve political power through an election. While it is trite to take the position that elections are the truest form of democracy, they can foster greater inclusivity, which can take place in both political and non-political realms.
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24

Nadzri, Muhamad M. N. "The 14th General Election, the Fall of Barisan Nasional, and Political Development in Malaysia, 1957-2018." Journal of Current Southeast Asian Affairs 37, no. 3 (2018): 139–71. http://dx.doi.org/10.1177/186810341803700307.

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The results of the recent 2018 general election (GE14) in Malaysia were exceptional. The ruling party – Barisan Nasional (BN) – was ousted from power after over six decades of authoritarian rule, by a new opposition coalition – the Pakatan Harapan (PH). In this historic election, BN lost all the federal states in Peninsular Malaysia except for the two less developed ones of Perlis and Pahang. BN was also defeated in Sabah for the second time since its dramatic recapture in 1995. However, these results are not as surprising if one looks at the outcome from its historical and developmental perspectives. The indication of the breakdown of the one-party dominant state of Malaysia can (at least) be traced back to 10 years ago – since the 2008 general election (GE12). BN then lost several parliamentary seats in the urban centres, even with a less unified opposition. It had also lost four states on the west coast of Peninsular Malaysia, and had been fairly incompetent in reclaiming control over Selangor and Penang since that particular election. Five years later, in the 2013 general election (GE13), the results aggravated BN. It had lost its popular votes to the then opposition coalition – the Pakatan Rakyat (PR). The main objectives of this article, therefore, are twofold. First, it intends to shed light on the recent general elections through historical and developmental approaches by linking them to the electoral results, and political development in Malaysia, respective to GE12 and GE13. Second, it strives to make available for analysis the arguments on how the opposition pact managed to unseat BN in GE14. The analysis in this article is based on the data gathered by the author through a mixture of media studies, library research, and direct observation – as this author was one of the official observers appointed by the Election Commission of Malaysia for GE14. The main argument of this article on the breakthrough of PH to the federal government is that the opposition managed to reshape the multiparty electoral system to a “two-plus-one party system” from late 2016, which boosted the level of political competition between the two main parties in Malaysia – namely, BN and PH – in GE14. Four major factors have been identified as constituting the triumph of PH and the fall of BN in the election. These are: the existence of a credible representative and strong opposition, with the inclusion of Mahathir and two Malay/ Bumiputra (“the natives”) political parties; the rupture of the elites within the ruling regime; the presence of impactful issues surrounding Najib's administration; and, the advancement of information and communications technology as well as its impact on the emergence of a digital and much more participative society in Malaysia.
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Liu, Zhuo-Yan, Guang-Hai Yan, Xiao-Yu Li, et al. "GE11 peptide modified CSO-SPION micelles for MRI diagnosis of targeted hepatic carcinoma." Biotechnology & Biotechnological Equipment 35, no. 1 (2021): 1574–86. http://dx.doi.org/10.1080/13102818.2021.1997154.

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Rahmanian, Najmeh, Seyed Jalal Hosseinimehr, Ali Khalaj, Zohreh Noaparast, Seyed Mohammad Abedi, and Omid Sabzevari. "99mTc labeled HYNIC-EDDA/tricine-GE11 peptide as a successful tumor targeting agent." Medicinal Chemistry Research 27, no. 3 (2017): 890–902. http://dx.doi.org/10.1007/s00044-017-2111-7.

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27

Bouhali, O., V. Bhatnagar, A. Castaneda, et al. "Radiation background estimation for the GE11 Triple-GEM detectors in the CMS endcap." Journal of Physics: Conference Series 2374, no. 1 (2022): 012161. http://dx.doi.org/10.1088/1742-6596/2374/1/012161.

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The Compact Muon Solenoid (CMS) is a general-purpose particle detector at the Large Hadron Collider (LHC) designed to study a wide range of particles produced in high energy collisions. The interaction of the beams with the pipe, shielding and detector supporting materials can produce neutrons, photons, electrons and positrons, forming a common background radiation field for CMS detector. A Monte-Carlo simulation is used to predict the background rate for a newly installed detector. In the forward region, the upgrade includes Gas Electron Multiplier (GEM) detectors called GE1/1. In this study, an estimate of the GE1/1 detector response to the background radiation is presented. The flux of background radiation is predicted using the FLUKA framework and the response of the detector is predicted using the GEANT4 framework. A comparison with actual GEM slice data is used as validation.
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Hailing, Tang, Pan Yonghong, Zhang Yufeng, and Tang Haitao. "Challenges for the application of EGFR-targeting peptide GE11 in tumor diagnosis and treatment." Journal of Controlled Release 349 (September 2022): 592–605. http://dx.doi.org/10.1016/j.jconrel.2022.07.018.

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29

T. DeJesus, Onofre. "Synthesis of [64Cu]Cu-NOTA-Bn-GE11 for PET Imaging of EGFR-Rich Tumors." Current Radiopharmaceuticalse 5, no. 1 (2012): 15–18. http://dx.doi.org/10.2174/1874471011205010015.

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30

Chen, Chien-Jen, Chen-Hsin Chan, Kun-Liang Lin, et al. "68Ga-labelled NOTA-RGD-GE11 peptide for dual integrin and EGFR-targeted tumour imaging." Nuclear Medicine and Biology 68-69 (January 2019): 22–30. http://dx.doi.org/10.1016/j.nucmedbio.2018.11.003.

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Tang, Hailing, Xiaojing Chen, Mengjie Rui, et al. "Effects of Surface Displayed Targeting Ligand GE11 on Liposome Distribution and Extravasation in Tumor." Molecular Pharmaceutics 11, no. 10 (2014): 3242–50. http://dx.doi.org/10.1021/mp5001718.

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32

Striese, Franziska, Wiebke Sihver, Feng Gao, et al. "Exploring pitfalls of 64Cu-labeled EGFR-targeting peptide GE11 as a potential PET tracer." Amino Acids 50, no. 10 (2018): 1415–31. http://dx.doi.org/10.1007/s00726-018-2616-5.

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33

King, R. Bruce. "Trivalent Polyhedra as Duals of Borane Deltahedra: From Molecular Endohedral Germanium Clusters to the Smallest Fullerenes." Molecules 28, no. 2 (2023): 496. http://dx.doi.org/10.3390/molecules28020496.

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The duals of the most spherical closo borane deltahedra having from 6 to 16 vertices form a series of homologous spherical trivalent polyhedra with even numbers of vertices from 8 to 28. This series of homologous polyhedra is found in endohedral clusters of the group 14 atoms such as the endohedral germanium cluster anions [M@Ge10]3– (M = Co, Fe) and [Ru@Ge12]3– The next members of this series have been predicted to be the lowest energy structures of the endohedral silicon clusters Cr@Si14 and M@Si16 (M = Zr, Hf). The largest members of this series correspond to the smallest fullerene polyhedra found in the endohedral fullerenes M@C28 (M = Zr, Hf, Th, U). The duals of the oblate (flattened) ellipsoidal deltahedra found in the dirhenaboranes Cp*2Re2Bn–2Hn–2 (Cp* = h5-Me5C5; 8 ≤ n ≤ 12) are prolate (elongated) trivalent polyhedra as exemplified experimentally by the germanium cluster [Co2@Ge16]4– containing an endohedral Co2 unit.
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34

Lunsford, Dale L. "Exploring Students' Perceptions of the Web as an Information Source." Journal of Educational Technology Systems 27, no. 4 (1999): 337–47. http://dx.doi.org/10.2190/ge11-34cn-adlt-py3x.

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35

Adem, B., A. L. Teixeira, F. Dias, C. Ruivo, R. Medeiros, and S. A. Melo. "GE11 positive exosomes as a potential RNAi delivery system in clear cell Renal Cell Carcinoma." Porto Biomedical Journal 2, no. 5 (2017): 181. http://dx.doi.org/10.1016/j.pbj.2017.07.016.

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36

Koay, Hean Wei, and Salwa Mokhtar Khairiah. "The role of political marketing and its importance in Barisan Nasional at Malaysia general election." Technium Social Sciences Journal 29 (March 9, 2022): 548–60. http://dx.doi.org/10.47577/tssj.v29i1.6138.

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This study discusses the political marketing tools based on the research in Barisan Nasional (BN) at Malaysia general election. According to the Malaysian law, the date of the last election and subsequent election is to be held at 5-year intervals. Thus, after GE12 in 2008, GE13 was held in 2013. Since 1969 from Alliance coalition to 1973 BN coalition never lost a general election in parliamentary constituency. The political tsunami in GE12 BN won 140 seats in Dewan Rakyat out of 222 seats, opposition parties such as Pakatan Rakyat (PR) won 82 seats out of 222 Dewan Rakyat of seats in Malaysia (Election Commission of Malaysia, 2008, 2013, 2018). The GE13 result was almost the same as GE12 in which BN won 133 seats in Dewan Rakyat or 47.38% of the votes. Pakatan Rakyat (PR) won the support for 89 seats in Dewan Rakyat or 50.87% of the votes. This is first time BN won in the general election but with less of the votes. In GE12 and GE13 voters started to support the opposition rather than BN. Specifically, direct voter contact, indirect voter contact, dominant party, party leader, gerrymandering, malapportionment, re-delineation, first-past-the-post system (FPTP) are the political marketing tools implement by BN. This paper discusses about political marketing tools employed by BN during general election. Therefore, this paper can provide information to political parties and help them to identify the suitable political marketing tools for coming elections.
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Iijima, Junko, Yanyang Zhao, Tomoya Isaji, et al. "Cell-Cell Interaction-dependent Regulation ofN-Acetylglucosaminyltransferase III and the BisectedN-Glycans in GE11 Epithelial Cells." Journal of Biological Chemistry 281, no. 19 (2006): 13038–46. http://dx.doi.org/10.1074/jbc.m601961200.

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Xu, Qingsong, Chen Qu, Wenjing Wang, Jianguo Gu, Yuguang Du, and Linsheng Song. "SpecificN-glycan alterations are coupled in epithelial-mesenchymal transition induced by EGF in GE11 epithelial cells." Cell Biology International 41, no. 2 (2016): 124–33. http://dx.doi.org/10.1002/cbin.10707.

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39

Haddick, Lisa, Wei Zhang, Sören Reinhard, et al. "Particle-Size-Dependent Delivery of Antitumoral miRNA Using Targeted Mesoporous Silica Nanoparticles." Pharmaceutics 12, no. 6 (2020): 505. http://dx.doi.org/10.3390/pharmaceutics12060505.

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Multifunctional core-shell mesoporous silica nanoparticles (MSN) were tailored in size ranging from 60 to 160 nm as delivery agents for antitumoral microRNA (miRNA). The positively charged particle core with a pore diameter of about 5 nm and a stellate pore morphology allowed for an internal, protective adsorption of the fragile miRNA cargo. A negatively charged particle surface enabled the association of a deliberately designed block copolymer with the MSN shell by charge-matching, simultaneously acting as a capping as well as endosomal release agent. Furthermore, the copolymer was functionalized with the peptide ligand GE11 targeting the epidermal growth factor receptor, EGFR. These multifunctional nanoparticles showed an enhanced uptake into EGFR-overexpressing T24 bladder cancer cells through receptor-mediated cellular internalization. A luciferase gene knock-down of up to 65% and additional antitumoral effects such as a decreased cell migration as well as changes in cell cycle were observed. We demonstrate that nanoparticles with a diameter of 160 nm show the fastest cellular internalization after a very short incubation time of 45 min and produce the highest level of gene knock-down.
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Xu, Wei-Wei, Da-yu Liu, Ying-chun Cao, and Xiang-yun Wang. "GE11 peptide-conjugated nanoliposomes to enhance the combinational therapeutic efficacy of docetaxel and siRNA in laryngeal cancers." International Journal of Nanomedicine Volume 12 (September 2017): 6461–70. http://dx.doi.org/10.2147/ijn.s129946.

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41

Zou, Yan, Yifeng Xia, Fenghua Meng, Jian Zhang, and Zhiyuan Zhong. "GE11-Directed Functional Polymersomal Doxorubicin as an Advanced Alternative to Clinical Liposomal Formulation for Ovarian Cancer Treatment." Molecular Pharmaceutics 15, no. 9 (2018): 3664–71. http://dx.doi.org/10.1021/acs.molpharmaceut.8b00024.

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42

Hui, Hon Chung. "Were Foreign Exchange Markets Reacting Negatively to Political Events? The Case of Malaysia." South Asian Journal of Macroeconomics and Public Finance 10, no. 1 (2021): 105–29. http://dx.doi.org/10.1177/2277978721995649.

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This article explores the effects of political events on foreign exchange returns in Malaysia. We identify five political events in recent history, namely the 13th General Election (GE13), the imprisonment of a key opposition politician, the scandal from the 1MDB exposé, the appointment of a new Central Bank Governor and the 14th General Election (GE14). Using event studies, our findings show that the imprisonment of the opposition party leader triggered a favourable response from the foreign exchange market. However, market reactions to the 1MDB scandal were largely unfavourable. The GE13 triggered unfavourable market response, while the reverse is true for market reactions to GE14. Market response to the appointment of the new Central Bank Governor was rather positive. The Event Study is the first of its kind that examines the foreign exchange market implications of key political events in Malaysia. There are practical considerations that emanate from these findings. JEL Classification: F31, D72, D73, O38
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Xin, Xiaofei, Virender Kumar, Feng Lin, et al. "Redox-responsive nanoplatform for codelivery of miR-519c and gemcitabine for pancreatic cancer therapy." Science Advances 6, no. 46 (2020): eabd6764. http://dx.doi.org/10.1126/sciadv.abd6764.

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Desmoplastic and hypoxic pancreatic cancer microenvironment induces aberrant expression of miRNAs and hypoxia-inducible factor-1α (HIF-1α) responsible for gemcitabine (GEM) resistance. We demonstrated that miR-519c was down-regulated in pancreatic cancer and transfection of miR-519c in GEM-resistant pancreatic cancer cells inhibited HIF-1α level under hypoxia. We synthesized redox-sensitive mPEG-co-P(Asp)-g-DC-g-S-S-GEM polymer, with GEM payload of 14% (w/w) and 90% GEM release upon incubation with l-glutathione. We synthesized mPEG-co-P(Asp)-g-TEPA-g-DC for complex formation with miRNA. Chemical modification of miR-519c with 2′-O-methyl phosphorothioate (OMe-PS) at 3′ end enhanced its stability and activity without being immunogenic. Epidermal growth factor receptor targeting peptide GE11 decoration increased tumor accumulation of micelles after systemic administration and significantly inhibited orthotopic desmoplastic pancreatic cancer growth in NSG mice by down-regulating HIF-1α and genes responsible for glucose uptake and cancer cell metabolism. Our multifunctional nanomedicine of GEM and OMe-PS–miR-519c offers a novel therapeutic strategy to treat desmoplasia and hypoxia-induced chemoresistance in pancreatic cancer.
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Zhou, Cheng, Yifeng Xia, Yaohua Wei, et al. "GE11 peptide-installed chimaeric polymersomes tailor-made for high-efficiency EGFR-targeted protein therapy of orthotopic hepatocellular carcinoma." Acta Biomaterialia 113 (September 2020): 512–21. http://dx.doi.org/10.1016/j.actbio.2020.06.020.

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45

Hu, Danrong, Omar Mezghrani, Lei Zhang, Yi Chen, Xue Ke, and Tianyuan Ci. "GE11 peptide modified and reduction-responsive hyaluronic acid-based nanoparticles induced higher efficacy of doxorubicin for breast carcinoma therapy." International Journal of Nanomedicine Volume 11 (October 2016): 5125–47. http://dx.doi.org/10.2147/ijn.s113469.

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46

Yu, Hung-Man, Jyun-Hong Chen, Kun-Liang Lin, and Wuu-Jyh Lin. "Synthesis of68Ga-labeled NOTA-RGD-GE11 heterodimeric peptide for dual integrin and epidermal growth factor receptor-targeted tumor imaging." Journal of Labelled Compounds and Radiopharmaceuticals 58, no. 7 (2015): 299–303. http://dx.doi.org/10.1002/jlcr.3296.

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47

Li, Xueli, Kongzhen Hu, Wenfeng Liu, et al. "Synthesis and evaluation of [18F]FP-Lys-GE11 as a new radiolabeled peptide probe for epidermal growth factor receptor (EGFR) imaging." Nuclear Medicine and Biology 90-91 (November 2020): 84–92. http://dx.doi.org/10.1016/j.nucmedbio.2020.10.004.

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48

Paiva, Igor, Stephanie Mattingly, Melinda Wuest, et al. "Synthesis and Analysis of 64Cu-Labeled GE11-Modified Polymeric Micellar Nanoparticles for EGFR-Targeted Molecular Imaging in a Colorectal Cancer Model." Molecular Pharmaceutics 17, no. 5 (2020): 1470–81. http://dx.doi.org/10.1021/acs.molpharmaceut.9b01043.

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49

Lan, Qinghua, Shuanghu Wang, Zhouming Chen, et al. "Near-infrared-responsive GE11-CuS@Gal nanoparticles as an intelligent drug release system for targeting therapy against oral squamous cell carcinoma." International Journal of Pharmaceutics 649 (January 2024): 123667. http://dx.doi.org/10.1016/j.ijpharm.2023.123667.

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50

Korolev, Konstantin. "Morphophysiological test of Linum usitatissimum L. under conditions of different levels of chloride salinity." АгроЭкоИнфо 5, no. 65 (2024): 19. http://dx.doi.org/10.51419/202145519.

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The selection of resistant varieties under conditions of abiotic stress is an urgent direction in the adaptive selection of flax. The presented work reflects the assessment of the phenotypic variability of 12 hybrid combinations of flax-longshanks according to the morphophysiological parameters of seedlings under the action of chloride salinization of two levels (E1, E2). The genotypes of flax of the fourth (F4) – fifth (F5) generations were used as objects of research. Significant differences (p>0.05, p>0.01, p>0.001) between hybrid populations and media were revealed for most of the studied indicators. Genotypic features (G) caused the formation of flax combinations of dry shoot mass, chlorophyll content in cotyledon leaves (16.2 -37.7%), medium – raw shoot mass and chlorophyll content (30.6 – 50.0%), interaction of genotype and medium – root length, germination index (26.8 – 45.5%). The negative effect of two environmental conditions on seed germination and further development of flax seedlings has been established. By root length Gen1, Gen5, Gen9, Gen10, Gen11; shoot length – Gen1, Gen2, Gen3, Gen7, Gen12; raw root weight – Gen1, Gen4, Gen5, Gen10; dry root weight – Gen1, Gen4, Gen5; the crude mass of the shoot is Gen1, Gen5; the dry mass of the shoot is Gen1, Gen4, Gen5, Gen7; the chlorophyll content is Gen2, Gen8. Resistance to salt stress in two environmental conditions was characterized by 41.6% of combinations in shoot length, 33.3% in raw root weight, dry shoot weight, 25.0% in dry root weight, 16.6% in raw shoot weight, chlorophyll content, which can be recommended for further breeding work when developing an adaptive strategy for creating new flax varieties -dolgunts in the soil and climatic conditions of the Tyumen region. Keywords: FLAX, HYBRIDIZATION, STABILITY INDEX, SPAD-502 PLUS, SELECTION
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