Role Of Fes Research Articles

Enhancing ZnO monolayer nanosheets for photocatalysis: the role of FeSn and RuSn (n = 0–3) doping in electronic and structural properties

The role of FeSn- and RuSn-co-doping in the electronic properties of monolayer ZnO nanosheets.

Abstract PD6-10: 18F-fluoroestradiol (fes) and 18f-fluorodeoxyglucose (fdg) pet imaging in metastatic lobular breast cancer

Abstract Background: The histology and pattern of spread in lobular breast cancer has presented challenges in estimating extent of disease by traditional imaging methods. 18F-FES is an estrogen analogue PET imaging tracer which measures tumor ER expression at multiple tumor sites simultaneously. It is FDA approved in the US and will be available in 2021, pressing clinicians to define the role of FES in patients with breast cancer before use in practice. We compared quantitative FES-PET and clinical FDG-PET SUV uptake between patients with metastatic lobular carcinoma. Methods: Metastatic lesions in patients with primary ER+ lobular breast cancer were retrospectively evaluated with FES- and FDG-PET. SUV uptake was calculated in 38 patients enrolled in various studies at our institution. Up to ten matched lesions in each patient were assessed for a total of 192 lesions. Pairwise t-tests were performed to measure the difference between paired FES and FDG lesions. Results: Among metastatic breast cancer patients with lobular histology, 87% of patients had a positive FES scan. The majority of positive scans demonstrated uptake in all sites, with only a small percentage (6%) lacking FES uptake in at least one lesion. Uptake was noted in various metastatic tumor sites including bone (78%), soft tissue/lymph node (17%), breast (8%) and lung (1%). Mean (range) SUVmax in FES and FDG respectively was 3.38 (0.88, 9.08) and 4.14 (1.25, 9.49). Paired lesion analysis showed concordance between the two imaging modalities in lesions with low SUV uptake. FES and FDG uptake, however, could be discordant in both directions (FES > FDG, and FDG > FES) when there is higher level of uptake in at least one of the tracers. This was specifically seen in the 150 bone lesions, possibly indicating differences in lesion phenotype or response to therapy. Conclusions: FES and FDG scans demonstrate similar average SUV uptake in metastatic lobular breast cancer, suggesting that both scans have utility in detecting lobular histology. Our data suggests that at higher SUV values, FES may provide additional information to FDG. Discordance between FES and FDG SUV uptake in the same lesions, especially in bone, has important implications for staging and assessing response to therapy. Large prospective trials are needed to define the clinical utility of FES-PET in metastatic lobular breast cancer. Research Support: P01CA42045, R01CA72064, U01CA148131, DOD W81XWH-04-01-0675 Citation Format: Poorni Manohar, Lanell Peterson, Vicky Wu, Isaac Jenkins, Mark Muzi, Jennifer Specht, Delphine Chen, Jeanne Link, Kenneth Krohn, Paul Kinahan, David Mankoff, Hannah Linden. 18F-fluoroestradiol (fes) and 18f-fluorodeoxyglucose (fdg) pet imaging in metastatic lobular breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD6-10.

Trichloroethene degradation by nanoscale CaO2 activated with Fe(II)/FeS: The role of FeS and the synergistic activation mechanism of Fe(II)/FeS

The performance of trichloroethene (TCE) degradation was significantly improved with the addition of FeS in nanoscale calcium peroxide (nCP) environment and the enhancement of HO generation in nCP/Fe(II)/FeS system was confirmed by comparison with nCP/Fe(II) and nCP/FeS systems. The role of FeS in nCP/Fe(II)/FeS system demonstrated that the majority of reactive oxygen radicals (ROSs) was generated on the catalyst surface due to the heterogeneous reaction through FeS activated nCP in one hand, and the reductive FeS could promote TCE degradation by regenerating Fe(II) from Fe(III) in the other hand. The probe as well as scavenger test results suggested that the major ROSs was HO rather than O2−. Over 91.5% TCE could be degraded at the molar ratio of 2/2/4/1 of nCP/Fe(II)/FeS/TCE, in which more than 95.5% TCE was dechlorinated. The effect of surfactants on TCE degradation was evaluated. In contrast, further investigation found that BTEX removal was inhibited with the addition of FeS. In conclusion, this study revealed the well function and fundamental synergistic mechanism of FeS. Moreover, the degradation of TCE in actual groundwater confirmed that nCP/Fe(II)/FeS technique has a great advantage and potential in TCE contaminated groundwater remediation in ISCO practice.

Efficient removal of trichloroethene in oxidative environment by anchoring nano FeS on reduced graphene oxide supported nZVI catalyst: The role of FeS on oxidant decomposition and iron leakage

The performance of trichloroethene (TCE) removal was initially investigated in sodium persulfate (SPS) or potassium monopersulfate triple salt (PMS) oxidative environment by reduced graphene oxide (rGO) supported nZVI (nZVI-rGO) catalyst and further the role of sulphur by anchoring nano FeS on nZVI-rGO (FeS@nZVI-rGO) was evaluated. The high usage of oxidants and stability of FeS@nZVI-rGO catalyst were significantly improved due to the insoluble nature of this innovative catalyst by involvement of nano FeS which limited the rapid iron loss caused by the corrosion of active sites and mitigated rapid oxidants decomposition in FeS@nZVI-rGO/SPS and FeS@nZVI-rGO/PMS systems. The tests for target contaminant removal showed that over 95 % TCE could be removed at 100 mg L−1 FeS@nZVI-rGO and 1.2 mM SPS or 0.3 mM PMS dosages, in which over 85 % TCE could be dechlorinated. The reactive oxygen radicals (ROSs) generation mechanisms and their contribution to TCE removal were investigated through radical scavenge tests in both systems, indicating that both HO and SO4− were the major ROSs rather than O2−. In conclusion, this study revealed the well function and fundamental mechanism of this innovative catalyst by anchoring nano FeS and worth of further demonstration of this technique in TCE contaminated groundwater remediation application.

Abstract A25: Dual inhibition of Flt3 and Fes tyrosine kinases potently blocks proliferation of AML cells expressing an active Flt3 mutant.

Abstract Acute myelogenous leukemia (AML) is a hematologic cancer associated with a relatively poor prognosis, especially in the elderly. Although the diverse genetic changes associated with AML make treatment a challenge, about one-third of cases involve activating mutations in the receptor tyrosine kinase, Flt3. While many Flt3 tyrosine kinase inhibitors have been tested in the clinic, most have performed poorly as single agents indicating that additional signaling pathways contribute to the transformed phenotype. Previous studies have linked the Fes protein-tyrosine kinase to Flt3 in AML, and RNAi-knockdown studies suggest that Fes may be required for Flt3 function. In the present study, we tested the phenoxyquinazoline Fes kinase inhibitor, TL02-59, for its growth-suppressive activity against MV4-11 myeloid leukemia cells. These cells have an activating mutation in Flt3 (internal tandem duplication or ITD) that causes constitutive Fes activation downstream. TL02-59 blocked MV4-11 cell proliferation with an IC50 value of 25 nM, rivaling the potency of the clinical Flt3 inhibitors lestaurtinib and tandutinib in this cell line. In contrast, TL02-59 had no effect on the growth of THP-1 cells, which are wild-type for Flt3. We next explored the inhibitory activity of TL02-59 against Fes using an in vitro kinase assay. Surprisingly, TL02-59 inhibited recombinant Fes with an IC50 value of only 1.5 µM, suggesting that it may have additional kinase targets in AML cells. In vitro kinase assays with recombinant Flt3 support this idea, where TL02-59 also blocked Flt3 kinase activity with an IC50 value of 0.6 µM. This observation suggests that the potency of TL02-59 in MV4-11 cells may be the result of dual inhibition of both Fes and Flt3-ITD kinase activities, a possibility confirmed by anti-phosphotyrosine immunoblotting of Fes and Flt3 immunoprecipitates from TL02-59-treated cells. We next investigated downstream targets linked uniquely to Fes by engineering mutants of Flt3-ITD that are resistant to TL02-59 based on clinical cases of acquired drug resistance to other Flt3 inhibitors. These mutants were used to transform human TF-1 myeloid cells to cytokine independence, resulting in constitutive activation of endogenous Fes and sensitization to growth suppression by TL02-59 (IC50 = 24 nM). Interestingly, TF-1 cells transformed with TL02-59-resistant mutants of Flt3-ITD were less sensitive to the growth-suppressive actions of the inhibitor, consistent with its dual specificity. Using these cell lines, we will be able to identify downstream phosphorylation targets unique to Fes, because TL02-59 treatment will only affect Fes and not Flt3-ITD directly. Preliminary experiments performed in TF-1 cells transformed with one TL02-59-resistant mutant of Flt3-ITD, show inhibitor treatment still results in inhibition of STAT5 phosphorylation. These results support a critical role for Fes in downstream signaling from Flt3-ITD+ AML, and suggest that dual inhibition of both Flt3-ITD and Fes may provide a therapeutic advantage for the treatment of this subtype of AML. Citation Format: Mark Weir, Sabine Hellwig, Nathanael S. Gray, Thomas E. Smithgall. Dual inhibition of Flt3 and Fes tyrosine kinases potently blocks proliferation of AML cells expressing an active Flt3 mutant. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr A25.

The role of FeS in initial activation and performance degradation of Na–NiCl2 batteries

The role of iron sulfide (FeS) in initial cell activation and degradation in Na–NiCl2 battery was investigated in this work. The research focused on identifying the effects of FeS levels on the electrochemical performance and morphological changes in the cathode. The x-ray photoelectron spectroscopy study along with battery tests revealed that FeS plays a critical role in initial battery activation by removing passivation layers on Ni particles. It was also found that the optimum level of FeS in the cathode resulted in suppressing Ni particle growth and improved battery cycling performance. The results of electrochemical characterization indicated that sulfur species generated in situ during initial charging, such as polysulfide and element sulfur, are responsible for removing the passivation layer. Consequently, the cells containing elemental sulfur in the cathode exhibited similar electrochemical behavior during initial charging compared to the cells containing FeS.

Oxidative Remobilization of Technetium Sequestered by Sulfide-Transformed Nano Zerovalent Iron

Our previous study showed that formation of TcS2-like phases is favored over TcO2 under sulfidic conditions stimulated by nano zerovalent iron. This study further investigates the stability of Tc(IV) sulfide upon reoxidation by solution chemistry, solid phase characterization, and X-ray absorption spectroscopy. Tc dissolution data showed that Tc(VII) reduced by sulfide-transformed nZVI has substantially slower reoxidation kinetics than Tc(VII) reduced by nZVI only. The initial inhibition of Tc(IV) dissolution at S/Fe = 0.112 is due to the redox buffer capacity of FeS, which is evidenced by the parallel trends in oxidation-reduction potentials (ORP) and Tc dissolution kinetics. The role of FeS in inhibiting Tc oxidation is further supported by the Mössbauer spectroscopy and micro X-ray diffraction data at S/Fe = 0.112, showing persistence of FeS after 24-h oxidation but complete oxidation after 120-h oxidation. X-ray absorption spectroscopy data for S/Fe = 0.011 showed significantly increasing percentages of TcS2 in the solid phase after 24-h oxidation, indicating stronger resistance of TcS2 to oxidation. At S/Fe = 0.112, the XAS results revealed significant transformation of Tc speciation from TcS2 to TcO2 after 120-h oxidation. Given that no apparent Tc dissolution occurred during this period, the speciation transformation might play a secondary role in hindering Tc oxidation. Collectively, the results indicate that sequestrating Tc as TcS2 under stimulated sulfate reduction is a promising strategy to improve the long-term stability of reduced Tc in subsurface remediation.

Abstract A076: Deficiency of Fes tyrosine kinase expression correlates with delayed mammary tumor onset in a HER2/Neu overexpressing transgenic mouse model

Abstract Fes (a.k.a. Fps) is a cytoplasmic protein tyrosine kinase that is highly expressed in breast epithelial cells during lactation, as well as in vascular endothelial and myeloid cells. Retrovirally encoded oncogenic alleles of Fes are associated with tumors in chickens and cats and cause tumors in transgenic mice; however, a role for Fes in human cancer has not been established. Using an orthotopic mouse mammary engraftment model, we previously found that Fes deficiency correlated with reduction in engrafted tumor growth rates, lung metastasis, and circulating tumor cells. Reduced vascularity and fewer infiltrating macrophages suggested the tumor microenvironment of Fes-deficient mice was less supportive of tumor growth and metastasis. In co-culture with tumor cells, Fes-deficiency in macrophages correlated with a reduced ability to promote tumor cell invasive behavior. These results suggested a tumor promoting role of Fes kinase in breast cancer through roles in cells of the tumor microenvironment. In a transgenic mouse model of breast cancer driven by an activated HER2/Neu allele expressed in the mammary epithelium, we observed delayed tumor onset in Fes-deficient mice compared to wild-type mice. However, there was no difference in tumor growth rates. Taken together, these observations argue that Fes inhibition might provide therapeutic benefits in breast cancer, by attenuating tumor-associated angiogenesis and the metastasis-promoting functions of tumor-associated macrophages, or by delaying breast tumor onset in women with HER2 overexpression. Note:This abstract was not presented at the conference. Citation Format: Connie Shengnan Zhang, Peter A. Greer. Deficiency of Fes tyrosine kinase expression correlates with delayed mammary tumor onset in a HER2/Neu overexpressing transgenic mouse model. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr A076.

Abstract 1405: Deficiency of Fes tyrosine kinase expression correlates with delayed mammary tumor onset in a HER2/Neu over-expressing transgenic mouse model.

Abstract Fes (a.k.a. Fps) is a cytoplasmic protein tyrosine kinase that is highly expressed in breast epithelial cells during lactation, as well as in vascular endothelial and myeloid cells. Retrovially encoded oncogenic alleles of Fes are associated with tumors in chickens and cats and cause tumors in transgenic mice; however, a role for Fes in human cancer has not been established. Using an orthotopic mouse mammary engraftment model, we previously found that Fes deficiency correlated with reduction in engrafted tumor growth rates, lung metastasis, and circulating tumor cells. Reduced vascularity and fewer infiltrating macrophages suggested the tumor microenvironment of Fes-deficient mice was less supportive of tumor growth and metastasis. In co-culture with tumor cells, Fes-deficiency in macrophages correlated with a reduced ability to promote tumor cell invasive behavior. These results suggested a tumor promoting role of Fes kinase in breast cancer through roles in cells of the tumor microenvironment. In a transgenic mouse model of breast cancer driven by an activated HER2/Neu allele expressed in the mammary epithelium, we observed delayed tumor onset in Fes-deficient mice compared to wild-type mice. However, there was no difference in tumor growth rates. Taken together, these observations argue that Fes inhibition might provide therapeutic benefits in breast cancer, by attenuating tumor-associated angiogenesis and the metastasis-promoting functions of tumor-associated macrophages, or by delaying breast tumor onset in women with HER2 overexpression. Citation Format: Connie S. Zhang, Peter A. Greer. Deficiency of Fes tyrosine kinase expression correlates with delayed mammary tumor onset in a HER2/Neu over-expressing transgenic mouse model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1405. doi:10.1158/1538-7445.AM2013-1405 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.

Abstract 3683: Small molecule inhibitors of the Fes non-receptor tyrosine kinase

Abstract The c-fes/fps proto-oncogene encodes a unique 93 kDa protein-tyrosine kinase (Fes) expressed in myeloid, vascular endothelial, neuronal and epithelial cell types. Basal Fes catalytic activity is tightly regulated in vivo, with Fes adopting an inactive conformation in the absence of activating signals. The role of Fes in cancer is paradoxical, with some observations pointing to a tumor-suppressor role. For example, while Fes is strongly expressed in normal colonic epithelium, promoter methylation represses Fes expression in primary tumor tissue and many colorectal cancer cell lines. Restoration of Fes expression from a viral vector suppresses anchorage-independent growth of colorectal cancer cells. In a mouse model of breast cancer, disruption of the c-fes/fps locus correlates with more rapid tumor onset, and this effect can be rescued with a c-fes/fps transgene. In contrast to these observations, other lines of evidence support a pro-oncogenic role for Fes. Constitutively active mutants of Fes are capable of transforming rodent fibroblasts. In the mouse, expression of a gain-of-function human c-fes/fps allele results in hypervascularization and hemangioma formation. Fes has been identified as a phosphorylation target for a Kit mutant (D816V) implicated in mastocytosis, hematologic neoplasms, germ-cell tumors and melanomas. Targeting of Fes by siRNA knockdown inhibited proliferation of cells carrying the KITD816V mutation, identifying Fes as a potential therapeutic target in this cellular context. Another study demonstrated that siRNA knockdown of Fes reduces proliferation of two human renal carcinoma cell lines. One caveat of siRNA-mediated knockdown of Fes is that the resulting growth-inhibitory effect can not be attributed to loss of Fes activity as opposed to loss of the Fes protein. Delineation of kinase-dependent vs. kinase-independent cellular functions of Fes calls for Fes-specific kinase inhibitors, which have not been reported to date. In this study we aimed to identify inhibitors of the Fes tyrosine kinase. Using the recombinant Fes SH2-kinase region and an in vitro kinase assay (Z’-Lyte; Invitrogen), we screened a kinase-biased library of 586 compounds for inhibition of Tyr2 peptide phosphorylation by Fes. Lead compounds identified in vitro were then tested for their ability to inhibit full-length Fes autophosphorylation and microtubule association in transfected COS-7 cells and for their effect on rodent fibroblast transformation driven by constitutively active Fes mutants. A subset of active compounds was further evaluated for inhibition of tubulin phosphorylation by wild-type and active Fes in vitro. We will present a panel of type I and type II small molecule kinase inhibitors from various chemical classes with activity against Fes that are also non-toxic at inhibitory concentrations in cell lines. Our findings represent the first step towards developing a potent and selective inhibitor of Fes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3683.

The role of FeS and (NH4)2CO3 additives on the pressed type Fe electrode

Abstract In the present work the influence of the FeS and (NH 4 ) 2 CO 3 additives on the Ni–Fe battery negative plate was studied through galvanostatic and potentiostatic discharges. Some aspects of the Fe electrode discharge mechanism in the presence of the FeS were elucidated. The presence of (NH 4 ) 2 CO 3 as pore forming agent in the Fe electrode was advantageous since it increased the capacity.