New carbon composite materials were prepared by pyrolysis of mixture of coffee wastes and red mud at 700 °C with the inorganic: organic ratios of 1.9 (CC-1.9) and 2.2 (CC-2.2). These adsorbents were ...used to remove reactive orange 16 (RO-16) and reactive red 120 (RR-120) textile dyes from aqueous solution. The CC-1.9 and CC-2.2 materials were characterized using Fourier transform infrared spectroscopy, Nitrogen adsorption/desorption curves, scanning electron Microscopy and X-ray diffraction. The kinetic of adsorption data was fitted by general order kinetic model. A three-parameter isotherm model, Liu isotherm model, gave the best fit of the equilibrium data (298 to 323 K). The maximum amounts of dyes removed at 323 K were 144.8 (CC-1.9) and 139.5 mg g
−1
(CC-2.2) for RO-16 dye and 95.76 (CC-1.9) and 93.80 mg g
−1
(CC-2.2) for RR-120 dye. Two simulated dyehouse effluents were used to investigate the application of the adsorbents for effluent treatment.
The SOCS1 gene is a frequent target of epigenetic repression in hepatocellular carcinoma. Many other types of cancer also harbor methylated SOCS1 gene. Besides, recent studies implicate microRNAs ...targeting SOCS1 in cancer progression. These findings suggest a broad tumor suppressor role of SOCS1 and have stimulated the quest to elucidate the underlying molecular mechanisms. The essential physiological function of SOCS1 is to attenuate interferon gamma signaling in immune cells. SOCS1 binds activated JAK kinases and the receptor chains of several cytokines, some of which are implicated in cancer progression. SOCS1 also facilitates ubiquitination and proteasomal degradation of many signaling molecules downstream of cytokine and growth factor receptors. We have shown that SOCS1 inhibits signaling via the hepatocyte growth factor receptor c-MET in hepatocytes. Aberrant MET signaling, implicated in the progression of many types of cancers, also contributes to the development of chemoresistance to tyrosine kinase inhibitors and drugs targeting other oncogenic signaling pathways. Here, we discuss the SOCS1-dependent regulation of MET signaling as an important mechanism underlying the tumor suppressor role of SOCS1 that is relevant not only to hepatocellular carcinoma but also to other types of cancers.
Signals downstream of growth factor receptors play an important role in mammary carcinogenesis. Recently, we demonstrated that the small GTPases ARF1 and ARF6 were shown to be activated downstream of ...the epidermal growth factor receptor (EGFR) and act as a key regulator of growth, migration, and invasion of breast cancer cells. However, the mechanism via which the EGFR recruits and activates ARF1 and ARF6 to transmit signals has yet to be fully elucidated. Here, we identify adaptor proteins Grb2 and p66Shc as important regulators mediating ARF activation. We demonstrate that ARF1 can be found in complex with Grb2 and p66Shc upon EGF stimulation of the basal-like breast cancer MDA-MB-231 cell line. However, we report that these two adaptors regulate ARF1 activation differently, with Grb2 promoting ARF1 activation and p66Shc blocking this response. Furthermore, we show that Grb2 is essential for the recruitment of ARF1 to the EGFR, whereas p66Shc hindered ARF1 receptor recruitment. We demonstrate that the negative regulatory role of p66Shc stemmed from its ability to block the recruitment of Grb2/ARF1 to the EGFR. Conversely, p66Shc potentiates ARF6 activation as well as the recruitment of this ARF isoform to the EGFR. Interestingly, we demonstrate that Grb2 is also required for the activation and receptor recruitment of ARF6. Additionally, we show an important role for p66Shc in modulating ARF activation, cell growth, and migration in HER2-positive breast cancer cells. Together, our results highlight a central role for adaptor proteins p66Shc and Grb2 in the regulation of ARF1 and ARF6 activation in invasive breast cancer cells.
ADP-ribosylation factors (ARF) 1 and 6 play an important role in breast cancer cell proliferation, migration, and invasion.
In invasive breast cancer cells, EGF-mediated ARF1 and ARF6 activation is regulated by p66Shc and Grb2.
Adaptor proteins are required to promote ARF activation.
Understanding the signaling mechanisms leading to ARF activation may identify novel therapeutic targets for the treatment of breast cancer.
We have shown previously that either Grb2- or Shc-mediated signaling from the oncogenic Met receptor Tpr-Met is sufficient to trigger cell cycle progression in Xenopus oocytes. However, direct ...binding of these adaptors to Tpr-Met is dispensable, implying that another Met binding partner mediates these responses. In this study, we show that overexpression of Grb2-associated binder 1 (Gab1) promotes cell cycle progression when Tpr-Met is expressed at suboptimal levels. This response requires that Gab1 possess an intact Met-binding motif, the pleckstrin homology domain, and the binding sites for phosphatidylinositol 3-kinase and tyrosine phosphatase SHP-2, but not the Grb2 and CrkII/phospholipase Cgamma binding sites. Importantly, we establish that Gab1-mediated signals are critical for cell cycle transition promoted by the oncogenic Met and fibroblast growth factor receptors, but not by progesterone, the natural inducer of cell cycle transition in Xenopus oocytes. Moreover, Gab1 is essential for Tpr-Met-mediated morphological transformation and proliferation of fibroblasts. This study provides the first evidence that Gab1 is a key binding partner of the Met receptor for induction of cell cycle progression, proliferation, and oncogenic morphological transformation. This study identifies Gab1 and its associated signaling partners as potential therapeutic targets to impair proliferation or transformation of cancer cells in human malignancies harboring a deregulated Met receptor.
The etiology and progression of a variety of human malignancies are linked to the deregulation of receptor tyrosine kinases (RTKs). To define the role of RTK-dependent signals in various oncogenic ...processes, we have previously engineered RTK oncoproteins that recruit either the Shc or Grb2 adaptor proteins. Although these RTK oncoproteins transform cells with similar efficiencies, fibroblasts expressing the Shc-binding RTK oncoproteins induced tumors with short latency (≈24 days), whereas cells expressing the Grb2-binding RTK oncoproteins induced tumors with delayed latency (≈24 days). The early onset of tumor formation correlated with the ability of cells expressing the Shc-binding RTK oncoproteins to produce vascular endothelial growth factor (VEGF) in culture and an angiogenic response in vivo. Consistent with this, treatment with a VEGF inhibitor, VEGF-Trap, blocked the in vivo angiogenic and tumorigenic properties of these cells. The importance of Shc recruitment to RTKs for the induction of VEGF was further demonstrated by using mutants of the Neu/ErbB2 RTK, where the Shc, but not Grb2, binding mutant induced VEGF. Moreover, the use of fibroblasts derived from ShcA-deficient mouse embryos, demonstrated that Shc was essential for the induction of VEGF by the Met/hepatocyte growth factor RTK oncoprotein and by serum-derived growth factors. Together, our findings identify Shc as a critical angiogenic switch for VEGF production downstream from the Met and ErbB2 RTKs.
The Gab1 docking protein forms a platform for the assembly of a multiprotein signaling complex downstream from receptor tyrosine kinases. In general, recruitment of Gab1 occurs indirectly, via the ...adapter protein Grb2. In addition, Gab1 interacts with the Met/hepatocyte growth factor receptor in a Grb2-independent manner. This interaction requires a Met binding domain (MBD) in Gab1 and is essential for Met-mediated epithelial morphogenesis. The Gab1 MBD has been proposed to act as a phosphotyrosine binding domain that binds Tyr-1349 in the Met receptor. We show that a 16-amino acid motif within the Gab1 MBD is sufficient for interaction with the Met receptor, suggesting that it is unlikely that the Gab1 MBD forms a structured domain. Alternatively, the structural integrity of the Met receptor, and residues upstream of Tyr-1349 located in the C-terminal lobe of the kinase domain, are required for Grb2-independent interaction with the Gab1 MBD. Moreover, the substitution of Tyr-1349 with an acidic residue allows for the recruitment of the Gab1 MBD and for phosphorylation of Gab1. We propose that Gab1 and the Met receptor interact in a novel manner, such that the activated kinase domain of Met and the negative charge of phosphotyrosine 1349 engage the Gab1 MBD as an extended peptide ligand.
Porous activated carbons (ACs) prepared from a lignocellulosic waste, Caesalpinia ferrea seed pod wastes (CF) were utilised for removing captopril pharmaceutical from synthetic hospital effluents and ...aqueous effluents. Chemical activation using ZnCl2 was performed. It was utilised the following proportions CF-Biomass: ZnCl2 (1: 0.5, 1:1 and 1:1.5, obtaining CFAC.0.5, CFAC.1.0, and CFAC.1.5 activated carbons. These mixtures were pyrolysed at 600 °C in a conventional furnace. The ACs were characterised by FTIR, hydrophobic/hydrophilic ratio (HI), CHN/O elemental analysis, Boehm titration, surface areas (SBET), total pore volumes, and pore size distribution. These analyses show that the ACs presents several functional groups on AC surfaces and there is a predominance of hydrophilic surfaces. All the activated carbons prepared presented surface area 1050–1480 m2 g−1. Regarding the adsorption process, the kinetics data were fitted to General-order kinetic model and equilibrium of adsorption data were well represented by and Liu isotherm model. The maximum adsorption capacity of 535.5 mg g−1 was obtained at 25 °C for the sample CFAC.1.5. The thermodynamic studies have shown that the adsorption process of captopril is spontaneous and favourable. The employment of the ACs for treating simulated effluents, with different emerging contaminants, showed an excellent removal (up to 97.67%). This result is evidence that Caesalpinia ferrea seed pod wastes were a high-efficiency precursor for AC preparation and that such activated carbons could be used for treating hospital effluents containing pharmaceuticals.
•Caesalpinia ferrea seed pods were used as carbon source for preparation of activated carbon.•Efficient removal of captopril pharmaceutical from hospital effluents was obtained.•Maximum captopril sorption capacity of 776.2 mg g−1.•The several functional groups of ACs surface leads to a hydrophilic surface of ACs.
•Microwave-assisted cocoa shell activated carbon was prepared and characterized.•The anti-inflammatories, diclofenac and nimesulide, were adsorbed onto MWCS-1.0.•Adsorption maximum values are 63.47 ...(diclofenac) and 74.81mgg−1 (nimesulide).•General order kinetic model suitably explained the adsorption process.•MWCS-1.0 was effectively used for treatment of simulated hospital effluents.
Microwave-induced chemical activation process was used to prepare an activated carbon from cocoa shell for efficient removal of two anti-inflammatories, sodium diclofenac (DFC) and nimesulide (NM), from aqueous solutions. A paste was obtained from a mixture of cocoa shell and inorganic components; with a ratio of inorganic: organic of 1 (CSC-1.0). The mixture was pyrolyzed in a microwave oven in less than 10min. The CSC-1.0 was acidified with a 6molL−1 HCl under reflux to produce MWCS-1.0. The CSC-1.0 and MWCS-1.0 were characterized using FTIR, SEM, N2 adsorption/desorption curves, X-ray diffraction, and point of zero charge (pHpzc). Experimental variables such as initial pH of the adsorbate solutions and contact time were optimized for adsorptive characteristics of MWCS-1.0. The optimum pH for removal of anti-inflammatories ranged between 7.0 and 8.0. The kinetic of adsorption was investigated using general order, pseudo first-order and pseu do-second order kinetic models. The maximum amounts of DCF and NM adsorbed onto MWCS-1.0 at 25°C are 63.47 and 74.81mgg−1, respectively. The adsorbent was tested on two simulated hospital effluents. MWCS-1.0 is capable of efficient removal of DCF and NM from a medium that contains high sugar and salt concentrations.
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•Co, Ni, Cu and Zn are successfully used in the preparation of activated carbons by microwave radiation.•The metal atoms have an impact on physicochemical and adsorptive ...properties.•SBET and pore volumes increase with atomic number and decrease with melting point.•Cu-MC, Co-MC and Ni-MC exhibit high hydrophobic properties compared to Zn-MC.•O-nitro phenol is the most adsorbed molecule from aqueous solution.
First-row transition metals (Co, Ni, Cu and Zn) were successfully used in the preparation of activated carbons from wood biomass via microwave-assisted irradiation. Physical-chemical properties of the produced materials (MWAC) were studied by nitrogen adsorption–desorption curves, SEM, FTIR, UV–vis DRS and synchronous fluorescence spectroscopy, CHN elemental analysis, TGA/DTG, pHzpc, hydrophobic properties, and total acidity and basicity groups. Results showed that the metals were bound successfully in different amounts with surface functional groups of the wood biomass through ion exchange and surface complexation interaction during the impregnation step. Zn2+ and Cu2+ formed the most complexes. MWAC impregnated with Zn2+ showed higher pore volumes and surface areas, followed by Cu2+, Co2+ and Ni2+, independently of the ratio used. As the metal : biomass ratio was increased from 0.5 to 2, the surface area of MWAC increased from 300 to 620m2g−1 for Co-MC, 260 to 381m2g−1 for Ni-MC, 449 to 765m2g−1 for Cu-MC and from 572 to 1780m2g−1 for Zn-MC. The samples showed high values of carbon contents and oxygen-containing groups. An adsorption experiment revealed that samples prepared using ZnCl2 showed the highest sorption capacities (qe) for the tested adsorbates, followed by CuCl2, CoCl2 and NiCl2. These results matched with the surface areas and pore volumes trends, which were found to follow atomic number and melting point trends–Ni(II)<Co(II)<Cu(II)<Zn(II), rather than the Irving-Williams Series. The sorption capacities (qe) of molecules followed this order: 2-nitro phenol>bisphenol A>hydroquinone>4-nitro phenol>2-naphtol>paracetamol>caffeine>resorcinol.
This study evaluated the feasibility of removing Alizarin Red S dye (ARS) from aqueous solutions, using nanoadsorbents such as single and multiwalled carbon nanotubes (SWCNT and MWCNT, respectively). ...The effect of pH, shaking time, and temperature on adsorption was studied. The pH 2.0 was observed to show optimum removal for both of the carbon nanotubes. The equilibrium time (298–318 K) was fixed at 65 and 100 min for SWCNT and MWCNT, respectively. The kinetics of adsorption was calculated using pseudo-first-order, pseudo-second-order, and general-order equations. The calculations revealed that the general-order kinetic equation best-fit the adsorption data. The Liu isotherm model best fit the equilibrium data (298–318 K). The maximum sorption capacity at 318 K for ARS dye was 312.5 and 135.2 mg g–1 for SWCNT and MWCNT, respectively. Change in entropy (Δ S°), Gibb’s free energy change (Δ G°), and enthalpy (Δ H°) were calculated for the adsorption of ARS dye. The electrostatic interaction between nanoadsorbent–adsorbate was conveyed using the magnitude of change in enthalpy. Ab initio simulation was used to study the interaction of ARS with (5,5) and (8,0) SWCNTs, and (16,0) and (25,0) SWCNTs with and without vacancy. The theoretical calculations showed that the binding energies between ARS dye and SWCNTs are enhanced as the nanotube diameter gets bigger; however, the distance of binding remains unchanged. Therefore, the results from first principle calculations indicated that electrostatic interaction may be responsible for the adsorption of ARS dye onto SWCNT. The theoretical outcomes were found to be in coordination with the experimental estimates.
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