Accumulating lines of experimental evidence have revealed that hypoxia‐inducible factors, HIF‐1α and HIF‐2α, are key regulators of the adaptation of cancer‐ and metastasis‐initiating cells and their ...differentiated progenies to oxygen and nutrient deprivation during cancer progression under normoxic and hypoxic conditions. Particularly, the sustained stimulation of epidermal growth factor receptor (EGFR), insulin‐like growth factor‐1 receptor (IGF‐1R), stem cell factor (SCF) receptor KIT, transforming growth factor‐β receptors (TGF‐βRs) and Notch and their downstream signalling elements such as phosphatidylinositol 3′‐kinase (PI3K)/Akt/molecular target of rapamycin (mTOR) may lead to an enhanced activity of HIFs. Moreover, the up‐regulation of HIFs in cancer cells may also occur in the hypoxic intratumoral regions formed within primary and secondary neoplasms as well as in leukaemic cells and metastatic prostate and breast cancer cells homing in the hypoxic endosteal niche of bone marrow. The activated HIFs may induce the expression of numerous gene products such as induced pluripotency‐associated transcription factors (Oct‐3/4, Nanog and Sox‐2), glycolysis‐ and epithelial‐mesenchymal transition (EMT) programme‐associated molecules, including CXC chemokine receptor 4 (CXCR4), snail and twist, microRNAs and angiogenic factors such as vascular endothelial growth factor (VEGF). These gene products in turn can play critical roles for high self‐renewal ability, survival, altered energy metabolism, invasion and metastases of cancer cells, angiogenic switch and treatment resistance. Consequently, the targeting of HIF signalling network and altered metabolic pathways represents new promising strategies to eradicate the total mass of cancer cells and improve the efficacy of current therapies against aggressive and metastatic cancers and prevent disease relapse.
In this study, we report on recent advances on the functions of embryonic, fetal, and adult stem cell progenitors for tissue regeneration and cancer therapies. We describe new procedures for ...derivation and maturation of these stem cells into the tissue‐specific cell progenitors. The localization of the adult stem cells and their niches, as well as their implication in the tissue repair after injuries and during cancer progression, are also described. The emphasis is on the interactions among certain developmental signaling factors, such as hormones, epidermal growth factor, hedgehog, Wnt/β‐catenin, and Notch. These factors and their pathways are involved in the stringent regulation of the self‐renewal and/or differentiation of adult stem cells. Novel strategies for the treatment of both diverse degenerating disorders, by cell replacement, and some metastatic cancer types, by molecular targeting multiple tumorigenic signaling elements in cancer progenitor cells, are also illustrated.
Curcumin has attracted great attention in the therapeutic arsenal in clinical oncology due to its chemopreventive, antitumoral, radiosensibilizing and chemosensibilizing activities against various ...types of aggressive and recurrent cancers. These malignancies include leukemias, lymphomas, multiple myeloma, brain cancer, melanoma and skin, lung, prostate, breast, ovarian, liver, gastrointestinal, pancreatic and colorectal epithelial cancers. Curcumin mediates its anti-proliferative, anti-invasive and apoptotic effects on cancer cells, including cancer stem/progenitor cells and their progenies, through multiple molecular mechanisms. The oncogenic pathways inhibited by curcumin encompass the members of epidermal growth factor receptors (EGFR and erbB2), sonic hedgehog (SHH)/GLIs and Wnt/β-catenin and downstream signaling elements such as Akt, nuclear factor-kappa B (NF-κB) and signal transducers and activators of transcription (STATs). In counterbalance, the high metabolic instability and poor systemic bioavailability of curcumin limit its therapeutic efficacy in human. Of great therapeutic interest, the selective delivery of synthetic analogs or nanotechnology-based formulations of curcumin to tumors, alone or in combination with other anticancer drugs, may improve their chemopreventive and chemotherapeutic efficacies against cancer progression and relapse. Novel curcumin formulations may also be used to reverse drug resistance, eradicate the total cancer cell mass and improve the anticarcinogenic efficacy of the current anti-hormonal and chemotherapeutic treatments for patients with various aggressive and lethal cancers.
A study of carbon dioxide sequestration has been performed in aqueous electric arc furnace (EAF) and ladle furnace (LF) slag suspensions, in leached hydrated-matrixes, and in leachates to estimate ...their intrinsic sequestration potential at ambient conditions (temperature of 20 ± 1 °C and atmospheric pressure). The CO2 sequestration was tested in aqueous suspensions of steel slags at a liquid-to-solid ratio of 10 kg/kg as well as in leached hydrated-matrixes and leachates isolated from these fresh slag suspensions after three consecutive leachings. The sequestration assays were performed at 20 °C with a flow rate of 5 mL/min of a CO2 concentration of 15.00 vol %. The results have revealed that the CO2 sequestration capacity of the LF slag suspension (24.7 g of CO2/100 g of slag) is 14 times superior to that of the EAF slag suspension. This greater CO2 sequestration capacity of the LF slag suspension may be associated in large part to its higher content of portlandite, which reacts with CO2 relative to the EAF slag suspension. Moreover, the separation of hydrated-matrixes and leachates significantly enhanced the CO2 sequestration capacity of EAF slag while a slight decrease was observed for the LF slags. This may be due to an obstruction of the CO2 binding sites of LF slag hydrated-matrixes following the accumulation of calcium carbonate. Taken together, these results suggest that EAF and LF slags could be used for the CO2 sequestration and given a good yield as well in aqueous suspension as in separated matrixes and leachates.
The progression of prostate cancers (PCs) to locally invasive, androgen-independent and metastatic disease states is generally associated with treatment resistance and disease relapse. The present ...study was undertaken to establish the possibility of using a combination of specific oncogenic products, including epidermal growth factor receptor (EGFR), pAkt, nuclear factor-kappaB (NF-κB) and macrophage inhibitory cytokine-1 (MIC-1) as biomarkers and therapeutic targets for optimizing the management of patients with localized PC at earlier disease stages. The immunohistochemical and immunofluorescence data have revealed that the expression levels of EGFR, Ser(473)-pAkt, NF-κB p65 and MIC-1 proteins were significantly enhanced in the same subset of 76 cases of prostatic adenocarcinoma specimens during the disease progression and these biomarkers were expressed in a small subpopulation of CD133(+) PC cells and the bulk tumor mass of CD133(-) PC cells. Importantly, all of these biomarkers were also overexpressed in 80-100% of 30 PC metastasis bone tissue specimens. Moreover, the results have indicated that the EGF-EGFR signaling pathway can provide critical functions for the self-renewal of side population (SP) cells endowed with stem cell-like features from highly invasive WPE1-NB26 cells. Of therapeutic interest, the targeting of EGFR, pAkt, NF-κB or MIC-1 was also effective at suppressing the basal and EGF-promoted prostasphere formation by SP WPE1-NB26 cells, inducing disintegration of SP cell-derived prostaspheres and decreasing the viability of SP and non-SP WPE1-NB26 cell fractions. Also, the targeting of these oncogenic products induced the caspase-dependent apoptosis in chemoresistant SP WPE1-NB26 cells and enhanced their sensibility to the cytotoxic effects induced by docetaxel. These findings suggest that the combined use of EGFR, pAkt, NF-κB and/or MIC-1 may represent promising strategies for improving the accuracy of current diagnostic and prognostic methods and efficacy of treatments of PC patients in considering the disease heterogeneity, thereby preventing PC progression to metastatic and lethal disease states.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent data on the cellular ceramide functions and its involvement in the apoptotic/necrotic cell death as well as its anticarcinogenic properties are presented. The emphasis is on the connections ...between the ceramide and caspase signaling pathways during the apoptotic cell death process. Notably, the experimental strategies and pharmacological tools used for establishment of the role of ceramide in triggering cell death are described. Moreover, the importance of a compartmentation of endogenous ceramide within the plasma membrane microdomains, lysosomes and mitochondria is discussed. Information on the deregulated functions of ceramide and caspase signaling pathways in several metastatic cancer types is also presented.
A study of carbon dioxide (CO2) absorption/desorption has been carried out to estimate the influence of the structural features of distinct amines on their CO2 absorption and regeneration. The ...absorption has been made at two different CO2 flow rates with a series of aqueous 5 wt % ammonia, monoethanolamine (MEA), triethanolamine (TEA), triethylamine, pyridine, pyrrolidine, 2-(2-aminoethylamino)ethanol (AEE), and N-(2-aminoethyl)-1,3-propanediamine (AEPDNH2) solutions, while the CO2 desorption has been performed by heating these solutions. The presence of two or three amino groups in AEE and AEPDNH2, the structure of tertiary amine and alkanolamine, and a nonaromatic ring of pyrrolidine might favor the CO2 absorption, while the structural features of ammonia and pyridine seem to be unfavorable. The tertiary alkanolamine is the most easy to regenerate and looses less of its CO2 loading after regeneration. It appears that AEE and AEPDNH2 would represent interesting compounds which could be used as CO2 absorbents in industrial technologies to prevent CO2 release into the atmosphere.
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