The in vitro and in vivo characterization of adult stem cells has allowed researchers to identify certain specific functional features to each tissue-specific stem cell. Moreover, recent studies ...revealed that their malignant counterparts, the cancer progenitor cells with stem cell-like properties, may assume a crucial role for the initiation and progression of locally invasive cancers into disseminated and incurable disease states. Therefore, a new direction in cancer research appears necessary in considering the critical functions of cancer progenitor cells. In this review, we discuss recent concepts on the critical roles of tumorigenic and migrating cancer progenitor cells in carcinogenesis. Particularly, we describe the tumorigenic cascades that are frequently activated through the interplay of diverse hormones, growth factors, cytokines and integrins in cancer progenitor cells versus their further differentiated progeny. The emphasis is on the oncogenic signaling pathways activated during the localized cancer progression and micrometastatic events involved in tumor formation at distant sites such as bone marrow. Of therapeutic interest, important information for the selective molecular targeting of cancer progenitor cells, which must now be considered in developing new effective diagnostic and prognostic methods and curative treatments against the most locally advanced and metastatic cancers, is also described.
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Introduction
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Functions of skin‐resident adult stem/progenitor cells in skin regeneration
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Altered functions of skin‐resident adult stem/progenitor cells during chronological aging
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...Potential implications of skin‐resident stem/progenitor cells in skin aging‐related disorders
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Animal models of skin‐resident stem/progenitor cell aging and disorders
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Altered functions of skin‐resident adult stem/progenitor cells in skin hyperproliferative disorders and cancers
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Potential implications of cancer stem/progenitor cells in basal cell and squamous cell cancers
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Potential implications of cancer stem/progenitor cells in melanoma
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Molecular events associated with melanoma progression
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Novel stem cell‐based therapies
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Novel anti‐aging therapies
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Modulation of aging process by calorie restriction and pharmacological agents
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Novel cell‐replacement and gene therapies
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Novel cancer therapies targeting skin cancer stem/progenitor cells and their microenvironment
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Conclusions and future directions
Recent advances in skin‐resident adult stem/progenitor cell research have revealed that these immature and regenerative cells with a high longevity provide critical functions in maintaining skin homeostasis and repair after severe injuries along the lifespan of individuals. The establishment of the functional properties of distinct adult stem/progenitor cells found in skin epidermis and hair follicles and extrinsic signals from their niches, which are deregulated during their aging and malignant transformation, has significantly improved our understanding on the etiopathogenesis of diverse human skin disorders and cancers. Particularly, enhanced ultraviolet radiation exposure, inflammation and oxidative stress and telomere attrition during chronological aging may induce severe DNA damages and genomic instability in the skin‐resident stem/progenitor cells and their progenies. These molecular events may result in the alterations in key signalling components controlling their self‐renewal and/or regenerative capacities as well as the activation of tumour suppressor gene products that trigger their growth arrest and senescence or apoptotic death. The progressive decline in the regenerative functions and/or number of skin‐resident adult stem/progenitor cells may cause diverse skin diseases with advancing age. Moreover, the photoaging, telomerase re‐activation and occurrence of different oncogenic events in skin‐resident adult stem/progenitor cells may also culminate in their malignant transformation into cancer stem/progenitor cells and skin cancer initiation and progression. Therefore, the anti‐inflammatory and anti‐oxidant treatments and stem cell‐replacement and gene therapies as well as the molecular targeting of their malignant counterpart, skin cancer‐initiating cells offer great promise to treat diverse skin disorders and cancers.
An analysis of carbonation was carried out with the aqueous fresh red mud suspension at a liquid-to-solid ratio of 10 kg/kg, as well as in the leached-hydrated matrixes and leachates isolated from ...this red mud suspension after three successive leachings, to evaluate their intrinsic carbonation potential at ambient conditions (temperature of 20 ± 1 °C and atmospheric pressure). The carbonation assays were performed at 20 °C using a CO2 concentration of 15.00 vol% at a flow rate of 5 mL/min. The red mud matrix has a great leaching capacity of Na−(hydr)oxide, which is the principal hydroxide that seems to be implicated in the carbonation of leachates that have half-carbonation capacity of red mud. Moreover, the carbonation of the red mud suspension also involves a portlandite-containing matrix. The carbonation of the red mud suspension and leachates implicates a complete neutralization of their content in Ca− and Na−(hydr)oxides. Although the leached hydrated-matrixes seem to be partially carbonated, it preserves a carbonation capacity near to that of leachate after three successive leachings. Moreover, three leached hydrated-matrixes and leachates have a carbonation capacity (7.09 g of CO2/100 g of red mud) higher than the carbonation capacity obtained for the red mud suspension, which is evaluated to 4.15 g of CO2/100 g of red mud. Taken together, these results suggest that the carbonation of the red mud may be enhanced by the use of leached hydrated-matrixes and leachates obtained from multiple leaching.
The present study has been undertaken to establish the therapeutic benefit of cotargeting epidermal growth factor receptor (EGFR) and sonic hedgehog pathways by using gefitinib and cyclopamine, ...respectively, for improving the efficacy of the current chemotherapeutic drug docetaxel to counteract the prostate cancer progression from locally invasive to metastatic and recurrent disease stages. The data from immuofluorescence analyses revealed that EGFR/Tyr(1173)-pEGFR, sonic hedgehog ligand, smoothened coreceptor, and GLI-1 were colocalized with the CD133(+) stem cell-like marker in a small subpopulation of prostate cancer cells. These signaling molecules were also present in the bulk tumor mass of CD133(-) prostate cancer cells with a luminal phenotype detected in patient's adenocarcinoma tissues. Importantly, the results revealed that the CD133(+)/CD44(high)/AR(-/low) side population (SP) cell fraction endowed with a high self-renewal potential isolated from tumorigenic and invasive WPE1-NB26 cells by the Hoechst dye technique was insensitive to the current chemotherapeutic drug, docetaxel. In contrast, the docetaxel treatment induced significant antiproliferative and apoptotic effects on the CD133(-)/CD44(low)/AR(+) non-SP cell fraction isolated from the WPE1-NB26 cell line. Of therapeutic interest, the results have also indicated that combined docetaxel, gefitinib, and cyclopamine induced greater antiproliferative and apoptotic effects on SP and non-SP cell fractions isolated from WPE1-NB26 cells than individual drugs or two-drug combinations. Altogether, these observations suggest that EGFR and sonic hedgehog cascades may represent the potential therapeutic targets of great clinical interest to eradicate the total prostate cancer cell mass and improve the current docetaxel-based therapies against locally advanced and invasive prostate cancers, and thereby prevent metastases and disease relapse.
A study was carried out by ultraviolet-visible (UV-vis) and Fourier transform infrared (FTIR) spectroscopies to establish the efficiency of adsorption of fluoxetine hydrochloride (FLU), onto a ...crosslinked β-cyclodextrin-carboxymethylcellulose (β-CD-CMC) polymer. The adsorption was performed in mixtures containing aqueous FLU solution at 20 mg/L and 0.01-0.30 g of the β-CD-CMC polymer, at 25 °C, and atmospheric pressure under stirring. The results have revealed that the adsorption is a rapid process and the polymer possesses a high affinity for FLU with an adsorption capacity of 5.076 mg of FLU/g of polymer. This adsorption may involve the formation of a stable inclusion compound β-CD-CMC/FLU through the penetration of the FLU aromatic ring (A and/or B) into the β-CD cavity, and a physical adsorption with the polymer network. The inclusion compound can be stabilized by the formation of H-bonds between the -CF(3) group of FLU and the 6'-OH group of β-CD, and van der Waals interactions between the FLU aromatic ring and β-CD cavity. The data from a kinetic study have also indicated that the adsorption process was well described by the pseudo-second-order kinetic model, in which the initial adsorption rate and constant were estimated at 1.938 mg/g min and 0.075 g/mg min, respectively. Moreover, the results of adsorption equilibrium fitted the Freundlich isotherm, indicating a multilayer coverage and heterogeneous surface. Together, these results suggest that the adsorption of FLU onto the crosslinked β-CD-CMC polymer could constitute an advantageous technology for removing this commonly used antidepressant drug from wastewater due to the high adsorption capacity of the polymer and non-toxic character of β-CD to humans and environment.
This review summarizes the recent advancements that have improved our understanding of the functions of prostatic stem/progenitor cells in maintaining homeostasis of the prostate gland. We also ...describe the oncogenic events that may contribute to their malignant transformation into prostatic cancer stem/progenitor cells during cancer initiation and progression to metastatic disease stages. The molecular mechanisms that may contribute to the intrinsic or the acquisition of a resistant phenotype by the prostatic cancer stem/progenitor cells and their differentiated progenies with a luminal phenotype to the current therapies and disease relapse are also reviewed. The emphasis is on the critical functions of distinct tumorigenic signaling cascades induced through the epidermal growth factor system, hedgehog, Wnt/β-catenin, and/or stromal cell-derived factor-1/CXC chemokine receptor-4 pathways as well as the deregulated apoptotic signaling elements and ATP-binding cassette multidrug transporter. Of particular therapeutic interest, we also discuss the potential beneficial effects associated with the targeting of these signaling elements to overcome the resistance to current treatments and prostate cancer recurrence. The combined targeted strategies toward distinct oncogenic signaling cascades in prostatic cancer stem/progenitor cells and their progenies as well as their local microenvironment, which could improve the efficacy of current clinical chemotherapeutic treatments against incurable, androgen-independent, and metastatic prostate cancers, are also described.
A study of adsorption/recovery of nonylphenol 9 mole ethoxylate (NP9EO) on a crosslinked beta-cyclodextrin-carboxymethylcellulose (beta-CD-CMC) polymer was carried out by ultraviolet-visible (UV-vis) ...and Fourier transform infrared (FTIR) spectroscopies. The adsorption was performed in mixtures containing 500 mg of the beta-CD-CMC polymer and aqueous NP9EO solutions at concentrations 12-82 mg/L, whereas the recovery of NP9EO was effectuated by shaking the beta-CD-CMC polymer loaded with methanol. The assays were made at 25 degrees C and atmospheric pressure under agitation. The results have shown that the adsorption is a rapid process and the beta-CD-CMC polymer exhibits a high NP9EO adsorption capacity of 83-92 w% (1.1-6.8 mg NP9EO/g beta-CD-CMC polymer) dependent of the initial NP9EO concentration in liquid phase. This adsorption may involve the formation of an inclusion complex beta-CD-NP9EO and a physical adsorption in the polymer network. The adsorption equilibrium measurements, which were analyzed using the Langmuir isotherm, have indicated a monolayer coverage and the homogeneous distribution of active sites at the surface of the beta-CD-CMC polymer. Moreover, the negative value obtained for the free energy change (-13.2 kJ/mol) has indicated that the adsorption process is spontaneous. In parallel, the beta-CD-CMC polymer exhibited a high NP9EO recovery efficiency of 97 w% that may occur through a decrease of binding strength between beta-CD-CMC polymer and NP9EO. Together, these results suggest that the beta-CD-CMC polymer could constitute a good adsorbent for removing nonylphenol ethoxylates from wastewater due to its high adsorption capacity and non-toxic character of beta-CD and CMC to environment.
Recent advances in skin-resident adult stem/progenitor cell research have revealed that these immature and regenerative cells with a high longevity provide critical functions in maintaining skin ...homeostasis and repair after severe injuries along the lifespan of individuals. The establishment of the functional properties of distinct adult stem/progenitor cells found in skin epidermis and hair follicles and extrinsic signals from their niches, which are deregulated during their aging and malignant transformation, has significantly improved our understanding on the etiopathogenesis of diverse human skin disorders and cancers. Particularly, enhanced ultraviolet radiation exposure, inflammation and oxidative stress and telomere attrition during chronological aging may induce severe DNA damages and genomic instability in the skin-resident stem/ progenitor cells and their progenies. These molecular events may result in the alterations in key signalling components controlling their self-renewal and/or regenerative capacities as well as the activation of tumour suppressor gene products that trigger their growth arrest and senescence or apoptotic death. The progressive decline in the regenerative functions and/or number of skin-resident adult stem/progenitor cells may cause diverse skin diseases with advancing age. Moreover, the photoaging, telomerase re-activation and occurrence of different oncogenic events in skin-resident adult stem/progenitor cells may also culminate in their malignant transformation into cancer stem/progenitor cells and skin cancer initiation and progression. Therefore, the anti-inflammatory and anti-oxidant treatments and stem cell-replacement and gene therapies as well as the molecular targeting of their malignant counterpart, skin cancer-initiating cells offer great promise to treat diverse skin disorders and cancers. PUBLICATION ABSTRACT
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