Proliferation versus regeneration: the good, the bad and the ugly.
TL;DR: It is crucial that a diagnosis of the tumor to take place before any therapeutic intervention, and the tissue need for reconstruction would most probably implicate new stem cells that possess the ability to recognize the site of defect, locate it and initiate the reconstruction, which involves regeneration.
Abstract: Adult stem cells represent quiescent cells that once prompted, they proliferate with the potential to differentiate into a range of progeny providing regenerative medicine with novel tools for cure and rehabilitation. However, the risk that these proliferating stem cells could easily become a tumor cell sets barriers for their use. But, how are stem cells involved in tumor formation? The answer is that they possess a common mechanism: their ability for proliferation, differentiation, and of self-renewing beyond the body's capabilities. This exact trait is that makes stem cells so promisable and terrifying at the same moment, leading to Erebus. Tumors are interpreted in two distinct ways. Either as a disease, where the cause is interpreted as a cellular/genomic malfunction or as a reaction where the cause is interpreted as a natural consequence of evolutionary origin. As a result, treatment modalities could depend on this initial interpretation.
Generally though, tumorigenesis is described as a normal cell initially being transformed to a tumor cell that starts to proliferate. This cell could be a differentiated somatic cell or an adult stem cell that could develop into a cancer stem cell (CSC). It is crucial that a diagnosis of the tumor to take place before any therapeutic intervention. Most of the times therapies involve surgical or chemical elimination of the tumor. Thus at that point, the tissue need for reconstruction would most probably implicate new stem cells that possess the ability to recognize the site of defect, locate it and initiate the reconstruction, which involves regeneration.
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TL;DR: The proposed scheme can be effectively used for neurofeedback training and rehabilitation of lower-limb amputees and paralyzed patients.
Abstract: In this paper, a novel functional near-infrared spectroscopy (fNIRS)-based brain-computer interface (BCI) framework for control of prosthetic legs and rehabilitation of patients suffering from locomotive disorders is presented. fNIRS signals are used to initiate and stop the gait cycle, while a nonlinear proportional derivative computed torque controller (PD-CTC) with gravity compensation is used to control the torques of hip and knee joints for minimization of position error. In the present study, the brain signals of walking intention and rest tasks were acquired from the left hemisphere’s primary motor cortex for nine subjects. Thereafter, for removal of motion artifacts and physiological noises, the performances of six different filters (i.e. Kalman, Wiener, Gaussian, hemodynamic response filter (hrf), Band-pass, finite impulse response) were evaluated. Then, six different features were extracted from oxygenated hemoglobin signals, and their different combinations were used for classification. Also, the classification performances of five different classifiers (i.e. k-Nearest Neighbour, quadratic discriminant analysis, linear discriminant analysis (LDA), Naive Bayes, support vector machine (SVM)) were tested. The classification accuracies obtained from SVM using the hrf were significantly higher (p < 0.01) than those of the other classifier/ filter combinations. Those accuracies were 77.5, 72.5, 68.3, 74.2, 73.3, 80.8, 65, 76.7, and 86.7% for the nine subjects, respectively. The control commands generated using the classifiers initiated and stopped the gait cycle of the prosthetic leg, the knee and hip torques of which were controlled using the PD-CTC to minimize the position error. The proposed scheme can be effectively used for neurofeedback training and rehabilitation of lower-limb amputees and paralyzed patients.
83 citations
TL;DR: This study investigates the transcriptome and biomineralization responses of Pinctada fucata to elevated CO2 and temperature, suggesting that the pearl oyster utilizes anti-oxidative and lysosome strategies to alleviate the effects of temperature stress.
Abstract: Ocean acidification and global warming have been shown to significantly affect the physiological performances of marine calcifiers; however, the underlying mechanisms remain poorly understood. In this study, the transcriptome and biomineralization responses of Pinctada fucata to elevated CO2 (pH 7.8 and pH 7.5) and temperature (25 °C and 31 °C) are investigated. Increases in CO2 and temperature induced significant changes in gene expression, alkaline phosphatase activity, net calcification rates and relative calcium content, whereas no changes are observed in the shell ultrastructure. “Ion and acid-base regulation” related genes and “amino acid metabolism” pathway respond to the elevated CO2 (pH 7.8), suggesting that P. fucata implements a compensatory acid-base mechanism to mitigate the effects of low pH. Additionally, “anti-oxidation”-related genes and “Toll-like receptor signaling”, “arachidonic acid metabolism”, “lysosome” and “other glycan degradation” pathways exhibited responses to elevated temperature (25 °C and 31 °C), suggesting that P. fucata utilizes anti-oxidative and lysosome strategies to alleviate the effects of temperature stress. These responses are energy-consuming processes, which can lead to a decrease in biomineralization capacity. This study therefore is important for understanding the mechanisms by which pearl oysters respond to changing environments and predicting the effects of global climate change on pearl aquaculture.
69 citations
TL;DR: Cross-species comparative studies can generate mechanistic insights in regeneration for animals with long gestation periods e.g. Newts, and extrapolation of regenerative capabilities from highly regenerative species to animals with low regeneration potential, e.
36 citations
TL;DR: In this paper, an up-regulation of OIP5-AS1 attenuated infarct volume, neuronal apoptosis, microglia/macrophage inflammation and oxidative stress responses induced by MCAO/R or OGD/R.
33 citations
TL;DR: Comparing comparisons with potassium-binding, the binding of sodium ions appears to shift the population toward conformational states that might be catalytically favorable, suggesting Na+-mediated generalized allostery is the mechanism of thrombin's functional switch between the "fast" and "slow" forms.
Abstract: Thrombin is a multifunctional enzyme that plays an important role in blood coagulation, cell growth, and metastasis. Depending upon the binding of sodium ions, thrombin presents significantly different enzymatic activities. In the environment with sodium ions, thrombin is highly active in cleaving the coagulated substrates and this is referred to as the "fast" form; in the environment without sodium ions, thrombin turns catalytically less active and is in the "slow" form. Although many experimental studies over the last two decades have attempted to reveal the structural and kinetic differences between these two forms, it remains vague and disputed how the functional switch between the "fast" and "slow" forms is mediated by Na+ cations. In this work, we employ microsecond-scale all-atom molecular dynamics simulations to investigate the differences in the structural ensembles in sodium-bound/unbound and potassium-bound/unbound thrombin. Our calculations indicate that the regulatory regions, including the 60s, γ loops, and exosite I and II, are primarily affected by both the bound and unbound cations. Conformational free energy surfaces, estimated from principal component analysis, further reveal the existence of multiple conformational states. The binding of a cation introduces changes in the distribution of these states. Through comparisons with potassium-binding, the binding of sodium ions appears to shift the population toward conformational states that might be catalytically favorable. Our study of thrombin in the presence of sodium/potassium ions suggests Na+-mediated generalized allostery is the mechanism of thrombin's functional switch between the "fast" and "slow" forms.
26 citations
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TL;DR: The development of a xenograft assay that identified human brain tumour initiating cells that initiate tumours in vivo gives strong support for the CSC hypothesis as the basis for many solid tumours, and establishes a previously unidentified cellular target for more effective cancer therapies.
Abstract: The cancer stem cell (CSC) hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell properties. Although the existence of CSCs in human leukaemia is established, little evidence exists for CSCs in solid tumours, except for breast cancer. Recently, we prospectively isolated a CD133+ cell subpopulation from human brain tumours that exhibited stem cell properties in vitro. However, the true measures of CSCs are their capacity for self renewal and exact recapitulation of the original tumour. Here we report the development of a xenograft assay that identified human brain tumour initiating cells that initiate tumours in vivo. Only the CD133+ brain tumour fraction contains cells that are capable of tumour initiation in NOD-SCID (non-obese diabetic, severe combined immunodeficient) mouse brains. Injection of as few as 100 CD133+ cells produced a tumour that could be serially transplanted and was a phenocopy of the patient's original tumour, whereas injection of 10(5) CD133- cells engrafted but did not cause a tumour. Thus, the identification of brain tumour initiating cells provides insights into human brain tumour pathogenesis, giving strong support for the CSC hypothesis as the basis for many solid tumours, and establishes a previously unidentified cellular target for more effective cancer therapies.
7,120 citations
Journal Article•
TL;DR: The identification and purification of a cancer stem cell from human brain tumors of different phenotypes that possesses a marked capacity for proliferation, self-renewal, and differentiation is reported.
Abstract: Most current research on human brain tumors is focused on the molecular and cellular analysis of the bulk tumor mass. However, there is overwhelming evidence in some malignancies that the tumor clone is heterogeneous with respect to proliferation and differentiation. In human leukemia, the tumor clone is organized as a hierarchy that originates from rare leukemic stem cells that possess extensive proliferative and self-renewal potential, and are responsible for maintaining the tumor clone. We report here the identification and purification of a cancer stem cell from human brain tumors of different phenotypes that possesses a marked capacity for proliferation, self-renewal, and differentiation. The increased self-renewal capacity of the brain tumor stem cell (BTSC) was highest from the most aggressive clinical samples of medulloblastoma compared with low-grade gliomas. The BTSC was exclusively isolated with the cell fraction expressing the neural stem cell surface marker CD133. These CD133+ cells could differentiate in culture into tumor cells that phenotypically resembled the tumor from the patient. The identification of a BTSC provides a powerful tool to investigate the tumorigenic process in the central nervous system and to develop therapies targeted to the BTSC.
4,899 citations
TL;DR: Tumors of epithelioma are composed of two discrete but interdependent compartments: the malignant cells themselves and the stroma that they induce and in which they are dispersed.
Abstract: SOLID tumors are composed of two discrete but interdependent compartments: the malignant cells themselves and the stroma that they induce and in which they are dispersed.1 , 2 In tumors of epitheli...
4,132 citations
"Proliferation versus regeneration: ..." refers background in this paper
...The application of the term “wound” was given to cancer by Dvorak (1986), highlighting the fact that both wound healing and tumor development require a microenvironment and a support of stromal cells in order to occur....
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TL;DR: This review focuses on the healing processes of the skin and highlights the classical wound healing phases and the physiological endpoint of mammalian wound repair displays the formation of a scar, which is directly linked to the extent of the inflammatory process throughout wound healing.
Abstract: The skin is the biggest organ of the human being and has many functions. Therefore, the healing of a skin wound displays an extraordinary mechanism of cascading cellular functions which is unique in nature. As healing and regeneration processes take place in all parts of the human body, this review focuses on the healing processes of the skin and highlights the classical wound healing phases. While regeneration describes the specific substitution of the tissue, i.e. the superficial epidermis, mucosa or fetal skin, skin repair displays an unspecific form of healing in which the wound heals by fibrosis and scar formation. The first stage of acute wound healing is dedicated to hemostasis and the formation of a provisional wound matrix, which occurs immediately after injury and is completed after some hours. Furthermore, this phase initiates the inflammatory process. The inflammatory phase of the wound healing cascade gets activated during the coagulation phase and can roughly be divided into an early phase with neutrophil recruitment and a late phase with the appearance and transformation of monocytes. In the phase of proliferation the main focus of the healing process lies in the recovering of the wound surface, the formation of granulation tissue and the restoration of the vascular network. Therefore, next to the immigration of local fibroblasts along the fibrin network and the beginning of reepithelialization from the wound edges, neovascularization and angiogenesis get activated by capillary sprouting. The formation of granulation tissue stops through apoptosis of the cells, characterizing a mature wound as avascular as well as acellular. During the maturation of the wound the components of the extracellular matrix undergo certain changes. The physiological endpoint of mammalian wound repair displays the formation of a scar, which is directly linked to the extent of the inflammatory process throughout wound healing.
2,242 citations
"Proliferation versus regeneration: ..." refers background in this paper
...However, regeneration could emerge from tumor cells and as a result, tissue recovery becomes linked to cancerrelated cellular anomalies (Beachy et al., 2004; Gurtner et al., 2008; Schafer and Werner, 2008; Pellettieri et al., 2010)....
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TL;DR: This work shows that endothelial cells interact closely with self-renewing brain tumor cells and secrete factors that maintain these cells in a stem cell-like state, and proposes that brain CSCs are maintained within vascular niches that are important targets for therapeutic approaches.
2,065 citations
"Proliferation versus regeneration: ..." refers background in this paper
...Indeed, tumor microenvironment orchestrates a vascular niche formation, determining the fate of CSCs (Calabrese et al., 2007)....
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...As feeding becomes an urgent requirement to support the rapid growth of the www.frontiersin.org January 2014 | Volume 5 | Article 10 | 1 tumor, microenvironmental stimuli facilitate CSCs vasculature crosstalk....
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...Tumors could stem from CSCs (Oishi and Wang, 2011), as evidence suggests for different tumors types, such as glioblastoma (Singh et al., 2003, 2004) breast cancer (Jain and Alahari, 2011), ovarian cancer (Curley et al., 2011) and gastrointestinal cancer (Davies et al., 2011; Skoudy et al., 2011; Zheng et al., 2011)....
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...An interplay between CSCs and microenvironment has been observed in colon cancer, where the pluripotency of CSCs is maintained at the base of colon crypts influenced by fibroblast, endothelium and inflammatory cells, cytokines and growth factors secreted by these cells (in particular HGF) and by that means ultimately the balance between self-renewal and differentiation of the staminal population is regulated (Adegboyega et al., 2002; De Sousa et al., 2011; Catalano et al., 2013)....
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