Tumors are consisted of monoclonal cells, but the individual cells in tumors show various phenotypes. Recently, it has been reported that tumors are derived from a limited population of cells, called tumor-initiating cells, that are resistant to chemo-radio therapies and are tumorigenic. Tumor-initiating cells are considered to cause recurrence and metastasis of tumors. Here, we summarized the markers characteristic to tumor-initiating cells
In this study, we investigated the impact of UE6E7T-12 bone marrow-derived mesenchymal stem cells (BM-MSCs) on the proliferation and cluster formation of gastric carcinoma (GC)-derived MKN-7 cells. Interestingly, co-culture with UE6E7T-12 BM-MSCs increased the population of CD133+ MKN-7 cells in vitro and co-implantation of MKN-7 cells and UE6E7T-12 BM-MSCs in mice resulted in subcutaneous tumors in vivo, suggesting BM-MSCs’ function in the restoration of cancer stem cells (CSCs). By a differential analysis of gene expression profiles, we identified that co-incubation of MKN-7 cells and UE6E7T-12 BM-MSCs induced WNT5A expression in MKN-7 cells and TGF-β1 expression in UE6E7T-12 BM-MSCs, respectively. Of note, WNT5A and TGF-β1 independently enlarged the population of CD133+ MKN-7 cells, even in the absence of co-culture with UE6E7T-12 BM-MSCs. In human diffuse-type GC tissues, recruitment of CD271+ BM-MSC was detected in the tumor stroma and GC cells showed frequent positivity against WNT5A, TGF-β type I receptor and CD133. These findings suggest that BM-MSCs provide an advantageous microenvironment for cancer progression by supporting the re-acquisition and maintenance of CSCs. BM-MSC-mediated activations of the WNT and TGF-β signaling pathways may be attractive therapeutic targets for blocking the evolution of GC cells.
Blood vessels have a fundamental role in supplying oxygen, nutrient, inflammatory cells. Moreover, they are also involved in organ generation and maintenance. For instance, blood vessels provide a niche, a microenvironment that supports self-renew of stem cell population in normal organ. This concept expands to the field of cancer biology and it has been suggested that cancer stem cells are located in a perivascular region for their proliferation. Moreover, through cell-to-cell contact, arteries guide adequate migration direction of neurite. Therefore, analysis of molecular mechanism in blood vessel formation and maintenance is important to develop a strategy for the regulation of tissue regeneration. In usual concept of angiogenesis, it has been widely accepted that endothelial cells from preexisting vessels sprout and proliferate monotonously during angiogenesis; however, recently at least three different endothelial cells such as tip, stalk and phalanx cells have been suggested to be involved in new blood vessel formation in sprouting angiogenesis. In such heterogeneity of endothelial cells, involvement of stem cell system is argued in preexisting blood vessels.
Cancer stem-like cells/ tumor-initiating cells (CSCs/TICs) have been reported in several malignancies. CSCs/TICs are defined as a highly tumorigenic small subpopulation of cancer cells and they are thought to maintain tumor. CSCs/TICs are known to be resistant to standard cancer therapies including chemotherapy and radiotherapy. Therefore, CSCs/TICs are thought to be deeply related to distant metastasis and/or recurrence after treatment, and elimination of CSCs/TICs is essential to cure the disease. Cancer immunotherapy research have greatly developed in the last two decades, and now several clinical trials for the cancer immunotherapy have already been launched throughout the world. It is now expected as the fourth standard cancer therapy following operative therapy, chemotherapy and radiotherapy. In this review article, we summerize the recent progress of cancer immunotherapy targeting CSCs/TICs, and discuss how it will become to be practicable.
Recent developments of X-ray emission spectroscopy instruments for electron microscopy for obtaining a density of states of valence bands are briefly described. The latest TEM-SXES instrument (ver.6) for 50-4000eV and its spectrum of Li-K emission are presented. An example of anisotropic N-K emission spectra obtained from a single crystalline h-BN is shown. From the spectra, density of states of π- and σ-bondings were separately derived. Those results demonstrated a method to analyze the electronic states of valence electrons of materials based of electron microscopy.
A newly reported bioactive peptide, kisspeptin and its receptor (Kiss1r or GPR54) have an important role as key player in the regulation of reproduction. Mutations of the peptide and its receptor cause profound hypothalamic hypogonadotropic hypogonadism. Kisspeptin neurons are expressed in the hypothalamus, as well as other brain region in many vertebrates. Kisspeptin neurons directly project to GnRH neurons and may stimulate to secrete GnRH. Kisspeptin neurons show sexually difference with respect to the number of neurons and transcription activity in certain nuclei in the brain, and some kisspeptin neurons coexpress other transmitters, dynorphin and neurokinin B. Kisspeptin signaling system mediated by estrogen via estrogen receptor a has been related in mediateing the positive and negative feedback action of sex steroids on LH/FSH secretion, generating the preovulatory GnRH and/or LH surge, and triggering and guiding the onset of puberty.In this review, we introduce the morphological characteristics and many important physiological function of kisspeptin and its receptor.
The paraxial trajectory method has been generalized for the application to the cathode rays inside electron guns. The generalized method can handle rays that initially make a large angle with the optical axis. The key to success of the generalization is the adoption of the trigonometric function sine for the trajectory slope specification, instead of the conventional use of the tangent. It is possible to relate the ray conditions (position and slope of the ray at reference planes) on the cathode to those at the crossover plane using third-order polynomial functions, whose coefficients can be used as the optical parameters in the characterization of electron sources. Among them the electron gun focal length can be used for a quantitative estimate of both the crossover size and the angular current intensity. An electron gun simulation program G-optk has been developed based on the generalized paraxial trajectory theory. The program calculates the principal paraxial trajectories and the relevant optical parameters from axial potentials and fields. It gives a clear physical picture of the electron gun in a much more faster way than the conventional ray-tracing methods.
Novel methods for Golgi-stain-like labeling of neurons have been developed by applying molecular biological technique. Using replication-deficient Sindbis viral vectors expressing membrane-targeted green fluorescent protein (GFP) or monomeric red fluorescent protein (mRFP), we visualized the neuronal processes of the infected neurons completely. Furthermore, when sufficiently diluted Sindbis virus solution was injected into the brain, the entire axonal arborization of the infected neurons was recovered at a single cell level, giving new insights into neuronal networks. Since neuronal processes, axons and dendrites, are key structures of neuronal information processing, the Sindbis viral vectors introduced here are useful for the morphological analysis of neuronal networks and thus helpful for understanding the functional design of the nervous system.
Recent biological imaging is developing into a powerful technique for visualization of particular neurons, dendritic trees, and axons. Neuron tracing is also effective tool to understand anatomical structure. Although manual tracing is available for only cell shape with 2 dimensional(D) information, digital tracing gives us morphometric date and 3D reconstructed neurons. Based on these data, characteristics of each neuron are expressed as a numerical value and we can accurately classify neurons by statistical analysis, and elucidate to its neuronal network and functional role. Here, we would like to show some of useful analyses by using Neurolucida.
We have developed an Atmospheric Scanning Electron Microscope (ASEM), which has a sample space open to the air. In this study, materials in liquid or gas were dynamically observed with Optical Microscope (OM) and Electron Microscope (EM). We video-recorded in-situ SEM observation of limited Brownian motion and the radiateon-induced self-organization of small particles in liquid, dendritic salt crystal formation due to evaporation, electrochemical reactions in electrolytes, and melting and solidification of solder. The ASEM is expected to be applicable for various kinds of dynamic phenomena in liquid or gas.
Sub-nanometer atomic scale characterization has been applied widely with aberration-corrected electron microscopy. We have been studying atomic-resolution secondary electron imaging with aberration-corrected scanning transmission electron microscope. As a result of a series of experiments, we have succeeded in observing isolated single uranium atoms using secondary electron signals. In addition, we observed atomic-resolution images not only for heavy elements like uranium but also light ones like silicon and carbon.