CD133(+) liver tumor-initiating cells promote tumor angiogenesis, growth, and self-renewal through neurotensin/interleukin-8/CXCL1 signaling

A novel theory in the field of tumor biology postulates that cancer growth is driven by a population of stem-like cells, called tumor-initiating cells (TICs). We previously identified a TIC population derived from hepatocellular carcinoma (HCC) that is characterized by membrane expression of CD133. Here, we describe a novel mechanism by which these cells mediate tumor growth and angiogenesis by systematic comparison of the gene expression profiles between sorted CD133 liver subpopulations through genome-wide microarray analysis. A significantly dysregulated interleukin-8 (IL-8) signaling network was identified in CD133(+) liver TICs obtained from HCC clinical samples and cell lines. IL-8 was found to be overexpressed at both the genomic and proteomic levels in CD133(+) cells isolated from HCC cell lines or clinical samples. Functional studies found enhanced IL-8 secretion in CD133(+) liver TICs to exhibit a greater ability to self-renew, induce tumor angiogenesis, and initiate tumors. In further support of these observations, IL-8 repression in CD133(+) liver TICs by knockdown or neutralizing antibody abolished these effects. Subsequent studies of the IL-8 functional network identified neurotensin (NTS) and CXCL1 to be preferentially expressed in CD133(+) liver TICs. Addition of exogenous NTS resulted in concomitant up-regulation of IL-8 and CXCL1 with simultaneous activation of p-ERK1/2 and RAF-1, both key components of the mitogen-activated protein kinase (MAPK) pathway. Enhanced IL-8 secretion by CD133(+) liver TICs can in turn activate an IL-8-dependent feedback loop that signals through the MAPK pathway. Further, in its role as a liver TIC marker CD133 also plays a functional part in regulating tumorigenesis of liver TICs by way of regulating NTS, IL-8, CXCL1, and MAPK signaling. CONCLUSION: CD133(+) liver TICs promote angiogenesis, tumorigenesis, and self-renewal through NTS-induced activation of the IL-8 signaling cascade.     

Recent trends in cartilage regenerative medicine and its application to oral and maxillofacial surgery

Greater progress has been made in the clinical application of cartilage regenerative medicine, compared with that of other organs. A typical example of cartilage regenerative medicine is autologous chondrocyte implantation, in which chondrocytes isolated from the patient's cartilage are cultured and injected into the cartilage defects in a liquid- or gel-form. However, the classic autologous chondrocyte implantation has been applicable to only limited diseases, including focal cartilage lesion. Therefore, we developed “implant-type” tissue-engineered cartilage that shows mechanical strength and three-dimensional shape. This type of tissue-engineered cartilage uses scaffold composed of atelocollagen hydrogel and poly-l-lactic acid porous material, which is administered with cultured autologous auricular chondrocytes. Its clinical application to nasal deformity of cleft lip and palate patients has been ongoing at present. This review presents an overview of the current situation regarding cartilage regenerative medicine, as well as introducing our research and the development of implant-type tissue-engineered cartilage for the cleft-lip nose. The discussion of the future development of regenerative medicine is also mentioned.     

Risk Factors of Local Oropharyngeal and Laryngeal Adverse Effects from Use of Single Inhaled Corticosteroids and Long-Acting Beta-Agonists

Background: Single inhaled corticosteroids and long-acting beta-agonists (ICS/LABA) are clinically effective and safe. However, if local oropharyngeal and laryngeal adverse effects (LOLAE) appear, adherence to the use of ICS is impaired. To minimize the development of adverse effects, it is essential to identify the underlying risk factors.Methods: The study included 481 asthmatic patients who were prescribed ICS/LABA for the first time in their life between January and September of 2010. Patients ranged in age from 14 to 86 years old and consisted of 281 never smokers and 200 smokers. All data were collected retrospectively by respirologists.Results: Seventy-three out of 481 patients suffered from one or more adverse effects, with 54 of these exhibiting LOLAE. Patients with LOLAE (51.4 ± 16.2 yrs) were significantly older than those without LOLAE (43.7 ± 15.9 yrs) (p = 0.0011) and were also prescribed a significantly higher dose of ICS. The pack-years of patients with LOLAE (2.1 ± 4.9) were significantly lowerthan those without LOLAE (6.0 ± 13.0) (p = 0.0087). The type of administered ICS was also significantly associated with a risk of developing LOLAE.Conclusions: Our survey indicated that a greater age, a higher dose of ICS, and the type of ICS were potential risk factors of LOLAE. The identified factors should be considered in a clinical setting in order to prevent the development of LOLAE and provide optimal treatment to patients.     

Inorganic/organic nanocomposite ion gels with well dispersed secondary silica nanoparticles

We have previously reported tough inorganic/organic nanocomposite (NC) ion gels composed of silica particles and poly(N,N-dimethylacrylamide) (PDMAAm) networks and a large amount of ionic liquid. In this study, the network structure and toughening mechanism of NC ion gels were investigated. The NC ion gels showed characteristic mechanical properties; i.e. the stress was significantly increased at a highly elongated state. In addition, the NC ion gels showed an almost elastic mechanical property, which was completely different from that of our other developed inorganic/organic tough ion gels named double-network (DN) ion gels. It was found from structural observation that secondary silica nanoparticles dispersed well in the NC ion gel. It was also found that some of the secondary silica nanoparticles had a ring-like structure which would incorporate PDMAAm chains. From the silica particle content dependency on stress–strain curves of inorganic/organic NC ion gels, it was inferred that the secondary silica particles could serve as a movable cross-linker of PDMAAm chains in the NC ion gel.

Tough inorganic/organic nanocomposite (NC) ion gels with silica nanoparticle aggregates having a characteristic structure.     

Transcatheter closure of secundum atrial septal defect

Since the introduction of transcatheter closure of atrial septal defect, device closure has become the alternative treatment of selected atrial defects. Although excellent results have been reported for transcatheter closure, concerns have arisen regarding complications, including residual shunt, systemic or pulmonary embolization of the device, and erosion and perforation of the cardiac chamber. Those complications are rare but potentially serious adverse events that may require immediate surgical intervention. This review summarizes the current trends in patient selection, result of device closure and typical complications. Comparison between transcatheter device closure and surgical closure is also made.