The metastasis suppressor protein NM23-H1 modulates the PI3K-AKT axis through interaction with the p110α catalytic subunit.

The PI3K pathway is one of the most deregulated pathways in cancer, which is predominantly due to gain of function mutations or altered expression of the PI3KCA gene. This is codified by what is seen for the class I PI3K catalytic subunit p110α, a common feature of many cancers. The metastasis suppressor protein NM23-H1 (NME1), whose ability to suppress the metastasis activities of different tumors has been widely described and was previously reported to alter phosphatidylinositol signaling.

Power scalable 30-W mid-infrared fluoride fiber amplifier.

A fluoride-fiber-based master oscillator power amplifier (MOPA) for 30-W class continuous-wave (cw) operation at 2.8-μm wavelength has been demonstrated. To overcome the low durability of ZBLAN fibers, various novel technologies for using fluoride glass with a ZBLAN-fiber-based side-pump combiner have been adopted in the system.

Plane-by-plane femtosecond laser inscription of first-order fiber Bragg gratings in fluoride glass fiber for in situ monitoring of lasing evolution.

We report the femtosecond laser inscription of fiber Bragg gratings (FBGs) in an Er-doped fluoride glass fiber used for lasing at a mid-infrared wavelength of 2.8 µm. The lasing evolution is discussed in terms of the FBG reflectivity, wavelength transition to the Bragg wavelength, and output power of the mid-infrared fiber laser.

Optimization of laser emission at 2.8 μm by Er:LuO ceramics.

We have demonstrated the continuous-wave operation of a highly efficient 2.8 μm Er-doped LuO ceramic laser at room temperature. An Er:LuO ceramic with a doping concentration of 11 at.

Efficient continuous wave and quasi-continuous wave operation of a 2.8 μm Er:LuO ceramic laser.

We have demonstrated a highly efficient 2.8 μm Er-doped LuO ceramic laser and investigated the lasing dynamics by time-resolved spectroscopy. During room-temperature continuous wave operation, a slope efficiency of 22% was achieved with a high-quality transparent ceramic.

High load of Merkel cell polyomavirus DNA detected in the normal skin of Japanese patients with Merkel cell carcinoma.

Background: Although Merkel cell polyomavirus (MCPyV) has the potential to cause Merkel cell carcinoma (MCC), it is also found in the normal skin of healthy individuals. However, the mechanism for transformation of MCPyV to an oncogenic form is unknown.

Objectives: To investigate the levels of MCPyV infection in the normal skin patients with MCC compared with those in a control cohort.

Ecology of Merkel Cell Polyomavirus in Healthy Skin Among Individuals in an Asian Cohort.

Background: Despite the oncogenic potential of Merkel cell polyomavirus (MCPyV), it has been found in the normal skin of healthy individuals; however, little is known about geographical variations in the ecology of MCPyV in this tissue.

Methods: This study included 284 Japanese participants. Sun-unexposed arm and sun-exposed forehead skin swab samples were obtained and analyzed for MCPyV infection, using quantitative polymerase chain reaction.

Prevalence of human cytomegalovirus, polyomaviruses, and oncogenic viruses in glioblastoma among Japanese subjects.

Background: The association between human cytomegalovirus (HCMV) and glioblastoma multiforme (GBM) is becoming a new concept. However, information on the geographic variability of HCMV prevalence in GBM remains scarce. Moreover, the potential roles of various viruses, such as polyomaviruses and oncogenic viruses, in gliomagenesis remain unclear.

PCR array analysis of gene expression profiles in chronic active Epstein-Barr virus infection.

To determine the host cellular gene expression profiles in chronic active Epstein-Barr virus infection (CAEBV), peripheral blood samples were obtained from three patients with CAEBV and investigated using a PCR array analysis that focused on T-cell/B-cell activation. We identified six genes with expression levels that were tenfold higher in CAEBV patients compared with those in healthy controls. These results were verified by quantitative reverse transcription-PCR.

Characterization of Epstein-Barr virus (EBV) BZLF1 gene promoter variants and comparison of cellular gene expression profiles in Japanese patients with infectious mononucleosis, chronic active EBV infection, and EBV-associated hemophagocytic lymphohistiocytosis.

Epstein-Barr virus (EBV) genotypes can be distinguished based on gene sequence differences in EBV nuclear antigens 2, 3A, 3B, and 3C, and the BZLF1 promoter zone (Zp). EBV subtypes and BZLF1 Zp variants were examined in Japanese patients with infectious mononucleosis, chronic active EBV infection, and EBV-associated hemophagocytic lymphohistiocytosis. The results of EBV typing showed that samples of infectious mononucleosis, chronic active EBV infection, and EBV-associated hemophagocytic lymphohistiocytosis all belonged to EBV type 1.

Promoter methylation of the bone morphogenetic protein 6 gene in multiple myeloma.

Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-β superfamily, are multifunctional signaling molecules that have become of increasing interest in cancer research. Recent observations suggest that alterations in BMPs and BMP signaling are associated with tumorigenesis and disease progression in various types of malignancies. This study investigated the methylation status of the BMP6 gene promoter in various types of plasma cell proliferative disorders by combined bisulfite restriction analysis.

12 W Q-switched Er:ZBLAN fiber laser at 2.8 μm.

A diode-pumped, actively Q-switched 2.8 μm fiber laser oscillator with an average output power of more than 12 W has been realized through the use of a 35 μm core erbium-doped ZBLAN fiber and an acousto-optic modulator; to our knowledge, this is the first 3 μm pulsed fiber laser in the 10 W class. Pulse energy up to 100 μJ and pulse duration down to 90 ns, corresponding to a peak power of 0.

Epstein-Barr virus nuclear antigen 3C facilitates G1-S transition by stabilizing and enhancing the function of cyclin D1.

EBNA3C, one of the Epstein-Barr virus (EBV)-encoded latent antigens, is essential for primary B-cell transformation. Cyclin D1, a key regulator of G1 to S phase progression, is tightly associated and aberrantly expressed in numerous human cancers. Previously, EBNA3C was shown to bind to Cyclin D1 in vitro along with Cyclin A and Cyclin E.

EBNA3C attenuates the function of p53 through interaction with inhibitor of growth family proteins 4 and 5.

Epstein-Barr virus (EBV)-encoded EBNA3C is one of the latent proteins essential for the efficient transformation of human primary B lymphocytes into continuously proliferating lymphoblastoid cell lines (LCLs) in vitro through manipulation of a number of major cellular pathways. Although it does not have direct DNA-binding activity, EBNA3C plays a central role in the transcriptional modulation of a wide range of both viral and cellular genes during latent infection. Recently, we showed that EBNA3C can directly bind to the tumor suppressor protein p53 and repress its functions, in part by blocking its transcriptional activity as well as facilitating its degradation through stabilization of its negative regulator, Mdm2.

Stable 10 W Er:ZBLAN fiber laser operating at 2.71-2.88 μm.

We have developed a diode-pumped tunable 3 μm fiber laser with a cw output power of the order of 10 W with the use of an erbium-doped ZBLAN fiber. A tunability range of 110 nm (2770 to 2880 nm) with an output power between 8 and 11 W was demonstrated. As the pump power was increased, the center of the wavelength range was shifted toward longer wavelengths, but the width of the wavelength range was largely unaffected.

Characterization of lytic enzyme open reading frame 9 (ORF9) derived from Enterococcus faecalis bacteriophage phiEF24C.

In bacteriophage (phage) therapy against Gram-positive bacteria, such as Staphylococcus aureus, Listeria monocytogenes, and Enterococcus faecalis, members of a genus of SPO1-like viruses are typically employed because of their extreme virulence and broad host spectrum. Phage φEF24C, which is a SPO1-like virus infecting E. faecalis, has previously been characterized as a therapeutic phage candidate.

Epstein-Barr Virus nuclear antigen 1 (EBNA1) confers resistance to apoptosis in EBV-positive B-lymphoma cells through up-regulation of survivin.

Resistance to apoptosis is an important component of the overall mechanism which drives the tumorigenic process. EBV is a ubiquitous human gamma-herpesvirus which preferentially establishes latent infection in viral infected B-lymphocytes. EBNA1 is typically expressed in most forms of EBV-positive malignancies and is important for replication of the latent episome in concert with replication of the host cells.

Tumor viruses and cancer biology: Modulating signaling pathways for therapeutic intervention.

Tumor viruses have provided relatively simple genetic systems, which can be manipulated for understanding the molecular mechanisms of the cellular transformation process. A growing body of information in the tumor virology field provides several prospects for rationally targeted therapies. However, further research is needed to better understand the multiple mechanisms utilized by these viruses in cancer progression in order to develop therapeutic strategies.

Presence of Merkel cell polyomavirus in Japanese cutaneous squamous cell carcinoma.

Background: Merkel cell polyomavirus (MCPyV) was first identified in Merkel cell carcinoma (MCC) as a new tumor virus. Studies have also reported differing frequencies of MCPyV detection in other skin cancers in western countries.

Objectives: Little is known about geographical differences of MCPyV prevalence in non-MCC tumors.

Nm23-H1 can induce cell cycle arrest and apoptosis in B cells.

Nm23-H1 is a well-known tumor metastasis suppressor, which functions as a nucleoside-diphosphate kinase converting nucleoside diphosphates to nucleoside triphosphates with an expense of ATP. It regulates a variety of cellular activities, including proliferation, development, migration and differentiation known to be modulated by a series of complex signaling pathway. Few studies have addressed the mechanistic action of Nm23-H1 in the context of these cellular processes.

Multiple oncogenic viruses identified in Ocular surface squamous neoplasia in HIV-1 patients.

Background: Ocular surface squamous neoplasia (OSSN) is a rare cancer that has increased in incidence with the HIV pandemic in Africa. The underlying cause of this cancer in HIV-infected patients from Botswana is not well defined.

Results: Tissues were obtained from 28 OSSN and 8 pterygia patients.

Liquid-cooled 24 W mid-infrared Er:ZBLAN fiber laser.

A 24 W liquid-cooled CW 3 microm fiber laser with a multimode-core Er-doped ZBLAN fiber has been developed. The output power of 24 W and an optical-to-optical efficiency of 14.5% (with respect to incident pump power) were obtained with 975 nm diode pumping.