Masanao Murakami

Kochi Gakuen University · Medical Laboratory Science

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 p...

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 lymphohistiocytos...

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. In the pr...

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 c...

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 th...

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 sup...

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...

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 swabs...

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. Our aim was to...

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 mal...

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 b...

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 th...

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. Little is known about geographical differences of MCPyV prevalence in non-MCC tumors. We examined the existence of MCPyV in non-MCC...

Nm23 was first cloned from a murine melanoma cell line wherein its expression correlated inversely with metastatic potential (Steeg et al. 1988). While it is abundantly expressed in aggressive neuroblastoma, the NB alleles typically encode the S120G substitution, which is likely to be a hypomorphic variant with reduced function (Chang et al. 1994,...

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...

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. Tissues were obtained from 28 OSSN and 8 pterygia patients. The tissues analyzed from OSSN patients were 83% positive for EBV, 75%...

Primary effusion lymphoma (PEL) is a common cancer in AIDS patients closely associated with Kaposi's sarcoma-associated herpesvirus (KSHV). Previously, we showed that KSHV latency associated nuclear antigen (LANA) stabilizes intracellular activated Notch1 (ICN) involved in maintenance of the malignant phenotype of KSHV infected PEL cells in vitro....

Epstein Barr virus (EBV) is closely associated with the development of a vast number of human cancers. To develop a system for monitoring early cellular and viral events associated with EBV infection a self-recombining BAC containing 172-kb of the Epstein Barr virus genome BAC-EBV designated as MD1 BAC (Chen et al., 2005, J.Virology) was used to in...

Nm23-H1 was discovered as the first metastasis suppressor gene about 20 years ago. Since then, extensive work has contributed to understanding its role in various cellular signaling pathways. Its association with a range of human cancers as well as its ability to regulate cell cycle and suppress metastasis has been explored. We have determined that...

Survivin is a master regulator of cell proliferation and cell viability and is highly expressed in most human tumors. The molecular network linked to survivin expression in tumors has not been completely elucidated. In this study, we show that latency-associated nuclear antigen (LANA), a multifunctional protein of Kaposi's sarcoma-associated herpes...

Previous studies have demonstrated the interaction between the Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) and the metastatic suppressor Nm23-H1 both in vitro and in vivo (C. Subramanian, M. A. Cotter II, and E. S. Robertson, Nat. Med. 7:350-355, 2001). Importantly EBNA3C can reverse the ability of Nm23-H1 to suppress migration of human ce...

The p53 tumor suppressor gene is one of the most commonly mutated genes in human cancers and the corresponding encoded protein induces apoptosis or cell-cycle arrest at the G1/S checkpoint in response to DNA damage. To date, previous studies have shown that antigens encoded by human tumor viruses such as SV40 large T antigen, adenovirus E1A and HPV...

Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) is one of the essential latent antigens for primary B-cell transformation. Previous studies established that EBNA3C facilitates degradation of several vital cell cycle regulators, including the retinoblastoma (pRb) and p27(KIP) proteins, by recruitment of the SCF(Skp2) E3 ubiquitin ligase complex...

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus associated with a large number of lymphoid and epithelial malignancies. As a successful pathogen it has co-evolved with its human host for millions of years. EBV has the unique ability to establish life-long latent infection in primary human B lymphocytes. During latent infection, a small s...

Epstein-Barr virus (EBV) is closely associated with the development of a number of tumors. During latent infection, EBV continuously expresses a number of viral genes which are essential for cell transformation and maintenance of the malignant phenotype of EBV-related tumors. There has been no previous link between EBV and T-cell prolymphocytic leu...

Commentary to:The metastasis-associated gene MTA1 is upregulated in advanced ovarian cancer, represses ERβ, and enhances expression of oncogenic cytokine GROChristine Dannenmann, Naim Shabani, Klaus Friese, Ioannis Mylonas, Ansgar BrA¼ning

Cytoskeleton rearrangement is necessary for tumor invasion and metastasis. Cellular molecules whose role is to regulate components of the cytoskeletal structure can dictate changes in cellular morphology. One of these molecules is the suppressor of tumor metastasis Nm23-H1. The level of Nm23-H1 expression has been linked to the invasiveness and met...

Tumor invasion and metastasis is regulated by a number of cellular molecules known to be involved in signaling and cytoskeletal rearrangement. One of these molecules is the suppressor of tumor metastasis Nm23-H1 which linked to invasiveness and metastatic potential of human cancers. Nm23-H1 expression is down-regulated in human melanoma and invasiv...

Epstein-Barr virus (EBV) was the first human DNA virus to be associated with cancer. Its oncogenic potential was further demonstrated by its ability to transform primary B lymphocytes in vitro. EBV nuclear antigen 3C (EBNA3C) is one of a small subset of latent antigens critical for the transformation of human primary B lymphocytes. Although EBNA3C...

Deregulation of the evolutionarily conserved Notch signaling is highly correlated with oncogenesis. Intracellular activated Notch (ICN) is a protooncogene linked to the transcription activation of a number of cellular genes involved in cell cycle regulation, differentiation, and proliferation. Stability of ICN is tightly regulated by the Sel10-medi...

Hypoxia-inducible factor 1 (HIF-1) is a ubiquitously expressed transcriptional regulator involved in induction of numerous genes associated with angiogenesis and tumor growth. Kaposi's sarcoma, associated with increased angiogenesis, is a highly vascularized, endothelial cell-derived tumor. Previously, we have shown that the latency-associated nucl...

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus associated with the development of both lymphoid and epithelial tumors. The EBV critical latent antigens EBNA1 and EBNA3C interact with Nm23-H1, a known suppressor of cell migration and tumor metastasis. This interaction is critical for the regulation of downstream cellular genes involved i...

In this appendix, several basic methods are described for preparation of primary B lymphocyte.

Epstein-Barr virus (EBV) was first reported as the etiological agent of Burkitt's lymphoma in 1964. Since then, EBV has also been associated with nasopharyngeal carcinoma, which is highly prevalent in Southeast Asia, as well as infectious mononucleosis, complications of AIDS, and transplant-related B cell lymphomas. This virus has further been link...

Epstein-Barr virus (EBV) infects most of the human population and persists in B lymphocytes for the lifetime of the host. The establishment of latent infection by EBV requires the expression of a unique repertoire of genes. The product of one of these viral genes, the EBV nuclear antigen 3C (EBNA3C), is essential for the growth transformation of pr...

Epstein-Barr virus (EBV) is a gammaherpesvirus of the Lymphocryptovirus genus, which infects greater than 90% of the world's population. Infection is nonsymptomatic in healthy individuals, but has been associated with a number of lymphoproliferative disorders when accompanied by immunosuppression. Like all herpesviruses, EBV has both latent and lyt...

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a predominantly latent infection in the infected host. Importantly, during latency, only a small number of viral encoded genes are expressed. This viral gene expression pattern contributes to the establishment of long-term infection as well as the ability of the virus to evade the immune sy...

Kaposi's sarcoma-associated herpesvirus (KSHV) is a human tumor virus expressing latent antigens critical for pathogenesis. The mechanism by which KSHV mediates oncogenesis has not been fully elucidated. Notch signaling is an evolutionarily conserved pathway controlling diverse events related to development, proliferation, and tissue homeostasis. D...

Previous studies have demonstrated the interaction between the Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) and the metastatic suppressor Nm23-H1 both in vitro and in vivo (C. Subramanian, M. A. Cotter II, and E. S. Robertson, Nat. Med. 7:350-355, 2001). EBNA3C can reverse the ability of Nm23-H1 to suppress migration of Burkitt's lymphoma a...

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent contributing to development of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman desease. Following primary infection, latency is typically established. However, the mechanism by which KSHV establishes latency is not understood. We have reported that the l...

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is expressed in the majority of latency programs in EBV-infected cells and is critical for the maintenance of EBV episomes in the infected cells. EBNA1 is also known to be involved in transcriptional activation and regulates expression of the EBV latent genes, including the EBNAs and LMP1. Thus, EB...

We report an autopsy case of Epstein-Barr virus (EBV)-infected malignant lymphoma in a young male who had hypersensitivity to mosquito bites. The autopsy revealed multiple confluent lymphoma lesions in the lungs, and on the right leg irregular-shaped skin ulcers were seen. The left pleural effusion also contained a large number of lymphoma cells. T...

In order to study the mechanism of Epstein-Barr virus (EBV) infection in gastric carcinoma cells, we characterized the EBV infection in signet ring cell line HSC-39, derived from a human gastric carcinoma. HSC-39 cells were highly susceptible to cell-free EBV infection by Akata and P3HR-1 EBV strains. EBV nuclear antigen (EBNA) and EBV-encoded smal...

To understand Epstein-Barr virus (EBV) infection of gastric carcinoma cells. The authors tested the infection of a signet ring cell line HSC-39 derived from human gastric carcinoma with Akata and P3HR-1 strains of EBV. Akata and P3HR-1 infected of EBV cell clones were isolated by a limiting dilution method. EBV-encoded small RNAs (EBERs) were expre...

Eliminating Epstein-Barr virus (EBV) genomes from infected cells is an intriguing theoretical strategy in therapy for EBV-associated malignant diseases. Respective patterns were characterized for hydroxyurea (HU)-promoted loss of EBV genomes from EBV-infected epithelioid cell lines derived from the noncancerous portion of gastric carcinoma tissues...

Twenty-one cases of gastric carcinoma were tested for the presence of Epstein-Barr virus (EBV) genome by polymerase chain reaction (PCR) analysis. EBV genome was detected in 3 (14%) of the 21 cases. In situ hybridization for EBV-encoded small RNA 1 showed that EBV genomes were present in almost all carcinoma cells of the 3 cases. Southern hybridiza...

We found that spontaneous and 12-0-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus (EBV) reactivation occurred in short-term (ST)-cultured EBV-infected epithelial cell lines GT38 and GT39 after their establishment; however, it diminished in the long-term (LT)-cultured cells passaged for more than 2 years from ST-cultured cells. We hypoth...

We describe a unique patient with mosquito-bite hypersensitivity who had extremely high titres of Epstein-Barr virus antibodies. For many years he developed intractable ulcers on the sites of mosquito-bite. Epstein-Barr virus infection was detected in almost all inflammatory cells in the ulcers and in the peripheral blood lymphocytes by using in si...

The long-term goal of our study is to explore how Epstein-Barr virus (EBV) associates with the pathogenesis of gastric carcinoma. The first goal is to establish EBV-positive epithelial cell lines from EBV-infected gastric carcinoma tissues and to characterize the cell lines and EBV infection in the cells. EBV, a ubiquitous human herpesvirus with on...

To study the tumorigenesis of Epstein–Barr virus (EBV)-positive epithelial cell lines GT38 and GT39 derived from human gastric tissues, we inoculated these cells under the skin of severe combined immunodeficient (SCID) mice. The development of tumors was observed in each of the mice about 2 months after the inoculation. The tumors were diagnosed wi...

The intramedullary infiltration type, cell morphology and the pathological condition of bone lesion are closely related to diagnostic and clinical features in multiple myeloma. They are important factors to evaluate treatment effects and prognosis and to determine therapeutic strategy. In addition to various clinical parameters to determine prognos...