-
[show abstract]
[hide abstract]
ABSTRACT: Heparin is a polysulfated glycosaminoglycan that has been shown to have antiproliferative and apoptotic effects in addition to its anticoagulant effects.
The present work investigated the effects of unfractioned heparin (UFH) on cell growth and apoptosis in four oral squamous cell carcinoma (SCC) cell lines and the mechanism(s) underlying its actions using MTT assay, Annexin-V-FITC and Western blotting.
Treatment with UFH resulted in significant reduction in cell viability and increase in apoptosis in three of the four tested cell lines. Further, such treatment resulted in a significant decrease in phosphorylated AKt, and consequently led to activation of the mitochondrial pathway in heparin-sensitive cells. Moreover, pretreatment with UFH significantly increased the apoptosis induced by cisplatin.
These findings indicate that heparin induces apoptosis through suppression of AKt, and suggest a potential utility of heparin for development of less toxic chemotherapy in treatment of oral SCC.
Anticancer research 05/2009; 29(4):1079-88. · 1.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The John Cunningham virus (JCV) asymptomatically infects a large proportion (approximately 90%) of the population worldwide but may be activated in immunodeficient patients, resulting in progressive multifocal leukoencephalopathy. Recent reports demonstrated its oncogenic role in malignancies. In this paper, the presence of JCV-targeting T antigen was investigated in tongue carcinoma (TC, n = 39), dysplastic tongue epithelium (DTE, n = 15) and glossitis (n = 15) using real-time polymerase chain reaction (PCR) and in situ PCR and immunohistochemistry, and JCV copies were analyzed with the clinicopathological parameters of TCs. The results demonstrated that glossitis and DTEs had significantly lower copies of JCV (410.5 +/- 44.3 and 658.3 +/- 53.3 copies/mug DNA respectively) than TCs (981.5 +/- 14.0, p < 0.05). When they were divided into three groups with 0-200 copies/mug DNA (low), 201-1,000 (moderate) and more than 1001 (high), TCs showed 3 (7.6%) in the low group, 21 (53.8%) in the moderate group and 15 (38.4%) in the high group and glossitis showed 11 (73.3%) in the low group, 0 (0%) in the moderate group and 4 (26.6%) in the high group. The DTEs occupied an intermediate position between them (p < 0.001). In situ PCR demonstrated that the nuclei of TC and DTE cells are sporadically T-antigen positive but not in nasal turbinate epithelial cells. Immunohistochemistry for T-antigen protein revealed four positive cases only in TCs. The existence of JCV T-antigen DNA was not associated with the clinicopathological variables of TCs. In conclusion, the presence of JCV may be a risk factor of tongue carcinogenesis.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 04/2008; 452(4):405-10. · 2.49 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The JC virus (JCV) infects a large proportion of the population worldwide and 80% to 90% of adults are seropositive and it may be activated in immunodeficient patients, resulting in progressive multifocal leukoencephalopathy. Recent reports described the possibility of its oncogenetic role in several malignancies. To clarify whether JCV might have a potential role in the genesis of lung cancers, we investigated the presence of its genome in 62 tumors, along with 23 samples of normal lung tissue, targeting the T-antigen, VP, and Agnoprotein by nested polymerase chain reaction/Southern blotting followed by direct DNA sequencing. Immunohistochemistry was performed to assess links between p53 and beta-catenin in lung cancers and the presence of T-antigen. The T-antigen was detected in 25 of 62 lung cancers but only 4 of 23 normal lung samples (P=0.048). In total, the JCV genome was present in 33 of the lung cancers and 10 of the normal samples. Furthermore, T-antigen was found in cancer cells in metastatic lymph nodes in 3 of 4 cases (P=0.042) and was more frequently detected in adenocarcinomas than in squamous cell carcinomas (P=0.038). Immunohistochemistry showed significant correlations between T-antigen and p53 (P=0.022) and also nuclear detection of beta-catenin (P=0.021). It is concluded that the JCV genome might be present in cancer cells in approximately half of all Japanese lung cancer cases, and that the T-antigen may play a role in oncogenesis of lung cancers through inactivation of p53 and dysregulation of the Wnt signaling pathway.
Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 01/2008; 15(4):394-400. · 1.63 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The JC virus (JCV) infects a large proportion of the worldwide population and approximately 90% of adults are seropositive. Recent reports have described the possibility of its oncogenetic role in several malignancies. The aim of the present study was to assess the oncogenetic significance of JCV for gastric cancer. Twenty-two sample pairs of fresh tumor and adjacent non-cancerous tissue (ANCT) as well as 10 normal gastric mucosa specimens were investigated on the basis of nested polymerase chain reaction (PCR) followed by Southern blotting, DNA direct sequencing, real-time PCR, in situ PCR and immunohistochemistry. The T antigen sequence was detected in 86.4% of gastric cancers and ANCT, and in 100% of the normal mucosa samples, as for virus capsid protein, 54.1%, 68.1% and 70%, respectively. A generally low incidence was noted for agnoprotein. The JCV DNA load was approximately 10-fold higher in both gastric cancers and paired ANCT (4784 +/- 759 and 5394 +/- 1466 copies/microg DNA, respectively) than in normal gastric tissue (542.4 +/- 476.0 copies/microg DNA, P < 0.0001). In situ PCR revealed sporadic JCV genome-positive cancer cells and foveolar epithelial cells. T antigen protein expression assessed by immunohistochemistry was detected only in one case (1/22; 4.5%), probably because the half life of T antigen might be short. It was concluded that the gastric epithelium in most Japanese people is infected with JCV at a low rate but levels of infection are increased markedly in both cancer cells and ANCT, indicating that multiplication of JCV copies might be a risk factor and a background for gastric carcinogenesis.
Cancer Science 02/2007; 98(1):25-31. · 3.33 Impact Factor
-
Mei Hong,
Yoshihiro Murai, Tomohiko Kutsuna,
Hiroyuki Takahashi,
Kazuhiro Nomoto,
Chun-Mei Cheng,
Shin Ishizawa,
Qing-Li Zhao,
Ryohei Ogawa,
Brian V Harmon,
Koichi Tsuneyama,
Yasuo Takano
[show abstract]
[hide abstract]
ABSTRACT: Epstein-Barr virus (EBV) is associated with the development of several lymphoid and epithelial malignancies, including Burkitt's lymphoma. The EBV latent protein, EBV Nuclear Antigen 1 (EBNA1), is detectable in almost all types of EBV-associated tumors and is essential for replication and maintenance of the latent episome of EBV. We here examined whether the RNA interference (RNAi) technique could be employed to suppress expression of EBNA1 in EBV-positive Burkitt's lymphoma cells.
A Raji cell line expressing small hairpin RNAs (shRNAs) against EBNA1 was established and EBNA1 mRNA level was determined by real-time RT-PCR analysis. We investigated the effects of EBNA1 silence on lymphoma cell growth and cell cycle progression.
Transfection of an EBNA1 RNAi plasmid resulted in substantial loss of EBNA1 mRNA and significantly inhibited proliferation of Raji cells relative to the control plasmid case. Suppression of EBNA1 was also associated with downregulation of EBV oncogene EBNA2, a decreased PCNA labeling index and increased G0/G1 fraction in cell cycle analysis.
These findings point to potential therapeutic applications for vector-mediated siRNA delivery to control EBV-associated malignant disorders.
Journal of Cancer Research and Clinical Oncology 02/2006; 132(1):1-8. · 2.56 Impact Factor
