Human Papillomavirus Genome in Oral Carcinoma and Their Metastatic Cervical Lymph Node Tissues.

Twenty cases of oral squamous cell carcinoma (SCC) with cervical lymph node metastasis were investigated. Both primary lesions and metastatic lymph nodes were analyzed for the involvement of human papillomavirus (HPV) DNAs utilizing the polymerase chain reaction (PCR) method and dot blot hybridization. HPV DNAs were detected in five cases. Four primary lesions contained HPV-16 DNA, and one contained both HPV-16 and HPV-18 DNAs out of 20 cases examined. No HPV DNAs were detected in metastatic lymph node tissues in cases where HPV DNAs could not be detected in primary cancer tissues. The same types of HPV DNAs as those found in primary lesions were detected in metastatic lymph nodes including those with HPV-16 and HPV-18

Adenovirus E4orf6 targets pp32/LANP to control the fate of ARE-containing mRNAs by perturbing the CRM1-dependent mechanism

E4orf6 plays an important role in the transportation of cellular and viral mRNAs and is known as an oncogene product of adenovirus. Here, we show that E4orf6 interacts with pp32/leucine-rich acidic nuclear protein (LANP). E4orf6 exports pp32/LANP from the nucleus to the cytoplasm with its binding partner, HuR, which binds to an AU-rich element (ARE) present within many protooncogene and cytokine mRNAs. We found that ARE-mRNAs, such as c-fos, c-myc, and cyclooxygenase-2, were also exported to and stabilized in the cytoplasm of E4orf6-expressing cells. The oncodomain of E4orf6 was necessary for both binding to pp32/LANP and effect for ARE-mRNA. C-fos mRNA was exported together with E4orf6, E1B-55kD, pp32/LANP, and HuR proteins. Moreover, inhibition of the CRM1-dependent export pathway failed to block the export of ARE-mRNAs mediated by E4orf6. Thus, E4orf6 interacts with pp32/LANP to modulate the fate of ARE-mRNAs by altering the CRM1-dependent export pathway

Detection of Human Papillomavirus (HPV) DNA Sequences in Normal Oral Scrapes Using the Nested PCR.

We investigated the prevalence rate of HPV DNAs in normal mucosa in the oral region. The nested PCR method was utilized to detect target DNA sequences using HPV E6/E7 consensus primer pairs. Of 56 patients examined, HPV 6 and HPV 16 DNA sequences were detected in a 46-year-old male and a 35-year-old female, respectively. These results suggest that HPVs are uncom-mon in normal oral epithelium, and that we should carry out careful follow-up in HPV DNA-positive cases

The enhancing effect of excess retinol palmitate on induction of odontogenic tumors and inhibitory effect on squamous cell carcinoma of the gingiva in hamsters treated with N-methylnitrosourea

The influence of excess retinol palmitate on induction of tumors in the oral region was examined histopathologically. Sixty-three weanling Syrian golden hamsters were divided into five groups and received either 0.2% N-methylnitrosourea (MNU) (lmg1100g body weight) or retinol palmitate (RP) (25,000 IU/100g body weight) twice a week for 16 weeks, singly or in combination. Animals received RP intraperitoneally or intragastrically and then, 6 hours later, the animals received intragastric administration of MNU. To accelerate the cell activity of the incisal tooth buds, intentional disocclusion of the left upper and lower incisor of all hamsters was carried out by repeated cutting with cooled diamond disks to a level just above the inter-dental papilla twice a week for 12 weeks. The right incisors were left in occlusion. In all animals exposed to RP+MNU, while the induction of squamous cell carcinomas of the gingiva and forestomach were prevented, the notable findings were a significantly increased incidence of odontogenic tumors in cut incisal regions of the animals with intragastric administration of RP+MNU and an induction of maxillary neurogenic tumors. The incidence of MNU-induced disturbances in odontogenesis in the incisors was reduced but marked disturbances were increased. RP seemed to have opposite effects of prevention and enhancement for development of neoplastic changes in the oral region

Activation of the FGF signaling pathway and subsequent induction of mesenchymal stem cell differentiation by inorganic polyphosphate

<p>Inorganic polyphosphate [poly(P)] is a biopolymer existing in almost all cells and tissues, although its biological functions in higher eukaryotes have not been completely elucidated. We previously demonstrated that poly(P) enhances the function of fibroblast growth factors (FGFs) by stabilizing them and strengthening the affinity between FGFs and their cell surface receptors. Since FGFs play crucial roles in bone regeneration, we further investigated the effect of poly(P) on the cell differentiation of human stem cells via FGF signaling systems. Human dental pulp cells (HDPCs) isolated from human dental pulp show the characteristics of multipotent mesenchymal stem cells (MSCs). HDPCs secreted FGFs and the proliferation of HDPCs was shown to be enhanced by treatment with poly(P). Cell surface receptor-bound FGF-2 was stably maintained for more than 40 hours in the presence of poly(P). The phosphorylation of ERK1/2 was also enhanced by poly(P). The effect of poly(P) on the osteogenic differentiation of HDPCs and human MSCs (hMSCs) were also investigated. After 5 days of treatment with poly(P), type-I collagen expression of both cell types was enhanced. The C-terminal peptide of type-I collagen was also released at higher levels in poly(P)-treated HDPCs. Microarray analysis showed that expression of matrix metalloproteinase-1 (MMP1), osteopontin (OPN), osteocalcin (OC) and osteoprotegerin was induced in both cell types by poly(P). Furthermore, induced expression of MMP1, OPN and OC genes in both cells was confirmed by real-time PCR. Calcification of both cell types was clearly observed by alizarin red staining following treatment with poly(P). The results suggest that the activation of the FGF signaling pathway by poly(P) induces both proliferation and mineralization of stem cells.</p