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Cyclooxygenase-2: A Potential Target in the Treatment of Oral Cancers

Oral Science International.2005;2(1):1-7. doi:10.11277/osi.2.1

Results from epidemiological studies indicate that long-term intake of non-steroidal anti-inflammatory drugs, which inhibit cyclooxygenase (COX) enzymes involved in prostaglandin biosynthesis, reduces the risk of several forms of human malignancies. Expression of COX-2 in tumors is known to be associated with enhanced angiogenesis, suppression of host immunity, and tumor invasion. Genetic or pharmacological inhibition of COX-2 has been shown to protect against experimentally-induced carcinogenesis and to reduce the growth of xenografted tumors in animal models. A number of studies also revealed that COX-2 inhibition suppresses proliferation, metastatic potential, and other functions of cancer cell lines. Thus, it is conceivable that targeted inhibition of abnormally or improperly elevated COX-2 provides one of the most effective and promising strategies for cancer therapy. In this review, the involvement of COX-2 in the tumorigenesis of oral cancers and the potential mechanisms of tumor suppressive effects of COX-2 inhibition are discussed.

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Adenoid Cystic Carcinoma: Participation of Urokinase-type Plasminogen Activator (uPA) and its Receptor (uPAR) in Tumor Invasion

Kanemitsu Shirasuna

Oral Science International.2005;2(2):69-79. doi:10.11277/osi.2.69

Adenoid cystic carcinoma (AdCC) is one of the most common malignant tumors of the salivary glands and has unique clinical features and behavior. AdCC grows slowly, but spreads relentlessly into adjacent tissues, with a proclivity for invading nerve and endothelial sheaths. Moreover, the frequency of recurrence and distant metastasis of AdCC is very high. In vivo and in vitro, AdCC produces a large amount of extracellular matrix (ECM), including basement membrane (BM) components, elastin, and mucopolysaccharides. The accumulation of ECM components in intercellular spaces results in the formation of a pseudocyst, which is the characteristic architecture of AdCC. AdCC cells degrade considerable amounts of mesenchymal-elaborated ECM through the urokinase-type plasminogen activator (uPA)-plasmin system. By contrast, tumor-produced ECM is resistant to degradation, because it contains plasminogen activator inhibitor type 1 (PAI-1). The migration response of AdCC cell lines to ECM, especially type I and type IV collagens, is much stronger than that of oral squamous cell carcinoma (SCC) cell lines, while both cell types generally show similar patterns of integrin subunit expression. The AdCC cell response to collagens is largely and exclusively inhibited by anti-α₂ integrin antibody. Surface uPA receptor (uPAR) expression by AdCC cell lines is greater than that by SCC cell lines and increases in response to collagen stimulation. This is accompanied by the assembly of numerous focal adhesions, consisting of the adapter proteins uPAR, α₂ integrin, vinculin, and paxillin. A role for uPAR in cell migration and assembly of adaptor proteins was also demonstrated by transfecting AdCC cells with an antisense uPAR RNA, which strongly reduced both responses. Therefore, the proclivity of AdCC cells to migrate to type I and IV collagens might be due to the overexpression of uPAR, which also plays a key role in focal adhesion assembly. In conclusion, the invasiveness of AdCC cells might be regulated by the interaction of uPA-uPAR with integrin.

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Single-nucleotide Polymorphism (SNP) in .BETA.-Defensin 2 in a Japanese Population and an Effect of -1029 SNP on Promoter Activity

Kaoru Kusano ; Yoshihiro Abiko ; Michiko Nishimura ; Toshiya Arakawa ; Maiko Takeshima ; Atsushi Fujimoto ; Taishin Takuma ; Tohru Kaku

Oral Science International.2005;2(2):80-84. doi:10.11277/osi.2.80

Human β-defensin (hBD) 2 is an epithelial antimicrobial peptide. We studied single-nucleotide polymorphisms in the gene of hBD-2 in a Japanese population, and estimated the effect of a polymorphism in the promoter/enhancer region on the transcriptional activity. By sequencing the hBD-2 gene of 50 unrelated individuals, we detected one SNP in exon 2 and nine SNPs in the promoter/enhancer region. The SNP in the coding region at the +1765 position is synonymous [CCC (Pre)→CCT (Pre)]. One SNP in the promoter region (-1029) is located at the consensus sequence for NF-IL6 binding. By luciferase reporter assay and electrophoretic mobility shift assay, the wild-type (G) of -1029 showed significantly lower transcriptional activity than did the variant-type (A). The SNP at position -1029 may influence the hBD-2 expression and cause genetic variations in susceptibility to infectious diseases.

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Antisense Ets-1 Transfection Restrains Oral Cancer Invasion by Reducing Matrix Metalloproteinase Activities

Chihiro Taguchi ; Yuichi Ohnishi ; Kenji Kakudo

Oral Science International.2006;3(2):84-89. doi:10.11277/osi.3.84

Ets-1 is an Ets family transcription factor, can up-regulate the transcription of matrix metalloproteinase (MMP) genes and confers an invasive phenotype on human cancer cells. HSC3 is an oral squamous cell carcinoma-derived cell line, and it manifests high levels of Ets-1 and MMP-9 gene expression that are associated with invasive potential. In this study, we investigated the effect of Ets-1 on the invasive properties of oral cancer from a molecular biological perspective. We constructed an Ets-1 antisense (AS) expression vector, transfected HSC3 cells with the vector, and obtained HSC3AS cells that express Ets-1 AS RNA. The expression of Ets-1 and MMP-9 was analyzed with RT-PCR. The invasive ability of the HSC3AS cells was determined using a matrigel invasion assay and MMP-9 production was measured using gelatin zymography. The amount of Ets-1 mRNA was significantly reduced in HSC3AS cells compared with parental HSC3 cells and the control transfected with empty vector. Matrigel invasion assay revealed that the HSC3AS cells had lower invasive ability. Gelatin zymography demonstrated that HSC3AS MMP-9 productions were decreased compared with those of parental HSC3 cells and the control. These results imply that transfection of AS Ets-1 inhibits oral cancer invasion by down-regulating MMP-9 genes.

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Trigeminal Neuralgia-Symptoms, Diagnosis, Classification, and Related Disorders-

Katsuhiro Toda

Oral Science International.2007;4(1):1-9. doi:10.11277/osi.4.1

Trigeminal neuralgia (TN) causes sudden, usually unilateral, severe, brief stabbing recurrent pains in the distribution of one or more branches of the trigeminal nerve. Radiological examination is not required, however, patient interview and physical examination are necessary for diagnosis alone. When a patient is diagnosed with TN, an MRI is recommended to exclude tumor, cyst or multiple sclerosis, irrespective of the patient's age. From the etiological viewpoint, TN is classified into primary or idiopathic TN and secondary or symptomatic TN. From the symptomatic viewpoint, TN is classified into typical TN and atypical TN. Atypical TN, trigeminal neuropathy, pretrigeminal neuralgia, and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) are also described.

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Detection and Analysis of Helicobacter pylori DNA in the Gastric Juice, Saliva, and Urine by Nested PCR

Ryuhei Yamada ; Akira Yamaguchi ; Koichi Shibasaki

Oral Science International.2008;5(1):24-34. doi:10.11277/osi.5.24

The aim of this study was to investigate the strain heterogeneity of Helicobacter pylori (H. pylori) in saliva, gastric juice, and urine by nested PCR and the direct sequence method, and to clarify the mode of transmission by examining whether H. pylori in the stomach and saliva are identical.
Thirty-nine patients undergoing endoscopy were enrolled in this study. H. pylori DNA was assayed in 104 samples using two sets of primers, EHC-U/EHC-L and ET-5U/ET-5L. DNA sequencing was performed in 24 samples.
H. pylori DNA was detected in 39 gastric juice samples (100%) and in 28 saliva samples (71.8%). The prevalence in urine samples was 50% (13/26). All samples except one were identical with over 97% identity to the DNA sequence of H. pylori type strain J99 (USA).
Nested PCR was highly sensitive for detection of H. pylori DNA in saliva, and DNA sequencing may be useful to clarify the mode of transmission.

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Intramuscular Lipoma of the Cheek: Report of Two Cases

Susumu Hashitani ; Yukiyo Toyohara ; Kazunari Sakurai ; Masahiro Urade

Oral Science International.2008;5(1):69-71. doi:10.11277/osi.5.69

Two cases of intramuscular lipoma occurring in the cheek of a 39-year-old and of a 55-year-old Japanese males are presented. These were excised by the intraoral approach. Histopathologically, these lesions were composed of the adipose cell-like tumor cells infiltrating in the striated muscles. There has been no evidence of tumor recurrence after operation.

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Swallowing in Cockayne Syndrome: A Case Report

Iwao Hara ; George Umemoto ; Hiromasa Takahashi ; Toshihiro Kikuta

Oral Science International.2008;5(2):141-145. doi:10.11277/osi.5.141

The case of a 20-year-old female with Cockayne syndrome, presenting with reduced intake of food, is described. At admission, her intake of food and her body weight were low. The patient's food swallowing function was recorded by video fluorography and evaluated. Reduced transfer of food boluses to the posterior site of the oral cavity, incomplete formation of boluses in the oral phase, and residual food after swallowing in the pharynx phase were observed. No aspiration was observed, however, during video fluorography. The patient's nutrition was managed by changing her meals to fluid-type food to shorten the eating time.

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Side-to-side Asymmetry in Trigeminal Neuralgia-Multiple Factors Theory-

Katsuhiro Toda

Oral Science International.2009;6(2):95-99. doi:10.11277/osi.6.95

The right side was affected in 61% of reported cases and the left side was affected in 39% of approximately 30,000 patients with trigeminal neuralgia (TN) affected on only one side. Side-to-side asymmetry of neurovascular compression in healthy persons cannot account for side-to-side asymmetry in TN. Size asymmetry and shape asymmetry of the rotundum and ovale foramens may account for the higher incidence of TN on the right side. This paper proposes a multiple factors theory: the summation of multiple factors reaches a critical level at which TN occurs. It is rational that entrapment of the maxillary and mandibular nerves when they cross the ovale and rotundum foramens is one of the factors which cause TN. The multiple factors theory can account for a TN patient without neurovascular compression and a healthy person with neurovascular compression.

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Analysis of Biological Apatite Orientation in Rat Mandibles

Noriko Nagisa ; Takayoshi Nakano ; Norihiro Hashiguchi ; Wataru Fujitani ; Yukichi Umakoshi ; Masashi Shimahara

Oral Science International.2010;advpub(0):1004270001-.

Recently, significant progress has been made in medical techniques for regenerating bone. However, bone evaluation techniques generally assess bone quantity as opposed to bone quality. The use of c-axis crystallite orientation of biological apatite (BAp) as a bone quality index has recently generated great interest. BAp demonstrates strong crystallographic anisotropy, and preferential alignment of BAp in each bone varies depending on the shape and stress conditions in vivo. In the mandible, complicated bone shape and stress conditions in vivo might be associated with both bone quantity and quality. In this study, we aimed to elucidate changes in the bone microstructure in the mandible using crystallographic orientation of BAp as a bone quality index. Using Crj: CD (SD) IGS female rats, we observed changes in the dentulous mandible during bone growth. Measuring points on the mandible were determined based on its positional relationship with the teeth. For analysis of bone quantity, the area and bone mineral density of cortical bone were evaluated using peripheral quantitative computed tomography (pQCT), while the orientation of the BAp c-axis, as analyzed by a micro-beam X-ray diffraction system, was used to assess bone quality. The results of both bone quantity and quality assessments indicated that changes during bone growth varied depending on the presence of teeth. We concluded that the microstructure (especially the texture) of BAp crystallite changes in correlation with variations in stress distribution in vivo resulting from changes in chewing conditions designed to optimize the dynamic chewing function.

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