Nerve growth factor (NGF) and nerve growth factor receptors (NGFRs) play important roles in tissue remodeling during the would healing process of the skin, oral and paranasal mucosa, and cornea. The interactions between NGF and NGFRs are influenced by or interact with a number of molecules in the tissue remodeling process, in which key niche components are varieties of growth factors and their receptors, including NGF and NGFR. In addition to those interactions mentioned above, cell-cell contacts as well as cell-matrix interactions have also been considered to promote wound healing events. The present review focuses on the pathophysiological roles of NGF and NGFR in saliva and salivary glands, and in tear and lacrimal glands under inflammatory and tissue remodeling conditions, as well as their expression profiles in various kinds of cells including mast cells, macrophages, lymphocytes, and those involved in angiogenesis. Finally, we describe how the expression modes of NGF and NGFR regulate the peripheral nerve fiber growth and stimulate wound healing or tissue remodeling in the organs or tissues mentioned above as well as in pressure wounds and diabetic skin lesions. Based on these lines of evidence, we emphasize that NGF and NGFR could represent new and powerful regimens for treatment of tissue injuries.
Background: In addition to keratocystic odontogenic tumor (KCOT), orthokeratinized odontogenic cyst (OOC) has recently been recognized as a different jaw cyst entity whose lining epithelia are markedly keratinized. However, the odontogenic background of OOC remains still controversial. To clarify the difference in the lining epithelial natures of KCOT and OOC, we investigated differentiation modes for keratinization and neoplastic characteristics of these two cysts by immunohistochemistry for keratin subtypes and apoptosis-related proteins. Methods: Surgical specimens of KCOT (n = 20) and OOC (n = 15), as well as dentigerous cyst (DC, n = 15), which was used as a control, were examined by immunohistochemistry and western blotting for their expressions for cytokeratin (CK) 1, CK13, Bcl-2, and Bax. Immunohistochemical reactions were evaluated separately in two epithelial layers: upper spinous and basal. Results: Most of the spinous cells in the upper layer of KCOT and DC were CK13 positive (90-100%), while they were not as conspicuous in OOC (20%). In contrast, CK1 was positive in OOC (100%), while it was not positive in KCOT and DC. Basal layer cells in KCOT were positive for Bcl-2 (100%) but not for Bax (0%). Instead, they were not positive for Bcl-2 but positive Bax in OOC and DC. These immunohistochemical profiles in the three cystic lesions were confirmed by western blot analyses showing CK13 in KCOT and DC and CK1 in OOC. Conclusions: The CK expression modes were similar between KCOT and DC, indicating their odontogenic characteristics, which were not evident in OOC. The Bcl-2 positivity in KCOT suggested its neoplastic nature, though there was no neoplastic evidence in OOC and DC.
Background: Eosinophilic round bodies (ERBs) are composed of fragments of amino acid sequences of varying lengths, which represent a portion of exon 5 of amelogenin gene. ERBs have previously been shown to accumulate in the backs of rats subcutaneously injected with the product Emdogain®. In the present study, an oligopeptide with an amino acid sequence similar to this portion was artificially synthesized, and its effects were examined. Methods: The peptide solution was applied to periodontal defects created on the maxillae of rats. Sections from these tissues were histopathologically and immunohistochemically examined at 7 and 14 days after the start of the experiment. Results: In the experimental group, hard tissue had formed on the surface of exposed dentin, and both osteopontin and collagen type I (COLI) were localized around the hard tissue. The hard tissue was stained with periodic acid-Schiff (PAS) more deeply than was the dentin, and the fibers that were positive for COLI were vertically inserted in the rim of the newly-formed hard tissue. No hard tissue formation was found in the control group. Conclusion: These results suggest that synthetic oligopeptide administration can induc
Background: Oral cancers with sequential backgrounds have been increasing in number in recent years in Japan, although their disease entity is not always well defined. To characterize their clinicopathological nature, we compared oral cancers having sequential backgrounds with those lacking an apparent sequential history. Methods: From primary oral cancer cases filed in Niigata University Hospital, tongue cancer cases were selected and analyzed for their clinical factors (sex, age, location, TNM stages, local recurrences, and multiple occurrences), and for oral environmental factors (smoking and drinking habits, as well as the wearing of dentures or crown bridges). The histopathological characteristics were examined using surgical specimens. Results: Using samples from a 38-year period, 1970 to 2007, we were able to confirm 119 cases of squamous cell carcinoma of the tongue. Based on the clinicopathological analyses, we separated them into two categories: de novo type and sequential type. The latter was characterized by its superficial spread associated with precursor lesions, while the former appeared as an exophytic tumor mass with intrinsic growth and ulceration, without associations with a precursor lesion in the vicinity of the main cancer foci. There were 44 de novo types (28 males, 16 females, average age 54.0 years) and 75 sequential types (38 males, 37 females, 62.1 years). Clinically, there were no statistically significant differences in age, sex, location, local recurrence, multiple occurrence, and distant metastasis between the two types, although sequential types were found more frequently in older females. Tumor sizes of sequential types were smaller than those of de novo type (P<0.05), and they had obviously less cervical lymph node metastasis than did de novo types (P<0.001). In addition, smoking and drinking habits were not as prevalent among sequential type female patients as among de novo type patients (P<0.001). Conclusion: The findings indicated that two different disease categories of oral squamous cell carcinoma could be identified. The sequential type, a newly-recognized one, frequently arises in older female individuals who report no conventional risk factors, such as smoking and drinking. This type has the better prognosis. Clinical interventions should distinguish between the two types.
Background: Adenoid cystic carcinoma (AdCC) displays morphological diversity within its characteristic tumor cell nests, which are primarily classified into tubular, cribriform, and solid patterns. Such histological diversity should result from the proportional proliferation between neoplastic myoepithelial cells (NMC)/basal cells and ductal epithelial cells. The aim of this study was to clarify the relationship between this morphological diversity and the development of AdCC in the salivary gland using double immunostaining with monoclonal antibodies to p16 and p63 gene products. Methods: We examined 10 samples of formalin-fixed, paraffin-embedded AdCC tissues. Results: In the normal salivary gland, p16 protein (P16) was not expressed in any cells, whereas p63 protein (P63)-positivities were observed in ductal basal cells and in acinar myoepithelial cells. In AdCC foci showing the tubular pattern, P16 expression was localized in the inner cells of the ductal structure, while P63 was localized in the outer NMC of them within the same sections. In tumor foci with the cribriform pattern, P16 was expressed in several cells forming pseudocysts and in some of the inner cells. P63 was expressed in many cells in the cancer nests. In those with the solid pattern, P16 and P63 were intermixed within the same foci. Conclusions: Thus, the double immunohistochemistry for P16 and P63 was useful for observing the morphological diversity of AdCC cells within the same foci on the same tissue section. These data suggest that P16 and P63 may play important roles in the morphological diversity and development of AdCC tissue architectures.
This paper describes the first documented case of chronic focal sclerosing osteomyelitis accompanied by bony mass protrusion into the maxillary sinus manifested in a 34-year-old Japanese woman. The lesion was a circumscript radiopaque mass in the left maxillary sinus close to the apex of the left upper second molar. The tooth and adjacent molars were vital, and there was no apparent inflammation, though diffuse and sclerotic changes were observed around the left molar region of the maxilla on simple X-ray and CT images. Histopathological examinations of resected tissue showed that the protrusive hard mass was composed of dense bony trabeculae with prominent mature lamella covered by mucosal epithelia of the maxillary sinus with an inner granulation tissue zone, and of fibrous granulation tissue fragments with focal dense inflammatory cells including foamy macrophages and plasma cells and prominent Russell body formations. The patient was finally diagnosed as having chronic focal sclerosing osteomyelitis based on the radiographic and clinicopathological findings. As of about 35 months after the operation, there has been no sign of recurrence.
Purpose: The orbit, a major esthetic constituent of the face, is important in our social lives. Therefore, a careful approach is required for orbital tumor surgery, during both radical treatment and biopsy. To achieve a wider operative field, we developed a frontal-zygomatic (FZ) approach, in which bone of the superior or inferior wall is resected en block. Methods: The subjects consisted of 42 patients for whom a diagnosis of orbital tumor was made by preoperative diagnostic imaging and histopathological examination. Tumor resection was performed in 16 patients and tumor biopsy in 26. Following the adoption of the FZ approach for surgical intervention, we evaluated the postoperative complications and classified them into one of four categories: diplopia, enopthalmos, paralysis, or scar formation. Results: In all patients, a definite diagnosis was made by surgical intervention, showing that tumor resection and biopsy were useful. Conclusions: Because the FZ approach caused no significant postoperative complications and produced excellent results, we believe that this approach should be followed in most cases other than tumors centering on the orbital apex or extending into the optic canal.
Basaloid squamous cell carcinoma (BSCC) is a rare distinct variant of squamous cell carcinoma. We report a case of basaloid squamous cell carcinoma of the tongue in a 76-year-old Japanese man. The initial clinical examinations revealed a 23 × 25 × 15 mm reddish ulcerated mass with an elastic hard texture at the left lateral border of the tongue. The histopathological findings revealed invasive growth of basaloid epithelial tumor cells that formed nests in the subepithelial layer to the muscle layer. Immunohistochemically, the tumor was positive for p63 protein and had a high Ki-67 labeling index of more than 70% in parts. The patient underwent chemotherapy involving super-selective intra-arterial administration of carboplatin and local irradiation, followed by a subtotal tongue resection. The patient has been followed for 48 months postoperatively without any evidence of disease. The super-selective intra-arterial chemotherapy is a feasible and important application in treating BSCC of the tongue showing aggressive biological behavior.
Background: The purpose of this study was to investigate the differentiation and maturation of osteoblasts on surfaces with different roughnesses. Methods: Blasting a culture dish surface with Al2O3 particles of 25 μm, 50 μm or 180 μm diameter produces mean surface a roughness (Ra) of 0.48 ± 0.07, 1.02 ± 0.14 or 3.10 ± 0.36, respectively. Morphological changes of cells were compared, and the expression of mRNAs of osteopontin and osteocalcin were evaluated. Further, the ratio of alizarin red positive area was calculated. Results: Cells cultured on the 180 μm blasted surface had almost the same morphology as those cultured on the 50 μm blasted surface; however, cellular bridges tended to be much wider and more spread out. The expressions of osteopontin and osteocalcin mRNAs in cells cultured on the 180 μm blasted surface have greater up-regulation than the other cells. Further, the ratio of alizarin red positive area in180 μm blasted surface was significantly higher than those of others. Conclusions: These results suggest that the 180 μm blasted surface, with a surface roughness of approximately 3 μm in width, is the best surface for MC3T3-E1 cells to differentiate and mature in vitro.
Peculiar findings of orofacial actinomycosis mimicking the clinical appearance of a tumor of the upper lip were reported. A 68-year-old woman (case 1) and a 62-year-old woman (case 2) visited our hospitals towards the end of 2004 and 2007; the clinical diagnosis for each patient was upper labial tumor, and the lesions were surgically removed. Histologically, the excised specimens showed granulomas including bacterial colonies consisting of club-shaped filaments that formed a radiating rosette pattern in the submucosal layer. DNA samples were extracted from paraffin sections and examined by PCR for Actinomyces species. The PCR products examined by direct DNA sequencing demonstrated the presence of Actinomyces israelii and Actinomyces gerencseriae in both case 1 and case 2. Finally, pathological diagnoses of actinomycosis were made for each. Actinomycosis mimicking a tumor is very uncommon in the oral mucosa, and the use of PCR is an effective means of early and accurate diagnosis.
Background: Molecular mechanisms of bone resorption during odontogenesis are entirely unknown. In this study, we investigated the expressions of receptor activator nuclear factor κB ligand (RANKL), osteoprotegerin (OPG) and tumor necrosis factor-α (TNF-α) during early-stage tooth germ development. Methods: Developing tooth germs in rats, including Hertwig's epithelial root sheaths (HERS) at prenatal day 20 and postnatal days 1, 3, 5, 7 and 9, were examined. Expressions for RANKL, OPG, and TNF-α in mRNA, as well as protein levels, were evaluated by RT-PCR and immunohistochemistry. Results: mRNA expression levels for RANKL were significantly increased at postnatal days 3 to 9. Those for OPG increased from 1 to 5 days. However, those for TNF-α did not change between prenatal day 20 and postnatal day 5. On each postnatal day, RANKL was immunohistochemically localized in dental follicle cells attached to HERS, as well as in the crown region. HERS cells were also immunopositive for RANKL at postnatal day 7 and later. OPG was weakly immunolocalized in dental follicle cells from postnatal days 1 to 5, whereas after postnatal day 7 it disappeared. Conclusions: These findings revealed that the RANKL-RANK signaling, but not TNF-α signaling, plays a major role during bone resorption in the dental follicle surface to the HERS during early-stage tooth development.
Following two major redesigns of Oral Medicine & Pathology (OMP) in the last five years, the journal is approaching yet another important milestone: soon it will merge with the Asian Journal of Oral and Maxillofacial Surgery.This latest change is being made in order to increase readership as well as to strengthen academic quality by attracting more papers.
Sclerosing mucoepidermoid carcinoma (SMEC) has been rarely documented, and previously reported cases have suggested that this histologic variation is basically low-grade with a favorable prognosis. In an earlier report on the firstdescribed intraoral case of SMEC of intermediate grade that recurred as a nonsclerosed, high-grade tumor 13 years after the initial surgery, we presented a primary gingival tumor that occurred in a 28-year-old man as a non-ulcerated, polypoid, 2-cm mass on the retromolar pad. The present report, which briefly summarizes the further clinical course of that case, clearly demonstrates that stromal sclerosis is not a permanent feature of SMEC. Although SMEC has not been extensively studied, it is likely that the presence of extensive scar-like areas seems to have no prognostic significance.
Background: The major function of Malassez's epithelial rest (ERM) cells is thought to be maintenance of the homeostasis of the periodontal ligament. The purpose of this study was to investigate the effect of aging on the functions of ERM cells in vitro. Methods: ERM cells cultured from porcine teeth were used in this study, and cells at passages 3, 11 and 17 were analyzed by DNA microarray to evaluate gene expression profiles. Furthermore, quantitative real-time RT-PCR was performed to confirm the microarray data for selected genes. Results: The microarray data revealed that approximately 4,300 of the 21,123 genes on the array were expressed at significantly different levels. Among them, 230 genes, including BMP2, were significantly decreased between the 3rd to the 11th passage. Moreover, 23 genes, including beta-defensin1, MMP13 and CD61, were significantly down-regulated from the 3rd to the 11th and from the 11th to the 17th passages(P<0.05). Conclusion: These results suggest that cementogenesis, antibacterial effects, collagenase activity and cell adhesive functions of the ERM are affected by aging.
Background: CD44, a family of alternatively spliced transmembrane cell adhesion molecules, is expressed in many types of tumors, including oral squamous cell carcinoma. CD44 variant 3 and 6 (CD44v3 and CD44v6) expression in head and neck squamous cell carcinoma has been suggested to correlate with a poor prognosis. We investigated the relationship between CD44 variant forms and clinicopathological parameters in oral squamous cell carcinoma of the tongue (OSCCT). Methods: Immunohistochemical analysis of 60 cases of OSCCT was performed to investigate the relationship of CD44v3 and CD44v6 expression with clinicopathological parameters and clinical outcome. Results: Significant correlations were present between CD44v3 expression and clinicopathological parameters, such as mode of invasion (P<0.0001), differentiation type (P<0.0001), local recurrence (P<0.05), and secondary metastasis to lymph nodes (P<0.05). Loss of staining of CD44v3 also significantly correlated with a poor prognosis (P<0.001). On the other hand, CD44v6 expression showed no correlation with clinicopathological parameters. Conclusion: CD44v3 may be useful as a diagnostic/prognostic biomarker of OSCCT because low CD44v3 immunoreactivity is associated with high invasive potential and poor prognosis.
Carcinoma cuniculatum (CC) has been regarded as a well differentiated subtype of oral squamous cell carcinoma (SCC) that is characterized by keratin cores and keratin-filled crypts, but lacking obvious cytological malignancy. There have been relatively few case reports of oral CC, and descriptions of the long-term prognosis are scarce. In addition, the process of change from CC to conventional SCC is still poorly understood. In 1983, an 80-year-old woman admitted for a white spot underwent an excision biopsy, and CC was diagnosed. This lesion then recurred in 1993, with the same diagnosis, but it changed into conventional SCC when it recurred in 1994. Tissue materials from the three surgical treatments were examined with hematoxylin and eosin stain as well as with immunohistochemical stains for Ki-67 and for p53 and p63 gene products (P53, P63). While expressions of P53 protein and Ki-67 became stronger with every recurrence, the opposite tendency was obtained for P63 expression. This is the first report to describe a case of long-term follow-up of CC in which the expression modes of oncogene products were analyzed.
Podoplanin, a transmembrane glycoprotein that was originally detected in puromycin-induced nephrosis on the surface of rat podocytes, is expressed specifically by lymphatic endothelium. Recent studies have shown that the protein is expressed in a variety of normal as well as neoplastic tissues, and that its expression might be related to cell migration and invasion. In this review, we describe the expression and function of podoplanin under normal as well as pathological conditions of the oral and maxillofacial regions, and we discuss its significance.
We report a case of necrotizing sialometaplasia arising as bilateral ulcers in the palate of a 20-year-old Japanese female patient. Based on histopathological and immunohistochemical findings, we discuss how to distinguish the condition from neoplastic lesions such as squamous cell carcinoma or mucoepidermoid carcinoma. Histopathologically, the ulcer bed of granulation tissue contained hyperplastic capillary vessels, inflammatory cell infiltrates, necrotizing and degenerating palatal glands, and squamous metaplasia of ducts and acini leaving lobular structures of the mucous gland. Immunohistochemically, the epithelial islands were positive for pancytokeratin (CK), CK7 and S-100 protein, partially positive for α-smooth muscle actin, and not positive for periodic acid-Schiff reaction. We diagnosed the lesion as a necrotizing sialometaplasia. It healed spontaneously without treatment, and there was no recurrence.
=Background: The major function of epithelial rests of Malassez (ERM) cells is to maintain the homeostasis of the periodontal ligament (PDL). The purpose of this study was to characterize the effects of ERM cells on PDL fibroblasts in vitro using a co-culture system. Methods: PDL fibroblasts and ERM cells derived from porcine tissues were used. PDL fibroblasts were seeded in 6-welldishes. ERM cells plated in a chamber with a 0.4 μm pore membrane, were placed into the wells for 5 days. Osteocalcin (OCN), bone sialoprotein (BSP), osteoprotegerin (OPG) and receptor activator of NF-k B ligand (RANKL) mRNA levels in the PDL fibroblasts were then analyzed using real time RT-PCR. Alkaline phosphatase (ALP) activity was also measured. PDL fibroblasts cultured without ERM cells were used as a control. Results: OCN, BSP and OPG mRNA levels in PDL fibroblasts co-cultured with ERM cells were lower than the levels in the control group. Meanwhile, the RANKL mRNA level in PDL fibroblasts co-cultured with ERM cells was significantly higher than that of the controls (P<0.01). ALP activity of PDL fibroblasts co-cultured with ERM cells was significantly lower than in the controls (P<0.01). Conclusion: This study shows that ERM cells affect the functions of PDL fibroblasts, which decrease hard tissue formation and increase bone resorption. Therefore, ERM cells prevent dento-alveolar ankylosis of the PDL.
Odontogenic tumors are lesions derived from the elements of the tooth-forming apparatus and are found exclusively within the jawbones. This review presents a contemporary outline of our current understanding of the molecular and genetic alterations associated with the development and progression of odontogenic tumors, including apoptosis-related factors, telomerase, cell cycle regulators, growth factors, regulators of tooth development, hard tissue-related proteins, cell adhesion molecules, matrix-degrading proteinases, angiogenic factors, and osteolytic cytokines. It is hoped that better understanding of related molecular mechanisms will help to predict the course of odontogenic tumors and lead to the development of new therapeutic concepts for their management.
