Basal cell hamartia: a rudiment no longer.
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Adolescent↗
Biomedical subjects
F Ide
Publications and source records attributed to F Ide.
Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo-dGTPase.
Oxygen radicals, which can be produced through normal cellular metabolism, are thought to play an important role in mutagenesis and tumorigenesis. Among various classes of oxidative DNA damage, 8-oxo-7,8-dihydroguanine (8-oxoG) is most important because of its abundance and mutagenicity. The MTH1 gene encodes an enzyme that hydrolyzes 8-oxo-dGTP to monophosphate in the nucleotide pool, thereby preventing occurrence of transversion mutations. By means of gene targeting, we have established MTH1 gene-knockout cell lines and mice. When examined 18 months after birth, a greater number of tumors were formed in the lungs, livers, and stomachs of MTH1-deficient mice, as compared with wild-type mice. The MTH1-deficient mouse will provide a useful model for investigating the role of the MTH1 protein in normal conditions and under oxidative stress.
Adenocarcinoma↗
Importance of DNA repair in carcinogenesis: evidence from transgenic and gene targeting studies.
We have generated transgenic mice by introducing copies of the E. coli O6-methylguanine-DNA methyltransferase gene, ada. Liver extracts from homozygotes demonstrate about three times the control enzyme activity and increase up to about eight-fold can be induced by treatment with zinc, since the metal-responsive metallothionein promoter is attached to the ada gene. Furthermore, studies of liver carcinogenesis in our transgenic mice demonstrated significantly reduced rates of development of hepatocellular tumors after treatment with dimethylnitrosamine or diethylnitrosamine. It is well known that xeroderma pigmentosum (XP) patients are deficient in DNA repair. The availability of XPA (XP group A complementing) knockout mice has enabled us to investigate the functional role of the XPA nucleotide excision repair gene in carcinogenesis in vivo, first using the mouse skin as a model system. XPA-/- mice demonstrated skin ulcers 5-7 days after 7,12-dimethylbenz[a]anthracene (DMBA) treatment and papilloma development within 4 weeks prior to promotion, skin tumor incidence being also much higher than in heterozygous and wild-type mice. Experiments targeting the lung, liver and tongue have also been conducted to answer the question of whether the internal organs of these mice are also susceptible to chemical carcinogens. For lung carcinogenesis, mice were instilled intratracheally with a small dose of benzo[a]pyrene. The pulmonary tumor incidence in XPA-/- mice was significantly higher than in XPA+/- and XPA+/+ mice. XPA-/- mice were also found to be have enhanced sensitivity to aflatoxin B1 regarding liver tumor induction. In addition, administration of 4-nitroquinoline-1-oxide in drinking water for 50 weeks resulted in tongue tumors only in XPA-/- mice. These studies, thus, provided convincing evidence that XPA mice are also sensitive to carcinogenesis in organs other than the skin.
Animals↗
Xeroderma pigmentosum group A gene action as a protection factor against 4-nitroquinoline 1-oxide-induced tongue carcinogenesis.
To test the hypothesis that nucleotide excision repair (NER) plays a protective role in chemical carcinogenesis in internal organs, xeroderma pigmentosum group A gene-deficient (XPA(-/-)) mice, heterozygous (XPA(+/-)) and wild-type (XPA(+/+)) mice were orally administered 0.001% 4-nitroquinoline 1-oxide (4NQO) in their drinking water and compared. After 50 weeks of 4NQO exposure, tongue squamous cell carcinomas (SCCs) occurred in XPA(-/-) mice only, no tumors being observed in XPA(+/-) and XPA(+/+) animals. Of the XPA(-/-) mice 86% had tumors and 100% demonstrated multiple foci of dysplastic epithelium in the tongue. Accumulation of p53 protein was immunohistochemically detected in 56% of the SCCs. Mutational analysis of the p53 gene (exons 4-10) in carcinoma DNA revealed missense mutations in exons 5 and 9 in four of 20 samples. Our results clearly demonstrate that the NER gene XPA acts as a defensive factor against 4NQO-induced tongue carcinogenesis in vivo.
4-Nitroquinoline-1-oxide↗
Adenomatoid hyperplasia of the palate mimicking clinically as a salivary gland tumor.
This report describes an illustrative case of adenomatoid hyperplasia (AH) of the minor salivary glands on the palate of a 31-year-old man. The clinical features of the present lesion corresponded with those of pleomorphic adenoma, but histologically large lobules of normal-appearing mucous acini were found. The cell proliferative activity demonstrated in histological sections, by an immunohistochemical staining of proliferating cell nuclear antigen and Ki-67, showed no statistically significant differences among AH and a matched control group of normal palatal salivary glands. This case suggests that AH apparently exhibits an idiopathic, focal hypertrophic lesion of intraoral mucous glands with limited growth potential.
Adenoma, Pleomorphic↗
Primary intraosseous carcinoma associated with impacted third molar of the mandible: review of the literature and report of a new case.
This study investigated the clincopathologic features of primary intraosseous carcinoma (PIOC) related to the third molar of the mandible. Six cases (5 from the literature and 1 new case; mean patient age 73 years) of PIOC associated with completely impacted lower third molar were analyzed. For comparison, 8 cases of PIOC presenting after extraction of the lower third molar were also evaluated, with a significantly lower mean patient age of 56 years. Most lesions were deceptively similar to those related to the lateral type of dentigerous cyst, and half of the impacted cases revealed an asymptomatic fracture of the mandible. In all patients except for the present case, metastasis had not been recorded. Surprisingly, no patients are known to have died of PIOC. In our experience the prognosis of PIOC associated with a completely impacted third molar is much better than commonly believed, although the number of cases involved is too small to make a general conclusion. However, delay in establishing the correct diagnosis followed by extraction without awareness of the carcinoma is know to adversely affect the prognosis.
Age Factors↗
Juvenile xanthogranuloma of the lip: case report and literature review.
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Child↗
Post-traumatic spindle cell nodule misdiagnosed as a herniation of the buccal fat pad.
We studied a quasi-neoplastic lesion that developed in the oral mucosa secondarily to trauma. The female patient, 2 years of age, presented with a rapidly growing nodule and the lesion was diagnosed as a herniation of the buccal fat pad. Following partial resection, no recurrence was seen. The ulcerated polypoid mass was composed of compact spindle-cell proliferation with invasion of underlying muscle and fat. Atypical stromal cells were present in the myxoid areas. The surface edematous stroma contained abundant granulation tissue-type vascularity and a mixed population of chronic inflammatory cells. On immunohistochemical study, the spindle cells were consistent with myofibroblasts. The morphologic features, proliferating cell type, and benign clinical course are identical to the post-operative spindle cell nodules that occur in the genitourinary tract.
Child, Preschool↗
Peripheral ameloblastic fibroma.
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Humans↗
Sclerosing inflammatory myofibroblastic tumour of the tongue: an immunohistochemical and ultrastructural study.
A case of inflammatory myofibroblastic tumour (IMT) arising in the tongue of a 27-year-old man is described. The patient presented with a solitary, well-circumscribed submucosal mass of 4 months duration. The tumour showed in its largest part a paucicellular sclerosing lesion resembling a hyalinizing granuloma surrounded by a thin rim of an admixture of myofibroblasts, plasma cells and foamy histiocytes. Myofibroblasts expressed vimentin and alpha-smooth muscle actin positive immunophenotypes. Ultrastructurally the hyaline areas were composed of abundant collagen fibres with sparse myofibroblasts. Extensive scar-like change in this IMT may be related to a traumatic insult.
Adult↗
In vivo detection of ultraviolet photoproducts and their repair in purkinje cells.
We previously developed a highly sensitive method to assess in situ repair kinetics of ultraviolet (UV)-induced DNA photoproducts in epidermal cells using monoclonal antibodies specific for cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts (64PPs) by immunohistochemistry. In order to determine whether nucleotide excision repair capacity is operative in postmitotic mature neurons, brain surfaces of adult mice were exposed to UVB, and induction and removal of CPDs and 64PPs in Purkinje cell DNA were assessed immunohistochemically. UVB penetrated brain tissue to a depth sufficient to allow quantitative study. CPDs but not 64PPs were clearly detectable in the nuclei of Purkinje cells at doses >500 J/m2, in a dose-dependent manner. A time course experiment showed a statistically significant decrease of CPDs with time after irradiation. Although there was no apparent removal on Day 1, about half of CPDs were removed within 5 days, and the repair was essentially completed by Day 10. We conclude that non-dividing cerebellar neuronal cells can indeed repair UV-induced DNA damage, but with relatively low efficiency as compared with dividing epidermal cells.
Animals↗
Parotid lymph node metastasis from adenocarcinoma of the urachus.
The parotid gland and its lymph nodes are frequent sites of metastases from head and neck cancers. However, metastasis from a distant primary below the clavicle is unusual. These originate from a variety of sites, most commonly the lung, kidney and breast. A case of a 59-year-old woman with parotid lymph node metastasis from an adenocarcinoma of the urachus, diagnosed on the basis of two discrete periparotid masses on CT and the patient's history, is presented.
Adenocarcinoma↗
Epithelioid hemangioma of the tongue mimicking a malignancy.
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Adult↗
Plasma cell granuloma of the oral mucosa with angiokeratomatous features: a possible analogue of cutaneous angioplasmocellular hyperplasia.
We report a plasma cell granuloma arising in the movable mucosa of the oral cavity of a 50-year-old man. Histologically, the lesion was characterized by a dense nodular infiltrate of mature plasma cells. Immunostaining for kappa and lambda light chains confirmed a polyclonal plasma cell population. Elongated rete ridges of the overlying epithelium formed collarettes around dilated blood and lymph vessels in focal areas. Based on the overall histologic architecture, we hypothesize that these peculiar changes are secondary to local blood flow alteration with congestive vasodilation caused by a dense plasma cell infiltrate. We believe that the plasma cell population may represent the oral counterpart of the cutaneous angioplasmocellular hyperplasia.
Angiokeratoma↗
A defect in a single allele of the Mlh1 gene causes dissociation of the killing and tumorigenic actions of an alkylating carcinogen in methyltransferase-deficient mice.
Mice with mutations in both alleles of the Mgmt and the Mlh1 gene, the former encoding a DNA repair methyltransferase and the latter a protein functioning at an early step of mismatch repair, are as resistant to the killing action of alkylating agents as are wild-type mice. These mice yielded a large number of tumors when exposed to alkylating carcinogens, but this characteristic was subdued since they also showed a relatively high level of spontaneous tumorigenicity, as a consequence of the defect in mismatch repair. This complexity is now resolved by introducing the Mlh1(+/-) mutation, instead of Mlh1(-/-), in these methyltransferase-deficient mice. Mgmt(-/-) Mlh1(+/-) mice, with about half the amount of MLH1 protein as Mgmt(-/-) Mlh1(+/+) mice, were resistant to the killing action of N-methyl-N-nitrosourea (MNU), up to the level of 30 mg/kg body wt. Eight weeks after exposure to this dose of MNU, 40% of MNU-treated Mgmt(-/-) Mlh1(+/-) mice had thymic lymphomas and there were no tumors in those mice not given the treatment. It seems that the cellular content of MLH1 protein is a critical factor for determining if damaged cells enter into either one of the two pathways leading to mutation induction or to apototic cell death. Loss of Mlh1 expression was frequently observed in tumors of Mgmt(-/-) Mlh1(+/-) mice and this might be related to progression of the tumors.
Adaptor Proteins, Signal Transducing↗
Gingival peripheral odontoma in an adult: case report.
BACKGROUND: Odontoma arising in the extraosseous soft tissue is extremely uncommon. We describe our experience of gingival peripheral odontoma in which the initial presentation was a small asymptomatic nodule. METHODS: Case study. RESULTS: A 44-year-old man reported with a firm gingival mass of the anterior maxilla which had been gradually enlarging over 5 years. Radiographic examination showed a dense radiopaque mass occupying most of the tumor and no evidence of underlying intraosseous lesion. The pathology was reported as odontoma. CONCLUSIONS: This is the fourth reported case of peripheral odontoma in the gingiva.
Adult↗
Soft tissue myxoma of the gingiva: report of a case and review of the literature of soft tissue myxoma in the oral region.
Soft tissue myxoma of the oral cavity is extremely rare. We present a case of soft tissue myxoma arising from a mandibular anterior gingiva in a 51-year-old male patient. Histological examination showed islands of odontogenic epithelium scattered in the mucinous stroma. This lesion was supposed to have a odontogenic origin. The clinical differences between soft tissue myxoma with bone destruction and those without bone destruction are also discussed by a review of the literature.
Collagen↗
Cellular hemangioma in an adult.
This report describes an adult case of cellular hemangioma arising in the lower lip. A 39-year-old healthy woman presented with a polypoid mass of 4 months duration. The tumor imparted little color to the overlying mucosa and was misdiagnosed as a mucous granuloma preoperatively. The lobular proliferation of plump endothelial cells with inconspicuous vascular spaces was a cardinal morphologic feature of the present tumor.
Actins↗