Henry M. Cherrick

Inactivation of the p53 gene by either mutation or HPV infection is extremely frequent in human oral squamous cell carcinoma cell lines

The state of p53 tumour suppressor and the frequency of high-risk human papillomavirus (HPV) infections were studied in nine human oral cancer cell lines. Three cancer cell lines (SCC-4, Tu-177 and FaDu) had similar amounts of p53 transcripts to normal cells, but contained significantly higher levels of p53 protein than the normal control cells. Sequencing highly conserved open reading frames of the p53 gene of these cancer cells showed point mutations in the SCC-4 and Tu-177 cell lines, a base transition from CCC to TCC occurred at codon 151; and in the line FaDu, a mutation of CGG to CTG occurred at codon 248. The HEp-2 and 1483 cancer lines contained significantly lower levels of p53 protein compared to the normal counterpart. Sequencing of p53 cDNA for HEp-2 and 1483 lines showed no mutations, but northern analysis revealed that these cell lines expressed HPV-18 E6/E7 messages. Four cell lines (SCC-9, SCC-15, SCC-25, and Tu-139) expressed negligible amounts of p53 transcripts compared to the normal counterpart and undetectable levels of p53 protein. These cell lines contained mutations in the highly conserved open reading frames of the p53 gene as follows: the SCC-9 had a deletion of 32 base pairs between codons 274 and 285; the line SCC-15 had an insertion of five base pairs between codons 224 and 225; the line SCC-25 had a deletion of two base pairs in codon 209; and the Tu-139 line had a deletion of 46 base pairs between codons 171 and 186.(ABSTRACT TRUNCATED AT 250 WORDS)

Leiomyomas of the oral cavity. Review of the literature and clinicopathologic study of seven new cases.

Abstract Intraoral leiomyomas have been reported to be rare neoplasms because of the paucity of smooth muscle within the oral cavity. A review of the literature yielded twenty-eight cases, and a clinicopathologic study of the twenty-eight previously reported cases and our seven cases suggests that this tumor is not as rare as previously suspected. The results suggest that this entity has a predilection for the 40 to 59-year age group, a male: female ratio of 2:1, and was most frequently encountered on the tongue. The intraoral leiomyoma does not appear to be estrogen dependent, as are those seen in the uterus.

Histogenesis of odontogenic tumors

Abstract A theoretical presentation concerning the histogenesis of mixed odontogenic tumors in relation to tooth germ embryogenesis is discussed. It is proposed that the individual tumors that make up this group are solely and totally dependent upon the presence of differentiation factors which are or are not elaborated by a particular tumor. The probability of sequential differentiating events resulting in the progression of an immature entity (ameloblastic fibroma) to a highly differentiated entity (odontoma) has been discounted, with reservations. Rather, it is postulated that individual mixed odontogenic tumors arise at comparable stages observed during normal odontogenesis and, as such, are incapable of further differentiation and thus proliferate within the histologic confines of their innate differentiated capacity.

In vitro and animal studies of the role of viruses in oral carcinogenesis

The linkage of herpes simplex virus (HSV) and human papillomavirus (HPV) to the development of oral cancer has been studied. In spite of the presence of viral nucleic acids in some human oral cancer specimens, HSV alone is not carcinogenic in animals: repeated viral inoculation to mouse or hamster oral mucosa fails to produce tumours or histopathological evidence of malignancy. However, HSV demonstrates co-carcinogenicity in vivo: viral inoculation significantly enhances the oncogenic capacity of chemical carcinogens in the oral cavity of mice and hamsters. Though the detailed mechanisms of HSV cocarcinogenicity are unknown, HSV promotes the chemical carcinogen-induced activation of certain cellular proto-oncogenes and inactivation of p53 tumour suppressor gene. Human papillomaviruses type 16 (HPV-16) and 18 (HPV-18) demonstrate oncogenicity by transforming normal human oral keratinocytes in vitro. While normal cells exhibit a limited life-span, cells transformed by these viruses show immortality and altered morphology in comparison with their normal counterparts. The HPV-immortalised cells contain multiple copies of intact viral genome integrated into cellular chromosomes. These cells also express several viral-specific mRNAs including viral E6/E7 mRNAs. Notably, these cells contain low levels of p53 protein and overexpressed cellular myc proto-oncogene compared to their normal counterpart; however, the immortilised cell lines are non-tumorigenic in nude mice.

Benign cementoblastoma: A clinicopathologic evaluation

Abstract The benign cementoblastoma is a neoplasm of cementum which has an unlimited growth potential. A review of the world literature reveals eight reported cases, and a clinicopathologic study of these eight previously reported cases and our two new cases suggests that this lesion is more common than previously thought but that it is not commonly recognized by clinicians. This clinicopathologic study suggests that the radiographic appearance of the lesion is pathognomonic and consists of a radiopaque mass surrounded by a thin radiolucent line. This mass is inseparable, radiologically, from the tooth root and is attached to it. Microscopic evaluation suggests that the lesion enlarges by peripheral growth, with the center of the neoplasm being more calcified and inactive than the periphery.

Intraoral juvenile xanthogranuloma

A case of juvenile xanthogranuloma of the gingiva is presented. This uncommon, benign disorder has rarely been histologically documented in the oral cavity, and rarely have oral lesions been described as presenting symptoms prior to this report. The pertinent literature is reviewed and possible etiologic factors are discussed.

Low p53 level in immortal, non-tumorigenic oral keratinocytes harboring HPV-16 DNA

The p53 protein level was determined in normal oral keratinocytes and two non-tumorigenic, immortal oral keratinocyte lines harboring human papillomavirus-16 (HPV-16)DNA. The p53 mRNA level in the immortal cells was higher than the normal counterpart, but the p53 protein level was notably lower in the immortalised cells. The half-life of p53 protein in the normal and immortal cells was < 1 h, and the p53 cDNA sequence of these cells showed no mutation. The immortal cells transcribed a high amount of E6/E7 mRNA encoded by HPV-16, but normal cells did not. These observations suggest that the immortal keratinocytes may translate normal level of wild-type p53 protein, and the low p53 level in these cells may be due to the enhanced degradation of the protein by HPV-16 E6 protein.

Effect of snuff extract on the replication and synthesis of viral DNA and proteins in cells infected with herpes simplex virus

The water-extractable component of snuff (snuff extract) inhibits the replication of herpes simplex virus (HSV) by suppressing the synthesis of viral DNA. This process probably causes HSV to be oncogenic. To further understand the mechanism of inhibitory action of snuff extract on HSV replication, the effect of snuff extract on the synthesis of viral DNA and proteins in type 1 HSV (HSV-1) infected cells was investigated. Snuff extract inhibited the synthesis of viral DNA and altered the production of certain classes of viral proteins. The syntheses of ICP4, a viral alpha-protein, and ICP8, a beta-protein, were not generally reduced by noncytotoxic concentrations of snuff extract (where ICP = infected cell polypeptide). However, snuff extracts significantly inhibited the production of ICP gC (glycoprotein C), a gamma 2-protein, and the inhibition was in a concentration-dependent fashion: the higher the concentration of snuff extracts, the greater the inhibition. Based on the fact that the production of alpha- and beta-proteins is absolutely necessary for and precedes the viral DNA synthesis and that viral gamma 2-proteins are mostly produced by the newly synthesized viral DNA, it is concluded that snuff extract inhibits HSV-1 DNA replication directly rather than indirectly via the alteration of viral protein synthesis.

Active HSV-1 immunization prevents the cocarcinogenic activity of HSV-1 in the oral cavity of hamsters☆

Previous investigations have demonstrated that herpes simplex virus (HSV) increased the oral carcinogenic activity of 7,12-dimethylbenz[a]anthracene (DMBA) probably by enhancing the DMBA-induced amplification and overexpression of c-erb-B-1 proto-oncogene in hamster buccal pouch epithelium. The present study investigated the effect of active type 1 HSV (HSV-1) immunization on the development of oral cancer induced by HSV-1 and DMBA, alone or in combination, in the hamster buccal pouch. The results were similar to our previous report in that HSV-1 significantly enhanced the oncogenic effect of DMBA, and the numbers of pouches harboring tumor nodules and the numbers and sizes of tumors developed by topical DMBA were significantly increased by HSV-1 inoculation to the site of the DMBA application. Although HSV-1 immunization did not alter the carcinogenic activity of DMBA in animals receiving topical DMBA in combination with mock inoculation, it prevented the cocarcinogenic effect of HSV-1 in animals receiving topical DMBA in conjunction with HSV-1 inoculation. These data indicate that active HSV-1 immunization completely obstructs the co-oncogenic effect of HSV-1 in the oral cavity of hamsters.

Anchorage-independent growth and the expression of cellular proto-oncogenes in normal human epidermal keratinocytes and in human squamous cell carcinoma cell lines

The expression of multiple cellular proto-oncogenes and the in vitro anchorage-independent growth of normal human epidermal keratinocytes and several human squamous cell carcinoma cell lines were studied and correlated. Squamous cell carcinoma cell lines KB, Si Ha, HEp-2, and Fa Du showed high anchorage independency, and MS 751 and A-253 cell lines had minimum independency. However, the normal keratinocytes and the A-431 cell line did not show anchorage-independent growth. Both the normal human epidermal keratinocytes and cancer cell lines expressed multiple proto-oncogenes such as src, erb B-1, abl, fos, raf, H-ras, and myc, and the amount of expression of these oncogenes was notably higher in the cancer cell lines than in the normal keratinocytes. The expression of proto-oncogenes from the monolayer cultures of the cancer cell lines is poorly correlated with the anchorage independency of the cells. These data indicate that the anchorage independency is not directly linked to the expression of specific cellular proto-oncogene(s) of the monolayer cancer cell cultures.