Apoptosis in normal epithelium, premalignant and malignant lesions of the oropharynx and oral cavity: a preliminary study

Birchall, MA; Winterford, Clay; Allan, David J.; Harmon, Brian V.

doi:10.1016/0964-1955(95)00048-8

Cited by 55 publications

(40 citation statements)

References 9 publications

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“…It is possible that the high apoptotic activity in a premalignant lesion reflects an attempt to eliminate genetically damaged cells and that, in the following invasive carcinoma, the aggregated mutations somehow interfere with the apoptosis-regulating mechanisms. In line with our observations, Birchall et al (1995) and Ishida et al (1996) have demonstrated that the apoptotic activity is higher in premalignant gastric lesions and in dysplasias of the oral cavity than in the corresponding invasive carcinomas.…”

Section: Discussionsupporting

confidence: 78%

Apoptotic activity is increased in parallel with the metaplasia–dysplasia–carcinoma sequence of the bronchial epithelium

et al. 1999

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Summary A high level of apoptotic activity and an independence of apoptosis from the expression of p53 and bcl-2 have been observed in non-small-cell lung carcinoma. We examined 44 samples of normal, metaplastic and premalignant (i.e. mild, moderate and severe dysplasias and carcinoma in situ) bronchial epithelia to evaluate whether differences in the apoptotic activity could already be seen in the stages preceding squamous cell carcinoma of the lung (SQCLC). Apoptotic cells and bodies were visualized by 3′ end labelling. The expression of p53 and members of the bcl-2 gene family, such as bcl-2, bax and mcl-1, were determined immunohistochemically with specific antibodies. The relative number of apoptotic cells and bodies [apoptotic index (AI%)] was already increased threefold as the normal bronchial epithelium changed to squamous metaplasia, and the AIs of the dysplastic lesions were about four times higher than those of the normal epithelium. Apoptosis was significantly associated with cell proliferation, as determined by proliferating cell nuclear antigen (PCNA) immunohistochemistry. However, the extent of apoptosis did not correlate with the expression of p53, bcl-2, bax and mcl-1. We conclude that, in the metaplasia-dysplasia-carcinoma sequence in the lung, the elevation of the AI% is an early event associated with cell proliferation activity, but is independent of the expression of p53, bcl-2, mcl-1 and bax.

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Section: Discussionsupporting

confidence: 78%

Apoptotic activity is increased in parallel with the metaplasia–dysplasia–carcinoma sequence of the bronchial epithelium

et al. 1999

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“…Birchall et al (1995) observed in six biopsies of normal buccal epithelium an apoptotic index of 0.12 ± 0.07. The apparent difference between biopsy and washing could be explained by the selection of non-viable cells by washing.…”

Section: Resultsmentioning

confidence: 89%

A new in vitro assay for quantitation of chemotherapy-induced mucositis

Wymenga

Vandergraaf²,

Spijkervet

et al. 1997

Br J Cancer

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Summary Patients receiving high-dose chemotherapy (HD-CT) are at risk of severe mucositis. Most prevention studies evaluate the degree of mucositis on clinical, and therefore subjective, measurements. The aim of this study was to develop an objective in vitro assay of chemotherapy-induced mucositis. Twelve patients with locally advanced breast carcinoma received HD-CT followed by peripheral stem cell reinfusion. Before and twice weekly after HD-CT, the mucosa was evaluated by an oral washing, a buccal smear and the World Health Organization (WHO) toxicity grading; furthermore, blood leucocyte levels were determined. For the oral washings, the percentage of viable epithelial cells was determined by trypan blue dye exclusion and leucocytes were counted by fluorescence microscopy after incubation with acridine orange. Maturity of buccal cells was assessed by staining buccal smears for morphology according to Papanicolaou (Whitacker D and Williams V, 1994). Eight healthy volunteers served as controls. The mean percentage (± s.e.m.) of viable oral epithelial cells was stable in controls (44 ± 2%). In patients, they increased after HD-CT, which was significant after day 7 compared with pretreatment (P < 0.05). In addition, a shift from mature to immature epithelial cells in buccal smears was observed. Oral leucocyte levels were closely correlated with the blood leucocyte counts. The WHO score followed the results of these other evaluations with some delay. The viability of buccal cells obtained by oral washings increases after HD-CT. This is possibly because of desquamation of the upper oral mucosa layer, with a shift from mature to more immature cells. These data can be quantitated, and this assay may therefore be useful in studies aimed at prevention of mucositis.Keywords: mucositis; in vitro assay; quantitation Mucositis is a common, always unpleasant, sometimes unbearable toxic side-effect of chemotherapy. In particular, in patients receiving high-dose chemotherapy followed by bone marrow or peripheral stem cell transplantation, mucositis can be dose limiting. Chemotherapy causes a direct toxic effect on the rapidly dividing cells of the basal oral epithelium, which can result in mucosal atrophy, erythema and ulceration. The severe stages of mucositis with disruption of the oral mucosal barrier can lead to mucosal ulcers and secondary infection. In addition, it can provide a portal of entry for micro-organisms into the systemic circulation, which can lead to life-threatening septicaemia in myelosuppressed patients. Mucositis causes major discomfort, such as pain requiring intensive analgesia, and may restrict or even prohibit normal oral feeding and drug intake (Sonis, 1989;Sonis et al, 1990;Toth et al, 1990;Peterson, 1992; Woo et al, 1993).Grading of mucositis is necessary to document its degree and to evaluate the effect of measures for prevention or intervention. Most available scoring systems are based on a combination of objective changes in the mucosa (e.g. erythema, ulceration), subjective complaints (e.g....

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“…Vascular damage in oral acute GVHD C Deschaumes et al feature of aGVHD, but also of other diseases affecting the oral mucosa, such as Behcet syndrome, paraneoplasic oral mucosa dysplasia, in situ carcinoma, oral erythema multiforme [50][51][52][53][54][55] and typical cutaneous adverse drug reactions, such as Stevens-Johnson syndrome, that has been reported to be induced by soluble CD95L. 56 Whether early CD95L-mediated endothelial-cell death and vascular damage may also be involved in the pathogenesis of these diseases is an interesting possibility that remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

CD95 ligand-dependant endothelial cell death initiates oral mucosa damage in a murine model of acute graft versus host disease

Deschaumes

Verneuil

Ertault-Daneshpouy

et al. 2007

Laboratory Investigation

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Oral mucosa lesions are one of the common pathological consequences of acute graft versus host disease (aGVHD), the major complication of allogeneic bone marrow transplantation caused by mature T lymphocytes of donor origin. Oral mucosa damage in aGVHD is characterized by apoptosis induction in the basal keratinocytes, associated with immune effector T-cell infiltration, but its pathogenesis remains unclear because these lesions might result from the patient conditioning therapy that includes radiation and/or chemotherapy. Here, using a murine model of aGVHD that does not involve any conditioning treatment, we show that the earliest detectable oral mucosa lesion is apoptosis of the endothelial cells from chorion capillaries, which precedes basal keratinocyte apoptosis induction. Neither vascular damage nor epithelial-cell death occurred in recipients of allogeneic lymphocytes from CD95 ligand (CD95L)-defective mice. Our findings indicate that oral mucosa lesions in aGVHD are initiated by endothelial-cell death and require CD95L expression by the allogeneic lymphocytes. This early vascular damage may contribute to the induction of further tissue damage in the oral mucosa, through the induction of hypoxia and vascular leakage of immune cells or soluble proapoptotic mediators.

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Apoptosis in normal epithelium, premalignant and malignant lesions of the oropharynx and oral cavity: a preliminary study

Cited by 55 publications

References 9 publications

Apoptotic activity is increased in parallel with the metaplasia–dysplasia–carcinoma sequence of the bronchial epithelium

Apoptotic activity is increased in parallel with the metaplasia–dysplasia–carcinoma sequence of the bronchial epithelium

A new in vitro assay for quantitation of chemotherapy-induced mucositis

CD95 ligand-dependant endothelial cell death initiates oral mucosa damage in a murine model of acute graft versus host disease

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