Biomedical subjects

S C Girod

Publications and source records attributed to S C Girod.

14 recordsLinked to original sources

PubMed1998

[p53 as a biomarker in radiotherapy of carcinoma of the mouth cavity].

Multimodal therapy of oral squamous cell carcinomas today is based on surgery, radiotherapy and chemotherapy. Despite the combination of all three therapeutic options, there is still a large number of treatment failures and therefore major questions remain. Recent investigations suggest that mutations of the p53 tumor suppressor gene may account for some of the therapeutic failures. Inactivation of the gene may be an important determinant of the efficacy of today's multimodal therapy protocols. In 90 patients with squamous cell carcinomas of the oral cavity biopsy specimens were taken before and after preoperative radiochemotherapy. From all patients, biopsy and resection material was available for immunohistochemical analysis of p53. After radiation treatment, 51 patients (57%) showed a complete response; 39 patients (43%) only showed a partial response or did not respond at all. Among the responders, 82% of the pretherapeutic tumors were p53 positive, whereas among the nonresponders only 56% of the pretherapeutic tumors were p53 positive. The majority of the residual tumors were also p53 negative according to immunohistology after radiation treatment. In our study, detection of p53 protein by immunohistochemistry seemed to be connected with a more radiosensitive reaction of the tumors. Nevertheless, successful strategies for radiation therapy may need to take into account the tissue of origin and the status of p53 in the tumor.

Biomarkers, Tumor↗

PubMed1998

Proliferative activity and loss of function of tumour suppressor genes as 'biomarkers' in diagnosis and prognosis of benign and preneoplastic oral lesions and oral squamous cell carcinoma.

Oral cancer is a disease of the elderly and is closely connected with cigarette smoking and alcohol consumption. Since the successful introduction of multidisciplinary treatment, the survival rate has not changed. Because of the high mortality and potentially disfiguring treatment, today's efforts are aimed at eliminating risk factors, chemoprophylaxis, improvement in diagnostic procedures, and understanding of the genetic mechanisms of oral carcinogenesis. Immunohistochemical and molecular biology analysis of biopsy tissue and cell lines of preneoplastic and neoplastic lesions that originate from the oral mucosa have shown that alterations in tumour suppressor genes such as p53 and Rb gene may have an important role in oral carcinogenesis and may be potentially useful prognostic 'biomarkers' in oral carcinogenesis. Statistical analysis of immunohistochemical data from 216 patients did not identify significant or consistent differences of p53, MDM2, or RB expression with respect to stage of disease, malignant transformation, metastatic node involvement, recurrence, or survival. Nevertheless, p53 overexpression seems to correlate strongly with histological progression of the disease, which confirms the importance of p53 alterations in oral carcinogenesis. Overexpression of p53 is usually found in the less differentiated proliferating cells in benign and malignant oral lesions. Assessment of the proliferating activity is possible by immunohistochemical staining with monoclonal antibodies against proliferating nuclear antigen and Ki-67. Statistical analysis shows that overexpression of p53 combined with high proliferative activity predicts a less favourable course of disease in oral squamous cell carcinoma.

Aged↗

PubMed1997

Radiosensitivity and double-strand break rejoining in tumorigenic and non-tumorigenic human epithelial cell lines.

Radiosensitivity and repair of DNA damage induced by ionizing radiation and restriction enzymes were investigated in three human epithelial cell lines: two tumorigenic squamous carcinoma cell lines (SCC-4 and SCC-25), and a non-tumorigenic epidermal keratinocyte cell line (RHEK-1). Sensitivity to ionizing radiation was determined using a clonogenic cell survival assay, which showed SCC-4 to be more radiosensitive than SCC-25 and RHEK-1, which in turn displayed about equal sensitivity. Using DNA precipitation under alkaline conditions for the analysis of induction and repair of DNA single-strand breaks (ssb), an increased level of ssb induction was found for SCC-4 while the efficiency of ssb repair was about equal in all three cell lines. Using pulsed-field gel electrophoresis (PFGE) for the measurement of induction and repair of DNA double-strand breaks (dsb), no consistent differences were detected between the three cell lines. A plasmid reconstitution assay was used to determine the capacity to rejoin restriction enzyme-induced dsb in whole-cell extracts prepared from the three cell lines. In these experiments, dsb rejoining was shown to be significantly reduced in the most radiosensitive SCC-4 cell line while it was about equal in RHEK-1 and SCC-25. The results indicate that plasmid reconstitution in cell-free extracts is a sufficiently sensitive assay to detect differences in repair capacity among tumour cell lines of different radiosensitivity which remain undetectable by DNA precipitation and PFGE.

Amino Acid Sequence↗

PubMed1996

Retinoid actions and implications for prevention and therapy of oral cancer.

Squamous cell carcinomas of the oral cavity can be preceded by clinically obvious premalignant changes, and they have a high rate of incidence of development of second primary tumors. Recent studies suggest retinoids not only for the treatment of oral eukoplakia, but also for the prevention of second primaries. Although retinoids are promising therapeutic agents, their therapeutic potential has been limited by their undesirable side-effects. A complete network of nuclear receptors has now been identified that mediate the action of retinoids and can interfere directly with cell proliferation signals by interacting with transcription factors. It has recently been shown that retinoids with receptor-selective activities can be obtained that are likely to have fewer side-effects because of their restricted biologic activities.

Antineoplastic Agents↗

PubMed1994

p53 expression in the carcinogenesis in the oral mucosa.

Hyperplastic lesions of the oral mucosa such as leukoplakia and oral lichen planus can eventually develop into squamous cell carcinomas. In the clinical treatment of these lesions it would be very important to be able to predict the biological behaviour of an individual lesion. In 64 hyperplastic lesions and 85 squamous cell carcinomas of the oral mucosa, the expression of the mutant tumor suppressor gene p53 was investigated. A positive correlation was seen between the expression of the mutant tumor suppressor gene p53 and the grade of dysplasia of the lesions.

Gene Expression↗

PubMed1994

p53 and PCNA expression in carcinogenesis of the oropharyngeal mucosa.

Hyperplastic lesions of the oral mucosa such as leukoplakia and oral lichen planus can eventually develop into squamous cell carcinomas (SCC) and provide an excellent model for multistage carcinogenesis. The development of carcinomas is assumed to be the result of interaction of genetic factors, locally applied carcinogens and immunological unresponsiveness. The purpose of this study was, therefore, to determine the role of alterations of the tumour suppressor gene p53, and the proliferation status of the lesions determined by PCNA expression. We investigated p53 and PCNA expression in 265 tissue sections of normal mucosa, premalignant, malignant and metastatic lesions of the oral mucosa by immunohistology. Quantitative analysis showed a gradual increase in PCNA expression from normal mucosa to moderately differentiated SCC. p53 expression was detectable in benign premalignant lesions. The increase in the number of p53-positive biopsies was correlated with the dysplasia and loss of differentiation in the premalignant and malignant lesions.

Carcinoma, Squamous Cell↗

PubMed1994

p53 and PCNA expression in malignant melanomas of the head and neck.

Mutation in the p53 tumor suppressor gene is the most common genetic alteration in human cancer. As in mutant p53 the protein is stabilised and the half-life is extended, it becomes detectable by immunohistological staining. p53 immunoreactivity thus seems to be a potential biomarker for the assessment of the oncogenic potential of malignant melanomas. In 103 tissue sections of primary and metastatic malignant melanomas of the head and neck detectable levels of p53 were only found in 3 of the primary tumors and in none of the metastases. At the same time the proliferation status of the malignant melanoma lesions was determined using the cell cycle specific antibody PCNA. 55 primary and metastatic tumors were stained with a PCNA-MAb to determine the proliferation activity of the tumors. The results of our immunohistochemical investigation suggest that immunoreactivity of p53 cannot be used to determine the malignant potential of melanomas in the head and neck. PCNA staining showed that the majority of the tumors and metastases were proliferating rapidly.

Antibodies, Monoclonal↗

PubMed1993

p53 and Ki 67 expression in preneoplastic and neoplastic lesions of the oral mucosa.

Some lesions of the oral mucosa such as leukoplakia and erythroplakia may develop into squamous cell carcinoma (SCC). At present, however, there is no method available to predict malignant transformation. It is known that the grade of dysplasia is related to the potential malignant development, but this is unreliable as the only indicator. In 64 hyperplastic lesions and 85 SCC of the oral mucosa, a correlation between the expression of the mutated tumor-suppressor gene p53 and the dysplasia of the lesions was found. Ki 67 was used as a proliferation marker. The results imply that expression of mutated p53 is an indicator for potential malignant development in benign lesions of the oral mucosa.

Antigens, Neoplasm↗

PubMed1993

Cysts associated with long-standing impacted third molars.

Three patients are described in whom large cysts developed around third molars that had purposely been left in place. The cases presented emphasize the need for an adequate prospective study to evaluate the long-term morbidity of asymptomatic third molars that are left in place.

Adult↗

PubMed1989

The fascicular structure of the lingual nerve and the chorda tympani: an anatomic study.

Damage of the lingual nerve is one of the most common problems in oral surgery, especially during removal of the third molar. After microsurgery of the lingual nerve, there is a lack of regeneration of the gustatory fibers in comparison with the sensory fibers. The histologic investigation of ten human lingual nerve preparations showed that the chorda tympani fibers distribute widely in the fascicles of the lingual nerve. Therefore, after microsurgical reconstruction of the lingual nerve in the third molar region, the chance of the gustatory fibers meeting and regenerating is very low.

Chorda Tympani Nerve↗

PubMedDate not supplied

Correlation of telomerase activity, clinical prognosis and therapy in oral carcinogenesis.

Telomerase activity is associated with most malignant tumors. To evaluate the role of telomerase reactivation as a diagnostic and prognostic marker in oral carcinogenesis activity was investigated in mortal and immortal cell lines in eight oral leukoplakias (OL) and 46 oral squamous cell carcinomas (OSCC). Activity was also investigated in 13 histopathologically unaffected mucosas from distant sites or tumor-free margins of the same patients using a modified, highly sensitive, non-radioactive telomeric repeat amplification protocol (TRAP). This was correlated with histopathological stages and the clinical course of the disease. 50% of OL and 46% of OSCC showed activity. One patient with positive, high dysplastic OL developed an OSCC 11 month later. One of three specimens of adjacent tissue presented activity and a recurrence occurred after 6 months. Out of 10 tissues of distal normal mucosa, 2 demonstrated activity which could also be proved in the corresponding tumor. Detection of telomerase reactivation may be a novel method for early detection of immortalised cell clones and malignant cells in histopathologically normal oral squamous epithelium.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Detection of p53 and MDM2 protein expression in head and neck carcinogenesis.

Hyperplastic lesions of the oropharyngeal mucosa such as leukoplakia and oral lichen planus can eventually develop into squamous cell carcinomas (SCC) and provide an excellent model for multistage carcinogenesis. The development of carcinomas is assumed to be the result of the interaction of genetic factors, locally applied carcinogens and immunological unresponsiveness. Recently a novel gene termed mdm2 has been isolated that is found to be involved in transcriptional regulation and can inhibit p53 function by forming a complex with p53. In this study the immunohistochemical detection of the MDM2 protein in 186 paraffin embedded tissue sections of normal mucosa, premalignant, malignant and metastatic lesions of the oropharyngeal mucosa is reported for the first time. p53 protein expression was also investigated in the same tissue samples. The increase in the number of p53 and MDM2 positive biopsies was correlated with the dysplasia grade and the loss of differentiation in the premalignant and malignant lesions. In late stages of the disease the number of biopsies that expressed both p53 and MDM2 increased. Inactivation of p53 function in head and neck carcinogenesis may also be due to MDM2 binding. Detection of MDM2 protein expression by immunohistochemistry may be an important diagnostic tool in the future.

Head and Neck Neoplasms↗

PubMedDate not supplied

Langerhans cells in epithelial tumors and benign lesions of the oropharynx.

Hyperplastic lesions of the oral mucosa such as leukoplakia and oral lichen planus can eventually develop into squamous cell carcinomas. The development of carcinomas may be the result of the interaction of genetic factors, carcinogens and an impaired immune response. The presence of S-100 positive Langerthans cells in normal mucosa, premalignant and malignant lesions of the oral mucosa was investigated by immunohistology. Quantitative analysis showed that in benign lesions of the oral mucosa the average number of S-100 positive cells was much higher than in normal mucosa. In the neoplastic lesions the number of S-100 positive cells was in general lower than in the benign lesions and decreased even more with loss of differentiation. The data suggest that the infiltration of dendritic cells increases in benign lesions of the oral mucosa, implying a normal immunostimulatory potential, and decreases in malignant lesions in relation to the loss of differentiation in the tumors.

Antibodies, Monoclonal↗

PubMedDate not supplied

p53 mutation and detection of p53 protein expression in oral leukoplakia and oral squamous cell carcinoma.

In many studies the detection of p53 protein by immunohistochemistry (IHC) with one antibody is assumed to be consistent with a mutation of the gene. To determine the correlation of protein detection by immunohistochemistry and gene mutation, paraffin embedded specimens of 60 oral leukoplakias (OL) and 73 oral squamous cell carcinomas (OSCC) were analysed by IHC with two different antibodies (Do7; Pab 1801), PCR-SSCP and sequencing. In 98% of OLs and 94% of OSSCs p53 protein expression was detected with at least one antibody. Only 49% of all tissue specimen were positive with both antibodies. Molecular analysis of the same specimen showed mutations of the p53 gene in 13.3% of OLs and 9, 6% of OSCCs. p53 protein expression was not detected by IHC in 3 out of 7 OSCC with p53 mutations. According to these results detection of p53 expression by IHC is not always correlated with p53 gene mutation and failure to detect p53 protein by IHC does not prove the absence of mutation of the gene in the carcinogenesis in the oral mucosa.

Antibodies, Monoclonal↗