p53基因突變普遍發生於口腔鱗狀細胞癌（Oral squamous cell carcinoma, OSCC），此一基因含約20kb的DNA，393個氨基酸。現今對於口腔鱗狀細胞癌的治療仍具相當數目的治療失敗情形。最近有研究指出p53腫瘤抑制基因（p53 tumor suppressor gene）可能關連於某些治療失敗的情形，此一基因的不活化可能是現今與癌症治療效率有關的一個重要因子。於細胞培養中，惡性腫瘤之特性常可藉由植入正常的腫瘤抑制基因而致改善。正常野生型p53（Wild type p53, wt-p53）關聯於細胞週期進行。不正常或突變的p53基因可致突變基因積存及染色體重新排列。許多研究顯示，改正p53的異常有助於腫瘤的治療。於突變或缺失（deletion）p53的人類肺癌細胞株及以裸鼠為模式的人類肺癌中植入野生型p53基因，可降低惡性腫瘤的表現。Clayman等人利用野生型p53基因於治療頭頸部腫瘤，結果顯示在體外（in vitro）野生型p53基因能阻止頭頸部鱗狀細胞癌（Head and neck squamous cell carcinoma, HNSCC）細胞的增殖，且野生型p53蛋白質能誘發HNSCC細胞出現凋亡，其結果指出p53腫瘤抑制基因於治療頭頸部腫瘤具極佳的療效與較佳的應用前景。為了評估野生型p53基因對頭頸部鱗狀細胞癌的基因療效，將經重組含野生型p53的腺病毒轉殖於頭頸部鱗狀細胞癌的細胞株以探討其治療效率。本研究乃藉由現代分子生物學技術將野生型p53基因與腺病毒（Adenovirus）載體（Vector）構建重組體（Recombinant），經選殖重組的腺病毒液後將其轉染受體細胞，最後觀察經轉染的受體細胞對頭頸部鱗狀細胞癌於體內外的影響，進而對口腔癌的治療提供一條新的途徑。本計劃第一年為針對TSCCA及GNM二株癌細胞，對照正常細胞BF、GF及癌前細胞OSF之p53基因部份之變異，初步序列分析證實p53與口腔癌細胞之形成有相關聯性。
It is well established that a high incidence of p53 mutations exist in oral cavity squamous cell carcinomas. The p53 gene is contained within 20 kb of cellular DNA located on the short arm of human chromosome 17 at 17p13.1. Despite the combination of therapeutic options, there are still a large number of treatment failures and therefore major questions remain. Recent investigations suggest that mutations of the p53 tumour suppressor gene may account for some of the therapeutic failures. Inactivation of the gene may be an important determinant of the efficiency of today's multimodal therapy protocols. In cell culture, malignant properties can often be reversed by inserting normal tumor suppressor genes. Normal (wild-type) p53 is involved in the control of cell cycle progression as well as in arresting replication to permit repair in DNA damaged cells. It may also be involved in restricting precursor populations by mediating apoptosis or programmed cell death. Abnormal or mutant p53 permits the accumulation of gene mutations and chromosomal rearrangements. There is experimental evidence showing the benefits derived from the correction of p53 abnormalities. Replacement of wild type p53 using adenoviral expression vectors in both human lung cancer cell lines with mutant or deleted p53 in vitro and in nude mouse model of orthotopic human lung cancer resulted in suppression of the malignant phenotype. The aim of this study is to estimate the efficacy of the tumor suppressor gene wild-type p53 as single-agent gene therapy for squamous cell carcinoma of the head and neck (HNSCC). Recombinant cytomagalovirus (CMV) -promoted adenoviruses containing the wild-type p53 gene was transiently introduced into squamous cell carcinoma of the head and neck cell lines. This first year study has finished the comparison of p53 mutations of two oral cancer cell lines TSCCa and GNM, two normal cells BF and GF, and one precancer cells OSF. Preliminary sequencing data suggested the p53 mutations were correlated with the oncogenesis of oral cells.
