• Maxillofacial Plastic and Reconstructive Surgery
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• v.23 no.4
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• pp.295-305
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• 2001

Protein kinase C (PKC) is known to play a pivotal role in neoplastic transformation cells and its high expression is often found in a variety of types of tumors including oral cancer. While PKC is associated with the altered signal transduction pathway of the tumor cells, it is still unclear which isoform is involved in the carcinogenesis process. Since the cellular distributions and the roles of PKC are isoform-specific, it is very important to identify the specific target molecules to improve our understanding of the carcinogenesis processes. Thus, the present study attempted to perform chemical carcinogen-induced neoplastic transformation of human epithelial cells and analyze the specific isoform of PKCs involved in the cellular transformation. The study analyzed overall PKC responses upon MNNG(N-Methyl-N'-nitro-N-nitroso guanidine) exposure with [$^3H$] PDBu binding assay. PKC translocation was observed at high doses of MNNG treatment in the presence of extracellular calcium. Such effects were not observed in the absence of extracellular calcium. Translocational effects with exposure of MNNG was further enhanced in the presence of hydrocortisone. The result suggests that the type of PKC involved may be $Ca^{2+}$-dependent classical isoform and steroid hormone enhances PKC activation. Among cPKC isoforms examined, only $PKC-{\alpha}$ and r showed significant translocation of protein levels from cytosolic fraction to membrane fraction, as analyzed by immunoblot. $PKC-{\varepsilon}$ in nPKC class showed an inch·eased translocation, but other forms in this class did not show the effect. None of isoforms in aPKC class was affected by MNNG treatment. The study demonstrated that there was a certain specificity in the patterns of isoform induction follwong chemical carcinogen exposure and helped identify all the types of PKC isoforms expressed in human epithelial cells. It was revealed that PKC isoforms were activated in an early resonse to chemical carcinogen, suggesting that PKC be associated with carcinogenesis process from an early stage in this particular cell system. The study will contribute to improving our understanding of chemical-induced carcinogenesis in human cells and may provide a scientific basis to introduce the specific PKC inhibitors as an anticancer drug of epithelial cell-origin cancers including oral cancer.

• Radiation Oncology Journal
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• v.8 no.2
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• pp.207-212
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• 1990

To determine the correlation between the response to induction chemotherapy and subsequent radiotherapy we analyzed the clinical records of 60 patients with locally advanced carcinoma of the head and neck retrospectively who had completed a full course ($2\~3$ cycle) of induction chemotherapy and curative radiotherapy in Korea Cancer Center Hospital between 1986 and 1989. Chemotherapy was administeredd with CDDP+Bleomycin (BP) in 20, CDDP+5-FU (FP) in 37, and hybrid of BP and FP in three patients. Radiotherapy was giver conventionally with a dose of 65 to 75 Gy or more over seven to eight weeks according to the size of lesion. Response rates following induction chemotherapy were $80\%$ for the tumors and $879\%$ for the nodes whereas complete reponse rates were $12\%\;and\;13\%$, respectively. Six months after radiotherapy $67\%$ of the tumors and $77\%$ of the nodes achieved a complete response. Among the 48 tumor responders and the 31 nodal responders to chemotherapy,39 ($81\%$) and 28 ($90\%$), respectively, achieved complete response after radiotherapy. Thus, whether or not the tumor and node respond to induction chemotherapy was predictive of the response to subsequent radiotherapy (p<0.0005 in tumor, p<0.0001 in node). By reanalyzing according to disease subsets (i.e. primary site, T-stage, N-stage) this relationship was not observed at T1-T2 disease (p>0.3). Therefore the tumor or node's response to induction chemotherapy is a predictor for subsequent radiotherapy except in T1-T2 tumors, and complete response to radiotherapy can be expected despite the failure of induction chemotherapy in $T_1-T_2$ tumors.