• Radiation Oncology Journal
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• v.21 no.4
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• pp.269-275
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• 2003

Purpose: To evaluate the results of radiation management on recurrence, survival and prognostic factors of patients with nasopharyngeal cancer Materials and Methods: Forty-nine patients, treated for nasopharyngeal cancer by radiotherapy between January 1984 and June 2000, were retrospectively studied. All patients were followed up for at least 2.5 years. Their median age was 52 years (range 17$\~$78). The histological types were 21 squamous cell carcinoma, 25 undifferentiated carcinoma, and 3 adenoid cystic carcinoma. The tumor stages were as follows: T1 in 14 patients, T2 in 24, T3 in 3, and T4 in 8, and N0 in 17 patients, Nl in 15, N2 in 4 and N3 in 13. Stages I, IIa, IIb ,III, IV and IVb were 4, 7, 12, 5, 8, and 13 patients respectively. Radiation doses of 58$\~$70 Gy (median 68.7 Gy) were given to the nasopahryngeal and involved lymphatic areas and of 46 $\~$ 50 Gy to the uninvolved neck areas. Results: The overall 5 and 10-year actuarial and disease free survival rates were 54.53$\%$ and 47$\%$ and 55.7$\%$ and 45.3$\%$, respectively The overall five-year survival rates were 100$\%$ in stage I , 80$\%$ in stage IIa, 59.5$\%$ in stage IIIb, 40$\%$ in stage III, and 42.2$\%$ in stage IV tumors. Twenty-three patients fatted either loco-regionally or distantly. Incidences of local failure, regional failure and distant metastasis for the first failure were 20.4$\%$, 8.2$\%$ and 20.4$\%$, respectively. Local recurrences were 4.3$\%$ in T1, 12.5$\%$ in T2, 0$\%$ in T3, and 62.5$\%$ in T4 lesions. Distant metastasis was seen in 41.2$\%$ of N2-3 lesions. Fifty percent of local recurrence appeared within 2 years of treatment at the primary lesion, whereas 70$\%$ of distant metastasis appeared within 2 years following treatment. Young age, female, early T stage, N0 stage; and poorly differentiated carcinoma were all related with good survival. However only stage showed statistically significance. Conclusionn: Based on the results of this study, radiation therapy to nasopharyngeal cancer showed high local recurrence in T4 and increased metastasis in N2-3 lesions. To improve local failure, further radiation doses, such as stereotactic radiation or IMRT radiation, are necessary especially in T4 lesions. The high incidence of distant metastasis in positive lymph node patients, indicates that combined radiation and effective chemotherapeutic agents with appropriated schedule are necessary.

• Radiation Oncology Journal
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• v.21 no.4
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• pp.322-329
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• 2003

Purpose: It is difficult to exactly determine the surface dose and the dose distribution In buildup region of high energy X-rays by using the conventional ion chamber. The aim of this study Is to evaluate the accuracy of widely used dosimetry systems to measure the surface dose and the depth of maximum dose (d$_{max}$). Materials and Methods: We measured the percent depth dose (PDD) from the surface to the d$_{max}$ in either a water phantom or in a solid water phantom using TLD-100 chips, thimble type ion chamber, diode detector, diamond detector and Markus parallel plate ion chamber for 6 MV and 15 MV X-rays, 10$\times$10 cm$^{2}$, at SSD=100cm. We analysed the surface dose and the d$_{max}$. In order to verify the accuracy of the TLD data, we executed the Monte Carlo simulation for 5 MV X-ray beams. Results: The surface doses In 6 MV and IS MV X-rays were 29.31% and 23.36% ior Markus parallel plate ion chamber, 37.17$\%$ and 24.01$\%$ for TLD, 34.87$\%$ and 24.06$\%$ for diamond detector, 38.13$\%$ and 27.8$\%$ for diode detector, and 47.92$\%$ and 35.01$\%$ for thimble type ion chamber, respectively. in Monte Carlo simulation for 6 MV X-rays, the surface dose was 36.22$\%$, which Is similar to the 37.17$\%$ of the TLD measurement data. The d$_{max}$ In 6 WV and 15 MV X-rays was 14$\~$16 mm and 27$\~$29 mm, respectively. There was no significant difference in the d$_{max}$ among the detectors. Conclusion: There was a remarkable difference in the surface dose among the detectors. The Markus parallel plate chamber showed the most accurate result. The surface dose of the thimble ion chamber was 10$\%$ higher than that of other detectors. We suggest that the correction should be made when the surface dose of the thimble ion chamber Is used for the treatment planning ion the supeficial tumors. All the detectors used In our study showed no difference in the d$_{max}$.

• 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.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.2
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• pp.95-110
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• 2006

The treatment for oral and maxillofacial carcinoma with chemotherapeutic agents is evaluated by many effective methods to reduce the tumor mass and cancer cell proliferation. However these chemotherapy have many serious side effects, such as bone marrow suppression, renal toxicity, G-I troubles. Therefore a possible approach to develop a clinically applicable chemotherapeutic agent is to screen anticancer activity of Taxol which is known to have very little side effect and have been used to breast cancer and ovarian carcinoma. Taxol is a new anti-microtubular anti-cancer agent extracted from the bark of the Pacific yew, Taxus brevifolia. Paclitaxel(Taxol) acts by promoting tubulin polymerization and over stabilizing microtubules agianst depolymerization. Despite the constant improvements of methods of the cancer treatment especially chemotherapy, the rate of cancer metastasis and recurrent are not decreased. Thus the investigation of new drug which have very little side effect and a possible clinically application continues to be a high priority. Considering that the Taxol have shown very effective chemotherapeutic agent with relatively low toxicity in many solid tumors, it deserves to evaluate its efficacy in oral squamous cell carcinoma. In this study, to investigate the in-vivo and in-vitro anti-cancer efficacy of Taxol in oral squamous cell carcinoma and lastly, the potency of Paclitaxel in the clinical application for oral cancer was evaluated. In vivo study, after HN22 cell line were xenografted in nude mice, the growth of tumor mass was observed, 3 mg/Kg taxol was injected intraperitoneally into nude mice containing tumor mass. The methods of these study were measurement of total volume of tumor mass, histopathologic study, immunohistochemical study, drug resistance assay, growth curve, MTT assay, flow cytometry, cDNA microarray in vivo and in vitro. The results were obtained as following. 1. The visual inspection of the experimental group showed that the volume of the tumor mass was slightly decreased but no significant difference with control group. 2. Ki-67 index was decreased at weeks 4 in experimental group. 3. Microscopic view of the xenografted tumor mass showed well differentiated squamous cell carcinoma and after Taxol injection, some necrotic tissue was seen weeks 4. 4. The growth curve of the tumor cells were decreased after 1day Taxol treatment. 5. According to the MTT assay, HN22 cell line showed relative drug resistancy above $5\;{\mu}g/ml$ concentrations of Taxol. 6. In drug resistance assay, the decrease of cell counts was seen relatively according to concentration. 7. In Flow cytometry, G2M phase cell arrests were seen in low concentration of the Taxol, while S phase cell arrests were seen in high concentration of the Taxol. 8. Using cDNA microarray technique, variable gene expression of ANGPTL4, TXNRD1, FAS, RRAGA, CTGF, CYCLINEA, P19, DUSP5, CEBPG, BTG1 were detacted in the oral squamous cell carcinoma cell after taxol treatment. In this study paclitaxel is effective against oral squamous cell carcinoma cell lines in vitro, but week effect was observed in vivo. So we need continuous study about anticancer effect of taxol in vivo in oral squamous cell carcinoma.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.3
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• pp.245-253
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• 2000

The development and progression of oral cancer is associated with an accumulation of multiple genetic alterations through the multistep processes. Comparative genomic hybridization(CGH), newly developed cytogenetic and molecular biologic technique, has been widely accepted as a useful method to allow the detection of genetic imbalance in solid tumors and the screening for chromosome sites frequently affected by gains or losses in DNA copy number. The authors examined 19 primary oral squamous cell carcinomas using CGH to identify altered chromosome regions that might contain novel oncogenes and tumor suppressor genes. Interrelationship between these genetic aberrations detected and major oncogenes and tumor suppressor genes previously recognized in carcinogenesis of oral cancers was studied. 1. Changes in DNA copy number were detected in 14 of 19 oral cancers (78.9%, mean: 5.58, range: $3{\sim}13$). High level amplification was present in 4 cases at 9p23, $12p21.1{\sim}q13.1$, 3q and $8q24{\sim}24.3$. Fourteen cases(78.9%, mean: 3.00, range: $1{\sim}8$) showed gains of DNA copy number and 12 cases(70.5%, mean: 2.58, range: $1{\sim}9$) revealed losses of DNA copy number. 2. The most common gains were detected on 3q(52.6%), 5p(21.0%), 8q(21.0%), 9p(21.0%), and 11q(21.0%). The losses of DNA copy number were frequently occurred at 9p(36.8%), 17q(36.8%), 13q(26.3%), 4p(21.0%) and 9p(21.0%). 3. The minimal common regions of gains were repeatedly observed at $3q24{\sim}26.7$, $3q27{\sim}29$, $1q22{\sim}31$, $5p12{\sim}13.3$, $8q23{\sim}24$, and 11q13.1-13.3. The minimal common regions of losses were detected at $9q11{\sim}21.3$, 17p31, $13q22{\sim}34$, and 14p16. 4. In comparison of CGH results with tumor stages, the lower stage group showed more frequent gain at 3q, 5q, 9p, and 14q, whereas gains at 1q($1q22{\sim}31$) and 11q($11q13.1{\sim}13.3$) were mainly detected in higher stage group. The loss at $13q22{\sim}34$ was exclusively detected in higher stage. The results indicate that the most frequent genetic alterations in the development of oral cancers were gains at $3q24{\sim}26.3$, $1q22{\sim}31$, and $5p12{\sim}13.3$ and losses at $9q11{\sim}21.3$, 17p31, and 13q. It is suggested that genetic alterations manifested as gains at $3q24{\sim}26.3$, $3q27{\sim}29$, $5p12{\sim}13.3$ and 5p are associated with the early progression of oral cancer. Gains at $1q22{\sim}31$ and $11q13.1{\sim}13.3$ and loss at 13q22-34 could be involved in the late progression of oral cancers.

• Tuberculosis and Respiratory Diseases
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• v.50 no.6
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• pp.676-685
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• 2001

Background : Angiogenesis is an essential component of tumor growth and metastasis, and the vascular endothelial growth factor (VEGF) is one of the most important angiogenic factors. Several solid tumors produce substantial amounts of VEGF, which stimulates proliferation and the migration of endothelial cells, thereby inducing neovasculization by a paracrine mechanism. To evaluate the prognostic roles of angiogenesis and VEGF expression in patients with non-small cell lung cancer, the relationship between VEGF expression in tumor tissues, the clinicopathologic features and the overall survival rate were analysed. Methods : Sixty-nine resected primary non-small cell lung cancer specimens were evaluated. The paraffin-embedded tumor tissues were stained by anti-VEGF polyclonal antibodies using an immunohistochemical method to assess VEGF expression. Results : In Forty-one patients (59%), the VEGF antigen was expressed weakly in their tumor tissue, whereas in twenty-eight patients (41%) the VEGF antigen was expressed strongly. The median survival time of the weak VEGF expression group was 24 months, and that of the strong VEGF expression group was 19 months. The three year-survival rates were 35%, 33%, respectively. The survival difference between both groups was not statistically significant. Conclusion : Although results were not statistically significant, the strong expression group tended to poorer prognosis than the weak expression group.

• Tuberculosis and Respiratory Diseases
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• v.57 no.2
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• pp.160-168
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• 2004

Background : The role of second-line chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC) is known to be limited. Recently, ZD1839, the small molecule epidermal growth factor receptor-tyrosine kinase inhibitor, has been developed and has shown anti-tumor activity in patients with solid malignant tumors including lung cancer. We evaluated the response rate and toxicities of ZD1839 in patients with advanced NSCLC which has progressed after previous chemotherapy. Patients and Methods : We examined 83 patients with advanced NSCLC treated with ZD1839 for more than 1 month in Korea Cancer Center Hospital during the period from January 2002 to September 2003. All the patients were enrolled in the international expanded access program (EAP) with ZD1839 by AstraZeneca. The administered dose of ZD1839 was 250 mg once daily. Chest radiography and laboratory tests were followed-up. We evaluated the response rate, median survival, and toxicity after treatment. Results : Median age of the patients was 59 years (range 33-76). The most predominant cell type was adenocarcinoma and the most stage of the patients was IV. ECOG performance status was as follows; grade 0-1 in 10, grade 2 in 42, and grade 3 in 31 patients. Partial response was achieved in 12 patients (14.5%). Median overall survival was 9.2 (range 1.3-21.6+) months and median time to progression was 3.1 (range 1-21.2+) months. The most common adverse effect of ZD1839 was skin eruption which developed in 25 patients (25.8%). Significantly higher response rate and survival was found in patients with adenocarcinoma or good performance status. Conclusion : ZD1839 showed modest activity and tolerable toxicity in the treatment for patients with NSCLC which has progressed after previous chemotherapy.

• The Journal of the Korean bone and joint tumor society
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• v.7 no.1
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• pp.20-27
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• 2001

Purpose : The giant cell tumor of tendon sheath is the second most common tumor of the hand, but recurred frequently although excision was performed. Authors analyzed and would report clinical findings and postoperative results of it. Materials and Methods : Between January 1991 and December 1998, 38 patients, 41 cases which the authors had performed excisional biopsy to the mass in the hand and diagnosed with the giant cell tumor of tendon sheath, was analyzed with age, sex, chief complaint, symptom duration, involved finger, involved tendon, frequently developed site in fingers, size, multiplicity, radiologic findings and recurrence. The mean duration of follow-up was 13.1 months (5~40 months). Results : Of 38 patients, twenty-nine were female. It is frequent in the fourth decade and mean age was 40.1 years old. The neurological compression symptom was found in 5 cases. The mean duration of symptom was 23.4 months. Flexor tendon was involved in 24 cases. The distal interphalangeal joint area in digit was involved most frequently in 20 cases. Index finger was the most common involved finger (14 cases), and long finger was the second most common (9 cases). All tumors were unilateral. The majority of patients had solitary lesion but one case had multiple lesion. In the radiologic findings, erosion or pressure indentation of bone was seen in 3 cases. All patients were operated by marginal excision. Recurrence rate was 5.1%. Conclusion : The risk factors in giant cell tumor of tendon sheath were female, forth decade, index finger, flexor tendon, and distal interphalangeal joint area. The recurrence was increased in marginal excision of recurred cases, in cases with multiple developed lesions or in multilobular lesion, so wide surgical excision is necessary to prevent recurrence.

• Journal of Gastric Cancer
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• v.9 no.4
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• pp.262-268
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• 2009

Purpose: We wanted to analyze the clinicopathologic characteristics of patients with gastric carcinoid tumor, which is a rare gastric tumor (less than 2% of all gastric tumors). Materials and Methods: We reviewed all the carcinoid patients who were treated from 1996 to 2006. The clinicopathologic characteristics, the treatment modalities and the survival rates were retrospectively analysed. Results: There were 8 type I patients and 10 type III patients, but there were no type II patients. The mean age of onset for type I was 47.75 years and that for type III was 57.90 years. More type III patients were female, but the gender ratio of type I patients was equal at a ratio of 1：1. There were 4 cases of solitary tumor, which were all T1 except for one case, and there was neither distant metastasis nor lymph node involvement for the type T1 cases. In the 13 patients who had no metastasis, 5 underwent endoscopic mucosal resection and 8 underwent surgery, and their combined 5 year survival rate was 92.3%. For the 5 cases who had metastastses, their mean survival was 22 months and especially, 3 of them underwent palliative surgery and their median survival were 24 months (95%, ${\pm}6.52$). Conclusion: Higher incidence of type III gastric carcinoid tumor and less multiplicity in type I gastric tumor were identified in our study compared with previous reports. For the type III cases, there were some noteable differences compared with the Western country's survival rate for the patients who underwent palliative surgery, so physicians must pay close attention to the definite clinicopathologic characteristics of gastric carcinoid patients.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.22 no.2
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• pp.164-173
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• 2000

The p16 protein is a cyclin dependent kinase inhibitor that inhibits cell cycle progression from $G_1$ phase to S phase in cell cycle. Many p16 gene mutations have been noted in many cancer-cell lines and in some primary cancers, and alterations of p16 gene function by DNA methylation have been noticed in various kinds of cancer tissues and cell-lines. There have been a large body of literature has accumulated indicating that abnormal patterns of DNA methylation (both hypomethylation and hypermethylation) occur in a wide variety of human neoplasma and that these aberrations of DNA methylation may play an important epigenetic role in the development and progression of neoplasia. DNA methylation is a part of the inheritable epigenetic system that influences expression or silencing of genes necessary for normal differentiation and proliferation. Gene activity may be silenced by methylation of up steream regulatory regions. Reactivation is associated with demethylation. Although evidence or a high incidence of p16 alterations in a variety of cell lines and primary tumors has been reported, that has been contested by other investigators. The precise mechanisms by which abnormal methylation might contribute to carcinogenesis are still not fully elucidated, but conceivably could involve the modulation of oncogene and other important regulatory gene expression, in addition to creating areas of genetic instability, thus predisposing to mutational events causing neoplasia. There have been many variable results of studies of head and neck squamous cell carcinoma(HNSCC). This investigation was studied on 13 primary HNSCC for p16 gene status by protein expression in immunohistochemistry, and DNA genetic/epigenetic analyzed to determine the incidence, the mechanisms, and the potential biological significance of its Inactivation. As methylation detection method of p16 gene, the methylation specific PCR(MSP) is sensitive and specific for methylation of any block of CpG sites in a CpG islands using bisulfite-modified DNA. The genomic DNA is modified by treatment with sodium bisulfate, which converts all unmethylated cytosines to uracil(thymidine). The primers designed for MSP were chosen for regions containing frequent cytosines (to distinguish unmodified from modified DNA), and CpG pairs near the 5' end of the primers (to provide maximal discrimination in the PCR between methylated and unmethylated DNA). The two strands of DNA are no longer complementary after bisulfite treatment, primers can be designed for either modified strand. In this study, 13 paraffin embedded block tissues were used, so the fragment of DNA to be amplified was intentionally small, to allow the assessment of methylation pattern in a limited region and to facilitate the application of this technique to samlples. In this 13 primary HNSCC tissues, there was no methylation of p16 promoter gene (detected by MSP and automatic sequencing). The p16 protein-specific immunohistochemical staining was performed on 13 paraffin embedded primary HNSCC tissue samples. Twelve cases among the 13 showed altered expression of p16 proteins (negative expression). In this study, The author suggested that low expression of p16 protein may play an important role in human HNSCC, and this study suggested that many kinds of genetic mechanisms including DNA methylation may play the role in carcinogenesis.