• 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.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.1
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• pp.55-59
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• 2009

Purpose: Lymphoscintigraphy and sentinel node biopsy are used in detection of axillary lymph node metastasis in breast cancer patients, but standardized technique is not established. We compared the results of the injection the morning of surgery (1 day protocol) with the subareolar injection the day before surgery (2 day protocol) with the subareolar injection in patients with breast cancer having lymphoscintigraphy and sentinel node biopsy. Materials and Methods: This study included 349 patients who underwent the breast cancer operation during 2001-2004. One hundred seventy one patients (1 day protocol, 1 hour) was injected 0.8ml of Tc-99m Tin-Colloid (37 MBq) by subareolar injection on the morning of surgery. One hundred seventy eight patients (2 day protocol, 16 hour) was injected 0.8 ml of T c-99m Tin-Colloid (185 MBq) on the afternoon before surgery. Lymphoscintigraphy was performed in sitting position and sentinel node localization was performed by hand-held gamma probe during operation. Result: In the 1 day protocol, 153 cases (89.5%) of the sentinel node were localized by lymphoscintigraphy and 150 cases (87.7%) were localized by gamma probe. In the 2 day protocol, 159 cases (89.3%) were localized by lymphoscintigraphy and 154 cases (86.5%) were localized by gamma probe. There was no significant difference in localization of sentinel node between the 1 day and the 2 day protocol by lymphoscintigraphy and gamma probe (p>0.05, p>0.05). Conclusion: There was no difference the result of localization of sentinel node with subareolar injection between the 1 day and the 2 day protocol in breast cancer patients. Because the 2 day protocol allows the enough time of performing lymphoscintigraphy, it is more useful in localization of sentinel node in breast cancer patients.

• Tuberculosis and Respiratory Diseases
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• v.66 no.3
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• pp.205-210
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• 2009

Background: CXCL10 and CXCL11, which are family of CXCR3 ligands, are expressed by lymphocytes and even by bronchial epithelial cells if the cellular immunity is activated. This study evaluated the potential utility of CXCL10 and CXCL11 in the serum for active pulmonary tuberculosis in comparison with lung cancer, which activates the cellular immunity, and benign lung diseases. Methods: Patients who newly visited Pusan National University Hospital from January 2007 to December 2007 and were suspected of having lung cancer or tuberculosis were enrolled prospectively. The patients were classified pathologically and clinically into three groups, 47 with lung cancer, 18 with active pulmonary tuberculosis and 38 control patients with benign pulmonary disease. ELISA was used to determine the levels of CXCL10 and CXCL11 were determined in the serum. Results: The level of CXCL10 and CXCL11 were significantly higher in the active pulmonary tuberculosis group than in the lung cancer and benign lung disease groups (p<0.001, Kruskal-Wallis). The level of CXCL11 was significantly higher in the lung cancer group than in the benign pulmonary disease group, but there was no significant difference in level of CXCL10 between the three groups (p<0.001, p=0.655, respectively, Mann-Whitney U). The level of CXCL10 in patients with stage III+IV lung cancer was significantly higher than those with stage I+II, but there was no significant difference in the level of CXCL11 between the groups (p<0.001, p=0.07, respectively, Mann-Whitney U). There was no significant difference in the level of CXCL10 and CXCL11 between those with the presence and absence of lung cancer metastasis. There was a significant correlation between the level of CXCL10 and CXCL11 (r=0.223, p<0.001). Conclusion: CXCL10 and CXCL11 may be a potential useful markers for active pulmonary tuberculosis if used alongside other diagnostic methods.

• Journal of Chest Surgery
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• v.41 no.1
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• pp.74-81
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• 2008

Background: Fascin is an actin-bundling protein that induces membrane protrusions and it increases cell motility in various transformed cells. Esophageal cancer is one of the most lethal malignancies, and it exhibits extensive local invasion or frequent regional lymph node metastasis even after curative surgery. We investigate the expression of fascin by performing immunohistochemistry to evaluate the clinical characteristics and prognostic significance of its expression in esophageal cancer patients. Material and Method: Immunochemistry for fascin was performed on 76 tumor samples from 76 patients who underwent esophageal cancer operations. The expression levels of fascin in the 76 esophageal cancer tissues were compared with those in the corresponding normal esophageal epithelium. The fascin-positive samples were defined as those showing more than 75% of fascin-positive cells. Result: Overall, a fascin positive expression was detected in 39 (51.3%) out of the total 76 cases. The tumors with positive fascin expression tended to more frequently show a higher stage (p=0.030), and a higher T-factor (p=0.031). The prognosis of the fascin negative group was significantly better than that of the fascin positive group (p=0.004). Multivariate analysis revealed that lymphovascular invasion and the fascin expression were independent prognostic factors. Conclusion: Fascin was expressed in 513% of the esophageal cancer tissues and a positive expression of fascin was associated with more advanced tumor progression and recurrence. Our study suggests that the fascin expression may be an independent prognostic factor for an unfavorable clinical course few those patients suffering with esophageal cancer.

• Tuberculosis and Respiratory Diseases
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• v.47 no.5
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• pp.642-649
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• 1999

Background: It is very important to determine an accurate staging of the non-small cell lung cancer(NSCLC) for an assessment of operability and it's prognosis. However, it is difficult to evaluate tumor involvement of mediastinal lymph nodes accurately utilizing noninvasive imaging modalities. PET is one of the sensitive and specific imaging modality. Unfortunately PET is limited use because of prohibitive cost involved with it's operation. Recently hybrid SPECT/PET(single photon emission computed tomography/positron emission tomography) camera based PET imaging was introduced with relatively low cost. We evaluated the usefulness of coincidence detection(CoDe) PET in the detection of metastasis to the mediastinal lymph nodes in patients with NSCLC. Methods: Twenty one patients with NSCLC were evaluated by CT or MRI and they were considered operable. CoDe PET was performed in all 21 patients prior to surgery. Tomographic slices of axial, coronal and sagittal planes were visually analysed. At surgery, mediastinal lymph nodes were removed and histological diagnosis was performed. CoDe PET findings were correlated with histological findings. Results: Twenty of 21 primary tumor masses were detected by the CoDe PET. Thirteen of 21 patients was correctly diagnosed mediastinal lymph node metastasis by the CoDe PET. Pathological N0 was 14 cases and the specificity of N0 of CoDe PET was 64.3%. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of N1 node was 83.3%, 73.3%, 55.6%, 91.7%, and 76.2% respectively. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of N2 node was 60.0%, 87.5%, 60.0%,87.5%, and 90.0% respectively. There were 3 false negative cases but the size of the 3 nodes were less than 1cm. The size of true positive nodes were 1.1cm, 1.0cm, 0.5cm respectively. There were 1 false positive among the 12 lymph nodes which were larger than 1cm. False positive cases consisted of 1 tuberculosis case, 1 pneumoconiosis case and 1 anthracosis case. Conclusion: CoDe PET has relatively high negative predictive value in the enlarged lymph node in staging of mediastinal nodes in patients with NSCLC. Therefore CoDe PET is useful in ruling out metastasis of enlarged N3 nodes. However, further study is needed including more number of patients in the future.

• Radiation Oncology Journal
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• v.26 no.4
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• pp.204-212
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• 2008

Purpose: This study was performed to evaluate the disease-free survival and risk factors of recurrence in early breast cancer patients who have undergone breast conserving surgery and radiation therapy. Materials and Methods: From March 1997 to December 2002, 77 breast cancer patients who underwent breast conserving surgery and radiation therapy were reviewed retrospectively. The median follow-up time was 58.4 months (range $43.8{\sim}129.4$ months) and the mean subject age was 41 years. The frequency distribution of the different T stages, based on the tumor characteristics was 38 (49.3%) for T1, 28 (36.3%) for T2, 3 for T3, 7 for T is and 1 for an unidentified sized tumor. In addition, 52 patients (67.5%) did not have axillary lymph metastasis, whereas 14 patients (18.1%) had $1{\sim}3$ lymph node metastases and 3 (0.03%) had more than 4 lymph node metastases. The resection margin was negative in 59 patients, close (${\leq}2\;mm$) in 15, and positive in 4. All patients received radiation therapy at the intact breast using tangential fields with a subsequent electron beam boost to the tumor bed at a total dose ranging from 59.4 Gy to 66.4 Gy. Patients with more than four positive axillary lymph nodes received radiation therapy ($41.4{\sim}60.4\;Gy$) at the axillary and supraclavicular area. Chemotherapy was administered in 59 patients and tamoxifen or fareston was administered in 29 patients. Results: The 5 year overall survival and disease-free survival rates were 98.08% and 93.49%, respectively. Of the 77 patients, a total of 4 relapses (5.2%), including 1 isolated supraclavicular relapse, 1 supraclavicular relapse with synchronous multiple distant relapses, and 2 distant relapses were observed. No cases of local breast relapses were observed. Lymph node metastasis or number of metastatic lymph nodes was not found to be statistically related with a relapse (p=0.3289) nor disease-free survival (p=0.1430). Patients with positive margins had a significantly shorter disease-free survival period (p<0.0001) and higher relapse rates (p=0.0507). However, patients with close margins were at equal risk of relapse and disease-free survival as with negative margins (p=1.000). Patients younger than 40 years of age had higher relapse rates (9.3% vs. 0%) and lower disease-free survival periods, but the difference was not statistically significant (p=0.1255). The relapse rates for patients with tumors was 14% for tumor stage T2, compared to 0% for tumor stage T1 tumors (p=0.0284). A univariate analysis found that disease-free survival and relapse rates, T stage, positive resection margin and mutation of p53 were significant factors for clinical outcome. Conclusion: The results of this study have shown that breast conservation surgery and radiation therapy in early breast cancer patients has proven to be a safe treatment modality with a low relapse rate and high disease-free survival rate. The patients with a positive margin, T2 stage, and mutation of p53 are associated with statistically higher relapse rates and lower disease-free survival.

• Radiation Oncology Journal
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• v.16 no.1
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• pp.35-41
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• 1998

Purpose : To investigate the role of adjuvant chemoradiotherapy in adenocarcinoma of the rectum, we retrospectively compared the treatment results between postoperative adjuvant radiotherapy alone and combined chemoradiotherapy. Material and Methods : From October 1989 to May 1994, 141 patients with rectal carcinoma were treated by postoperative adjuvant therapy in Yonsei Cancer Center. Sixty eight patients were treated by radiation therapy alone. Seventy three patients were treated by combined chemoradiotherapy. Radiation therapy was delivered with 10 MV linear accelerator, 180cGy fraction/5 days per week. Total radiation doses were 5400cGy in the postoperative radiotherapy alone group. Three to twelve cycles of Fluorouracil(mean dose $393.9mg/m^2$) with Leucovorin($20mg/m^2$) and 5040cGy of radiation were delivered in the combined chemoradiotherapy group. Third and 4th cycle of chemotherapy were administrated during the radiation treatment in the combined group. The median follow up was 38 months with a range of 3 to 81 months. Results : The 5 year overall survival rate of radiation alone group and combined group were $60.1\%$ and $66.3\%$, respectively. The 5 year disease free survival rate of radiation aione group and combined group were $54.2\%$ and $65.5\%$, respectively There was no significant difference of overall survival and disease free survival between RT alone group and combined group(p<0.05). But the 5 year Local failure free survival rate of combined group was significantly better than radiotherapy alone group($05.8\%\;vs.\;50.3\%.\;p=0.04$). Conclusion : There was no significant difference in overall survival, disease free survival, and distant metastasis free survival between postoperative adjuvant radiotheray alone group and combinded chemoradiotherapy group. Only the Local failure free survival rate was superior in the combined treatment group. These results confirm the radiosensitizing effect of the chemotherapeutic agent in the combined chemoradiotherapy treatment.

• Journal of Life Science
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• v.26 no.4
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• pp.439-445
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• 2016

Soybean leaves, a Korean edible plant material, have been reported to prevent the development of osteoporosis and breast cancer. Based on this rational, soybean fallen leaves ethanolic extract (SBFL) was used for the experiment of cell invasion related to metastasis and antioxidant activity. The effect of SBFL on matrix metalloproteinases (MMPs) in human fibrosarcoma cells, HT1080 as well as its anti-oxidant activity was investigated in this study. The effect of SBFL on scavenging activity of reactive oxygen species was evaluated in vitro using lipid peroxidation assay,DPPH radical and reducing power assay. SBFL showed the positive effects on antioxidant activity, compared with vitamin C and vitamin E used as positive controls. Furthermore, SBFL showed cytotoxicity above 16 µg/ml in MTT assay. In particular, it was found that SBFL decreased the activation of MMP-9 stimulated by phorbol 12-myristate 13-acetae (PMA) and phenazine methosulfate (PMS). SBFL treatment increased the expression levels of p-FoxO-1 and SOD-1. Moreover, SBFL inhibited cell invasion stimulated by vascular endothelial growth Factor (VEGF). These results indicate that SBFL could inhibit cell invasion related to the activation of MMP-9 and oxidative stress, suggesting that it could be available as a main ingredient for prevention of metastasis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.2
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• pp.105-115
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• 2005

Purpose: The lymph node status assessed by conventional histological examination is the most important prognostic factor in patients undergoing surgery for oral squamous cell carcinoma. The presence of lymph node metastasis has a strong adverse impact on patient survival even after extended radical resection. Despite these findings, tumour recurrence is not rare after surgery, even when histological examination shows no lymph node metastasis. Recently, molecular-genetically and immunohistochemically demonstrated micrometastasis to the lymph nodes has been shown to have a significant adverse influence on survival in patients with squamous cell carcinoma and histologically negative nodes. The present study sought to determine the incidence and clarify the clinical significance of molecular-genetically and immunohistochemically demonstrated nodal micrometastases and to correlate these data with the stage of oral cancer. Methods: Lymph nodes systematically removed from 71 patients who underwent curative resection between 1998 and 2003 with head and neck squamous cell carcinoma were examined molecular-genetically to detect cytokeratin 5 mRNA with RT-PCR and immunohistochemically to detect cells that stained positively for cytokeratins with the monoclonal antibody cocktail AE1/AE3. The postoperative course and survival rates were compared among patients with and without micrometastases, after numerical classification of overt metastatic nodes. Results: micrometastases were detected in 43(60%) of 71 patients by RT-PCR and 26(36%) of 71 patients by immunohistochemistry. By RT-PCR analysis, patients exhibiting a positive band for CK 5 mRNA had a significantly worse prognosis than those were RT-PCR negative. By immunohistochemistry, the presence of micrometastasis did not predict patient outcome. Conclusion: Micrometastases detected by RT-PCR may be of clinical value in identifying patients who may be at high risk for recurrence and who are therefore likely to benefit from systemic adjuvant therapy.

• The Korean Journal of Food And Nutrition
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• v.25 no.4
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• pp.941-950
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• 2012

In order to develop new physiologically active polysaccharides from persimmon leaves, two different crude polysaccharides were prepared using hot water (PLW-0) and pectinase digestion (PLE-0) and their immuno-stimulating activities were estimated. PLW-0 and PLE-0 showed similar sugar compositions with 15 different sugars, including rarely observed sugars in general polysaccharides such as 2-O-methyl-fucose, 2-O-methyl-xylose, apiose, aceric acid, 3-deoxy-D-manno-2-octulosonic acid, and 3-deoxy-D-lyxo-2-heptulosaric acid, but the uronic acid content of PLE-0 was lower than that of PLW-0 caused by pectinase treatment. Both PLW-0 and PLE-0 showed potent anti-complementary activity in a dose-dependent manner which was similar to a known immuno-stimulating polysaccharide, PSK, from Coriolus versicolor. The activity of PLE-0 at a low concentration ($100{\mu}g/m{\ell}$) was higher than that of PLW-0. In an in vitro cytotoxicity analysis, PLW-0 and PLE-0 (up to $1,000{\mu}g/m{\ell}$) did not affect the growth of peritoneal macrophages and Colon 26-M3.1 carcinoma cells. In contrast, they enhanced lymphocyte proliferation activity. Peritoneal macrophages stimulated with PLW-0 and PLE-0 produced various cytokines, such as IL-6 and IL-12. However, PLE-0 was more effective on the cytokine production. Intravenous administration of PLW-0 and PLE-0 significantly augmented natural killer (NK) cell cytotoxicity against Yac-1 tumor cells 3 days after the treatment of polysaccharide fractions. But NK cells obtained from the PLE-treated group showed higher tumoricidal activity even at a low dose of $40{\mu}g$/mouse. In experimental lung metastasis of Colon 26-M3.1 carcinoma cells, prophylactic administration of PLW-0 and PLE-0 significantly inhibited lung metastasis in a dose-dependent manner and PLE-0 was more effective on the inhibition of cancer metasasis. The results lead us to conclude that the pectinase-treated process is indispensable to preparing polysaccharides with higher immune-stimulating activity from persimmon leaves.