• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.7 no.1
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• pp.39-60
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• 2001

Fuzhengfangaitang is a prescript for inhibiting recurrence and metastasis of cancer. We had examined the anti-metatstastic effect of Fuzhengfangaitang. Furthermore, we performed the following experiments with ingredients of Fuzhengfangaitang. The purpose of this thesis is to study what ingredients of Fuzhengfangaitang have more valuable anti-cancer effects. And the results are listed below: 1. Cell Viability assay At the dose of 400$\mu$g/ml, most ingredients of Fuzhengfangaitang depressed viability of ECV-304. And especially, Scutellaria barbata D. DON$50{\mu}g/ml$ : 53.118%, $100{\mu}g/ml$: 49.092%, $200{\mu}g/ml$ : 43.765%, $400{\mu}g/ml$ : 12.747%), Polygonum bistorta L.($50{\mu}g/ml$ : 45.554%, $100{\mu}g/ml$ : 45.554%, $200{\mu}g/ml$ : 0.0%, $400{\mu}g/ml$ : 0.0%) and Psoralea corylifolia L.($50{\mu}g/ml$ : 86.591%, $100{\mu}g/ml$ : 81.307%, $200{\mu}g/ml$ : 24.801%, $400{\mu}g/ml$ : 3.111%) highly depressed cell viability more than the other ingredients. (${\alpha}$<0.05) 2. Cell Proliferation assay Proliferation assay with ingredients of Fuzhengfangaitang on ECV-304 showed that Crataegus pinnatifuda BGE ($50{\mu}g/ml$: 63.276%, $100{\mu}g/ml$ : 64.092%, $200{\mu}g/ml$ : 68.966% $400{\mu}g/ml$ : 38.517%, ED50=$296.974{\mu}g/ml$), Polygonum bistorta L.($50{\mu}g/ml$ : 83.981%, $100{\mu}g/ml$ : 86.997%, $200{\mu}g/ml$ : 58.780%, $400{\mu}g/ml$ : 26.408%), ED50=$266.725{\mu}g/ml$) and Psoralea corylifolia L.($50{\mu}g/ml$ : 103.037%, $100{\mu}g/ml$ : 82.529%, $200{\mu}g/ml$ : 2.829%, $400{\mu}g/ml$ : 0.998%), ED50=$177.369{\mu}g/ml$) depressed cell proliferation more than the other ingredients. 3. Tube Formation assay Compared with the control group, most ingredients of Fuzhengfangaitang did not remarkably inhibited the Tube Formation assay of ECV-304 at the dose of $100{\mu}g/ml$. But, Polygonum bistorta L. highly inhibited the tube formation of ECV -304 at the lower dose of $50{\mu}g/ml$. 4. Rat Aortic Ring assay In comparison with the control group, Scutellaria barbata D. DON., root of Polygonum bistorta L. and Psoralea corylifolia L. restricted the angiogenesis of the rat aortic ring at the dose of $100{\mu}g/ml$. And the other ingredients of Fuzhengfangaitang did not restricted the angiogenesis of the rat aortic ring at that dose. Especially, Polygonum bistorta L. highly inhibited the angiogenesis of the rat aortic ring at the lower dose of $50{\mu}g/ml$. From our research, the anti-angiogenic effects of the ingredients of Fuzhengfangaitang was proven. Moreover, it will be helpful for designing more effective prescription for anti angiogenesis.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.5
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• pp.359-363
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• 2007

Purpose: Incidental parotid lesions on F-18 FDG-PET can mimic distant metastasis of underlying malignancy. The prevalence and the clinico-pathologic findings of PET positive parotid lesions have not been known. We investigated how often incidental parotid lesions are found on clinical FDG-PET studies and what the clinico-pathologic characteristics of those parotid lesions are in the present study. Materials and Methods: We retrospectively reviewed 3,344 cases of FDG-PET which had been obtained in our hospital from May 2003 to Dec 2006. The indications of FDG-PET were: evaluation of known/suspected cancer (n= 3,212) or screening of cancer in healthy subjects (n=132). Incidental parotid lesion on FDG-PET was defined as an un-expected FDG uptake in one of parotid glands which was not primary target lesion of current FDG-PET. FDG uptake was represented by maximum standardized uptake value (maxSUV). Final diagnosis was made by pathologic analysis or clinical follow-up assessment. Results: Fifteen (0.45% = 15/3,344) incidental parotid lesions were found and they were all benign lesions. The maxSUV ranged from 1.7 to 8.6 (mean${\pm}$s.d. = $3.7{\pm}1.9$). Final diagnoses of the incidental parotid lesions were; Warthin's tumor (n=2), pleomorphic adenoma (n=1), other un-specified benign lesion (n=1), and benign lesions under bases of imaging studies (n=3) and of clinical follow-up (n=8). Conclusion: All of incidentally found parotid lesions in clinical FDG-PET studies were confirmed as benign lesions with prevalence of 0.45%. Close follow up using PET or CT might be a reasonable approach for determining the nature of incidentally found parotid lesions.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.259-265
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• 1993

Between January 1985 and July 1992, 52 patients with locally advanced nasopharyngeal carcinoma were studied retrospectively for the effectiveness of sequential chemotherapy and radiation therapy. The male to female ratio was 3.3:1 with a median age of 41 years. Forty patients had squamous cell carcinoma and the remaining 12 had undifferentiated carcinoma. Seven patients had stage III disease and the remainder had stage IV disease at time of presentation. All patients were treated two courses of chemotherapy followed by radiation therapy. Chemotherapy consisted of either CVB (cisplatin, vincristine and bleomycin) or CF (cisplatin and 5-FU). Total radiation dose to the primary site ranged from 6000 cGy to 7500 cGy. Neck nodes were given booster treatment to maximum of 7000 cGy, depending on the extent of disease. Local control, overall survival and disease-free survival rates were analyzed. The complete response (CR) rate to chemotherapy was $15\%$ and the partial response (PR) rate was $46\%,$ for overall major response rate of $61\%.$ The CR rate was $87\%$ after radiation therapy. Median follow-up time was 51 months. The overall survival and disease-free survival rates at 36 months were $54\%\;and\;49\%,$ respectively. Median time to relapse was 15 months. The patterns of initial relapse in CR patients was as follows: locoregional failure only, 12 patients; distant metastasis only,11: both,2. Cox's multivariate regression model revealed that nodal status was the single most important independant prognostic factor influencing disease-free survival (p=0.001). Comparision of these results with other published reports with radiation therapy alone showed that a high rate of initial response to chemotherapy did not translate into local control or survival. At present time radiation therapy alone remains the standard treatment for locoregional cancer of the nasopharyngeal cancer. More controlled clinical trials must be completed before acceptance of chemotherapy as a part of treatment of advanced nasopharyngeal carcinoma.

• Journal of Chest Surgery
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• v.39 no.11 s.268
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• pp.828-837
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• 2006

Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

• The Korean Journal of Nuclear Medicine
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• v.28 no.3
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• pp.384-390
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• 1994

Authors retrospectively compared the 99mTc MDP bone scans and corresponding MR imagings in 20 patients with histologically proven malignancy, Mean interval of the two studies was 16.6 days, Cancer diagnosis Included 8 lung, 2 each of colon, breast, stomach, 1 each of prostate, thyroid, malignant lymphoma and 3 adenocarcinoma of unknown primary site. Of the 105 regions compared, :t6 regions were positive for metastases in bone scans or MR imagings. 30 regions(65.2%) were positive by bone scan and 44 regions(95.7%) by MR imaging. 87 regions(82.9%) were concordantly positive or negative by bone scan and MR imaging, but 18 regions(17.1%) were discordant. In the discordant regions, 16 regions positive in MR imaging were negative in bone scan. The greatest number of discordant findings occured in the cervical region and in the patient with stomach cancer. Our results suggest that the sensitivity of MR Imaging is greater than that of bone scan in detecting spinal metastases. And bone scan is useful screening test of metastasis for evaluating entire skeleton including spine.

• Journal of Life Science
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• v.25 no.6
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• pp.693-702
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• 2015

Blocking new blood-vessel formation (angiogenesis) is now recognized as a useful approach to the therapeutic treatment of many solid tumors. The best validated approach to date is to target the vascular endothelial growth-factor (VEGF) pathway, a key regulator of angiogenesis. Many natural products and extracts that contain a variety of chemopreventive compounds have been shown to suppress the development of malignancies through their anti-angiogenic properties. Phellodendron amurense, which is widely used in Korean traditional medicine, has been shown to possess antitumor, antimicrobial, and anti-inflammatory properties, among others. The present study investigated the effects of P. amurense hot-water extract (PAHWE) on angiogenesis, a key process in tumor growth, invasion, and metastasis. To investigate PAHWE’s anti-angiogenic properties, this study’s authors performed an analysis of angiogenesis and endothelial-cell proliferation, migration, invasion, and tube formation, as well as zymogram assays and the rat aortic ring-sprouting assay. PAHWE inhibited cell growth, mobility, and vessel formation in response to VEGF in vitro and ex vivo. Furthermore, it reduced VEGF-induced intracellular signaling events, such as the activation of matrix metalloproteinases (MMPs) -2 and -9. These results indicate that PAHWE’s anti-angiogenic properties might lead to the development of potential drugs for treating angiogenesis-associated diseases such as cancer.

• Journal of Gastric Cancer
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• v.5 no.1
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• pp.40-46
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• 2005

Purpose: Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms of the gastrointestinal tract. GISTs are positive for the expression of c-Kit protein at immunohistochemistry, and their clinical presentations vary. This retrospective study was performed to evaluate the clincopathologic characteristics of GISTs and to define the prognostic factors. Materials and Methods: 40 patients who underwent a complete resection of a GIST during the period $1996\~2003$ at the Department of Surgery, Korea University College of Medicine, were studied. We divided them into low- and high-risk. groups by using tumor size and mitotic count: 23 cases were low risk, and 17 were high risk. Clinicopathologic features, immunohistochemical findings, and prognoses were compared between the low- and the high-risk groups. Results: The mean age of the 40 patients was $61.3\pm11.1$years, and the male-to-female ratio was 1：1.1. There was no significant difference in age and sex between the groups. A comparative analysis revealed tumor size, mitotic count, clinical symptoms, preoperative pathologic diagnosis, ulceration, and necrosis to be variables that had statistically significant differences between the high- and the low-risk groups. In the univariate analysis, tumor size, mitotic count, ulceration, necrosis, and abnormal endoscopic ultrasound findings were associated with disease-free survival, but in the multivariate analysis, mitotic activity was the only independent factor associated with disease-free survival. 8 patients had recurrences during the follow-up period, and four of them were treated with STI-571 (imatinib mesylate, $Gleevec^{(R)}$). The treated patients have survived until now; however, two of non-treated patients died from disease progression. Conclusion: Based on this study, tumor size, ulceration, and necrosis are significant factors affecting survival, and mitotic activity may be a useful prognostic marker. STI-571 may be used in an adjuvant setting because the drug has shown anticancer activity in patients with recurrence or metastasis.

• Food Science and Preservation
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• v.23 no.7
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• pp.1033-1041
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• 2016

In this study, we evaluated antioxidant and antiproliferating effects of Setaria italica extract (SIE), Panicum miliaceum extract (PME) and Sorghum bicolor extract (SBE). Antioxidant effects of these extracts were determined by assessing DPPH radical scavenging activity, $ABTS^+$ radical scavenging activity, reducing power and superoxide dismutase (SOD)-like activity. From high concentrations ($1,000{\mu}g/mL$) of each extract at DPPH radical scavenging activities of SIE, PME and SBE were 10.5%, 5.5% and 86.8% respectively, $ABTS^+$ radical activities were 4.92%, 5.9% and 62.3% respectively, reducing powers (OD 700) were 0.15, 0.18 and 1.7 respectively, and SOD-like activities were 17.0%, 15.9% and 38.6% respectively. In addition, SBE significantly decreased the cell viability of androgen-sensitive lymph node metastasis type of prostate cancer (LNCaP) cells in a dose-dependent manner. Morphological study of SBE-treated LNCaP cells revealed distorted and shrunken cell masses. SBE-induced cell death was confirmed by observation of nuclear condensation and increased formation of apoptotic bodies. The antiproliferative effect of SBE seems to be associated with the antioxidant activity of its polyphenol content. The results of this study indicate that SBE can exert antioxidant and antiproliferative effects and may be as a useful food material.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.171-180
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• 2001

Purpose : Expression of TIMP, intrinsic inhibitor of MMP, is regulated by signal transduction in response to genotoxins and is likely to be an important step in metastasis, angiogenesis and wound healing after ionizing radiation. Therefore, we studied radiation mediated TIMP expression and its mechanism in head and neck cancer cell lines. Materials and Methods : Human head and neck cancer cell lines established at Asan Medical Center were used and radiosensitivity $(D_0)$, radiation cytotoxicity and metastatic potential were measured by clonogenic assay, n assay and invasion assay, respectively. The conditioned medium was prepared at 24 hours and 48 hours after 2 Gy and 10 Gy irradiation and expression of TIMP protein was measured by Elisa assay with specific antibodies against human TIMP. hTIMP1 promoter region was cloned and TIMP1 luciferase reporter vector was constructed. The reporter vector was transfected to AMC-HN-1 and -HN-9 cells with or without expression vector Ras, then the cells were exposed to radiation or PMA, PKC activator. EMSA was peformed with oligonucleotide (-59/-53 element and SP1) of TIMP1 promoter. Results : $D_0$ of HN-1, -2, -3, -5 and -9 cell lines were 1.55 Gy, 1.8 Gy, 1.5 Gt, 1.55 Gy and 2.45 Gy respectively. n assay confirmed cell viability, over $94\%$ at 24hrs, 48hrs after 2 Gy irradiation and over 73% after 10 Gy irradiation. Elisa assay confirmed that cells secreted TIMP1, 2 proteins continuously. After 2 Gy irradiation, TIMP2 secretion was decreased at 24hrs in HN-1 and HN-9 cell lines but after 10 Gy irradiation, it was increased in all cell lines. At 48hrs after irradiation, it was increased in HN-1 but decreased in HN-9 cells. But the change in TIMP secretion by RT was mild. The transcription of TIMP1 gene in HN-1 was induced by PMA but in HN-9 cell lines, it was suppressed. Wild type Ras induced the TIMP-1 transcription by 20 fold and 4 fold in HN-1 and HN-9 respectively. The binding activity to -59/-53, AP1 motif was increased by RT, but not to SP1 motif in both cell lines. Conclusions : We observed the difference of expression and activity of TIMPs between radiosensitive and radioresistant cell line and the different signal transduction pathway between in these cell lines may contribute the different radiosensitivity. Further research to investigate the radiation response and its signal pathway of TIMPs is needed.

• Radiation Oncology Journal
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• v.28 no.3
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• pp.125-132
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• 2010

Purpose: To retrospectively assess the advantages and side effects of prophylactic Paraaortic irradiation in cervical cancer patients with common iliac nodal involvement, the results for survival, patterns of failure, and treatment-related toxicity. Materials and Methods: From May 1985 to October 2004, 909 patients with cervical carcinoma received postoperative radiotherapy at the Seoul National University Hospital. Among them, 54 patients with positive common iliac nodes on pathology and negative Paraaortic node were included in the study. In addition, 44 patients received standard pelvic irradiation delivered 50.4 Gy per 28 fractions (standard irradiation group), and chemotherapy was combined in 16 of them. The other 10 patients received pelvic irradiation at a dose of 50.4 Gy per 28 fractions in addition to Paraaortic irradiation at 45 Gy per 25 fractions (extended irradiation group). In addition, all of them received chemotherapy in combination with radiation. Follow-up times for pelvic and Paraaortic irradiation ranged from 6 to 201 months (median follow-up time, 58 months) and 21 to 58 months (median follow-up time, 47 months), respectively. Results: The 4-year overall survival, disease free survival, and distant metastasis free survival in the standard irradiation group and extended irradiation group were 67.2% vs. 90.0% (p=0.291), 59.0% vs. 70.0% (p=0.568) and 67.5% vs. 90.0% (p=0.196), respectively. The most common site of first failure for the standard irradiation group was the paraaortic lymph node, while no paraaortic failure was observed in the extended irradiation group. Relatively, hematologic toxicity grade 3 or greater was common in the extended irradiation group (2/10 extended vs. 2/44 standard), while gastrointestinal toxicity of grade 3 or greater was lower (2/10 extended vs. 6/44 standard), and urologic toxicity of grade 3 or greater was observed in the standard irradition group only (0/10 vs. 3/44). Conclusion: Concurrent chemotherapy and prophylactic Paraaortic irradiation in patients with common iliac nodal involvement showed slightly improved clinical outcomes aside from increased hematologic toxicity, which was statistically insignificant. Considering the relatively small number of patients and short follow-up times, additional studies are needed to obtain more conclusive outcomes.