• Toxicological Research
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• 제24권2호
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• pp.101-107
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• 2008

Studies on hypoxia-signaling pathways have revealed novel Fe(II) and $\alpha$-ketoglutarate-dependent dioxygenases that hydroxylate prolyl or asparaginyl residues of a transactivator, Hypoxia-Inducible $Factor-\alpha(HIF-\alpha)$ protein. The recognition of these unprecedented dioxygenases has led to open a new paradigm that the hydroxylation mediates an instant post-translational modification of a protein in response to the changes in cellular concentrations of oxygen, reducing agents, or $\alpha$-ketoglutarate. Activity of $HIF-\alpha$ is repressed by two hydroxylases. One is $HIF-\alpha$ specific prolyl-hydroxylases, referred as prolyl-hydroxylase domain(PHD). The other is $HIF-\alpha$ specific asparaginyl-hydroxylase, referred as factor-inhibiting HIF-1(FIH-1). The facts (i) that many dioxygenases commonly use molecular oxygen and reducing agents during detoxification of xenobiotics, (ii) that detoxification reaction produces radicals and reactive oxygen species, and (iii) that activities of both PHD and FIH-1 are regulated by the changes in the balance between oxygen species and reducing agents, imply the possibility that the activity of $HIF-\alpha$ can be increased during detoxification process. The importance of $HIF-\alpha$ in cancer and ischemic diseases has been emphasized since its target genes mediate various hypoxic responses including angiogenesis, erythropoiesis, glycolysis, pH balance, metastasis, invasion and cell survival. Therefore, activators of PHDs and FIH-1 can be potential anticancer drugs which could reduce the activity of HIF, whereas inhibitors, for preventing ischemic diseases. This review highlights these novel dioxygenases, PHDs and FIH-1 as specific target against not only cancers but also ischemic diseases.

• 대한한의학회지
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• 제30권5호
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• pp.157-162
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• 2009

Objectives: The purpose of this study is reporting the possibility of the treatment of metastatic brain tumors with allergen removed Rhus verniciflua Stokes (aRVS) after gamma knife radiosurgery. Methods: A patient with lung cancer felt a headache about one year after conventional therapies, and metastatic brain tumors were diagnosed. He received gamma knife radiosurgery twice but refused to get more conventional therapies afterwards. So he has been treating with aRVS since then. Results: During 143 weeks of administration of aRVS, the size of brain masses has decreased continuously without extracranial metastasis and the patient has maintained a good performance status. Conclusions: This report suggests that aRVS may play a therapeutic role in the treatment of metastatic brain tumors. Further studies will be needed to determine the effect of aRVS on metastatic brain tumors.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권2호
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• pp.66-73
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• 2009

Tumor angiogenesis is a process leading to formation of blood vessels within tumors and is crucial for maintaining a supply of oxygen and nutrients to support tumor growth and metastasis. Vascular endothelial growth factor(VEGF) plays a key role in tumor angiogenesis including induction of endothelial cell proliferation, migration, survival and capillary tube formation. VEGF binds to two distinct receptors on endothelial cells. VEGFR-2 is considered to be the dominant signaling receptor for endothelial cell permeability, proliferation, and differentiation. Bevacizumab(Avastin, Genetech, USA) is a monoclonal antibody against vascular endothelial growth factor. It is used in the treatment of cancer, where it inhibits tumor growth by blocking the formation of new blood vessels. The goal of this study is to identify the anti-tumor effect of Bevacizumab(Avastin) for oral squamous cell carcinoma cell lines. Human squamous cell carcinoma cell line(HN4) was used in this study. We examined the sensitivity of HN4 cell line to Bevacizumab(Avastin) by using in vitro proliferation assays. The results were as follows. 1. In the result of MTT assay according to concentration of Bevacizumab(Avastin), antiproliferative effect for oral squamous cell carcinoma cell lines was observed. 2. The growth curve of cell line showed the gradual growth inhibition of oral squamous cell carcinoma cell lines after exposure of Bevacizumab(Avastin). 3. In the apoptotic index, groups inoculated Bevacizumab(Avastin) were higher than control groups. 4. In condition of serum starvation, VEGFR-2 did not show any detectable autophosphorylation, whereas the addition of VEGF activated the receptor. Suppression of phosphorylated VEGFR-2 and phosphorylated MAPK was observed following treatment with Bevacizumab(Avastin) in a dose-dependent manner. 5. In TEM view, dispersed nuclear membrane, scattered many cytoplasmic vacuoles and localized chromosomal margination after Bevacizumab(Avastin) treatment were observed. These findings suggest that Bevacizumab(Avastin) has the potential to inhibit MAPK pathway in proliferation of oral squamous cell carcinoma cell lines via inhibition of VEGF-dependent tumor growth.

• Journal of Korean Neurosurgical Society
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• 제45권5호
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• pp.275-283
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• 2009

Objective : We retrospectively analyzed survival, local control rate, and incidence of radiation toxicities after radiosurgery for recurrent metastatic brain lesions whose initial metastases were treated with whole-brain radiotherapy. Various radiotherapeutical indices were examined to suggest predictors of radiation-related neurological dysfunction. Methods : In 46 patients, total 100 of recurrent metastases (mean 2.2, ranged 1-10) were treated by CyberKnife radiosurgery at average dose of 23.1 Gy in 1 to 3 fractions. The median prior radiation dose was 32.7 Gy, the median time since radiation was 5.0 months, and the mean tumor volume was $12.4cm^3$. Side effects were expressed in terms of radiation therapy oncology group (RTOG) neurotoxicity criteria. Results : Mass reduction was observed in 30 patients (65%) on MRI. After the salvage treatment, one-year progression-free survival rate was 57% and median survival was 10 months. Age(<60 years) and tumor volume affected survival rate(p=0.03, each). Acute (${\leq}$1 month) toxicity was observed in 22% of patients, subacute and chronic (>6 months) toxicity occurred in 21 %, respectively. Less acute toxicity was observed with small tumors (<$10cm^3$. p=0.03), and less chronic toxicity occurred at lower cumulative doses (<100 Gy, p=0.004). "Radiation toxicity factor" (cumulative dose times tumor volume of <1,000 Gy${\times}cm^3$) was a significant predictor of both acute and chronic CNS toxicities. Conclusion: Salvage CyberKnife radiosurgery is effective for recurrent brain metastases in previously irradiated patients, but careful evaluation is advised in patients with large tumors and high cumulative radiation doses to avoid toxicity.

• Clinical and Experimental Pediatrics
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• 제53권4호
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• pp.603-606
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• 2010

부신생물 변연계뇌염(paraneoplastic limbic encephalitis)은 신경계의 전이가 없이 종양의 원격 작용에 의해 발생하는 질환으로 소아에서는 드물게 보고되고 있다. 저자들은 사춘기 여아에서 발생한 성숙 난소기형종에 동반된 부신생물 변연뇌염을 경험하고 보고하고자 한다. 15세 여자 환자가 신경정신증상, 기억력 저하, 경련, 의식 저하를 주소로 내원하였다. 뇌척수액 검사, 뇌 MRI는 정상이었으나, 뇌 SPECT 검사에서 양측 측두엽의 저관류가 관찰되었다. 복부 초음파와 MRI에서 좌측 난소의 낭성 종양이 발견되었다. 종양의 수술적 제거 후 성숙 난소기형종으로 확인되었으며, 종양 제거 및 면역글로불린 정맥 투여로 완전한 인지 기능의 회복을 보였다.

• Archives of Plastic Surgery
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• 제40권3호
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• pp.238-243
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• 2013

Background Primary malignant tumors of the hand, although unusual, may present varied and often complex clinical problems. The main treatment modality of skin cancer of the hand has changed. Methods We retrospectively reviewed the medical records of 43 patients who underwent surgery for malignant skin tumors of the hand during an 18-year period, from September 1994 to February 2012. The characteristics of the tumor, methods of reconstruction, and long-term results were reviewed. Results We had 43 patients with 27 melanomas, 14 squamous cell carcinomas, and 2 sarcomas. Their ages ranged from 19 to 74 years (mean, $53.4{\pm}14.5$ years), from 46 to 79 years (mean, $59.7{\pm}9.6$ years), and from 15 to 43 years (mean, $29{\pm}19.8$ years), respectively. Thirty-four cases occurred on the fingertip (16 of those cases on the thumb), 5 cases occurred on the palm, and 4 cases on the dorsum of the hand. Amputation was most frequently used in early cases, but recently, tissue-sparing excision has been performed frequently. The incidence of local recurrence was 3 cases and distant metastasis was 1 case, and the 5-year survival rate was 100%, except in 4 cases due to follow-up loss. Conclusions The principles of treatment-to be curative and to preserve function and appearance-are important points. "Preservative surgery" preserves function and cosmesis of the involved finger or hand dorsum or palm. Preservative surgery not only emphasizes less resection and surgery of a smaller scale, but also optimal reconstruction of the soft tissue defect of the digit.

• 대한두경부종양학회지
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• 제27권1호
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• pp.38-41
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• 2011

Background and Objectives : Although it is well established that patients with papillary thyroid microcarcinoma (PTMC) have a highly favorable prognosis, the extent of thyroid surgery for PTMC remains unclear. According to the 2011 revised Korean Thyroid Association guideline, the choice of surgical strategy(total thyroidectomy versus lobectomy) for PTMC depends on solely preoperative diagnostic scrutinies-ultrasonography and fine needle aspiration cytology. We want to know how accurately these preoperative diagnostic scrutinies define the choice of surgical strategy for PTMC. Materials and Methods : For 119 patients who underwent total thyroidectomy with central neck dissection for PTMC, retrospectively, we compared the choice of surgery according to preoperative work up and postoperative pathologic findings. Results : Overall accuracy of the choice of surgery by preoperative work up was 61%. Among patients recommended lobectomy on preoperative work up, completion thyroidectomy on postoperative pathology might be necessary for 60% of patients and hidden central node metastasis was revealed in 31% of patients. Conclusions : The results of this study compel us to reinvestigate the current treatment guideline for PTMC. On current guideline according to the sonography and fine needle aspiration cytology, it might be thought to be better to choose more aggressive surgical strategy.

• Radiation Oncology Journal
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• 제11권2호
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• pp.303-309
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• 1993

Between November 1983 and December 1992, 121 patients with non-small cell lung cancer were treated with radiotherapy alone or combined with chemotherapy in Inje University, Seoul Paik Hospital. Of these,97 patients were evaluable and analyzed retrospectively. Group 1 (n=62)was treated with radiotherapy alone and group 2 (n=35) combined with chemotherapy. There were 7 patients, 1 patient with stage I and II ,20 patients, 11 patients with stage IIIA,28 patients, 20 patients with stage IIIB, and 6 patients, 3 patients with stage IV, respectively. Ninety percent of patients received more than 5000 cGy of radiaton. Median survival of patients in group 1 was 9 months, group 2 was 15 months. Overall 2 year survival rates of group 1 and 2 were $37\%\;and\;27\%$, respectively. Relapse free survival rates at 2 year were $27\%\;and\;15\%$, respectively. Overall survival rates at 5 year for group 1 and 2 were $15\%\;and\;11\%$, and relapse free survival rates were $16\%\;and\;6\%,$ respectively. Median survival of complete and partial responders was 47 months in group 1,18 months in group 2, and those of stable or progression was 6 months,11 months, respectively. The proportion of locoregional relapse and distant metastasis was not significantly different between group 1 and 2. The majority of relapse developed within 2 years. Although 2 cases of severe esophagitis and myelosuppression were noted in group 2, the treatment related toxicity was relatively acceptable. Our analysis showed no statistically significant differences between the two treatment groups in terms of response rate, survival, and sites of relapse.

• Biomolecules & Therapeutics
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• 제21권3호
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• pp.204-209
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• 2013

Osteoprotegerin (OPG) is a secreted glycoprotein and a member of the tumor necrosis factor receptor superfamily. It usually functions in bone remodeling, by inhibiting osteoclastogenesis through interaction with a receptor activator of the nuclear factor ${\kappa}B$ (RANKL). Transglutaminases-2 (Tgase-2) is a group of multifunctional enzymes that plays a role in cancer cell metastasis and bone formation. However, relationship between OPG and Tgase-2 is not studied. Therefore, we investigated the involvement of 12-O-Tetradecanoylphorbol 13-acetate in the expression of OPG in MG-63 osteosarcoma cells. Interleukin-$1{\beta}$ time-dependently induced OPG and Tgase-2 expression in cell lysates and media of the MG-63 cells by a Western blot. Additional 110 kda band was found in the media of MG-63 cells. 12-O-Tetradecanoylphorbol 13-acetate also induced OPG and Tgase-2 expression. However, an 110 kda band was not found in TPA-treated media of MG-63 cells. Cystamine, a Tgase-2 inhibitor, dose-dependently suppressed the expression of OPG in MG-63 cells. Gene silencing of Tgase-2 also significantly suppressed the expression of OPG in MG-63 cells. Next, we examined whether a band of 110 kda of OPG contains an isopeptide bond, an indication of Tgase-2 action, by monoclonal antibody specific for the isopeptide bond. However, we could not find the isopeptide bond at 110 kda but 77 kda, which is believed to be the band position of Tgase-2. This suggested that 110 kda is not the direct product of Tgase-2's action. All together, OPG and Tgase-2 is induced by IL-$1{\beta}$ or TPA in MG-63 cells and Tgase-2 is involved in OPG expression in MG-63 cells.

• Archives of Reconstructive Microsurgery
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• 제18권1호
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• pp.31-34
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• 2009

Purpose: Merkel cell carcinoma, also called neuroendocrine carcinoma, is a very rare type of skin cancer that develops as Merkel cells grow out of control. Merkel cell carcinoma is reported below 1% of whole skin neoplasms in the United States and is known that the 2-year survival rate is about 50~70%. The principles of treatment are wide excision of primary lesion with radiotherapy and/or chemotherapy that decrease the local recurrent rate. There has been no report of reconstruction with free flap after resection of Merkel cell carcinoma in Korea. Methods: We reconstructed the skin and soft tissue defect after wide excision of Merkel cell carcinoma with anterolateral thigh perforator free flap in two cases. No distant metastasis was found at the preoperative imaging work-up. In one case, preoperative chemotherapy was performed and the size of lesion was decreased. Results: There were no recurrence and significant complications. Functionally and aesthetically satisfactory results were obtained with reconstruction. Conclusion: Wide excision and reconstruction with anterolateral thigh perforator free flap for Merkel cell carcinoma patient is the first report in Korea. We regard this method as the treatment of choice in Merkel cell carcinoma.