• Radiation Oncology Journal
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• 제33권4호
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• pp.301-309
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• 2015

Purpose: To identify prognostic factors for disease progression and survival of patients with extracranial oligometastatic breast cancer (EOMBC), and to investigate the role of radiation therapy (RT) for metastatic lesions. Materials and Methods: We retrospectively reviewed the medical records of 50 patients who had been diagnosed with EOMBC following standard treatment for primary breast cancer initially, and received RT for metastatic lesions, with or without other systemic therapy between January 2004 and December 2008. EOMBC was defined as breast cancer with five or less metastases involving any organs except the brain. All patients had bone metastasis (BM) and seven patients had pulmonary, hepatic, or lymph node metastasis. Median RT dose applied to metastatic lesions was 30 Gy (range, 20 to 60 Gy). Results: The 5-year tumor local control (LC) and 3-year distant progression-free survival (DPFS) rate were 66.1% and 36.8%, respectively. High RT dose (${\geq}50Gy_{10}$) was significantly associated with improved LC. The 5-year overall survival (OS) rate was 49%. Positive hormone receptor status, pathologic nodal stage of primary cancer, solitary BM, and whole-lesion RT (WLRT), defined as RT whose field encompassed entire extent of disease, were associated with better survival. On analysis for subgroup of solitary BM, high RT dose was significantly associated with improved LC and DPFS, shorter metastasis-to-RT interval (${\leq}1month$) with improved DPFS, and WLRT with improved DPFS and OS, respectively. Conclusion: High-dose RT in solitary BM status and WLRT have the potential to improve the progression-free survival and OS of patients with EOMBC.

• Toxicological Research
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• 제31권1호
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• pp.11-16
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• 2015

Our body's immune system has defense mechanisms against pathogens such as viruses and bacteria. Immune responses are primarily initiated by the activation of toll-like receptors (TLRs). In particular, TLR4 is well-characterized and is known to be activated by gram-negative bacteria and tissue damage signals. TLR4 requires myeloid differentiation factor 2 (MD2) as a co-receptor to recognize its ligand, lipopolysaccharides (LPS), which is an extracellular membrane component of gram-negative bacteria. Gambogic acid is a xanthonoid isolated from brownish or orange resin extracted from Garcinia hanburyi. Its primary effect is tumor suppression. Since inflammatory responses are related to the development of cancer, we hypothesized that gambogic acid may regulate TLR4 activation. Our results demonstrated that gambogic acid decreased the expression of pro-inflammatory cytokines ($TNF-{\alpha}$, IL-6, IL-12, and $IL-1{\beta}$) in both mRNA and protein levels in bone marrow-derived primary macrophages after stimulation with LPS. Gambogic acid did not inhibit the activation of Interferon regulatory factor 3 (IRF3) induced by TBK1 overexpression in a luciferase reporter gene assay using IFN-${\beta}$-PRD III-I-luc. An in vitro kinase assay using recombinant TBK1 revealed that gambogic acid did not directly inhibit TBK1 kinase activity, and instead suppressed the binding of LPS to MD2, as determined by an in vitro binding assay and confocal microscopy analysis. Together, our results demonstrate that gambogic acid disrupts LPS interaction with the TLR4/MD2 complex, the novel mechanism by which it suppresses TLR4 activation.

• 대한골관절종양학회지
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• 제6권1호
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• pp.1-9
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• 2000

목적 : 전이성 척추 종양은 가장 흔한 전이성 종양 중의 하나로 치료에 있어 보통 보존적 요법이 선호되어 왔으나 신경학적 증상과 삶의 질의 개선이 극히 불량하였다. 수술적 치료 후에 신경학적 증상의 변화와 임상증상의 개선정도, 생존 기간의 증가 등에 대해 평가하였다. 대상 및 방법 : 1991년 8월부터 1999년 6월까지 본원에서 경험하였던 전이성 척추 종양 중 수술적 치료 후 추시관찰이 가능하였던 14례를 대상으로 하여 의무기록과 방사선학적 검사 등을 후향적으로 검토하여 연령별, 성별, 해부학적 발생 부위별 분포와 각각의 원발 종양에 따른 골 전이의 양상에 대해 조사하였고, 방사선 치료로 도움이 안될 때, 신경학적 증상이 악화될 때, 척추 불안정성이 있을 때, 원발 종양을 알지 못할 때, 병적 골절이 있을 때, 기대여명이 6주 이상일 때, 만성적인 통증이 있을 때 시행하였던 수술적 치료 전후의 증상의 개선 정도를 평가하여 문헌 고찰과 함께 분석하였다. 결과 : 전이성 척추 종양은 여자에서 더 많이 발생하였고 30대에서 70대까지 연령이 다양하였으며 원발 종양으로 여자는 유방암, 남자는 폐암이 가장 많았고 가장 흔한 전이 부위는 흉추부였다. 수술 전 마비의 정도가 수술 후 임상 증상의 호전에 영향을 미친 것으로 나타났으며 수술 후 전이성 척추 종양의 평균 여명은 사망한 11례에서 8.9개월, 살아있는 3례에서 14.7개월이었다. 결론 : 전이성 종양에 대한 수술적 치료는 전이성 척수 종양이 의심될 때, 치료와 동시에 조기 진단이 가능하며 그 방법과 관계없이 동통과 신경학적 증상의 회복에 큰 도움을 줄 수 있고, 초기의 적극적 치료로 삶의 질과 생존 기간을 향상시킬 수 있다. 추후 원발 종양의 종류에 따른 전이성 척수 종양의 분류와 이에 따른 수술적 치료의 역할에 대한 평가가 더 필요하리라 사료된다.

• Investigative Magnetic Resonance Imaging
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• 제18권1호
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• pp.25-33
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• 2014

목적: 확산강조영상 (DW-MRI)과 역동적 조영증강 자기공명영상 (DCE-MRI)에서 도출한 정량적 매개변수들이 서로 연관되어 있는지 알아보고자 하였다. 대상과 방법: 치료시작 전 DWI와 DCE-MRI를 시행한 조직학적으로 혹은 임상적으로 진단된 골전이암을 가진 13명의 환자를 대상으로 하였다. 주 병변의 겉보기 확산계수 (ADC) 그리고 관류지수 중 $K^{trans}$와 $V_e$ 값을 측정하여 Pearson 연관분석을 사용하여 통계적으로 분석하였다. 결과: 15개의 병변 중 11개는 ADC와 $K^{trans}$ 값 간에 유의한 상관관계를 보였다. 이 중 7개의 병변은 음의 연관성을, 그리고 4개는 양의 연관성을 보였다. 9개의 병변은 ADC와 $V_e$ 값 간에 유의한 상관관계를 보였다. 이 중 4개는 음의 연관성을, 그리고 5개는 양의 연관성을 보였다. 결론: 골전이암의 ADC 값과 $K^{trans}$ 값, 혹은 ADC 값과 $V_e$ 값은 일정한 연관성이 없었다.

• 대한골관절종양학회지
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• 제13권1호
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• pp.60-66
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• 2007

목적: 비구주변 악성 골종양에 대한 재건술을 동반하지 않은 내골반골 절제술의 기능적 결과를 알아보았다. 대상 및 방법: 1996년 1월부터 2005년 12월까지 비구주변을 침범한 악성 골종양에 대하여 내골반골 절제술 후 특별한 재건술을 시행하지 않았던 8예의 기능적 결과를 평가하였다. 남자가 6명, 여자가 2명이었으며 평균연령은 42세였다. 골육종이 3예였고, 연골육종 3예, 전이성 골종양2예였다. 골반골 절제유형은 I+II+III 형 6예, I+II형 1예, II+III형 1예였다. 기능적 결과는 ISOLS의 수정된 기준에 따라 평가하였으며 추시 기간은 최단 6개월에서 최장 84개월이었다. 결과: 최종 추시시 무병생존이 5예, 유병생존이 2예였고 나머지 1예는 질병으로 인하여 사망하였다. 기능적 평가에서 통증, 기능, 정서적 만족도, 보조기구 사용, 보행능력, 보행양상은 각각 4.9, 2.9, 2.9, 1.5, 2.3 및 2.5점이었으며 정상 측의 37~70%(평균 56%)에 해당하였다. 3예에서 일시적인 신경마비가 발생하였다. 결론: 비구주변 악성 골종양에 대한 제건술을 동반하지 않은 내골반골 절제술은 합병증 발생이 적고 양호한 기능적 결과를 보여 재건이 어려울 것으로 예상되는 환자들에게 적용할 수 있는 방법으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6267-6272
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• 2015

Background: Extra nodal lymphoma (ENL) constitutes about 33 % of all non-Hodgkin's lymphoma. 18-28% develops in the head and neck region. A multimodality treatment with multi-agent chemotherapy (CT) and radiotherapy (RT) is considered optimum. Materials and Methods: We retrieved the treatment charts of patients of HNENL treated in our institute from 2001-2012. The charts were reviewed and the demographic, treatment details and outcome of HNENL patients were retrieved using predesigned pro-forma. Results: We retrieved data of 75consecutive patients HNENL. Median age was 47years (Range: 8-76 years). Of the 75 patients 51 were male and 24 were female. 55patients were evaluable. The patient and tumor characteristics are summarized in Table 1. All patients were staged comprehensively with contrast enhanced computed tomography of head, neck, thorax, abdomen, pelvis and bone marrow aspiration and biopsy 66 patients received a combination multi-agent CT with CHOP being the commonest regimen. 42 patients received 4 or lesser number of cycles of chemotherapy whereas 24received more than 4 cycles chemotherapy. Post radiotherapy, 41 out of 42 patients had a complete response at 3 months. Only 21patients had a complete response after chemotherapy. All patients received radiation (mostly involved field radiation) as a part of the treatment. The median radiation dose was 45 Gray (Range: 36 Gray-50 Gray). The radiation was planned by 2D fluoro simulation based technique in 37cases and by 3 Dimensional conformal radiation therapy (3DCRT) in 36 cases. Two patients were planned by the intensity modulated radiation therapy (IMRT) technique. IMRT was planned for one thyroid and one nasal cavity primary. 5 patients experienced relapse after a median follow up of 19 months. The median survival was not reached. The estimated two and three year survival were 92.9% (95%CI- 68.6- 95.35) and 88% (95%CI- 60.82 - 92.66) respectively. Univariate analysis revealed higher stage and poorer baseline performance status to be significantly associated with worse progression free survival. 5 patients progressed (relapse or primary disease progression) after treatment. Of the 5 patients, two patients were primary orbital NHL, two patients had NHL nasal cavity and one was NHL thyroid. Conclusions: Combined modality treatment in HNENL confers excellent disease control with acceptable side effects.

• 치위생과학회지
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• 제19권4호
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• pp.254-260
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• 2019

Background: The primary aims of periodontal disease treatment is to remove dental plaque and calculus, the main causes of tooth loss, and restore periodontal tissue destroyed by inflammation. Periodontal disease treatment should also help maintain the alveolar bone, alleviate inflammation, and promote periodontal ligament cell proliferation, which is essential for tissue regeneration. Conventional antibiotics and anti-inflammatories have adverse side effects, especially during long-term use, so there is a need for adjunct treatment agents derived from natural products. The purpose of this study was to investigate whether the herbal flavone baicalein has the osteogenic activity under inflammatory conditions, and assess the involvement of osteoblast immediate early response 3 (IER3) expression. Methods: Human osteoblastic MG-63 cells were cultured with the pro-inflammatory cytokines tumor necrosis factor α and interleukin 1β in the presence and absence of baicalein. Proliferation was assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, and expression of IER3 mRNA was assessed using real-time polymerase chain reaction. The expression of IER3 protein levels and activation of associated signal transduction pathways were assessed using western blotting. Results: Baicalein increased IER3 mRNA and protein expression synergistically. In addition, baicalein reversed the suppression of cell proliferation, and the downregulation of osteogenic transcription factor runt-related transcription factor 2 and osterix induced by pro-inflammatory cytokines. Baicalein also upregulated the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK 1/2). The upregulation of IER3 by pro-inflammatory cytokines was blocked by pretreatment with inhibitors of AKT, p38, JNK, and ERK 1/2. Conclusion: Baicalein mitigates the deleterious responses of osteoblasts to pro-inflammatory cytokines. Further, IER3 enhanced the effect of baicalein via activation of AKT, p38, JNK, and ERK pathways.

• Clinical and Experimental Pediatrics
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• 제61권2호
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• pp.53-58
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• 2018

Purpose: Although the prognosis is generally good in patients with intermediate-risk neuroblastoma, no consensus has been reached on the ideal treatment regimen. This study analyzed treatment outcomes and toxicities in patients younger than 18 months with stage 4 MYCN nonamplified neuroblastoma. Methods: We retrospectively analyzed 20 patients younger than 18 months newly diagnosed with stage 4 MYCN nonamplified neuroblastoma between January 2009 and December 2015. Patients received 9 cycles of chemotherapy and surgery, with or without local radiotherapy, followed by 12 cycles of differentiation therapy with 13-cis-retinoic acid. Chemotherapy consisted of alternating cycles of cisplatin, etoposide, doxorubicin, and cyclophosphamide (CEDC) and ifosfamide, carboplatin, and etoposide (ICE) regimens. Results: The most common primary tumor site was the abdomen (85%), and the most common metastatic sites were the lymph nodes (65%), followed by the bones (60%), liver (55%), skin (45%), and bone marrow (25%). At the end of induction therapy, 14 patients (70%) achieved complete response, with 1 achieving very good partial response, 4 achieving partial response, and 1 showing mixed response. Nine patients (45%) received local radiotherapy. At a median follow-up of 47 months (range, 17-91 months), none of these patients experienced relapse, progression, or secondary malignancy, or died. Three years after chemotherapy completion, none of the patients had experienced grade ${\geq}3$ late adverse effects. Conclusion: Patients younger than 18 months with stage 4 MYCN nonamplified neuroblastoma showed excellent outcomes, without significant late adverse effects, when treated with alternating cycles of CEDC and ICE, followed by surgery and differentiation therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2447-2451
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• 2014

Human papillomavirus (HPV) is the primary etiologic agent of cervical cancer. Consideration of safety and non human leukocyte antigen restriction, protein vaccine has become the most likely form of HPV therapeutic vaccine, although none have so far been reported as effective. Since tumor cells consistently express the two proteins E6 and E7, most therapeutic vaccines target one or both of them. In this study, we fabricated DC vaccines by transducing replication-defective recombinant adenoviruses expressing E6/E7 fusion gene of HPV-16, to investigate the lethal effects of specific cytotoxic T lymphocytes (CTL) against CaSki cells in vitro. Mouse immature dendritic cells (DC) were generated from bone marrow, and transfected with pAd-E6/E7 to prepare a DC vaccine and to induce specific CTL. The surface expression of CD40, CD68, MHC II and CD11c was assessed by flow cytometry (FCM), and the lethal effects of CTL against CaSki cells were determined by DAPI, FCM and CCK-8 methods. Immature mouse DC was successfully transfected by pAd-E6/E7 in vitro, and the transfecting efficiency was 40%-50%. A DC vaccine was successfully prepared and was used to induce specific CTL. Experimental results showed that the percentage of apoptosis and killing rate of CaSki cells were significantly increased by coculturing with the specific CTL (p <0.05). These results illustrated that a DC vaccine modified by HPV-16 E6/E7 gene can induce apoptosis of CaSki cells by inducing CTL, which may be used as a new strategy for biological treatment of cervical cancer.

• Journal of Periodontal and Implant Science
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• 제50권5호
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• pp.291-302
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• 2020

Purpose: The objective of this study was to investigate whether phelligridin D could reduce glucose-induced oxidative stress, attenuate the resulting inflammatory response, and restore the function of human periodontal ligament cells (HPDLCs). Methods: Primary HPDLCs were isolated from healthy human teeth and cultured. To investigate the effect of phelligridin D on glucose-induced oxidative stress, HPDLCs were treated with phelligridin D, various concentrations of glucose, and glucose oxidase. Glucose-induced oxidative stress, inflammatory molecules, osteoblast differentiation, and mineralization of the HPDLCs were measured by hydrogen peroxide (H₂O₂) generation, cellular viability, alkaline phosphatase (ALP) activity, alizarin red staining, and western blot analyses. Results: Glucose-induced oxidative stress led to increased production of H₂O₂, with negative impacts on cellular viability, ALP activity, and calcium deposition in HPDLCs. Furthermore, HPDLCs under glucose-induced oxidative stress showed induction of inflammatory molecules (intercellular adhesion molecule-1, vascular cell adhesion protein-1, tumor necrosis factor-alpha, interleukin-1-beta) and disturbances of osteogenic differentiation (bone morphogenetic protein-2, and -7, runt-related transcription factor-2), cementogenesis (cementum protein-1), and autophagy-related molecules (autophagy related 5, light chain 3 I/II, beclin-1). Phelligridin D restored all these molecules and maintained the function of HPDLCs even under glucose-induced oxidative stress. Conclusions: This study suggests that phelligridin D reduces the inflammation that results from glucose-induced oxidative stress and restores the function of HPDLCs (e.g., osteoblast differentiation) by upregulating autophagy.