• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제29권6호
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• pp.379-391
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• 2003

The present study was undertaken to evaluate bone regenerative capacity around titanium screw implants placed in irradiated rat's tibiae. At one week after single 15-Gy dose irradiation, miniaturized titanium screw implants were inserted into anterior aspect of the upper tibia of rats weighing 200-250g. Seventy rats were involved: 35 rats were control and 35 rats radiation group. The rats were killed at different intervals as 1, 2, 3, 4, 6, 8, 12 weeks after implantation for histologic observation, histomorphometric analysis and immunohistochemical study with fibronectin and CD34 antibody. 1. Histologically, various stages of bone maturation and ossification can be seen at 4 weeks and regenerated bone close to edges demonstrates more advanced calcification, and network of new bone are well formed at 12 weeks in non-irradiated group. In contrast, active bone formation with increased contact of newly formed bone to implant surface was noted at 4 weeks and a significant amount of new bone formation and bone-implant contact is oberved at 12 weeks in irradiated group. 2. Histomorphometrical analysis confirmed these histologic findings. A significant difference in implant-bone contact and bone density was measured between the control and radiation group. Mean MBD was 62.2% in control group and 27.5% in radiation group, mean MBIC was 86.6% in control group and 47.7% in radiation group, and mean TBIC was 87.3% in control group and 45.6% in radiation group at 12 weeks after implantation. 3. In immunohistochemical study with fibronectin and CD34, radiation reduced hematopoietic progenitor cells severely and disturbed differentiation of osteoblast in bone marrow. The results of this study revealed bone healing capacity around implant after radiation therapy was severely impaired and irradiation reduces the capacity for osseointegration of titanium implants. Many factors including radiation dose, period between radiation and implantation, bone quality, time elapse between first and second surgery, type of prosthetics and hyperbaric oxygen therapy must be considered carefully in postradiation implantation.

• Journal of Gastric Cancer
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• 제17권2호
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• pp.132-144
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• 2017

Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64-0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.

• 대한한방내과학회지
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• 제29권4호
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• pp.856-870
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• 2008

Objectives : Consumption is a chronic wasting disease and major portion of Oriental Medicine's therapy. However, there is no standard diagnostic method for consumption that is $q{\grave{i}}-x{\bar{u}}$, $xu{\grave{e}}-x{\bar{u}}$, $yang-x{\bar{u}}$, $y{\bar{i}}n-x{\bar{u}}$. Methods : A questionnaire which includes symptoms and signs for diagnosis of $q{\grave{i}}-x{\bar{u}}$, $xu{\grave{e}}-x{\bar{u}}$, $yang-x{\bar{u}}$, $y{\bar{i}}n-x{\bar{u}}$ was evaluated by Delphi technique. Each question was valuated by interviewing 27 oriental medicine doctors. Then. we choose questions given over 5 points and reorganized some items according to the recommendations by interviewed-doctors. We then accessed the value of re-organized questions composing of the questionnaires. Conclusion : We finally chose each 9 items of $q{\grave{i}}-x{\bar{u}}$, $xu{\grave{e}}-x{\bar{u}}$, $yang-x{\bar{u}}$, $y{\bar{i}}n-x{\bar{u}}$'s questionnaire. Further study is necessary for modification of questionnaire by statistics and certification by clinical trial.

• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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• pp.4013-4018
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• 2014

Because of its importance in tumor invasion and metastasis, the epithelial-mesenchymal transition (EMT) has become a research focus in the field of cancer. Recently, evidence has been presented that FoxO4 might be involved in EMT. Our study aimed to detect the expression of FoxO4, E-cadherin and vimentin in non-small cell lung cancers (NSCLCs). We also investigated clinical features and their correlations with the markers. In our study, FoxO4, E-cadherin and vimentin were assessed by immunohistochemistry in a tissue microarray (TMA) containing 150 cases of NSCLC. In addition, the expression level of FoxO4 protein was determined by Western blotting. The percentages of FoxO4, E-cadherin and vimentin positive expression in NSCLCs were 42.7%, 38.7% and 55.3%, respectively. Immunoreactivity of FoxO4 was low in NSCLC when compared with paired normal lung tissues. There were significant correlations between FoxO4 and TNM stage (P<0.001), histological differentiation (P=0.004) and lymph node metastasis (P<0.001), but no significant links with age (P=0.323), gender (P=0.410), tumor size (P=0.084), smoking status (P=0.721) and histological type (P=0.281). Our study showed that low expression of FoxO4 correlated with decreased expression of E-cadherin and elevated expression of vimentin. Cox regression analysis indicated FoxO4 to be an independent prognostic factor in NSCLC (P=0.046). These data suggested that FoxO4 might inhibit the process of EMT in NSCLC, and might therefore be a target for therapy.

• 대한두개안면성형외과학회지
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• 제10권2호
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• pp.138-141
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• 2009

Purpose: Squamous cell carcinoma of the scalp sometimes exhibits unusually aggressive behavior. We report a case of extradordinarily aggressive squamous cell carcinoma of the scalp with invasion into the skull and dura mater. Method: The patient is a 38-year-old man with two cystic masses on the occipital area. He was diagnosed as squamous cell carcinoma in that region and have undergone surgical resections including cortical osteotomy of the skull, several years ago. On this occasion, 3-dimensional computed tomographic imaging revealed an erosive lesion on the occipital bone and magnetic resonance imaging showed two cystic masses invasion into the skull and dura mater. Results: He has undergone wide resection of the masses and cranioplasty with dural repair. Histopathologic examination indicated squamous cell carcinoma with moderate differentiation of the masses, bone marrow and dura mater. Conclusion: Squamous cell carcinoma on the scalp can readily penetrate the full thickness of the cranium and invade the dura mater, sagittal sinus and brain. We suggest wide resection of the scalp and split thickness skin graft with sentinel lymph node biopsy, following by postoperative radiation therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3751-3755
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• 2013

Backgroud and Aims: MicroRNA-206 has proven to be down-regulated in many human malignancies in correlation with tumour progression. Our study aimed to characterize miR-206 contributions to initiation and malignant progression of human osteosarcoma. Methods: MiR-206 expression was detected in human osteosarcoma cell 1ine MG63, human normal osteoblastic cell line hFOB 1.19, and paired osteosarcoma and normal adjacent tissues from 65 patients using quantitative RT-PCR. Relationships of miR-206 levels to clinicopathological characteristics were also investigated. Moreover, miR-206 mimics and negative control siRNA were transfected into MG63 cells to observe effects on cell viability, apoptosis, invasion and migration. Results: We found that miR-206 was down-regulated in the osteosarcoma cell line MG63 and primary tumor samples, and decreased miR-206 expression was significantly associated with advanced clinical stage, T classification, metastasis and poor histological differentiation. Additionally, transfection of miR-206 mimics could reduce MG-63 cell viability, promote cell apoptosis, and inhibit cell invasion and migration. Conclusions: These findings indicate that miR-206 may have a key role in osteosarcoma pathogenesis and development. It could serve as a useful biomarker for prediction of osteosarcoma progression, and provide a potential target for gene therapy.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제16권3호
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• pp.309-314
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• 1994

지방육종은 주로 근간 간엽조직으로부터 발생되어지며, 중년이상의 남성에서 호발하고 주된 발병부위는 하지 및 후복막강이고 구강 주위조직에 이환되는 경우는 극히 드문 악성종양이며, 본 증례에서는 4년 전 좌측 하지에서 발생되어 우측 하지 및 좌측 협부에 전이된 것으로 생각되어지는 점액양의 지방육종으로 종물의 외과적 절제술 및 화학요법을 시행하였고 장기적인 관찰이 요구된다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권5호
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• pp.2555-2558
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• 2016

Background: Gastric cancer is the second most common gastrointestinal cancer and is still associated with significant morbidity and mortality due to late presentation and diagnosis at advanced stages. Studies have reported that a variable proportion of gastric cancer is positive for the human epidermal growth factor receptor 2 (HER2) and patients with HER2 positive (HER2 +ve) lesions can benefit from targeted therapy. This study was conducted to assess the prevalence of HER2 +ve gastric cancers in Brunei Darussalam, a developing Southeast Asian nation. Materials and Methods: Patients were identified from the Department of Pathology registry and retrospectively reviewed. HER2 expression was assessed by immunohistochemistry and only those staining 3+were considered positive. Results: Our study included 103 cases (66 males and 37 females) with a mean age of $65.1{\pm}14.8$ years old. There were 14 cases positive for HER2 (10 males and 4 females) giving a prevalence of 13.6%. The HER2 +ve cases were significantly older ($70.6{\pm}19.3$ years old) than the negative cases ($64.2{\pm}13.8$, p=0.041) and had significantly more advanced disease (stages 3 and 4, p=0.026). There were no significant differences in gender distribution, presence of intestinal metaplasia, EBV status, Helicobacter pylori status, tumor location (proximal vs. distal) and degree of tumor differentiation (all p values >0.05). Conclusions: Our study showed that 13.6% of our gastric cancers are positive for HER2, the affected patients being older and having more advanced disease at diagnosis.

• Asian Pacific Journal of Cancer Prevention
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• 제17권5호
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• pp.2637-2641
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• 2016

Tumor necrosis factor ($TNF-{\alpha}$), an inflammatory cytokine that plays an important role in the control of cell proliferation, differentiation, and apoptosis, has previously been used in anti-cancer therapy. However, the therapeutic applications of $TNF-{\alpha}$ are largely limited due to its general toxicity and anti-apoptotic influence. To overcome this problem, the present study focused on the effect of active constituents isolated from a medicinal plant on $TNF-{\alpha}$-induced apoptosis in human colon adenocarcinoma (HT-29) cells. Nimbolide from Azadirachta indica was evaluated for cytotoxicity by methyl tetrazolium 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay and phase contrast microscopy. Effects on apoptotic signaling proteins were investigated using Western blot analysis. Nimbolide showed cytotoxicity against HT-29 cells that was significantly different from the control group (p<0.01), a concentration of $10{\mu}M$ significantly inducing cell death (p<0.01). In combination with $TNF-{\alpha}$, nimbolide significantly enhanced-induced cell death. In apoptotic pathway, nimbolide activated c-Jun N-terminal kinase (JNK) phosphorylation, BH3 interacting-domain death agonist (Bid) and up-regulated the death receptor 5 (DR5) level. In the combination group, nimbolide markedly sensitized $TNF-{\alpha}$-induced JNK, Bid, caspase-3 activation and the up-regulation of DR5. Our findings overall indicate that nimbolide may enhance $TNF-{\alpha}$-mediated cellular proliferation inhibition through increasing cell apoptosis of HT-29 cells by up-reglation of DR5 expression via the JNK pathway.

• 대한의생명과학회지
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• 제15권2호
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• pp.161-166
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• 2009

Human erythropoietin(EPO) is a glycoprotein that enhances red blood cell production by stimulating proliferation and differentiation of erythroid progenitor cells in the bone marrow. Patients with chronic kidney disease(CKD) suffer from anemia caused by reduced production of EPO in the kidney. Recombinant human EPO protein has been used successfully for the treatment of anemia associated with CKD. Recently, attention has been paid to the development of side effect of EPO, pure red cell aplasia(PRCA), in some patients with CKD. PRCA is a rare disorder of erythropoiesis that leads to a severe anemia due to an almost complete cessation of red blood cell production. EPO-related PRCA is caused by the production of EPO-neutralizing antibodies(Abs) that eliminate the biological activity of EPO as well as endogenous EPO in patients undergoing therapy. Since 1988, almost 200 cases worldwide have been reported with Ab-positive PRCA after receiving EPO therapeutics. The underlying mechanisms of the breaking of immune tolerance to self-EPO have been investigated. Modification of formulation, organic compounds of container closures, and route of administration has been suggested for the possible mechanism of increased immunogenicity of EPO. A number of assays have been used to detect Abs specific to EPO. These assays are generally grouped into two major categories: binding Ab assays and neutralizing Ab assays(bioassays). There are several types of binding Ab assays, including radioimmunoprecipitation assay, enzyme-linked immunosorbent assay, and the BIAcore biosensor assay. In vitro cell-based bioassays have been utilized for the detection of neutralizing Abs. Finally, the recent experience with anti-EPO Abs may have considerable implications for the future development and approval of EPO preparations. Also, considering that millions of patients are being treated with EPO, clinicians need to be aware of signs and consequences of this rare but severe clinical case.