• Tissue Engineering and Regenerative Medicine
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• 제15권6호
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• pp.735-750
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• 2018

BACKGROUND: The major challenge of tissue engineering is to develop constructions with suitable properties which would mimic the natural extracellular matrix to induce the proliferation and differentiation of cells. Poly(${\varepsilon}$-caprolactone)-poly(ethylene glycol)-poly(${\varepsilon}$-caprolactone) (PCL-PEG-PCL, PCEC), chitosan (CS), nano-silica ($n-SiO_2$) and nano-hydroxyapatite (n-HA) are biomaterials successfully applied for the preparation of 3D structures appropriate for tissue engineering. METHODS: We evaluated the effect of n-HA and $n-SiO_2$ incorporated PCEC-CS nanofibers on physical properties and osteogenic differentiation of human dental pulp stem cells (hDPSCs). Fourier transform infrared spectroscopy, field emission scanning electron microscope, transmission electron microscope, thermogravimetric analysis, contact angle and mechanical test were applied to evaluate the physicochemical properties of nanofibers. Cell adhesion and proliferation of hDPSCs and their osteoblastic differentiation on nanofibers were assessed using MTT assay, DAPI staining, alizarin red S staining, and QRT-PCR assay. RESULTS: All the samples demonstrated bead-less morphologies with an average diameter in the range of 190-260 nm. The mechanical test studies showed that scaffolds incorporated with n-HA had a higher tensile strength than ones incorporated with $n-SiO_2$. While the hydrophilicity of $n-SiO_2$ incorporated PCEC-CS nanofibers was higher than that of samples enriched with n-HA. Cell adhesion and proliferation studies showed that n-HA incorporated nanofibers were slightly superior to $n-SiO_2$ incorporated ones. Alizarin red S staining and QRT-PCR analysis confirmed the osteogenic differentiation of hDPSCs on PCEC-CS nanofibers incorporated with n-HA and $n-SiO_2$. CONCLUSION: Compared to other groups, PCEC-CS nanofibers incorporated with 15 wt% n-HA were able to support more cell adhesion and differentiation, thus are better candidates for bone tissue engineering applications.

• 대한정형외과학회지
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• 제55권6호
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• pp.511-519
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• 2020

목적: 신경초종은 말초신경에 주로 발생하는 양성종양이나 크기가 크거나 신경 이외의 부위에서 발견될 경우 악성 연부조직 종양으로 오인하기 쉽다. 저자들은 크기 5 cm 이상의 신경초종 50예의 1) 원발 위치의 분포 및 임상증상여부, 2) 술 전 방사선 및 병리학적 진단 결과와 진단적 정확도에 대해 알아보았다. 대상 및 방법: 신경초종으로 확진된 214예 중 자기공명영상(magnetic resonance imaging, MRI)상 종양의 최대직경이 5 cm 이상인 종양 50예를 추출하였다. 이를 주요신경 기원, 근육 내, 골 내의 원발위치에 따라 분류하였고 구체적인 해부학적 위치를 분석하였다. 결과: 전체 코호트에서 원발위치에 따라 분류하였을 때 주요 말초신경에 생긴 종양이 14예, 근육 내 발생이 31예, 골 내 발생이 5예였다. 신경초종의 평균크기는 7 cm였으며 근육내 신경초종이 평균 8 cm로 가장 컸다. MRI를 통한 영상학적 진단에서 전체 50예 중 33예(66.0%)는 양성 신경종양으로, 15예(30.0%)는 악성종양으로 판독하였으며, 나머지 2예(4.0%)는 각각 결핵 농양, 건활막 거대세포종으로 보고되었다. 골내 신경초종 5예 중 영상학적으로 신경초종으로 진단한 예는 없었다. 임상증상에서는 주요 신경기원의 경우는 Tinel sign이 78.6%로 많았고(11/14), 주요 신경 외 기원 종양에서는 종괴 촉지 증상이 93.5%로 가장 많았으며(29/31) 증상기간도 평균 66.6개월로 가장 길었다. 병리학적 진단을 위해 생검을 시행한 총 38예 중 86.8%에서는 신경초종으로 진단하였다. 합병증은 수술 후 합병증이 총 2예였으며 종양절제 후 출혈로 재수술이 필요했던 경우와 수술 후 경한 신경마비가 발생한 경우였다. 결론: 5 cm 이상의 근육 내 종양을 진단할 때 장기간의 종괴인지 소견이 있고, MRI상 비특이적인 소견일 경우에는 양상 신경종양일 가능성도 염두에 두고 조직학적 확진 후 치료를 시행하는 것이 과잉 치료 가능성을 줄이는 데 도움이 될 것으로 생각된다.

• 대한골관절종양학회지
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• 제1권2호
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• pp.205-209
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• 1995

A desmoid tumor is a locally aggressive growth of connective tissue origin which infiltrates the surrounding tissue and has a marked tendency for recurrence. And so it was also called as an aggressive fibromatosis, musculofascial fibromatosis or fibrosarcoma etc. Thirteen cases of desmoid tumor was treated since 1980, and their retrospective study was done with 79 months of follow-up after initial surgical excision. The female was involved in 12 cases(one male) with the age ranged from 7-50 years, average 28 years, and seven patients in third decade. A slowly growing mass was excised on average 4 months after first notice of the mass, but their margins are not demarcated clearly in most cases. Wide excision in 12 cases was done, but wide excision and saphenous vein graft was performed in one case because of invasion of posterior tibial artery by tumor mass. The tumor was found on extraabdominal region in 8 cases(61.5%) but 5 cases in abdominal wall(38.5%). The recurrence rate was high(6/13, 46.2%), and 11 times in 6 patients were recurred(average 1.8 times), within 27 months of initial excision. Six cases of recurrence were treated with wide excision again in 3 cases, wide excision combined with radiotherapy(4,000-6,000cGy) in 4 cases and wide excision with chemotherapy in one case. During the follow-up for average 21 months after treatment, no recurrences are found. Tumor remission periods without recurrence are average 67 months in all, and 11 years in longest case. Histologically it was very mimic with fibrosarcoma but could be differentiated with Trichrome stain, and their findings are not changed after recurrence.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1603-1609
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• 2014

Background: The response to treatment and overall survival (OS) of patients with acute myeloid leukemia (AML) is variable, with a median ranging from 6 months to 11.5 years. TP53 is associated with old age, chemotherapy resistance, and worse OS. Using genetic sequencing, we set out to look at our own experience with AML, and hypothesized that both TP53 mutations and SNPs at codon 72 would mimic the literature by occurring in a minority of patients, and conferring a worse OS. Materials and Methods: We performed a pilot study of randomly selected, newly diagnosed AML patients at Mount Sinai Medical Center, diagnosed from 2005-2008 (n=10). TP53 PCR sequencing was performed using DNA from bone marrow smears. Analysis was accomplished using Mutation Surveyor software with confirmation of the variants using the COSMIC and dbSNP databases. Results: Fewer than half of the patients harbored TP53 mutations (40%). There was no significant difference in OS based on gender, AML history, risk-stratified karyotype, or TP53 mutation. There were possible trends toward improved survival among patients less than 60 (11 vs 4 months, p=0.09), Hispanics (8 vs 1 months, p=0.11), and those not harboring SNP P72R (8 vs 2 months, p=0.10). There was a significant improvement in survival among patients with better performance status (28 vs 4 months, p=0.01) and those who did not have a complex karyotype (8 vs 1 months, p=0.03). The most commonly observed TP53 mutation was a missense N310K (40%) and the most commonly observed SNP was P72R (100.0%). Conclusions: Our study confirms previous reports that poor PS and the presence of a complex karyotype are associated with a decreased OS. In our cohort, TP53 mutations were relatively common, occurring more frequently in male patients with an adverse karyotype. Although there was no significant difference in survival between TP53 mutated and un-mutated patients, there was a possible trend toward worse OS among patients with SNP P72R. Larger studies are needed to validate these findings.

• 생명과학회지
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• 제20권11호
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• pp.1577-1581
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• 2010

조혈촉진 cytokine인 Granulocyte colony stimulating factor (G-CSF)는 골수세포를 자극하여 granulocyte로 증식, 분화시키는 기능을 가지며, 현재 아주 고가의 치료제로 사용되고 있다. 인간 G-CSF (hG-CSF)를 아직 시도되지 않은 누에 유래 세포주인 BM5 세포에서 발현시키고 생산 효율을 높이기 위해 hG-CSF cDNA를 변형하였다. hG-CSF의 cDNA의 endoplasmic reticulum (ER) signal sequence 부분을 누에의 소포체에서 분비되는 단백질인 prophenoloxidase (PPAE), protein disulfide isomerase (PDI)와 bombyxin (BX)에서 유래한 누에특이 ER signal sequence로 대체한 hG-CSF의 cDNA 함유 벡터를 구축하였다. 이들 벡터를 사용하여 형질전환한 BM5 세포의 배양액에 분비된 G-CSF 단백질을 western blot으로 분석하여 발현을 확인하였다. 누에특이 ER signal sequence들로 대체된 hG-CSF cDNA를 포함하는 벡터에 의한 hG-CSF 단백질 생산이 인간 G-CSF cDNA가 든 벡터에 의한 hG-CSF의 생산보다 월등히 효율적이었다. 또한, PPAE-signal sequence를 포함하는 hG-CSF 단백질은 배양배지에서 형질전환 4일 후에 최고에 달하였고, 7 일째까지 비슷한 양이 배지 내에서 검출되었다. 이상의 결과는 인간유래 유전자가 곤충세포 내에서 발현 될 때 인간유래 유전자 보다는 곤충 유전자발현 시스템에 맞게 변형했을 경우 더 효율적인 단백질 발현을 얻을 수 있음을 보여 준다.

• Molecules and Cells
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• 제43권8호
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• pp.718-727
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• 2020

The imbalance between the proliferation and apoptosis of B-cell precursors is an important contributor to the pathogenesis of B-cell precursor acute lymphoblastic leukemia (BCP-ALL), while its specific regulatory mechanism remains perplexing. This study aimed to expound the underlying mechanism of the proliferation and apoptosis of BCP-ALL cells from the perspective of non-coding RNA. In this study, long non-coding RNA colorectal neoplasia differentially expressed (LncRNA CRNDE) was upregulated in the bone marrow of BCP-ALL patients and BCP-ALL cell lines (NALM-6 and RS4;11). Functionally, LncRNA CRNDE knockdown restrained cell proliferation and boosted cell apoptosis in NALM-6 and RS4;11 cells. The subsequent investigation confirmed that LncRNA CRNDE bound to miR-345-5p and negatively regulated miR-345-5p expression. The overexpression of miR-345-5p suppressed cell proliferation and boosted cell apoptosis in NALM-6 and RS4;11 cells. Further experiments revealed that miR-345-5p downregulated cyclic AMP response element-binding protein (CREB) expression by targeting its mRNA directly. CREB overexpression reversed the effect of miR-345-5p mimic on cell proliferation and apoptosis in NALM-6 and RS4;11 cells. Finally, in vivo experiments showed that LncRNA CRNDE knockdown prolonged the survival of mice xenotransplanted with NALM-6 cells. In conclusion, LncRNA CRNDE upregulated CREB expression by suppressing miR-345-5p, thus promoting cell proliferation and reducing cell apoptosis in BCP-ALL.

• Pediatric Infection and Vaccine
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• 제22권3호
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• pp.210-215
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• 2015

대식세포 활성 증후군(MAS, Macrophage activation syndrome)은 전신 홍반성 루푸스(SLE, systemic lupus erythematous) 환자에서 감염에 의해 나타날 수 있는 드문 합병증이다. MAS는 기저의 자가면역질환의 임상양상과 유사하게 나타나거나 혹은 감염성 합병증과 혼돈될 수 있어 감별에 주의 하여야 한다. 14세 여환이 2주간 지속되는 발열과 통증을 동반하는 얼굴의 피부 발진을 주소로 내원하였다. 피부 발진과 간비대, 범혈구 감소증, aspartate aminotransferase, lactate dehydrogenase, 혈청 ferritin이 상승하여, MAS를 의심하였다. 피부 병변과 항핵체 양성, C3와 C4의 감소, 간접 쿰스검사 양성으로 SLE를 진단하였다. 따라서 본 증례는 MAS가 HSV에 의하여 촉발된 것을, SLE의 첫 증상으로서 나타낸 증례로서, 촉발 요인 및 기저질환을 치료함으로써 중증의 합병증 없이 호전되었다.

• Molecules and Cells
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• 제40권2호
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• pp.123-132
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• 2017

Insulin signaling is coordinated by insulin receptor substrates (IRSs). Many insulin responses, especially for blood glucose metabolism, are mediated primarily through Irs-1 and Irs-2. Irs-1 knockout mice show growth retardation and insulin signaling defects, which can be compensated by other IRSs in vivo; however, the underlying mechanism is not clear. Here, we presented an Irs-1 truncated mutated mouse ($Irs-1^{-/-}$) with growth retardation and subcutaneous adipocyte atrophy. $Irs-1^{-/-}$ mice exhibited mild insulin resistance, as demonstrated by the insulin tolerance test. Phosphatidylinositol 3-kinase (PI3K) activity and phosphorylated Protein Kinase B (PKB/AKT) expression were elevated in liver, skeletal muscle, and subcutaneous adipocytes in Irs-1 deficiency. In addition, the expression of IRS-2 and its phosphorylated version were clearly elevated in liver and skeletal muscle. With miRNA microarray analysis, we found miR-33 was down-regulated in bone marrow stromal cells (BMSCs) of $Irs-1^{-/-}$ mice, while its target gene Irs-2 was up-regulated in vitro studies. In addition, miR-33 was down-regulated in the presence of Irs-1 and which was up-regulated in fasting status. What's more, miR-33 restored its expression in re-feeding status. Meanwhile, miR-33 levels decreased and Irs-2 levels increased in liver, skeletal muscle, and subcutaneous adipocytes of $Irs-1^{-/-}$ mice. In primary cultured liver cells transfected with an miR-33 inhibitor, the expression of IRS-2, PI3K, and phosphorylated-AKT (p-AKT) increased while the opposite results were observed in the presence of an miR-33 mimic. Therefore, decreased miR-33 levels can up-regulate IRS-2 expression, which appears to compensate for the defects of the insulin signaling pathway in Irs-1 deficient mice.

• Korean Journal of Radiology
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• 제25권1호
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• pp.62-73
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• 2024

Objective: This study aimed to determine the prevalence of vertebral venous congestion (VVC) in patients with chemoport insertion, evaluate the imaging characteristics of nodular VVC, and identify the factors associated with VVC. Materials and Methods: This retrospective single-center study was based on follow-up contrast-enhanced chest computed tomography (CT) of 1412 adult patients who underwent chemoport insertion between January 2016 and December 2016. The prevalence of venous stenosis, reflux, and VVC were evaluated. The imaging features of nodular VVC, including specific locations within the vertebral body, were analyzed. To identify the factors associated with VVC, patients with VVC were compared with a subset of patients without VVC who had been followed up for > 3 years without developing VVC after chemoport insertion. Toward this, a multivariable logistic regression analysis was performed. Results: After excluding 333 patients, 1079 were analyzed (mean age ± standard deviation, 62.3 ± 11.6 years; 540 females). The prevalence of VVC was 5.8% (63/1079), with all patients (63/63) demonstrating vertebral venous reflux and 67% (42/63) with innominate vein stenosis. The median interval between chemoport insertion and VVC was 515 days (interquartile range, 204-881 days). The prevalence of nodular VVC was 1.5% (16/1079), with a mean size of 5.9 ± 3.1 mm and attenuation of 784 ± 162 HU. Nodular VVC tended to be located subcortically. Forty-four patients with VVC underwent CT examinations with contrast injections in both arms; the VVC disappeared in 70% (31/44) when the contrast was injected in the arm contralateral to the chemoport site. Bevacizumab use was independently associated with VVC (odds ratio, 3.45; P < 0.001). Conclusion: The prevalence of VVC and nodular VVC was low in patients who underwent chemoport insertion. Nodular VVC was always accompanied by vertebral venous reflux and tended to be located subcortically. To avoid VVC, contrast injection in the arm contralateral to the chemoport site is preferred.

• 대한핵의학회지
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• 제38권4호
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• pp.325-329
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• 2004

목적: 생쥐 간에서 분리한 S9 분획을 사용하여 방사성추적자의 대사물질을 측정함으로써 S9 분획이 새로운 방사성추적자의 대사물질 측정에 사용될 수 있는가를 평가하였다. 대상 및 방법 : 저자들에 의하여 체내 대사경로가 연구된 방사성추적자를 사용하였으며, 생쥐 간 S9 분획은 마이크로솜을 얻는 과정에서 생쥐의 간으로부터 얻어졌다. 체외 대사물질 측정방법을 방사성추적자에 S9 분획과 NADPH를 넣고 $37^{\circ}C$에서 반응하였으며 해당하는 시간대에 반응용액의 일부를 취하여 대사물질을 방사능 TLC로 측정하였다. 대사로 인한 탈불소화는 뼈 모사물질인 인산칼슘과 반응하여 흡착 정도를 측정함으로써 확인하였다. 결과: S9 분획을 사용한 체외 대사물질 측정방법에서 방사성추적자 $[^{18}F]1$은 대사로 인한 탈불소화가 일어나 15분 이내에 거의 모두 $[^{18}F]$ 플루오라이드 이온으로 대사되었다. 이 결과는 동일한 방사성추적자를 사용하여 저자들이 보고한 체내방법 및 마이크로솜을 사용한 체외방법에서 얻은 결과와 일치하였다. 방사성추적자 $[^{18}F]2$는 60분 이내에 모두 대사되었으며, $4-[^{18}F]$플루오로벤조산을 포함한 3개의 대사물질이 확인되었다. 이 중에서 원점에 위치한 대사물질은 체내방법 및 마이크로솜을 사용한 체외 대사물질 측정방법에서 얻은 대사물질과 일치하였다. 마이크로솜을 사용한 체외방법에서 얻은 결과와 비교할 때 대사물질을 유사하였으나 대사물질들의 비율은 상이하였으며, 이 결과는 S9 분획에 있는 세포질의 영향으로 여겨진다. 결론: S9 분획을 사용한 체외 대사물질 측정법은 체내의 간 대사물질을 예측하는데 매우 유용성이 크며, 특히 대사로 인한 탈불소화를 추적하는 데는 인산칼슘을 이용한 흡착법과 함께 높은 신뢰성을 갖는 것이 확인되었다. 각 횡단면에 대한 랜덤계수율, 산란계수율, NECR을 구하였다. 결과: 스캐너의 중심에서 1 cm 벗어난 지점에서 횡축방향, 축방향 공간분해능은 (1) 5.3, 6.5 mm (FBP), (2) 5.1, 5.9 mm (3D RAMLA)이었다. 횡단면의 중심에서 10 cm 벗어난 지점에서 횡축반경방향, 횡축접선방향, 축방향 공간분해능은 (1) 5.7, 5.7, 7.0 mm (FBP), (2) 5.4, 5.4, 6.4 mm (3D RAMLA)이었다. 감쇠매질이 없는 이상적인 상황에서의 민감도는 횡단면의 중심에서 3,620 counts/sec/MBq, 횡단면의 중심에서 10 cm 벗어난 지점에서 4,324 counts/sec/MBq이었다. 산란분획은 40.6%, 최대 참계수율과 최대 NECR은 각각 88.9 kcps @ 12.9 kBq/mL, 34.3 kcps @ 8.84 kBq/mL이었다. 결론: 이 실험에서 NEMA NU2-2001을 이용해 GSO 섬광결정을 사용해 제작된 PET/CT에 대한 성능 평가를 실시하였다. 이는 BGO, LSO 섬광결정을 사용해 제작된 PET 스캐너의 특성과 비교할 수 있는 자료를 제공하며 PET 영상 획득 시 객관적 평가와 분석에 유용하였다.tinning 시간은 20분 이상(20-35분)을 유지하고, 가능한 rotating invertor를 사용하는 것이 좋을 것으로 생각된다.KC $\varepsilon$이 K562(Adr)세포에서 많이 발현되었으나, K562와 K562(Adr)세포에서는 verapamil처리에 따른 PKC 아형의 변화는 없었다. 결론: Verapamil은 암세포의 종류에 따라 MIBI와 TF의 섭취를 감소시켰고, 고용량에는 MDR세포의 섭취도 감소시켰으며 이러한 현상은 세포독성 이나 PKC효소 아형과는 관련이 없었다. 그러므로 MDR의 진단시 verapamil을 처치에 따른 MIBI와 TF의 섭취 정도를 기준으로 하는